Nur77 ameliorates age-related renal tubulointerstitial fibrosis by suppressing the TGF-ß/Smads signaling pathway.

Nerve growth factor-induced gene B (Nur77) has been shown to ameliorate several biological processes in chronic diseases, including inflammatory response, cellular proliferation, and metabolism. Chronic kidney disease (CKD) is characterized by tubulointerstitial fibrosis for which no targeted therapies are available as yet. In this study, we performed in vivo and in vitro experiments to demonstrate that Nur77 targets fibrosis signals and attenuates renal tubulointerstitial fibrosis during the aging process. We observed that the TGF-ß/Smads signal pathway was significantly suppressed by Nur77, suggesting that Nur77 controlled the activation of key steps in TGF-ß/Smads signaling. We further showed that Nur77 interacted with Smad7, the main repressor of nuclear translocation of Smad2/3, and stabilized Smad7 protein homeostasis. Nur77 deficiency resulted in Smad7 degradation, aggravating Smad2/3 phosphorylation, and promoting transcription of its downstream target genes, ACTA2 and collagen I. Our findings demonstrate that Nur77 is a potential therapeutic target for age-related kidney diseases including CKD. Maintenance of Nur77 may be an effective strategy for blocking renal tubulointerstitial fibrosis and improving renal function in the elderly.

Mating Disruption of Chilo suppressalis From Sex Pheromone of Another Pyralid Rice Pest Cnaphalocrocis medinalis (Lepidoptera: Pyralidae).

The rice stem borer, Chilo suppressalis (Walker), and the rice leaf folder, Cnaphalocrocis medinalis Guenée, are two of the most destructive lepidopteran pests in rice. Since these two pyralid insects overlap in their occurrence in rice paddy fields, farmers prefer to set their pheromone-baited traps together in the rice fields for their monitoring. However, our field observation demonstrated that no male adult of C. suppressalis was captured in traps baited with commercial sex pheromone of C. suppressalis (CCS) combined with commercial sex pheromone of C. medinalis (CCM). To confirm that the C. medinalis sex pheromone component(s) interfere with the attraction of males of the rice stem borers to their conspecific females, single components of C. medinalis sex pheromone combined with CCS in traps were tested in the laboratory and rice paddy field. The results revealed that the two alcohol components in CCM, i.e., (Z)-11-octadecen-1-ol (Z11-18: OH) and (Z)-13-octadecen-1-ol (Z13-18: OH) may cause a significant reduction in capturing C. suppressalis males caused by CCS. We recommend against using these sex pheromones together in the field and suggest that Z11-18: OH and Z13-18: OH could be potential inhibitors or antagonists of C. suppressalis sex pheromone to control the rice stem borer.

A Novel Microwave Treatment for Sleep Disorders and Classification of Sleep Stages Using Multi-Scale Entropy.

The aim of this study was to develop an integrated system of non-contact sleep stage detection and sleep disorder treatment for health monitoring. Hence, a method of brain activity detection based on microwave scattering technology instead of scalp electroencephalogram was developed to evaluate the sleep stage. First, microwaves at a specific frequency were used to penetrate the functional sites of the brain in patients with sleep disorders to change the firing frequency of the activated areas of the brain and analyze and evaluate statistically the effects on sleep improvement. Then, a wavelet packet algorithm was used to decompose the microwave transmission signal, the refined composite multiscale sample entropy, the refined composite multiscale fluctuation-based dispersion entropy and multivariate multiscale weighted permutation entropy were obtained as features from the wavelet packet coefficient. Finally, the mutual information-principal component analysis feature selection method was used to optimize the feature set and random forest was used to classify and evaluate the sleep stage. The results show that after four times of microwave modulation treatment, sleep efficiency improved continuously, the overall maintenance was above 80%, and the insomnia rate was reduced gradually. The overall classification accuracy of the four sleep stages was 86.4%. The results indicate that the microwaves with a certain frequency can treat sleep disorders and detect abnormal brain activity. Therefore, the microwave scattering method is of great significance in the development of a new brain disease treatment, diagnosis and clinical application system.

Effects of Winter Cover Crops on Rice Pests, Natural Enemies, and Grain Yield in a Rice Rotation System.

Rotations that include winter cover crops are widely used in agricultural systems and can provide numerous agroecological and economic benefits. However, the effects of winter cover crops on arthropod diversity, specifically rice pests and related natural enemies in rice rotation systems, are still largely unknown. We compared the effects of three winter cover crops, rapeseed, Brassica napus L. (Brassicales: Brassicaceae), Chinese milkvetch, Astragalus sinicus L. (Fabales: Fabaceae), and garlic, Allium sativum L. (Asparagales: Amaryllidaceae), on arthropods species diversity and evenness, densities of populations of major rice pests and major natural enemies, and grain yield in an experimental double cropping rotational rice field in Jiangxi Province, China. We did not observe any effects of cover crops on arthropod species diversity and evenness. The presence of prior cover crops also had no effect on the number of plants infested by the two major rice pests, Chilo suppressalis Walker (Lepidoptera: Pyralidae) and Cnaphalocrocis medinalis (Guenée) (Lepidoptera: Pyralidae). Our study did not show any effects of rapeseed and Chinese milkvetch on grain yield. However, grain yield was increased in the garlic treatment. Our results suggest that although the winter cover crops we tested in our study do not affect the number of rice plants infected by major rice pests, they do not negatively affect the arthropod community and grain yields in rice rotation systems. Therefore, planting of winter cover crops may increase agricultural land utilization and have an overall economic benefit in rice rotational systems.

[Effect of different fertilization treatments on growth,secondary metabolites,and seed yield and quality of Perilla frutescens].

Perilla frutescens,an annual plant in Labiatae family,is grown throughout China and can be used for medicine purposes and as food additives. The present field experiment was carried out to study the effects of different fertilizer treatments on the concentrations and accumulations of antioxidant components,including flavonoids and polyphenols,growth,seed yields and qualities of this plant.The main aim of this study is to provide farmers some advice for improving the yields and qualities of P. frutescens in theory and practice.Five treatments were set up,including a no fertilizer control(CK),chemical fertilizers(CF),organic fertilizers(M),organic fertilizers plus chemical fertilizers at the rates of 1 ∶1 and 1 ∶3 in terms of nitrogen(50 M,25 M). Plant growth parameters were recorded and total flavonoids and polyphenols were determined in three key growth stages of P. frutescens. At the fast growth period,samples of roots,leaves,and stems were collected for determining a total of flavonoids and polyphenols as well as DPPH removal rate of ethanol extracts. Seed yields and qualities were also recorded at harvest. The results showed fertilization enhanced growth and seed yields although no significant difference was observed in growth and seed yields in inorganic-organic fertilizer treatments. The total flavonoids,polyphenols,and DPPH removal rate of ethanol extracts followed the sequence leaves>stems>roots,indicating synthesis of these metabolites in the leaves. DPPH removal rate showed a positive linear correlation with total flavonoid and polyphenol concentrations. In addition,organic-inorganic fertilization significantly increased the numbers of both effective panicles and paniclegrains. Fertilizer treatments had no effect on seed qualities of P. frutescens,while 50 M achieved the highest yield,which increased by 14. 73% compared to CF alone. In general,50 M increased antioxidant components,biomass,and seed yield of P. frutescens,meriting advocate in cultivation.

A critical review on the sources and instruments of marine microplastics and prospects on the relevant management in China.

The world's oceans are suffering a constant and unprecedented accumulation of emerging plastic contaminants known as microplastics with a particle diameter smaller than 5mm. Microplastics exhibit a widespread distribution in various habitats from land to the oceans, and even reach the most remote regions - the deep sea and the polar, receiving attention exponentially in the past few years. Owing to their small size, marine species risk getting ingested and entangled in microplastics, causing suffocation, starvation, physical trauma or damage from chemicals, which poses vast and growing threats to biodiversity and the food web. This review article focuses on the various sources attributed to marine microplastics, the latest international, regional and national countermeasures to combat marine litter, as well as the status quo of microplastics pollution, legislation and regulations in China, and furthermore provides improving proposals/solutions on key research gaps, governance and management for future environmental control and policymaking in China.

Waste electrical and electronic equipment management and Basel Convention compliance in Brazil, Russia, India, China and South Africa (BRICS) nations.

Brazil, Russia, India, China and South Africa (BRICS) nations account for one-quarter of the world's land area, having more than 40% of the world's population, and only one-quarter of the world gross national income. Hence the study and review of waste electrical and electronic equipment management systems in BRICS nations is of relevance. It has been observed from the literature that there are studies available comparing two or three country's waste electrical and electronic equipment status, while the study encompassing the BRICS nations considering in a single framework is scant. The purpose of this study is to analyse the existing waste electrical and electronic equipment management systems and status of compliance to Basel convention in the BRICS nations, noting possible lessons from matured systems, such as those in the European Union EU) and USA. The study introduced a novel framework for a waste electrical and electronic equipment management system that may be adopted in BRICS nations and revealed that BRICS countries have many similar types of challenges. The study also identified some significant gaps with respect to the management systems and trans-boundary movement of waste electrical and electronic equipment, which may attract researchers for further research.

Clinical and laboratory features of seven patients with acute myeloid leukemia (AML)-M2/M3 and elevated myeloblasts and abnormal promyelocytes.

BACKGROUND: There is limited information on a special subtype of Acute myeloid leukemia (AML) characterized by >20% myeloblasts and >20% abnormal promyelocytes in bone marrow and peripheral blood. OBJECTIVE: The objective of the present investigation was to explore the clinical and laboratory features of seven patients with AML-M2/M3. METHOD: We retrospectively assessed cell morphology, cytochemistry, immunophenotype, cytogenetics, and clinical features of seven patients with this rare subtype of AML. RESULTS: All seven cases had thrombocytopenia, coagulation abnormalities, >20% myeloblasts and abnormal promyelocytes. The PML/RARα fusion gene was present in six patients and two patients presented a mixed PML/RARα and AML1/ETO genotype. Five cases achieved CR and two cases did not achieve remission and one case transform into AML-M2 after CR1. CONCLUSIONS: The clinical and laboratory features of seven patients with AML-M2/M3 are demonstrated in the present study, providing information on the FAB sub-classification.

Locking the lattice oxygen in RuO2 to stabilize highly active Ru sites in acidic water oxidation.

Ruthenium dioxide is presently the most active catalyst for the oxygen evolution reaction (OER) in acidic media but suffers from severe Ru dissolution resulting from the high covalency of Ru-O bonds triggering lattice oxygen oxidation. Here, we report an interstitial silicon-doping strategy to stabilize the highly active Ru sites of RuO2 while suppressing lattice oxygen oxidation. The representative Si-RuO2-0.1 catalyst exhibits high activity and stability in acid with a negligible degradation rate of ~52 µV h-1 in an 800 h test and an overpotential of 226 mV at 10 mA cm-2. Differential electrochemical mass spectrometry (DEMS) results demonstrate that the lattice oxygen oxidation pathway of the Si-RuO2-0.1 was suppressed by ∼95% compared to that of commercial RuO2, which is highly responsible for the extraordinary stability. This work supplied a unique mentality to guide future developments on Ru-based oxide catalysts' stability in an acidic environment.

Adipose-derived miRNAs as potential biomarkers for predicting adulthood obesity and its complications: A systematic review and bioinformatic analysis.

Adipose tissue is the first and primary target organ of obesity and the main source of circulating miRNAs in patients with obesity. This systematic review aimed to analyze and summarize the generation and mechanisms of adipose-derived miRNAs and their role as early predictors of various obesity-related complications. Literature searches in the PubMed and Web of Science databases using terms related to miRNAs, obesity, and adipose tissue. Pre-miRNAs from the Human MicroRNA Disease Database, known to regulate obesity-related metabolic disorders, were combined for intersection processing. Validated miRNA targets were sorted through literature review, and enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes via the KOBAS online tool, disease analysis, and miRNA transcription factor prediction using the TransmiR v. 2.0 database were also performed. Thirty miRNAs were identified using both obesity and adipose secretion as criteria. Seventy-nine functionally validated targets associated with 30 comorbidities of these miRNAs were identified, implicating pathways such as autophagy, p53 pathways, and inflammation. The miRNA precursors were analyzed to predict their transcription factors and explore their biosynthesis mechanisms. Our findings offer potential insights into the epigenetic changes related to adipose-driven obesity-related comorbidities.

Dysfunction of Akt/FoxO3a/Atg7 regulatory loop magnifies obesity-regulated muscular mass decline.

BACKGROUND: Myoprotein degradation accelerates in obese individuals, resulting in a decline in muscular mass. Atg7 plays a crucial role in regulating protein stability and function through both autophagy-dependent and independent pathways. As obesity progresses, the expression of Atg7 gradually rises in muscle tissue. Nonetheless, the precise impact and mechanism of Atg7 in promoting muscle mass decline in obesity remain uncertain. The study aimed to elucidate the role and underly mechanism of Atg7 action in the context of obesity-induced muscle mass decline. METHODS: In this study, we established a murine model of high-fat diet-induced obesity (DIO) and introduced adeno-associated virus delivery of short hairpin RNA to knock down Atg7 (shAtg7) into the gastrocnemius muscle. We then examined the expressions of Atg7 and myoprotein degradation markers in the gastrocnemius tissues of obese patients and mice using immunofluorescence and western blotting techniques. To further investigate the effects of Atg7, we assessed skeletal muscle cell diameter and the myoprotein degradation pathway in C2C12 and HSkMC cells in the presence or absence of Atg7. Immunofluorescence staining for MyHC and western blotting were utilized for this purpose. To understand the transcriptional regulation of Atg7 in response to myoprotein degradation, we conducted luciferase reporter assays and chromatin immunoprecipitation experiments to examine whether FoxO3a enhances the transcription of Atg7. Moreover, we explored the role of Akt in Atg7-mediated regulation and its relevance to obesity-induced muscle mass decline. This was accomplished by Akt knockdown, treatment with MK2206, and GST pulldown assays to assess the interaction between Atg7 and Akt. RESULTS: After 20 weeks of being on a high-fat diet, obesity was induced, leading to a significant decrease in the gastrocnemius muscle area and a decline in muscle performance. This was accompanied by a notable increase in Atg7 protein expression (p < 0.01). Similarly, in gastrocnemius tissues of obese patients when compared to nonobese individuals, there was a significant increase in both Atg7 (p < 0.01) and TRIM63 (p < 0.01) levels. When palmitic acid was administered to C2C12 cells, it resulted in increased Atg7 (p < 0.01), LC3Ⅱ/Ⅰ (p < 0.01), and p62 levels (p < 0.01). Additionally, it promoted FoxO3a-mediated transcription of Atg7. The knockdown of Atg7 in the gastrocnemius partially reversed DIO-induced muscle mass decline. Furthermore, when Atg7 was knocked down in C2C12 and HSkMC cells, it mitigated palmitic acid-induced insulin resistance, increased the p-Akt/Akt ratio (p < 0.01), and reduced TRIM63 (p < 0.01). Muscular atrophy mediated by Atg7 was reversed by genetic knockdown of Akt and treatment with the p-Akt inhibitor MK2206. Palmitic acid administration increased the binding between Atg7 and Akt (p < 0.01) while weakening the binding of PDK1 (p < 0.01) and PDK2 (p < 0.01) to Akt. GST pulldown assays demonstrated that Atg7 directly interacted with the C-terminal domain of Akt. CONCLUSION: The consumption of a high-fat diet, along with lipid-induced effects, led to the inhibition of Akt signaling, which, in turn, promoted FoxO3a-mediated transcription, increasing Atg7 levels in muscle cells. The excess Atg7 inhibited the phosphorylation of Akt, leading to a cyclic activation of FoxO3a and exacerbating the decline in muscle mass regulated by obesity. Consequently, Atg7 serves as a regulatory point in determining the decline in muscle mass induced by obesity.

The phosphorylation-deubiquitination positive feedback loop of the CHK2-USP7 axis stabilizes p53 under oxidative stress.

p53 regulates multiple signaling pathways and maintains cell homeostasis under conditions of DNA damage and oxidative stress. Although USP7 has been shown to promote p53 stability via deubiquitination, the USP7-p53 activation mechanism has remained unclear. Here, we propose that DNA damage induces reactive oxygen species (ROS) production and activates ATM-CHK2, and CHK2 then phosphorylates USP7 at S168 and T231. USP7 phosphorylation is essential for its deubiquitination activity toward p53. USP7 also deubiquitinates CHK2 at K119 and K131, increasing CHK2 stability and creating a positive feedback loop between CHK2 and USP7. Compared to peri-tumor tissues, thyroid cancer and colon cancer tissues show higher CHK2 and phosphorylated USP7 (S168, T231) levels, and these levels are positively correlated. Collectively, our results uncover a phosphorylation-deubiquitination positive feedback loop involving the CHK2-USP7 axis that supports the stabilization of p53 and the maintenance of cell homeostasis.

Correlation of serum levels of LH, IGF-1 and leptin in girls with the development of idiopathic central precocious puberty.

BACKGROUND: This paper aims to investigate the correlation between serum levels of luteinizing hormone (LH), insulin-like growth factor-1 (IGF-1) and leptin and the incidence of idiopathic central precocious puberty (ICPP) in girls, and to explore the clinical values in the diagnosis of ICPP. METHODS: A total of 48 girls with ICPP were selected in our hospital from March 2014 to March 2015 to serve as ICPP group. At the same time, 48 girls with the same age distribution were selected as control group. Bone age, body weight, Body Mass Index (BMI) and gender development index of girls in each group were recorded. Levels of LH, IGF-1 and leptin in serum were measured by chemiluminescence immunoassay. The correlations within levels of LH, IGF-1 and leptin, and the correlations between levels of LH, IGF-1 and leptin and body height, body weight and gender development index were analyzed. RESULTS: Levels of LH, IGF-1 and leptin in ICPP group were significantly higher than those in control group (P<0.01). Body weight and BMI of ICPP group were significantly higher than those of control group (P<0.01), and were positively correlated with the expression level of leptin; ovarian volume and thickness of breast of ICPP group were significantly higher than those of control group (P<0.01), and were positively correlated with serum level of LH; serum level of IGF-1 was positively correlated with bone age. Levels of LH, IGF-1 and leptin in serum of ICPP girls were all increased compared with control group. CONCLUSIONS: LH peak value and levels of IGF-1 and leptin in serum can be used as diagnostic indexes of ICPP.

Novel resorbable bone wax containing ß-TCP and starch microspheres for accelerating bone hemostasis and promoting regeneration.

Traditional non-resorbable bone wax has been used in clinical surgery for more than 100 years. However, residual bone wax has been proven to cause numerous complications. In this study, a novel resorbable bone wax was designed to overcome the disadvantages of traditional non-resorbable bone wax. Alkylene oxide copolymers were used as the main component of resorbable bone wax; additionally, ß-tricalcium phosphate and starch microspheres were added to enhance bone regeneration and hemostatic ability. This novel resorbable bone wax has a high potential for clinical translation and is expected to be developed as a substitute for traditional bone wax.

HCN-induced embryo arrest: passion fruit as an ecological trap for fruit flies.

BACKGROUND: Fruit flies are important economic pests of fruits, vegetables, and nuts all over the world. In this study, a permanent ecological trap, which was created by the ovicidal effect of phytogenic hydrogen cyanide (HCN) liberated from passion fruits due to oviposition by fruit flies and can be used in the pest management, were determined. RESULTS: Observation of fruit fly eggs in Passiflora within the passion fruit cultivation region in southern China, from Aug 2019 to Oct 2020 showed that the exotic Passiflora attracted the native fruit flies to oviposit, but the eggs could not hatch. Using classical staging to categorize embryonic development and fumigation assays, we show that oviposition by fruit fly on passion fruits, release HCN from the cyanogenic mesocarp. Exposure of the eggs to HCN causes arrest of embryonic development and finally the death of eggs. CONCLUSION: Our results reveal that the life cycle of fruit fly in Passiflora is interrupted at the egg stage. Consequently, we predict that this ecological trap may be permanent. Extensive cultivation of the Passiflora vine as a dead-end trap crop may be an effective avenue to reduce populations of fruit fly pests. © 2023 Society of Chemical Industry.

A DUSP6 inhibitor suppresses inflammatory cardiac remodeling and improves heart function after myocardial infarction.

Acute myocardial infarction (MI) results in loss of cardiomyocytes and abnormal cardiac remodeling with severe inflammation and fibrosis. However, how cardiac repair can be achieved by timely resolution of inflammation and cardiac fibrosis remains incompletely understood. Our previous findings have shown that dual-specificity phosphatase 6 (DUSP6) is a regeneration repressor from zebrafish to rats. In this study, we found that intravenous administration of the DUSP6 inhibitor (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI) improved heart function and reduced cardiac fibrosis in MI rats. Mechanistic analysis revealed that BCI attenuated macrophage inflammation through NF-κB and p38 signaling, independent of DUSP6 inhibition, leading to the downregulation of various cytokines and chemokines. In addition, BCI suppressed differentiation-related signaling pathways and decreased bone-marrow cell differentiation into macrophages through inhibiting DUSP6. Furthermore, intramyocardial injection of poly (D, L-lactic-co-glycolic acid)-loaded BCI after MI had a notable effect on cardiac repair. In summary, BCI improves heart function and reduces abnormal cardiac remodeling by inhibiting macrophage formation and inflammation post-MI, thus providing a promising pro-drug candidate for the treatment of MI and related heart diseases. This article has an associated First Person interview with the first author of the paper.

Chemical screening links disulfiram with cardiac protection after ischemic injury.

Ischemia-reperfusion injury occurs after reperfusion treatment for patients suffering myocardial infarction, however the underlying mechanisms are incompletely understood and effective pharmacological interventions are limited. Here, we report the identification and characterization of the FDA-approved drug disulfiram (DSF) as a cardioprotective compound. By applying high-throughput chemical screening, we found that DSF decreased H2O2-induced cardiomyocyte death by inhibiting Gasdermin D, but not ALDH1, in cardiomyocytes. Oral gavage of DSF decreased myocardial infarct size and improved heart function after myocardial ischemia-reperfusion injury in rats. Therefore, this work reveals DSF as a potential therapeutic compound for the treatment of ischemic heart disease.

Oxidative stress impairs the Nur77-Sirt1 axis resulting in a decline in organism homeostasis during aging.

Sirt1 is an NAD+ -dependent deacetylase that protects against premature aging and cell senescence. Aging accompanied by oxidative stress leads to a decrease in Sirt1 levels and activity, but the regulatory mechanism that connects these events remains unclear. Here, we reported that Nur77, which shares similar biological pathways with Sirt1, was also decreased with age in multiple organs. Our in vivo and in vitro results revealed that Nur77 and Sirt1 decreased during aging and oxidative stress-induced cell senescence. Deletion of Nr4a1 shortened the lifespan and accelerated the aging process in multiple mouse tissues. Overexpression of Nr4a1 protected the Sirt1 protein from proteasomal degradation through negative transcriptional regulation of the E3 ligase MDM2. Our results showed that Nur77 deficiency markedly aggravated aging-related nephropathy and elucidated a key role for Nur77 in the stabilization of Sirt1 homeostasis during renal aging. We proposed a model wherein a reduction of Nur77 in response to oxidative stress promotes Sirt1 protein degradation through MDM2, which triggers cell senescence. This creates additional oxidative stress and provides positive feedback for premature aging by further decreasing Nur77 expression. Our findings reveal the mechanism by which oxidative stress reduces Sirt1 expression during aging and offers an attractive therapeutic strategy for targeting aging and homeostasis in organisms.

Immediate early response 3 gene promotes aggressive progression and autophagy of AML by negatively regulating AKT/mTOR.

BACKGROUND: Immediate early response 3 (IER3) plays a vital role in many tumors. This study aims to explore the function and mechanism of IER3 in Acute myeloid leukemia (AML). METHODS: The expression of IER3 in AML was performed by bioinformatics analysis. CCK-8 proliferation assay, flow cytometry cycle assay, clone formation assay, and tumorigenic ability were used to investigate the effect of IER3 on AML cells. Unbiased label-free quantitative proteomics and label-free quantitative phosphoproteomics analysis were performed. The regulatory relationship between SATB1(Special AT-rich sequence binding protein 1) and IER3 was investigated by Real time-PCR, Western blot, Chromatin immunoprecipitation (CHIP), and PCR. RESULTS: The result indicated that the prognosis of the high IER3 expression group was significantly worse than that of the low expression group. CCK-8 assay showed that IER3 enhanced the proliferation ability. Cell cycle analysis showed IER3 could promote HL60 cells to enter the S phase of DNA synthesis from the quiescent phase. IER3 could stimulate HEL cells to enter mitosis. Clone-formation experiments suggested that IER3 enhanced clonogenic ability.IER3 promoted the tumorigenesis of AML. Further experimental investigation revealed that IER3 promoted autophagy and induced the occurrence and development of AML by negatively regulating the phosphorylation activation of AKT/mTOR pathway. SATB1 was found to bind to the promoter region of IER3 gene and negatively regulate its transcription. CONCLUSION: IER3 could promote the development of AML and induce autophagy of AML cells by negatively regulating the phosphorylation and activation of AKT/mTOR. By the way, SATB1 may negatively target regulates IER3 transcription.

ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initiate autophagy under oxidative stress.

Oxidative stress-induced autophagy helps to prevent cellular damage and to maintain homeostasis. However, the regulatory pathway that initiates autophagy remains unclear. We previously showed that reactive oxygen species (ROS) function as signaling molecules to activate the ATM-CHK2 pathway and promote autophagy. Here, we find that the E3 ubiquitin ligase TRIM32 functions downstream of ATM-CHK2 to regulate ATG7 ubiquitination. Under metabolic stress, ROS induce ATM phosphorylation at S1981, which in turn phosphorylates CHK2 at T68. We show that CHK2 binds and phosphorylates TRIM32 at the S55 site, which then mediates K63-linked ubiquitination of ATG7 at the K45 site to initiate autophagy. In addition, Chk2-/- mice show an aggravated infarction phenotype and reduced phosphorylation of TRIM32 and ubiquitination of ATG7 in a stroke model. We propose a molecular mechanism for autophagy initiation by ROS via the ATM-CHK2-TRIM32-ATG7 axis to maintain intracellular homeostasis and to protect cells exposed to pathological conditions from stress-induced tissue damage.