p53 Acetylation Exerts Critical Roles in Pressure Overload-Induced Coronary Microvascular Dysfunction and Heart Failure in Mice.

BACKGROUND: Coronary microvascular dysfunction (CMD) has been shown to contribute to cardiac hypertrophy and heart failure (HF) with preserved ejection fraction. At this point, there are no proven treatments for CMD. METHODS: We have shown that histone acetylation may play a critical role in the regulation of CMD. By using a mouse model that replaces lysine with arginine at residues K98, K117, K161, and K162R of p53 (p534KR), preventing acetylation at these sites, we test the hypothesis that acetylation-deficient p534KR could improve CMD and prevent the progression of hypertensive cardiac hypertrophy and HF. Wild-type and p534KR mice were subjected to pressure overload by transverse aortic constriction to induce cardiac hypertrophy and HF. RESULTS: Echocardiography measurements revealed improved cardiac function together with a reduction of apoptosis and fibrosis in p534KR mice. Importantly, myocardial capillary density and coronary flow reserve were significantly improved in p534KR mice. Moreover, p534KR upregulated the expression of cardiac glycolytic enzymes and Gluts (glucose transporters), as well as the level of fructose-2,6-biphosphate; increased PFK-1 (phosphofructokinase 1) activity; and attenuated cardiac hypertrophy. These changes were accompanied by increased expression of HIF-1α (hypoxia-inducible factor-1α) and proangiogenic growth factors. Additionally, the levels of SERCA-2 were significantly upregulated in sham p534KR mice, as well as in p534KR mice after transverse aortic constriction. In vitro, p534KR significantly improved endothelial cell glycolytic function and mitochondrial respiration and enhanced endothelial cell proliferation and angiogenesis. Similarly, acetylation-deficient p534KR significantly improved coronary flow reserve and rescued cardiac dysfunction in SIRT3 (sirtuin 3) knockout mice. CONCLUSIONS: Our data reveal the importance of p53 acetylation in coronary microvascular function, cardiac function, and remodeling and may provide a promising approach to improve hypertension-induced CMD and to prevent the transition of cardiac hypertrophy to HF.

Ferrostatin-1 specifically targets mitochondrial iron-sulfur clusters and aconitase to improve cardiac function in Sirtuin 3 cardiomyocyte knockout mice.

AIMS: Ferroptosis is a form of iron-regulated cell death implicated in ischemic heart disease. Our previous study revealed that Sirtuin 3 (SIRT3) is associated with ferroptosis and cardiac fibrosis. In this study, we tested whether the knockout of SIRT3 in cardiomyocytes (SIRT3cKO) promotes mitochondrial ferroptosis and whether the blockade of ferroptosis would ameliorate mitochondrial dysfunction. METHODS AND RESULTS: Mitochondrial and cytosolic fractions were isolated from the ventricles of mice. Cytosolic and mitochondrial ferroptosis were analyzed by comparison to SIRT3loxp mice. An echocardiography study showed that SIRT3cKO mice developed heart failure as evidenced by a reduction of EF% and FS% compared to SIRT3loxp mice. Comparison of mitochondrial and cytosolic fractions of SIRT3cKO and SIRT3loxp mice revealed that, upon loss of SIRT3, mitochondrial, but not cytosolic, total lysine acetylation was significantly increased. Similarly, acetylated p53 was significantly upregulated only in the mitochondria. These data demonstrate that SIRT3 is the primary mitochondrial deacetylase. Most importantly, loss of SIRT3 resulted in significant reductions of frataxin, aconitase, and glutathione peroxidase 4 (GPX4) in the mitochondria. This was accompanied by a significant increase in levels of mitochondrial 4-hydroxynonenal. Treatment of SIRT3cKO mice with the ferroptosis inhibitor ferrostatin-1 (Fer-1) for 14 days significantly improved preexisting heart failure. Mechanistically, Fer-1 treatment significantly increased GPX4 and aconitase expression/activity, increased mitochondrial iron­sulfur clusters, and improved mitochondrial membrane potential and Complex IV activity. CONCLUSIONS: Inhibition of ferroptosis ameliorated cardiac dysfunction by specifically targeting mitochondrial aconitase and iron­sulfur clusters. Blockade of mitochondrial ferroptosis may be a novel therapeutic target for mitochondrial cardiomyopathies.

Charged Microdroplets as Microelectrochemical Cells for CO2 Reduction and C-C Coupling.

Charged microdroplets offer novel electrochemical environments, distinct from traditional solid-liquid or solid-liquid-gas interfaces, due to the intense electric fields at liquid-gas interfaces. In this study, we propose that charged microdroplets serve as microelectrochemical cells (MECs), enabling unique electrochemical reactions at the gas-liquid interface. Using electrospray-generated microdroplets, we achieved multielectron CO2 reduction and C-C coupling to synthesize ethanol using molecular catalysts. These catalysts effectively harness and relay electrons, enhancing the longevity of solvated electrons and enabling multielectron reactions. Importantly, we revealed the intrinsic relationship between the size and charge density of a MEC and its reaction selectivity. Employing in situ mass spectrometry, we identified reaction intermediates (molecular catalyst adducts with HCOO) and oxidation products, elucidating the CO2 reduction mechanism and the comprehensive reaction procedure. Our research underscores the promising role of charged microdroplets in pioneering new electrochemical systems.

LINC00839 promotes colorectal cancer progression by recruiting RUVBL1/Tip60 complexes to activate NRF1.

The long noncoding RNA LINC00839 has been shown to be involved in the progression of some cancer types, such as bladder cancer, prostate cancer, breast cancer, and neuroblastoma. However, if LINC00839 has roles in colorectal cancer (CRC), it has not been elucidated so far. Here, we focus on the biological role and involved mechanisms of LINC00839 in CRC. We show that LINC00839 is selectively upregulated in CRC and locates to the nucleus. High expression of LINC00839 is associated with poor outcomes in CRC patients. Functional experiments show that LINC00839 promotes CRC proliferation, invasion, and metastasis in vitro and in vivo. Mechanistically, LINC00839 recruits Ruvb1 to the Tip60 complex and increases its acetylase activity. LINC00839 guides the complex to the NRF1 promoter and promotes acetylation of lysines 5 and 8 of histones H4, thereby upregulating the expression of NRF1. Subsequently, NRF1 activates mitochondrial metabolism and biogenesis, thereby promoting CRC progression. In summary, our study reports on a mechanism by which LINC00839 positively regulates NRF1, thus promoting mitochondrial metabolism and biogenesis, as well as CRC progression.

The Therapeutic Potential of Targeting Ferroptosis in the Treatment of Mitochondrial Cardiomyopathies and Heart Failure.

ABSTRACT: Ferroptosis is a form of iron-regulated cell death implicated in a wide array of diseases, including heart failure, hypertension, and numerous cardiomyopathies. In addition, mitochondrial dysfunction has been associated with several of these same disease states. However, the role of the mitochondrion in ferroptotic cell death remains debated. As a major regulator of cellular iron levels, the mitochondria may very well play a crucial role in the mechanisms behind ferroptosis, but at this point, this has not been adequately defined. Emerging evidence from our laboratory and others indicates a critical role of mitochondrial Sirtuin 3, a deacetylase linked with longevity and protection against numerous conditions, in the prevention of cardiovascular diseases. Here, we provide a brief overview of the potential roles of Sirtuin 3 in mitochondrial iron homeostasis and its contribution to the mitochondrial cardiomyopathy of Friedreich's ataxia and diabetic cardiomyopathy. We also discuss the current knowledge of the involvement of ferroptosis and the mitochondria in these and other cardiovascular disease states, including doxorubicin-induced cardiomyopathy, and provide insight into areas requiring further investigation.

TIGAR Deficiency Blunts Angiotensin-II-Induced Cardiac Hypertrophy in Mice.

Hypertension is the key contributor to pathological cardiac hypertrophy. Growing evidence indicates that glucose metabolism plays an essential role in cardiac hypertrophy. TP53-induced glycolysis and apoptosis regulator (TIGAR) has been shown to regulate glucose metabolism in pressure overload-induced cardiac remodeling. In the present study, we investigated the role of TIGAR in cardiac remodeling during Angiotensin II (Ang-II)-induced hypertension. Wild-type (WT) and TIGAR knockout (KO) mice were infused with Angiotensin-II (Ang-II, 1 µg/kg/min) via mini-pump for four weeks. The blood pressure was similar between the WT and TIGAR KO mice. The Ang-II infusion resulted in a similar reduction of systolic function in both groups, as evidenced by the comparable decrease in LV ejection fraction and fractional shortening. The Ang-II infusion also increased the isovolumic relaxation time and myocardial performance index to the same extent in WT and TIGAR KO mice, suggesting the development of similar diastolic dysfunction. However, the knockout of TIGAR significantly attenuated hypertension-induced cardiac hypertrophy. This was associated with higher levels of fructose 2,6-bisphosphate, PFK-1, and Glut-4 in the TIGAR KO mice. Our present study suggests that TIGAR is involved in the control of glucose metabolism and glucose transporters by Ang-II and that knockout of TIGAR attenuates the development of maladaptive cardiac hypertrophy.

PLOD2 promotes colorectal cancer progression by stabilizing USP15 to activate the AKT/mTOR signaling pathway.

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) has been reported as an oncogenic gene, affecting various malignant tumors, including endometrial carcinoma, osteosarcoma, and gastric cancer. These effects are mostly due to the enhanced deposition of collagen precursors. However, more studies need to be conducted on how its lysyl hydroxylase function affects cancers like colorectal carcinoma (CRC). Our present results showed that PLOD2 expression was elevated in CRC, and its higher expression was associated with poorer survival. Overexpression of PLOD2 also facilitated CRC proliferation, invasion, and metastasis in vitro and in vivo. In addition, PLOD2 interacted with USP15 by stabilizing it in the cytoplasm and then activated the phosphorylation of AKT/mTOR, thereby promoting CRC progression. Meanwhile, minoxidil was demonstrated to downregulate the expression of PLOD2 and suppress USP15, and the phosphorylation of AKT/mTOR. Our study reveals that PLOD2 plays an oncogenic role in colorectal carcinoma, upregulating USP15 and subsequently activating the AKT/mTOR pathway.

Direct Analysis of Micro-biopsy Samples by Polarity Gradient Focusing Dip-and-Go Mass Spectrometry.

Direct analysis of micro-biopsy samples by mass spectrometry at single-cell level still faces major challenges. In this work, we developed a polarity gradient focusing dip-and-go strategy (PGF-Dip&Go) during induced electrospray ionization mass spectrometry (iESI-MS) analysis for real-time enrichment and spatial separation of compounds such as lipids, alkaloids, fatty amines, and drugs. Compared with direct iESI-MS analysis, enrichment of analytes (enrichment factor of 5.0-100.0) and spatial separation between different analytes were achieved. Owing to the enrichment effect and salt cleanup effect, the sensitivity of PGF-Dip&Go has been improved by 25-10,000 times compared with direct iESI-MS. PGF-Dip&Go has been successfully applied for the analysis of lipids in a 200 pL micro-biopsy section from an individual fish egg. Lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and triglyceride (TG) were significantly enriched and separated according to their polarity differences, proving the potential of PGF-Dip&Go to be a noninvasive and powerful analytical tool for in situ analysis of complex small volumes in the future.

Uncoupling of the center-to-periphery arterial stiffness gradient and pulse pressure amplification in viral pneumonia infection.

OBJECTIVES: Arterial stiffness is a common manifestation of viral pneumonia infections, including COVID-19. Nevertheless, the relationship between the center-to-periphery arterial stiffness gradient and pulse pressure amplification (PPA) in infectious diseases remains unclear. This study aimed to investigate this relationship utilizing arterial pressure volume index (API) and arterial velocity pulse index (AVI) ratio. METHODS: API/AVI and PPA were measured in 219 participants with COVID-19 and 374 normal participants. Multiple linear regression was used to assess the association of API/AVI and PPA, and restricted cubic spline was used to investigate the non-linear relationship between API/AVI and PPA. Receiver operating characteristic curve (ROC) analysis was used to evaluate the effects of API/AVI in identifying COVID-19 infection and severe stage. RESULTS: There was a significant J-shaped relationship between API/AVI and PPA in COVID-19 group, while a M-shaped relationship was observed in normal group. API/AVI decreased rapidly as PPA decreased until API/AVI decreased slowly at PPA of 1.07, and then API/AVI decreased slowly again at PPA of 0.78. ROC results showed that API/AVI demonstrated excellent accuracy in identifying COVID-19 infection (AUC = 0.781) and a high specificity (84.88%) in identifying severe stage. CONCLUSIONS: There was a J-shaped association between the API/AVI and PPA in viral infected patients, while a M-shaped relationship in the normal participants. API/AVI is better for identifying infected and uninfected patients, with a high specificity in identifying those in severe stages of the disease. The attenuation or reversal of API/AVI may be associated with the loss of PPA coupling.

MTM-HCC at Previous Liver Resection as a Predictor of Overall Survival in Salvage Liver Transplantation.

OBJECTIVES: Salvage liver transplantation (sLT) is considered an effective method to treat hepatocellular carcinoma (HCC) recurrence. This multicenter research aimed to identify the prognostic factors associated with recurrence-free survival (RFS) and overall survival (OS) after sLT. MATERIAL AND METHODS: A retrospective analysis of 114 patients who had undergone sLT for recurrent HCC between February 2012 and September 2020 was performed. The baseline and clinicopathological data of the patients were collected. RESULTS: The 1-, 3-, and 5-year RFS rates after sLT were 88.9%, 75.2%, and 69.2%, respectively, and the OS rates were 96.4%, 78.3%, and 70.8%. A time from liver resection (LR) to recurrence < 1 year, disease beyond the Milan criteria at sLT and macrotrabecular massive (MTM)-HCC were identified as risk factors for RFS and were further identified as independent risk factors. A time from LR to recurrence < 1 year, disease beyond the Milan criteria at sLT and MTM-HCC were also risk factors for OS and were further identified as independent risk factors. CONCLUSIONS: Compared with primary liver transplantation (pLT), more prognostic factors are available from patients who had undergone LR. We suggest that in cases of HCC recurrence within 1 year after LR, disease beyond the Milan criteria at sLT and MTM-HCC patients, sLT should be used with caution.

Gender and age disparities in small-to-medium arterial stiffness among the Chinese population.

BACKGROUND AND AIMS: Arterial pressure-volume index (API) is a non-invasive tool for assessing small-to-medium-sized arterial stiffness. This study aimed to investigate the potential age- and sex-related differences in the API and explore the practical implications of such differences. METHODS AND RESULTS: The study analysed 7620 subjects for whom API measurements were available. Linear regression and restrictive cubic spline models were used to investigate the associations between potential risk conditions and the API. Additionally, this study employed a backward stepwise regression method to identify the independent factors associated with a high API. Middle-aged to older women had higher API values and a higher prevalence of high API than men in the same age group. However, the opposite was observed among younger individuals, with women having lower API values than men. This study also identified a J-shaped relationship between API and age, where API values began to increase at a certain age and rapidly increased after that. In women, the API started to increase at 31 years of age and rapidly increased after 54 years of age. In men, the API started to increase at 38 years of age, followed by a rapid increase after 53 years of age. CONCLUSION: This study's observation of a significant age-sex interaction in small-to-medium-sized arterial stiffening offers a valuable explanation for cardiovascular disease risk and provides important parameters for using API measurements to evaluate such risk.

Efficient fabrication method for non-periodic microstructures using one-step two-photon lithography and a metal lift-off process.

This paper presents a mask-less, flexible, efficient, and high-resolution fabrication method for non-periodic microstructures. Sub-wavelength micro-polarizer arrays, (MPAs) which are the most essential part of the focal plane polarimeters, are typical non-periodic structures. The grating ridges of each polarizer were oriented in four different directions offset by 45°, corresponding to different polarization directions. The finite element method was introduced to optimize the structural parameters of the MPA in the far-infrared region. The numerical results demonstrated that the designed MPA had a TM transmittance of more than 55% and an extinction ratio no less than 7 dB. An aluminum MPA that operates in the 8-14 µm infrared region was prepared by one-step two-photon lithography (TPL) and the metal lift-off process. The femtosecond laser exposed the photoresist with only a single scan, making TPL very efficient. The fabricated single-layer sub-wavelength MPAs with a period of 3 µm, a duty cycle of 0.35-0.5, and a height of 150 nm, were analyzed by an optical microscope and an atomic force microscope. The successful fabrication of the MPA indicated that one-step TPL could be a viable and efficient method for pattern preparation in the fabrication of non-periodic microstructures.

AutoBar: Automatic Barrier Coverage Formation for Danger Keep Out Applications in Smart City.

Barrier coverage is a fundamental application in wireless sensor networks, which are widely used for smart cities. In applications, the sensors form a barrier for the intruders and protect an area through intrusion detection. In this paper, we study a new branch of barrier coverage, namely warning barrier coverage (WBC). Different from the classic barrier coverage, WBC has the inverse protect direction, which moves the sensors surrounding a dangerous region and protects any unexpected visitors by warning them away from the dangers. WBC holds a promising prospect in many danger keep out applications for smart cities. For example, a WBC can enclose the debris area in the sea and alarm any approaching ships in order to avoid their damaging propellers. One special feature of WBC is that the target region is usually dangerous and its boundary is previously unknown. Hence, the scattered mobile nodes need to detect the boundary and form the barrier coverage themselves. It is challenging to form these distributed sensor nodes into a barrier because a node can sense only the local information and there is no global information of the unknown region or other nodes. To this end, in response to the newly proposed issue of the formation of barrier cover, we propose a novel solution AutoBar for mobile sensor nodes to automatically form a WBC for smart cities. Notably, this is the first work to trigger the coverage problem of the alarm barrier, wherein the regional information is not pre-known. To pursue the high coverage quality, we theoretically derive the optimal distribution pattern of sensor nodes using convex theory. Based on the analysis, we design a fully distributed algorithm that enables nodes to collaboratively move toward the optimal distribution pattern. In addition, AutoBar is able to reorganize the barrier even if any node is broken. To validate the feasibility of AutoBar, we develop the prototype of the specialized mobile node, which consists of two kinds of sensors: one for boundary detection and another for visitor detection. Based on the prototype, we conduct extensive real trace-driven simulations in various smart city scenarios. Performance results demonstrate that AutoBar outperforms the existing barrier coverage strategies in terms of coverage quality, formation duration, and communication overhead.

In Situ Probing and Identification of Electrochemical Reaction Intermediates by Floating Electrolytic Electrospray Mass Spectrometry.

The in-depth study of electrochemical (EC) synthesis can require a powerful mass spectrometry (MS) analytical platform which can discover and identify fleeting intermediates in EC reactions. Here we report a floating electrolytic electrospray ionization (FE-ESI) strategy that can perform EC processes in a floating electrolytic cell and monitor intermediates by high-resolution MS. Compared with previous EC-MS methods, a significant advantage of FE-ESI-MS is that it allows one to modulate the electrolytic and electrospray process individually, ensuring its high sensitivity in discovering intermediates and universality to investigate redox reactions in different scenarios. This powerful platform has been successfully used to investigate the EC reductive coupling of p-tolylboronic acid and p-nitrotoluene. A series of nitrene intermediates were discovered and identified by FE-ESI-MS, indicating that a hidden mechanism involving nitrene formation might play a key role in EC reductive coupling process.

Knockout of TIGAR enhances myocardial phosphofructokinase activity and preserves diastolic function in heart failure.

Hypertension is an important risk factor in the pathogenesis of diastolic dysfunction. Growing evidence indicates that glucose metabolism plays an essential role in diastolic dysfunction. TP53-induced glycolysis and apoptosis regulator (TIGAR) has been shown to regulate glucose metabolism and heart failure (HF). In the present study, we investigated the role of TIGAR in diastolic function and cardiac fibrosis during pressure overload (PO)-induced HF. WT mice subjected to transverse aortic constriction (TAC), a commonly used method to induce diastolic dysfunction, exhibited diastolic dysfunction as evidenced by increased E/A ratio and E/E' ratio when compared to its sham controls. This was accompanied by increased cardiac interstitial fibrosis. In contrast, the knockout of TIGAR attenuated PO-induced diastolic dysfunction and interstitial fibrosis. Mechanistically, the levels of glucose transporter Glut-1, Glut-4, and key glycolytic enzyme phosphofructokinase 1 (PFK-1) were significantly elevated in TIGAR KO subjected to TAC as compared to that of WT mice. Knockout of TIGAR significantly increased fructose 2,6-bisphosphate levels and phosphofructokinase activity in mouse hearts. In addition, PO resulted in a significant increase in perivascular fibrosis and endothelial activation in the WT mice, but not in the TIGAR KO mice. Our present study suggests a necessary role of TIGAR-mediated glucose metabolism in PO-induced cardiac fibrosis and diastolic dysfunction.

MIER3 induces epithelial-mesenchymal transition and promotes breast cancer cell aggressiveness via forming a co-repressor complex with HDAC1/HDAC2/Snail.

Breast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer death in women. MIER3 (Mesoderm induction early response 1, family member3) is considered as a potential oncogene for breast cancer. However, the role of MIER3 in breast cancer remain largely unknown. The expression of MIER3 was detected and the relationship between its expression and clinicopathological characteristics was also analyzed. The effect of MIER3 on proliferation and migration of breast cancer cells was detected in vitro and in vivo. Western blot, IF, and Co-IP were employed to detect the relationship between MIER3, HDAC1, HDAC2, and Snail. ChIP assay was performed to determine the binding of MIER3/HDAC1/HDAC2/Snail complex to the promoter of E-cadherin. In this study, we found that MIER3 was upregulated in breast cancer tissue and closely associated with poor prognosis of patients. MIER3 could promote the proliferation, migration, and epithelial-mesenchymal transition (EMT) of breast cancer cells. Further studies showed that MIER3 interacted with HDAC1/HDAC2 and Snail to form a repressive complex which could bind to E-cadherin promoter and was related to its deacetylation. Our study concluded that MIER3 was involved in forming a co-repressor complex with HDAC1/HDAC2/Snail to promote EMT by silencing E-cadherin.

Profile analysis with reconstruction robustness for measurement data subject to outliers.

In the surface profile analysis, there are often a few observations that contain outliers. Due to the existence of outliers, the application of non-robust reconstruction algorithms for measurement data will become a huge problem because these methods are often sensitive to outliers and the approximation effectiveness will be greatly aggravated. In view of this, this paper presents a novel angle-based moving total least squares reconstruction method, to the best of our knowledge, that applies two-step pre-treatment to handle outliers. The first step is an abnormal point detection process that characterizes the geometric features of discrete points in the support domain through a new angle-based parameter constructed by total least square. Then, the point with the largest anomaly degree is removed, and a relevant weight function is defined to adjust the weights of the remaining points. After pre-treatment, the final estimates are calculated by weighted total least squares (WTLS) based on the compact weight function. The detection and removal of outliers are automatic, and there is no need to set a threshold value artificially, which effectively avoids the adverse impacts of human operation. Numerical simulations and experiments verify the applicability of the proposed algorithm as well as its accuracy and robustness.

Regulatory role of TIGAR on endothelial metabolism and angiogenesis.

Endothelial glycolytic metabolism plays an important role in the process of angiogenesis. TP53-induced glycolysis and apoptosis regulator (TIGAR) is a significant mediator of cellular energy homeostasis. However, the role of TIGAR in endothelial metabolism, angiogenesis, and coronary flow reserve (CFR) has not been studied. The present study investigated whether knockout (KO) of TIGAR improves endothelial glycolytic function and angiogenesis. In vitro, aortic endothelial cells (ECs) from TIGAR KO mice exhibited increased expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform-3 (PFKFB3) and increased glycolytic function. These were accompanied by increased mitochondrial basal/maximal respiration and ATP production. Furthermore, knockout of TIGAR in ECs enhanced endothelial proliferation, migration, and tube formation. Knockout of TIGAR also significantly increased aortic sprouting ex vivo. In vivo, knockout of TIGAR increased the expression of proangiogenic factor, angiopoietin-1 (Ang-1) in mouse hearts. Knockout of TIGAR also significantly increased coronary capillary density with enhanced CFR in these hearts. Furthermore, TIGAR KO mice subjected to pressure overload (PO), a common model to study angiogenesis and cardiac hypertrophy, exhibited elevated expression of Ang-1, VEGF, and PFKFB3 than that of the wild-type (WT) mice. WT mice subjected to PO exhibited a significant reduction of coronary capillary density and impaired CFR, but TIGAR KO mice did not. In addition, knockout of TIGAR blunted TAC-induced cardiac hypertrophy and dysfunction seen in the WT mice. In conclusion, knockout of TIGAR improves endothelial angiogenetic capabilities by enhancing the endothelial glycolytic function, mitochondrial respiration, and proangiogenic signaling, which leads to increased coronary capillary density and vascular function and protects against chronic stress.

POTEE promotes colorectal carcinoma progression via activating the Rac1/Cdc42 pathway.

Current studies have shown that POTE ankyrin domain family members have high expressions as tumor antigens in malignant tumors, such as prostate cancer, ovarian cancer, breast cancer and the like. POTEE is a member of the POTE anchor protein family E. However, its role in colorectal carcinoma (CRC) has not been studied. In this study, the function of POTEE in CRC was examined for the first time and its correlation with CRC cell biological behaviors was analyzed. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry revealed that POTEE was remarkably overexpressed in CRC and associated with an aggressive phenotype. We also found that POTEE was localized in the cytoplasm. In addition, downregulation of POTEE expression can notably inhibit the proliferation, migration, and invasion of CRC cell in vitro, and repressed tumor growth and metastasis in vivo. In contrast, overexpression of POTEE could promote the aggressive behaviors of CRC cells. Mechanistically, POTEE promoted CRC migration, invasion and epithelial-mesenchymal transition (EMT) by increasing the activation of Rac1 and Cdc42. To summarize, these results suggested that POTEE might serve as an oncogene for CRC tumorigenesis and progression, and may become a novel molecular marker for clinical diagnosis and treatment.

Fabrication of novel Ag4Bi2O5-x towards excellent photocatalytic oxidation of gaseous toluene under visible light irradiation.

In this work, a novel oxide combined with bismuth (Bi) and silver (Ag) was prepared via simple ball milling. This substance was optimized by adjusting the amount of pre-source. Preliminary characterization results confirmed the successful synthesis of Ag4Bi2O5. Subsequently, gaseous toluene was selected as model compound to evaluate the photocatalytic activity of Ag4Bi2O5 photocatalyst. According to the degradation results, Ag4Bi2O5 performed excellent visible light-driven photocatalytic activity with high stability. For the oxidation process of gaseous compound, reactive oxygen species (ROS) were responsible for the achievement, and the formation of oxygen vacancies on Ag4Bi2O5 were involved in the generation of ROS to promote the transfer of photogenerated electrons, and improving photocatalytic activity. DFT calculations revealed the theoretical band gap of Ag4Bi2O5 bulk is 1.758 eV. And the work function of Ag4Bi2O5 (112)ov was ca. at 4.447 eV. The material was easily fabricated and a reliable path was provided for the synthesis of new and efficient photocatalyst for the remediation of polluted indoor air.