LSD2 Is an Epigenetic Player in Multiple Types of Cancer and Beyond.

Histone demethylases, enzymes responsible for removing methyl groups from histone proteins, have emerged as critical players in regulating gene expression and chromatin dynamics, thereby influencing various cellular processes. LSD2 and LSD1 have attracted considerable interest among these demethylases because of their associations with cancer. However, while LSD1 has received significant attention, LSD2 has not been recognized to the same extent. In this study, we conduct a comprehensive comparison between LSD2 and LSD1, with a focus on exploring LSD2's implications. While both share structural similarities, LSD2 possesses unique features as well. Functionally, LSD2 shows diverse roles, particularly in cancer, with tissue-dependent roles. Additionally, LSD2 extends beyond histone demethylation, impacting DNA methylation, cancer cell reprogramming, E3 ubiquitin ligase activity and DNA damage repair pathways. This study underscores the distinct roles of LSD2, providing insights into their contributions to cancer and other cellular processes.

The structural basis of eukaryotic chaperonin TRiC/CCT: Action and folding.

Accurate folding of proteins in living cells often requires the cooperative support of molecular chaperones. Eukaryotic group II chaperonin Tailless complex polypeptide 1-Ring Complex (TRiC) accomplishes this task by providing a folding chamber for the substrate that is regulated by an Adenosine triphosphate (ATP) hydrolysis-dependent cycle. Once delivered to and recognized by TRiC, the nascent substrate enters the folding chamber and undergoes folding and release in a stepwise manner. During the process, TRiC subunits and cochaperones such as prefoldin and phosducin-like proteins interact with the substrate to assist the overall folding process in a substrate-specific manner. Coevolution between the components is supposed to consult the binding specificity and ultimately expand the substrate repertoire assisted by the chaperone network. This review describes the TRiC chaperonin and the substrate folding process guided by the TRiC network in cooperation with cochaperones, specifically focusing on recent progress in structural analyses.

Clinical pathways for Korean medicine: An implementation approach to impact on the clinical process and association with attitudes.

Background: South Korea's Ministry of Health and Welfare has developed clinical pathways for Korean Medicine (KM-CPs). As part of this initiative, a panel comprising Korean Medicine doctors (KMD) was assembled. This implementation study aimed to preliminarily explore how KM-CP implementation affects the appropriateness and efficiency of the clinical process and its relation to attitude. Methods: Through random sampling, 311 KMDs were recruited as panelists to participate in two surveys. The surveys included information regarding the KM clinical environment and KM-CP implementation. A panel management program and educational materials were provided to KMDs between the two survey periods. Only 262 KMDs who responded to both surveys were included in the analysis. Three analyses were conducted: 1) descriptive analysis of the study variables, 2) panel analysis using the ordered logit regression model to elucidate the impact of KM-CP on the appropriateness and efficiency of the clinical process, and 3) ordered logit regression analysis of the association between KM-CP implementation and attitude. Results: More than two-thirds of the KMDs attempted to adopt KM-CP, with mostly positive perception expressed by these doctors. However, expectations and concerns coexist with the standardization of KM-CP. Cases in which KM-CPs were partially and mostly implemented respectively had negative and positive effects on the appropriateness and efficiency of the clinical process compared to those in which KM-CPs were not implemented. Compared to neutral attitude, positive and very positive attitudes tended to be associated with increased implementation of KM-CP. However, statistical significances were not observed. Conclusions: The impact of KM-CP on the clinical process and its association with attitude were found to be statistically unclear or inconsistent. Considering the study limitations and implications, we suggest a policy and academic strategies aimed at fostering improvement to enhance its utility.

Torenia sp. Extracts Contain Multiple Potent Antitumor Compounds with Nematocidal Activity, Triggering an Activated DNA Damage Checkpoint and Defective Meiotic Progression.

Previously, we analyzed 316 herbal extracts to evaluate their potential nematocidal properties in Caenorhabditis elegans. In this study, our attention was directed towards Torenia sp., resulting in reduced survival and heightened larval arrest/lethality, alongside a noticeable decrease in DAPI-stained bivalent structures and disrupted meiotic progression, thus disrupting developmental processes. Notably, Torenia sp. extracts activated a DNA damage checkpoint response via the ATM/ATR and CHK-1 pathways, hindering germline development. LC-MS analysis revealed 13 compounds in the Torenia sp. extracts, including flavonoids, terpenoids, tanshinones, an analog of resveratrol, iridoids, carotenoids, fatty acids, and alkaloids. Of these, 10 are known for their antitumor activity, suggesting the potential of Torenia species beyond traditional gardening, extending into pharmaceutical and therapeutic applications.

Impact of Residential Segregation on Healthcare Utilization and Perceived Quality of Care Among Informal Caregivers in the United States.

This study aimed to investigate the impact of racial residential segregation on healthcare utilization and perceived quality of care among informal caregivers in the US. It further assessed potential variations in the estimated impact across caregivers' race and socioeconomic status. We used data from the Health Information National Trends Survey Data Linkage Project (fielded in 2020) for a sample of 583 self-identified informal caregivers in the US. Fitting a series of regression models with the maximum likelihood estimation, we computed the beta coefficients (ß) of interest and their associated Wald 95% confidence limits (CI). Caregivers who resided in areas with higher segregation, compared to those living in lower segregated areas, were less likely to visit a healthcare professional [ß = - 2.08; Wald 95%CI - 2.093, - 2.067] (moderate); [ß = - 2.53; Wald 95%CI - 2.549, - 2.523] (high)]. Further, caregivers residing in moderate [ß = - 0.766; Wald 95%CI - 0.770, - 0.761] and high [ß = - 0.936; Wald 95%CI - 0.941, - 0.932] segregation regions were less likely to perceive a better quality of care compared to those located in low segregation areas. Moreover, as segregation level increased, Black caregivers were less likely to see a health professional, less frequently used healthcare services, and had poorer perceived healthcare quality when compared to Whites. Our findings indicate that higher residential segregation is associated with lower healthcare utilization, such as visiting a healthcare professional, and poorer perceived healthcare quality among informal caregivers. Given the essential role of informal caregivers in the current healthcare system, it is vital to investigate and address challenges associated with access to and quality of essential healthcare services to improve caregivers' health and well-being, specifically for caregivers of minority backgrounds.

A structural vista of phosducin-like PhLP2A-chaperonin TRiC cooperation during the ATP-driven folding cycle.

Proper cellular proteostasis, essential for viability, requires a network of chaperones and cochaperones. ATP-dependent chaperonin TRiC/CCT partners with cochaperones prefoldin (PFD) and phosducin-like proteins (PhLPs) to facilitate folding of essential eukaryotic proteins. Using cryoEM and biochemical analyses, we determine the ATP-driven cycle of TRiC-PFD-PhLP2A interaction. PhLP2A binds to open apo-TRiC through polyvalent domain-specific contacts with its chamber's equatorial and apical regions. PhLP2A N-terminal H3-domain binding to subunits CCT3/4 apical domains displace PFD from TRiC. ATP-induced TRiC closure rearranges the contacts of PhLP2A domains within the closed chamber. In the presence of substrate, actin and PhLP2A segregate into opposing chambers, each binding to positively charged inner surface residues from CCT1/3/6/8. Notably, actin induces a conformational change in PhLP2A, causing its N-terminal helices to extend across the inter-ring interface to directly contact a hydrophobic groove in actin. Our findings reveal an ATP-driven PhLP2A structural rearrangement cycle within the TRiC chamber to facilitate folding.

Strain modulation in crumpled Si nanomembranes: Light detection beyond the Si absorption limit.

Although Si is extensively used in micro-nano electronics, its inherent optical absorption cutoff at 1100-nm limits its photonic and optoelectronic applications in visible to partly near infrared (NIR) spectral range. Recently, strain engineering has emerged as a promising approach for extending device functionality via tuning the material properties, including change in optical bandgap. In this study, the reduction in bandgap with applied strain was used for extending the absorption limit of crystalline Si up to 1310 nm beyond its intrinsic bandgap, which was achieved by creating the crumpled structures in Si nanomembranes (NMs). The concept was used to develop a prototype NIR image sensor by organizing metal-semiconductor-metal-configured crumpled Si NM photosensing pixels in 6 × 6 array. The geometry-controlled, self-sustained strain induction in Si NMs provided an exclusive photon management with shortening of optical bandgap and enhanced photoresponse beyond the conventional Si absorption limit.

Nonconventional Strain Engineering for Uniform Biaxial Tensile Strain in MoS2 Thin Film Transistors.

Strain engineering has been employed as a crucial technique to enhance the electrical properties of semiconductors, especially in Si transistor technologies. Recent theoretical investigations have suggested that strain engineering can also markedly enhance the carrier mobility of two-dimensional (2D) transition-metal dichalcogenides (TMDs). The conventional methods used in strain engineering for Si and other bulk semiconductors are difficult to adapt to ultrathin 2D TMDs. Here, we report a strain engineering approach to apply the biaxial tensile strain to MoS2. Metal-organic chemical vapour deposition (MOCVD)-grown large-area MoS2 films were transferred onto SiO2/Si substrate, followed by the selective removal of the underneath Si. The release of compressive residual stress in the oxide layer induces strain in MoS2 on top of the SiO2 layer. The amount of strain can be precisely controlled by the thickness of oxide stressors. After the transistors were fabricated with strained MoS2 films, the array of strained transistors was transferred onto plastic substrates. This process ensured that the MoS2 channels maintained a consistent tensile strain value across a large area.

Aster glehni Extract, Including Caffeoylquinic Acids as the Main Constituents, Induces PPAR ß/δ-Dependent Muscle-Type Change and Myogenesis in Apolipoprotein E Knockout Mice.

To probe the functions of Aster glehni (AG) extract containing various caffeoylquinic acids on dyslipidemia, obesity, and skeletal muscle-related diseases focused on the roles of skeletal muscle, we measured the levels of biomarkers involved in oxidative phosphorylation and type change of skeletal muscle in C2C12 cells and skeletal muscle tissues from apolipoprotein E knockout (ApoE KO) mice. After AG extract treatment in cell and animal experiments, western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) were used to estimate the levels of proteins that participated in skeletal muscle type change and oxidative phosphorylation. AG extract elevated protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), phosphorylated 5'-AMP-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor beta/delta (PPARß/δ), myoblast determination protein 1 (MyoD), and myoglobin in skeletal muscle tissues. Furthermore, it elevated the ATP concentration. However, protein expression of myostatin was decreased by AG treatment. In C2C12 cells, increments of MyoD, myoglobin, myosin, ATP-producing pathway, and differentiation degree by AG were dependent on PPARß/δ and caffeoylquinic acids. AG extract can contribute to the amelioration of skeletal muscle inactivity and sarcopenia through myogenesis in skeletal muscle tissues from ApoE KO mice, and function of AG extract may be dependent on PPARß/δ, and the main functional constituents of AG are trans-5-O-caffeoylquinic acid and 3,5-O-dicaffeoylquinic acid. In addition, in skeletal muscle, AG has potent efficacies against dyslipidemia and obesity through the increase of the type 1 muscle fiber content to produce more ATP by oxidative phosphorylation in skeletal muscle tissues from ApoE KO mice.

Deep-learning model for diagnostic clue: detecting the dural tail sign for meningiomas on contrast-enhanced T1 weighted images.

Background: Meningiomas are the most common primary central nervous system tumors, and magnetic resonance imaging (MRI), especially contrast-enhanced T1 weighted image (CE T1WI), is used as a fundamental imaging modality for the detection and analysis of the tumors. In this study, we propose an automated deep-learning model for meningioma detection using the dural tail sign. Methods: The dataset included 123 patients with 3,824 dural tail signs on sagittal CE T1WI. The dataset was divided into training and test datasets based on specific time point, and 78 and 45 patients were comprised for the training and test dataset, respectively. To compensate for the small sample size of the training dataset, 39 additional patients with 69 dural tail signs from the open dataset were appended to the training dataset. A You Only Look Once (YOLO) v4 network was trained with sagittal CE T1WI to detect dural tail signs. The normal group dataset, comprised of 51 patients with no abnormal finding on MRI, was employed to evaluate the specificity of the trained model. Results: The sensitivity and false positive average were 82.22% and 29.73, respectively, in the test dataset. The specificity and false positive average were 17.65% and 3.16, respectively, in the normal dataset. Most of the false-positive cases in the test dataset were enhancing vessels, misinterpreted as dural thickening. Conclusions: The proposed model demonstrates an automated detection system for the dural tail sign to identify meningioma in general screening MRI. Our model can facilitate and alleviate radiologists' reading process by notifying the possibility of incidental dural mass based on dural tail sign detection.

Exploring the Impact of Onobrychis cornuta and Veratrum lobelianum Extracts on C. elegans: Implications for MAPK Modulation, Germline Development, and Antitumor Properties.

In an era of increasing interest in the potential health benefits of medicinal foods, the need to assess their safety and potential toxicity remains a critical concern. While these natural remedies have garnered substantial attention for their therapeutic potential, a comprehensive understanding of their effects on living organisms is essential. We examined 316 herbal extracts to determine their potential nematocidal attributes in Caenorhabditis elegans. Approximately 16% of these extracts exhibited the capacity to induce diminished survival rates and larval arrest, establishing a correlation between larval arrest and overall worm viability. Certain extracts led to an unexpected increase in male nematodes, accompanied by a discernible reduction in DAPI-stained bivalent structures and perturbed meiotic advancement, thereby disrupting the conventional developmental processes. Notably, Onobrychis cornuta and Veratrum lobelianum extracts activated a DNA damage checkpoint response via the ATM/ATR and CHK-1 pathways, thus hindering germline development. Our LC-MS analysis revealed jervine in V. lobelianum and nine antitumor compounds in O. cornuta. Interestingly, linoleic acid replicated phenotypes induced by O. cornuta exposure, including an increased level of pCHK-1 foci, apoptosis, and the MAPK pathway. Mutants in the MAPK pathway mitigated the decline in worm survival, underscoring its importance in promoting worm viability. This study reveals complex interactions between herbal extracts and C. elegans processes, shedding light on potential antitumor effects and mechanisms. The findings provide insights into the complex landscape of herbal medicine's impact on a model organism, offering implications for broader applications.

PAX3-FOXO1 uses its activation domain to recruit CBP/P300 and shape RNA Pol2 cluster distribution.

Activation of oncogenic gene expression from long-range enhancers is initiated by the assembly of DNA-binding transcription factors (TF), leading to recruitment of co-activators such as CBP/p300 to modify the local genomic context and facilitate RNA-Polymerase 2 (Pol2) binding. Yet, most TF-to-coactivator recruitment relationships remain unmapped. Here, studying the oncogenic fusion TF PAX3-FOXO1 (P3F) from alveolar rhabdomyosarcoma (aRMS), we show that a single cysteine in the activation domain (AD) of P3F is important for a small alpha helical coil that recruits CBP/p300 to chromatin. P3F driven transcription requires both this single cysteine and CBP/p300. Mutants of the cysteine reduce aRMS cell proliferation and induce cellular differentiation. Furthermore, we discover a profound dependence on CBP/p300 for clustering of Pol2 loops that connect P3F to its target genes. In the absence of CBP/p300, Pol2 long range enhancer loops collapse, Pol2 accumulates in CpG islands and fails to exit the gene body. These results reveal a potential novel axis for therapeutic interference with P3F in aRMS and clarify the molecular relationship of P3F and CBP/p300 in sustaining active Pol2 clusters essential for oncogenic transcription.