Monitoring dynamics of Kyagar Glacier surge and repeated draining of Ice-dammed lake using multi-source remote sensing.

Glacier surges, a primary factor contributing to various glacial hazards, has long captivated the attention of the global glaciological community. This study delves into the dynamics of Kyagar Glacier surging and the associated drainage features of its Ice-dammed lake, employing high temporal resolution optical imagery. Our findings indicate that the surge on Kyagar Glacier began in late spring and early summer of 2014 and concluded during the summer of 2016. This surge resulted in the transfer of 0.321 ± 0.012 km3 of glacier mass from the reservoir zone to the receiving zone, leading to the formation of an ice-dammed lake at the glacier's terminus. The lake experienced five outbursts between 2015 and 2019, with the largest discharge occurring in 2017. And the maximum water depth during this period was 112 ± 11 m, resulting in a water storage volume of (158.37 ± 28.32) × 106 m3. On the other hand, our analysis of the relationship between glacier surface velocity and albedo, coupled with an examination of subglacial dynamics, revealed that increased precipitation during the active phase of the Kyagar Glacier results in accumulation of mass in the upper glacier. This accumulation induces changes in basal shear stress, triggering the glacier's transition into an unstable state. Consequently, glacier deformation rates escalate, surface crevasses proliferate, potentially providing conduits for surface meltwater to infiltrate the glacier bed. This, in turn, leaded to elevated basal water pressure, initiating glacier sliding. Furthermore, we postulated that the repetitive drainage of Kyagar Ice-dammed lake was primarily influenced by the opening and closing of subglacial drainage pathways and variations in inflow volumes. Future endeavors necessitate rigorous field observations to enhance glacier surge simulations, deepening our comprehension of glacier surge mechanisms and mitigating the impact of associated glacial hazards.

Teadenol B as a Component of Microorganism-Fermented Tea Extract Inhibited Breast Cancers by Promoting Autophagy.

Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B's anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.

Corrigendum: Cardiovascular risk according to body mass index in reproductive-aged women with polycystic ovary syndrome: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fcvm.2022.822079.].

Corrigendum: Research on the mechanism and prevention of hypertension caused by apatinib through the RhoA/ROCK signaling pathway in a mouse model of gastric cancer.

[This corrects the article DOI: 10.3389/fcvm.2022.873829.].

Research on the Mechanism and Prevention of Hypertension Caused by Apatinib Through the RhoA/ROCK Signaling Pathway in a Mouse Model of Gastric Cancer.

Hypertension is one of the main adverse effects of antiangiogenic tumor drugs and thus limits their application. The mechanism of hypertension caused by tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factors is mainly related to inhibition of the nitric oxide (NO) pathway and activation of the endothelin pathway, as well as vascular rarefaction and increased salt sensitivity; consequently, prevention and treatment differ for this type of hypertension compared with primary hypertension. Apatinib is a highly selective TKI approved in China for the treatment of advanced or metastatic gastric cancer. The RhoA/ROCK pathway is involved in the pathogenesis of hypertension and mediates smooth muscle contraction, eNOS inhibition, endothelial dysfunction and vascular remodeling. In this study, in vivo experiments were performed to explore whether the RhoA/ROCK signaling pathway is part of a possible mechanism of apatinib in the treatment of gastric cancer-induced hypertension and the impairment of vascular remodeling and left ventricular function. Y27632, a selective small inhibitor of both ROCK1 and ROCK2, was combined with apatinib, and its efficacy was evaluated, wherein it can reduce hypertension induced by apatinib treatment in gastric cancer mice and weaken the activation of the RhoA/ROCK pathway by apatinib and a high-salt diet (HSD). Furthermore, Y-27632 improved aortic remodeling, fibrosis, endothelial dysfunction, superior mesenteric artery endothelial injury, left ventricular dysfunction and cardiac fibrosis in mice by weakening the activation of the RhoA/ROCK pathway. The expression of RhoA/ROCK pathway-related proteins and relative mRNA levels in mice after apatinib intervention were analyzed by various methods, and blood pressure and cardiac function indexes were compared. Endothelial and cardiac function and collagen levels in the aorta were also measured to assess vascular and cardiac fibrosis and to provide a basis for the prevention and treatment of this type of hypertension.

Apatinib Through Activating the RhoA/ROCK Signaling Pathway to Cause Dysfunction of Vascular Smooth Muscle Cells.

Vascular smooth muscle cells (VSMCs) are associated with differentiated, organized, and contractile phenotype under the effect of various types of physiological conditions those are associated with migratory, proliferative, and synthetic phenotype under the effect of various types of stimuli, which dysfunction drives many cardiovascular diseases. Abnormal cell proliferation and invasion of VSMCs are among the primary causes of hypertension. Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) that highly selectively binds to and strongly inhibits VEGFR-2. Previous studies have confirmed that the TKIs can raise blood pressure through RhoA/ROCK pathway. LARG is a key gene in the RhoA/ROCK pathway and plays a critical role in the continuous vasoconstriction function because it regulates part of signal transduction in VSMCs. In this study, an in vitro experiment was conducted to observe that apatinib caused dysfunction of MOVAS cells through the RhoA/ROCK signalling pathway and Y27632, a nonspecific ROCK inhibitor, and knockout of LARG gene can improve the proliferation, antiapoptosis, oxidative stress, and mitochondrial autophagy of apatinib-induced MOVAS cells. These findings suggest that activation of the RhoA/ROCK signalling pathway could be the underlying mechanism of apatinib-induced dysfunction of MOVAS cells, while ROCK inhibitor and knockout of LARG gene have potential therapeutic value.

Glucose Fluctuations Aggravate Myocardial Fibrosis via the Nuclear Factor-κB-Mediated Nucleotide-Binding Oligomerization Domain-Like Receptor Protein 3 Inflammasome Activation.

Background: Glucose fluctuations may be associated with myocardial fibrosis. This study aimed to investigate the underlying mechanisms of glucose fluctuation-related myocardial fibrosis. Methods: Streptozotocin (STZ)-injected type 1 diabetic rats were randomized to five groups: the controlled blood glucose (CBG) group, uncontrolled blood glucose (UBG) group, fluctuated blood glucose (FBG) group, FBG rats injected with 0.9% sodium chloride (NaCl) (FBG + NaCl) group, and FBG rats injected with MCC950 (FBG + MCC950) group. Eight weeks later, left ventricular function was evaluated by echocardiography and myocardial fibrosis was observed by Masson trichrome staining. The primary neonatal rat cardiac fibroblasts were cultured with different concentrations of glucose in vitro. Results: The left ventricular function was impaired and myocardial fibrosis was aggravated most significantly in the FBG group compared with the CBG and UBG groups. The levels of interleukin (IL)-1ß, IL-18, transforming growth factor-ß1 (TGF-ß1), collagen type 1 (collagen I), nuclear factor (NF)-κB, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome were significantly increased in the FBG group. In vitro, the inhibition of NF-κB and inflammasome reversed these effects. In vivo, NLRP3 inhibition with MCC950 reversed left ventricular systolic dysfunction and myocardial fibrosis induced by glucose fluctuations. Conclusion: Glucose fluctuations promote diabetic myocardial fibrosis by the NF-κB-mediated inflammasome activation.

PTEN inhibitor attenuates cardiac fibrosis by regulating the M2 macrophage phenotype via the PI3K/AKT/TGF-ß/Smad 2/3 signaling pathway.

Cardiac fibrosis is a key feature of hypertensive cardiac remodeling. In response to microenvironmental stimuli, phenotypic and functional changes in macrophages are considered important determinants of cardiac fibrosis attenuation. VO-OHpic, a phosphatase and tension homolog of chromosome 10 (PTEN) inhibitor, has been demonstrated to be cardioprotective in cardiac remodeling. However, whether VO-OHpic can improve cardiac fibrosis and macrophage polarization remains elusive. The interaction between VO-OHpic and the macrophage phenotype to attenuate cardiac fibrosis was studied in both spontaneously hypertensive rats in vivo and an Ang II-induced hypertension model in vitro. In vitro experiments showed that VO-OHpic promoted M2 macrophage polarization and markedly inhibited proinflammatory M1 macrophages, while VO-OHpic treatment of protein kinase B (AKT)-knockdown/LY294002 (a PI3K inhibitor) macrophages exerted a reduced effect. In a coculture system, culturing cardiac fibroblasts with VO-OHpic-treated macrophages led to significant suppression of proliferation, fibrotic marker expression, and transforming growth factor (TGF)-ß and Smad 2/3 protein expression. Taken together, VO-OHpic mediated a fibro-protective effect and increased M2 macrophage polarization via the phosphatidylinositol 3-kinase (PI3K)/AKT/TGF-ß/Smad2/3 pathway.

Sacubitril/Valsartan Improves Sexual Function and Fibrosis of the Clitoral and Vaginal Tissues in Female Spontaneously Hypertensive Rats.

ABSTRACT: Female sexual dysfunction is common in hypertension. The effects of sacubitril/valsartan (SAC/VAL) as a potential therapy for hypertension and heart failure have not been studied in relation to sexual function and genital fibrosis in female spontaneously hypertensive rats (SHRs). Thirty female SHRs were administered VAL, SAC/VAL, or saline. Ten normotensive female Wistar-Kyoto (WKY) rats were included in the control group. We assessed estrous cyclicity and sexual behavior in the female rats. In addition, the morphology of clitoral and vaginal tissues was evaluated by histological analyses. Western blotting and enzyme-linked immunosorbent assays were used to assess the levels of fibrotic markers in vaginal and clitoral tissues. Furthermore, the protein levels of phosphatase and tensin homolog deleted from chromosome 10 (PTEN), phosphoinositide-3-kinase (PI3K), and AKT expression were measured by Western blotting. SAC/VAL treatment improved hypertension-induced sexual dysfunction, exhibited as a prolonged estrus phase, increased receptivity and proceptive events, and decreased aggressive events, compared with those of VAL treatment and control SHRs without treatments. In addition, SAC/VAL-treated SHRs had lower levels of fibrotic markers, estradiol, and estrogen receptor α/ß than the levels of VAL-treated SHRs or SHRs without treatment. Moreover, SAC/VAL decreased p-PTEN expression and increased p-PI3K and p-AKT expression at the protein level compared with those in VAL treatment alone. VAL and SAC/VAL treatments have significantly increased sexual receptivity and proceptivity, decreased aggressiveness, and improved the fibrosis of vaginal and clitoral tissues in female SHRs. However, SAC/VAL treatment shows more effective results compared with VAL treatment, which may be related to the PTEN/PI3K/AKT pathway.

Cardiovascular Risk According to Body Mass Index in Women of Reproductive Age With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous condition that affects women of reproductive age. The association between PCOS and cardiovascular risk according to body mass index (BMI) categories is unclear. OBJECTIVE: We evaluated the association between cardiovascular risk according to BMI categories and PCOS in women of reproductive age. METHODS: A literature search was conducted in the EMBASE, MEDLINE, Cochrane Library, and PubMed databases from their inception to 9 September, 2021. Observational cross-sectional, retrospective, and prospective controlled studies were included. The main analyses examined the relationship between cardiovascular risks (i.e., blood pressure and lipid levels) and BMI in women of reproductive age with PCOS. RESULTS: Thirty-eight studies, with a total of 6,078 subjects, were included in this metaanalysis. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in women of reproductive age with PCOS. Lower high-density lipoprotein (HDL)-cholesterol [SMD (95% CI): -0.21 (-0.35, -0.08), p = 0.002], higher triglycerides [SMD (95% CI): 0.38 (0.29, 0.48), p < 0.001], higher low-density lipoprotein (LDL)-cholesterol [SMD (95% CI): 0.29 (0.20, 0.39), p < 0.001], higher nonHDL-cholesterol [SMD (95% CI): 0.42 (0.31, 0.52), p < 0.001] and waist-to-hip ratio (WHR) [MD (95% CI): 0.03 (0.02, 0.04), p < 0.001] were seen in women of reproductive age with PCOS. In addition, the subgroup analysis revealed that systolic BP and HDL-cholesterol increased at BMI < 25 kg/m2 and BMI 25-30 kg/m2. Diastolic BP increased at BMI 25-30 kg/m2. Triglycerides, LDL-cholesterol, nonHDL-cholesterol, and WHR increased in all BMI categories. CONCLUSIONS: PCOS is associated with cardiovascular risk. Lipid levels and BP increased in women of reproductive age with PCOS, regardless of BMI. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework (10.17605/OSF.IO/92NBY).

Berberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 1.

G protein-coupled estrogen receptor 1 (GPER1) is a potential therapeutic target for treating triple-negative breast cancers (TNBC). However, modulators for GPER1 that can be used to treat TNBC have not appeared. Berberine (BBR) is a bioactive isoquinoline alkaloid with high oral safety. In recent years, BBR has shown an inhibitory effect on TNBC tumors such as MDA-MB-231, but the molecular target remains unclear, which hinders related clinical research. Our work proved that BBR is a modulator of GPER1 that can inhibit cell viability, migration, and autophagy of MDA-MB-231 cells. The inhibitory effect of BBR on MDA-MB-231 cells has a dependence on estrogen levels. Although BBR promoted the proteasome, which is a major factor in the degradation of GPER1, it could still induce the protein level of GPER1. Correspondingly, the transcription of cellular communication network factor 2 (CCN2) was promoted. BBR could bind to GPER1 directly and change the secondary structure of GPER1, as in the case of 17ß-estradiol (E2). In addition, BBR induced not only a high degree of co-localization of GPER1 and microtubule-associated protein 1 light chain 3 (MAP1LC3), but also the accumulation of sequestosome 1 (SQSTM1/p62) by the inhibition of the nuclear translocation of the nuclear factor-kappa B (NF-κB) subunit (RELA/p65), which indicates NF-κB inhibition and anti-cancer effects. This result proved that the promotional effect of BBR on the GPER1/NF-κB pathway was closely related to its inhibitory effect on autophagy, which may serve as a new mechanism by which to explain the inhibitory effect of BBR on MDA-MB-231 cells and expand our understanding of the function of both BBR and GPER1.

Peripheral Artery Disease on The Prognosis Value of Patients with Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: A Retrospective, Single-Center Cohort Study.

OBJECTIVE: The purpose of this investigation aimed to clarify the impact of peripheral artery disease (PAD) on the prognosis value of patients with stable coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). METHODS: The SPSS 16 software was used for secondary analysis of DRYAD database data. A total of 204 patients were enrolled from Shinonoi General Hospital for newly diagnosed stable CAD and received PCI performance between October 2014 and October 2017. Patients with old myocardial infarction (MI) were excluded. We divided patients into two groups with PAD and without PAD. The primary endpoints were major adverse cardiac events (MACE, defined as all-cause death, non-fatal MI, and non-fatal stroke) and cardiovascular events (defined as cardiovascular death, non-fatal MI, and non-fatal stroke). The secondary outcomes were the individual components of the composite primary outcomes. The median follow-up time was 783 days. RESULTS: No statistical difference was found between PAD and non-PAD patients of lesional characteristics. Spearman's rank correlations indicate diabetes mellitus (DM) (P = 0.019) and HbA1c (P = 0.009) are positively correlated with PAD. In Kaplan-Meier analysis, patients with PAD predicted poor prognosis in MACE (P < 0.05) and cardiovascular events (P < 0.05). In Multivariable Cox proportional hazards analysis, patients with PAD independently predicted MACE and cardiovascular events. CONCLUSIONS: PAD is a significant mediator for the prognosis of patients with stable CAD who underwent PCI treatment.

Overview of terrestrial water storage changes over the Indus River Basin based on GRACE/GRACE-FO solutions.

Water resources are under severe stress in the highly populated Indus River Basin due to the increased consumption of water across different sectors and climate change. Coping with these challenges, requires a clear understanding on hydrological processes and anthropogenic activities, and how these are influencing recharging and spatiotemporal availability of groundwater in the basin. The present study aims to investigate the natural and anthropogenic impact on Terrestrial Water Storage (TWS) over the Indus River Basin by using a series of statistical methods and the observation data from the Gravity Recovery and Climate Experiment (GRACE) and Follow-On (GRACE-FO). Our results show that (i) TWS Anomaly (TWSA) experienced a significant decrease from 2002 to 2020, particularly in the MUIP; (ii) the UIB showed a weak decreasing trend in TWSA as a result of the accelerated glacier melting; (iii) there was significant loss of groundwater (1.57 mm/month) caused by ineffective water management and over-exploitation; and (iv) assisted by favorable meteorological conditions, the precipitation presented a positive trend against the weakness of the Westerlies, which exerted the positive influence on TWSA.

The Mechanism of Dehydrating Bimodules in trans-Acyltransferase Polyketide Biosynthesis: A Showcase Study on Hepatoprotective Hangtaimycin.

A bioassay-guided fractionation led to the isolation of hangtaimycin (HTM) from Streptomyces spectabilis CCTCC M2017417 and the discovery of its hepatoprotective properties. Structure elucidation by NMR suggested the need for a structural revision. A putative HTM degradation product was also isolated and its structure was confirmed by total synthesis. The biosynthetic gene cluster was identified and resembles a hybrid trans-AT PKS/NRPS biosynthetic machinery whose first PKS enzyme contains an internal dehydrating bimodule, which is usually found split in other trans-AT PKSs. The mechanisms of such dehydrating bimodules have often been proposed, but have never been deeply investigated. Here we present in vivo mutations and in vitro enzymatic experiments that give first and detailed mechanistic insights into catalysis by dehydrating bimodules.

Modulation of SK Channels: Insight Into Therapeutics of Atrial Fibrillation.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in the world. Although much technological progress in the treatment of AF has been made, there is an urgent need for better treatment of AF due to its high rates of morbidity and mortality. The anti-arrhythmic drugs currently approved for marketing have significant limitations and side effects such as life-threatening ventricular arrhythmias and hypotension. The small conductance Ca2+-activated K+ channels (SK channels) are dependent on intracellular Ca2+ concentrations, which tightly integrate with membrane potential. Given the predominant expression in the atria of many species, including humans, they are now emerging as a therapeutic target for treating AF. This review aimed to illustrate the characteristics and function of SK channels. Moreover, it discussed the regulation of SK channels and their potential as a therapeutic target of AF.

Microbiota-Meditated Immunity Abnormalities Facilitate Hepatitis B Virus Co-Infection in People Living With HIV: A Review.

Hepatitis B virus (HBV) co-infection is fairly common in people living with HIV (PLWH) and affects millions of people worldwide. Identical transmission routes and HIV-induced immune suppression have been assumed to be the main factors contributing to this phenomenon. Moreover, convergent evidence has shown that people co-infected with HIV and HBV are more likely to have long-term serious medical problems, suffer more from liver-related diseases, and have higher mortality rates, compared to individuals infected exclusively by either HIV or HBV. However, the precise mechanisms underlying the comorbid infection of HIV and HBV have not been fully elucidated. In recent times, the human gastrointestinal microbiome is progressively being recognized as playing a pivotal role in modulating immune function, and is likely to also contribute significantly to critical processes involving systemic inflammation. Both antiretroviral therapy (ART)-naïve HIV-infected subjects and ART-treated individuals are now known to be characterized by having gut microbiomic dysbiosis, which is associated with a damaged intestinal barrier, impaired mucosal immunological functioning, increased microbial translocation, and long-term immune activation. Altered microbiota-related products in PLWH, such as lipopolysaccharide (LPS) and short-chain fatty acids (SCFA), have been associated with the development of leaky gut syndrome, favoring microbial translocation, which in turn has been associated with a chronically activated underlying host immune response and hence the facilitated pathogenesis of HBV infection. Herein, we critically review the interplay among gut microbiota, immunity, and HIV and HBV infection, thus laying down the groundwork with respect to the future development of effective strategies to efficiently restore normally diversified gut microbiota in PLWH with a dysregulated gut microbiome, and thus potentially reduce the prevalence of HBV infection in this population.

Molecular Mechanisms of Glucose Fluctuations on Diabetic Complications.

Accumulating evidence indicates the occurrence and development of diabetic complications relates to not only constant high plasma glucose, but also glucose fluctuations which affect various kinds of molecular mechanisms in various target cells and tissues. In this review, we detail reactive oxygen species and their potentially damaging effects upon glucose fluctuations and resultant downstream regulation of protein signaling pathways, including protein kinase C, protein kinase B, nuclear factor-κB, and the mitogen-activated protein kinase signaling pathway. A deeper understanding of glucose-fluctuation-related molecular mechanisms in the development of diabetic complications may enable more potential target therapies in future.

Self-Limited Nanosoldering of Silver Nanowires for High-Performance Flexible Transparent Heaters.

Silver nanowires (Ag NWs) are key materials to fabricate next-generation flexible transparent electrodes (FTEs). Currently, the applications of Ag NWs are impeded by the large wire-wire contact resistance. Herein, a self-limited nanosoldering method is proposed to reduce the contact resistance by epitaxially depositing silver nanosolders at the Ag NW junctions, which have a negligible effect on the optical transparency, while decreasing the sheet resistance of the Ag NW film from 18.6 to 7.7 Ω/sq at a transmittance of 90%. In addition, the deposited nanosolders at the junctions remarkably improve the electrical and mechanical stabilities of the Ag NW electrodes. Notably, this simple nanosoldering process can be rapidly conducted under room temperature and ambient conditions and is free of any technical support or specific equipment. This technique is easily applied to the nanosoldering of 210 × 297 mm FTEs. Based on these FTEs, a high-performance flexible transparent heater with a sheet resistance 3.7 Ω/sq at a transmittance of 82.5% is constructed. Because of the high heating rate (4.8 °C/s), the heater can produce uniform heating (145 °C) at a short response time (30 s) and low input voltage (6 V).

How does estrogen work on autophagy?

Macroautophagy/autophagy is vital for intracellular quality control and homeostasis. Therefore, careful regulation of autophagy is very important. In the past 10 years, a number of studies have reported that estrogenic effectors affect autophagy. However, some results, especially those regarding the modulatory effect of 17ß-estradiol (E2) on autophagy seem inconsistent. Moreover, several clinical trials are already in place combining both autophagy inducers and autophagy inhibitors with endocrine therapies for breast cancer. Not all patients experience benefit, which further confuses and complicates our understanding of the main effects of autophagy in estrogen-related cancer. In view of the importance of the crosstalk between estrogen signaling and autophagy, this review summarizes the estrogenic effectors reported to affect autophagy, subcellular distribution and translocation of estrogen receptors, autophagy-targeted transcription factors (TFs), miRNAs, and histone modifications regulated by E2. Upon stimulation with estrogen, there will always be opposing functional actions, which might occur between different receptors, receptors on TFs, TFs on autophagy genes, or even histone modifications on transcription. The huge signaling network downstream of estrogen can promote autophagy and reduce overstimulated autophagy at the same time, which allows autophagy to be regulated by estrogen in a restricted range. To help understand how the estrogenic regulation of autophagy affects cell fate, a hypothetical model is presented here. Finally, we discuss some exciting new directions in the field. We hope this might help to better understand the multiple associations between estrogen and autophagy, the pathogenic mechanisms of many estrogen-related diseases, and to design novel and efficacious therapeutics. Abbreviations: AP-1, activator protein-1; HATs, histone acetyltransferases; HDAC, histone deacetylases; HOTAIR, HOX transcript antisense RNA.