Deciphering the interaction between PKM2 and the built-in thermodynamic properties of the glycolytic pathway in cancer cells.

Most cancer cells exhibit high glycolysis rates under conditions of abundant oxygen. Maintaining a stable glycolytic rate is critical for cancer cell growth as it ensures sufficient conversion of glucose carbons to energy, biosynthesis, and redox balance. Here we deciphered the interaction between PKM2 and the thermodynamic properties of the glycolytic pathway. Knocking down or knocking out PKM2 induced a thermodynamic equilibration in the glycolytic pathway, characterized by the reciprocal changes of the Gibbs free energy (ΔG) of the reactions catalyzed by PFK1 and PK, leading to a less exergonic PFK1-catalyzed reaction and a more exergonic PK-catalyzed reaction. The changes in the ΔGs of the two reactions cause the accumulation of intermediates, including the substrate PEP (the substrate of PK), in the segment between PFK1 and PK. The increased concentration of PEP in turn increased PK activity in the glycolytic pathway. Thus, the interaction between PKM2 and the thermodynamic properties of the glycolytic pathway maintains the reciprocal relationship between PK concentration and its substrate PEP concentration, by which, PK activity in the glycolytic pathway can be stabilized and effectively counteracts the effect of PKM2 KD or KO on glycolytic rate. In line with our previous reports, this study further validates the roles of the thermodynamics of the glycolytic pathway in stabilizing glycolysis in cancer cells. Deciphering the interaction between glycolytic enzymes and the thermodynamics of the glycolytic pathway will promote a better understanding of the flux control of glycolysis in cancer cells.

Downregulation of malic enzyme 3 facilitates progression of gastric carcinoma via regulating intracellular oxidative stress and hypoxia-inducible factor-1α stabilization.

BACKGROUND: Gastric cancer (GC) is one of the most malignant cancers worldwide. Metabolism disorder is a critical characteristic of malignant tumors related to tumor progression and metastasis. However, the expression and molecular mechanism of malic enzyme 3 (ME3) in GC are rarely reported. In this study, we aim to investigate the molecular mechanism of ME3 in the development of GC and to explore its potential value as a prognostic and therapeutic target in GC. METHOD: ME3 mRNA and protein expression were evaluated in patients with GC using RT-qPCR, WB, and immunohistochemistry, as well as their correlation with clinicopathological indicators. The effect of ME3 on proliferation and metastasis was evaluated using Cell Counting Kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU) assay, transwell assay, wound healing assay, and subcutaneous injection or tail vein injection of tumor cells in mice model. The effects of ME3 knockdown on the level of metabolites and hypoxia-inducible factor-1α (HIF-1α) protein were determined in GC cells. Oxidative phosphorylation was measured to evaluate adenosine triphosphate (ATP) production. RESULTS: ME3 was downregulated in human GC tissues (P < 0.001). The decreased ME3 mRNA expression was associated with younger age (P = 0.02), pathological staging (P = 0.049), and lymph node metastasis (P = 0.001), while low ME3 expression was associated with tumor size (P = 0.048), tumor invasion depth (P < 0.001), lymph node metastasis (P = 0.018), TNM staging (P < 0.001), and poor prognosis (OS, P = 0.0206; PFS P = 0.0453). ME3 knockdown promoted GC cell malignancy phenotypes. Moreover, α-ketoglutarate (α-KG) and NADPH/NADP+ ratios were reduced while malate was increased in the ME3 knockdown group under normoxia. When cells were incubated under hypoxia, the NADPH/NADP+ ratio and α-KG decreased while intracellular reactive oxygen species (ROS) increased significantly. The ME3 knockdown group exhibited an increase in ATP production and while ME3 overexpression group exhibited oppositely. We discovered that ME3 and HIF-1α expression were negatively correlated in GC cells and tissues, and proposed the hypothesis: downregulation of ME3 promotes GC progression via regulating intracellular oxidative stress and HIF-1α. CONCLUSION: We provide evidence that ME3 downregulation is associated with poor prognosis in GC patients and propose a hypothesis for the ME3 regulatory mechanism in GC progression. The present study is of great scientific significance and clinical value for exploring the prognostic and therapeutic targets of GC, evaluating and improving the clinical efficacy of patients, reducing recurrence and metastasis, and improving the prognosis and quality of life of patients.

Amino-Induced Modulation of Electronic State and Neighboring Site Distance through Second Shell Boosted Catecholase-Mimicking Activity of Electron-Rich Cu Center.

Boosting the biomimetic catalytic activity of nanozyme is important for its potential application. One common strategy to achieve this goal mainly focused on manipulating the electronic state of metal site through the first coordination shell to modulate the adsorption/desorption strength of related reactant, intermediate and/or product, but remained challenging. Taking Cu-based catecholase-mimicking nanozyme for example, this work herein reports a different strategy involving amino-induced modulation of electronic state through the second shell to raise the electron density of Cu site, which further triggers the repulsion effect between neighboring geminal Cu centers to increase the Cu─Cu distance. The resulting nanozyme with electron-rich Cu site (DT-Cu) presents a lower work function and an upshifted d-band center in comparison with its counterpart (i.e., relatively electron-deficient TA-Cu), which promotes the electron transfer and enhances the adsorption strengths of Cu site for O2, catechol and H2O2 intermediate. The longer Cu─Cu distance of DT-Cu accelerated the O─O bond dissociation of H2O2 intermediate. This expedites the oxygen reduction process during catecholase-like catalysis, which together with the enhanced O2/H2O2/catechol adsorption corporately boosts the catecholase-like activity of DT-Cu.

Rapid and Green Fabrication of Nanozyme with Geminal CuN3O Configuration for Efficient Catecholase-Mimicking.

Fabrication of nanozyme with catecholase-like catalytic activity faces the great challenge of merging outstanding activity with low cost as well as simple, rapid, and low-energy-consumed production, restricting its industrial applications. Herein, an inexpensive yet robust nanozyme (i.e., DT-Cu) via simple one-step coordination between diaminotriazole (DT) and CuSO4 within 1 h in water at room temperature is constructed. The asymmetric dicopper site with CuN3O configuration for each copper as well as Cu─O bond length of ≈1.83 Å and Cu···Cu distance of ≈3.5 Å in DT-Cu resemble those in catechol oxidase (CO), which ensure its prominent intrinsic activity, outperforming most CO-mimicking nanozymes and artificial homogeneous catalysts. The use of inexpensive DT/CuSO4 in this one-pot strategy endows DT-Cu with only ≈20% cost of natural CO per activity unit. During catalysis, O2 experienced a 4e-dominated reduction process accompanied by the formation of 1O2 and H2O2 intermediates and the product of H2O. Benefiting from the low cost as well as the distinctive structure and superior intrinsic activity, DT-Cu presents potential applications ranging from biocatalysis to analytical detection of biomolecules such as epinephrine and beyond.

Development of a novel percutaneous digital flexible nephroscope: its use and application.

BACKGROUND: Renal calculi are one of the most frequent diseases in urology, and percutaneous nephrolithotomy (PCNL) being the gold standard for treating renal calculi larger than 2 cm. However, traditional rigid nephroscope cannot bend, presents significant limitations during PCNL. This study aims to develop a novel digital flexible nephroscope for PCNL and verify its safety and efficacy using 3D printed models and ex vivo porcine kidney models, providing new equipment for PCNL. METHODS: Based on the determined technical parameters, the novel digital flexible nephroscope was manufactured. First, 3D-printed model and ex vivo porcine kidney models were utilized to simulate the PCNL procedures. Then, the traditional rigid nephroscope and the novel digital flexible nephroscope were utilized to simulate the PCNL procedures on 10 ex vivo porcine kidneys for comparison. We observed and recorded the renal calyces visualized and accessed by both the traditional rigid nephroscope and the novel digital flexible nephroscope. RESULTS: In both the 3D printing and ex vivo porcine kidney models, the novel percutaneous digital flexible nephroscope smoothly entered the renal collecting system through the percutaneous renal tract. It freely changed angles to reach most target calyces, demonstrating significant advantages over the traditional rigid nephroscope. CONCLUSION: The successful development of the novel percutaneous digital flexible nephroscope allows it to be used either independently or as an adjunct in complex stone cases, providing more effective and safer surgical equipment for percutaneous nephrolithotomy.

Unveiling drastic influence of cross-interactions in hydrothermal carbonization of spirulina with cellulose, lignin or poplar on nature of hydrochar and activated carbon.

Spirulina platensis contains abundant nitrogen-containing organics, which might react with derivatives of cellulose/lignin during hydrothermal carbonization (HTC), probably affecting yield, property of hydrochar, and pore development in activation of hydrochar. This was investigated herein by conducting co-HTC of spirulina platensis with cellulose, lignin, and sawdust at 260 °C and subsequent activation of the resulting hydrochars with K2C2O4 at 800 °C. The results showed that cross-condensation of spirulina platensis-derived proteins with cellulose/lignin-derived ketones and phenolics did take place in the co-HTC, forming more π-conjugated heavier organics, retaining more nitrogen species in hydrochar, reducing yields of hydrochar, making the hydrochar more aromatic and increasing the thermal stability and resistivity towards activation. This enhanced the yield of activated carbon (AC) by 7 %-20 % and significantly increased specific surface area of the AC from activation of hydrochar of spirulina platensis + lignin to 2074.5 m2/g (859.3 m2/g from spirulina platensis only and 1170.1 m2/g from lignin only). Furthermore, more mesopores from activation of hydrochar of spirulina platensis + cellulose (47 %) and more micropores from activation of hydrochar of spirulina + sawdust (93 %) was generated. The AC from spirulina platensis + lignin with the developed pore structures generated sufficient sites for adsorption of tetracycline from aqueous phase and minimized steric hindrance for mass transfer with the abundant mesopores (43 %).

Artificial LiF-Rich Interface Enabled by In situ Electrochemical Fluorination for Stable Lithium-Metal Batteries.

Lithium (Li)-metal batteries are promising next-generation energy storage systems. One drawback of uncontrollable electrolyte degradation is the ability to form a fragile and nonuniform solid electrolyte interface (SEI). In this study, we propose the use of a fluorinated carbon nanotube (CNT) macrofilm (CMF) on Li metal as a hybrid anode, which can regulate the redox state at the anode/electrolyte interface. Due to the favorable reaction energy between the plated Li and fluorinated CNTs, the metal can be fluorinated directly to a LiF-rich SEI during the charging process, leading to a high Young's modulus (~2.0 GPa) and fast ionic transfer (~2.59×10-7  S cm-1 ). The obtained SEI can guide the homogeneous plating/stripping of Li during electrochemical processes while suppressing dendrite growth. In particular, the hybrid of endowed full cells with substantially enhanced cyclability allows for high capacity retention (~99.3 %) and remarkable rate capacity. This work can extend fluorination technology into a platform to control artificial SEI formation in Li-metal batteries, increasing the stability and long-term performance of the resulting material.

Tracing the electron flow in redox metabolism: The appropriate distribution of electrons is essential to maintain redox balance in cancer cells.

Cancer cells are characterized by sustained proliferation, which requires a huge demand of fuels to support energy production and biosynthesis. Energy is produced by the oxidation of the fuels during catabolism, and biosynthesis is achieved by the reduction of smaller units or precursors. Therefore, the oxidation-reduction (redox) reactions in cancer cells are more active compared to those in the normal counterparts. The higher activity of redox metabolism also induces a more severe oxidative stress, raising the question of how cancer cells maintain the redox balance. In this review, we overview the redox metabolism of cancer cells in an electron-tracing view. The electrons are derived from the nutrients in the tumor microenvironment and released during catabolism. Most of the electrons are transferred to NAD(P) system and then directed to four destinations: energy production, ROS generation, reductive biosynthesis and antioxidant system. The appropriate distribution of these electrons achieved by the function of redox regulation network is essential to maintain redox homeostasis in cancer cells. Interfering with the electron distribution and disrupting redox balance by targeting the redox regulation network may provide therapeutic implications for cancer treatment.

Lactic acidosis switches cancer cells from dependence on glycolysis to OXPHOS and renders them highly sensitive to OXPHOS inhibitors.

Targeting oxidative phosphorylation (OXPHOS) has emerged as a strategy for cancer treatment. However, most tumor cells exhibit Warburg effect, they primarily rely on glycolysis to generate ATP, and hence they are resistant to OXPHOS inhibitors. Here, we report that lactic acidosis, a ubiquitous factor in the tumor microenvironment, increases the sensitivity of glycolysis-dependent cancer cells to OXPHOS inhibitors by 2-4 orders of magnitude. Lactic acidosis reduces glycolysis by 79-86% and increases OXPHOS by 177-218%, making the latter the main production pathway of ATP. In conclusion, we revealed that lactic acidosis renders cancer cells with typical Warburg effect phenotype highly sensitive to OXPHOS inhibitors, thereby greatly expanding the anti-cancer spectrum of OXPHOS inhibitors. In addition, as lactic acidosis is a ubiquitous factor of TME, it is a potential indicator to predict the efficacy of OXPHOS inhibitors in cancer treatment.

Enhanced light extraction efficiency of GaN-based green micro-LED modulating by a thickness-tunable SiO2 passivation structure.

Green micro-light emitting diodes (micro-LEDs) is one of the three primary color light sources as full-color display, which serves as a key research object in the field of micro-LED display. As the micro-LED size decreases, the surface-area-to-volume ratio of the device increases, leading to more serious damage on the sidewall by inductively coupled plasma (ICP) etching. The passivation process of SiO2 provides an effective method to reduce sidewall damage caused by ICP etching. In this work, green rectangular micro-LEDs with passivation layer thickness of 0∼600 nm was designed using the finite-difference time-domain (FDTD) simulation. In order to verify the simulation results, the micro-LED array was fabricated by parallel laser micro-lens array (MLA) lithography in high speed and large area. The effect of the SiO2 passivation layer thickness on the performance of the green micro-LED was analyzed, which shows that the passivation layer thickness-light extraction efficiency curve fluctuates periodically. For the sample with 90 nm thickness of SiO2 passivation layer, there exists a small leakage current and higher operating current density, and the maximum external quantum efficiency (EQE) is 2.8 times higher than micro-LED without SiO2 passivation layer.

Brain transcriptome-wide association study implicates novel risk genes underlying schizophrenia risk.

BACKGROUND: To identify risk genes whose expression are regulated by the reported risk variants and to explore the potential regulatory mechanism in schizophrenia (SCZ). METHODS: We systematically integrated three independent brain expression quantitative traits (eQTLs) (CommonMind, GTEx, and BrainSeq Phase 2, a total of 1039 individuals) and GWAS data (56 418 cases and 78 818 controls), with the use of transcriptome-wide association study (TWAS). Diffusion magnetic resonance imaging was utilized to quantify the integrity of white matter bundles and determine whether polygenic risk of novel genes linked to brain structure was present in patients with first-episode antipsychotic SCZ. RESULTS: TWAS showed that eight risk genes (CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, PCDHA8, THOC7, and TYW5) reached transcriptome-wide significance (TWS) level. These findings were confirmed by an independent integrative approach (i.e. Sherlock). We further conducted conditional analyses and identified the potential risk genes that driven the TWAS association signal in each locus. Gene expression analysis showed that several TWS genes (including CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, THOC7 and TYW5) were dysregulated in the dorsolateral prefrontal cortex of SCZ cases compared with controls. TWS genes were mainly expressed on the surface of glutamatergic neurons, GABAergic neurons, and microglia. Finally, SCZ cases had a substantially greater TWS genes-based polygenic risk (PRS) compared to controls, and we showed that fractional anisotropy of the cingulum-hippocampus mediates the influence of TWS genes PRS on SCZ. CONCLUSIONS: Our findings identified novel SCZ risk genes and highlighted the importance of the TWS genes in frontal-limbic dysfunctions in SCZ, indicating possible therapeutic targets.

Expression Levels of MicroRNA-300/BCL2L11 in Papillary Thyroid Cancer and Their Clinical Diagnostic Values.

INTRODUCTION: This research aims to explore the expression levels of microRNA (miRNA)-300/BCL-2-like protein 11 (BCL2L11) and their values in the clinical diagnosis of papillary thyroid cancer (PTC). METHODS: Pathological tissues that were surgically removed for thyroid disease were selected. miR-300 and BCL2L11 expression levels in the samples were measured. Receiver operating characteristic (ROC) curves were plotted to analyze miR-300 and BCL2L11 predictive values for PTC. Upon silencing miR-300 and silencing BCL2L11 in PTC cells, the corresponding miR-300 and BCL2L11 expression levels were tested, followed by examining PTC cell activities. The targeting relationship of miR-300 and BCL2L11 was detected by the bioinformatics website and luciferase activity assay. RESULTS: miR-300 expression levels were elevated and BCL2L11 expression levels were reduced in PTC tissues. miR-300 and BCL2L11 expression levels in PTC tissues had a correlation with TNM stage and lymph node metastasis. The results of ROC curve revealed that both miR-300 and BCL2L11 had clinical predictive values for PTC. Mechanistically, miR-300 negatively regulated BCL2L11. The functional assays unveiled that silencing miR-300 impeded PTC cell activities, and silencing BCL2L11 induced PTC cell activities. In the rescue experiment, silencing BCL2L11 reversed the impacts of silencing miR-300 on PTC cell development. CONCLUSION: This study underlines that miR-300 expression is increased and BCL2L11 expression is declined in PTC. miR-300 and BCL2L11 both have clinical predictive values for diagnosing PTC.

Determining the quantitative relationship between glycolysis and GAPDH in cancer cells exhibiting the Warburg effect.

Previous studies have identified GAPDH as a promising target for treating cancer and modulating immunity because its inhibition reduces glycolysis in cells (cancer cells and immune cells) with the Warburg effect, a modified form of cellular metabolism found in cancer cells. However, the quantitative relationship between GAPDH and the aerobic glycolysis remains unknown. Here, using siRNA-mediated knockdown of GAPDH expression and iodoacetate-dependent inhibition of enzyme activity, we examined the quantitative relationship between GAPDH activity and glycolysis rate. We found that glycolytic rates were unaffected by the reduction of GAPDH activity down to 19% ± 4.8% relative to untreated controls. However, further reduction of GAPDH activity below this level caused proportional reductions in the glycolysis rate. GAPDH knockdown or inhibition also simultaneously increased the concentration of glyceraldehyde 3-phosphate (GA3P, the substrate of GAPDH). This increased GA3P concentration countered the effect of GAPDH knockdown or inhibition and stabilized the glycolysis rate by promoting GAPDH activity. Mechanistically, the intracellular GA3P concentration is controlled by the Gibbs free energy of the reactions upstream of GAPDH. The thermodynamic state of the reactions along the glycolysis pathway was only affected when GAPDH activity was reduced below 19% ± 4.8%. Doing so moved the reactions catalyzed by GAPDH + PGK1 (phosphoglycerate kinase 1, the enzyme immediate downstream of GAPDH) away from the near-equilibrium state, revealing an important biochemical basis to interpret the rate control of glycolysis by GAPDH. Collectively, we resolved the numerical relationship between GAPDH and glycolysis in cancer cells with the Warburg effect and interpreted the underlying mechanism.

Comprehensive and integrative analyses identify TYW5 as a schizophrenia risk gene.

BACKGROUND: Identifying the causal genes at the risk loci and elucidating their roles in schizophrenia (SCZ) pathogenesis remain significant challenges. To explore risk variants associated with gene expression in the human brain and to identify genes whose expression change may contribute to the susceptibility of SCZ, here we report a comprehensive integrative study on SCZ. METHODS: We systematically integrated the genetic associations from a large-scale SCZ GWAS (N = 56,418) and brain expression quantitative trait loci (eQTL) data (N = 175) using a Bayesian statistical framework (Sherlock) and Summary data-based Mendelian Randomization (SMR). We also measured brain structure of 86 first-episode antipsychotic-naive schizophrenia patients and 152 healthy controls with the structural MRI. RESULTS: Both Sherlock (P = 3. 38 × 10-6) and SMR (P = 1. 90 × 10-8) analyses showed that TYW5 mRNA expression was significantly associated with risk of SCZ. Brain-based studies also identified a significant association between TYW5 protein abundance and SCZ. The single-nucleotide polymorphism rs203772 showed significant association with SCZ and the risk allele is associated with higher transcriptional level of TYW5 in the prefrontal cortex. We further found that TYW5 was significantly upregulated in the brain tissues of SCZ cases compared with controls. In addition, TYW5 expression was also significantly higher in neurons induced from pluripotent stem cells of schizophrenia cases compared with controls. Finally, combining analysis of genotyping and MRI data showed that rs203772 was significantly associated with gray matter volume of the right middle frontal gyrus and left precuneus. CONCLUSIONS: We confirmed that TYW5 is a risk gene for SCZ. Our results provide useful information toward a better understanding of the genetic mechanism of TYW5 in risk of SCZ.

Reasons for lesion uncrossability as assessed by intravascular ultrasound.

OBJECTIVES: The purpose of the current study was to use intravascular ultrasound (IVUS) to clarify anatomical and morphological lesion characteristics of uncrossable lesions. BACKGROUND: Uncrossable lesions are not always severely calcified. The prevalence of uncrossable lesions that are nonseverely calcified as well as other mechanisms for uncrossability has not been well clarified. METHODS: A total of 252 de novo uncrossable lesions in native coronary arteries that underwent either rotational or orbital atherectomy due to inability of any balloon to cross the lesion and 38 lesions with severe calcium in which IVUS crossed preatherectomy were included. Severe calcium is defined as maximum arc of calcium ≥270°. RESULTS: Severe calcification was absent in 16% of uncrossable lesions, 83% of which had a significant vessel bend. Compared with crossable lesions with severe calcium, uncrossable lesions with severe calcium more often had a bend in the vessel (71% vs. 21%, p < 0.001) and a longer length of continuous severe calcium (median length of calcium ≥270° 3.8 mm vs. 1.9 mm, p = 0.001). Other than severe calcium (especially long continuous calcium) or a bend in the vessel, anatomical factors associated with uncrossabilty were aorto-ostial lesion location and small vessels. CONCLUSIONS: Uncrossable lesions are not always severely calcified. The interaction of lesion morphology (continuous long and large arcs of calcium) and vessel geometry (bend in the vessel or ostial lesion location) affect lesion crossability.

A state of the art review on electrochemical technique for the remediation of pharmaceuticals containing wastewater.

Pharmaceutical wastewater is a frequent kind of wastewater with high quantities of organic pollutants, although little research has been done in the area. Pharmaceutical wastewaters containing antibiotics and high salinity may impair traditional biological treatment, resulting in the propagation of antibiotic resistance genes. The potential for advanced oxidation processes (AOPs) to break down hazardous substances instead of present techniques that essentially transfer contaminants from wastewater to sludge, a membrane filter, or an adsorbent has attracted interest. Among a variety of AOPs, electrochemical systems are a feasible choice for treating pharmaceutical wastewater. Many electrochemical approaches exist now to remediate rivers polluted by refractory organic contaminants, like pharmaceutical micro-pollutants, which have become a severe environmental problem. The first part of this investigation provides the bibliometric analysis of the title search from 1970 to 2021 for keywords such as wastewater and electrochemical. We have provided information on relations between keywords, countries, and journals based on three fields plot, inter-country co-authorship network analysis, and co-occurrence network visualization. The second part introduces electrochemical water treatment approaches customized to these very distinct discarded flows, containing how processes, electrode materials, and operating conditions influence the results (with selective highlighting cathode reduction and anodic oxidation). This section looks at how electrochemistry may be utilized with typical treatment approaches to improve the integrated system's overall efficiency. We discuss how electrochemical cells might be beneficial and what compromises to consider when putting them into practice. We wrap up our analysis with a discussion of known technical obstacles and suggestions for further research.

Circulating long non-coding RNA Coromarker expression correlated with inflammation, coronary artery stenosis, and plaque vulnerability in patients with coronary artery disease.

BACKGROUND: The aim of the study was to assess the correlation between circulating long non-coding RNA (lncRNA) OTTHUMT00000387022 (named Coromarker) expression and disease severity, inflammatory cytokine levels, and plaque vulnerability in patients with coronary artery disease (CAD). METHODS: A total of 134 participants who received coronary angiography were enrolled and classified them as CAD patients (N = 89) and controls (N = 45). Blood samples were obtained from all subjects. Quantitative polymerase chain reaction was used to evaluate Coromarker expression. The enzyme-linked immunosorbent test was used to measure inflammatory cytokines including high sensitivity C reactive protein (hsCRP), interleukin (IL)-1ß (IL-1ß), IL-6, NOD-like receptor protein 3 (NLRP3), and markers of coronary plaque stability including matrix metallopeptidase 9 (MMP-9) and soluble CD40 ligand (sCD40L). The severity of coronary stenosis was determined from the Gensini Score. RESULTS: LncRNA Coromarker expression was elevated to a greater extent in CAD patients than in control subjects before and after adjustments for age/gender (both p < 0.001); it was an independent predictor of CAD risk (area under curve: 0.824, 95% CI: 0.732-0.915). Additionally, Coromarker expression was significantly associated with Gensini Score (r = 0.574, p < 0.001), hsCRP (r = 0.221, p = 0.015), IL-1ß (r = 0.351, p < 0.001), IL-6 (r = 0.286, p < 0.01), and NLRP3 levels (r = 0.312, p < 0.001). Coromarker expression was found to be linked with MMP-9 (r = 0.260, p < 0.01) and sCD40L (r = 0.441, p < 0.001). CONCLUSION: Circulating lncRNA Coromarker expression correlates with increased disease severity and inflammation as well as plaque vulnerability in patients with CAD.

Pyrolysis of furfural residues: Property and applications of the biochar.

Furfural residue (FR) is a solid waste generated during the production of furfural from corn cobs. The chemical energy and material potential of FR can be potentially recovered via pyrolysis. In this study, the pyrolysis of FR at the temperature ranging from 350 to 650 °C at the varied heating rate was investigated, aiming to understand the characteristics of the pyrolysis products. The results indicate that the organic components of FR tend to be cracked to form biochar and gases as the dominate products, due to the high ash content of FR. The FR-derived bio-oil also contained abundant organics derived from cellulose and lignin. Increasing pyrolysis temperature favored formation of the organics with fused ring structures. Lower heating rate in pyrolysis also formed biochar with higher thermal stability and higher fixed carbon content by enhancing the extent of deoxygenation. Additionally, the transformation of -OH via dehydration, -C-H into = C-H via dehydrogenation, and the cracking of CO during carbonization of biochar in the pyrolysis were also observed during pyrolysis of FR. Activation of the FR-derived biochar generated abundant micropores and mesopores, rendering the activated carbon with superior specific capacitance as electrodes of electrocapacitors (329 Fg-1) and the excellent adsorption efficiency of phosphate (up to 98.81%).

Perturbation of phosphoglycerate kinase 1 (PGK1) only marginally affects glycolysis in cancer cells.

Phosphoglycerate kinase 1 (PGK1) plays important roles in glycolysis, yet its forward reaction kinetics are unknown, and its role especially in regulating cancer cell glycolysis is unclear. Here, we developed an enzyme assay to measure the kinetic parameters of the PGK1-catalyzed forward reaction. The Km values for 1,3-bisphosphoglyceric acid (1,3-BPG, the forward reaction substrate) were 4.36 µm (yeast PGK1) and 6.86 µm (human PKG1). The Km values for 3-phosphoglycerate (3-PG, the reverse reaction substrate and a serine precursor) were 146 µm (yeast PGK1) and 186 µm (human PGK1). The Vmax of the forward reaction was about 3.5- and 5.8-fold higher than that of the reverse reaction for the human and yeast enzymes, respectively. Consistently, the intracellular steady-state concentrations of 3-PG were between 180 and 550 µm in cancer cells, providing a basis for glycolysis to shuttle 3-PG to the serine synthesis pathway. Using siRNA-mediated PGK1-specific knockdown in five cancer cell lines derived from different tissues, along with titration of PGK1 in a cell-free glycolysis system, we found that the perturbation of PGK1 had no effect or only marginal effects on the glucose consumption and lactate generation. The PGK1 knockdown increased the concentrations of fructose 1,6-bisphosphate, dihydroxyacetone phosphate, glyceraldehyde 3-phosphate, and 1,3-BPG in nearly equal proportions, controlled by the kinetic and thermodynamic states of glycolysis. We conclude that perturbation of PGK1 in cancer cells insignificantly affects the conversion of glucose to lactate in glycolysis.

Robust Anode-Supported Cells with Fast Oxygen Release Channels for Efficient and Stable CO2 Electrolysis at Ultrahigh Current Densities.

High-temperature electrolysis using solid oxide electrolysis cells (SOECs) provides a promising way for the storage of renewable energy into chemical fuels. During the past, nickel-based cathode-supported thin-film electrolyte configuration was widely adopted. However, such cells suffer from the serious challenge of anode delamination at high electrolysis currents due to enormous gaseous oxygen formation at the anode-electrolyte interface with insufficient adhesion caused by low sintering temperatures for ensuring high anode porosity and cathode pulverization because of potential nickel redox reaction. Here, the authors propose, fabricate, and test asymmetric thick anode-supported SOECs with firm anode-electrolyte interface and graded anode gas diffusion channel for realizing efficient and stable electrolysis at ultrahigh currents. Such a specially structured anode allows the co-sintering of anode support and electrolyte at high temperatures to form strong interface adhesion while suppressing anode sintering. The mixed oxygen-ion and electron conducting anode with graded channel structure provides a fast oxygen release pathway, large anode surface for oxygen evolution reaction, and excellent support for depositing nanocatalysts, to further improve oxygen evolution activity. As a result, the as-prepared cells demonstrate both high performance, comparable or even higher than state-of-the-art cathode-supported SOECs, and outstanding stability at a record current density of 2.5 A cm-2 .