PARP1-TRIM44-MRN loop dictates the response to PARP inhibitors.

PARP inhibitors (PARPi) show selective efficacy in tumors with homologous recombination repair (HRR)-defects but the activation mechanism of HRR pathway in PARPi-treated cells remains enigmatic. To unveil it, we searched for the mediator bridging PARP1 to ATM pathways by screening 211 human ubiquitin-related proteins. We discovered TRIM44 as a crucial mediator that recruits the MRN complex to damaged chromatin, independent of PARP1 activity. TRIM44 binds PARP1 and regulates the ubiquitination-PARylation balance of PARP1, which facilitates timely recruitment of the MRN complex for DSB repair. Upon exposure to PARPi, TRIM44 shifts its binding from PARP1 to the MRN complex via its ZnF UBP domain. Knockdown of TRIM44 in cells significantly enhances the sensitivity to olaparib and overcomes the resistance to olaparib induced by 53BP1 deficiency. These observations emphasize the central role of TRIM44 in tethering PARP1 to the ATM-mediated repair pathway. Suppression of TRIM44 may enhance PARPi effectiveness and broaden their use even to HR-proficient tumors.

SrTiO3 and (Ba,Sr)TiO3 Films Epitaxially Grown on SrRuO3 Using Atomic Layer Deposition.

High dielectric constant (k) materials have been investigated to improve the performance of dynamic random access memory (DRAM) capacitors. However, the conventional binary oxides have reached their fundamental limit of k < 100. In this study, we investigated alternative ternary oxides, SrTiO3 (STO) and (Ba,Sr)TiO3 (BSTO), which were epitaxially grown on SrRuO3 (SRO) using atomic layer deposition (ALD). The structural compatibility between SRO and STO enables the in situ crystallization of STO during ALD at a low temperature of 300 °C. Consequently, STO on SRO exhibited no film deformation, a common issue during high temperature postdeposition annealing, and maintained superior crystallinity at a thin thickness down to 50 Å. Furthermore, the dielectric constant of STO can be adjusted by modulating its tunable ferroelectric and dielectric properties through Ba doping. BSTO, with a high dielectric constant (kmax:527) achieved at a Ba doping concentration of approximately 50%, displayed a low leakage current density (3.9 × 10-8 A cm-2 @ 1 V) and demonstrated excellent reliability of 1012 cycles in the metal-insulator-metal capacitors. This study proposes a promising alternative to satisfy the extreme EOT required for next-generation DRAM capacitors.

Oral hygiene changes & compliance with telemonitoring device in individuals with intellectual/developmental disabilities: a randomized controlled crossover trial.

OBJECTIVE: Advances in mobile technology are helping with health management practices, and smart toothbrushes provide proper dental care by collecting and analyzing users' toothbrushing data. The purpose of this study is to assess the effect of a telemonitoring device on oral hygiene management in individuals with intellectual or developmental disabilities and its role in promoting oral health. MATERIALS AND METHODS: Participants were split into two groups: one initially using the telemonitoring device (telemonitoring device/manual toothbrush) and the other using it later (manual toothbrush/telemonitoring device), with a one-month washout period. The study compared plaque index, halitosis, changes in oral microbiota, and guardian questionnaire responses between the groups. RESULTS: In period 1, the QHI index score significantly decreased from 1.93 to 0.83 in the group using the remote monitoring device, compared to an increase from 1.75 to 2.01 in the manual toothbrush group. Additionally, toothbrushing frequency, time, and cooperation increased by 0.82 ± 0.60, 0.82 ± 1.16, and 1.09 ± 0.94, respectively, with initial telemonitoring device use. However, these measures decreased by -1.45 ± 0.68, -1.09 ± 0.70, and - 1.00 ± 1.00 after switching to a manual toothbrush, and decreased by -0.64 ± 0.67, -0.27 ± 1.19, and 0.09 ± 0.94 overall, respectively. However, there were no significant differences in oral microbiota between the groups at these different time points. CONCLUSIONS: The study shows that telemonitoring devices effectively reduce plaque index and improve toothbrushing frequency, time, and cooperation. However, these benefits decrease after switching to a manual toothbrush. Follow-up is needed to assess satisfaction and compliance with telemonitoring device use. CLINICAL RELEVANCE: Using telemonitoring devices in the oral health management of individuals with intellectual and developmental disabilities can improve their oral health quality.

Incidence and outcomes of delayed intracranial hemorrhage: a population-based cohort study.

Head trauma is a common reason for emergency department (ED) visits. Delayed intracranial hemorrhage (ICH) in patients with minor head trauma is a major concern, but controversies exist regarding the incidence of delayed ICH and discharge planning at the ED. This study aimed to determine the incidence of delayed ICH in adults who developed ICH after a negative initial brain computed tomography (CT) at the ED and investigate the clinical outcomes for delayed ICH. This nationwide population cohort study used data from the National Health Insurance Service of Korea from 2013 to 2019. Adult patients who presented to an ED due to trauma and were discharged after a negative brain CT examination were selected. The main outcomes were the incidence of ICH within 14 days after a negative brain CT at initial ED visit and the clinical outcomes of patients with and without delayed ICH. The study patients were followed up to 1 year after the initial ED discharge. Cox proportional hazard regression analysis was used to estimate the hazard ratio for all-cause 1-year mortality of delayed ICH. During the 7-year study period, we identified 626,695 adult patients aged 20 years or older who underwent brain CT at the ED due to minor head trauma, and 2666 (0.4%) were diagnosed with delayed ICH within 14 days after the first visit. Approximately two-thirds of patients (64.3%) were diagnosed with delayed ICH within 3 days, and 84.5% were diagnosed within 7 days. Among the patients with delayed ICH, 71 (2.7%) underwent neurosurgical intervention. After adjustment for age, sex, Charlson Comorbidity Index, and insurance type, delayed ICH (adjusted hazard ratio, 2.15; 95% confidence interval, 1.86-2.48; p < 0.001) was significantly associated with 1-year mortality. The incidence of delayed ICH was 0.4% in the general population, with the majority diagnosed within 7 days. These findings suggest that patient discharge education for close observation for a week may be a feasible strategy for the general population.

Targeted Delivery of Nanoparticle-Conveyed Neutrophils to the Glioblastoma Site for Efficient Therapy.

Glioblastoma is a common brain tumor that poses considerable challenges in drug delivery. In this study, we investigated the potential of cell-based nanoparticles for targeted drug delivery to the glioblastoma sites. The anticancer drug of temozolomide (TMZ)-loaded T7-cholesterol nanoparticle micelles efficiently delivered nanoparticles to neutrophils and, subsequently, to the tumors. T7 is a cell-penetrating peptide that enhances the delivery of T7/TMZ to the target cells. T7 also serves as a transferrin target peptide, enabling targeted delivery to tumors. T7-conjugated cholesterol can self-assemble into micelles in aqueous solution and attach to the membrane of neutrophils. We confirmed that T7/TMZ nanoparticle micelles were efficiently located inside the neutrophils. Thereafter, T7/TMZ-conveyed neutrophils were administered to a glioblastoma mouse model, enabling neutrophils to penetrate the blood-brain barrier and deliver drugs directly to the tumor site. We evaluated the drug delivery efficiency and therapeutic effects of intravenous injection of T7/TMZ-conveyed neutrophils to a glioblastoma mouse model. These results demonstrate the promising role of neutrophil-based nanoparticle delivery systems in the targeted therapy of glioblastoma.

Prognostic Significance of 18 F-FDG PET/CT Radiomics in Patients With Resectable Pancreatic Ductal Adenocarcinoma Undergoing Curative Surgery.

PURPOSE: This study aimed to investigate the prognostic significance of PET/CT radiomics to predict overall survival (OS) in patients with resectable pancreatic ductal adenocarcinoma (PDAC). METHODS: We enrolled 627 patients with resectable PDAC who underwent preoperative 18 F-FDG PET/CT and subsequent curative surgery. Radiomics analysis of the PET/CT images for the primary tumor was performed using the Chang-Gung Image Texture Analysis toolbox. Radiomics features were subjected to least absolute shrinkage and selection operator (LASSO) regression to select the most valuable imaging features of OS. The prognostic significance was evaluated by Cox proportional hazards regression analysis. Conventional PET parameters and LASSO score were assessed as predictive factors for OS by time-dependent receiver operating characteristic curve analysis. RESULTS: During a mean follow-up of 28.8 months, 378 patients (60.3%) died. In the multivariable Cox regression analysis, tumor differentiation, resection margin status, tumor stage, and LASSO score were independent prognostic factors for OS (HR, 1.753, 1.669, 2.655, and 2.946; all P < 0.001, respectively). The time-dependent receiver operating characteristic curve analysis showed that the LASSO score had better predictive performance for OS than conventional PET parameters. CONCLUSIONS: The LASSO score using the 18 F-FDG PET/CT radiomics of the primary tumor was the independent prognostic factor for predicting OS in patients with resectable PDAC and may be helpful in determining therapeutic and follow-up plans for these patients.

Neutrophil Migration Is Mediated by VLA-6 in the Inflamed Adipose Tissue.

Adipose tissue, well known for its endocrine function, plays an immunological role in the body. The inflamed adipose tissue under LPS-induced systemic inflammation is characterized by the dominance of pro-inflammatory immune cells, particularly neutrophils. Although migration of macrophages toward damaged or dead adipocytes to form a crown-like structure in inflamed adipose tissue has been revealed, the neutrophilic interaction with adipocytes or the extracellular matrix remains unknown. Here, we demonstrated the involvement of adhesion molecules, particularly integrin α6ß1, of neutrophils in adipocytes or the extracellular matrix of inflamed adipose tissue interaction. These results suggest that disrupting the adhesion between adipose tissue components and neutrophils may govern the accumulation of excessive neutrophils in inflamed tissues, a prerequisite in developing anti-inflammatory therapeutics by inhibiting inflammatory immune cells.

Highly Efficient Preparation of Length and Width-Controllable Donor-Acceptor Nanoribbons via Polymerization-Induced Crystallization-Driven Self-Assembly of Fully Conjugated Block Copolymers.

Despite the high potential of one-dimensional (1D) donor-acceptor (D-A) coaxial nanostructures in bulk-heterojunction solar cell applications, the preparation of such 1D nanostructures using π-conjugated polymers has remained elusive. Herein, we demonstrate the first example of D-A semiconducting nanoribbons based on fully conjugated block copolymers (BCPs) prepared in a highly efficient procedure with controllable width and length via living crystallization-driven self-assembly (CDSA). Initially, Suzuki-Miyaura catalyst-transfer polymerization was employed to successfully synthesize BCPs containing two types of acceptor shells as the first block, followed by a donor poly(3-propylthiophene) core as the second block. The limited solubility and high crystallinity of the core induced a polymerization-induced crystallization-driven self-assembly (PI-CDSA) of the BCPs into nanoribbons during polymerization, providing a tunable width (7.6-39.6 nm) depending on the length of the polymer backbone. Surprisingly, purifying as-synthesized BCPs via simple precipitation directly yielded short and uniform seed structures, greatly shortening the overall protocol by eliminating the time-consuming process of initial aging and breaking down to the seed required for the conventional CDSA. With this new highly efficient method, we achieved length control over a broad range from 169 to 2210 nm, with high precision (Lw/Ln < 1.20). Furthermore, combining self-seeding and seeded growth from two different D-A-type BCPs enabled continuous living epitaxial growth from each end of the nanoribbons, resulting in B-A-B triblock D-A semiconducting comicelles with controlled length.

Different Role of TRF1 and TRF2 Expression in Non-Small Cell Lung Cancers.

Background: TRF1, TRF2, and TERT (Telomerase reverse transcriptase) are telomere-associated factors that regulate telomere length. Genetic changes in these genes may be associated with cancer pathogenesis; however, this relationship has not yet been comprehensively elucidated in lung cancer. Aim: : Exploring the clinicopathologic and prognostic values of TRF1, TRF2, and TERT mRNA expression in non-small cell lung cancers (NSCLC). Methods: : The clinical significance of TRF1, TRF2, and TERT expression in 141 patients with NSCLC was investigated. Additionally, these findings were supported by the open big data from The Cancer Genome Atlas (TCGA). Results: : TRF1 and TRF2 expression levels tended to be associated with smoking, and TERT expression was positively correlated with age. The survival analysis showed that TRF1 expression predicted a better prognosis for squamous cell carcinoma (SCC), whereas TRF2 expression was associated with a shorter survival in adenocarcinoma. TCGA data also showed a better prognosis for SCC with TRF1 expression. However, the TRF2 results were not in agreement with our data. Conclusions: : We present the clinical and prognostic values of TRF1, TRF2, and TERT expression in NSCLC tissues and TCGA. Our findings suggest that TRF1 expression is a possible prognostic marker for NSCLC, particularly SCC.

Comparison of the efficacy and safety of SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration.

To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration, this randomized, double-masked, parallel-group, multicenter study was conducted in 14 countries from 13 August 2020 to 8 September 2022. Patients with neovascular age-related macular degeneration. With subfoveal, juxtafoveal, or extrafoveal choroidal neovascularization were aged 50 years or older. Intravitreal injection of SCD411 or aflibercept (2.0 mg) were administered every 4 weeks for the first three injections and every 8 weeks until week 48. The primary efficacy endpoint was the change in best-corrected visual acuity from baseline to week 8 with an adjusted equivalence margin of ± 3.0 letters. Patients were randomly assigned to receive either SCD411 (n = 288) or reference aflibercept (n = 288). A total of 566 participants (98.3%) completed week 8 of the study. The least-squares mean difference of change in best-corrected visual acuity from baseline to week 8 (SCD411-aflibercept) was - 0.4 letters (90% confidence interval = - 1.6 to 0.9). The incidence of ocular (69 of 287 [24.0%] vs. 71 of 286 [24.8%]) and serious ocular (5 of 287 [1.7%] vs. 3 of 286 [1.0%]) treatment-emergent adverse effects were similar between the SCD411 and aflibercept groups. Immunogenicity analysis revealed a low incidence of neutralizing antibody formation in both groups. In conclusion, SCD411 has equivalent efficacy compared with reference aflibercept in patients with neovascular age-related macular degeneration and has a comparable safety profile. The results support the potential use of SCD411 for the treatment of neovascular age-related macular degeneration.

Nationwide evaluation of microplastic properties in municipal wastewater treatment plants in South Korea.

Wastewater treatment plants (WWTPs) are considered a significant microplastic discharge source. To evaluate the amount and characteristics of microplastics discharged from WWTPs in South Korea, we selected 22 municipal WWTPs nationally and investigated microplastics at each treatment stage. The mean microplastic removal efficiency by WWTPs was >99%, and most of the microplastics were removed by sedimentation with the second clarifier during wastewater treatment. Consequently, the microplastic removal efficiency of WWTPs did not significantly differ from that of the adopted wastewater treatment technology because a second clarifier was applied in most WWTPs. However, for WWTPs operating a tertiary treatment process, the removal efficiency was enhanced compared with that of WWTPs discharging after a second clarifier. Although the microplastic removal efficiency was high by WWTP, the discharge contribution to the water environment could not be ignored because of the amount of treated wastewater, resulting in an increase of 5.8-270.9 items/m3 of microplastics in the receiving water. The characteristics of microplastics in WWTPs, including their components, shape, and size, were also evaluated. The most detected components included polytetrafluoroethylene and polyester. Most microplastics detected were categorized as fragments and fibers, while other types were hardly detected. The size of more than 70% of the microplastics detected in WWTPs was under 300 µm, implying that the size of microplastics required to control in WWTPs was much smaller than the defined size of microplastics. An evaluation of the correlation between other pollution factors and microplastic abundance did not reveal positive correlations, and microplastic occurrence was not affected by changing seasons, which may need to be evaluated with further studies. Research should also be performed on the effect of influent sources on the level of microplastic abundance and fate of ultrafine plastics in WWTPs.

USP11 modulates mitotic progression and senescence by regulating the p53-p21 axis through MDM2 deubiquitination.

USP11 is overexpressed in colorectal cancer (CRC) and breast cancer tissues compared to normal tissues, suggesting a role in promoting cell proliferation and inhibiting cell death. In this study, we observed that depleting USP11 inhibits cell proliferation and delays cell cycle progression. This depletion leads to increased p53 protein levels due to an extended half-life, resulting in elevated p21 mRNA levels in a p53-dependent manner. The rise in p53 protein upon USP11 depletion is linked to a reduced half-life of MDM2, a known E3 ligase for p53, via enhanced polyubiquitination of MDM2. These findings indicate that USP11 might act as a deubiquitinase for MDM2, regulating the MDM2-p53-p21 axis. Additionally, USP11 depletion promotes the induction of senescent cells in a manner dependent on its deubiquitinase activity. Our findings provide insights into the physiological significance of high USP11 expression in primary tumors and its reduction in senescent cells, highlighting its potential as a therapeutic target.

Myeloid-derived suppressor cells in pleural effusion as a diagnostic marker for early discrimination of pulmonary tuberculosis from pneumonia.

Introduction: Tuberculous pleural effusion (TPE) stands as one of the primary forms of extrapulmonary tuberculosis (TB) and frequently manifests in regions with a high prevalence of TB, consequently being a notable cause of pleural effusion in such areas. However, the differentiation between TPE and parapneumonic pleural effusion (PPE) presents diagnostic complexities. This study aimed to evaluate the potential of myeloid-derived suppressor cells (MDSCs) in the pleural fluid as a potential diagnostic marker for distinguishing between TPE and PPE. Methods: Adult patients, aged 18 years or older, who presented to the emergency room of a tertiary referral hospital and received a first-time diagnosis of pleural effusion, were prospectively enrolled in the study. Various immune cell populations, including T cells, B cells, natural killer (NK) cells, and MDSCs, were analyzed in both pleural fluid and peripheral blood samples. Results: In pleural fluid, the frequency of lymphocytes, including T, B, and NK cells, was notably higher in TPE compared to PPE. Conversely, the frequency of polymorphonuclear (PMN)-MDSCs was significantly higher in PPE. Notably, compared to traditional markers such as the neutrophil-to-lymphocyte ratio and adenosine deaminase level, the frequency of PMN-MDSCs emerged as a more effective discriminator between PPE and TPE. PMN-MDSCs demonstrated superior positive and negative predictive values and exhibited a higher area under the curve in the receiver operating characteristic curve analysis. PMN-MDSCs in pleural effusion increased the levels of reactive oxygen species and suppressed the production of interferon-gamma from T cells following nonspecific stimulation. These findings suggest that MDSC-mediated immune suppression may contribute to the pathology of both TPE and PPE. Discussion: The frequency of PMN-MDSCs in pleural fluid is a clinically useful indicator for distinguishing between TPE and PPE.

Intelligent Resource Allocation Scheme Using Reinforcement Learning for Efficient Data Transmission in VANET.

Vehicular ad hoc networks (VANETs) use multiple channels to communicate using wireless access in vehicular environment (WAVE) standards to provide a variety of vehicle-related applications. The current IEEE 802.11p WAVE communication channel structure is composed of one control channel (CCH) and several service channels (SCHs). SCHs are used for non-safety data transmission, while the CCH is used for broadcasting beacons, control, and safety. WAVE devices transmit data that alternate between CCHs and SCHs, and each channel is active for a duration called the CCH interval (CCHI) and SCH interval (SCHI), respectively. Currently, both intervals are fixed at 50 ms. However, fixed-length intervals cannot effectively respond to dynamically changing traffic loads. Additionally, when many vehicles are simultaneously using the limited channel resources for data transmission, the network performance significantly degrades due to numerous packet collisions. Herein, we propose an adaptive resource allocation technique for efficient data transmission. The technique dynamically adjusts the SCHI and CCHI to improve network performance. Moreover, to reduce data collisions and optimize the network's backoff distribution, the proposed scheme applies reinforcement learning (RL) to provide an intelligent channel access algorithm. The simulation results demonstrate that the proposed scheme can ensure high throughputs and low transmission delays.

A Comprehensive Analysis of HOXB13 Expression in Hepatocellular Carcinoma.

Background and objectives: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is caused by multiple factors. To explore novel targets for HCC treatment, we comprehensively analyzed the expression of HomeoboxB13 (HOXB13) and its role in HCC. Materials and Methods: The clinical significance of HCC was investigated using open gene expression databases, such as TIMER, UALCAN, KM, OSlihc, and LinkedOmics, and immunohistochemistry analysis. We also analyzed cell invasion and migration in HCC cell lines transfected with HOXB13-siRNA and their association with MMP9, E2F1, and MEIS1. Results: HOXB13 expression was higher in fibrolamellar carcinoma than in other histological subtypes. Its expression was associated with lymph node metastasis, histological stage, and tumor grade. It was positively correlated with immune cell infiltration of B cells (R = 0.246), macrophages (R = 0.182), myeloid dendritic cells (R = 0.247), neutrophils (R = 0.117), and CD4+ T cells (R = 0.258) and negatively correlated with immune cell infiltration of CD8+ T cells (R = -0.107). A positive correlation was observed between HOXB13, MMP9 (R = 0.176), E2F1 (R = 0.241), and MEIS1 (R = 0.189) expression (p < 0.001). The expression level of HOXB13 was significantly downregulated in both HepG2 and PLC/PFR/5 cell lines transfected with HOXB13-siRNA compared to that in cells transfected with NC siRNA (p < 0.05). Additionally, HOXB13 significantly affected cell viability and wound healing. Conclusions: HOXB13 overexpression may lead to poor prognosis in patients with HCC. Additional in vivo studies are required to improve our understanding of the biological role and the exact mechanism of action of HOXB13 in HCC.

Advancements in Interfacial Engineering for Perovskite Light-Emitting Diodes.

Perovskite light-emitting diodes (PeLEDs) have gained significant attention due to their promising optoelectronic properties and potential applications in the fields of lighting and display devices. Despite their potential, PeLEDs face challenges related to stability, high turn-on voltage, and low external quantum efficiency (EQE) which has restricted their broad acceptance. Most research efforts have predominantly focused on refining the properties of the perovskite films. However, it is becoming more apparent that interfacial layers and device architecture are crucial for achieving stability and high efficiency, making them indispensable components in PeLED development. This perspective highlights remarkable advancements in PeLED devices, with a primary focus on modifying adjacent layers interfacing with the perovskite film.

Current Health Data Standardization Project and Future Directions to Ensure Interoperability in Korea.

OBJECTIVES: The need for interoperability at the national level was highlighted in Korea, leading to a consensus on the importance of establishing national standards that align with international technological standards and reflect contemporary needs. This article aims to share insights into the background of the recent national health data standardization policy, the activities of the Health Data Standardization Taskforce, and the future direction of health data standardization in Korea. METHODS: To ensure health data interoperability, the Health Data Standardization Taskforce was jointly organized by the public and private sectors in December 2022. The taskforce operated three working groups. It reviewed international trends in interoperability standardization, assessed the current status of health data standardization, discussed its vision, mission, and strategies, engaged in short-term standardization activities, and established a governance system for standardization. RESULTS: On September 15, 2023, the notice of "Health Data Terminology and Transmission Standards" in Korea was thoroughly revised to improve the exchange of health information between information systems and ensure interoperability. This notice includes the Korea Core Data for Interoperability (KR CDI) and the Korea Core Data Transmission Standard (HL7 FHIR KR Core), which are outcomes of the taskforce's efforts. Additionally, to reinforce the standardized governance system, the Health-Data Standardization Promotion Committee was established. CONCLUSIONS: Active interest and support from medical informatics experts are needed for the development and widespread adoption of health data standards in Korea.

Empowering Healthcare through Comprehensive Informatics Education: The Status and Future of Biomedical and Health Informatics Education.

OBJECTIVES: Education in biomedical and health informatics is essential for managing complex healthcare systems, bridging the gap between healthcare and information technology, and adapting to the digital requirements of the healthcare industry. This review presents the current status of biomedical and health informatics education domestically and internationally and proposes recommendations for future development. METHODS: We analyzed evidence from reports and papers to explore global trends and international and domestic examples of education. The challenges and future strategies in Korea were also discussed based on the experts' opinions. RESULTS: This review presents international recommendations for establishing education in biomedical and health informatics, as well as global examples at the undergraduate and graduate levels in medical and nursing education. It provides a thorough examination of the best practices, strategies, and competencies in informatics education. The review also assesses the current state of medical informatics and nursing informatics education in Korea. We highlight the challenges faced by academic institutions and conclude with a call to action for educators to enhance the preparation of professionals to effectively utilize technology in any healthcare setting. CONCLUSIONS: To adapt to the digitalization of healthcare, systematic and continuous workforce development is essential. Future education should prioritize curriculum innovations and the establishment of integrated education programs, focusing not only on students but also on educators and all healthcare personnel in the field. Addressing these challenges requires collaboration among educational institutions, academic societies, government agencies, and international bodies dedicated to systematic and continuous workforce development.

Regulation of Betaine Homocysteine Methyltransferase by Liver Receptor Homolog-1 in the Methionine Cycle.

Betaine-homocysteine S-methyltransferase (BHMT) is one of the most abundant proteins in the liver and regulates homocysteine metabolism. However, the molecular mechanisms underlying Bhmt transcription have not yet been elucidated. This study aimed to assess the molecular mechanisms underlying Bhmt transcription and the effect of BHMT deficiency on metabolic functions in the liver mediated by liver receptor homolog-1 (LRH-1). During fasting, both Bhmt and Lrh-1 expression increased in the liver of Lrh-1f/f mice; however, Bhmt expression was decreased in LRH-1 liver specific knockout mice. Promoter activity analysis confirmed that LRH-1 binds to a specific site in the Bhmt promoter region. LRH-1 deficiency was associated with elevated production of reactive oxygen species (ROS), lipid peroxidation, and mitochondrial stress in hepatocytes, contributing to hepatic triglyceride (TG) accumulation. In conclusion, this study suggests that the absence of an LRH-1-mediated decrease in Bhmt expression promotes TG accumulation by increasing ROS levels and inducing mitochondrial stress. Therefore, LRH-1 deficiency not only leads to excess ROS production and mitochondrial stress in hepatocytes, but also disrupts the methionine cycle. Understanding these regulatory pathways may pave the way for novel therapeutic interventions against metabolic disorders associated with hepatic lipid accumulation.

Boltzmann Switching MoS2 Metal-Semiconductor Field-Effect Transistors Enabled by Monolithic-Oxide-Gapped Metal Gates at the Schottky-Mott Limit.

A gate stack that facilitates a high-quality interface and tight electrostatic control is crucial for realizing high-performance and low-power field-effect transistors (FETs). However, when constructing conventional metal-oxide-semiconductor structures with two-dimensional (2D) transition metal dichalcogenide channels, achieving these requirements becomes challenging due to inherent difficulties in obtaining high-quality gate dielectrics through native oxidation or film deposition. Here, a gate-dielectric-less device architecture of van der Waals Schottky gated metal-semiconductor FETs (vdW-SG MESFETs) using a molybdenum disulfide (MoS2) channel and surface-oxidized metal gates such as nickel and copper is reported. Benefiting from the strong SG coupling, these MESFETs operate at remarkably low gate voltages, <0.5 V. Notably, they also exhibit Boltzmann-limited switching behavior featured by a subthreshold swing of ≈60 mV dec-1 and negligible hysteresis. These ideal FET characteristics are attributed to the formation of a Fermi-level (EF) pinning-free gate stack at the Schottky-Mott limit. Furthermore, authors experimentally and theoretically confirm that EF depinning can be achieved by suppressing both metal-induced and disorder-induced gap states at the interface between the monolithic-oxide-gapped metal gate and the MoS2 channel. This work paves a new route for designing high-performance and energy-efficient 2D electronics.