Flexoelectricity is an electromechanical coupling between electrical polarization and a strain gradient
that enables mechanical manipulation of polarization without applying an electrical bias
. ...Recently, flexoelectricity was directly demonstrated by mechanically switching the out-of-plane polarization of a uniaxial system with a scanning probe microscope tip
. However, the successful application of flexoelectricity in low-symmetry multiaxial ferroelectrics and therefore active manipulation of multiple domains via flexoelectricity have not yet been achieved. Here, we demonstrate that the symmetry-breaking flexoelectricity offers a powerful route for the selective control of multiple domain switching pathways in multiaxial ferroelectric materials. Specifically, we use a trailing flexoelectric field that is created by the motion of a mechanically loaded scanning probe microscope tip. By controlling the SPM scan direction, we can deterministically select either stable 71° ferroelastic switching or 180° ferroelectric switching in a multiferroic magnetoelectric BiFeO
thin film. Phase-field simulations reveal that the amplified in-plane trailing flexoelectric field is essential for this domain engineering. Moreover, we show that mechanically switched domains have a good retention property. This work opens a new avenue for the deterministic selection of nanoscale ferroelectric domains in low-symmetry materials for non-volatile magnetoelectric devices and multilevel data storage.
Apocrine carcinoma is a rare breast cancer subtype. As such, the genomic characteristics of apocrine carcinoma with triple negative immunohistochemical results (TNAC), which has been treated as ...triple negative breast cancer (TNBC), have not been revealed. In this study, we evaluated the genomic characteristics of TNAC compared to TNBC with low Ki-67 (LK-TNBC). In the genetic analysis of 73 TNACs and 32 LK-TNBCs, the most frequently mutated driver gene in TNAC was TP53 (16/56, 28.6%), followed by PIK3CA (9/56, 16.1%), ZNF717 (8/56, 14.3%), and PIK3R1 (6/56, 10.71%). Mutational signature analysis showed enrichment of defective DNA mismatch repair (MMR)-related signatures (SBS6 and SBS21) and the SBS5 signature in TNAC, whereas an APOBEC activity-associated mutational signature (SBS13) was more prominent in LK-TNBC (Student's t test, p < 0.05). In intrinsic subtyping, 38.4% of TNACs were classified as luminal A, 27.4% as luminal B, 26.0% as HER2-enriched (HER2-E), 2.7% as basal, and 5.5% as normal-like. The basal subtype was the most dominant subtype (43.8%) in LK-TNBC (p < 0.001), followed by luminal B (21.9%), HER2-E (21.9%), and luminal A (12.5%). In the survival analysis, TNAC had a five-year disease-free survival (DFS) rate of 92.2% compared to 59.1% for LK-TNBC (P = 0.001) and a five-year overall survival (OS) rate of 95.3% compared to 74.6% for LK-TNBC (P = 0.0099). TNAC has different genetic characteristics and better survival outcomes than LK-TNBC. In particular, normal-like and luminal A subtypes in TNAC have much better DFS and OS than other intrinsic subtypes. Our findings are expected to impact medical practice for patients diagnosed with TNAC.
Artemisia in East Asia includes a number of economically important taxa that are widely used for food, medicinal, and ornamental purposes. The identification of taxa, however, has been hampered by ...insufficient diagnostic morphological characteristics and frequent natural hybridization. Development of novel DNA markers or barcodes with sufficient resolution to resolve taxonomic issues of Artemisia in East Asia is significant challenge.
To establish a molecular basis for taxonomic identification and comparative phylogenomic analysis of Artemisia, we newly determined 19 chloroplast genome (plastome) sequences of 18 Artemisia taxa in East Asia, de novo-assembled and annotated the plastomes of two taxa using publicly available Illumina reads, and compared them with 11 Artemisia plastomes reported previously. The plastomes of Artemisia were 150,858-151,318 base pairs (bp) in length and harbored 87 protein-coding genes, 37 transfer RNAs, and 8 ribosomal RNA genes in conserved order and orientation. Evolutionary analyses of whole plastomes and 80 non-redundant protein-coding genes revealed that the noncoding trnH-psbA spacer was highly variable in size and nucleotide sequence both between and within taxa, whereas the coding sequences of accD and ycf1 were under weak positive selection and relaxed selective constraints, respectively. Phylogenetic analysis of the whole plastomes based on maximum likelihood and Bayesian inference analyses yielded five groups of Artemisia plastomes clustered in the monophyletic subgenus Dracunculus and paraphyletic subgenus Artemisia, suggesting that the whole plastomes can be used as molecular markers to infer the chloroplast haplotypes of Artemisia taxa. Additionally, analysis of accD and ycf1 hotspots enabled the development of novel markers potentially applicable across the family Asteraceae with high discriminatory power.
The complete sequences of the Artemisia plastomes are sufficiently polymorphic to be used as super-barcodes for this genus. It will facilitate the development of new molecular markers and study of the phylogenomic relationships of Artemisia species in the family Asteraceae.
Flexoelectricity can play an important role in the reversal of the self‐polarization direction in epitaxial BiFeO3 thin films. The flexoelectric and interfacial effects compete with each other to ...determine the self‐polarization state. In Region I, the self‐polarization is downward because the interfacial effect is more dominant than the flexoelectric effect. In Region II, the self‐polarization is upward, because the flexoelectric effect becomes more dominant than the interfacial effect.
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•Chitin were successfully extracted from shrimp shell using deep eutectic solvent (DES).•High yield of chitin was obtained using DES compared with conventional method.•13CNMR confirms ...that obtained chitin has a high purity.•Chitin films were produced and physicochemically characterized.•DES chitin films showed similar properties to commercial chitin film.
In this study, chitin was exclusively extracted from shrimp shells (Marsupenaeus japonicas) through a green solvent called deep eutectic solvent (DES), and various types of DES were utilized to extract chitin. The physicochemical properties of the obtained chitin were compared with the conventional method. A high purity of chitin was obtained while using DES-8 (choline chloride-malonic acid) with a yield of 19.41% ± 1.35%, and purity was confirmed using 13C nuclear magnetic resonance. The DES-produced chitin was utilized to produce chitin films and was compared with standard chitin films. The obtained films were characterized by SEM, AFM, TGA, DSC, FTIR, mechanical properties, moisture sorption, swelling behavior, and biodegradation. The DES film showed similar properties to the standard film, while the mechanical properties, swelling behavior, and biodegradation of the DES chitin films proved to be similar to standard chitin film. These chitin films can be used as wound healing resources.
Paclitaxel (PTX), etoposide (ETP), and rapamycin (RAPA) have different mechanisms, allowing multiple pathways to be targeted simultaneously, effectively treating various cancers. However, these drugs ...have a low hydrosolubility, limiting clinical applications. Therefore, we used pH-sensitive polymeric micelles to effectively control the drug release in cancer cells and to improve the water solubility of PTX, ETP, and RAPA. The synergistic effect of PTX, ETP, and RAPA was evaluated in gastric cancer, and the combination index values were evaluated. Thin-film hydration was used to prepare PTX/ETP/RAPA-loaded mPEG-pH-PCL micelles, and various physicochemical properties of these micelles were evaluated. In vitro cytotoxicity, pH-sensitivity, drug release profiles, in vivo pharmacokinetics, and biodistribution studies of PTX/ETP/RAPA-loaded mPEG-pH-PCL micelles were evaluated. In the pH-sensitivity evaluation, the size of the micelles increased more rapidly at a pH of 5.5 than at a pH of 7.4. The release rate of each drug increased with decreasing pH values in PTX/ETP/RAPA-loaded mPEG-pH-PCL micelles. In vitro and in vivo studies demonstrated that PTX/ETP/RAPA-loaded mPEG-pH-PCL micelles exhibit different drug release behaviors depending on the pH of the tumor and normal tissues and increased bioavailability and circulation time in the blood than solutions. Therefore, we propose that PTX/ETP/RAPA- loaded mPEG-pH-PCL micelles are advantageous for gastric cancer treatment in drug delivery systems.
Although estrogen receptor (ER) expression levels affect the prognosis of breast cancer, studies about progesterone receptor (PR) expression levels are insufficient, especially in young breast cancer ...(YBC). The purpose of this study was to compare clinical characteristics and prognosis according to PR expression levels in invasive breast cancer patients.
A prospective cohort study was conducted to identify YBC patients with invasive carcinoma diagnosed at an age of less than 40 years old between 2013 and 2018. Clinicopathologic features and prognosis of ER-positive and human epidermal growth factor receptor 2 (HER2)-negative patients were investigated. Patients were stratified into strong PR (PR-positive cell proportion > 10%), low PR (PR-positive cell proportion = 1~10%), and PR-negative (PR-positive cell proportion < 1%).
Among 458 patients enrolled, 386 (84.3%), 26 (5.7%), and 46 (10.0%) were categorized into strong PR, low PR, and PR-negative groups, respectively. The median follow-up duration was 58.6 months. Compared with the strong PR group, low PR and PR-negative groups were more likely to have high Ki-67 and a high nuclear grade. Low R and PR-negative groups had significantly worse disease-free survival (DFS) and distant metastasis-free survival (DMFS) than the strong PR group (
= 0.0033,
= 0007). Low PR group had an even higher risk of distant metastasis than PR-negative patients. Low PR patients and PR-negative had significantly lower overall survival (OS) rates than strong PR.
Low PR might be a prognostic factor of ER-positive/HER2-negative in YBC.
Ovarian cancer has a high mortality rate due to difficult detection at an early stage. It is necessary to develop a novel anticancer treatment that demonstrates improved efficacy while reducing ...toxicity. Here, using the freeze-drying method, micelles encapsulating paclitaxel (PTX) and sorafenib (SRF) with various polymers were prepared, and the optimal polymer (mPEG-
-PCL) was selected by measuring drug loading (%), encapsulation efficiency (%), particle size, polydispersity index, and zeta potential. The final formulation was selected based on a molar ratio (PTX:SRF = 1:2.3) with synergistic effects on two ovarian cancer cell lines (SKOV3-red-fluc, HeyA8). In the in vitro release assay, PTX/SRF micelles showed a slower release than PTX and SRF single micelles. In pharmacokinetic evaluation, PTX/SRF micelles showed improved bioavailability compared to PTX/SRF solution. In in vivo toxicity assays, no significant differences were observed in body weight between the micellar formulation and the control group. The anticancer effect of PTX/SRF combination therapy was improved compared to the use of a single drug. In the xenografted BALB/c mouse model, the tumor growth inhibition rate of PTX/SRF micelles was 90.44%. Accordingly, PTX/SRF micelles showed improved anticancer effects compared to single-drug therapy in ovarian cancer (SKOV3-red-fluc).
AIMThe role of regional nodal irradiation (RNI) after preoperative systemic treatment (PST) with targeted therapy for HER2-positive breast cancer remains uncertain. This study aimed to investigate ...the impact of RNI on locoregional recurrence (LRR) and disease-free survival (DFS) outcomes after docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) for PST.METHODSWe retrospectively analyzed 255 patients who were treated with six cycles of TCHP between 2016 and 2019. The patients were divided into four groups based on clinical nodal involvement: group A, with no nodal disease; group B, with axillary lymph node (AXL) level I; group C, with AXL level I with II/III; and group D, with supraclavicular or internal mammary nodes.RESULTSThe RNI group had more advanced nodal disease (C/D) than the no RNI group (56.9 % vs. 6.8 %). With a median follow-up of 51.3 months, there were two (0.8 %), three (1.2 %), and 15 (5.9 %) local, regional, and distant metastases, respectively. LRR did not differ significantly according to the RNI (2.6 % vs. 1.0 %, p = 0.651). Group D had the most frequent distant metastases (17.5 %; p = 0.005). The 4-year DFS rate was 92.7 %, and DFS did not improve significantly after RNI (p = 0.074). When stratified by clinical nodal groups and pathological axillary response, RNI had no effect on LRR/DFS outcomes.CONCLUSIONWith a rare incidence of LRR, RNI did not significantly affect LRR or DFS in patients with HER2-positive breast cancer after with PST-TCHP. However, intensive systemic treatment is required for advanced diseases (C/D). Selective de-intensified RNI and intensified systemic treatment should be investigated in future studies.
Accurate risk stratification can improve lymphoma management, but current volumetric
F-fluorodeoxyglucose (FDG) indicators require time-consuming segmentation of all lesions in the body. Herein, we ...investigated the prognostic values of readily obtainable metabolic bulk volume (MBV) and bulky lesion glycolysis (BLG) that measure the single largest lesion.
The study subjects were a homogeneous cohort of 242 newly diagnosed stage II or III diffuse large B-cell lymphoma (DLBCL) patients who underwent first-line R-CHOP treatment. Baseline PET/CT was retrospectively analyzed for maximum transverse diameter (MTD), total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), MBV, and BLG. Volumes were drawn using 30% SUVmax as threshold. Kaplan-Meier survival analysis and the Cox proportional hazards model assessed the ability to predict overall survival (OS) and progression-free survival (PFS).
During a median follow-up period of 5.4 years (maximum of 12.7 years), events occurred in 85 patients, including progression, relapse, and death (65 deaths occurred at a median of 17.6 months). Receiver operating characteristic (ROC) analysis identified an optimal TMTV of 112 cm
, MBV of 88 cm
, TLG of 950, and BLG of 750 for discerning events. Patients with high MBV were more likely to have stage III disease; worse ECOG performance; higher IPI risk score; increased LDH; and high SUVmax, MTD, TMTV, TLG, and BLG. Kaplan-Meier survival analysis showed that high TMTV (
= 0.005 and < 0.001), MBV (both
< 0.001), TLG (
< 0.001 and 0.008), and BLG (
= 0.018 and 0.049) were associated with significantly worse OS and PFS. On Cox multivariate analysis, older age (> 60 years; HR, 2.74; 95% CI, 1.58-4.75;
< 0.001) and high MBV (HR, 2.74; 95% CI, 1.05-6.54;
= 0.023) were independent predictors of worse OS. Older age (hazard ratio HR, 2.90; 95% CI, 1.74-4.82;
< 0.001) and high MBV (HR, 2.36; 95% CI, 1.15-6.54;
= 0.032) were also independent predictors of worse PFS. Furthermore, among subjects ≤60 years, high MBV remained the only significant independent predictor of worse OS (HR, 4.269; 95% CI, 1.03-17.76;
= 0.046) and PFS (HR, 6.047; 95% CI, 1.73-21.11;
= 0.005). Among subjects with stage III disease, only greater age (HR, 2.540; 95% CI, 1.22-5.30;
= 0.013) and high MBV (HR, 6.476; 95% CI, 1.20-31.9;
= 0.030) were significantly associated with worse OS, while greater age was the only independent predictor of worse PFS (HR, 6.145; 95% CI, 1.10-4.17;
= 0.024).
MBV easily obtained from the single largest lesion may provide a clinically useful FDG volumetric prognostic indicator in stage II/III DLBCL patients treated with R-CHOP.
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