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Abstract The Ames test is used worldwide to initially screen the mutagenic potential of new chemicals. In the standard Ames test, S. typhimurium strains (TA100, TA98, TA1535, and TA1537) and Escherichia coli (WP2uvrA) are treated with substances with/without cytochrome P450s (CYPs)-induced rat S9 fractions for identifying mutagens and pro-mutagens. However, many substances show completely different toxicity patterns depending on whether the liver S9 fraction belongs to rats or humans. The natural product Polygoni Multiflori Radix (PMR) can also show bacterial reverse mutation, followed by the rat or human liver S9 fraction. While PMR elicits reverse mutations in the TA1537 strain in rat liver S9 but not in human liver S9, this mechanism has not been verified yet. To explain this, the differences in metabolic enzymes compositions commonly observed between rats and humans have been implicated. This study aimed to explore the key factors that cause differences in the genotoxicity of PMR between rat and human liver S9 metabolic enzymes. The results of next-generation sequencing (NGS) analysis showed that both rat and human metabolic enzymes caused similar mutations in TA1537. However, when the metabolic enzymes in each S9 fraction were analyzed using ion mobility tandem mass spectrometry (IM-MS), rat- and human-specific enzymes were identified among the cytochrome (CYP) family, especially aryl hydrocarbon receptor (AHR)-related CYPs. These findings suggest that CYP1A1 isoforms contribute to the mechanism of PMR in the Ames test. Therefore, an in vitro Ames test might be more reliable in predicting genotoxicity for both rodents and humans. This will also help overcome the limitations of laboratory animal-based toxicity evaluations, which provide unreliable results due to interspecies differences between humans and rodents.

Abstract The pursuit of advanced brain‐inspired electronic devices and memory technologies has led to explore novel materials by processing multimodal and multilevel tailored conductive properties as the next generation of semiconductor platforms, due to von Neumann architecture limits. Among such materials, antimony sulfide (Sb2S3) thin films exhibit outstanding optical and electronic properties, and therefore, they are ideal for applications such as thin‐film solar cells and nonvolatile memory systems. This study investigates the conduction modulation and memory functionalities of Sb2S3 thin films deposited via the vapor transport deposition technique. Experimental results indicate that the Ag/Sb2S3/Pt device possesses properties suitable for memory applications, including low operational voltages, robust endurance, and reliable switching behavior. Further, the reproducibility and stability of these properties across different device batches validate the reliability of these devices for practical implementation. Moreover, Sb2S3‐based memristors exhibit artificial neuroplasticity with prolonged stability, promising considerable advancements in neuromorphic computing. Leveraging the photosensitivity of Sb2S3 enables the Ag/Sb2S3/Pt device to exhibit significant low operating potential and conductivity modulation under optical stimulation for memory applications. This research highlights the potential applications of Sb2S3 in future memory devices and optoelectronics and in shaping electronics with versatility.

Abstract As global urbanization intensifies, there is an increasing need for highly sensitive and accurate environmental monitoring devices that can meet the demands of specific gas sensing applications with low power consumption. This study focuses on enhancing the sensitivity of MXene‐based chemiresistive sensors for detecting CO2(g) and NO2(g) under zero‐bias operation. This study shows that lignin hybridization effectively improves the sensitivity of a Ti3C2Tx MXene‐based chemiresistive sensor; under zero‐bias operation, lignin hybridization increases the sensitivity to 15 ppm NO2(g) and CO2(g) by 157.38% and 297.95%, respectively. When deposited on a flexible substrate, the MXene/lignin flexible sensor shows a similar response and sensitivity to 15 ppm NO2(g) and CO2(g) under 38° curvature compared to the planar sensor. Consequently, the MXene/lignin hybrid sensor is attractive for room temperature and zero‐bias NO2(g) and CO2(g) detection. The MXene/lignin flexible sensor serves as a model system for advanced solid‐state sensory platforms suitable for curved structures.

Abstract Introduction Cytokines of the common γ chain (γc) family are critical for the development, differentiation, and survival of T lineage cells. Cytokines play key roles in immunodeficiencies, autoimmune diseases, allergies, and cancer. Although γc is considered an assistant receptor to transmit cytokine signals and is an indispensable receptor in the immune system, its regulatory mechanism is not yet well understood. Objective This study focused on the molecular mechanisms that γc expression in T cells is regulated under T cell receptor (TCR) stimulation. Methods The γc expression in TCR-stimulated T cells was determined by flow cytometry, western blot and quantitative RT-PCR. The regulatory mechanism of γc expression in activated T cells was examined by promoter-luciferase assay and chromatin immunoprecipitation assays. NFAT1 and NFκB deficient cells generated using CRISPR-Cas9 and specific inhibitors were used to examine their role in regulation of γc expression. Specific binding motif was confirmed by γc promotor mutant cells generated using CRISPR-Cas9. IL-7TgγcTg mice were used to examine regulatory role of γc in cytokine signaling. Results We found that activated T cells significantly upregulated γc expression, wherein NFAT1 and NFκB were key in transcriptional upregulation via T cell receptor stimulation. Also, we identified the functional binding site of the γc promoter and the synergistic effect of NFAT1 and NFκB in the regulation of γc expression. Increased γc expression inhibited IL-7 signaling and rescued lymphoproliferative disorder in an IL-7Tg animal model, providing novel insights into T cell homeostasis. Conclusion Our results indicate functional cooperation between NFAT1 and NFκB in upregulating γc expression in activated T cells. As γc expression also regulates γc cytokine responsiveness, our study suggests that γc expression should be considered as one of the regulators in γc cytokine signaling and the development of T cell immunotherapies. Video Abstract

Abstract Conventional chemotherapy methods have adverse off-target effects and low therapeutic efficiencies of drug release in target tumors. In this study, we proposed a combination therapy of doxorubicin (DOX)-loaded ultrasound (US)-sensitive liposomal nanocarriers (IMP301), microbubbles (MBs) under focused US exposure using convex acoustic lens-attached US (LENS) to tumor treatment. The therapeutic effects of each treatment in a murine melanoma model were evaluated using contrast-enhanced US (CEUS) and micro-computed tomography (micro-CT) imaging, bioluminescence and confocal microscopy imaging, and liquid chromatography–mass spectroscopy (LC/MS) analysis. Tumor-bearing mice were randomly assigned to one of the following groups: (1) G1: IMP301 only (n = 9); (2) G2: IMP301 + LENS (n = 9); (3) G3: IMP301 + MB + LENS (n = 9); (4) G4: DOXIL only (n = 9); and (5) G5: IMP301 without DOXIL group as a control group (n = 4). Ten days after tumor injection, tumor-bearing mice were treated according to each treatment strategy on 10th, 12th, and 14th days from the day of tumor injection. The CEUS images of the tumors in the murine melanoma model clearly showed increased echo signal intensity from MBs as resonant US scattering. The relative tumor volume of the G2 and G3 groups on the micro-CT imaging showed inhibited tumor growth than the reference baseline of the G5 group. DOX signals on bioluminescence and confocal microscopy imaging were mainly located at the tumor sites. LC/MS showed prominently higher intratumoral DOX concentration in the G3 group than in other treated groups. Therefore, this study effectively demonstrates the feasibility of the synergistic combination of IMP301, MBs, and LENS-application for tumor-targeted treatment. Thus, this study can enable efficient tumor-targeted treatment by combining therapy such as IMP301 + MBs + LENS-application.

Metal oxide resistive memory is a potential device that can substantially influence the current roadmap for nonvolatile memory and neuromorphic computing. However, common amorphous oxide-based resistive random-access memory suffers from high forming voltages that complicate circuit design and abrupt SET behavior incompatible with analog weight updates. To overcome such limitations, wurtzite ZnO nanorods were synthesized on a fluorine-doped tin oxide (FTO) substrate and a bipolar resistive memory with the Ag/w-ZnO/FTO stacking sequence was fabricated. The hexagonal NR morphology of w-ZnO with controlled vertical growth and nanochannel formation between the NRs were produced by in situ crystalline growth. This morphology enabled a forming-free switching and an analog switching effect that emulated neuromorphic functionalities such as potentiation–depression and complex spike-time dependent plasticity-based Hebbian learning rules. Importantly, the device exhibited nonabrupt switching behavior suitable for analog weight updates in neuromorphic computing in contrast to conventional resistive memory.

Abstract Rehmannia glutinosa (Gaertn.) DC., belonging to the family Scrophulariaceae, is an important medicinal herb cultivated in East Asia. Traditionally, R. glutinosa is steam processed to increase its efficacy in treating various ailments such as diabetes, hematinic deficiencies and adrenal disorder. However, standardization of processed R. glutinosa is highly needed to increase its quality to fulfill global market demand that is safe and possess high level of efficacy. Therefore, this study aimed to optimize the R. glutinosa steam processing methods by evaluating some key parameters such as steaming temperature, number of steaming times, steaming duration, and additive supplementation. R. glutinosa samples were steam processed at different temperatures (100 °C, 110 °C, and 120 °C), various steaming times (1 to 5 times), several steaming duration (1 to 4 h), and additives supplementation (rice wine, 5% EtOH, 10% EtOH, 20% EtOH, 30% EtOH, and 40% EtOH). As the result, 2 h, 3 replications, and supplementation with 20% EtOH at 120 °C were identified as the optimal conditions for R. glutinosa steam processing. Optimized processed R. glutinosa (SPRR 20%EtOH) resulted in significantly higher content of 5-HMF (7648.60 ± 150.08 µg/g) and iso-verbacoside (203.80 ± 10.72 µg/g) compared with unprocessed R. glutinosa (UPR). Compared to those of other samples, SPRR 20% EtOH samples had higher total flavonoid (55.36 ± 1.68 mg/g) and phenolic (69.24 ± 4.56 mg/g) contents and stronger DPPH antioxidant activity (56%). Furthermore, SPRR 20% EtOH had excellent anti-inflammatory activity, as evidenced by the suppression of inducible nitric oxide synthase (iNOS) caused by activation of nuclear factor-κB (NF-κB) through p-p65 pathway in LPS-stimulated RAW 264.7 cells. These findings will provide a basis towards industrialization of R. glutinosa processing technology that will be very helpful for oriental medication field.

Tungsten diselenide (WSe2) is one of the promising transition metal dichalcogenides (TMDs) for nanoelectronics and optoelectronics. To enhance and tune the electronic performance of TMDs, chemical functionalization via covalent and van der Waals approaches has been suggested. In the present report, the electric and structural transition of WSe2 oxidized by exposure to O3 is investigated using scanning tunneling microscopy. It is demonstrated that the exposure of WSe2/high-ordered pyrolytic graphite sample to O3 induces the formation of molecular adsorbates on the surface, which enables to increase in the density of states near the valence band edge, resulting from electric structural modification of domain boundaries via exposure of atomic O. According to the work function extracted by Kelvin probe force microscopy, monolayer WSe2 with the O3 exposure results in a gradual increase in work function as the exposure to O3. Therefore, the present report demonstrates the potential pathway for the chemical functionalization of TMDs to enhance the electric performance of TMDs devices.

A tremendous effort has been made to develop 2D materials-based FETs for electronic applications due to their atomically thin structures. Typically, the electrical performance of the device can vary with the surface roughness and thickness of the channel layer. Therefore, a two-step surface engineering process is demonstrated to tailor the surface roughness and thickness of MoSe2 multilayers involving exposure of O2 plasma followed by dipping in (NH4)2S(aq) solution. The O2 plasma treatment generated an amorphous MoOx layer to form a MoOx/MoSe2 heterojunction, and the (NH4)2S(aq) treatment tailored the surface roughness of the heterojunction. The ON/OFF current ratio of MoSe2 FET is about 1.1 × 105 and 5.7 × 104 for bare and chemically etched MoSe2, respectively. The surface roughness of the chemically treated MoSe2 is higher than that of the bare, 4.2 ± 0.5 nm against 3.6 ± 0.5 nm. Conversely, a 1-hour exposure of the multilayer MoOx/MoSe2 heterostructure with the (NH4)2S(aq) solution removed the amorphous oxide layer and scaled down the thickness of MoSe2 from ~92.2 nm to ~38.9 nm. The preliminary study shows that this simple two-step strategy can obtain a higher surface-area-to-volume ratio and thickness engineering with acceptable variation in electrical properties.

Whilst sonothrombolysis is a promising and noninvasive ultrasound technique for treating blood clots, bleeding caused by thrombolytic agents used for dissolving clots and potential obstruction of blood flow by detached clots (i.e., embolus) are the major limitations of the current approach. In the present study, a new sonothrombolysis method is proposed for treating embolus without the use of thrombolytic drugs. Our proposed method involves (a) generating a spatially localised acoustic radiation force in a blood vessel against the blood flow to trap moving blood clots (i.e., generation of an acoustic net), (b) producing acoustic cavitation to mechanically destroy the trapped embolus, and (c) acoustically monitoring the trapping and mechanical fractionation processes. Three different ultrasound transducers with different purposes were employed in the proposed method: (1) 1-MHz dual focused ultrasound (dFUS) transducers for capturing moving blood clots, (2) a 2-MHz High Intensity Focused Ultrasound (HIFU) source for fractionating blood clots and (3) a passive acoustic emission detector with broad bandwidth (10 kHz to 20 MHz) for receiving and analysing acoustic waves scattered from a trapped embolus and acoustic cavitation. To demonstrate the feasibility of the proposed method, in vitro experiments with an optically transparent blood vessel-mimicking phantom filled with a blood mimicking fluid and a blood clot (1.2 to 5 mm in diameter) were performed with varying the dFUS and HIFU exposure conditions under various flow conditions (from 1.77 to 6.19 cm/s). A high-speed camera was used to observe the production of acoustic fields, acoustic cavitation formation and blood clot fragmentation within a blood vessel by the proposed method. Numerical simulations of acoustic and temperature fields generated under a given exposure condition were also conducted to further interpret experimental results on the proposed sonothrombolysis. Our results clearly showed that fringe pattern-like acoustic pressure fields (fringe width of 1 mm) produced in a blood vessel by the dFUS captured an embolus (1.2 to 5 mm in diameter) at the flow velocity up to 6.19 cm/s. This was likely to be due to the greater magnitude of the dFUS-induced acoustic radiation force exerted on an embolus in the opposite direction to the flow in a blood vessel than that of the drag force produced by the flow. The acoustically trapped embolus was then mechanically destructed into small pieces of debris (18 to 60 μm sized residual fragments) by the HIFU-induced strong cavitation without damaging the blood vessel walls. We also observed that acoustic emissions emitted from a blood clot captured by the dFUS and cavitation produced by the HIFU were clearly distinguished in the frequency domain. Taken together, these results can suggest that our proposed sonothrombolysis method could be used as a promising tool for treating thrombosis and embolism through capturing and destroying blood clots effectively.

Asthma is a pulmonary disease induced by the inhalation of aeroallergens and subsequent inappropriate immune responses. Camellia sinensis (L.) Kuntze has been evaluated as an effective antioxidant supplement produced from bioactive compounds, including flavonoids. In this study, we aimed to determine the effects of Camellia sinensis (L.) Kuntze extract (CE) on ovalbumin-induced allergic asthma. The components of CE were analyzed using high-performance liquid chromatography (HPLC) chromatogram patterns, and asthmatic animal models were induced via ovalbumin treatment. The antioxidant and anti-inflammatory effects of CE were evaluated using 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS), and nitric oxide (NO) assays. Seven compounds were detected in the CE chromatogram. In the ovalbumin-induced mouse model, CE treatment significantly decreased the inflammation index in the lung tissue. CE also significantly decreased eosinophilia and the production of inflammatory cytokines and OVA-specific IgE in animals with asthma. Collectively, our results indicate that CE has anti-inflammatory and antioxidant activities, and that CE treatment suppresses asthmatic progression, including mucin accumulation, inflammation, and OVA-specific IgE production.

Sepsis is a systemic inflammatory disease to infections and results in tissue damage and multiple organ failure. Ponciri Fructus Immaturus (PFI) is widely used in traditional medicine for allergic inflammation and gastrointestinal disorders. However, the effect of PFI on sepsis is still unknown. This study investigated the anti-inflammatory and antiseptic effects of PFI ethanol extract (PFIE) in LPS-stimulated J774 macrophages and mice with CLP- or LPS-induced sepsis, respectively. PFIE attenuates the LPS-induced production of the proinflammatory mediator NO by inhibiting the expression of iNOS in J774 cells. Real-time RT-PCR data and ELISA showed that the mRNA and protein levels of TNF-α, IL-1β, and IL-6 increased in LPS-stimulated J774 cells. However, this induction was significantly suppressed in PFIE pre-treated J774 cells. We also found that PFIE administration increased the survival rate of mice with LPS- and CLP-induced sepsis. Decreased serum levels of AST, ALT, and CK were observed after administration of PFIE, which was associated with reduced production of proinflammatory factors, such as NO, TNF-α, IL-1β, and IL-6. Moreover, PFIE suppressed the phosphorylation and nuclear translocation of STAT1 in LPS-stimulated J774 cells, suggesting that PFIE can inhibit LPS- and CLP-induced septic shock by suppressing the STAT1 activation. These findings provide the potential therapeutic relevance of PFIE in treating acute inflammatory disease.

Abstract Amphiregulin (AREG) is a transmembrane glycoprotein recently implicated in kidney fibrosis. Previously, we reported that the AREG-targeting Self-Assembled-Micelle inhibitory RNA (SAMiRNA-AREG) alleviated fibrosis by stably silencing the AREG gene, and reduced the side effects of conventional siRNA treatment of pulmonary fibrosis. However, the therapeutic effect of SAMiRNA-AREG in renal fibrosis has not been studied until now. We used two animal models of renal fibrosis generated by a unilateral ureteral obstruction (UUO) and an adenine diet (AD) to investigate whether SAMiRNA-AREG inhibited renal fibrosis. To investigate the delivery of SAMiRNA-AREG to the kidney, Cy5-labeled SAMiRNA-AREG was injected into UUO- and AD-induced renal fibrosis models. In both kidney disease models, SAMiRNA-AREG was delivered primarily to the damaged kidney. We also confirmed the protective effect of SAMiRNA-AREG in renal fibrosis models. SAMiRNA-AREG markedly decreased the UUO- and AD-induced AREG mRNA expression. Furthermore, the mRNA expression of fibrosis markers, including α-smooth muscle actin, fibronectin, α1(I) collagen, and α1(III) collagen in the UUO and AD-induced kidneys, was diminished in the SAMiRNA-AREG-treated mice. The transcription of inflammatory markers (tumor necrosis factor-α and monocyte chemoattractant protein-1) and adhesion markers (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1) was attenuated. The hematoxylin and eosin, Masson’s trichrome, and immunohistochemical staining results showed that SAMiRNA-AREG decreased renal fibrosis, AREG expression, and epidermal growth factor receptor (EGFR) phosphorylation in the UUO- and AD-induced models. Moreover, we studied the effects of SAMiRNA-AREG in response to TGF-β1 in mouse and human proximal tubule cells, and mouse fibroblasts. TGF-β1-induced extracellular matrix production and myofibroblast differentiation were attenuated by SAMiRNA-AREG. Finally, we confirmed that upregulated AREG in the UUO or AD models was mainly localized in the distal tubules. In conclusion, SAMiRNA-AREG represents a novel siRNA therapeutic for renal fibrosis by suppressing EGFR signals.

The present safety pharmacology core battery studies (neurobehavior, respiratory, cardiovascular system, and human ether a-go-go (hERG) channel current) investigated the potential harmful effects of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG). The SAMiRNA-AREG was administered by single intravenous injection at up to 300 mg/kg and 100 mg/kg in mice and monkeys, respectively. The hERG assay was performed in Chinese hamster ovary (CHO) cells at SAMiRNA-AREG concentrations of up to 200 μg/mL. In the evaluation on neurobehavior, a transient decrease in body temperature was found at 0.5 h (30 min) post-dose at both sexes in mice, with a single 300 mg/kg dose of SAMiRNA-AREG. However, these effects had returned to normal at 1 h post-dose. In the evaluation on hERG channel current, there were statistically significant differences in the inhibition of peak hERG potassium channel current between the 20, 100, and 200 μg/mL SAMiRNA-AREG treatment groups and the vehicle control group. However, these effects were less potent than that of E-4031, a positive control article. For the respiratory and cardiovascular systems, no treatment-related changes were observed in mice or monkeys. Thus, under these experimental conditions, these studies suggest that SAMiRNA-AREG showed no adverse effects on the neurobehavior, respiratory, and cardiovascular function.

Abstract A clothing-type wearable display can be utilized in fashion, bio-healthcare, and safety industries as well as smart textiles for the internet of things (IoTs) and wearable devices. In response to this trend, we demonstrate a textile display that can endure the active movements of a human body. It can be applied to any kind of textile, and is durable against conditions such as rain, sweat, and washing. As a key technology for realizing the multi-directional wrinkle-able textile display, we fabricated a stress-lowering textile platform with an ultrathin planarization layer replicated from the flat surface of glass. An elastomeric strain buffer for reducing mechanical stress is also inserted into the textile platform. Here, organic light-emitting diodes (OLEDs) with red, green and blue color, thin film transistors (TFTs) fabricated at a low temperature below 150 °C, and a washable encapsulation layer blocking both gas and liquid were demonstrated on the textile platform.

Myelosuppression is a major adverse effect of chemotherapy. With the increasing number of cancer patients worldwide, there is a growing interest in therapeutic approaches that reduce the adverse effects of chemotherapy. Angelica gigas Nakai (AGN) roots have been widely used in oriental medicine to treat blood-related diseases, including cancer. However, the effects of AGN on myelosuppression have not been studied. Here, we investigated the effects of AGN ethanol extract (AGNEX) on cyclophosphamide-induced myelosuppression. AGNEX treatment significantly decreased white blood cell levels while increasing red blood cell and platelet levels in the peripheral blood. It inhibited thymus and spleen atrophy. It also enhanced serum levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. qRT-PCR results showed that AGNEX decreased the expression of IL-1b and stem cell factor (SCF) in the bone marrow (BM) while increasing the mRNA expression of IL-3 and IL-6 in the spleen. Although AGNEX did not significantly decrease apoptosis and cell cycle arrest in the BM and splenocytes, AGNEX plays a positive role in cyclophosphamide-induced myelosuppression. AGNEX administration increased BM cells in the femur while decreasing apoptotic BM cells. These findings suggest that AGNEX could be used to treat myelosuppression and as a combination therapy in cancer patients.

How the replisome machinery contributes to fork stability under replication stress is currently not clear. Here the authors reveal a role for ATAD5 in maintaining genome integrity during replication stress by promoting replication restart through RAD51/PCNA regulation.

Abstract Sepsis causes multiple organs failures and eventually death. Changes in blood constituents due to sepsis lead to alterations in hemorheological properties, and cell adhesiveness. In this study, a new microfluidic system is proposed to measure temporal variations in biophysical properties of blood after injecting lipopolysaccharide (LPS) into a rat extracorporeal model under ex vivo condition. To measure blood viscosity, the interfacial line between blood and a reference fluid is formed in a Y-shaped channel. Based on the relation between interfacial width and pressure ratio, the temporal variation in blood viscosity is estimated. Optical images of blood flows are analyzed by decreasing flow rate for examination of red blood cell (RBC) aggregation. Platelets initiated by shear acceleration around the stenosis adhere to the post-stenosed region. By applying a correlation map that visualizes the decorrelation of the streaming blood flow, the area of adhered platelets can be quantitatively attained without labeling of platelets. To assess sepsis inflammation, conventional biomarkers (PCT and IL-8) are also monitored. The increasing tendency for blood viscosity, RBC aggregation, platelet adhesion, and septic biomarkers are observed after LPS injection. This microfluidic system would be beneficial for monitoring the changes in hemorheological properties and platelet activation caused by sepsis.

For more than three decades, numerous studies have demonstrated the function of p53 in cell cycle, cellular senescence, autophagy, apoptosis, and metabolism. Among diverse functions, the essential role of p53 is to maintain cellular homeostatic response to stress by regulating proliferation and apoptosis. Recently, adipocytes have been studied with increasing intensity owing to the increased prevalence of metabolic diseases posing a serious public health concern and because metabolic dysfunction can directly induce tumorigenesis. The prevalence of metabolic diseases has steadily increased worldwide, and a growing interest in these diseases has led to the focus on the role of p53 in metabolism and adipocyte differentiation with or without metabolic stress. However, our collective understanding of the direct role of p53 in adipocyte differentiation and function remains insufficient. Therefore, this review focuses on the newly discovered roles of p53 in adipocyte differentiation and function.

Diabetes mellitus is a chronic metabolic disease, and its progression leads to serious complications. Although various novel therapeutic approaches for diabetes mellitus have developed in the last three decades, its prevalence has been rising more rapidly worldwide. Silk-related materials have been used as anti-diabetic remedies in Oriental medicine and many studies have shown the effects of silk fibroin (SF) in both in vitro and in vivo models. In our previous works, we reported that hydrolyzed SF improved the survival of HIT-T15 cells under high glucose conditions and ameliorated diabetic dyslipidemia in a mouse model. However, we could not provide a precise molecular mechanism. To further evaluate the functions of hydrolyzed SF on the pancreatic β-cell, we investigated the effects of hydrolyzed SF on the pancreatic β-cell proliferation and regeneration in the mouse model. Hydrolyzed SF induced the expression of the proliferating cell nuclear antigen (PCNA) and reduced the apoptotic cell population in the pancreatic islets. Hydrolyzed SF treatment not only induced the expression of transcription factors involved in the pancreatic β-cell regeneration in RT-PCR results but also increased neurogenin3 and Neuro D protein levels in the pancreas of those in the group treated with hydrolyzed SF. In line with this, hydrolyzed SF treatment generated insulin mRNA expressing small cell colonies in the pancreas. Therefore, our results suggest that the administration of hydrolyzed SF increases the pancreatic β-cell proliferation and regeneration in C57BL/KsJ-Leprdb/db mice.

Abstract Molybdenum diselenide (MoSe2) has attracted attention as a potential semiconductor platform. However, the as‐synthesized MoSe2 field‐effect transistors (FETs) tend to exhibit the arbitrary properties of n‐type, p‐type, or ambipolar behavior due to the uncontrolled growth condition. Here, two‐step functionalization is proposed to achieve n‐doping effect and long‐term stability in chemical vapor deposition (CVD)–grown MoSe2 FETs using oxygen plasma treatment followed by the deposition of an Al2O3 layer. After the two‐step surface functionalization procedure, three types of multilayer MoSe2 FETs are all converted to n‐type with the improvement of their electrical characteristics and stability; the n‐doped multilayer MoSe2 FETs exhibit an enhancement in field‐effect mobility from 12.23 to 31.57 cm2 V−1 s−1 and a 3 times higher Ion/Ioff, compared to pristine multilayer MoSe2 FETs. This enhancement of electric performance is attributed to the oxidation of topmost MoSe2 to interfacial MoOx with SeOx induced by the oxygen plasma treatment, as well as to the existence of fixed positive charges in deposited Al2O3. The functionalized devices exhibit excellent stability against stress, as confirmed with negative bias illumination stress tests for 7200 s. Moreover, an environmental stability test for 21 days reveals no degradation in electric performance of MoSe2 FETs.

A fire detection system requires accurate and fast mechanisms to make the right decision in a fire situation. Since most commercial fire detection systems use a simple sensor, their fire recognition accuracy is deficient because of the limitations of the detection capability of the sensor. Existing proposals, which use rule-based algorithms or image-based machine learning can hardly adapt to the changes in the environment because of their static features. Since the legacy fire detection systems and network services do not guarantee data transfer latency, the required need for promptness is unmet. In this paper, we propose a new fire detection system with a multifunctional artificial intelligence framework and a data transfer delay minimization mechanism for the safety of smart cities. The framework includes a set of multiple machine learning algorithms and an adaptive fuzzy algorithm. In addition, Direct-MQTT based on SDN is introduced to solve the traffic concentration problems of the traditional MQTT. We verify the performance of the proposed system in terms of accuracy and delay time and found a fire detection accuracy of over 95%. The end-to-end delay, which comprises the transfer and decision delays, is reduced by an average of 72%.

Ostericum koreanum maximowicz (Umbelliferae), a medicinal herb in Korean Oriental Medicine, has been applied to treat cold, headache, neuralgia and arthralgia. The ethyl acetate fraction of O. koreanum root was subjected to in vitro antioxidant activity with different methods for free radical scavenging activities. In addition, the cell viability and nitric oxide release assays were performed here for the first time in neuroblastoma (Neuro-2a) cell cultures. Among all the tested methods, the ethyl acetate fraction was expressed very active, exhibiting a good Trolox equivalent values and IC50, comparable to that of the commercial antioxidants, Trolox and ascorbic acid, respectively. The results showed that there was a reduction of cell viability by the fraction in a concentration dependent manner. These results suggest that O. koreanum shows good antioxidant activities in vitro by inhibiting free radicals. These findings provide a rationale for the in vivo testing. Also, the major constituents behind the antioxidant mechanisms of this fraction warrant further study.

Brown adipocytes are a specialized cell type that is critical for adaptive thermogenesis, energy homeostasis and metabolism. In response to cold, both classical brown fat and the newly identified beige or brite cells are activated by β-adrenergic signaling and catabolize stored lipids and carbohydrates to produce heat via UCP1 (Uncoupling protein 1). Once thought to be non-existent in adults, recent studies have discovered active classical brown and beige fat cells in humans, thus reinvigorating interest in brown and beige adipocytes. This review will focus on the newly discovered transcription factors and microRNAs (miRNAs) that specify and orchestrate the classical brown and beige fat cell development.

Transient receptor potential melastatin 8 (TRPM8) ion channels mediate the detection of noxious and innocuous cold and are expressed by primary sensory neurons, but little is known about the processing of the TRPM8-mediated cold information within the trigeminal sensory nuclei (TSN) and the spinal dorsal horn (DH). To address this issue, we characterized TRPM8-positive (+) neurons in the trigeminal ganglion and investigated the distribution of TRPM8+ axons and terminals, and their synaptic organization in the TSN and in the DH using light and electron microscopic immunohistochemistry in transgenic mice expressing a genetically encoded axonal tracer in TRPM8+ neurons. TRPM8 was expressed in a fraction of small myelinated primary afferent fibers (23.7%) and unmyelinated fibers (76.3%), suggesting that TRPM8-mediated cold is conveyed via C and Aδ afferents. TRPM8+ axons were observed in all TSN, but at different densities in the dorsal and ventral areas of the rostral TSN, which dominantly receive sensory afferents from intra- and peri-oral structures and from the face, respectively. While synaptic boutons arising from Aδ and non-peptidergic C afferents usually receive many axoaxonic contacts and form complex synaptic arrangements, TRPM8+ boutons arising from afferents of the same classes of fibers showed a unique synaptic connectivity; simple synapses with one or two dendrites and sparse axoaxonic contacts. These findings suggest that TRPM8-mediated cold is conveyed via a specific subset of C and Aδ afferent neurons and is processed in a unique manner and differently in the TSN and DH.

The use of colloidal silica as a substratum for primary cultures of differentiated cells has significant advantages over classic tissue culture polystyrene. In this report, the growth and the level of expression of differentiated function of primary rabbit renal proximal tubule (RPT) cell cultures on colloidal silica is examined, using hormonally defined serum-free medium. Primary RPT cells grew to confluence more rapidly on colloidal silica than on tissue culture polystyrene (TC+). Moreover, following three passages, the RPT cells increased in number threefold more than parallel cultures on TC+. The morphology of primary RPT cells on colloidal silica were found by means of transmission electron microscopy to possess a polarized morphology with a brush border, and differentiated markers were retained even after passaging, including the Na+/glucose cotransport system and Glut 7.

Background: Recent studies suggest a link between the Klotho protein, sex hormones, and insulin-like growth factor-1 (IGF-1), indicating that α-Klotho levels may rise during puberty, including in central precocious puberty (CPP) cases. This study aimed to explore α-Klotho levels in girls with CPP to assess its potential as a diagnostic and monitoring tool for this condition. Methods: In total, 139 girls, comprising 82 patients diagnosed with CPP and 57 healthy prepubertal controls, were enrolled in this study. From March 2020 to May 2023, we assessed both α-Klotho levels and clinical parameters. α-Klotho concentrations were measured using an α-Klotho ELISA kit. For the girls with CPP, we additionally analyzed samples taken 6 months after GnRH agonist treatment. Results: α-Klotho levels were higher in the CPP group compared with the control (CPP group: 2529 ± 999 ng/mL; control group: 1802 ± 675 pg/mL) (P < 0.001), and its level modest decreased after 6 months of GnRH agonist treatment (2147± 789 pg/mL) (P < 0.001). The association between α-Klotho and IGF-1 SDS, follicular stimulating hormone and baseline luteinizing hormone was assessed by partial correlation after adjusting for age, BMI SDS (r= 0.416, p= <0.001; r= 0.261, p= 0.005; r= 0.278, p= 0.002), respectively. Receiver operating characteristic curve analysis identified an α-Klotho cut-off differentiating CPP from controls, with a cut-off of 1914 pg/mL distinguishing girls with CPP from controls with a sensitivity of 69.5% and specificity of 70.2%; the area under the curve was 0.723. Conclusion: The findings of our study are the first step towards deciphering the role of α-Klotho in puberty induction. With additional data and further research, α-Klotho could potentially be utilized as a significant diagnostic and monitoring tool for CPP. [ABSTRACT FROM AUTHOR]