Bioengineered human gut-on-a-chip for advancing non-clinical pharmaco-toxicology.

INTRODUCTION: There is a growing need for alternative models to advance current non-clinical experimental models because they often fail to accurately predict drug responses in clinical trials. Human organ-on-a-chip models have emerged as promising approaches for advancing the predictability of drug behaviors and responses. AREAS COVERED: We summarize up-to-date human gut-on-a-chip models designed to demonstrate intricate interactions involving the host, microbiome, and pharmaceutical compounds since these models have been reported a decade ago. Our overview covers recent advances in gut-on-a-chip models as a bridge technology between non-clinical and clinical assessments of drug toxicity and metabolism. We highlight the promising potential of the gut-on-a-chip platforms, offering a reliable and valid framework for investigating the reciprocal crosstalk between the host, gut microbiome, and drugs. EXPERT OPINION: Gut-on-a-chip platforms can attract multiple end users as a predictive, human-relevant, and non-clinical model. Notably, the gut-on-a-chip platforms provide a unique opportunity to recreate a human intestinal microenvironment, including dynamic bowel movement, luminal flow, oxygen gradient, host-microbiome interactions, and disease-specific manipulations restricted in current animal and in vitro cell culture models. Additionally, given the profound impact of the gut microbiome on pharmacological bioprocess, it is critical to leverage the breakthroughs of the gut-on-a-chip technology to address knowledge gaps and drive innovation in predictive drug toxicology and metabolism.

Tailored surgical strategies for mini-access open total arch repair.

Objective: Open arch repair is perceived as a challenging, high-risk procedure, with a barrier against the use of a minimally invasive approach. We aimed to present a mini-access total arch replacement performed by stratified approaches and to evaluate perioperative outcomes to contribute to the body of evidence. Methods: We evaluated 40 consecutive patients (aged 69.5 years; interquartile range, 65.6-76.3 years) undergoing elective total arch replacement using 5- to 8-cm upper mini-sternotomy between 2018 and 2022. Surgical strategies, including arterial inflow site and methods of branching vessel reconstruction, were systematically selected at the individual level. To evaluate comparative outcomes, contemporary cases undergoing total arch replacement via sternotomy with similar eligibility criteria served as a control group, and the inverse-treatment-weighting method was used to adjust for baseline characteristics. Results: Arch-first anastomosis using trifurcate graft, distal-first anastomosis using 4-branch graft, and island anastomosis were used in 18 (45%), 12 (30.0%), and 10 (25%) patients, respectively. Lower body and cardiac ischemic times were 23.4 minutes (interquartile range, 18.0-29.0 minutes) and 66.7 minutes (interquartile range, 50.1-78.2 minutes). There was no early (30-day or in-hospital) mortality, and 2 patients experienced disabling stroke (5.0%). The contemporary control group comprised 55 patients. After an adjustment, a mini-access group showed lower risks of stroke (odds ratio, 0.88; 95% CI, 0.78-1.00; P = .049) and a composite of major complications (odds ratio, 0.79; 95% CI, 0.68-0.92; P = .003), compared with a sternotomy approach. Conclusions: Based on present results, mini-access total arch replacement may be performed with reasonable safety and efficiency.

Airborne and surface contamination after rotational intraperitoneal pressurized aerosol chemotherapy using cisplatin.

OBJECTIVE: We evaluated the occupational exposure levels of healthcare workers while conducting rotational pressurized intraperitoneal aerosol chemotherapy (RIPAC) using cisplatin in a large animal model. METHODS: We performed RIPAC using cisplatin in 6 female pigs and collected surface and air samples during the procedure. Surface samples were obtained from RIPAC devices and personal protective equipment (PPE) by wiping, and air samples were collected around the operating table. All samples were analyzed by inductively coupled plasma-mass spectrometry to detect platinum. RESULTS: Among all surface samples (n=44), platinum was detected in 41 samples (93.2%) but not in all air samples (n=16). Among samples collected from RIPAC devices (n=23), minimum and maximum cisplatin levels of 0.08 and 235.09 ng/cm² were detected, mainly because of direct aerosol exposure in the abdominal cavity. Among samples collected from healthcare workers' PPE (n=21), 18 samples (85.7%) showed contamination levels below the detection limit, with a maximum of 0.23 ng/cm². There was no significant contamination among samples collected from masks, shoes, or gloves. CONCLUSION: During the RIPAC procedures, there is a potential risk of dermal exposure, as platinum, a surrogate material for cisplatin, was detected at low concentration levels in some surface samples. However, the respiratory exposure risk was not identified, as platinum was not detected in the airborne samples in this study.

Therapeutic efficacy and anti-inflammatory mechanism of baicalein on endometriosis progression in patient-derived cell line and mouse model.

BACKGROUND: Baicalein is a flavonoid extracted from the roots of Scutellaria baicalensis G. that has anti-inflammatory and antitumor effects. However, therapeutic mechanisms of baicalein in patients with endometriosis in vivo have yet to be elucidated. As a chronic inflammatory gynecological disease, endometriosis causes pain and infertility, and has no complete treatment to date. Current treatment strategies cause several side effects and have high recurrence rates. PURPOSE: This study aimed to identify the in vivo therapeutic effects of baicalein on endometriosis and verify the action mechanisms of baicalein, focusing on regulating inflammation. METHODS: In this study, an autologous transplant mouse model and patient-derived immortalized human ovarian endometriotic stromal cells (ihOESCs) were used to investigate the therapeutic activities of baicalein. The mouse model was administered with 40 mg/kg baicalein by oral gavage for 4 weeks, and the treatment outcomes of baicalein-treated mice were compared with vehicle- and dienogest-treated groups. ihOESCs were treated with 0-5 µg/ml baicalein for in vitro studies. RESULTS: Baicalein significantly alleviated the progression of endometriosis in mouse models. Baicalein reduced the expression of proinflammatory cytokines in endometriotic lesions and ihOESCs, and cytokine expression and T cell proportions in mouse spleen. in vitro results showed that baicalein increased mitochondrial calcium flux and induced mitochondrial depolarization and ROS generation in ihOESCs. Ultimately, baicalein inactivated the MAPK/PI3K signaling and induced cell death in ihOESCs. CONCLUSION: In conclusion, baicalein effectively attenuated the progression of endometriosis through its anti-inflammatory activities. Baicalein can be an alternative or supplemental treatment for endometriosis to ameliorate the side effects of hormonal therapy.

Subnormothermic ex vivo lung perfusion possibly protects against ischemia-reperfusion injury via the mTORC-HIF-1α pathway.

Background: Ex vivo lung perfusion (EVLP) is a useful technique for evaluating and repairing donor lungs for transplantation. However, studies examining the effects of perfusate temperature on graft function are limited. Thus, this study aimed to examine these effects during EVLP on ischemic-reperfusion injury in the donor lung. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into three groups, as follows: no treatment (sham group, n=5), normothermic EVLP (37 °C, n=5), and subnormothermic EVLP (30 °C, n=5). Lung function analyses, including oxygen capacity (OC), compliance, and pulmonary vascular resistance (PVR), were performed hourly during EVLP. Further, after 4 h of EVLP, histological evaluation of the right lobe was performed using the lung injury severity (LIS) scale. The expression levels of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-18 were evaluated. Metabolomic analysis of left lung tissues was conducted using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) after 4 h of EVLP in the EVLP groups and after 1 h of cold preservation in the sham group. Results: Compared with those in the normothermic group, in the subnormothermic group, functional parameters during EVLP and subsequent histologic results were significantly superior, expression levels of inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and IL-18 were significantly lower, and glycolytic activity was significantly decreased. Furthermore, expression levels of mammalian target of rapamycin complex (mTORC), hypoxia-inducible factor (HIF) 1α, and nucleotide-binding domain, leucine-rich-containing family pyrin domain containing 3 (NLRP3) and its effector caspase-1 were significantly lower in the subnormothermic group than in the normothermic group. Conclusions: EVLP with subnormothermic perfusion improves lung graft function by reducing the expression of pro-inflammatory cytokines and glycolytic activity during EVLP. Additionally, EVLP can be a useful target for the improvement of graft function after transplantation.

Recent Progress and Challenges in Paper-Based Microsupercapacitors for Flexible Electronics: A Comprehensive Review.

Recent advances in paper-based microsupercapacitors (p-MSCs) have attracted significant attention due to their potential as substrates for flexible electronics. This review summarizes progress in the field of p-MSCs, discussing their challenges and prospects. It covers various aspects, including the fundamental characteristics of paper, the modification of paper with functional materials, and different methods for device fabrication. The review critically analyzes recent advancements, materials, and fabrication techniques for p-MSCs, exploring their potential applications and benefits, such as flexibility, cost-effectiveness, and sustainability. Additionally, this review highlights gaps in current research, guiding future investigations and innovations in the field. It provides an overview of the current state of p-MSCs and offers valuable insights for researchers and professionals in the field. The critical analysis and discussion presented herein offer a roadmap for the future development of p-MSCs and their potential impact on the domain of flexible electronics.

Uprighting a mesially impacted mandibular second molar with scissor bite using simple tubes.

Orthodontic uprighting or traction of an impacted mandibular second molar often necessitates invasive interventions. This report aims to illustrate the utilization of nickel-titanium wire segments inserted into small, simple tubes for uprighting mesially impacted mandibular second molars and also for scissor bite correction. The term "simple tube" refers to a tube without a bonding base attached to a tooth surface by covering it with flowable composite resin. Due to the absence of a bonding base, the simple tube is characterized by its diminutive size and minimal profile height, facilitating placement on partially exposed second molars and unconventional positioning to adjust the force geometry. In this case study, mesially-impacted mandibular second molars with scissor bite were uprighted in a 21-year-old male utilizing simple tubes. Simple tubes can be used for molar uprighting and scissor bite correction buccally and lingually.

Role of Copper Nanoparticles in the Thermal and Mechanical Properties of Expanded Graphite-Reinforced Epoxy Hybrids.

Epoxy resin is extensively applied in the electronics and electrical fields because of its outstanding comprehensive performance. However, the low thermal conductivity (TC) limits its application in thermal interface materials. In the present work, epoxy-based hybrid composites with high TC were prepared by using expanded graphite (EG) and copper (Cu) nanoparticles as thermally conductive hybrid fillers via hot blending and compression-curing processes. Additionally, the influence of the Cu content on the thermal properties, mechanical properties, and morphology of each epoxy/EG/Cu composite was investigated. According to the results, the epoxy/EG/Cu composite showed a maximum TC of 9.74 W/(m·K) at a fixed EG content of 60 wt % owing to the addition of 10 wt % Cu. After the addition of 10 wt % Cu, the flexural strength, flexural modulus, and impact strengths of epoxy/EG/Cu composites were improved from 27.9 MPa, 9.72 GPa, and 0.81 kJ/m2 to 37.5 MPa, 10.88 GPa, and 0.91 kJ/m2, respectively. Hence, this study offers a feasible strategy for the design of epoxy hybrid composites with excellent TC that can be applied to thermal interface materials.

Functionalized MXene ink enables environmentally stable printed electronics.

Establishing dependable, cost-effective electrical connections is vital for enhancing device performance and shrinking electronic circuits. MXenes, combining excellent electrical conductivity, high breakdown voltage, solution processability, and two-dimensional morphology, are promising candidates for contacts in microelectronics. However, their hydrophilic surfaces, which enable spontaneous environmental degradation and poor dispersion stability in organic solvents, have restricted certain electronic applications. Herein, electrohydrodynamic printing technique is used to fabricate fully solution-processed thin-film transistors with alkylated 3,4-dihydroxy-L-phenylalanine functionalized Ti3C2Tx (AD-MXene) as source, drain, and gate electrodes. The AD-MXene has excellent dispersion stability in ethanol, which is required for electrohydrodynamic printing, and maintains high electrical conductivity. It outperformed conventional vacuum-deposited Au and Al electrodes, providing thin-film transistors with good environmental stability due to its hydrophobicity. Further, thin-film transistors are integrated into logic gates and one-transistor-one-memory cells. This work, unveiling the ligand-functionalized MXenes' potential in printed electrical contacts, promotes environmentally robust MXene-based electronics (MXetronics).

Hybrid Lymphovenous Anastomosis Surgery Guided by Intraoperative Mesenteric Intranodal Lymphangiography for Refractory Nontraumatic Chylous Ascites: A Case Report.

Refractory chylous ascites can cause significant nutritional and immunologic morbidity, but no clear treatment has been established. This article introduces a case of a 22-year-old female patient with an underlying lymphatic anomaly who presented with refractory chylous ascites after laparoscopic adnexectomy for ovarian teratoma which aggravated after thoracic duct embolization. Ascites (>3,000 mL/d) had to be drained via a percutaneous catheter to relieve abdominal distention and consequent dyspnea, leading to significant cachexia and weight loss. Two sessions of hybrid lymphovenous anastomosis (LVA) surgery with intraoperative mesenteric lymphangiography guidance were performed to decompress the lymphatics. The first LVA was done between inferior mesenteric vein and left para-aortic enlarged lymphatics in a side-to-side manner. The daily drainage of chylous ascites significantly decreased to 130 mL/day immediately following surgery but increased 6 days later. An additional LVA was performed between right ovarian vein and enlarged lymphatics in aortocaval area in side-to-side and end-to-side manner. The chylous ascites resolved subsequently without any complications, and the patient was discharged after 2 weeks. The patient regained weight without ascites recurrence after 22 months of follow-up. This case shares a successful experience of treating refractory chylous ascites with lymphatic anomaly through LVA, reversing the patient's life-threatening weight loss. LVA was applied with a multidisciplinary approach using intraoperative mesenteric lipiodol, and results showed the possibility of expanding its use to challenging problems in the intraperitoneal cavity.

Advancements in Human Embryonic Stem Cell Research: Clinical Applications and Ethical Issues.

BACKGROUND: The development and use of human embryonic stem cells (hESCs) in regenerative medicine have been revolutionary, offering significant advancements in treating various diseases. These pluripotent cells, derived from early human embryos, are central to modern biomedical research. However, their application is mired in ethical and regulatory complexities related to the use of human embryos. METHOD: This review utilized key databases such as ClinicalTrials.gov, EU Clinical Trials Register, PubMed, and Google Scholar to gather recent clinical trials and studies involving hESCs. The focus was on their clinical application in regenerative medicine, emphasizing clinical trials and research directly involving hESCs. RESULTS: Preclinical studies and clinical trials in various areas like ophthalmology, neurology, endocrinology, and reproductive medicine have demonstrated the versatility of hESCs in regenerative medicine. These studies underscore the potential of hESCs in treating a wide array of conditions. However, the field faces ethical and regulatory challenges, with significant variations in policies and perspectives across different countries. CONCLUSION: The potential of hESCs in regenerative medicine is immense, offering new avenues for treating previously incurable diseases. However, navigating the ethical, legal, and regulatory landscapes is crucial for the continued advancement and responsible application of hESC research in the medical field. Considering both scientific potential and ethical implications, a balanced approach is essential for successfully integrating hESCs into clinical practice.

Lymphadenectomy in clinically early epithelial ovarian cancer and survival analysis (LILAC): a Gynecologic Oncology Research Investigators Collaboration (GORILLA-3002) retrospective study.

OBJECTIVE: This study aimed to evaluate the therapeutic role of lymphadenectomy in patients surgically treated for clinically early-stage epithelial ovarian cancer (EOC). METHODS: This retrospective, multicenter study included patients with clinically early-stage EOC based on preoperative abdominal-pelvic computed tomography or magnetic resonance imaging findings between 2007 and 2021. Oncologic outcomes and perioperative complications were compared between the lymphadenectomy and non-lymphadenectomy groups. Independent prognostic factors were determined using Cox regression analysis. Disease-free survival (DFS) was the primary outcome. Overall survival (OS) and perioperative outcomes were the secondary outcomes. RESULTS: In total, 586 patients (lymphadenectomy group, n=453 [77.3%]; non-lymphadenectomy groups, n=133 [22.7%]) were eligible. After surgical staging, upstaging was identified based on the presence of lymph node metastasis in 14 (3.1%) of 453 patients. No significant difference was found in the 5-year DFS (88.9% vs. 83.4%, p=0.203) and 5-year OS (97.2% vs. 97.7%, p=0.895) between the two groups. Using multivariable analysis, lymphadenectomy was not significantly associated with DFS or OS. However, using subgroup analysis, the lymphadenectomy group with serous histology had higher 5-year DFS rates than did the non-lymphadenectomy group (86.5% vs. 74.4%, p=0.048; adjusted hazard ratio=0.281; 95% confidence interval=0.107-0.735; p=0.010). The lymphadenectomy group had longer operating time (p<0.001), higher estimated blood loss (p<0.001), and higher perioperative complication rate (p=0.004) than did the non-lymphadenectomy group. CONCLUSION: In patients with clinically early-stage EOC with serous histology, lymphadenectomy was associated with survival benefits. Considering its potential harm, lymphadenectomy should be performed according to histologic subtype and subsequent chemotherapy in patients with clinically early-stage EOC. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0007309.

Mechanical versus Bioprosthetic Aortic Valve Replacement in Patients Aged 50 to 70 Years.

Background: This study compared the outcomes of surgical aortic valve replacement (AVR) in patients aged 50 to 70 years based on the type of prosthetic valve used. Methods: We compared patients who underwent mechanical AVR to those who underwent bioprosthetic AVR at our institution between January 2000 and March 2019. Competing risk analysis and the inverse probability of treatment weighting (IPTW) method based on propensity score were employed for comparisons. Results: A total of 1,580 patients (984 patients with mechanical AVR; 596 patients with bioprosthetic AVR) were enrolled. There was no significant difference in early mortality between the mechanical AVR and bioprosthetic AVR groups (0.9% vs. 1.7%, p=0.177). After IPTW adjustment, the risk of all-cause mortality was significantly higher in the bioprosthetic AVR group than in the mechanical AVR group (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.07-1.80; p=0.014). Competing risk analysis revealed lower risks of stroke (sub-distributional hazard ratio [sHR], 0.44; 95% CI, 0.28-0.67; p<0.001) and anticoagulation- related bleeding (sHR, 0.35; 95% CI, 0.23-0.53; p<0.001) in the bioprosthetic AVR group. Conversely, the risk of aortic valve (AV) reintervention was higher in the bioprosthetic AVR group (sHR, 6.14; 95% CI, 3.17-11.93; p<0.001). Conclusion: Among patients aged 50 to 70 years who underwent surgical AVR, those receiving mechanical valves showed better survival than those with bioprosthetic valves. The mechanical AVR group exhibited a higher risk of stroke and anticoagulation-related bleeding, while the bioprosthetic AVR group showed a higher risk of AV reintervention.

Effect of high-dose polymeric nanoparticle micellar paclitaxel on improved progression-free survival in patients with optimally resected stage III or IV high-grade carcinoma of the ovary: a prospective cohort study with historical controls.

Introduction: We evaluated the effect of high-dose polymeric nanoparticle micellar paclitaxel (PM-Pac) on survival in patients with stage III-IV high-grade serous ovarian cancer (HGSC) who underwent upfront surgery. Methods: We prospectively recruited the patients who received PM-Pac (280 mg/m2) and carboplatin at an area under the curve (AUC) of 5 (cohort 1) in two tertiary centers between October 2015 and June 2019. As historical controls, we retrospectively collected data on those who received paclitaxel (175 mg/m2) and carboplatin (AUC 5; cohort 2) or paclitaxel (175 mg/m2), carboplatin (AUC 5) and bevacizumab (15 mg/kg; cohort 3). Results: A total of 128 patients were divided into cohorts 1 (n=49, 38.3%), 2 (n=53, 41.4%), and 3 (n=26, 20.3%). Cohort 1 showed better progression-free survival (PFS) than cohort 2 in all patients and those treated with optimal debulking surgery (ODS; median, 35.5 vs. 28.1 and 35.5 vs. 28.9 months; p ≤ 0.01) despite no difference in PFS between cohorts 1 and 3 and between cohorts 2 and 3. In particular, stage III disease was a favorable factor for PFS, whereas cohort 2 was related to worse PFS (adjusted hazard ratios, 0.456 and 1.834; 95% confidence interval, 0.263 - 0.790 and 1.061 - 3.171), showing no difference in PFS between cohorts 1 and 3 in those treated with ODS. Conclusion: High-dose PM-Pac improved PFS compared to conventional chemotherapy, and the change of paclitaxel to PM-Pac had as much effect on PFS as the addition of bevacizumab in patients with stage III-IV HGSC who underwent ODS.

A Review of Rechargeable Zinc-Air Batteries: Recent Progress and Future Perspectives.

Zinc-air batteries (ZABs) are gaining attention as an ideal option for various applications requiring high-capacity batteries, such as portable electronics, electric vehicles, and renewable energy storage. ZABs offer advantages such as low environmental impact, enhanced safety compared to Li-ion batteries, and cost-effectiveness due to the abundance of zinc. However, early research faced challenges due to parasitic reactions at the zinc anode and slow oxygen redox kinetics. Recent advancements in restructuring the anode, utilizing alternative electrolytes, and developing bifunctional oxygen catalysts have significantly improved ZABs. Scientists have achieved battery reversibility over thousands of cycles, introduced new electrolytes, and achieved energy efficiency records surpassing 70%. Despite these achievements, there are challenges related to lower power density, shorter lifespan, and air electrode corrosion leading to performance degradation. This review paper discusses different battery configurations, and reaction mechanisms for electrically and mechanically rechargeable ZABs, and proposes remedies to enhance overall battery performance. The paper also explores recent advancements, applications, and the future prospects of electrically/mechanically rechargeable ZABs.

Enhanced Electrical Properties and Impact Strength of Phenolic Formaldehyde Resin Using Silanized Graphene and Ionic Liquid.

In this study, to improve the electrical properties and impact strength of phenolic formaldehyde (PF) resin, PF-based composites were prepared by mixing graphene and the ionic liquid 3-decyl-bis(1-vinyl-1H-imidazole-3-ium-bromide) (C10[VImBr]2) via hot blending and compression-curing processes. The graphene surface was modified using a silane coupling agent. The synergistic effect of graphene and C10[VImBr]2 on the electrical properties, electromagnetic shielding efficiency, thermal stability, impact strength, and morphology of PF/graphene and PF/graphene/C10[VImBr]2 composites was then investigated. It was found that the electrical conductivity of the composites significantly increased from 2.3 × 10-10 to 4.14 × 10-3 S/m with an increase in the graphene content from 0 to 15 wt %, increasing further to 0.145 S/m with the addition of 5 wt % C10[VImBr]2. The electromagnetic shielding efficiency of the composite increased from 4.70 to 28.64 dB with the addition of 15 wt % graphene, while the impact strength of the composites rose significantly from 0.59 to 1.13 kJ/m2 with an increase in the graphene content from 0 to 15 wt %, reaching 1.53 kJ/m2 with the addition of 5 wt % C10[VImBr]2. Scanning electron microscopy images of the PF/GNP/C10[VImBr]2 composites revealed a rough morphology with numerous microcracks.

Reconsidering repurposing: long-term metformin treatment impairs cognition in Alzheimer's model mice.

Metformin, a primary anti-diabetic medication, has been anticipated to provide benefits for Alzheimer's disease (AD), also known as "type 3 diabetes". Nevertheless, some studies have demonstrated that metformin may trigger AD pathology and even elevate AD risk in humans. Despite this, limited research has elucidated the behavioral outcomes of metformin treatment, which would hold significant translational value. Thus, we aimed to perform thorough behavioral research on the prolonged administration of metformin to mice: We administered metformin (300 mg/kg/day) to transgenic 3xTg-AD and non-transgenic (NT) C57BL/6 mice over 1 and 2 years, respectively, and evaluated their behaviors across multiple domains via touchscreen operant chambers, including motivation, attention, memory, visual discrimination, and cognitive flexibility. We found metformin enhanced attention, inhibitory control, and associative learning in younger NT mice (≤16 months). However, chronic treatment led to impairments in memory retention and discrimination learning at older age. Furthermore, metformin caused learning and memory impairment and increased levels of AMPKα1-subunit, ß-amyloid oligomers, plaques, phosphorylated tau, and GSK3ß expression in AD mice. No changes in potential confounding factors on cognition, including levels of motivation, locomotion, appetite, body weight, blood glucose, and serum vitamin B12, were observed in metformin-treated AD mice. We also identified an enhanced amyloidogenic pathway in db/db mice, as well as in Neuro2a-APP695 cells and a decrease in synaptic markers, such as PSD-95 and synaptophysin in primary neurons, upon metformin treatment. Our findings collectively suggest that the repurposing of metformin should be carefully reconsidered when this drug is used for individuals with AD.

Recent progress in graphene and its derived hybrid materials for high-performance supercapacitor electrode applications.

Graphene, the most fascinating 2D form of carbon with closely packed carbon atoms arranged in a layer, needs more attention in various fields. For its unique electrical, mechanical, and chemical properties with a large surface area, graphene has been in the limelight since its first report. Graphene has extraordinary properties, making it the most promising electrode component for applications in supercapacitors. However, the persistent re-stacking of carbon layers in graphene, caused by firm interlayer van der Waals attractions, significantly impairs the performance of supercapacitors. As a result, many strategies have been used to get around the aforementioned problems. The utilization of graphene-based nanomaterials has been implemented to surmount the aforementioned constraints and considerably enhance the performance of supercapacitors. This review highlights recent progress in graphene-based nanomaterials with metal oxide, sulfides, phosphides, nitrides, carbides, and conducting polymers, focusing on their synthetic approach, configurations, and electrochemical properties for supercapacitors. It discusses new possibilities that could increase the performance of next-generation supercapacitors.

Alteration in Effects of Endometriosis on Fecundity According to Pregnancy Experience in Mouse Model.

This study is aimed at identifying variations in the effect of endometriosis on fecundity in a mouse model based on prior pregnancy experience. Endometriosis is one of the most prevalent gynecological diseases and is known to impact female fecundity adversely. In this study, an endometriosis mouse model was established by allografting uterine horn tissue using Pelch's method. The effect of endometriosis on fecundity was confirmed in primiparous and multiparous female mice. As fecundity indicators, the pregnancy rate, number of litters, pregnancy period, and survival rate of the pups were investigated. As a result of the experiment, the pregnancy rate decreased, and the pregnancy period tended to be shorter in primiparous female mice. However, there was no significant change in the multiparous mice. In addition, it has been established that correlations exist between the size of lesions and certain fecundity indicators of the lesion, even among primiparous and multiparous females with endometriosis. The study attempted to demonstrate a link between pregnancy experience and fecundity changes caused by endometriosis by experimentally reproducing clinical results using mouse models. These results suggest strategies for identifying several pathophysiological characteristics of endometriosis.

Fraxetin reduces endometriotic lesions through activation of ER stress, induction of mitochondria-mediated apoptosis, and generation of ROS.

BACKGROUND: Fraxetin, a phytochemical obtained from Fraxinus rhynchophylla, is well known for its anti-inflammatory and anti-fibrotic properties. However, fraxetin regulates the progression of endometriosis, which is a benign reproductive disease that results in low quality of life and infertility. HYPOTHESIS/PURPOSE: We hypothesized that fraxetin may have therapeutic effects on endometriosis and aimed to elucidate the underlying mechanisms of mitochondrial function and tiRNA regulation. STUDY DESIGN: Endometriotic animal models and cells (End1/E6E7 and VK2/E6E7) were used to identify the mode of action of fraxetin. METHODS: An auto-implanted endometriosis animal model was established and the effects of fraxetin on lesion size reduction were analyzed. Cell-based assays including proliferation, cell cycle, migration, apoptosis, mitochondrial function, calcium efflux, and reactive oxygen species (ROS) were performed. Moreover, fraxetin signal transduction was demonstrated by western blotting and qPCR analyses. RESULTS: Fraxetin inhibited proliferation and migration by inactivating the P38/JNK/ERK mitogen-activated protein kinase (MAPK) and AKT/S6 pathways. Fraxetin dissipates mitochondrial membrane potential, downregulates oxidative phosphorylation (OXPHOS), and disrupts redox and calcium homeostasis. Moreover, it triggered endoplasmic reticulum stress and intrinsic apoptosis. Furthermore, we elucidated the functional role of tiRNAHisGTG in endometriosis by transfection with its inhibitor. Finally, we established an endometriosis mouse model and verified endometriotic lesion regression and downregulation of adhesion molecules with inflammation. CONCLUSION: This study suggests that fraxetin is a novel therapeutic agent that targets mitochondria and tiRNAs. This is the first study to demonstrate the mechanisms of tiRNAHisGTG with mitochondrial function and cell fates and can be applied as a non-hormonal method against the progression of endometriosis.