The constricting effect of reduced coronary artery compliance on the left ventricle is an important cause of reduced diastolic function in patients with coronary heart disease.

BACKGROUND: Previous studies of left ventricular diastolic function (LVDF) have focused on the decrease in active and passive diastolic function due to ischemic factors but have not investigated if the decrease in compliance of the coronary arteries that bypass the surface of the heart and travel between the myocardium could cause a constricting effect on the ventricular wall like that caused by myocardial fibrosis. METHODS AND RESULTS: 581 patients diagnosed with coronary heart disease (CHD) were divided into A group (patients are the control group), B group (patients with less than 50% coronary artery stenosis), C group (patients with coronary artery stenosis between 50 and 75%), D group (patients with coronary artery stenosis greater than 75%) according to the degree of coronary stenosis. The diastolic function of the ventricle is reflected by applying the relaxation time constant T value, which refers to the time between peak dp/dt and end-diastolic pressure in the left ventricle. It was concluded that there was a statistical difference in Gensini scores between patients in groups B, C and D (P < 0.001). And multiple linear regression analysis showed that T was correlated with Gensini score and C-dp/dtmax (R = 0.711, P < 0.001). Grouping according to the site of stent implantation and the number of stents implanted, it was found out that the changes in T values before and after left anterior descending artery (LAD) stent implantation were greater than left circumflex artery (LCX) and right coronary artery (RCA) (P < 0.001). And multiple linear regression revealed a correlation between T values and stent length, ventricular stiffness, and C-dp/dtmax (P = 0.001). CONCLUSIONS: The decrease in compliance of the coronary arteries bypassing the surface of the heart and travelling between the myocardium would cause a constricting effect on the ventricular wall like that caused by myocardial fibrosis.

Inhibitory Effects of the Natural Product Esculetin on Phytophthora capsici and Its Possible Mechanism.

Esculetin is an important plant-derived natural product that has multiple bioactivities and applications. Phytophthora capsici is a notorious plant pathogen capable of infecting a broad range of hosts. In this study, we evaluated the antifungal activity of esculetin against P. capsici. The baseline sensitivity of P. capsici to esculetin was established using 108 isolates collected from various geographical regions in the Jiangsu and Shandong Provinces of China. The median effective concentration (EC50) values for esculetin ranged from 2.08 to 16.46 µg/ml (mean, 6.87 ± 2.70 µg/ml) and were normally distributed. Furthermore, both zoospore production and germination were strongly inhibited by esculetin. Importantly, esculetin exhibited protective as well as curative activities against P. capsici on tomato and was capable of restricting the early infection of P. capsici on Nicotiana benthamiana. We found that the esculetin treatment led to cell membrane damage of P. capsici, as revealed by morphological observations and measurements of relative conductivity and malondialdehyde (MDA). Finally, our results also suggested that esculetin may adversely affect P. capsici by inhibiting its DNA and protein synthesis. These findings will contribute to the broader evaluation of the use of esculetin to control diseases caused by P. capsici and toward a better understanding of its mode of action as a potential fungicide.

Effects of camptothecin on the rice blast fungus Magnaporthe oryzae.

Rice blast caused by Magnaporthe oryzae B. Couch is one of the most devastating diseases on rice. Camptothecin (CPT), which was primarily isolated from Camptotheca acuminata, is well-known for its anti-tumor activities, and is also developed as a potential biological pesticide. We previously investigated the anti-microbial activities of CPT against 11 fungi, 3 oomycetes, and 4 bacteria, and found that CPT was strongly effective against M. oryzae, indicating its potential as a lead for developing fungicide against rice blast. However, the anti-fungal effects of CPT on M. oryzae need further elucidation. In this study, the anti-fungal activities of CPT against M. oryzae were further investigated, which revealed that CPT was effective against M. oryzae both in vitro and in vivo. The transcriptome of M. oryzae was analyzed after CPT treatment, which showed that CPT had a strong inhibitory effect on 'translation' and 'carbohydrate metabolism/energy metabolism' of M. oryzae. Some physiology characteristics of M. oryzae were also assayed, which confirmed that CPT inhibited RNA synthesis, protein synthesis, and carbohydrate metabolism/energy metabolism of M. oryzae, and caused membrane damage. The molecular simulation result showed that CPT binds to the interface of DNA-topoisomerase I complex of M. oryzae. In conclusion, CPT is a promising lead for developing fungicide against rice blast. CPT may bind to DNA-topoisomerase I complex of M. oryzae, thus affecting 'translation' and 'carbohydrate metabolism/energy metabolism', leading to cell death.

The role of E2F1-topoIIß signaling in regulation of cell cycle exit and neuronal differentiation of human SH-SY5Y cells.

This study aims to test the role of E2F1-topoIIß signaling in neuronal differentiation of SH-SY5Y cells. With retinoic acid (RA) induction, a high percentage of cells were found to be arrested at the G0/G1 phase, with decreased levels of cyclinD1, CDK4, phosphorylation status of pRb and E2F1, in addition to an elevated level of p27. The cells were shown to differentiate into neuronal phenotypes characterized by highly expressed neuronal markers, MAP2 and enriched topoIIß, and remarkable neurite outgrowth. Exogenously forced E2F1 expression with a specific E2F1 plasmid led to suppression of topoIIß expression and disruption of the neuronal differentiation of SH-SY5Y cells. On further examination using the ChIP assay, we found that E2F1 bound directly to the promoter region of topoIIß, and its binding ability was inversely correlated with topoIIß expression in response to RA induction. Thus, our findings suggest that E2F1-topoIIß signaling may play a role in regulation of cell cycle exit and neuronal differentiation.

Ribonucleic acid interference knockdown of IL-6 enhances the efficacy of cisplatin in laryngeal cancer stem cells by down-regulating the IL-6/STAT3/HIF1 pathway.

BACKGROUND: Cisplatin has been used in the treatment of many cancers, including laryngeal cancer; however, its efficacy can be reduced due to the development of drug resistance. This study aimed to investigate whether interleukin-6 (IL-6) knockdown may enhance the efficacy of cisplatin in laryngeal cancer stem cells (CSC) and the potential involvement of the signal transducer and activator of transcription 3 (STAT3) and hypoxia-inducible factor 1 (HIF1) in this effect. METHODS: The ALDH+ and CD44+ CSC in Hep2 human laryngeal squamous cancer cells were identified by the fluorescence-activated cell sorting technique. IL-6, STAT3 and HIF1 mRNA and protein expressions were examined with quantitative real-time polymerase chain reaction and Western blot, respectively. Cell proliferation was measured by MTT assay. Tumorigenicity was measured by a colony formation assay and invasion was determined by a cell invasion assay. Apoptotic cells were counted by flow cytometry. Immunohistochemistry was performed to detect immunoreactive IL-6, STAT3 and HIF1 cells in xenografts. RESULTS: The mRNA and protein levels of IL-6, STAT3 and HIF1 were significantly increased in Hep2-CSC as compared with those from Hep2 cells. Application of siRNA-IL-6 to knockdown IL-6 resulted in significantly decreased IL-6, STAT3 and HIF1 mRNA and protein levels. IL-6 knockdown reduced cell proliferation, tumorigenicity and invasion and increased apoptosis within CSC. Enhanced degrees of suppression in these parameters were observed when IL-6 knockdown was combined with cisplatin in these CSC. Results from the xenograft study showed that the combination of IL-6 knockdown and cisplatin further inhibited the growth of xenografts as compared with that obtained in the cisplatin-injected group alone. Immunoreactive IL-6, STAT3 and HIF1 cell numbers were markedly reduced in IL-6 knockdown tumor tissues. IL-6, STAT3 and HIF1 immunoreactive cell counts were further reduced in tissue where IL-6 knockdown was combined with cisplatin treatment as compared with tissue receiving cisplatin alone. CONCLUSIONS: IL-6 knockdown can increase chemo-drug efficacy of cisplatin, inhibit tumor growth and reduce the potential for tumor recurrence and metastasis in laryngeal cancer. The IL-6/STAT3/HIF1 pathway may represent an important target for investigating therapeutic strategies for the treatment of laryngeal cancer.

Characterization of solvent, detergent and oxidizing agent stable protease from isolated Antarctic marine Streptomyces sp. XE-1.

OBJECTIVE: A polar marine actinobacterium (XE-1) was selected and used to produce a protease with special characteristics. METHODS: The XE-1 was identified as Streptomyces based on morphological, biochemical and molecular characterizations (16S rRNA gene sequence analysis). The protease was purified by 3 purification steps, including ethanol precipitation, ion exchange and gel chromatography. Its apparent molecular mass was estimated by SDS-PAGE. RESULTS: A solvent, detergent and oxidizing agent stable alkaline serine protease (with a low weight molecular, 14 kDa by SDS-PAGE) , secreted by strain XE-1, was purified and characterized. The protease was stable in the pH range between 5 and 10, with optimal pH 8.2 and optimal temperature 55 degrees C. K(m) and V(max) towards casein activity were 1.9 mg/mL and 973 U/mL, respectively. The protease was more active and stable in various hydrophilic organic solvents (such as dimethylformamid and toluene). Moreover, it was also active and stable in bleaching agents (such as hydrogen peroxide) ; and stable in denaturant agents (such as urea and guanidine hydrochloride) at the concentration from 0.2 mol/L to 4 mol/L, which were the new characteristics. CONCLUSION: These biochemical characteristics suggest this enzyme has the potential value in numerous industrial applications.

Two novel functions of hyaluronidase from Streptococcus agalactiae are enhanced intracellular survival and inhibition of proinflammatory cytokine expression.

Streptococcus agalactiae is the causative agent of septicemia and meningitis in fish. Previous studies have shown that hyaluronidase (Hyl) is an important virulence factor in many Gram-positive bacteria. To investigate the role of S. agalactiae Hyl during interaction with macrophages, we inactivated the gene encoding extracellular hyaluronidase, hylB, in a clinical Hyl(+) isolate. The isogenic hylb mutant (Δhylb) displayed reduced survival in macrophages compared to the wild type and stimulated a significantly higher release of proinflammatory cytokines, such as interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α), than the wild type in macrophages as well as in mice. Furthermore, only Hyl(+) strains could grow utilizing hyaluronic acid (HA) as the sole carbon source, suggesting that Hyl permits the organism to utilize host HA as an energy source. Fifty percent lethal dose (LD50) determinations in zebrafish demonstrated that the hylb mutant was highly attenuated relative to the wild-type strain. Experimental infection of BALB/c mice revealed that bacterial loads in the blood, spleen, and brain at 16 h postinfection were significantly reduced in the ΔhylB mutant compared to those in wild-type-infected mice. In conclusion, hyaluronidase has a strong influence on the intracellular survival of S. agalactiae and proinflammatory cytokine expression, suggesting that it plays a key role in S. agalactiae pathogenicity.

Specificity protein 1 regulates topoisomerase IIß expression in SH-SY5Y cells during neuronal differentiation.

Topoisomerase IIß (top IIß) is a nuclear enzyme with an essential role in neural development. The regulation of top IIß gene expression during neural differentiation is poorly understood. Functional analysis of top IIß gene structure displayed a GC box sequence in its transcription promoter, which binds the nuclear transcription factor specificity protein 1 (Sp1). Sp1 regulates gene expression via multiple mechanisms and is essential for early embryonic development. This study seeks to determine whether Sp1 regulates top IIß gene expression during neuronal differentiation. For this purpose, human neuroblastoma SH-SY5Y cells were induced to neuronal differentiation in the presence of all-trans retinoic acid (RA) for 5 days. After incubation with 10 µM RA for 3-5 days, a majority of the cells exited the cell cycle to become postmitotic neurons, characterized by the presence of longer neurite outgrowths and expression of the neuronal marker microtubule-associated protein-2 (MAP2). Elevated Sp1 and top IIß mRNA and protein levels were detected and found to be positively correlated with the differentiation stage. Chromatin immunoprecipitation assay demonstrated an increased recruitment of Sp1 to the top IIß promoter after RA treatment. Mithramycin A, a compound that interferes with Sp1 binding to GC-rich DNA sequences, downregulated the expression of top IIß, resulting in reduced expression of MAP2 and decreased neurite length compared with the control group. Our results indicate that Sp1 regulates top IIß expression by binding to the GC box of the gene promoter during neuronal differentiation in SH-SY5Y cells.

ERCP-Net: a channel extension residual structure and adaptive channel attention mechanism for plant leaf disease classification network.

Plant leaf diseases are a major cause of plant mortality, especially in crops. Timely and accurately identifying disease types and implementing proper treatment measures in the early stages of leaf diseases are crucial for healthy plant growth. Traditional plant disease identification methods rely heavily on visual inspection by experts in plant pathology, which is time-consuming and requires a high level of expertise. So, this approach fails to gain widespread adoption. To overcome these challenges, we propose a channel extension residual structure and adaptive channel attention mechanism for plant leaf disease classification network (ERCP-Net). It consists of channel extension residual block (CER-Block), adaptive channel attention block (ACA-Block), and bidirectional information fusion block (BIF-Block). Meanwhile, an application for the real-time detection of plant leaf diseases is being created to assist precision agriculture in practical situations. Finally, experiments were conducted to compare our model with other state-of-the-art deep learning methods on the PlantVillage and AI Challenger 2018 datasets. Experimental results show that our model achieved an accuracy of 99.82% and 86.21%, respectively. Also, it demonstrates excellent robustness and scalability, highlighting its potential for practical implementation.

Sanshimao formula inhibits the hypoxia-induced pro-angiogenesis of hepatocellular carcinoma cells partly through regulating MKK6/p38 signaling pathway.

OBJECTIVES: Sanshimao (SSM) is a traditional Chinese medicine formula for advanced hepatocellular carcinoma (HCC). This study was designed to investigate the effect of SSM on HCC-induced angiogenesis and to explore the potential mechanism. METHODS: The endothelial cells were cultured with HCC cells conditioned medium in the 1% oxygen atmosphere to imitate tumor hypoxia microenvironment. EA.hy926 cells migration and tubulogenesis were detected by tube formation and scratch-wound assay. The protein microarray was employed to explore SSM-targeted proteins in Huh7 cells. We also established an animal model to observe the effects of SSM on angiogenesis in vivo. RESULTS: The data indicated that SSM reduced HCC-induced migration and tube formation of EA.hy926 cells at low dose under hypoxic conditions. These effects might be partly owing to suppression of HIF-1α-induced vascular endothelial growth factorα expression in Huh7 cells. Moreover, this inhibition was in an MKK6/P38-dependent way. Besides, Huh7 subcutaneous tumor models in nude mice further demonstrated the inhibition of SSM on tumor weight might be exerted partly by reduction of angiogenesis via blocking MKK6/P38 signaling pathways. CONCLUSION: SSM inhibits HCC-induced pro-angiogenesis under hypoxic conditions via suppression of MKK6/P38 signaling pathways, which is favorable for HCC tumor growth.

Nomogram to Predict the Prognosis of Oligodendroglioma Patients Undergoing Postoperative Adjuvant Chemoradiotherapy.

OBJECTIVE: The aim of this study was to develop a prognostic nomogram for predicting the prognosis of oligodendroglioma patients receiving combined chemoradiotherapy (CRT) after surgery. METHODS: The study used data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. The patients were randomly divided into a development cohort (700 patients) and a validation cohort (244 patients) in a 7:3 ratio. The Cox hazards regression model was used to identify predictors, and a nomogram was constructed to visualize the prognosis. The performance of the prognostic nomogram was evaluated using the consistency index (C-index), clinical net benefit, and calibration. RESULTS: The nomogram included 5 variables: age, marital status, tumor size, site of lesions, and surgery type. The C-index of the training set and validation set were 0.77 and 0.68, respectively. The calibration plots showed that the nomogram was in good agreement with the actual observation. The clinical decision curve indicated that the nomogram had a good clinical net benefit in oligodendroglioma patients receiving CRT after surgery. CONCLUSIONS: This study established and verified a prognostic nomogram for a large cohort of oligodendroglioma patients receiving CRT after surgery based on the SEER database. The nomogram may help clinicians provide personalized treatment services and clinical decisions for patients.

Fluoride-Catalyzed Arylation of α-(Trifluoromethyl)styrene Derivatives with Silicon-Masked, Functionalized Aryl Pronucleophiles.

An operationally simple transition-metal-free protocol for the arylation of α-(trifluoromethyl)styrene derivatives with silicon-protected functionalized aryl pronucleophiles is disclosed. Catalytic amounts of an anionic Lewis base such as fluoride trigger the release of the aryl nucleophile from N-aryl-N'-silyldiazenes by desilylation along with denitrogenation. The thus-generated carbon nucleophiles engage in an allylic displacement with α-(trifluoromethyl)styrene electrophiles to afford the corresponding geminal difluoroalkenes.

Effects of Charge Trapping on Memory Characteristics for HfO2-Based Ferroelectric Field Effect Transistors.

A full understanding of the impact of charge trapping on the memory window (MW) of HfO2-based ferroelectric field effect transistors (FeFETs) will permit the design of program and erase protocols, which will guide the application of these devices and maximize their useful life. The effects of charge trapping have been studied by changing the parameters of the applied program and erase pulses in a test sequence. With increasing the pulse amplitude and pulse width, the MW increases first and then decreases, a result attributed to the competition between charge trapping (CT) and ferroelectric switching (FS). This interaction between CT and FS is analyzed in detail using a single-pulse technique. In addition, the experimental data show that the conductance modulation characteristics are affected by the CT in the analog synaptic behavior of the FeFET. Finally, a theoretical investigation is performed in Sentaurus TCAD, providing a plausible explanation of the CT effect on the memory characteristics of the FeFET. This work is helpful to the study of the endurance fatigue process caused by the CT effect and to optimizing the analog synaptic behavior of the FeFET.

Isolation, identification and molecular docking of anti-inflammatory peptides from walnut (Juglans regia L.) meal hydrolysates.

The oil extraction residue of walnuts is rich in proteins and has been employed in the formulation of various functional food products. In this study, alcalase and neutrase were used to hydrolyze defatted walnut meal protein to obtain anti-inflammatory peptides. After separation by ultrafiltration and by using Sephadex G-25, the fraction with the highest anti-inflammatory activity was identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and 579 peptides were obtained. Then, four of the most stable binding tripeptides with the sequences Trp-Pro-Leu (WPL, MW: 414.2 Da), Trp-Ser-Leu (WSL, MW: 404.2 Da), Phe-Pro-Leu (FPL, MW: 375.2 Da) and Phe-Pro-Tyr (FPY, MW: 425.2 Da) were successfully identified by virtual screening. The anti-inflammatory activity determination of the synthetic peptide assay indicated that FPL (200 µM) exhibited excellent anti-inflammatory activity with inhibitory rates of 63.65 ± 2.64%, 68.25 ± 2.19%, 42.52 ± 2.01% and 59.39 ± 2.21% in terms of four inflammatory mediators (NO, TNF-α, IL-6 and IL-1ß), respectively. It was speculated that the anti-inflammatory activity of walnut peptides might be related to hydrophobic amino acids and aromatic amino acids. By molecular docking, further insight into the theoretical interaction mechanism of binding revealed that hydrophobic interactions and hydrogen bonds turned out to be the main interaction forces between the four peptides and iNOS. These results indicated that FPL screened in this study could be expected to be used as a natural anti-inflammatory active substance in the functional food and pharmaceutical industries.

An ascorbic acid-decorated nanostructured surface on titanium inhibits breast cancer development and promotes osteogenesis.

The chest wall is the most frequent metastatic site of breast cancer (BC) and the metastasis usually occurs in a solitary setting. Chest wall resection is a way to treat solitary BC metastasis, but intraoperative bone defects and local tumor recurrence still affect the life quality of patients. Titanium-based prostheses are widely used for chest wall repair and reconstruction, but their inherent bio-inertness makes their clinical performance unfavorable. Nanostructured surfaces can give titanium substrates the ability to excellently modulate a variety of cellular functions. Ascorbic acid is a potential stimulator of tumor suppression and osteogenic differentiation. An ascorbic acid-decorated nanostructured titanium surface was prepared through alkali treatment and spin-coating technique and its effects on the biological responses of BC cells and osteoblasts were assessed. The results exhibited that the nanorod structure and ascorbic acid synergistically inhibited the proliferation, spreading, and migration of BC cells. Additionally, the ascorbic acid-decorated nanostructured surface significantly promoted the proliferation and osteogenic differentiation of osteoblasts. This work may provide valuable references for the clinical application of titanium materials in chest wall reconstruction after the resection of metastatic BC.

Brain organoids are new tool for drug screening of neurological diseases.

At the level of in vitro drug screening, the development of a phenotypic analysis system with high-content screening at the core provides a strong platform to support high-throughput drug screening. There are few systematic reports on brain organoids, as a new three-dimensional in vitro model, in terms of model stability, key phenotypic fingerprint, and drug screening schemes, and particularly regarding the development of screening strategies for massive numbers of traditional Chinese medicine monomers. This paper reviews the development of brain organoids and the advantages of brain organoids over induced neurons or cells in simulated diseases. The paper also highlights the prospects from model stability, induction criteria of brain organoids, and the screening schemes of brain organoids based on the characteristics of brain organoids and the application and development of a high-content screening system.

BM-MSCs overexpressing the Numb enhance the therapeutic effect on cholestatic liver fibrosis by inhibiting the ductular reaction.

BACKGROUND: Cholestatic liver fibrosis (CLF) is caused by inflammatory destruction of the intrahepatic bile duct and abnormal proliferation of the small bile duct after cholestasis. Activation of the Notch signaling pathway is required for hepatic stem cells to differentiate into cholangiocytes during the pathogenesis of CLF. Our previous research found that the expression of the Numb protein, a negative regulator of Notch signaling, was significantly reduced in the livers of patients with primary biliary cholangitis and CLF rats. However, the relationship between the Numb gene and CLF is largely unclear. In this study, we investigated the role of the Numb gene in the treatment of bile duct ligation (BDL)-induced CLF. METHODS: In vivo, bone marrow-derived mesenchymal stem cells (BM-MSCs) with Numb gene overexpression or knockdown obtained using lentivirus transfection were transplanted into the livers of rats with BDL-induced CLF. The effects of the Numb gene on stem cell differentiation and CLF were evaluated by performing histology, tests of liver function, and measurements of liver hydroxyproline, cytokine gene and protein levels. In vitro, the Numb gene was overexpressed or knocked down in the WB-F344 cell line by lentivirus transfection, Then, cells were subjected immunofluorescence staining and the detection of mRNA levels of related factors, which provided further evidence supporting the results from in vivo experiments. RESULTS: BM-MSCs overexpressing the Numb gene differentiated into hepatocytes, thereby inhibiting CLF progression. Conversely, BM-MSCs with Numb knockdown differentiated into biliary epithelial cells (BECs), thereby promoting the ductular reaction (DR) and the progression of CLF. In addition, we confirmed that knockdown of Numb in sodium butyrate-treated WB-F344 cells aggravated WB-F344 cell differentiation into BECs, while overexpression of Numb inhibited this process. CONCLUSIONS: The transplantation of BM-MSCs overexpressing Numb may be a useful new treatment strategy for CLF.

Roles of hepatic stellate cells in NAFLD: From the perspective of inflammation and fibrosis.

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common diseases and severe problems worldwide because of the global increase in obesity, dyslipidemia, hypertension, and type 2 diabetes mellitus. NAFLD includes a wide spectrum of liver diseases, the histological forms of which range from non-alcoholic fatty liver (NAFL), which is generally nonprogressive, to non-alcoholic steatohepatitis (NASH), which can progress to chronic hepatitis, liver cirrhosis (LC), and sometimes hepatocellular carcinoma (HCC). Unlike NAFL, as the progressive form of NAFLD, NASH is characterized by the presence of inflammation with or without fibrosis in addition to hepatic steatosis. Although it is widely known and proved that persistent hepatic injury and chronic inflammation in the liver activate quiescent hepatic stellate cells (HSCs) and lead to hepatic fibrosis, the three-step process of "inflammation-fibrosis-carcinoma" in NAFLD has not been investigated and clarified clearly. In this process, the initiation of inflammation in the liver and the function of various liver inflammatory cells have been discussed regularly, while the activated HSCs, which constitute the principal cells responsible for fibrosis and their cross-talk with inflammation, seem not to be investigated specifically and frequently. Also, accumulated evidence suggests that HSCs can not only be activated by inflammation but also participate in the regulation of liver inflammation. Therefore, it is necessary to investigate the unique roles of HSCs in NAFLD from the perspective of inflammation and fibrosis. Here, we review the pivotal effects and mechanisms of HSCs and highlight the potential value of HSC-targeted treatment methods in NAFLD.

Improved Ferroelectric Properties in Hf0.5Zr0.5O2 Thin Films by Microwave Annealing.

In the doped hafnia(HfO2)-based films, crystallization annealing is indispensable in forming ferroelectric phases. In this paper, we investigate the annealing effects of TiN/Hf0.5Zr0.5O2/TiN metal-ferroelectric-metal (MFM) capacitors by comparing microwave annealing (MWA) and rapid thermal annealing (RTA) at the same wafer temperature of 500 °C. The twofold remanent polarization (2Pr) of the MWA device is 63 µC/cm2, surpassing that of the RTA device (40 µC/cm2). Furthermore, the wake-up effect is substantially inhibited in the MWA device. The orthorhombic crystalline phase is observed in the annealed HZO films in the MWA and RTA devices, with a reduced TiN and HZO interdiffusion in MWA devices. Moreover, the MFM capacitors subjected to MWA treatment exhibit a lower leakage current, indicating a decreased defect density. This investigation shows the potential of MWA for application in ferroelectric technology due to the improvement in remanent polarization, wake-up effect, and leakage current.

RASSF1A Suppression as a Potential Regulator of Mechano-Pathobiology Associated with Mammographic Density in BRCA Mutation Carriers.

High mammographic density (MD) increases breast cancer (BC) risk and creates a stiff tissue environment. BC risk is also increased in BRCA1/2 gene mutation carriers, which may be in part due to genetic disruption of the tumour suppressor gene Ras association domain family member 1 (RASSF1A), a gene that is also directly regulated by tissue stiffness. High MD combined with BRCA1/2 mutations further increase breast cancer risk, yet BRCA1/2 mutations alone or in combination do not increase MD. The molecular basis for this additive effect therefore remains unclear. We studied the interplay between MD, stiffness, and BRCA1/2 mutation status in human mammary tissue obtained after prophylactic mastectomy from women at risk of developing BC. Our results demonstrate that RASSF1A expression increased in MCF10DCIS.com cell cultures with matrix stiffness up until ranges corresponding with BiRADs 4 stiffnesses (~16 kPa), but decreased in higher stiffnesses approaching malignancy levels (>50 kPa). Similarly, higher RASSF1A protein was seen in these cells when co-cultivated with high MD tissue in murine biochambers. Conversely, local stiffness, as measured by collagen I versus III abundance, repressed RASSF1A protein expression in BRCA1, but not BRCA2 gene mutated tissues; regional density as measured radiographically repressed RASSF1A in both BRCA1/2 mutated tissues. The combinatory effect of high MD and BRCA mutations on breast cancer risk may be due to RASSF1A gene repression in regions of increased tissue stiffness.