YAP promotes global mRNA translation to fuel oncogenic growth despite starvation.

Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) play fundamental roles in stem/progenitor cell expansion during homeostasis, and their dysregulation often leads to tissue overgrowth. Here, we show that YAP activation is sufficient to overcome the restriction of global protein synthesis induced by serum starvation, enabling cells to sustain proliferation and survival despite an unfavorable environment. Mechanistically, YAP/TAZ selectively promoted the mTORC1-dependent translation of mRNAs containing 5' terminal oligopyrimidine (5'TOP) motifs, ultimately increasing the cellular polysome content. Interestingly, DNA damage-inducible transcript 4 (DDIT4), a negative regulator of mTORC1, was upregulated by serum starvation but repressed by YAP/TAZ. DDIT4 was sufficient to suppress the translation and transformative potential of uveal melanoma cells, which are often serum unresponsive due to G protein mutations. Our findings reveal a vital role for protein synthesis as a key modality of YAP/TAZ-induced oncogenic transformation and indicate the potential for targeting mTORC1 or translation to treat YAP/TAZ-driven malignancies.

Supramolecular Association of a Block Copolymer via Strong Hydrogen Bonding to Form Self-Healable Ionogels.

The drive to enhance the operational durability and reliability of stretchable and wearable electronic and electrochemical devices has led to the exploration of self-healing materials that can recover from both physical and functional failures. In the present study, we fabricated a self-healable solid polymer electrolyte, referred to as an ionogel, using reversible hydrogen bonding between the ureidopyrimidone units of a block copolymer (BCP) network swollen in an ionic liquid (IL). The BCP consisted of poly(styrene-b-(methyl acrylate-r-ureidopyrimidone methacrylate)) [poly(S-b-(MA-r-UPyMA)], with the IL-phobic polystyrene forming micellar cores that were interconnected via intercorona hydrogen bonding between the ureidopyrimidone units. By precisely regulating the molecular weight and the composition of the hydrogen-bondable motifs, the mechanical, electrical, and self-healing characteristics of the ionogel were systematically evaluated. The resulting ionogel samples exhibited suitable stretchability, ionic conductivity, and room-temperature self-healability due to reversible hydrogen bonding. To highlight the applicability of the self-healing ionogel as a high-capacitance gate insulator, an electrolyte-gated transistor (EGT) was fabricated using a poly(3-hexylthiophene-2,5-diyl) semiconductor, and the performance of the EGT was fully recovered from a complete cut without any external stimuli.

Spatial-temporal impacts of invasive Spartina anglica on the rates and pathways of organic carbon mineralization and resulting C-Fe-S cycles in the intertidal wetland of the Han River Estuary, Yellow Sea.

To elucidate the spatial-temporal impact of invasive saltmarsh plant Spartina anglica on the biogeochemical processes in coastal wetlands, we investigated the rates and partitioning of organic carbon (Corg) mineralization in three representative benthic habitats: (1) vegetated sediments inhabited by invasive S. anglica (SA); vegetated sediments by indigenous Suaeda japonica; and (3) unvegetated mud flats. Microbial metabolic rates were greatly stimulated at the SA site during the active growing seasons of Spartina, indicating that a substantial amount of organic substrates was supplied from the high below-ground biomass of Spartina. At the SA site, sulfate reduction dominated the Corg mineralization pathways during the plant growing season, whereas iron reduction dominated during the non-growing season. Overall, due to its greater biomass and longer growing season than native Suaeda, the expansion of invasive Spartina is likely to greatly alter the Corg-Fe-S cycles and carbon storage capacity in the coastal wetlands.

Alterations in Brain Morphometric Networks and Their Relationship with Memory Dysfunction in Patients with Type 2 Diabetes Mellitus.

Cognitive dysfunction, a significant complication of type 2 diabetes mellitus (T2DM), can potentially manifest even from the early stages of the disease. Despite evidence of global brain atrophy and related cognitive dysfunction in early-stage T2DM patients, specific regions vulnerable to these changes have not yet been identified. The study enrolled patients with T2DM of less than five years' duration and without chronic complications (T2DM group, n=100) and demographically similar healthy controls (control group, n=50). High-resolution T1-weighted magnetic resonance imaging data were subjected to independent component analysis to identify structurally significant components indicative of morphometric networks. Within these networks, the groups' gray matter volumes were compared, and distinctions in memory performance were assessed. In the T2DM group, the relationship between changes in gray matter volume within these networks and declines in memory performance was examined. Among the identified morphometric networks, the T2DM group exhibited reduced gray matter volumes in both the precuneus (Bonferroni-corrected p=0.003) and insular-opercular (Bonferroni-corrected p=0.024) networks relative to the control group. Patients with T2DM demonstrated significantly lower memory performance than the control group (p=0.001). In the T2DM group, reductions in gray matter volume in both the precuneus (r=0.316, p=0.001) and insular-opercular (r=0.199, p=0.047) networks were correlated with diminished memory performance. Our findings indicate that structural alterations in the precuneus and insular-opercular networks, along with memory dysfunction, can manifest within the first 5 years following a diagnosis of T2DM.

Ultrathin All-Solid-State MoS2-Based Electrolyte Gated Synaptic Transistor with Tunable Organic-Inorganic Hybrid Film.

Electrolyte-gated synaptic transistors (EGSTs) have attracted considerable attention as synaptic devices owing to their adjustable conductance, low power consumption, and multi-state storage capabilities. To demonstrate high-density EGST arrays, 2D materials are recommended owing to their excellent electrical properties and ultrathin profile. However, widespread implementation of 2D-based EGSTs has challenges in achieving large-area channel growth and finding compatible nanoscale solid electrolytes. This study demonstrates large-scale process-compatible, all-solid-state EGSTs utilizing molybdenum disulfide (MoS2) channels grown through chemical vapor deposition (CVD) and sub-30 nm organic-inorganic hybrid electrolyte polymers synthesized via initiated chemical vapor deposition (iCVD). The iCVD technique enables precise modulation of the hydroxyl group density in the hybrid matrix, allowing the modulation of proton conduction, resulting in adjustable synaptic performance. By leveraging the tunable iCVD-based hybrid electrolyte, the fabricated EGSTs achieve remarkable attributes: a wide on/off ratio of 109, state retention exceeding 103, and linear conductance updates. Additionally, the device exhibits endurance surpassing 5 × 104 cycles, while maintaining a low energy consumption of 200 fJ/spike. To evaluate the practicality of these EGSTs, a subset of devices is employed in system-level simulations of MNIST handwritten digit recognition, yielding a recognition rate of 93.2%.

Impact of sleep disturbance in shift workers on hippocampal volume and psychomotor speed.

STUDY OBJECTIVES: Shift work interferes with circadian rhythms, affecting sleep quality and cognitive function. Poor sleep quality in shift worker (SW)s can impair psychomotor performance due to fatigue and sleepiness, increasing the risk of errors, accidents, and reduced productivity. Given the potential for atrophic changes in the hippocampus due to sleep disturbances, our study investigates how poor sleep quality correlates with hippocampal structural alterations and impacts psychomotor performance among SWs. METHODS: We recruited 100 SWs, classifying them based on sleep quality into two groups: good sleep-SW group (n = 59) and poor sleep-SW group (n = 41). Sleep quality was assessed using both 7-day actigraphy for sleep efficiency and the Pittsburgh Sleep Quality Index. A control group of 106 non-SWs without sleep problems (non-SW group) was also included for comparison. The outcome measures were psychomotor speed and hippocampal volumes, both total and by subfield. RESULTS: The poor sleep-SW group showed significantly smaller hippocampal volumes than both the good sleep-SW group (p < .001) and the non-SW group (p = .003). Longer shift work years correlated with greater reductions in hippocampal volume in this group (r = -0.42, p = .009), unlike in the good sleep-SW group (r = 0.08, p = .541). Furthermore, they demonstrated declines in psychomotor speed relative to the non-SW group (p = .006), which correlated with smaller hippocampal volumes (r = 0.37, p = .020). CONCLUSIONS: SWs with poor sleep quality exhibit significant hippocampal volume reductions and psychomotor speed decline, underscoring the importance of early intervention and support for sleep issues in this population.

RNA helicase DEAD-box-5 is involved in R-loop dynamics of preimplantation embryos.

OBJECTIVE: R-loops are DNA:RNA triplex hybrids, and their metabolism is tightly regulated by transcriptional regulation, DNA damage response, and chromatin structure dynamics. R-loop homeostasis is dynamically regulated and closely associated with gene transcription in mouse zygotes. However, the factors responsible for regulating these dynamic changes in the R-loops of fertilized mouse eggs have not yet been investigated. This study examined the functions of candidate factors that interact with R-loops during zygotic gene activation. METHODS: In this study, we used publicly available next-generation sequencing datasets, including low-input ribosome profiling analysis and polymerase II chromatin immunoprecipitation-sequencing (ChIP-seq), to identify potential regulators of R-loop dynamics in zygotes. These datasets were downloaded, reanalyzed, and compared with mass spectrometry data to identify candidate factors involved in regulating R-loop dynamics. To validate the functions of these candidate factors, we treated mouse zygotes with chemical inhibitors using in vitro fertilization. Immunofluorescence with an anti-R-loop antibody was then performed to quantify changes in R-loop metabolism. RESULTS: We identified DEAD-box-5 (DDX5) and histone deacetylase-2 (HDAC2) as candidates that potentially regulate R-loop metabolism in oocytes, zygotes and two-cell embryos based on change of their gene translation. Our analysis revealed that the DDX5 inhibition of activity led to decreased R-loop accumulation in pronuclei, indicating its involvement in regulating R-loop dynamics. However, the inhibition of histone deacetylase-2 activity did not significantly affect R-loop levels in pronuclei. CONCLUSION: These findings suggest that dynamic changes in R-loops during mouse zygote development are likely regulated by RNA helicases, particularly DDX5, in conjunction with transcriptional processes. Our study provides compelling evidence for the involvement of these factors in regulating R-loop dynamics during early embryonic development.

Analysis of Out-of-Hospital First Aid for Recovery of Spontaneous Circulation after Cardiac Arrest in Korea.

The characteristics of an individual patient experiencing out-of-hospital cardiac arrest who recovered spontaneous circulation with the assistance of witnesses and paramedics were examined. The analysis of bystander cardiopulmonary resuscitation (CPR) and the professional first aid efforts of paramedics in the pre-hospital environment is pivotal to enhancing the survival rate of out-of-hospital cardiac arrest patients. The data used in this study were extracted from the Korea Centers for Disease Control and Prevention (KCDC) nationally recognized statistics, Acute Heart Failure big data survey. Out-of-hospital cardiac arrest (OHCA) customer data were collected from the Gangwon Fire Headquarters public information database as social management data. The data were analyzed using SPSS 24. The study's results emphasized the significance of offering basic CPR training to the public. This is evident from the fact that 90.5% of the first witnesses in the study performed CPR on OHCA patients, resulting in the recovery of spontaneous circulation (ROSC). The majority of patients with ROSC were male, with the highest age group being 41-50 years. Heart disease, hypertension, and diabetes were common medical conditions. The rate of witnessing cardiac arrest was high. Among the first witnesses, about 78.4% were of cardiac arrest incidents involving family members, co-workers, or acquaintances; 12.2% were on-duty medical healthcare personnel; and 9.5% were off-duty healthcare personnel. Cardiac arrest was treated in 83.8% of cases, with 90% of witnesses performing CPR. The percentage of witnesses that used an automated external defibrillator (AED) was 13.5%. In this study, the rates of ECG monitoring, CPR performance, and defibrillation performed by paramedics were high, but intravascular access and drug administration had a lower rate of performance. The time elapsed depended on the patient's physical fitness. The study found that paramedics had the highest CPC restoration rate in patients with cardiac arrest, followed by EMTs and nurses. Significant differences were observed in cerebral performance scores after care by these paramedics and nurses. To increase the performance of AEDs, more AEDs should be installed in public spaces so that the public can access them conveniently in cases of emergency. In addition, it is necessary to improve the quality of professional first aid physical activity services performed by first-class paramedics.

Healing Donor Defect States in CVD-Grown MoS2 Field-Effect Transistors Using Oxygen Plasma with a Channel-Protecting Barrier.

Molybdenum disulfide (MoS2 ), a metal dichalcogenide, is a promising channel material for highly integrated scalable transistors. However, intrinsic donor defect states, such as sulfur vacancies (Vs ), can degrade the channel properties and lead to undesired n-doping. A method for healing the donor defect states in monolayer MoS2 is proposed using oxygen plasma, with an aluminum oxide (Al2 O3 ) barrier layer that protects the MoS2 channel from damage by plasma treatment. Successful healing of donor defect states in MoS2 by oxygen atoms, even in the presence of an Al2 O3 barrier layer, is confirmed by X-ray photoelectron spectroscopy, photoluminescence, and Raman spectroscopy. Despite the decrease in 2D sheet carrier concentration (Δn2D = -3.82×1012 cm-2 ), the proposed approach increases the on-current and mobility by 18% and 44% under optimal conditions, respectively. Metal-insulator transition occurs at electron concentrations of 5.7×1012 cm-2 and reflects improved channel quality. Finally, the activation energy (Ea ) reduces at all the gate voltages (VG ) owing to a decrease in Vs , which act as a localized state after the oxygen plasma treatment. This study demonstrates the feasibility of plasma-assisted healing of defects in 2D materials and electrical property enhancement and paves the way for the development of next-generation electronic devices.

INO80 function is required for mouse mammary gland development, but mutation alone may be insufficient for breast cancer.

The aberrant function of ATP-dependent chromatin remodeler INO80 has been implicated in multiple types of cancers by altering chromatin architecture and gene expression; however, the underlying mechanism of the functional involvement of INO80 mutation in cancer etiology, especially in breast cancer, remains unclear. In the present study, we have performed a weighted gene co-expression network analysis (WCGNA) to investigate links between INO80 expression and breast cancer sub-classification and progression. Our analysis revealed that INO80 repression is associated with differential responsiveness of estrogen receptors (ERs) depending upon breast cancer subtype, ER networks, and increased risk of breast carcinogenesis. To determine whether INO80 loss induces breast tumors, a conditional INO80-knockout (INO80 cKO) mouse model was generated using the Cre-loxP system. Phenotypic characterization revealed that INO80 cKO led to reduced branching and length of the mammary ducts at all stages. However, the INO80 cKO mouse model had unaltered lumen morphology and failed to spontaneously induce tumorigenesis in mammary gland tissue. Therefore, our study suggests that the aberrant function of INO80 is potentially associated with breast cancer by modulating gene expression. INO80 mutation alone is insufficient for breast tumorigenesis.