Stearoyl-CoA desaturase 1 inhibition induces ER stress-mediated apoptosis in ovarian cancer cells.

Ovarian cancer is a leading cause of death among gynecologic tumors, often detected at advanced stages. Metabolic reprogramming and increased lipid biosynthesis are key factors driving cancer cell growth. Stearoyl-CoA desaturase 1 (SCD1) is a crucial enzyme involved in de novo lipid synthesis, producing mono-unsaturated fatty acids (MUFAs). Here, we aimed to investigate the expression and significance of SCD1 in epithelial ovarian cancer (EOC). Comparative analysis of normal ovarian surface epithelial (NOSE) tissues and cell lines revealed elevated SCD1 expression in EOC tissues and cells. Inhibition of SCD1 significantly reduced the proliferation of EOC cells and patient-derived organoids and induced apoptotic cell death. Interestingly, SCD1 inhibition did not affect the viability of non-cancer cells, indicating selective cytotoxicity against EOC cells. SCD1 inhibition on EOC cells induced endoplasmic reticulum (ER) stress by activating the unfolded protein response (UPR) sensors and resulted in apoptosis. The addition of exogenous oleic acid, a product of SCD1, rescued EOC cells from ER stress-mediated apoptosis induced by SCD1 inhibition, underscoring the importance of lipid desaturation for cancer cell survival. Taken together, our findings suggest that the inhibition of SCD1 is a promising biomarker as well as a novel therapeutic target for ovarian cancer by regulating ER stress and inducing cancer cell apoptosis.

Mitochondrial fission enhances IL-6-induced metastatic potential in ovarian cancer via ERK1/2 activation.

Ovarian cancer is a lethal gynecologic cancer mostly diagnosed in an advanced stage with an accumulation of ascites. Interleukin-6 (IL-6), a pro-inflammatory cytokine is highly elevated in malignant ascites and plays a pleiotropic role in cancer progression. Mitochondria are dynamic organelles that undergo fission and fusion in response to external stimuli and dysregulation in their dynamics has been implicated in cancer progression and metastasis. Here, we investigate the effect of IL-6 on mitochondrial dynamics in ovarian cancer cells (OVCs) and its impact on metastatic potential. Treatment with IL-6 on ovarian cancer cell lines (SKOV3 and PA-1) led to an elevation in the metastatic potential of OVCs. Interestingly, a positive association was observed between dynamin-related protein 1 (Drp1), a regulator of mitochondrial fission, and IL-6R in metastatic ovarian cancer tissues. Additionally, IL-6 treatment on OVCs was linked to the activation of Drp1, with a notable increase in the ratio of the inhibitory form p-Drp1(S637) to the active form p-Drp1(S616), indicating enhanced mitochondrial fission. Moreover, IL-6 treatment triggered the activation of ERK1/2, and inhibiting ERK1/2 mitigated IL-6-induced mitochondrial fission. Suppressing mitochondrial fission through siRNA transfection and a pharmacological inhibitor reduced the IL-6-induced migration and invasion of OVCs. This was further supported by 3D invasion assays using patient-derived spheroids. Altogether, our study suggests the role of mitochondrial fission in the metastatic potential of OVCs induced by IL-6. The inhibition of mitochondrial fission could be a potential therapeutic approach to suppress the metastasis of ovarian cancer.

Numerical study on particle behavior in a Y-junction mixer for supercritical water hydrolysis.

In the continuous-type supercritical water hydrolysis process, rapid mixing of supercritical and subcritical streams is important to maximize yield and minimize degradation from over-reaction. This work investigated the particle behavior in a Y-junction mixer using large eddy simulation coupled with a discrete phase model, aiming to optimize the supercritical hydrolysis process for biomass conversion. A series of numerical simulations analyzed the influence of the mixer's orientation, flow directions, and flow rates on effective mixing and backflow prevention. The results demonstrated that the most effective mixing occurred in a vertically oriented Y-junction mixer with an upward-directed supercritical water inlet, aligning the momentum direction of natural and forced convection effectively. Consequently, over 80% of particles reached the temperatures close to the mixing temperature of supercritical and subcritical water within the Y-junction mixing zone, indicating enhanced mixing effectiveness and potential for efficient hydrolysis. This configuration also minimized backflow.

Angelica gigas extract inhibits acetylation of eNOS via IRE1α sulfonation/RIDD-SIRT1-mediated posttranslational modification in vascular dysfunction.

Angelica gigas NAKAI (AG) is a popular traditional medicinal herb widely used to treat dyslipidemia owing to its antioxidant activity. Vascular disease is intimately linked to obesity-induced metabolic syndrome, and AG extract (AGE) shows beneficial effects on obesity-associated vascular dysfunction. However, the effectiveness of AGE against obesity and its underlying mechanisms have not yet been extensively investigated. In this study, 40 high fat diet (HFD) rats were supplemented with 100-300 mg/kg/day of AGE to determine its efficacy in regulating vascular dysfunction. The vascular relaxation responses to acetylcholine were impaired in HFD rats, while the administration of AGE restored the diminished relaxation pattern. Endothelial dysfunction, including increased plaque area, accumulated reactive oxygen species, and decreased nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation, were observed in HFD rats, whereas AGE reversed endothelial dysfunction and its associated biochemical signaling. Furthermore, AGE regulated endoplasmic reticulum (ER) stress and IRE1α sulfonation and its subsequent sirt1 RNA decay through controlling regulated IRE1α-dependent decay (RIDD) signaling, ultimately promoting NO bioavailability via the SIRT1-eNOS axis in aorta and endothelial cells. Independently, AGE enhanced AMPK phosphorylation, additionally stimulating SIRT1 and eNOS deacetylation and its associated NO bioavailability. Decursin, a prominent constituent of AGE, exhibited a similar effect in alleviating endothelial dysfunctions. These data suggest that AGE regulates dyslipidemia-associated vascular dysfunction by controlling ROS-associated ER stress responses, especially IRE1α-RIDD/sirt1 decay and the AMPK-SIRT1 axis.

Trametinib activates endogenous neurogenesis and recovers neuropathology in a model of Alzheimer's disease.

Enhancing adult neurogenesis in the brain has been suggested as a potential therapeutic strategy for AD. We developed a screening platform, ATRIVIEW®, for molecules that activate neuronal differentiation of adult mouse NSCs. The most potent hit from an FDA-approved drug library was SNR1611 (trametinib), a selective MEK1/2 inhibitor. We found that trametinib increases the levels of P15INK4b and Neurog2, suggesting a mechanism by which MEK1/2 inhibition induces neuronal differentiation. Oral administration of trametinib increased adult neurogenesis in the dentate gyrus and subventricular zone of the 5XFAD AD mouse model. Surprisingly, we also found that trametinib enhanced adult neurogenesis in the cortex. Consequently, trametinib rescued AD pathologies such as neuronal loss and cognitive impairment in 5XFAD mice. Finally, trametinib induced neurogenic differentiation of NSCs derived from AD patient iPSCs, which suggests its potential therapeutic application. Altogether, we suggest that restoration of endogenous adult neurogenesis by trametinib may be a promising therapeutic approach to AD.

Evaluation of the prediction of micropollutant elimination during bromide ion-containing industrial wastewater ozonation using the ROH, O3 value.

The composition of the wastewater matrix influences the oxidation potential of ozonation, a technique widely recognized efficient removal of micropollutants. Here, we developed a chemical kinetic model to determine the ozone dose required to minimize bromate production in wastewater containing bromine ions while achieving target removal rates. In wastewater ozonation, ozone decomposition comprises instantaneous ozone consumption and subsequent decomposition at first-order reaction rates. Under the injection condition of 1.5 g O3/g dissolved organic carbon (DOC), the instantaneous ozone demand was 62.7% of the injection concentration, and it increased proportionally with increasing injected ozone concentration. Ozone and hydroxyl radical exposures were proportional to the initial ozone dose, while hydroxyl radical exposure was proportional to ozone exposure, and the deviation was relatively high at 1.0-1.5 g O3/g DOC. The calculated hydroxyl radical exposure was 3.0 × 10-10 to 5.3 × 10-10 M s. Ozone and hydroxyl radicals are highly correlated with the ratio of ozone dose to organic matter concentration. Therefore, a trace substance removal rate evaluation model combined with the ROH, O3 model and a bromate generation model were also considered. For ibuprofen, the ozone dose for achieving the target removal rate of 80% while maintaining the bromate concentration below 50 µg L-1 was suitable in the operating range of 0.86 g O3/g DOC or more. The proposed method provides a practical operation strategy to calculate the appropriate ozone dose condition from the target compound removal rate prediction and bromate generation models considering the ratio of ozone dose to organic matter concentration in the incoming wastewater.

Electronic tongue for the simple and rapid determination of taste and odor compounds in water.

Taste and odor (T&O) compounds present in natural water bodies could originate from algae. In this study, alga-generated compounds that can cause T&O issues in water, such as geosmin (GE), 2-Methylisoborneol (MIB), 2,4,6-Trichloroanisole (TCA), 2-Methylbenzofuran (MB), 2-Isopropyl-3-methoxypyrazine (IPMP), 2-Isobutyl-3-methoxypyrazine (IBMP), cis-3-Hexenyl acetate (HA), trans,trans-2,4-Heptadienal (HD), trans,cis-2,6-Nonadienal (ND), and trans-2-Decenal (DN), were determined through solid-phase microextraction coupled with gas chromatography/mass spectrometry (HS-SPME GC/MS) and electronic tongue (E-tongue), and the results from the two techniques were compared. Although HS-SPME GC/MS facilitates the detection and quantification of T&O compounds with high precision and accuracy, the sample preparation and handling is difficult and the analysis time (1 h) is longer than those of other analytical methods. E-tongue can be used as an alternative analytical method for water quality analysis and risk management because it enables controlled and rapid analysis (3 min) of T&O compounds in water at a low cost. Notably, principal component analysis indicated that E-tongue can discriminate and quantify eight T&O compounds at as low as 0.02 µg L-1 concentration. Further, partial least squares analysis confirmed that the sensor exhibits high sensitivity to concentration changes. The sensors with the highest variable importance in projection scores were determined to be SCS (1.39 and 1.38) for GE and MIB, CTS (1.34) for IPMP, CPS (1.33) for IBMP, AHS (1.42) for HA, ANS (1.22) for HD, and NMS (1.14 and 1.19) for ND and DN.

Fluorescence excitation-emission matrix spectroscopy coupled with parallel factor analysis to determine chlorine decay constants in urban water distribution system.

This study applied a method for estimating chlorine decay constant (k) in urban water distribution systems using fluorescence excitation-emission matrix spectroscopy-parallel factor analysis (FEEM-PARAFAC), considering that it accounts for the influence of organic matter in the target area. The simultaneous impacts of seasonal variations on chlorine consumption and dissolved organic matter (DOM) composition were investigated for a year in three full-scale water distribution systems in I city (areas S, K, and G). Bulk decay constants (kb) were obtained through bottle tests, and the kb value was observed to differ by season and significantly affected by temperature. It exhibited its highest value, 0.794 d-1, in summer at area G. As a result of analyses through F-EEM-PARAFAC, it was determined that the components of the target raw water were humic-like and tryptophan-like. The quantitative analysis of organic substances through PARAFAC revealed that area G had the highest score (C1+C2) than other areas. 11.568, 10.578, and 11.771 in summer at areas S, K, and G, respectively. The model equations were derived such that the significant (R2 = 0.85-0.95) correlation between the C1 and C2 model scores and total chlorine decay constants (kt) verified via PARAFAC analysis of the target raw water was considered. Furthermore, a method for obtaining the wall decay constants at a target point based on the correlation equation was investigated.

Enhanced Photoresponse of High Crystalline Bi2Se3 Thin-Films Using Patterned Substrates.

High-quality Bi2Se3 thin films with topological insulating properties at room temperature have recently attracted much attention as one of the promising materials for realizing innovative electronic and optoelectronic devices. Here, we report the high crystallinity growth of Bi2Se3 thin films on a patterned sapphire substrate (PSS) by using a vapor-phase transport deposition with minimizing thermal dissociation of Se atoms vaporized in Bi2Se3 powder. This PSS not only reduces the large dislocation of heterogeneously grown Bi2Se3 on a sapphire substrate but also induces enhanced light absorption in the visible to near-infrared (IR) ranges compared to Bi2Se3 on planar sapphire substrates. Thus, the Bi2Se3 thin film laterally grown on the PSS reveals uniform surface properties and high crystallinity in the rhombohedral lattice phase with a full width at half maximum of 0.06° for the XRD (003) peak. Also, the photoresponse of the fabricated IR conversion device using Bi2Se3/PSS heterostructure exhibits excellent performance and high reliability with no degradation after continuous switching. As a result, the device constructed with the Bi2Se3/PSS exhibits one order of magnitude higher NIR induced-photocurrent and 1-2 orders of magnitude faster photo-switching than that with Bi2Se3/Al2O3. Such an enhancement in the device performance of Bi2Se3/PSS is confirmed by the increased absorption spectra in visible and NIR ranges and the improved light absorption distribution.

Older adults' support seeking from their adult children: The Support-Seeking Strategy Scale.

Due to the unavailability of assessment tools focused on support recipients, the aged-care literature has not been able to document the support seeking that occurs within familial support contexts. Therefore, we developed and validated a Support-Seeking Strategy Scale in a large sample of aging parents receiving care from their adult children. A pool of items was developed by an expert panel and administered to 389 older adults (over 60 years of age), all of whom were receiving support from an adult child. Participants were recruited on Amazon mTurk and Prolific. The online survey included self-report measures assessing parents' perceptions of support received from their adult children. The Support-Seeking Strategies Scale was best represented by 12 items across three factors-one factor representing the directness with which support is sought (direct) and two factors regarding the intensity with which support is sought (hyperactivated and deactivated). Direct support seeking was associated with more positive perceptions of received support from an adult child, whereas hyperactivated and deactivated support seeking were associated with more negative perceptions of received support. Older parents use three distinct support-seeking strategies: direct, hyperactivated, and deactivated with their adult child. The results suggest that direct seeking of support is a more adaptive strategy, whereas persistent and intense seeking of support (i.e., hyperactivated support seeking) or suppressing the need for support (i.e., deactivated support seeking) are more maladaptive strategies. Future research using this scale will help us better understand support seeking within the familial aged-care context and beyond. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Evolution of Local Structural Motifs in Colloidal Quantum Dot Semiconductor Nanocrystals Leading to Nanofaceting.

Colloidal nanocrystals (NCs) have shown remarkable promise for optoelectronics, energy harvesting, photonics, and biomedical imaging. In addition to optimizing quantum confinement, the current challenge is to obtain a better understanding of the critical processing steps and their influence on the evolution of structural motifs. Computational simulations and electron microscopy presented in this work show that nanofaceting can occur during nanocrystal synthesis from a Pb-poor environment in a polar solvent. This could explain the curved interfaces and the olivelike-shaped NCs observed experimentally when these conditions are employed. Furthermore, the wettability of the PbS NCs solid film can be further modified via stoichiometry control, which impacts the interface band bending and, therefore, processes such as multiple junction deposition and interparticle epitaxial growth. Our results suggest that nanofaceting in NCs can become an inherent advantage when used to modulate band structures beyond what is traditionally possible in bulk crystals.

Effect of optimized transcranial direct current stimulation on motor cortex activation in patients with sub-acute or chronic stroke: a study protocol for a single-blinded cross-over randomized control trial.

Introduction: Transcranial direct current stimulation (tDCS) has shown positive but inconsistent results in stroke rehabilitation. This could be attributed to inter-individual variations in brain characteristics and stroke lesions, which limit the use of a single tDCS protocol for all post-stroke patients. Optimizing the electrode location in tDCS for each individual using magnetic resonance imaging (MRI) to generate three-dimensional computer models and calculate the electric field (E-field) induced by tDCS at a specific target point in the primary motor cortex may help reduce these inconsistencies. In stroke rehabilitation, locating the optimal position that generates a high E-field in a target area can influence motor recovery. Therefore, this study was designed to determine the effect of personalized tDCS electrode positions on hand-knob activation in post-stroke patients. Method: This is a crossover study with a sample size of 50 participants, who will be randomly assigned to one of six groups and will receive one session of either optimized-active, conventional-active, or sham tDCS, with 24 h between sessions. The tDCS parameters will be 1 mA (5 × 5 cm electrodes) for 20 min. The motor-evoked potential (MEP) will be recorded before and after each session over the target area (motor cortex hand-knob) and the MEP hotspot. The MEP amplitude at the target location will be the primary outcome. Discussion: We hypothesize that the optimized-active tDCS session would show a greater increase in MEP amplitude over the target area in patients with subacute and chronic stroke than conventional and sham tDCS sessions.Clinical trial registration: https://cris.nih.go.kr, identifier KCT0007536.

Effects of Thermal Annealing on Optical and Microscopic Ferromagnetic Properties in InZnP:Ag Nano-Rods.

InZnP:Ag nano-rods fabricated by the ion milling method were thermally annealed in the 250~350 °C temperature range and investigated the optimum thermal annealing conditions to further understand the mutual correlation between the optical properties and the microscopic magnetic properties. The formation of InZnP:Ag nano-rods was determined from transmission electron microscopy (TEM), total reflectivity and Raman scattering analyses. The downward shifts of peak position for LO and TO modes in the Raman spectrum are indicative of the production of Ag ion-induced strain during the annealing process of the InZnP:Ag nano-rod samples. The appearance of two emission peaks of both (A0 X) and (e, Ag) in the PL spectrum indicated that acceptor states by Ag diffusion are visible due to the effective incorporation of Ag-creating acceptor states. The binding energy between the acceptor and the exciton measured as a function of temperature was found to be 21.2 meV for the sample annealed at 300 °C. The noticeable MFM image contrast and the clear change in the MFM phase with the scanning distance indicate the formation of the ferromagnetic spin coupling interaction on the surface of InZnP:Ag nano-rods by Ag diffusion. This study suggests that the InZnP:Ag nano-rods should be a potential candidate for the application of spintronic devices.

Smartphone Sensor-Based Human Motion Characterization with Neural Stochastic Differential Equations and Transformer Model.

With many conveniences afforded by advances in smartphone technology, developing advanced data analysis methods for health-related information from smartphone users has become a fast-growing research topic in the healthcare field. Along these lines, this paper addresses smartphone sensor-based characterization of human motions with neural stochastic differential equations (NSDEs) and a Transformer model. NSDEs and modeling via Transformer networks are two of the most prominent deep learning-based modeling approaches, with significant performance yields in many applications. For the problem of modeling dynamical features, stochastic differential equations and deep neural networks are frequently used paradigms in science and engineering, respectively. Combining these two paradigms in one unified framework has drawn significant interest in the deep learning community, and NSDEs are among the leading technologies for combining these efforts. The use of attention has also become a widely adopted strategy in many deep learning applications, and a Transformer is a deep learning model that uses the mechanism of self-attention. This concept of a self-attention based Transformer was originally introduced for tasks of natural language processing (NLP), and due to its excellent performance and versatility, the scope of its applications is rapidly expanding. By utilizing the techniques of neural stochastic differential equations and a Transformer model along with data obtained from smartphone sensors, we present a deep learning method capable of efficiently characterizing human motions. For characterizing human motions, we encode the high-dimensional sequential data from smartphone sensors into latent variables in a low-dimensional latent space. The concept of the latent variable is particularly useful because it can not only carry condensed information concerning motion data, but also learn their low-dimensional representations. More precisely, we use neural stochastic differential equations for modeling transitions of human motion in a latent space, and rely on a Generative Pre-trained Transformer 2 (GPT2)-based Transformer model for approximating the intractable posterior of conditional latent variables. Our experiments show that the proposed method can yield promising results for the problem of characterizing human motion patterns and some related tasks including user identification.

Increased Urination Urgency Exacerbates Sexual Risk-Taking Through Heightened Sexual Arousal.

Increased urination urgency has been shown to facilitate impulse control in cognitive domains, but its effects in other areas are unknown. We examined whether inhibitory spillover effects would replicate and extend to close relationships-specifically, influencing decision making related to sexual risk-taking. Across three studies, we either measured (Studies 1 and 3) or manipulated (Study 2) participants' bladder pressure and assessed sexual self-control using a questionnaire of sexual risk-taking intentions (Study 1) or a simulated semi-behavioral sexual risk-taking (Choose Your Own Sexual Adventure) task (Studies 2 and 3). Study 1 (N = 44 men, 59 women) showed greater urination urgency was associated with greater sexual risk-taking. Study 2 (N = 65 men, 91 women) showed that increasing urination urgency led to greater sexual risk-taking, but only among men. Study 3 (N = 86 men, 183 women) showed elevated urination urgency was associated with an increase in sexual arousal, which accounted for the greater sexual risk-taking.

Metabolic Syndrome as a Risk Factor of Endometrial Cancer: A Nationwide Population-Based Cohort Study of 2.8 Million Women in South Korea.

Background: A positive relationship was reported between metabolic syndrome and the risk of endometrial cancer. Studies on the relationship between metabolic syndrome and endometrial cancer have been mainly conducted in post-menopausal women. We aimed to investigate the risk of endometrial cancer according to metabolic syndrome and menopausal status using the Korean nationwide population-based cohort. Methods: We enrolled 2,824,107 adults (endometrial cancer group; N = 5,604 and control group; N= 2,818,503) from the Korean National Health Insurance Service checkup database from January 1 to December 31, 2009. The median follow-up duration was 8.37 years. Metabolic syndrome was diagnosed as having at least three of the following five components: abdominal obesity, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, raised blood pressure, and hyperglycemia. Multivariate Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate endometrial cancer risk. Results: The endometrial cancer risk was higher in the metabolic syndrome group than that in the non-metabolic syndrome group (HR, 1.362; 95% CI, 1.281-1.449). The association between metabolic syndrome and endometrial cancer risk was significant in the premenopausal subgroup (HR, 1.543; 95% CI, 1.39-1.713) and postmenopausal subgroup (HR, 1.306; 95% CI, 1.213-1.407). The incidence of endometrial cancer was more closely related to metabolic syndrome components in the pre-menopausal subgroup than those in the post-menopausal subgroup (for waist circumference, blood pressure, triglycerides and high-density lipoprotein cholesterol, all p for interaction <0.0001 respectively, and for fasting blood glucose, p for interaction 0.0188). The incidence of endometrial cancer positively correlated with the number of metabolic syndrome components (log-rank p <0.0001). Conclusion: Our large population-based cohort study in Korean women suggests that metabolic syndrome and its accumulated components may be risk factors for endometrial cancer, particularly in the pre-menopausal women.

Wnt/ß-Catenin Inhibition by CWP232291 as a Novel Therapeutic Strategy in Ovarian Cancer.

The poor prognosis of ovarian cancer patients mainly results from a lack of early diagnosis approaches and a high rate of relapse. Only a very modest improvement has been made in ovarian cancer patient survival with traditional treatments. More targeted therapies precisely matching each patient are strongly needed. The aberrant activation of Wnt/ß-catenin signaling pathway plays a fundamental role in cancer development and progression in various types of cancer including ovarian cancer. Recent insight into this pathway has revealed the potential of targeting Wnt/ß-catenin in ovarian cancer treatment. This study aims to investigate the effect of CWP232291, a small molecular Wnt/ß-catenin inhibitor on ovarian cancer progression. Various in vitro, in vivo and ex vivo models are established for CWP232291 testing. Results show that CWP232291 could significantly attenuate ovarian cancer growth through inhibition of ß-catenin. Noticeably, CWP232291 could also s suppress the growth of cisplatin-resistant cell lines and ovarian cancer patient-derived organoids. Overall, this study has firstly demonstrated the anti-tumor effect of CWP232291 in ovarian cancer and proposed Wnt/ß-catenin pathway inhibition as a novel therapeutic strategy against ovarian cancer.

Integrated analysis of ascites and plasma extracellular vesicles identifies a miRNA-based diagnostic signature in ovarian cancer.

Ovarian cancer is mostly diagnosed at advantaged stages due to the lack of early diagnostic biomarkers. The common metastasis pattern is characterized by peritoneal dissemination with a formation of malignant ascites. Extracellular vesicles (EVs) are emerging as promising clinical biomarkers in liquid biopsy. Here, we aimed to investigate robust liquid biopsy-based EV miRNA biomarkers for ovarian cancer diagnosis and metastasis regulation. EVs were isolated from malignant ascites and plasma of ovarian cancer patients as well as the benign control counterparts of patients with benign gynecologic diseases. EV small RNA sequencing identified a panel of eight miRNAs (miR-1246, miR-1290, miR-483, miR-429, miR-34b-3p, miR-34c-5p, miR-145-5p, miR-449a) based on dysregulated miRNAs overlapped in the ascites and plasma subset. The ovarian cancer EV miRNA (OCEM) signature developed based on these eight miRNAs demonstrated high diagnostic accuracy in our in-house dataset and multiple public datasets across diverse clinical samples (blood, tissue and urine). In addition, malignant ascites-derived EVs could significantly facilitate the aggressive property of ovarian cancer cells and boost the growth of ascites-derived organoids. Notably, miR-1246 and miR-1290 shuttled in malignant ascites-derived EVs were identified to promote the invasion and migration of ovarian cancer cells through regulating a common target RORα.

d-Allulose Ameliorates Hyperglycemia Through IRE1α Sulfonation-RIDD-Sirt1 Decay Axis in the Skeletal Muscle.

Aims: The skeletal muscle maintains glucose disposal via insulin signaling and glucose transport. The progression of diabetes and insulin resistance is critically influenced by endoplasmic reticulum (ER) stress. d-Allulose, a low-calorie sugar substitute, has shown crucial physiological activities under conditions involving hyperglycemia and insulin resistance. However, the molecular mechanisms of d-allulose in the progression of diabetes have not been fully elucidated. Here, we evaluated the effect of d-allulose on hyperglycemia-associated ER stress responses in human skeletal myoblasts (HSkM) and db/db diabetic and high-fat diet-fed mice. Results: d-allulose effectively controlled glycemic markers such as insulin and hemoglobin A1c (HbA1c), showing anti-diabetic effects by inhibiting the disruption of insulin receptor substrate (IRS)-1 tyrosine phosphorylation and glucose transporter 4 (GLUT4) expression, in which the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) pathway is involved. The levels of glucose dysmetabolism-based NADPH oxidase, such as NADPH-dependent oxidoreductase (Nox) 4, were highly increased, and their interaction with IRE1α and the resultant sulfonation-regulated IRE1-dependent decay (RIDD)-Sirt1 decay were also highly increased under diabetic conditions, which were controlled with d-allulose treatment. Skeletal muscle cells grown with a high glucose medium supplemented with d-allulose showed controlled IRE1α sulfonation-RIDD-Sirt1 decay, in which Nox4 was involved. Innovation and Conclusion: The study observations indicate that d-allulose contributes to the muscular glucose disposal in the diabetic state where ER-localized Nox4-induced IRE1α sulfonation results in the decay of Sirt1, a core factor for controlling glucose metabolism. Antioxid. Redox Signal. 37, 229-245.