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1.
Stat Med ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31621949

RESUMO

As biomarker information from early-phase trials can be unreliable due to high variability, it is logical to take a prospective two-stage approach when designing a late-phase confirmatory trial, ie, refining the target population at the first stage and performing the hypothesis testing at the second stage. The use of a reliable intermediate endpoint at the first stage can further improve the trial efficiency from both time and cost perspectives. Nevertheless, there are needs for expanding such two-stage confirmatory designs to more stages for monitoring efficacy on the refined population. There is limited literature on this matter, particularly for two popular designs with population selection midway, ie, the biomarker enrichment design and the basket design. In this manuscript, we focus on these two popular designs and discuss how to implement the interim efficacy analyses after population refinement while controlling type I error. Power and stopping probability are also explored for the two designs.

2.
ACS Appl Mater Interfaces ; 11(43): 39875-39881, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31576736

RESUMO

Formamidinium lead trihalide perovskites have emerged as promising photovoltaic materials owing to their superior absorption coefficient properties. However, one big challenge is the material phase stability and thermal stability at high temperature. In this work, a large quantity of rubidium (Rb) ions is incorporated into formamidinium (FA) perovskite thin films to improve the material phase stability and thermal stability. Photodiodes based on optimized FA0.7Rb0.3PbI3 perovskites deliver a high responsivity of 0.43 A W-1, a detectivity of >1012 Jones, a relatively large linear dynamic range of 125 dB, and an ultrafast response speed of approximately 300 ns. Moreover, these photodiodes present lower dark current and higher photocurrent after baking at high temperature. These results are very promising for photodetection at high operational temperature. In addition, the high-ratio rubidium-incorporated perovskite films may have great potential in fabricating other high-performance optoelectronic devices, i.e., light-emitting diodes and solar cells with excellent phase stability and high temperature thermostability.

3.
Inorg Chem ; 58(20): 13836-13842, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31578865

RESUMO

On the basis of the [Fe3(µ3-O)(COO)6] cluster and 3,3',5,5'-diphenyltetracarboxylic acid (H4BPTC), three novel metal-organic frameworks (MOFs), NJU-Bai25, NJU-Bai26, and NJU-Bai27 (NJU-Bai for Bai's group at Nanjing University ) with different (4,4,4,6)-, (4,4,4,4,4,6)-, and (4,4,6)-connected nets were obtained in different solvent systems, in which due to the steric hindrance of the coordinated solvents the conformations of BPTC gradually change from the planar to the torsional; thus, the pore sizes of those MOFs were also gradually narrowed. Interestingly, the MOFs show high thermal/chemical stabilities and selective CO2 adsorption: NJU-Bai27 exhibits larger CO2 uptake (5.0 and 13.8 wt %) at 298 K under 0.15 and 1 bar, whereas NJU-Bai26 has a higher selectivity for CO2/N2 (366).

4.
Inorg Chem ; 58(20): 13782-13787, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31591884

RESUMO

Amide-functionalized NJU-Bai45 exhibits high volumetric and gravimetric CH4 working capacities of 190 cm3 cm-3 and 298 cm3 g-1 (from 5.8 to 65 bar), higher than that of the similar NJU-Bai43 (187 cm3 cm-3 and 292 cm3 g-1). This finding indicates that nitrogen-functionalized aromatic ring may not always play a positive role in amide-MOF for CH4 storage.

5.
Opt Express ; 27(14): 19615-19623, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31503718

RESUMO

On-chip microlasers are desirable to meet the different control requirements and unique demands in different application scenarios. In this work, we obtained the on-chip microlaser by printing pixelated CdSe/ZnS colloidal quantum dots (CQDs), incorporating the quantum dot self-assembly mechanism and the external cavity-free configuration. The spectral purity of the microlaser can be significantly improved by slightly blending polymer into the CQD matrix. The quasitoroid profile was gradually changed to microdisks as the polystyrene (PS) concentration increased from 0 wt.% to 10 wt.%. Specially, when the PS solution varied from 0 wt.% to 1 wt.%, the lasing threshold of 1.4 µJ/mm2 was increased up to 14 µJ/mm2, meanwhile the emission wavelength range showed a 25 nm blue-shift approximately. The easy printing technologies and the low-cost polymer blending method employed in the obtained microlasers will further facilitate the development of printing photonics and electronics, especially in the high-performance microlaser displays and high-precision sensors.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31494547

RESUMO

In this letter, we reported an acoustic wave resonator for temperature monitorable kinetic analysis of human blood coagulation. The resonator operated in both Lamb wave mode at 860MHz and Rayleigh wave mode at 444MHz. The electrical parameter variation of the resonator induced by the increased plasma viscosity can be used to monitor the coagulation process. The Lamb mode of the resonator is sensitive to both the plasma viscosity and the plasma temperature, while the Rayleigh mode only responds to the temperature which is not affected by viscosity. These unique characteristics of the two modes are due to the different spatial distributions of the acoustic energy. Taking advantage of the aforementioned features, an acoustic wave resonator for study the human blood coagulation is designed to simultaneously monitor the temperature and plasma viscosity. The coagulation time and the plasma temperature were provided by fitting the time-frequency curves. Our design holds great promise for biological reaction monitoring with possible temperature changes.

7.
Br J Pharmacol ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31478560

RESUMO

BACKGROUND AND PURPOSE: Abdominal aortic aneurysm (AAA) is a degenerative disease with irreversible and progressive dilation of the artery. But there are few options for efficacious treatment except for traditional surgery. Probucol (PB) has been widely applied to treat hyperlipidemia and atherosclerosis in clinic, but whether it can protect against AAA remains unknown. In this study, the protective effects of PB against AAA and its related mechanisms were explored. EXPERIMENTAL APPROACH: Mouse AAA model was induced by incubating the abdominal aorta with elastase. PB at different doses was administrated to the mice by gavage beginning on the same day of AAA inducement and lasted for 14 days. In vitro experiments were constructed by stimulating rat vascular smooth muscle cells (VSMCs) with tumor necrosis factor (TNF)-α. Heme oxygenase (HO)-1 siRNA and HO-1 plasmid were used to regulate the expression or activity of HO-1 in the VSMCs and to clarify the effects of HO-1. KEY RESULTS: PB dose-dependently prevented the development of AAA, reflected by decrease of AAA incidence, diameters of aortic dilation, elastin degradation and inflammatory cells infiltration. PB could also protect VSMCs from oxidative injury and enhance elastin biosynthesis. But the anti-inflammatory effect of PB on VSMCs was weakened significantly when HO-1 was inhibited by siRNA. CONCLUSION AND IMPLICATIONS: PB exerted anti-AAA effects through inhibiting the degradation of elastin caused by inflammation and oxidation and facilitating the biosynthesis of elastin. HO-1 plays a crucial role in anti-inflammatory effect of PB on VSMCs.

8.
Chin J Nat Med ; 17(8): 591-599, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472896

RESUMO

Whitmania pigra has been used as a traditional Chinese medicine (TCM) for promoting blood circulation, alleviating blood coagulation, activating meridians and relieving stasis for several hundred years. However, the therapeutic components of this species, especially proteins and peptides were poorly exploited. Until now only a few of them were obtained by using chromatographic isolation and purification. In recent decade, transcriptome techniques were rapidly developed, and have been used to fully reveal the functional components of many animal venoms. In the present study, the cDNA of the salivary gland of Whitmania pigra was sequenced by illumina and the transcriptome was assembled by using Trinity. The proteome were analysed by LC-MS/MS. Based on the data of the transcriptome and the proteome, a potential antiplatelet protein named pigrin was found. Pigrin was cloned and expressed using P. pastoris GS115. The antiplatelet andantithrombotic bioactivities of pigrin were tested by using aggregometer and the rat arterio-venous shunt thrombosis model, respectively. Thebleeding time of pigrin was measured by a mice tail cutting method. The docking of pigrin and protease-activated receptor 1 (PAR1) or collagen were conducted using the ZDOCK Server. Pigrin was able to selectively inhibit platelet aggregation stimulated by PAR1 agonist and collagen. Pigrin attenuated thrombotic formation in vivo in rat, while did not prolong bleeding time at its effective dosage. There are significant differences in the key residues participating in binding of Pigrin-Collagen complex from Pigrin-PAR1 complex. In conclusion,a novel PAR1 inhibitor pigrin was found from the leech Whitmania pigra. This study helped to elucidate the mechanism of the leech for the treatment of cardiovascular disorder.

9.
IEEE Trans Cybern ; 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31545758

RESUMO

The community detection in dynamic networks is essential for important applications such as social network analysis. Such detection requires simultaneous maximization of the clustering accuracy at the current time step while minimization of the clustering drift between two successive time steps. In most situations, such objectives are often in conflict with each other. This article proposes the concept of consensus community. Knowledge from the previous step is obtained by extracting the intrapopulation consensus communities from the optimal population of the previous step. Subsequently, the intrapopulation consensus communities of the previous step obtained is voted by the population of the current time step during the evolutionary process. A subset of the consensus communities, which receives a high support rate, will be recognized as the interpopulation consensus communities of the previous and current steps. Interpopulation consensus communities are the knowledge that can be transferred from the previous to the current step. The population of the current time step can evolve toward the direction similar to the population in the previous time step by retaining such interpopulation consensus community during the evolutionary process. Community structure is subjected to evaluation, update, and mutation events, which are directed by using interpopulation consensus community information during the evolutionary process. The experimental results over many artificial and real-world dynamic networks illustrate that the proposed method produces more accurate and robust results than those of the state-of-the-art approaches.

10.
Ecotoxicol Environ Saf ; 183: 109507, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31386942

RESUMO

Multi-walled carbon nanotubes (MWCNTs) promote biodegradation in water treatment, but the effect of MWCNT on denitrification under aerobic conditions is still unclear. This investigation focused on the denitrification performance of MWCNT and its toxic effects on Alcaligenes sp. TB which showed that 30 mg/L MWCNTs increased NO3- removal efficiency from 84% to 100% and decreased the NO2-and N2O accumulation rates by 36% and 17.5%, respectively. Nitrite reductase and nitrous oxide reductase activities were further increased by 19.5% and 7.5%, respectively. The mechanism demonstrated that electron generation (NADH yield) and electron transportation system activity increased by 14.5% and 104%, respectively. Cell membrane analysis found that MWCNT caused an increase in polyunsaturated fatty acids, which had positive effects on electron transportation and membrane fluidity at a low concentration of 96 mg/kg but caused membrane lipid peroxidation and impaired membrane integrity at a high concentration of 115 mg/L. These findings confirmed that MWCNT affects the activity of Alcaligenes sp. TB and consequently enhances denitrification performance.

11.
J Am Chem Soc ; 141(37): 14539-14543, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31469955

RESUMO

A pure-supramolecular-linker (PSL) approach for the formation of metal-organic frameworks (MOFs) was initially given, which was demonstrated by syntheses of two highly connected and isostructural MOFs, {Fe3O(TPBTM6-)(Cl)(H2O)2}∞ (TPBTM = N,N',N″-tris(isophthalyl)-1,3,5-benzenetricarboxamide) (NJU-Bai52, NJU-Bai for Nanjing University Bai group) and {Sc3O(TPBTM6-)(OH)(H2O)2}∞ (NJU-Bai53). Very interestingly, they exhibit exceptional thermal stability, water stability, and highly selective CO2 capture properties. In particular, NJU-Bai53 with higher uptakes (2.74 wt % at 0.4 mbar and 298 K, 7.67 wt % at 298 K and 0.15 bar) and higher selectivity may be an excellent candidate for CO2 capture.

12.
Pharm Stat ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31424631

RESUMO

For oncology drug development, phase II proof-of-concept studies have played a key role in determining whether or not to advance to a confirmatory phase III trial. With the increasing number of immunotherapies, efficient design strategies are crucial in moving successful drugs quickly to market. Our research examines drug development decision making under the framework of maximizing resource investment, characterized by benefit cost ratios (BCRs). In general, benefit represents the likelihood that a drug is successful, and cost is characterized by the risk adjusted total sample size of the phases II and III studies. Phase III studies often include a futility interim analysis; this sequential component can also be incorporated into BCRs. Under this framework, multiple scenarios can be considered. For example, for a given drug and cancer indication, BCRs can yield insights into whether to use a randomized control trial or a single-arm study. Importantly, any uncertainty in historical control estimates that are used to benchmark single-arm studies can be explicitly incorporated into BCRs. More complex scenarios, such as restricted resources or multiple potential cancer indications, can also be examined. Overall, BCR analyses indicate that single-arm trials are favored for proof-of-concept trials when there is low uncertainty in historical control data and smaller phase III sample sizes. Otherwise, especially if the most likely to succeed tumor indication can be identified, randomized controlled trials may be a better option. While the findings are consistent with intuition, we provide a more objective approach.

13.
ACS Appl Mater Interfaces ; 11(37): 33868-33878, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31441638

RESUMO

Growing attention has been paid to CsPbIBr2 perovskite solar cells (PSCs) after balancing the band gap and stability features of the interested full-inorganic perovskites. However, their power-conversion efficiency (PCE) still lags behind that of the PSCs using hybrid halide perovskite and how to increase the corresponding PCE is still a challenge. Herein, antisolvents and organic ion surface passivation strategies were systematically applied to precisely control the growth of CsPbIBr2 crystals for constructing a high-quality full-inorganic perovskite film. Through careful adjustments, a CsPbIBr2 film with a pure phase, full coverage, and high crystallinity with preferable (100) orientation was successfully obtained by introducing diethyl ether as the antisolvent followed by guanidinium surface passivation. The optimal CsPbIBr2 film was composed by a large grain with an average size of 950 nm, few grain boundaries, and higher hydrophobic property. Planer PSC using the optimal CsPbIBr2 film and electron-beam-deposited TiO2 compact layer exhibits a PCE of 9.17%, which ranks among the highest PCE range of the reported CsPbIBr2 PSCs. Besides, the designed CsPbIBr2 PSC exhibited good long-term stability, which could maintain 90% of the initial PCE in 40% humidity ambient, which remained constant after heat treatment at 100 °C for 100 h. Based on the optimal CsPbIBr2 film, the flexible and large-area (up to 225 mm2) PSCs were further fabricated. The adopted film improvement methods were further extended to other kinds of full-organic PSCs, which demonstrated the universality of this strategy.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31403446

RESUMO

Sum-product networks (SPNs) constitute an emerging class of neural networks with clear probabilistic semantics and superior inference speed over other graphical models. This brief reveals an important connection between SPNs and tensor trains (TTs), leading to a new canonical form which we call tensor SPNs (tSPNs). Specifically, we demonstrate the intimate relationship between a valid SPN and a TT. For the first time, through mapping an SPN onto a tSPN and employing specially customized optimization techniques, we demonstrate improvements up to a factor of 100 on both model compression and inference speedup for various data sets with negligible loss in accuracy.

15.
J Cell Mol Med ; 23(10): 6930-6941, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31448883

RESUMO

The cysteine-rich lysosomal protein placenta-specific 8 (PLAC8), also called onzin, has been shown to be involved in many types of cancers, and its role is highly dependent on cellular and physiological contexts. However, the precise function of PLAC8 in breast cancer (BC) progression remains unclear. In this study, we investigated both the clinical significance and biological functions of PLAC8 in BC progression. First, high PLAC8 expression was observed in primary BC tissues compared with adjacent normal tissues through immunohistochemistry analysis. The results of in vitro and in vivo assays further confirmed that PLAC8 overexpression promotes cell proliferation and suppress BC cell apoptosis, whereas PLAC8 silencing has the opposite effect. In addition, the forced expression of PLAC8 greatly induces cell migration, partially by affecting the EMT-related genes, including down-regulating E-cadherin expression and facilitating vimentin expression. Further mechanistic analysis confirmed that PLAC8 contributes to cell proliferation and suppresses cell apoptosis in BC by activating the PI3K/AKT/NF-κB pathway. The results of our study provide new insights into an oncogenic role of PLAC8 and reveal a novel PLAC8/ PI3K/AKT/NF-κB pathway as a potential therapeutic target for BC.

16.
Clin Genet ; 96(5): 439-448, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31372974

RESUMO

Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited sensorimotor neuropathies. To clarify the genetic spectrum and clinical profiles in Chinese CMT patients, we enrolled 150 unrelated CMT patients from southeast China. We performed multiplex ligation-dependent probe amplification (MLPA) testing in all patients and next-generation sequencing (NGS) among those patients without PMP22 rearrangements. We identified PMP22 duplications in 40 patients and deletions in 12 patients. In addition, we found 19 novel variants and 36 known mutations in 57 patients. Among these 55 variants, 45 pathogenic or likely pathogenic variants were identified in 48 cases, and 10 variants with uncertain significance were identified in 9 cases. Therefore, we obtained a genetic diagnosis in 63.8% (88/138) of CMT patients and 66.7% (100/150) of all included patients. PMP22, GJB1, and MFN2 are the most common causative genes in CMT1 (demyelinated form), intermediate CMT, and CMT2 (axonal form), respectively. In this study, we identified a higher proportion of intermediate CMT, a relatively high frequency of NDRG1 mutations and clinical features of later onset age in CMT1A patients. Our results broaden the genetic and clinical spectrum of CMT patients, which can help optimize the genetic and clinical diagnosis.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31441961

RESUMO

BACKGROUND AND AIM: It has been well documented that Helicobacter pylori (H. pylori) infection is a risk factor for aggravating gastric mucosal atrophy. However, the exact molecular mechanism mediating this process is not fully elucidated. The purpose of this study was to identify biomarkers, which may predict the risk for progression of chronic atrophic gastritis (CAG) with H. pylori. METHODS: GSE27411 was downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) between H. pylori-infected samples without CAG and H. pylori-infected CAG samples were analyzed. Gene Ontology and pathway enrichment analyses were performed, followed by protein-protein interaction network construction. We used immunohistochemistry analysis to identify DEGs in 20 chronic gastritis, 20 CAG, and 22 gastric cancer (GC) specimens. RESULTS: A total of 303 upregulated and 26 downregulated DEGs were identified. The pathways enriched by upregulated DEGs were mainly related to fat digestion and absorption, peroxisome proliferator-activated receptor signaling pathway, and chemical carcinogenesis. Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) had the highest degrees in protein-protein interaction network. Moreover, the positive rates of CYP3A4 protein expression in chronic gastritis, CAG, and GC were 10% (2/20), 55% (11/20), and 77.3% (17/22), respectively (P < 0.001). The Kaplan-Meier analysis revealed that elevated expression of CYP3A4 was significantly associated with worse overall survival and first progression, respectively (P < 0.0001). CONCLUSION: According to the findings of this study, the expression of CYP3A4 might be related to the potential carcinogenic transformation of CAG to GC. Therefore, CYP3A4 may be biomarkers to predict progression of CAG and poor prognosis of gastric cancer.

18.
BMC Vet Res ; 15(1): 244, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307451

RESUMO

BACKGROUND: Porcine circovirus type 3 (PCV3) was first reported in US in 2016. The virus was also identified later in China. Prevalence of PCV3 in Zhejiang province in southeastern China is not clear though it has been reported in many parts of China. RESULTS: PCV3 infection and its co-infection with other swine viral pathogens in pig herds of Zhejiang province were retrospectively investigated by quantitative PCR (qPCR) and its sero-prevalence by indirect ELISA. PCV3 was found positive in 67.1% of the 283 clinical samples taken from 2014 to 2017 as shown by qPCR. Single infection with PCV3 accounted for only one-third of the samples, and majority were of co-infections, predominantly with PEDV (41.6%) but generally low with other swine viruses. Indirect ELISA using the PCV3 capsid protein as the coating antigen revealed an average sero-positive rate of 52.6% (40.8 to 60.8%) in 2345 serum samples from 2011 to 2017, with earliest yet high positive findings in samples taken in 2012. Of 203 serum samples, the qPCR method showed more positive findings than ELISA (81.3% vs 56.2%). With 89 serum samples negative by ELISA, vast majority (n = 81) were found positive by qPCR. There was negative correlation in levels of PCV3 DNA and anti-capsid antibody response. ORF2-based phylogenetic analysis revealed three major groups (PCV3a, PCV3b and PCV3c) of the 200 strains, 38 from this study and 162 reference strains from GenBank. Most of the strains from this study were clustered into PCV3c. Of the putative signature residues of the capsid protein (aa 24, 27, 77 and 150) relative to the three groups, only the PCV3a group strains showed a distinct pattern of residues VKSI (95% of the strains), while the other two groups did not have such a 'signature' pattern. CONCLUSIONS: Results from this study provided further evidence that the novel virus PCV3 was widely distributed in China and might have emerged in Zhejiang province before 2014, most probably back in 2012 when there was high PCV3 sero-prevalence. PCV3 might be viremic in pigs and could spread by fecal shedding.

19.
Sci Adv ; 5(7): eaaw6703, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31328167

RESUMO

Lysine 2-hydroxyisobutyrylation (Khib) has recently been shown to be an evolutionarily conserved histone mark. Here, we report that CobB serves as a lysine de-2-hydroxyisobutyrylation enzyme that regulates glycolysis and cell growth in prokaryotes. We identified the specific binding of CobB to Khib using a novel self-assembled multivalent photocrosslinking peptide probe and demonstrated that CobB can catalyze lysine de-2-hydroxyisobutyrylation both in vivo and in vitro. R58 of CobB is a critical site for its de-2-hydroxyisobutyrylase activity. Using a quantitative proteomics approach, we identified 99 endogenous substrates that are targeted by CobB for de-2-hydroxyisobutyrylation. We further demonstrated that CobB can regulate the catalytic activities of enolase (ENO) by removing K343hib and K326ac of ENO simultaneously, which account for changes of bacterial growth. In brief, our study dissects a Khib-mediated molecular mechanism that is catalyzed by CobB for the regulation of the activity of metabolic enzymes as well as the cell growth of bacteria.

20.
J Hematol Oncol ; 12(1): 81, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340867

RESUMO

BACKGROUND: Tamoxifen resistance remains a clinical challenge for hormone receptor-positive breast cancer. Recently, dysregulations in autophagy have been suggested as a potential mechanism for tamoxifen resistance. Although the long noncoding RNA H19 is involved in various stages of tumorigenesis, its role in tamoxifen resistance remains unknown. Here, we assessed the role of H19 in the development of tamoxifen-resistant breast cancer. METHODS: Quantitative real-time PCR analyzed expression of H19 in tamoxifen-resistant breast cancer tissues. Knockdown of H19 was used to assess the sensitivity to tamoxifen in vitro and in vivo. Both knockdown and overexpression of H19 were used to analyze the status of autophagy. Real-time quantitative methylation-specific polymerase chain reaction, chromatin immunoprecipitation, immunofluorescence, and Western blot were used to explore the tamoxifen resistance mechanism of H19. RESULTS: In this study, we observed that the expression of H19 was substantially upregulated in tamoxifen-resistant breast cancer cell line and tumor tissues, and knockdown of H19 enhanced the sensitivity to tamoxifen both in vitro and in vivo. Furthermore, knockdown of H19 significantly inhibited autophagy in MCF7 tamoxifen-resistant (MCF7/TAMR) cells. Conversely, overexpression of H19 promoted autophagy. Interestingly, overexpression of H19 in MCF7 tamoxifen-sensitive cells could recapitulate tamoxifen resistance. Moreover, an increase in methylation in the promoter region of Beclin1 was observed in MCF7/TAMR-shH19 cells. In the double knockdown groups, both shH19+shSAHH and shH19+shDNMT3B rescued the Beclin1 promoter region methylation levels and reactivated autophagy functions. A chromatin immunoprecipitation assay further validated that DNMT3B binds to the Beclin1 promoter region and the knockdown of H19 increases this binding. CONCLUSIONS: Our findings demonstrate that H19 induces autophagy activation via the H19/SAHH/DNMT3B axis, which could contribute to tamoxifen resistance in breast cancer.

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