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Existing solid state drive (SSD) simulators unfortunately lack hardware and/or software architecture models. Consequently, they are far from capturing the critical features of contemporary SSD devices. More importantly, while the performance of modern systems that adopt SSDs can vary based on their numerous internal design parameters and storage-level configurations, a full system simulation with traditional SSD models often requires unreasonably long runtimes and excessive computational resources. In this work, we propose SimpleSSD, a high-fidelity simulator that models all detailed characteristics of hardware and software, while simplifying the nondescript features of storage internals. In contrast to existing SSD simulators, SimpleSSD can easily be integrated into publicly-available full system simulators. In addition, it can accommodate a complete storage stack and evaluate the performance of SSDs along with diverse memory technologies and microarchitectures. Thus, it facilitates simulations that explore the full design space at different levels of system abstraction.

Purpose: This study aimed to demonstrate the safety of new double-stapling technique (nDST), without a crossing line and dog ears, by comparing with conventional DST (cDST) in laparoscopic low anterior resection (LAR)., Methods: We retrospectively reviewed 98 consecutive patients who underwent laparoscopic LAR for rectal cancer from January 2018 to December 2020. The inclusion criterion was an anastomosis level below the peritoneal reflection and 4 cm above the anal verge. In the nDST group, the staple line of the linear cutter was sutured using barbed sutures to shorten the staple line before firing the circular stapler. Therefore, there were no crossing lines after firing the circular stapler. A 2:1 propensity score matching was performed between the cDST and nDST groups., Results: After propensity score matching, 39 patients were in the cDST group and 20 were in the nDST group. There were no significant differences in patient demographics between the 2 groups. There was no difference in the total operation time between the cDST and nDST groups (124.0±26.2 minutes vs. 125.2±20.3 minutes, P=0.853). Morbidity rates were similar between the 2 groups (9 cases [23.1%] vs. 5 cases [25.0%], P=0.855). There was no significant difference in leakage rate (4 cases [10.3%] vs. 1 case [5.0%], P=0.847) and anastomotic bleeding rate (1 case [2.6%] vs. 3 cases [15.0%], P=0.211)., Conclusion: The nDST to eliminate the crossing line and dog ears in laparoscopic LAR is technically feasible and safe. However, more attention should be paid to anastomotic bleeding in such cases.

Traditionally, Lilium lancifolium bulb is known for its ability to nourish yin, nourish the lungs, clear the heart, soothe coughs, reduce irritability, and calm the mind. In Oriental Medicine, it is categorized as a tonic remedy for alleviating symptoms of fatigue and enhancing the strength of bones and muscles. In this study, we aimed to validate the effectiveness of the aquo-ethanolic extract of Lilli Bulbus (LBE) in a dexamethasone (DEX)-induced muscle atrophy model, both in vitro and in vivo, and elucidate its mechanism of action through muscle transcriptome analysis. The effects of LBE on the viability and myotube density of C2C12 myoblasts and differentiated C2C12 myotubes with and without DEX treatment were investigated. LBE pretreatment protected C2C12 myoblast cells and increased the muscle density of C2C12 myotubes in response to DEX. LBE showed potent free radical scavenging activities in cell-free biochemical assays as well as antioxidant activity in C2C12 myoblasts. LBE also exhibited protective effects in an experimental animal model of DEX-induced muscle atrophy, showing muscular function and motor coordination recovery. Transcriptomic analysis of three different muscle tissues from mice with DEX-induced muscle atrophy showed that the regulation of the extracellular matrix was perturbed by glucocorticoid treatment, and this perturbation was reversed by LBE treatment. Collectively, LBE alleviated skeletal muscle loss and maintained muscle function from the chronic toxicity of DEX by protecting muscle cells from various stressful conditions, as well as DEX itself, inhibiting muscle protein degradation, and preserving the muscle tissue microenvironment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Various bio-based recombinant proteins have been produced for industrial, medical, and research purposes. Plants are potential platforms for recombinant protein production because of several advantages. Therefore, establishing a system with high target gene expression to compensate for the low protein yield of plant systems is crucial. In particular, selecting and combining strong terminators is essential because the expression of target genes can be substantially enhanced. Here, we aimed to quantify the enhancement in the fluorescence intensity of the turbo green fluorescence protein (tGFP) caused by the best double-terminator combinations compared to that of the control vector using agroinfiltration in Nicotiana benthamiana leaves. tGFP fluorescence increased by 4.1-fold in leaf samples infiltrated with a vector containing a double terminator and markedly increased by a maximum of 23.7-fold when co-infiltrated with the geminiviral vector and P19 compared to that in constructs containing an octopine synthase terminator. Polyadenylation site analysis in leaf tissues expressing single or dual terminators showed that the first terminator influenced the polyadenylation site determination of the second terminator, resulting in different polyadenylation sites compared with when the terminator is located first. The combination of the high-expression terminators and geminiviral vectors can increase the production of target proteins.

Lilium lancifolium Thunb. is a herbal medicine that is widely used to treat inflammation and lung diseases. In this study, a simultaneous quantitative method was developed for the quality control of BLL using high-performance liquid chromatography coupled with a photodiode array detector (HPLC-PDA), and their antioxidant effects were evaluated. Eight regalosides (i.e., regaloside A, B, C, E, F, H, I, and K) were selected as marker substances and separated on a Gemini C 18 reversed-phase analytical column by gradient elution with distilled water-acetonitrile mobile phase containing 0.1% ( v/v ) formic acid. The method was validated with respect to linearity, sensitivities (limit of detection (LOD) and limit of quantitation (LOQ)), accuracy, and precision. The antioxidant effects of the extract and each component were evaluated using the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay and 2-2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay. The coefficients of determination values used as indicators of linearity for all components were ≥0.9999. LOD and LOQ concentrations were 0.10-0.66 μg/mL and 0.29-2.01 μg/mL, respectively. The recovery was 95.39-103.925% (relative standard deviation; RSD ≤ 2.55%), and precision RSD was <2.78%. The HPLC-PDA method was applied to real samples, and all components were detected at 1.12-29.76 mg/freeze-dried g. The evaluation of antioxidant effects showed that regalosides C, E, and K exhibited significant antioxidant effects. Our knowledge will be appropriately utilized in raw material management and conducting clinical and non-clinical studies on L. lancifolium or herbal medicine prescriptions containing L. lancifolium .

Introduction: Pharmacopuncture (PA) is widely used in traditional Korean medicine to treat various diseases, including abdominal obesity, nervous system diseases, and musculoskeletal disorders. In the present study, we attempted to identify the chemical components of SU-Eohyeol PA (SUEHP), comprising extracts of eight medicinal herbs and Cervi Parvum Cornu, using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) and evaluated the in vitro anti-inflammatory and antioxidant activities of SUEHP. Methods: Volatile components of SUEHP were identified by GC-MS analysis of the n-hexane, dichloromethane (DCM), and distilled water-acetonitrile (DW-CAN) solvent fractions. LC-MS was performed to identify small metabolites of SUEHP using a water-methanol solvent fraction. In vitro anti-inflammatory and antioxidant potential of SUEHP was evaluated using cell-free biochemical assays and a BV2 microglial cell culture system. Results: GC-MS of SUEHP using the n-hexane, DCM, and DW-ACN solvent fractions detected 32 components. The major components (>3%) were 9-octadecenamide (25.9%) and eicosane (5.4%) in n-hexane fraction, 9-octadecenamide (29.1%) and cis-11-octadecenoic acid (3.1%) in DCM fraction, and 9-octadecenamide (31.1%) and 9-octadecenoic acid (17.9%) in DW-CAN fraction. LC-MS of SUEHP using a water-methanol solvent fraction detected 36 primary metabolites, including (a)symmetric dimethylarginine, L -pyroglutamic acid, n , n -dimethylglycine, n -acetyl-L-aspartic acid, and amino acids. Enrichment analysis and subsequent network analysis of the primary metabolites suggested their association with neurodegenerative diseases, including Alzheimer's disease and schizophrenia. Cell-free biochemical assays and molecular signaling studies of lipopolysaccharide-stimulated BV2 murine microglial cells demonstrated the anti-inflammatory and antioxidant activities of SUEHP. Conclusion: The present study identified the biochemically active components of SUEHP and suggested their therapeutic potential against diseases related to inflammatory and oxidative stress., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Traditional herbal medicine, rooted in a long history of use in East Asia, combines several herbs to create treatments showing high efficacy with minimal side effects, for specific diseases. Such combination therapies represent a potential reservoir of new drugs for treating multifactorial and incurable chronic diseases. However, the complexity of their mechanisms of action due to the combination of multiple compounds, has limited their research integration into modern pharmacological science. To address this challenge, we constructed drug-induced transcriptome data for herbal medicines through systematic experiments, analyzed with the aid of various omics databases. We introduce KORE-Map 1.0 (Korean medicine Omics Resource Extension Map), the first comprehensive resource of drug-derived transcriptome data for representative tonifying herbal medicines, effective in enhancing the immune system. This dataset aims to provide novel insights into the combinatorial mechanisms of these herbal medicines and to aid in the discovery of new therapeutic targets and indications for various incurable diseases., (© 2024. The Author(s).)

To establish ubiquitous and energy-efficient wireless sensor networks (WSNs), short-range Internet of Things (IoT) devices require Bluetooth low energy (BLE) technology, which functions at 2.4 GHz. This study presents a novel approach as follows: a fully integrated all-digital phase-locked loop (ADPLL)-based Gaussian frequency shift keying (GFSK) modulator incorporating two-point modulation (TPM). The modulator aims to enhance the efficiency of BLE communication in these networks. The design includes a time-to-digital converter (TDC) with the following three key features to improve linearity and time resolution: fast settling time, low dropout regulators (LDOs) that adapt to process, voltage, and temperature (PVT) variations, and interpolation assisted by an analog-to-digital converter (ADC). It features a digital controlled oscillator (DCO) with two key enhancements as follows: ΔΣ modulator dithering and hierarchical capacitive banks, which expand the frequency tuning range and improve linearity, and an integrated, fast-converging least-mean-square (LMS) algorithm for DCO gain calibration, which ensures compliance with BLE 5.0 stable modulation index (SMI) requirements. Implemented in a 28 nm CMOS process, occupying an active area of 0.33 mm 2 , the modulator demonstrates a wide frequency tuning range of from 2.21 to 2.58 GHz, in-band phase noise of -102.1 dBc/Hz, and FSK error of 1.42% while consuming 1.6 mW.

Background: Periprosthetic osteolysis is a prevalent complication following total ankle arthroplasty (TAA), implicating various cytokines in osteoclastogenesis as pivotal in this process. This study aimed to evaluate the relationship between osteolysis and the concentrations of osteoclastogenesis-related cytokines in synovial fluid and investigate its clinical value following TAA., Methods: Synovial fluid samples from 23 ankles that underwent revision surgery for osteolysis following TAA were analyzed as the osteolysis group. As a control group, we included synovial fluid samples obtained from 23 ankles during primary TAA for osteoarthritis. The receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in these samples was quantified using sandwich enzyme-linked immunosorbent assay techniques, and a bead-based multiplex immunoassay facilitated the detection of specific osteoclastogenesis-related cytokines., Results: RANKL levels averaged 487.9 pg/mL in 14 of 23 patients in the osteolysis group, with no detection in the control group's synovial fluid. Conversely, a significant reduction in OPG levels was observed in the osteolysis group ( p = 0.002), resulting in a markedly higher mean RANKL/OPG ratio (0.23) relative to controls ( p = 0.020). Moreover, the osteolysis group had increased concentrations of various osteoclastogenesis-related cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, IL-8, IP-10, and monocyte chemotactic protein-1) in the synovial fluid relative to the control group., Conclusions: Our results demonstrated that periprosthetic osteolysis was associated with osteoclastogenesis activation through an elevated RANKL/OPG ratio following TAA. We assume that RANKL and other osteoclastogenesis-related cytokines in the synovial fluid have clinical value as a potential marker for the development and progression of osteolysis following TAA., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

We focused on the geminiviral vector systems to develop an efficient vector system for plant biotechnology. Begomoviruses and curtoviruses, which belong to the Geminiviridae family, contain an intergenic region (IR) and four genes involved in replication, including replication-associated protein (Rep, C1), transcriptional activator (TrAP, C2), and replication enhancer (REn, C3). Geminiviruses can amplify thousands of copies of viral DNA using plant DNA polymerase and viral replication-related enzymes and accumulate viral proteins at high concentrations. In this study, we optimized geminiviral DNA replicon vectors based on tomato yellow leaf curl virus (TYLCV), honeysuckle yellow vein virus (HYVV), and mild curly top virus (BMCTV) for the rapid, high-yield plant-based production of recombinant proteins. Confirmation of the optimal combination by co-delivery of each replication-related gene and each IR harboring the Pontellina plumata -derived turbo green fluorescence protein (tGFP) gene via agroinfiltration in Nicotiana benthamiana leaves resulted in efficient replicon amplification and robust protein production within 3 days. Co-expression with the p19 protein of the tomato bush stunt virus, a gene-silencing suppressor, further enhanced tGFP accumulation by stabilizing mRNA. With this system, tGFP protein was produced at 0.7-1.2 mg/g leaf fresh weight, corresponding to 6.9-12.1% in total soluble protein. These results demonstrate the advantages of rapid and high-level production of recombinant proteins using the geminiviral DNA replicon system for transient expression in plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Lee, Lee, Kil, Lee and Lee.)

As people age, the risk and progression of colorectal cancer (CRC), along with cholesterol levels, tend to increase. Nevertheless, epidemiological studies on serum lipids and CRC have produced conflicting results. We previously demonstrated that the reduction of squalene epoxidase (SQLE) due to accumulated cholesterol within cells accelerates CRC progression through the activation of the β-catenin pathway. This study aimed to investigate the mechanism by which age-related cholesterol accumulation within tissue accelerates CRC progression and to assess the clinical significance of SQLE in older individuals with elevated CRC risk. Using machine learning-based digital image analysis with fluorescence-immunohistochemistry, we assessed SQLE, GSK3β pS9 (GSK3β activity inhibition through serine 9 phosphorylation at GSK3β), p53 wild-type (p53 WT ), and p53 mutant (p53 MT ) levels in CRC tissues. Our analysis revealed a significant reduction in SQLE, p53 WT , and p53 MT and increase in GSK3β pS9 levels, all associated with the substantial accumulation of intra-tissue cholesterol in aged CRCs. Cox analysis underscored the significant influence of SQLE on overall survival and progression-free survival in grade 2-3 CRC patients aged over 50. SQLE and GSK3β pS9 consistently exhibited outstanding prognostic and diagnostic performance, particularly in older individuals. Furthermore, combining SQLE with p53 WT , p53 MT , and GSK3β pS9 demonstrated a robust diagnostic ability in the older population. In conclusion, we have identified that individuals aged over 50 face an increased risk of CRC progression due to aging-linked cholesterol accumulation within tissue and the subsequent reduction in SQLE levels. This study also provides valuable biomarkers, including SQLE and GSK3β pS9 , for older patients at elevated risk of CRC., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Introduction: Maternal epilepsy is a critical condition that can significantly affect mothers and fetuses. Notably, the admission of a laboring mother with uncontrolled refractory status epilepticus (RSE) to the operating room presents a challenging scenario for anesthesiologists., The Main Symptoms of the Patient and the Important Clinical Findings: A 30-year-old primigravida was transferred to the operating room for an emergency cesarean section. Cesarean section was performed after a provisional diagnosis of preeclampsia was made., The Main Diagnoses, Therapeutic Interventions, and Outcomes: Cesarean section was performed under general anesthesia. During the postoperative period, the patient exhibited no seizure activity in the brain; however, she experienced mild cognitive dysfunction for up to 6 months postdelivery. The neonate were discharged without any complications., Conclusion: Inducing anesthesia in pregnant women with ongoing seizure activity are challenging; however, anesthesiologists provide judgment based on the balance between the safety of the mother and fetus and the balance between patient monitoring and the progression of anesthesia. This challenge can be addressed through multidisciplinary collaboration., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

We characterized the therapeutic biological modes of action of several terpenes in Poria cocos F.A Wolf (PC) and proposed a broad therapeutic mode of action for PC. Molecular docking and drug-induced transcriptome analysis were performed to confirm the pharmacological mechanism of PC terpene, and a new analysis method, namely diffusion network analysis, was proposed to verify the mechanism of action against Alzheimer's disease. We confirmed that the compound that exists only in PC has a unique mechanism through statistical-based docking analysis. Also, docking and transcriptomic analysis results could reflect results in clinical practice when used complementarily. The detailed pharmacological mechanism of PC was confirmed by constructing and analyzing the Alzheimer's disease diffusion network, and the antioxidant activity based on microglial cells was verified. In this study, we used two bioinformatics approaches to reveal PC's broad mode of action while also using diffusion networks to identify its detailed pharmacological mechanisms of action. The results of this study provide evidence that future pharmacological mechanism analysis should simultaneously consider complementary docking and transcriptomics and suggest diffusion network analysis, a new method to derive pharmacological mechanisms based on natural complex compounds., Competing Interests: The authors declare no conflicts of interest.

The rapidly increasing prevalence of obesity and overweight, especially in children and adolescents, has become a serious societal issue. Although various genetic and environmental risk factors for pediatric obesity and overweight have been identified, the problem has not been solved. In this study, we examined whether environmental nanoplastic (NP) pollutants can act as environmental obesogens using mouse models exposed to NPs derived from polystyrene and polypropylene, which are abundant in the environment. We found abnormal weight gain in the progeny until 6 weeks of age following the oral administration of NPs to the mother during gestation and lactation. Through a series of experiments involving multi-omic analyses, we have demonstrated that NP-induced weight gain is caused by alterations in the lipid composition (lysophosphatidylcholine/phosphatidylcholine ratio) of maternal breast milk and he gut microbiota distribution of the progeny. These data indicate that environmental NPs can act as obesogens in childhood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Short-range Internet of Things (IoT) sensor nodes operating at 2.4 GHz must provide ubiquitous wireless sensor networks (WSNs) with energy-efficient, wide-range output power (POUT). They must also be fully integrated on a single chip for wireless body area networks (WBANs) and wireless personal area networks (WPANs) using low-power Bluetooth (BLE) and Zigbee standards. The proposed fully integrated transmitter (TX) utilizes a digitally controllable current-mode class-D (CMCD) power amplifier (PA) with a second harmonic distortion (HD2) suppression to reduce VCO pulling in an integrated system while meeting harmonic limit regulations. The CMCD PA is divided into 7-bit slices that can be reconfigured between differential and single-ended topologies. Duty cycle distortion compensation is performed for HD2 suppression, and an HD2 rejection filter and a modified C-L-C low-pass filter (LPF) reduce HD2 further. Implemented in a 28 nm CMOS process, the TX achieves a wide P OUT range of from 12.1 to -31 dBm and provides a maximum efficiency of 39.8% while consuming 41.1 mW at 12.1 dBm P OUT . The calibrated HD2 level is -82.2 dBc at 9.93 dBm P OUT , resulting in a transmitter figure of merit (TX&#95;FoM) of -97.52 dB. Higher-order harmonic levels remain below -41.2 dBm even at 12.1 dBm P OUT , meeting regulatory requirements.

Background: Although chronic treatment with glucocorticoids, such as dexamethasone, is frequently associated with muscle atrophy, effective and safe therapeutics for treating muscle atrophy remain elusive. Jakyak-gamcho-tang (JGT), a decoction of Paeoniae Radix and Glycyrrhizae Radix et Rhizoma, has long been used to relieve muscle tension and control muscle cramp-related pain. However, the effects of JGT on glucocorticoid-induced muscle atrophy are yet to be comprehensively clarified., Purpose: The objective of the current study was to validate the protective effect of JGT in dexamethasone-induced muscle atrophy models and elucidate its underlying mechanism through integrated in silico - in vitro - in vivo studies., Study Design and Methods: Differential gene expression was preliminarily analyzed using the RNA-seq data to determine the effects of JGT on C2C12 myotubes. The protective effects of JGT were further validated in dexamethasone-treated C2C12 myotubes by assessing cell viability, myotube integrity, and mitochondrial function or in C57BL/6 N male mice with dexamethasone-induced muscle atrophy by evaluating muscle mass and physical performance. Transcriptomic pathway analysis was also performed to elucidate the underlying mechanism., Results: Based on preliminary gene set enrichment analysis using the RNA-seq data, JGT regulated various pathways related to muscle differentiation and regeneration. Dexamethasone-treated C2C12 myotubes and muscle tissues of atrophic mice displayed substantial muscle protein degradation and muscle loss, respectively, which was efficiently alleviated by JGT treatment. Importantly, JGT-mediated protective effects were associated with observations such as preservation of mitochondrial function, upregulation of myogenic signaling pathways, including protein kinase B/mammalian target of rapamycin/forkhead box O3, inhibition of ubiquitin-mediated muscle protein breakdown, and downregulation of inflammatory and apoptotic pathways induced by dexamethasone., Conclusion: To the best of our knowledge, this is the first report to demonstrate that JGT could be a potential pharmaceutical candidate to prevent muscle atrophy induced by chronic glucocorticoid treatment, highlighting its known effects for relieving muscle spasms and pain. Moreover, transcriptomic pathway analysis can be employed as an efficient in silico tool to predict novel pharmacological candidates and elucidate molecular mechanisms underlying the effects of herbal medications comprising diverse biologically active ingredients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

ARL6IP1 is implicated in hereditary spastic paraplegia (HSP), but the specific pathogenic mechanism leading to neurodegeneration has not been elucidated. Here, we clarified the molecular mechanism of ARL6IP1 in HSP using in vitro and in vivo models. The Arl6ip1 knockout (KO) mouse model was generated to represent the clinically involved frameshift mutations and mimicked the HSP phenotypes. Notably, in vivo brain histopathological analysis revealed demyelination of the axon and neuroinflammation in the white matter, including the corticospinal tract. In in vitro experiments, ARL6IP1 silencing caused cell death during neuronal differentiation and mitochondrial dysfunction by dysregulated autophagy. ARL6IP1 localized on mitochondria-associated membranes (MAMs) to maintain endoplasmic reticulum and mitochondrial homeostasis via direct interaction with LC3B and BCl2L13. ARL6IP1 played a crucial role in connecting the endoplasmic reticulum and mitochondria as a member of MAMs. ARL6IP1 gene therapy reduced HSP phenotypes and restored pathophysiological changes in the Arl6ip1 KO model. Our results established that ARL6IP1 could be a potential target for HSP gene therapy., (© 2023 Lim et al.)

Dopamine system dysfunction is implicated in adolescent-onset neuropsychiatric disorders. Although psychosis symptoms can be alleviated by antipsychotics, cognitive symptoms remain unresponsive and novel paradigms investigating the circuit substrates underlying cognitive deficits are critically needed. The frontal cortex and its dopaminergic input from the midbrain are implicated in cognitive functions and undergo maturational changes during adolescence. Here, we used mice carrying mutations in Arc or Disc1 to model mesofrontal dopamine circuit deficiencies and test circuit-based neurostimulation strategies to restore cognitive functions. We found that in a memory-guided spatial navigation task, frontal cortical neurons were activated coordinately at the decision-making point in wild-type but not Arc -/- mice. Chemogenetic stimulation of midbrain dopamine neurons or optogenetic stimulation of frontal cortical dopamine axons in a limited adolescent period consistently reversed genetic defects in mesofrontal innervation, task-coordinated neuronal activity, and memory-guided decision-making at adulthood. Furthermore, adolescent stimulation of dopamine neurons also reversed the same cognitive deficits in Disc1 +/- mice. Our findings reveal common mesofrontal circuit alterations underlying the cognitive deficits caused by two different genes and demonstrate the feasibility of adolescent neurostimulation to reverse these circuit and behavioral deficits. These results may suggest developmental windows and circuit targets for treating cognitive deficits in neurodevelopmental disorders., Competing Interests: SM, XL, RS, MM, WZ, NK, KY, HS, GM, KW No competing interests declared

Childhood neglect and/or abuse can induce mental health conditions with unknown mechanisms. Here, we identified stress hormones as strong inducers of astrocyte-mediated synapse phagocytosis. Using in vitro, in vivo, and human brain organoid experiments, we showed that stress hormones increased the expression of the Mertk phagocytic receptor in astrocytes through glucocorticoid receptor (GR). In post-natal mice, exposure to early social deprivation (ESD) specifically activated the GR-MERTK pathway in astrocytes, but not in microglia. The excitatory post-synaptic density in cortical regions was reduced in ESD mice, and there was an increase in the astrocytic engulfment of these synapses. The loss of excitatory synapses, abnormal neuronal network activities, and behavioral abnormalities in ESD mice were largely prevented by ablating GR or MERTK in astrocytes. Our work reveals the critical roles of astrocytic GR-MERTK activation in evoking stress-induced abnormal behaviors in mice, suggesting GR-MERTK signaling as a therapeutic target for stress-induced mental health conditions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Loss of skeletal muscle mass and function has detrimental effects on quality of life, morbidity, and mortality, and is particularly relevant in aging societies. The enhancement of mitochondrial function has shown promise in promoting muscle differentiation and function. Ginsenoside Rc (gRc), a major component of ginseng, has various pharmacological activities; however, its effect on muscle loss remains poorly explored. In this study, we examined the effects of gRc on the hydrogen peroxide (H 2 O 2 )-induced reduction of cell viability in C2C12 myoblasts and myotubes and H 2 O 2 -induced myotube degradation. In addition, we investigated the effects of gRc on the production of intracellular reactive oxygen species (ROS) and mitochondrial superoxide, ATP generation, and peroxisome proliferator-activated receptor-gamma co-activator 1α (PGC-1α) activity in myoblasts and myotubes under H 2 O 2 treatment. Furthermore, to elucidate the mechanism of action of gRc, we conducted a transcriptome analysis of myotubes treated with or without gRc under H 2 O 2 treatment. gRc effectively suppressed H 2 O 2 -induced cytotoxicity, intracellular ROS, and mitochondrial superoxide production, restored PGC-1α promoter activity, and increased ATP synthesis. Moreover, gRc significantly affected the expression levels of genes involved in maintaining mitochondrial mass and biogenesis, while downregulating genes associated with muscle degradation in C2C12 myotubes under oxidative stress. We provide compelling evidence supporting the potential of gRc as a promising treatment for muscle loss and weakness. Further investigations of the pharmacological effects of gRc under various pathological conditions of muscle loss will contribute to the clinical development of gRc as a therapeutic intervention.

Quiescence is a hallmark of adult neural stem cells (NSCs) in the mammalian brain, and establishment and maintenance of quiescence is essential for life-long continuous neurogenesis. How NSCs in the dentate gyrus (DG) of the hippocampus acquire their quiescence during early postnatal stages and continuously maintain quiescence in adulthood is poorly understood. Here, we show that Hopx-CreER T2 -mediated conditional deletion of Nkcc1, which encodes a chloride importer, in mouse DG NSCs impairs both their quiescence acquisition at early postnatal stages and quiescence maintenance in adulthood. Furthermore, PV-CreER T2 -mediated deletion of Nkcc1 in PV interneurons in the adult mouse brain leads to activation of quiescent DG NSCs, resulting in an expanded NSC pool. Consistently, pharmacological inhibition of NKCC1 promotes NSC proliferation in both early postnatal and adult mouse DG. Together, our study reveals both cell-autonomous and non-cell-autonomous roles of NKCC1 in regulating the acquisition and maintenance of NSC quiescence in the mammalian hippocampus., Competing Interests: Conflict of interests G.-l.M. is on the editorial board of Stem Cell Reports., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Design: Retrospective study., Objective: To determine whether opioid use disorder (OUD) patients undergoing 1- to 2-level anterior cervical discectomy and fusion (1-2ACDF) have higher rates of: 1) in-hospital lengths of stay (LOS); 2) readmissions; 3) complications; and 4) costs., Methods: OUD patients undergoing primary 1-2ACDF were identified within the Medicare database and matched to a control cohort in a 1:5 ratio by age, sex, and medical comorbidities. The query yielded 80,683 patients who underwent 1-2 ACDF with (n = 13,448) and without (n = 67,235) OUD. Outcomes analyzed included in-hospital LOS, 90-day readmission rates, 90-day medical complications, and costs. Multivariate logistic regression analyses were used to calculate odds-ratios (OR) for medical complications and readmissions. Welch's t -test was used to test for significance for LOS and cost between the cohorts. An alpha value less than 0.002 was considered statistically significant., Results: OUD patients were found to have significantly longer in-hospital LOS compared to their counterparts (3.41 vs. 2.23-days, P < .0001), in addition to higher frequency and odds of requiring readmissions (21.62 vs. 11.57%; OR: 1.38, P < .0001). Study group patients were found to have higher frequency and odds of developing medical complications (0.88 vs. 0.19%, OR: 2.80, P < .0001) and incurred higher episode of care costs ($20,399.62 vs. $16,812.14, P < .0001)., Conclusion: The study can help to push orthopaedic surgeons in better managing OUD patients pre-operatively in terms of safe discontinuation and education of opioid drugs and their effects on complications, leading to more satisfactory outcomes.

Background: Although the advantages of laparoscopic Hartmann reversal (LHR) compared to open Hartmann reversal (OHR) have been reported in the literature, the number of multicenter studies with good matching investigating this topic is rare. In the present study, we aimed to confirm the advantages of LHR in terms of short-term outcomes through propensity score matching of LHR and OHR groups, using data collected from multiple institutions., Methods: Patients who underwent Hartmann reversal at six institutions under the Catholic Medical Center of the Catholic University of Korea between January 1, 2005, and December 31, 2021, were included. The patients were divided into the LHR and OHR groups based on the technique used. The two groups were matched using propensity score matching (1:1 ratio, logistic regression with the nearest-neighbor method). The primary outcome was postoperative ileus (POI) frequency, and secondary outcomes were time to solid diet (days) and length of stay (days)., Results: Among 337 patients, propensity score matching was performed on 322, after excluding 15 who had undergone open conversion. Of these, 63 patients were assigned to each group through propensity score matching. There was no difference in the frequency of adhesiolysis (77.8% vs. 82.5%, p = 0.503) or the operation time. (210 (IQR 159-290) vs. 233 (IQR 160-280), p = 0.718) between the two groups. As the primary outcome, the LHR group showed significantly lower POI frequency than the OHR group. (4.8% vs. 22.2%, p = 0.0041) Regarding the secondary outcomes, the LHR group showed a shorter period to solid diet than the OHR group. The length of hospital stay was also significantly shorter in the LHR group (4 vs. 6, p < 0.0001; 9 vs. 12, p<0.0001)., Conclusion: LHR is an effective method to ensure faster recovery of patients after surgery compared to OHR., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Caulophyllum robustum , commonly named Asian blue cohosh, is a perennial herb in the family Berberidaceae. It has traditionally been used for folk medicine in China. We isolated berberine from the leaves, stem, roots, and fruits of C. robustum , and this is the first report on berberine in this species. Transcriptome analysis was conducted for the characterization of berberine biosynthesis genes in C. robustum , in which, all the genes for berberine biosynthesis were identified. From 40,094 transcripts, using gene ontology (GO) analysis, 26,750 transcripts were assigned their functions in the categories of biological process, molecular function, and cellular component. In the analysis of genes expressed in different tissues, the numbers of genes in the categories of intrinsic component of membrane and transferase activity were up-regulated in leaves versus stem. The berberine synthesis genes in C. robustum were characterized by phylogenetic analysis with corresponding genes from other berberine-producing species. The co-existence of genes from different plant families in the deepest branch subclade implies that the differentiation of berberine synthesis genes occurred early in the evolution of berberine-producing plants. Furthermore, the copy number increment of the berberine synthesis genes was detected at the species level.

Increasing evidence implicates the critical roles of various epitranscriptomic RNA modifications in different biological processes. Methyltransferase METTL8 installs 3-methylcytosine (m 3 C) modification of mitochondrial tRNAs in vitro; however, its role in intact biological systems is unknown. Here, we show that Mettl8 is localized in mitochondria and installs m 3 C specifically on mitochondrial tRNA Thr/Ser(UCN) in mouse embryonic cortical neural stem cells. At molecular and cellular levels, Mettl8 deletion in cortical neural stem cells leads to reduced mitochondrial protein translation and attenuated respiration activity. At the functional level, conditional Mettl8 deletion in mice results in impaired embryonic cortical neural stem cell maintenance in vivo, which can be rescued by pharmacologically enhancing mitochondrial functions. Similarly, METTL8 promotes mitochondrial protein expression and neural stem cell maintenance in human forebrain cortical organoids. Together, our study reveals a conserved epitranscriptomic mechanism of Mettl8 and mitochondrial tRNA m 3 C modification in maintaining embryonic cortical neural stem cells in mice and humans., Competing Interests: Declaration of interests G.-l.M. is on the advisory board of Cell Stem Cell., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Prematurity is associated with surgical complications. This study sought to determine the risk of prematurity on 30-day complications, reoperations, and readmissions following ≥7-level PSF for AIS which has not been established. Utilizing the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP)-Pediatric dataset, all AIS patients undergoing ≥7-level PSF from 2012-2016 were identified. Cases were 1:1 propensity score-matched to controls by age, sex, and number of spinal levels fused. Prematurity sub-classifications were also evaluated: extremely (<28 weeks), very (28-31 weeks), and moderate-to-late (32-36 weeks) premature. Univariate analysis with post hoc Bonferroni compared demographics, hospital parameters, and 30-day outcomes. Multivariate logistic regression identified independent predictors of adverse 30-day outcomes. 5531 patients (term = 5099; moderate-to-late premature = 250; very premature = 101; extremely premature = 81) were included. Premature patients had higher baseline rates of multiple individual comorbidities, longer mean length of stay, and higher 30-day readmissions and infections than the term cohort. Thirty-day readmissions increased with increasing prematurity. Very premature birth predicted UTIs, superficial SSI/wound dehiscence, and any infection, and moderate-to-late premature birth predicted renal insufficiency, deep space infections, and any infection. Prematurity of AIS patients differentially impacted rates of 30-day adverse outcomes following ≥7-level PSF. These results can guide preoperative optimization and postoperative expectations.

Glucosinolates (GSLs) are secondary metabolites providing defense against pathogens and herbivores in plants, and anti-carcinogenic activity against human cancer cells. Profiles of GSLs vary greatly among members of genus Brassica . In this study, we found that a reference line of Chinese cabbage ( B. rapa ssp. pekinensis ), 'Chiifu' contains significantly lower amounts of total GSLs than the oilseed-type B. rapa ( B. rapa ssp. trilocularis ) line 'LP08'. This study aimed to identify the key regulators of the high accumulation of GSLs in Brassica rapa plants using transcriptomic and linkage mapping approaches. Comparative transcriptome analysis showed that, in total, 8,276 and 9,878 genes were differentially expressed between 'Chiifu' and 'LP08' under light and dark conditions, respectively. Among 162 B. rapa GSL pathway genes, 79 were related to GSL metabolism under light conditions. We also performed QTL analysis using a single nucleotide polymorphism-based linkage map constructed using 151 F 5 individuals derived from a cross between the 'Chiifu' and 'LP08' inbred lines. Two major QTL peaks were successfully identified on chromosome 3 using high-performance liquid chromatography to obtain GSL profiles from 97 F 5 recombinant inbred lines. The MYB-domain transcription factor gene BrMYB28.1 (Bra012961) was found in the highest QTL peak region. The second highest peak was located near the 2-oxoacid-dependent dioxygenase gene BrGSL-OH.1 (Bra022920). This study identified major genes responsible for differing profiles of GSLs between 'Chiifu' and 'LP08'. Thus, our study provides molecular insights into differences in GSL profiles between vegetative- and oilseed-type B. rapa plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Moon, Kim, Choi, Kim, Jang, Lee, Baskoro Dwi Nugroho and Kim.)

Mammalian carotid body arterial chemoreceptors function as an early warning system for hypoxia, triggering acute life-saving arousal and cardiorespiratory reflexes. To serve this role, carotid body glomus cells are highly sensitive to decreases in oxygen availability. While the mitochondria and plasma membrane signaling proteins have been implicated in oxygen sensing by glomus cells, the mechanism underlying their mitochondrial sensitivity to hypoxia compared to other cells is unknown. Here, we identify HIGD1C, a novel hypoxia-inducible gene domain factor isoform, as an electron transport chain complex IV-interacting protein that is almost exclusively expressed in the carotid body and is therefore not generally necessary for mitochondrial function. Importantly, HIGD1C is required for carotid body oxygen sensing and enhances complex IV sensitivity to hypoxia. Thus, we propose that HIGD1C promotes exquisite oxygen sensing by the carotid body, illustrating how specialized mitochondria can be used as sentinels of metabolic stress to elicit essential adaptive behaviors., Competing Interests: AT, AS, NW, EN, AR, ML, JC, JL, HH, NK, MJ, AG, RD, JG, RW, AB, AC No competing interests declared, (© 2022, Timón-Gómez, Scharr, Wong et al.)

Pharmacogenomic analysis based on drug transcriptomic signatures is widely used to identify mechanisms of action and pharmacological indications. Despite accumulating reports on the efficacy of medicinal herbs, related transcriptome-level analyses are lacking. The aim of the present study was to elucidate the underlying molecular mechanisms of action of Bupleuri Radix (BR), a widely used herbal medicine, through a systematic transcriptomic analysis. We analyzed the drug-responsive transcriptome profiling of A549 lung cancer cell line after treating them with multiple doses of BR water (W-BR) and ethanol (E-BR) extracts and their phytochemicals. In vitro validation experiments were performed using both A549 and the immortalized human keratinocyte line HaCaT. Pathway enrichment analysis revealed the anti-cancer effects of BR treatment via inhibition of cell proliferation and induction of apoptosis. Enhanced cell adhesion and migration were observed with the W-BR but not with the E-BR. Comparison with a disease signature database validated an indication of the W-BR for skin disorders. Moreover, W-BR treatment showed the wound-healing effect in skin and lung cells. The main active ingredients of BR showed only the anti-cancer effect of the E-BR and not the wound healing effect of the W-BR, suggesting the need for research on minor ingredients of BR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Park, Kim, Lee, Baek, Kim, Park, Yi and Cha.)

Berberine and berbamine are bioactive compounds of benzylisoquinoline alkaloids (BIAs) present in Berberis species. The contents of berbamine are 20 times higher than berberine in leaf tissues in three closely related species: Berberis koreana, B. thunbergii and B. amurensis . This is the first report on the quantification of berberine compared to the berbamine in the Berberis species. Comparative transcriptome analyses were carried out with mRNAs from the leaf tissues of the three-species. The comparison of the transcriptomes of B. thunbergii and B. amurensis to those of B. koreana, B. thunbergii showed a consistently higher number of differentially expressed genes than B. amurensis in KEGG and DEG analyses. All genes encoding enzymes involved in berberine synthesis were identified and their expressions were variable among the three species. There was a single copy of CYP80A/berbamunine synthase in B. koreana . Methyltransferases and cytochrome P450 mono-oxidases (CYPs) are key enzymes for BIA biosynthesis. The current report contains the copy numbers and other genomic characteristics of the methyltransferases and CYPs in Berberis species. Thus, the contents of the current research are valuable for molecular characterization for the medicinal utilization of the Berberis species.

Background: Postoperative nausea and vomiting (PONV) is a common complication of laparoscopic cholecystectomy. Although PONV is usually mild, severe thing can delay recovery and prolong hospitalization. We aimed to investigate the effects of ramosetron and esmolol, alone and in combination, on PONV, and pain., Methods: We enrolled 165 patients in their 20s to 50s who had an American Society of Anesthesiology physical status score of 1 or 2 and were scheduled to undergo laparoscopic cholecystectomy. They were randomly allocated into 3 groups: groups R, E, and E+R. Patients in group R received 0.3 mg of ramosetron following surgery. Those in group E were intravenously administered a bolus of esmolol (1.0 mg/kg) before endotracheal intubation. They were continuously infused with esmolol during the surgery to maintain their heart rate at 60 to 100 beats per minute and mean blood pressure at 60 to 100 mm Hg, followed by a bolus of esmolol (1.0 mg/kg) following surgery. Patients in group E+R were intravenously administered a bolus of esmolol (1.0 mg/kg) before endotracheal intubation, infused esmolol during surgery, and administered 0.3 mg of ramosetron and a bolus of esmolol (1.0 mg/kg) following surgery. We monitored the PONV stages (none, nausea, retching, and vomiting) and symptom severity in 3 postoperative stages (0-30 minutes, 30 minutes to 6 hours, and 6-24 hours), the latter by using the visual analog scale (VAS). We conducted an analysis of variance to compare VAS scores between groups., Results: Patients in groups E (mean ± standard deviation VAS score, 3.62 ± 1.00) and E+R (3.66 ± 0.71) exhibited less pain (P < .05) until 30 minutes following surgery compared to group R (5.72 ± 1.41). More patients in group E (28/50, 56%) experienced nausea compared to those in groups R (15/50, 30%) and E+R (8/50, 16%) until 30 minutes after surgery (P < .05). However, there were no differences in the severity of retching and vomiting between the groups in any of the phases (P > .05)., Conclusion: Despite reducing pain after laparoscopic cholecystectomy, esmolol did not prevent PONV, whether used alone or in combination with ramosetron., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Spastin significantly influences microtubule regulation in neurons and is implicated in the pathogenesis of hereditary spastic paraplegia (HSP). However, post-translational regulation of the spastin protein remains nebulous. The association between E3 ubiquitin ligase and spastin provides a potential therapeutic strategy., Results: As evidenced by protein chip analysis, FBXL17 inversely correlated with SPAST-M1 at the protein level in vitro and, also in vivo during embryonic developmental stage. SPAST-M1 protein interacted with FBXL17 specifically via the BTB domain at the N-terminus of SPAST-M1. The SCF FBXL17 E3 ubiquitin ligase complex degraded SPAST-M1 protein in the nuclear fraction in a proteasome-dependent manner. SPAST phosphorylation occurred only in the cytoplasmic fraction by CK2 and was involved in poly-ubiquitination. Inhibition of SCF FBXL17 E3 ubiquitin ligase by small chemical and FBXL17 shRNA decreased proteasome-dependent degradation of SPAST-M1 and induced axonal extension. The SPAST Y52C mutant, harboring abnormality in BTB domain could not interact with FBXL17, thereby escaping protein regulation by the SCF FBXL17 E3 ubiquitin ligase complex, resulting in loss of functionality with aberrant quantity. Although this mutant showed shortening of axonal outgrowth, low rate proliferation, and poor differentiation capacity in a 3D model, this phenotype was rescued by inhibiting SCF FBXL17 E3 ubiquitin ligase., Conclusions: We discovered that a novel pathway, FBXL17-SPAST was involved in pathogenicity of HSP by the loss of function and the quantitative regulation. This result suggested that targeting FBXL17 could provide new insight into HSP therapeutics., (© 2022. The Author(s).)

The annual herb Euphorbia maculata L. produces anti-inflammatory and biologically active substances such as triterpenoids, tannins, and polyphenols, and it is used in traditional Chinese medicine. Of these bioactive compounds, terpenoids, also called isoprenoids, are major secondary metabolites in E. maculata . Full-length cDNA sequencing was carried out to characterize the transcripts of terpenoid biosynthesis reference genes and determine the copy numbers of their isoforms using PacBio SMRT sequencing technology. The Illumina short-read sequencing platform was also employed to identify differentially expressed genes (DEGs) in the secondary metabolite pathways from leaves, roots, and stems. PacBio generated 62 million polymerase reads, resulting in 81,433 high-quality reads. From these high-quality reads, we reconstructed a genome of 20,722 genes, in which 20,246 genes (97.8%) did not have paralogs. About 33% of the identified genes had two or more isoforms. DEG analysis revealed that the expression level differed among gene paralogs in the leaf, stem, and root. Whole sets of paralogs and isoforms were identified in the mevalonic acid (MVA), methylerythritol phosphate (MEP), and terpenoid biosynthesis pathways in the E. maculata L. The nucleotide information will be useful for identifying orthologous genes in other terpenoid-producing medicinal plants.

The CRISPR/Cas9 site-directed gene-editing system offers great advantages for identifying gene function and crop improvement. The circadian clock measures and conveys day length information to control rhythmic hypocotyl growth in photoperiodic conditions, to achieve optimal fitness, but operates through largely unknown mechanisms. Here, we generated core circadian clock evening components, Brassica rapa PSEUDO-RESPONSE REGULATOR ( BrPRR ) 1a , 1b , and 1ab (both 1a and 1b double knockout) mutants, using CRISPR/Cas9 genome editing in Chinese cabbage, where 9-16 genetic edited lines of each mutant were obtained. The targeted deep sequencing showed that each mutant had 2-4 different mutation types at the target sites in the BrPRR1a and BrPRR1b genes. To identify the functions of BrPRR1a and 1b genes, hypocotyl length, and mRNA and protein levels of core circadian clock morning components, BrCCA1 ( CIRCADIAN CLOCK-ASSOCIATED 1 ) and BrLHY ( LATE ELONGATED HYPOCOTYL ) a and b were examined under light/dark cycles and continuous light conditions. The BrPRR1a and 1ab double mutants showed longer hypocotyls, lower core circadian clock morning component mRNA and protein levels, and a shorter circadian rhythm than wildtype (WT). On the other hand, the BrPRR1b mutant was not significantly different from WT. These results suggested that two paralogous genes may not be associated with the same regulatory function in Chinese cabbage. Taken together, our results demonstrated that CRISPR/Cas9 is an efficient tool for achieving targeted genome modifications and elucidating the biological functions of circadian clock genes in B. rapa , for both breeding and improvement.

Background: Recent studies have reported that steamed and freeze-dried mature silkworms, also known as HongJam, have various health-promoting effects., Objective: The goal of this study was to elucidate changes in the various health-promoting effects of HongJam, after its digestion with a food-grade protease., Materials and Methods: We examined whether healthspan-promotion and rotenone-induced loss of motor-control prevention effects were enhanced in Drosophila fed with food-grade alkaline protease-digested HongJam compared to those fed with non-digested HongJam. The differences in mitochondrial functions, chemical susceptibilities, and activations of signal transduction pathways between Drosophila supplemented with various feed were examined to elucidate the molecular and biochemical basis of healthspan-promotion and locomotor-improvement effects of protease-digested HongJam., Results: We first found that the healthspan-promotion effect of HongJam digested with a food-grade protease was different depending on the silkworm variety used for its production. Digestion with food-grade protease into White-Jade HongJam (WJ) as prepared from the White-Jade silkworm variety that spins white cocoons did not enhance its functionality. However, compared to Golden-Silk HongJam (GS), a food-grade protease-digested Golden-Silk HongJam (GSD) produced from the Golden-Silk silkworm variety that spins yellow cocoons, it further promoted the healthspan in a Drosophila model. By conducting a series of studies to reveal the molecular and biochemical basis for healthspan-promoting effects, we found that GS and GSD similarly enhanced mitochondrial activity, but GSD activated autophagy signaling more than GS. In addition, GSD feed (GSDf)-, GSD supernatant feed (GSDsupf)-, and GSD precipitate feed (GSDprecf)-reared Drosophila were also found to have increased resistance to an autophagy inhibitor compared to that of normal feed- or GS feed-reared Drosophila . Furthermore, we found that the rotenone-induced loss of motor control prevention effect was superior for GSDsup compared to GS, GSD, or GSDprec. This result may have occurred because GSDsup has more phenolic compounds and antioxidant activities than other samples., Conclusion: GSDsup contained more digested small peptides and free phytochemicals than other samples due to the digestion of proteins with a food-grade protease. Thus, GSDsup leads to further healthspan-promoting and locomotor-improvement effects than GS, GSD, or GSDprec., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mai, Kang, Jo, Nguyen, Kim, Kim, Kim and Koh.)

Background: Depression and suicide are critical social problems worldwide, but tools to objectively diagnose them are lacking. Therefore, this study aimed to diagnose depression through machine learning and determine whether it is possible to identify groups at high risk of suicide through words spoken by the participants in a semi-structured interview., Methods: A total of 83 healthy and 83 depressed patients were recruited. All participants were recorded during the Mini-International Neuropsychiatric Interview. Through the suicide risk assessment from the interview items, participants with depression were classified into high-suicide-risk (31 participants) and low-suicide-risk (52 participants) groups. The recording was transcribed into text after only the words uttered by the participant were extracted. In addition, all participants were evaluated for depression, anxiety, suicidal ideation, and impulsivity. The chi-square test and student's T -test were used to compare clinical variables, and the Naive Bayes classifier was used for the machine learning text model., Results: A total of 21,376 words were extracted from all participants and the model for diagnosing patients with depression based on this text confirmed an area under the curve (AUC) of 0.905, a sensitivity of 0.699, and a specificity of 0.964. In the model that distinguished the two groups using statistically significant demographic variables, the AUC was only 0.761. The DeLong test result ( p -value 0.001) confirmed that the text-based classification was superior to the demographic model. When predicting the high-suicide-risk group, the demographics-based AUC was 0.499, while the text-based one was 0.632. However, the AUC of the ensemble model incorporating demographic variables was 0.800., Conclusion: The possibility of diagnosing depression using interview text was confirmed; regarding suicide risk, the diagnosis accuracy increased when demographic variables were incorporated. Therefore, participants' words during an interview show significant potential as an objective and diagnostic marker through machine learning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shin, Kim, Lee, Lee, Bae, Cho, Kim, Hyung Keun Park, Chie, Kim and Ahn.)

Background and Purpose: Hereditary spastic paraplegia (HSP) progresses over time and is associated with locomotive dysfunction. Understanding the factors affecting disease severity and locomotive function is important in HSP. This study investigated the factors influencing disease severity and ambulation status of HSP., Methods: We consecutively enrolled 109 Korean patients (64 males, and 45 females)from 84 families with a clinical diagnosis of HSP. HSP was primarily diagnosed based on clinical criteria including clinical findings, family history, and supported by genetic studies. Epidemiological and clinical features of the patients were analyzed, and the Spastic Paraplegia Rating Scale (SPRS) score and ambulatory status were used to evaluate disease severity., Results: Ninety-two (84.4%) patients had pure HSP, and 55 (50.4%) had a dominant family history. Thirty-one (28.4%) patients required a mobility aid for locomotion. A Kaplan-Meier analysis showed that HSP patients lost their independent gait ability after a median disease duration of 34 years. Those with an age at onset of ≤18 years had a longer median independent walking time. Pure HSP is characterized by predominant bilateral lower extremity weakness and spasticity, whereas complicated HSP presents more complex neurological findings such as ocular and bulbar symptoms, ataxia, and cognitive impairment. Complicated HSP was significantly correlated with the SPRS mobility score (β=3.70, 95% confidence interval=0.45-6.94). The age at onset and disease duration were significantly correlated with disease severity, and they were significant predictors of the use of a mobility aid ( p <0.05)., Conclusions: These findings suggest that a later age at onset and longer disease duration are significant factors affecting the disease severity and ambulatory function in patients with HSP. These findings can help clinicians to identify subjects at risk of locomotive impairment., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2022 Korean Neurological Association.)

Accumulating evidence suggests that the medial prefrontal cortex (mPFC) has been implicated in the acquisition of fear memory during trace fear conditioning in which a conditional stimulus (CS) is paired with an aversive unconditional stimulus (UCS) separated by a temporal gap (trace interval, TI). However, little is known about the role of the prefrontal cortex for short- and long-term trace fear memory formation. Thus, we investigated how the prelimbic (PL) subregion within mPFC in rats contributes to short- and long-term trace fear memory formation using electrolytic lesions and d,l,-2-amino-5-phosphonovaleric acid (APV), an N-methyl-D-aspartate receptor (NMDAR) antagonist infusions into PL. In experiment 1, pre-conditioning lesions of PL impaired freezing to the CS as well as TI during the acquisition and retrieval sessions, indicating that PL is critically involved in trace fear memory formation. In experiment 2, temporary blockade of NMDA receptors in PL impaired the acquisition, but not the expression of short- and long-term trace fear memory. In addition, the inactivation of NMDAR in PL had little effect on locomotor activity, pre-pulse inhibition (PPI), or shock sensitivity. Taken together, these results suggest that NMDA receptor-mediated neurotransmission in PL is required for the acquisition of trace fear memory.

Heracleum moellendorffii Hance is a non-woody forest plant widely used in China, Korea, and Japan because of its various therapeutic properties. However, the genetic details of the carotenoid pathway (CP), xanthophyll pathway (XP), and apocarotenoid pathway (AP) genes have not been studied. Thus, the CP, XP, and AP genes of H. moellendorffii were detected and analyzed. A total of fifteen genes were identified, of which eight, four, and three belonged to CP, XP, and AP, respectively. All identified genes possessed full open reading frames. Phylogenetic characterization of the identified gene sequences showed the highest similarity with other higher plants. Multiple alignments and 3D dimensional structures showed several diverse conserved motifs, such as the carotene-binding motif, dinucleotide-binding motif, and aspartate or glutamate residues. The results of real-time PCR showed that the CP, XP, and AP genes were highly expressed in leaves, followed by the stems and roots. In total, eight different individual carotenoids were identified using HPLC analysis. The highest individual and total carotenoid content were achieved in the leaves, followed by the stems and roots. This study will provide more information on the gene structure of the CP, XP, and AP genes, which may help to increase the accumulation of carotenoids in H. moellendorffii through genetic engineering. These results could be helpful for further molecular and functional studies of CP, XP, and AP genes.

Paeoniae Radix (PR) has a great therapeutic value in many clinical applications; however, the presence of various bioactive compounds and its complicated effects on human health makes its precise mechanisms of action unclear. This study investigated the effects of PR at the molecular pathway level by profiling genome-wide gene expression changes following dose-dependent treatment of human lung cancer cells (A549) with PR water extract (WPR), PR ethanol extracts (EPR), as well as their individual components. We found that PR exerts anticancer effects in A549 cells by regulating numerous pathways. Specifically, EPR and two compounds, namely, hederagenin (HG) and oleanolic acid (OA), significantly downregulate the Aurora B pathway. Furthermore, we generated an integrated PR extracts-compounds-target genes network in the Aurora B pathway to understand their interactions. Our findings reinforce that inhibiting Aurora kinase activity is a therapeutic target for treating cancers, providing the potential for novel mechanisms of action for PR and its components against lung cancer., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)