A comprehensive numerical procedure for high-intensity focused ultrasound ablation of breast tumour on an anatomically realistic breast phantom.

High-Intensity Focused Ultrasound (HIFU) as a promising and impactful modality for breast tumor ablation, entails the precise focalization of high-intensity ultrasonic waves onto the tumor site, culminating in the generation of extreme heat, thus ablation of malignant tissues. In this paper, a comprehensive three-dimensional (3D) Finite Element Method (FEM)-based numerical procedure is introduced, which provides exceptional capacity for simulating the intricate multiphysics phenomena associated with HIFU. Furthermore, the application of numerical procedures to an anatomically realistic breast phantom (ARBP) has not been explored before. The integrity of the present numerical procedure has been established through rigorous validation, incorporating comparative assessments with previous two-dimensional (2D) simulations and empirical data. For ARBP ablation, the administration of a 0.1 MPa pressure input pulse at a frequency of 1.5 MHz, sustained at the focal point for 10 seconds, manifests an ensuing temperature elevation to 80°C. It is noteworthy that, in contrast, the prior 2D simulation using a 2D phantom geometry reached just 72°C temperature under the identical treatment regimen, underscoring the insufficiency of 2D models, ascribed to their inherent limitations in spatially representing acoustic energy, which compromises their overall effectiveness. To underscore the versatility of this numerical platform, a simulation of a more clinically relevant HIFU therapy procedure has been conducted. This scenario involves the repositioning of the ultrasound focal point to three separate lesions, each spaced at 3 mm intervals, with ultrasound exposure durations of 6 seconds each and a 5-second interval for movement between focal points. This approach resulted in a more uniform high-temperature distribution at different areas of the tumour, leading to the ablation of almost all parts of the tumour, including its verges. In the end, the effects of different abnormal tissue shapes are investigated briefly as well. For solid mass tumors, 67.67% was successfully ablated with one lesion, while rim-enhancing tumors showed only 34.48% ablation and non-mass enhancement tumors exhibited 20.32% ablation, underscoring the need for multiple lesions and tailored treatment plans for more complex cases.

2024 Guidelines of the Taiwan Society of Cardiology on the Primary Prevention of Atherosclerotic Cardiovascular Disease --- Part I.

Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of death worldwide and in Taiwan. It is highly prevalent and has a tremendous impact on global health. Therefore, the Taiwan Society of Cardiology developed these best-evidence preventive guidelines for decision-making in clinical practice involving aspects of primordial prevention including national policies, promotion of health education, primary prevention of clinical risk factors, and management and control of clinical risk factors. These guidelines cover the full spectrum of ASCVD, including chronic coronary syndrome, acute coronary syndrome, cerebrovascular disease, peripheral artery disease, and aortic aneurysm. In order to enhance medical education and health promotion not only for physicians but also for the general public, we propose a slogan (2H2L) for the primary prevention of ASCVD on the basis of the essential role of healthy dietary pattern and lifestyles: "Healthy Diet and Healthy Lifestyles to Help Your Life and Save Your Lives". We also propose an acronym of the modifiable risk factors/enhancers and relevant strategies to facilitate memory: " ABC2D2EFG-I'M2 ACE": Adiposity, Blood pressure, Cholesterol and Cigarette smoking, Diabetes mellitus and Dietary pattern, Exercise, Frailty, Gout/hyperuricemia, Inflammation/infection, Metabolic syndrome and Metabolic dysfunction-associated fatty liver disease, Atmosphere (environment), Chronic kidney disease, and Easy life (sleep well and no stress). Some imaging studies can be risk enhancers. Some risk factors/clinical conditions are deemed to be preventable, and healthy dietary pattern, physical activity, and body weight control remain the cornerstone of the preventive strategy.

TET1 overexpression affects cell proliferation and apoptosis in aging ovaries.

PURPOSE: Along with the progress of society, human life expectancy has been increasing, and late marriage and late childbearing are the current trend. Since reproductive aging affects fertility, ovarian aging in women has become a major reproductive health issue in the current society. During ovarian aging, DNA methylation levels may change. The ten-eleven translocation (TET) protein family proteins TET1, TET2, and TET3 are important DNA demethylation enzymes, and differential expression of TET1, TET2, and TET3 may affect the proliferation and apoptosis of aging ovarian cells. The aim of this study was to investigate the role of TET1 in the regulation of ovarian aging. METHODS: The expression of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) was analyzed by immunofluorescence (IF) in young and aging ovaries of six 6-8-week-old female mice and six 6-8-month-old female mice. Then, the expression pattern of the TET protein family in young and aging ovaries of mice was investigated. To determine the impact of TET1 on ovarian development, the aging of IOSE-80, KGN, and SKOV-3 cells was induced with D-galactosidase (D-gal). Cells were then transfected using the TET1 overexpression vector or si-TET1. We assessed the proliferation and apoptosis of aging cells after transfection and analyzed the regulatory effect of TET1 expression on aging cells. Additionally, we verified the Tet1 expression in Tet1-KO mice. RESULTS: The 5mC to 5hmC transition, oocyte maturation, and blastocyst rate were reduced in aging mice compared to young mice. In aging mice ovaries, the expression levels of Tet1, Tet2, and Tet3 were reduced significantly, with Tet1 being particularly pronounced. The overexpression of TET1 promoted proliferation and inhibited apoptosis in aging human ovarian cells. Furthermore, Tet1 expression was very low in Tet1-KO C57BL/6 J mice ovaries. CONCLUSION: This study demonstrates that the expression levels of TET family proteins are low in aging ovaries, and the overexpression of TET1 can promote proliferation and inhibit apoptosis in aging ovarian cells.

Catalytic Edges in One-Dimensional Covalent Organic Frameworks for the Oxygen Reduction Reaction.

Metal-free covalent organic frameworks (COFs) are employed in oxygen reduction reactions (ORR) because of their diverse structural units and controllable catalytic sites, and the edge sites have high catalytic activity than the basal sites. However, it is still challenge to modulate the edge sites in COFs, because the extended frameworks in two- or three-dimensional topologies resulted in limited edge parts. In this study, we have demonstrated the edge site modulation engineering based on one dimensional (1D) COFs to catalyze the ORR, which featured distinct edge groups-carbonyl, diaminopyrazine, phenylimidazole, and benzaldehyde imidazole units. The synthesized COFs had same ordered frameworks, similar pore structure, but had different electronic states of the carbons along the edge sites, which results in tailored catalytic properties. Notably, the COF functionalized with a phenylimidazole edge group exhibited superior catalytic performance compared to the other synthesized COFs. And the theoretical calculation further revealed the different edge sites have tunable binding ability of the intermediates OOH*, which contributed modulated activity. Our findings introduce a novel way for designing COFs optimized for ORR applications through molecular level control of edge sites.

Stimulated Emission and Lasing from Bulk CdSe Nanocrystals.

Nanocrystals with a size in the regime of vanishing quantum confinement, or bulk nanocrystals (BNCs), have emerged recently as viable solution processable optical gain materials in the green part of the spectrum. Here, we show that these properties can be extended to the crucial red region using CdSe BNCs. Through quantitative time-resolved spectroscopy, we can model these nanocrystals as bulk semiconductors, thereby revealing that the gain originates from an unbound electron-hole plasma state. The gain is broadband in nature and is not capped by Auger processes, but by a slower second-order recombination resulting in nanosecond gain lifetimes. Finally, optically pumped lasers under femtosecond pulsed and quasi-continuous wave operation are demonstrated using a photonic crystal surface emitting laser cavity, thereby stretching from 635 to 720 nm. Our results indicate that compositional variation can indeed provide spectral versatility to the BNC concept, while preserving the excellent gain metrics associated with it.

Operando Decoding Ion-Conductive Switch in Stimuli-Responsive Hydrogel by Nanodiamond-Based Quantum Sensing.

Thermal-responsive hydrogels are developed as ion-conductive switchs for energy storage devices, however, the molecule mechanism of switch on/off remains unclear. Here, poly(N-isopropylacrylamide-co-acrylamide) hydrogel is synthesized as a model material and nanodiamond (ND) based quantum sensing for phase change study is developed. First, micro-scale phase separation with cross-linked mesh structure after sol-gel transition is visualized in situ and water molecules are trapped by polymer chains and on a chemically "frozen" state. Then, the nano-scale inhomogeneous distributions of viscosity, thermal conductivity and ionic mobility in hydrogel at high temperature are observed by measuring the rotation, translation and zero-field splitting of NDs. Besides, the ionic mobility of hydrogel is found to be dependent not only on temperature but also on polymer concentration. These observations suggested that the physical "wall" induced by inhomogeneous phase separation at microscopic scale blocked the ion conduction pathways, providing a potential intrinsic explanation for ion migration shut-down of ionic hydrogels at high temperature.

Long non-coding RNA LNC-POTEM-4 promotes HCC progression via the LNC-POTEM-4/miR-149-5p/Wnt4 signaling axis.

Information on the potential role of the long non-coding RNA LNC-POTEM-4 in cancer progression is limited. Our preliminary study found that LNC-POTEM-4 was overexpressed in hepatocellular carcinoma (HCC) tissues, which led us to further investigate the biological function and molecular mechanism of LNC-POTEM-4 in HCC development. LNC-POTEM-4 expression in HCC tissues was examined using transcriptome sequencing and quantitative reverse transcription PCR. The relationships between LNC-POTEM-4 and the stage and prognosis of HCC in patient data from the TCGA database were analyzed. The effects of LNC-POTEM-4 on proliferation, invasion/migration, and epithelial-mesenchymal transition marker expression in HCC cells were evaluated in vitro using gain- and loss-of-function assays, while its effects on tumor growth and metastasis were explored through animal experiments. A LNC-POTEM-4/microRNA (miR)-149-5p/Wnt4 regulatory signaling axis was identified using bioinformatics analysis, and dual luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Co-transfection of LNC-POTEM-4 and Wnt4 expression plasmids was employed to confirm the new signaling pathway. We found that LNC-POTEM-4 was overexpressed in HCC tissues and was linked to poor staging and prognosis. LNC-POTEM-4 promoted proliferation, invasion, migration, and the epithelial-mesenchymal transition of HCC cells in vitro. Silencing of LNC-POTEM-4 inhibited HCC growth and distant metastasis in vivo. Mechanically, LNC-POTEM-4 was found to function as a competitive endogenous RNA, upregulating Wnt4 by sponging miR-149-5p to promote HCC progression. Wnt4 overexpression may have counteracted the tumor-inhibition effect of LNC-POTEM-4 silencing. In conclusion, LNC-POTEM-4 upregulated Wnt4 to activate the Wnt signaling pathway and stimulate the malignancy tendency of HCC by sponging miR-149-5p, providing a prospective target for the detection and therapy of HCC. However, the effects of LNC-POTEM-4 on the miR-149-5p/Wnt4 signaling axis should be further studied in animal experiments.

Associations between sleep duration, depression status, and cognitive function among Chinese elderly: A community-based study.

BACKGROUND: The associations of sleep duration and depressive status on cognitive function among the elderly remain controversial. This study aimed to investigate the associative effects and mediating mechanisms between sleep duration and depressive status on cognitive function in elderly adults. METHODS: Participants were recruited from cross-sectional and cohort surveys of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We identified thresholds for sleep duration and depression and used logistic regression to explore their independent and joint effects on cognitive impairment. Further, we analyze the mediating effects of depressive status on the association between sleep duration and cognitive function. RESULTS: Of 13840 elderly (median age: 84 years, female: 54.6 %), 2835 (20.5 %) had cognitive impairment. Compared with those who slept 6-8 h, the ORs (95%CIs) for those who slept < 6 h and > 8 h were 0.98 (0.85, 1.12) and 1.48 (1.32, 1.66). Compared with non-depressed, the OR (95%CI) for the depressed participants was 1.74 (1.53, 1.98). Compared with those with sleep 6-8 h and none-depression, those with sleep > 8 h and depression had the highest odds of cognitive impairment (OR = 2.40, 95%CI: 1.88-3.07). Additionally, Compared with those who slept 6-8 h, the associations between depression-mediated short and long sleep and cognitive impairment were 51.1 % and 6.5 %, respectively. LIMITATIONS: Cross-sectional studies require caution in the interpretation of causal associations. CONCLUSIONS: Long sleep and depression were independently and jointly associated with higher odds of cognitive impairment among the Chinese elderly, and short sleep increased the risk of cognitive impairment by promoting the prevalence of depression.

SCG2 mediates blood-brain barrier dysfunction and schizophrenia-like behaviors after traumatic brain injury.

Traumatic brain injury (TBI), which is characterized by acute neurological dysfunction, is also one of the most widely recognized environmental risk factors for various neurological and psychiatric disorders. However, the role of TBI in neurological perturbation and the mechanisms underlying these disorders remain unknown. We evaluated transcriptional changes in cells of the frontal cortex after TBI by exploiting single-cell RNA sequencing (scRNA-Seq). We adopted the gene expression omnibus and scRNA-Seq to identify the mediation by secretogranin II (SCG2) of TBI-induced schizophrenia. Astrocytes are a principal source of SCG2 in the frontal cortex after TBI. Our analysis indicated that SCG2-triggered disruption of the blood-brain barrier (BBB) via the CypA-MMP-9 signaling pathway. Furthermore, astrocytic SCG2 knockout in the frontal cortex reduced BBB damage, mitigated inflammation, and inhibited schizophrenia after TBI. In conclusion, we identified the SCG2-CypA-MMP-9 signaling pathway in reactive astrocytes as a key switch in the protection of the BBB and provided a novel therapeutic avenue for treating psychiatric disorders after TBI.

Relationship between genotype, phenotype, and refractive status in patients of inherited retinal degeneration.

BACKGROUND: To elucidate the relationship between inherited retinal disease, visual acuity and refractive error development in Asian patients. SUBJECTS: Five hundred phakic eyes with refractive data were analysed in this retrospective cohort. Diseases were categorized by clinical phenotypes, and the prevalent genotypes identified in the Taiwan Inherited Retinal Degeneration Project were analysed. Consecutive surveys in Taiwan have provided the rates of myopia in the general population. RESULTS: No differences were observed among the disease phenotypes with respect to myopia (P = 0.098) and high myopia rates (P = 0.037). The comparison of refractive error between retinitis pigmentosa and diseases mainly affecting the central retina showed no difference, and the refraction analyses in diseases of different onset ages yielded no significance. Moreover, there was no difference in the myopia rate between the diseases and general population. Among the genotypes, a higher spherical equivalent was seen in RPGR and PROM1-related patients and emmetropic trends were observed in patients with CRB1 and PRPF31 mutations. Furthermore, significantly poorer visual acuity was found in ABCA4, CRB1 and PROM1-related patients, and more preserved visual acuity was seen in patients with EYS, USH2A, and RDH12 mutations. CONCLUSIONS: No significant differences were observed in visual acuity, refractive state and myopia rate between patients with inherited retinal disease and the general population, and different subtypes of inherited retinal disease shared similar refractive state, except for higher cylindrical dioptres found in patients with Leber's congenital amaurosis. The heterogeneity of disease-causing genes in Asian patients may lead to variable refractive state.