Adipose triglyceride lipase suppresses noncanonical inflammasome by hydrolyzing LPS.

Intracellular recognition of lipopolysaccharide (LPS) by mouse caspase-11 or human caspase-4 is a vital event for the activation of the noncanonical inflammasome. Whether negative regulators are involved in intracellular LPS sensing is still elusive. Here we show that adipose triglyceride lipase (ATGL) is a negative regulator of the noncanonical inflammasome. Through screening for genes participating in the noncanonical inflammasome, ATGL is identified as a negative player for intracellular LPS signaling. ATGL binds LPS and catalyzes the removal of the acylated side chains that contain ester bonds. LPS with under-acylated side chains no longer activates the inflammatory caspases. Cells with ATGL deficiency exhibit enhanced immune responses when encountering intracellular LPS, including an elevated secretion of interleukin-1ß, decreased cell viability and increased cell cytotoxicity. Moreover, ATGL-deficient mice show exacerbated responses to endotoxin challenges. Our results uncover that ATGL degrades cytosolic LPS to suppress noncanonical inflammasome activation.

The Optimal Age to Stop Endoscopic Surveillance of Patients With Barrett's Esophagus Based on Sex and Comorbidity: A Comparative Cost-Effectiveness Analysis.

BACKGROUND AND AIMS: Current guidelines recommend surveillance for patients with nondysplastic Barrett's esophagus (NDBE) but do not include a recommended age for discontinuing surveillance. This study aimed to determine the optimal age for last surveillance of NDBE patients stratified by sex and level of comorbidity. METHODS: We used 3 independently developed models to simulate patients diagnosed with NDBE, varying in age, sex, and comorbidity level (no, mild, moderate, and severe). All patients had received regular surveillance until their current age. We calculated incremental costs and quality-adjusted life-years (QALYs) gained from 1 additional endoscopic surveillance at the current age versus not performing surveillance at that age. We determined the optimal age to end surveillance as the age at which incremental cost-effectiveness ratio of 1 more surveillance was just less than the willingness-to-pay threshold of $100,000/QALY. RESULTS: The benefit of having 1 more surveillance endoscopy strongly depended on age, sex, and comorbidity. For men with NDBE and severe comorbidity, 1 additional surveillance at age 80 years provided 4 more QALYs per 1000 patients with BE at an additional cost of $1.2 million, whereas for women with severe comorbidity the benefit at that age was 7 QALYs at a cost of $1.3 million. For men with no, mild, moderate, and severe comorbidity, the optimal ages of last surveillance were 81, 80, 77, and 73 years, respectively. For women, these ages were younger: 75, 73, 73, and 69 years, respectively. CONCLUSIONS: Our comparative modeling analysis illustrates the importance of considering comorbidity status and sex when deciding on the age to discontinue surveillance in patients with NDBE.

Endothelial ERG alleviates cardiac fibrosis via blocking endothelin-1-dependent paracrine mechanism.

Cardiac endothelium communicates closely with adjacent cardiac cells by multiple cytokines and plays critical roles in regulating fibroblasts proliferation, activation, and collagen synthesis during cardiac fibrosis. E26 transformation-specific (ETS)-related gene (ERG) belongs to the ETS transcriptional factor family and is required for endothelial cells (ECs) homeostasis and cardiac development. This study aims at investigating the potential role and molecular basis of ERG in fibrotic remodeling within the adult heart. We observed that ERG was abundant in murine hearts, especially in cardiac ECs, but decreased during cardiac fibrosis. ERG knockdown within murine hearts caused spontaneously cardiac fibrosis and dysfunction, accompanied by the activation of multiple Smad-dependent and independent pathways. However, the direct silence of ERG in cardiac fibroblasts did not affect the expression of fibrotic markers. Intriguingly, ERG knockdown in human umbilical vein endothelial cells (HUVECs) promoted the secretion of endothelin-1 (ET-1), which subsequently accelerated the proliferation, phenotypic transition, and collagen synthesis of cardiac fibroblasts in a paracrine manner. Suppressing ET-1 with either a neutralizing antibody or a receptor blocker abolished ERG knockdown-mediated deleterious effect in vivo and in vitro. This pro-fibrotic effect was also negated by RGD (Arg-Gly-Asp)-peptide magnetic nanoparticles target delivery of ET-1 small interfering RNA to ECs in mice. More importantly, we proved that endothelial ERG overexpression notably prevented pressure overload-induced cardiac fibrosis. Collectively, endothelial ERG alleviates cardiac fibrosis via blocking ET-1-dependent paracrine mechanism and it functions as a candidate for treating cardiac fibrosis. • ERG is abundant in murine hearts, especially in cardiac ECs, but decreased during fibrotic remodeling. • ERG knockdown causes spontaneously cardiac fibrosis and dysfunction. • ERG silence in HUVECs promotes the secretion of endothelin-1, which in turn activates cardiac fibroblasts in a paracrine manner. • Endothelial ERG overexpression prevents pressure overload-induced cardiac fibrosis.

Optimizing Management of Patients With Barrett's Esophagus and Low-Grade or No Dysplasia Based on Comparative Modeling.

BACKGROUND & AIMS: Endoscopic treatment is recommended for patients with Barrett's esophagus (BE) with high-grade dysplasia, yet clinical management recommendations are inconsistent for patients with BE without dysplasia (NDBE) or with low-grade dysplasia (LGD). We used a comparative modeling analysis to identify optimal management strategies for these patients. METHODS: We used 3 independent population-based models to simulate cohorts of 60-year-old individuals with BE in the United States. We followed up each cohort until death without surveillance and treatment (natural disease progression), compared with 78 different strategies of management for patients with NDBE or LGD. We determined the optimal strategy using cost-effectiveness analyses, at a willingness-to-pay threshold of $100,000 per quality-adjusted life-year (QALY). RESULTS: In the 3 models, the average cumulative incidence of esophageal adenocarcinoma was 111 cases, with costs totaling $5.7 million per 1000 men with BE. Surveillance and treatment of men with BE prevented 23% to 75% of cases of esophageal adenocarcinoma, but increased costs to $6.2 to $17.3 million per 1000 men with BE. The optimal strategy was surveillance every 3 years for men with NDBE and treatment of LGD after confirmation by repeat endoscopy (incremental cost-effectiveness ratio, $53,044/QALY). The average results for women were consistent with the results for men for LGD management, but the optimal surveillance interval for women with NDBE was 5 years (incremental cost-effectiveness ratio, $36,045/QALY). CONCLUSIONS: Based on analyses from 3 population-based models, the optimal management strategy for patient with BE and LGD is endoscopic eradication, but only after LGD is confirmed by a repeat endoscopy. The optimal strategy for patients with NDBE is endoscopic surveillance, using a 3-year interval for men and a 5-year interval for women.

Dietary soybean antigen impairs growth and health through stress-induced non-specific immune responses in Pacific white shrimp, Litopenaeus vannamei.

In order to compare the effect of substituting fish meal with fermented soybean meal and soybean meal, and confirmed whether the benefit from the two feed materials was related to the content of inclusive soybean antigen protein, two experiments were designed. In experiment 1, one of the two practical diets contained 24.9% soybean meal (SBM), the other one containing 8% fermented soybean meal and 16.95% soybean meal (FSBM); in experiment 2, two semi-purified diets were included with high antigen protein (SPD1) and low antigen protein (SPD2) approximately equal to SBM and FSBM group respectively in experiment 1. Diets were fed to Litopenaeus vannamei (initial weight: 7.48 ±â€¯0.24 g) for 60 days. The results showed that in experiment 1, growth performance was not significantly different between two groups, the enzyme activity (AKP, AST, ALT, SOD and LZM) and mRNA expression levels of TLR, LZM, IMD and HSP70 were significantly higher in the SBM group; In experiment 2, weight gain and specific growth rate were significantly higher in the SPD2 group, while higher activities of AKP, ALT and LZM, lower expression levels of TLRmRNA, LZMmRNA and IMDmRNA and higher expression level of HSP70mRNA were found in SPD1 group. These results implied SBM was more likely to induce stress reaction in shrimp than FSBM, which were closely related to the antigen protein in SBM.

A77 1726 (leflunomide) blocks and reverses cardiac hypertrophy and fibrosis in mice.

T-cell infiltration and the subsequent increased intracardial chronic inflammation play crucial roles in the development of cardiac hypertrophy and heart failure (HF). A77 1726, the active metabolite of leflunomide, has been reported to have powerful anti-inflammatory and T cell-inhibiting properties. However, the effect of A77 1726 on cardiac hypertrophy remains completely unknown. Herein, we found that A77 1726 treatment attenuated pressure overload or angiotensin II (Ang II)-induced cardiac hypertrophy in vivo, as well as agonist-induced hypertrophic response of cardiomyocytes in vitro In addition, we showed that A77 1726 administration prevented induction of cardiac fibrosis by inhibiting cardiac fibroblast (CF) transformation into myofibroblast. Surprisingly, we found that the protective effect of A77 1726 was not dependent on its T lymphocyte-inhibiting property. A77 1726 suppressed the activation of protein kinase B (AKT) signaling pathway, and overexpression of constitutively active AKT completely abolished A77 1726-mediated cardioprotective effects in vivo and in vitro Pretreatment with siRNA targetting Fyn (si Fyn) blunted the protective effect elicited by A77 1726 in vitro More importantly, A77 1726 was capable of blocking pre-established cardiac hypertrophy in mice. In conclusion, A77 1726 attenuated cardiac hypertrophy and cardiac fibrosis via inhibiting FYN/AKT signaling pathway.

Maslinic acid protects against pressure overload-induced cardiac hypertrophy in mice.

Cardiac hypertrophy is characterized by myocyte hypertrophy, accumulation of cardiac collagen, and reactivation of fetal genes. Maslinic acid (MA) is a pentacyclic triterpene with abundance in olive fruit skin and possesses a number of pharmacological actions. However, its effect on pressure overload-induced cardiac hypertrophy remains unknown. Here, we were to investigate the protective effect of MA on cardiac hypertrophy and fibrosis. C57 mice were subjected to aortic banding (AB) or sham surgery. One day after surgery, all the mice were orally given MA (20 mg/kg) or vehicle for the following four weeks. MA could protect against pressure overload-induced cardiac hypertrophy and cardiac fibrosis, as indicated by decreased heart weight/tibia length, and cardiomyocytes cell area and hypertrophic and fibrotic markers. MA treatment also improved cardiac function in mice with AB surgery, as assessed by echocardiographic and hemodynamic analysis. MA reduced phosphorylation of protein kinase B and extracellular regulated protein kinases in the hypertrophic hearts. MA could decrease cardiomyocyte hypertrophy, and inhibit the activation of AKT and ERK signaling pathway in vitro. In conclusion, we found that MA protected against cardiac hypertrophy. MA has the potential to become a therapeutic drug for cardiac hypertrophy.

Endoplasmic Reticulum Stress Induces HRD1 to Protect Alveolar Type II Epithelial Cells from Apoptosis Induced by Cigarette Smoke Extract.

BACKGROUND/AIMS: Cigarette smoking is a major risk factor of chronic obstructive pulmonary disease. This study aimed to examine the effects of cigarette smoke extract (CSE) on alveolar type II epithelial cells (AECII) and investigate the underlying mechanism. METHODS: Primary AECII were isolated from rat lung tissues and exposed to CSE. Apoptosis was detected by flow cytometry. Protein expression was detected by Western blot analysis. RESULTS: Primary rat AECII maintained morphological and physiological characteristic after 3 passages. CSE increased the expression of ER specific pro-apoptosis factors CHOP and caspase 12, and the phosphorylation of JNK in AECII. CSE activated ER stress signaling and increased the phosphorylation of PERK, eIF2α and IRE1. Furthermore, CSE induced the expression of Hrd1, a key factor of ER-associated degradation, in AECII. Knockdown of Hrd1 led to more than 2 fold increase of apoptosis, while overexpression of Hrd1 attenuated CSE induced apoptosis of AECII. CONCLUSIONS: Our results suggest that ER stress induces HRD1 to protect alveolar type II epithelial cells from apoptosis induced by CSE.

[Application of Bayes Probability Model in Differentiation of Yin and Yang Jaundice Syndromes in Neonates].

OBJECTIVE: To study the application of Bayes probability model in differentiating yin and yang jaundice syndromes in neonates. METHODS: Totally 107 jaundice neonates who admitted to hospital within 10 days after birth were assigned to two groups according to syndrome differentiation, 68 in the yang jaundice syndrome group and 39 in the yin jaundice syndrome group. Data collected for neonates were factors related to jaundice before, during and after birth. Blood routines, liver and renal functions, and myocardial enzymes were tested on the admission day or the next day. Logistic regression model and Bayes discriminating analysis were used to screen factors important for yin and yang jaundice syndrome differentiation. Finally, Bayes probability model for yin and yang jaundice syndromes was established and assessed. RESULTS: Factors important for yin and yang jaundice syndrome differentiation screened by Logistic regression model and Bayes discriminating analysis included mothers' age, mother with gestational diabetes mellitus (GDM), gestational age, asphyxia, or ABO hemolytic diseases, red blood cell distribution width (RDW-SD), platelet-large cell ratio (P-LCR), serum direct bilirubin (DBIL), alkaline phosphatase (ALP), cholinesterase (CHE). Bayes discriminating analysis was performed by SPSS to obtain Bayes discriminant function coefficient. Bayes discriminant function was established according to discriminant function coefficients. Yang jaundice syndrome: y1= -21. 701 +2. 589 x mother's age + 1. 037 x GDM-17. 175 x asphyxia + 13. 876 x gestational age + 6. 303 x ABO hemolytic disease + 2.116 x RDW-SD + 0. 831 x DBIL + 0. 012 x ALP + 1. 697 x LCR + 0. 001 x CHE; Yin jaundice syndrome: y2= -33. 511 + 2.991 x mother's age + 3.960 x GDM-12. 877 x asphyxia + 11. 848 x gestational age + 1. 820 x ABO hemolytic disease +2. 231 x RDW-SD +0. 999 x DBIL +0. 023 x ALP +1. 916 x LCR +0. 002 x CHE. Bayes discriminant function was hypothesis tested and got Wilks' λ =0. 393 (P =0. 000). So Bayes discriminant function was proved to be with statistical difference. To check Bayes probability model in discriminating yin and yang jaundice syndromes, coincidence rates for yin and yang jaundice syndromes were both 90% plus. CONCLUSION: Yin and yang jaundice syndromes in neonates could be accurately judged by Bayesian discriminating functions.

Tailoring hypervalent Nickel induced by oxygen vacancy toward enhanced oxygen evolution reaction performance in self-supporting NiFe-(oxy)hydroxides electrodes.

NiFe-(oxy)hydroxides are the most active transition metal oxide electrocatalysts for oxygen evolution reaction (OER) under the alkaline media. Herein, we controllably manipulated oxygen vacancy (VO)-tunable NiFe-(oxy) hydroxides that their OER performances possessed a volcano-type relationship with VO concentration, positively-correlated with Ni3+/Ni2+ ratio. Theoretical simulations further unearthed the enhanced activation and dissociation of H2O by the inserting of VO. As a result, the optimal sample featuring the Ni3+/Ni2+ ratio of 30.3 % and VO of 23.8 % exhibited the overpotential of 243 mV at the current density of 100 mA cm-2, simultaneously lasting 120 h durability without any attenuation, exceding the most reported NiFe-(oxy)hydroxides. This work offers an innovative view to understand the OER performance using hypervalent Ni ratio induced by VO defects.

A simplified electrochemical model for lithium-ion batteries based on ensemble learning.

The mass transfer in lithium-ion batteries is a low-frequency dynamic that affects their voltage and performance. To find an effective way to describe the mass transfer in lithium-ion batteries, a simplified electrochemical lithium-ion battery model based on ensemble learning is proposed. The proposed model simplifies lithium-ion transfer in electrode particles with ensemble learning which ensembles discrete-time realization algorithm (DRA), fractional-order Padé approximation model (FOM), and three parameters (TPM) parabolic. The lithium-ion transfer in the electrolyte is simplified by the first-order inertial element (FIE). The results show that the proposed model achieves not only accurate lithium-ion concentration prediction in solid and electrolyte phase but also precise voltage prediction with low computational complexity.

S100a8/9 (S100 Calcium Binding Protein a8/9) Promotes Cardiac Hypertrophy Via Upregulation of FGF23 (Fibroblast Growth Factor 23) in Mice.

BACKGROUND: S100a8/9 (S100 calcium binding protein a8/9) belongs to the S100 family and has gained a lot of interest as a critical regulator of inflammatory response. Our previous study found that S100a8/9 homolog promoted aortic valve sclerosis in mice with chronic kidney disease. However, the role of S100a8/9 in pressure overload-induced cardiac hypertrophy remains unclear. The present study was to explore the role of S100a8/9 in cardiac hypertrophy. METHODS AND RESULTS: Cardiomyocyte-specific S100a9 loss or gain of function was achieved using an adeno-associated virus system, and the model of cardiac hypertrophy was established by aortic banding-induced pressure overload. The results indicate that S100a8/9 expression was increased in response to pressure overload. S100a9 deficiency alleviated pressure overload-induced hypertrophic response, whereas S100a9 overexpression accelerated cardiac hypertrophy. S100a9-overexpressed mice showed increased FGF23 (fibroblast growth factor 23) expression in the hearts after exposure to pressure overload, which activated calcineurin/NFAT (nuclear factor of activated T cells) signaling in cardiac myocytes and thus promoted hypertrophic response. A specific antibody that blocks FGFR4 (FGF receptor 4) largely abolished the prohypertrophic response of S100a9 in mice. CONCLUSIONS: In conclusion, S100a8/9 promoted the development of cardiac hypertrophy in mice. Targeting S100a8/9 may be a promising therapeutic approach to treat cardiac hypertrophy.

Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization through the Creb5/NR4a1 axis.

Semaglutide, a glucagon-like peptide-1 receptor agonist, is clinically used as a glucose-lowering and weight loss medication due to its effects on energy metabolism. In heart failure, energy production is impaired due to altered mitochondrial function and increased glycolysis. However, the impact of semaglutide on cardiomyocyte metabolism under pressure overload remains unclear. Here we demonstrate that semaglutide improves cardiac function and reduces hypertrophy and fibrosis in a mouse model of pressure overload-induced heart failure. Semaglutide preserves mitochondrial structure and function under chronic stress. Metabolomics reveals that semaglutide reduces mitochondrial damage, lipid accumulation, and ATP deficiency by promoting pyruvate entry into the tricarboxylic acid cycle and increasing fatty acid oxidation. Transcriptional analysis shows that semaglutide regulates myocardial energy metabolism through the Creb5/NR4a1 axis in the PI3K/AKT pathway, reducing NR4a1 expression and its translocation to mitochondria. NR4a1 knockdown ameliorates mitochondrial dysfunction and abnormal glucose and lipid metabolism in the heart. These findings suggest that semaglutide may be a therapeutic agent for improving cardiac remodeling by modulating energy metabolism.

Photoperiodic and lighting treatments for flowering control and its genetic regulation in sugarcane breeding.

Improvement of sugarcane is hampered due to its narrow genetic base, and the difficulty in synchronizing flowering further hinders the exploitation of the genetic potential of available germplasm resources. Therefore, the continuous evaluation and optimization of flowering control and induction techniques are vital for sugarcane improvement. In view of this, the review was conducted to investigate the current understanding of photoperiodic and lighting treatment effects on sugarcane flowering and its genetic regulation. Photoperiod facilities have made a significant contribution to flowering control in sugarcane; however, inductive photoperiods are still unknown for some genotypes, and some intended crosses are still impossible to produce because of unresponsive varieties. The effectiveness of lower red/far-red ratios in promoting sugarcane flowering has been widely understood. Furthermore, there is vast potential for utilizing blue, red, and far-red light wavelengths in the flowering control of sugarcane. In this context, light-emitting diodes (LEDs) remain efficient sources of light. Therefore, the combined use of photoperiod regimes with different light wavelengths and optimization of such treatment combinations might help to control and induce flowering in sugarcane parental clones. In sugarcane, FLOWERING LOCUS T (ScFT) orthologues from ScFT1 to ScFT13 have been identified, and interestingly, ScFT3 has evidently been identified as a floral inducer in sugarcane. However, independent assessments of different FT-like gene family members are recommended to comprehensively understand their role in the regulation of flowering. Similarly, we believe this review provides substantial information that is vital for the manipulation of flowering and exploitation of germplasm resources in sugarcane breeding.

Genetic Engineering for Enhancing Sugarcane Tolerance to Biotic and Abiotic Stresses.

Sugarcane, a vital cash crop, contributes significantly to the world's sugar supply and raw materials for biofuel production, playing a significant role in the global sugar industry. However, sustainable productivity is severely hampered by biotic and abiotic stressors. Genetic engineering has been used to transfer useful genes into sugarcane plants to improve desirable traits and has emerged as a basic and applied research method to maintain growth and productivity under different adverse environmental conditions. However, the use of transgenic approaches remains contentious and requires rigorous experimental methods to address biosafety challenges. Clustered regularly interspaced short palindromic repeat (CRISPR) mediated genome editing technology is growing rapidly and may revolutionize sugarcane production. This review aims to explore innovative genetic engineering techniques and their successful application in developing sugarcane cultivars with enhanced resistance to biotic and abiotic stresses to produce superior sugarcane cultivars.

Feasibility and safety of left distal trans-radial approach for coronary angiogram and percutaneous coronary intervention in a center in Hong Kong.

INTRODUCTION: The left distal trans-radial approach is not only more convenient for the operator than the conventional left forearm radial approach, it is also more comfortable for right-hand patients during the peri-procedural period. Comparing with conventional approach, it has lower bleeding risk, less pain and lower risk of radial artery occlusion. The aim of this study was to determine the feasibility and the safety of left distal trans-radial approach for coronary angiogram and percutaneous coronary intervention in Hong Kong Chinese who had smaller body built and therefore smaller radial arterial size. METHOD: In this single-center prospective study, 72 patients undergoing elective coronary angiography and/or percutaneous coronary intervention were recruited from August to October 2018. All right-handed patients aged 18 or above undergoing elective procedures during the period were recruited. Exclusion criteria were non-palpable radial arteries, pregnancies, incapability to consent, abnormal Allen's test, and emergency procedures. Sixty patients (42 males, age ranging from 45 to 86 years old) were recruited and underwent the procedures via left distal radial approach. The measurements during access establishment, the procedure details, complications, patients' satisfaction, and arterial occlusion rate were studied. RESULTS: The procedures with left distal radial approach were successful in 51 patients (85%). Crossover rate to conventional right radial approach was 15% (nine patients). Among successful cases, the mean patients' satisfaction was 8.32/10 and the mean pain score was 1.6/10. Post-procedural radial artery occlusion was not encountered. CONCLUSION: Left distal radial approach is a feasible alternative for patients undergoing coronary angiography and/or percutaneous coronary intervention in Hong Kong Chinese patients. It provides good comfortability with minimal pain in right-handed patients. The risk of radial artery occlusion is minimal.

IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating EGR1 in male mice.

Cardiac fibrosis is a common feature of chronic heart failure. Iroquois homeobox (IRX) family of transcription factors plays important roles in heart development; however, the role of IRX2 in cardiac fibrosis has not been clarified. Here we report that IRX2 expression is significantly upregulated in the fibrotic hearts. Increased IRX2 expression is mainly derived from cardiac fibroblast (CF) during the angiotensin II (Ang II)-induced fibrotic response. Using two CF-specific Irx2-knockout mouse models, we show that deletion of Irx2 in CFs protect against pathological fibrotic remodelling and improve cardiac function in male mice. In contrast, Irx2 gain of function in CFs exaggerate fibrotic remodelling. Mechanistically, we find that IRX2 directly binds to the promoter of the early growth response factor 1 (EGR1) and subsequently initiates the transcription of several fibrosis-related genes. Our study provides evidence that IRX2 regulates the EGR1 pathway upon Ang II stimulation and drives cardiac fibrosis.

Tisp40 prevents cardiac ischemia/reperfusion injury through the hexosamine biosynthetic pathway in male mice.

The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to facilitate O-linked GlcNAc (O-GlcNAc) protein modifications, and subsequently enhance cell survival under lethal stresses. Transcript induced in spermiogenesis 40 (Tisp40) is an endoplasmic reticulum membrane-resident transcription factor and plays critical roles in cell homeostasis. Here, we show that Tisp40 expression, cleavage and nuclear accumulation are increased by cardiac ischemia/reperfusion (I/R) injury. Global Tisp40 deficiency exacerbates, whereas cardiomyocyte-restricted Tisp40 overexpression ameliorates I/R-induced oxidative stress, apoptosis and acute cardiac injury, and modulates cardiac remodeling and dysfunction following long-term observations in male mice. In addition, overexpression of nuclear Tisp40 is sufficient to attenuate cardiac I/R injury in vivo and in vitro. Mechanistic studies indicate that Tisp40 directly binds to a conserved unfolded protein response element (UPRE) of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) promoter, and subsequently potentiates HBP flux and O-GlcNAc protein modifications. Moreover, we find that I/R-induced upregulation, cleavage and nuclear accumulation of Tisp40 in the heart are mediated by endoplasmic reticulum stress. Our findings identify Tisp40 as a cardiomyocyte-enriched UPR-associated transcription factor, and targeting Tisp40 may develop effective approaches to mitigate cardiac I/R injury.

Mapping current research and identifying hotspots of ferroptosis in cardiovascular diseases.

Objective: Ferroptosis is a unique cell death depended on iron metabolism disorder which is different from previous apoptosis-regulated cell death. Early studies have proposed that ferroptosis is closely associated with multiple cardiovascular diseases (CVDs). However, the relationship of ferroptosis and CVDs has not been summarized by using bibliometric analysis. We intended to illustrate the development of ferroptosis in CVDs over the past years and provide relevant valuable information. Materials and methods: The authoritative database of Web of Science Core Collection was collected for retrieving ferroptosis studies in CVDs. In this work, statistical and visualization analysis were conducted using VOSviewer and Citespace. Results: A total of 263 studies were included in the final study. From the perspective of the overall literature, the study maintains an increased trend year by year and most manuscripts belonged to original article. China was the most productive country with the utmost scientific research output, as well as the institutions and authors, followed by Germany and the United States of America (USA). Jun Peng from China contributes to the most publications. Collaborative efforts between institutes and authors were limited and there was little widespread cooperation. In addition, burst keywords analysis discovered that ischemia-reperfusion (I/R) injury, heart failure (HF), and atherosclerosis were the top three research directions of ferroptosis in CVDs. The burst investigation and timeline views also indicated that endothelial injury and gut microbiota may also serve as new research topics in the future. Conclusion: This study provided comprehensive and specific information about the most influential articles on ferroptosis in CVDs. The relationship between ferroptosis and CVDs had attracted the scholar's concerns especially in China. Cooperations and communications between countries and institutions should be emphasized and future directions can be concentrated on endothelial disorder and gut microbiota.