Evaluation of the reliability and validity of the upright head roll test for lateral semicircular canal benign paroxysmal positional vertigo.

BACKGROUND: The upright head roll test (UHRT) is a recently introduced diagnostic maneuver for lateral semicircular canal benign paroxysmal positional vertigo (LSC-BPPV). OBJECTIVE: This study aimed to evaluate the reliability and validity of the UHRT. METHODS: Two separate studies were conducted. Study 1 analyzed 827 results of videonystagmography (VNG) to assess UHRT reliability, and Study 2 analyzed 130 LSC-BPPV cases to evaluate UHRT validity. RESULTS: The inter-test reliability between UHRT and the supine head roll test (SHRT) showed substantial agreement (Cohen's kappa = 0.753) in direction-changing positional nystagmus (DCPN) and almost perfect agreement (Cohen's kappa = 0.836) in distinguishing the direction of DCPN. The validity assessment of UHRT showed high accuracy in diagnosing LSC-BPPV (80.0%) and in differentiating the variant types (74.6%). UHRT was highly accurate in diagnosing the canalolithiasis type in LSC-BPPV patients (Cohen's kappa = 0.835); however, it showed only moderate accuracy in diagnosing the cupulolithiasis type (Cohen's kappa = 0.415). The intensity of nystagmus in UHRT was relatively weaker than that in SHRT (P < 0.05). CONCLUSION: UHRT is a reliable test for diagnosing LSC-BPPV and distinguishing subtypes. However, UHRT has a limitation in discriminating the affected side owing to a weaker intensity of nystagmus than SHRT.

Insect immune resolution with EpOME/DiHOME and its dysregulation by their analogs leading to pathogen hypersensitivity.

Upon immune challenge, recognition signals trigger insect immunity to remove the pathogens through cellular and humoral responses. Various immune mediators propagate the immune signals to nearby tissues, in which polyunsaturated fatty acid (PUFA) derivatives play crucial roles. However, little was known on how the insects terminate the activated immune responses after pathogen neutralization. Interestingly, C20 PUFA was detected at the early infection stage and later C18 PUFAs were induced in a lepidopteran insect, Spodoptera exigua. This study showed the role of epoxyoctadecamonoenoic acids (EpOMEs) in the immune resolution at the late infection stage to quench the excessive and unnecessary immune responses. In contrast, dihydroxy-octadecamonoenoates (DiHOMEs) were the hydrolyzed and inactive forms of EpOMEs. The hydrolysis is catalyzed by soluble epoxide hydrolase (sEH). Inhibitors specific to sEH mimicked the immunosuppression induced by EpOMEs. Furthermore, the inhibitor treatments significantly enhanced the bacterial virulence of Bacillus thuringiensis against S. exigua. This study proposes a negative control of the immune responses using EpOME/DiHOME in insects.

Validation of operational definitions of mortality in a nationwide hemodialysis population using the Health Insurance Review and Assessment Service databases of Korea.

BACKGROUND: Health Insurance Review and Assessment Service's (HIRA) claims data have been used in studies of hemodialysis patients even though information about mortality is not provided in this database. Mortality analysis using HIRA data has been conducted using various operational definitions that have not been validated. This study aimed to validate operational definitions of mortality for maintenance hemodialysis patients that have been used when analyzing the Korean HIRA database. METHODS: This study utilized claims data of the Korean National Health Insurance Service (NHIS) between January 2008 and December 2019. We estimated mortality based on operational definitions applied in previous studies using the HIRA database and compared it with NHIS mortality information to validate accuracy. RESULTS: A total of 128,876 patients who started maintenance hemodialysis between January 2009 and December 2019 were analyzed. The accuracy of estimated mortality was the highest at 96% in the group where mortality was defined as an absence of claims data for 150 days. If the period of no claims data was set to 90 days or less, there was a risk of overestimating the mortality for the entire study period. When it was set to 180 days or more, there was a risk of underestimating the mortality, as the follow-up time was close to the end of the study period. CONCLUSION: When mortality analysis of maintenance hemodialysis patients is performed using HIRA data, it is most accurate to set the operational definition period as the absence of claims data for 150 days.

Surveying Nutrient Assessment with Photographs of Meals (SNAPMe): A Benchmark Dataset of Food Photos for Dietary Assessment.

Photo-based dietary assessment is becoming more feasible as artificial intelligence methods improve. However, advancement of these methods for dietary assessment in research settings has been hindered by the lack of an appropriate dataset against which to benchmark algorithm performance. We conducted the Surveying Nutrient Assessment with Photographs of Meals (SNAPMe) study (ClinicalTrials ID: NCT05008653) to pair meal photographs with traditional food records. Participants were recruited nationally, and 110 enrollment meetings were completed via web-based video conferencing. Participants uploaded and annotated their meal photos using a mobile phone app called Bitesnap and completed food records using the Automated Self-Administered 24-h Dietary Assessment Tool (ASA24®) version 2020. Participants included photos before and after eating non-packaged and multi-serving packaged meals, as well as photos of the front and ingredient labels for single-serving packaged foods. The SNAPMe Database (DB) contains 3311 unique food photos linked with 275 ASA24 food records from 95 participants who photographed all foods consumed and recorded food records in parallel for up to 3 study days each. The use of the SNAPMe DB to evaluate ingredient prediction demonstrated that the publicly available algorithms FB Inverse Cooking and Im2Recipe performed poorly, especially for single-ingredient foods and beverages. Correlations between nutrient estimates common to the Bitesnap and ASA24 dietary assessment tools indicated a range in predictive capacity across nutrients (cholesterol, adjusted R2 = 0.85, p < 0.0001; food folate, adjusted R2 = 0.21, p < 0.05). SNAPMe DB is a publicly available benchmark for photo-based dietary assessment in nutrition research. Its demonstrated utility suggested areas of needed improvement, especially the prediction of single-ingredient foods and beverages.

Nanowire-Enhanced Fully Transparent and Flexible Indium Gallium Zinc Oxide Transistors with Chitosan Hydrogel Gate Dielectric: A Pathway to Improved Synaptic Properties.

In this study, a transparent and flexible synaptic transistor was fabricated based on a random-network nanowire (NW) channel made of indium gallium zinc oxide. This device employs a biocompatible chitosan-based hydrogel as an electrolytic gate dielectric. The NW structure, with its high surface-to-volume ratio, facilitated a more effective modulation of the channel conductance induced by protonic-ion polarization. A comparative analysis of the synaptic properties of NW- and film-type devices revealed the distinctive features of the NW-type configuration. In particular, the NW-type synaptic transistors exhibited a significantly larger hysteresis window under identical gate-bias conditions. Notably, these transistors demonstrated enhanced paired-pulse facilitation properties, synaptic weight modulation, and transition from short- to long-term memory. The NW-type devices displayed gradual potentiation and depression of the channel conductance and thus achieved a broader dynamic range, improved linearity, and reduced power consumption compared with their film-type counterparts. Remarkably, the NW-type synaptic transistors exhibited impressive recognition accuracy outcomes in Modified National Institute of Standards and Technology pattern-recognition simulations. This characteristic enhances the efficiency of practical artificial intelligence (AI) processes. Consequently, the proposed NW-type synaptic transistor is expected to emerge as a superior candidate for use in high-efficiency artificial neural network systems, thus making it a promising technology for next-generation AI semiconductor applications.

Combined impact of myosteatosis and liver steatosis on prognosis in stage I-III colorectal cancer patients.

BACKGROUND: Myosteatosis and liver steatosis (LS) have been recognized as patient-derived image biomarkers that correlate with prognosis in colorectal cancer (CRC) patients. However, the significance of considering fat deposition in multiple body areas simultaneously has been underestimated. This study aimed to investigate the combined effect of myosteatosis and LS in stage I-III CRC patients. METHODS: A total of 616 stage I-III CRC patients were included in the study. Myosteatosis was assessed using skeletal muscle radiodensity (SMD), and LS was estimated by calculating the Hounsfield unit of the liver and spleen ratio (LSR). Cox proportional hazard models were utilized to evaluate disease-free survival (DFS). A combination of myosteatosis and LS was proposed, and its discriminatory performance was compared using the C-index. RESULTS: Among the 616 participants, the median (interquartile) age was 64 (55-72) years, and 240 (38.9%) were female. The median and interquartile range of LSR were determined as 1.106 (0.967-1.225). The optimal cutoff value for LSR was identified as 1.181, leading to the classification of patients into low (410, 66.5%) and high LSR (206, 33.4%) groups. Among the patients, 200 were categorized into the low SMD group, while 416 were allocated to the high SMD group. Both myosteatosis and LS were identified as independent prognostic factors in the multivariable analysis. The combination of these two variables resulted in a three-group classification: high SMD with low LSR group, high SMD with high LSR group, and low SMD group. When comparing the C-index values, the three-group classification exhibited superior discriminatory performance compared with considering myosteatosis and LS separately. CONCLUSIONS: Myosteatosis was associated with poorer survival, while the presence of LS was linked to a better prognosis in non-metastatic CRC patients. Simultaneously considering fat infiltration can serve as a more effective prognosticator in non-metastatic CRC patients.

Metabolomic analysis reveals linkage between chemical composition and sensory quality of different floral honey samples.

Honey has a distinct flavor characterized by various volatiles and non-volatiles from diverse origins. In this study, metabolomics combined with sensory analysis was performed to identify relationships between chemical profile and sensory quality of honey. Targeted metabolomic analysis was conducted to determine volatile and non-volatile profiles of seven different honey. Volatile profile was analyzed using headspace solid-phase microextraction (HS-SPME) coupled to GC - MS. LC - MS/MS, HPLC - UV, and HPLC-RI were employed to analyze flavonoids, organic acids, and sugars, respectively. Authentic standards were utilized for confirmation of metabolites. Sensory evaluation included quantitative descriptive analysis and consumer acceptance test. The results showed that sucrose (sweetness) was responsible for a positive hedonic perception, while organic acids and flavonoids (sourness, astringency, bitterness) negatively affected consumer acceptance. Volatiles with floral notes (e.g. decyl formate) were preferred, but others with off-flavors (e.g. 2-methylbenzofuran) were not preferred by consumers. Flavor familiarity was strongly correlated with the consumer acceptance of honey, indicating that the balance between volatiles and non-volatiles is significant for honey flavor quality. This work demonstrates the role of key flavor compounds in honey quality, and may be applicable to the quality control of honey.

Advancements in Complementary Metal-Oxide Semiconductor-Compatible Tunnel Barrier Engineered Charge-Trapping Synaptic Transistors for Bio-Inspired Neural Networks in Harsh Environments.

This study aimed to propose a silicon-on-insulator (SOI)-based charge-trapping synaptic transistor with engineered tunnel barriers using high-k dielectrics for artificial synapse electronics capable of operating at high temperatures. The transistor employed sequential electron trapping and de-trapping in the charge storage medium, facilitating gradual modulation of the silicon channel conductance. The engineered tunnel barrier structure (SiO2/Si3N4/SiO2), coupled with the high-k charge-trapping layer of HfO2 and high-k blocking layer of Al2O3, enabled reliable long-term potentiation/depression behaviors within a short gate stimulus time (100 µs), even under elevated temperatures (75 and 125 °C). Conductance variability was determined by the number of gate stimuli reflected in the maximum excitatory postsynaptic current (EPSC) and the residual EPSC ratio. Moreover, we analyzed the Arrhenius relationship between the EPSC as a function of the gate pulse number (N = 1-100) and the measured temperatures (25, 75, and 125 °C), allowing us to deduce the charge trap activation energy. A learning simulation was performed to assess the pattern recognition capabilities of the neuromorphic computing system using the modified National Institute of Standards and Technology datasheets. This study demonstrates high-reliability silicon channel conductance modulation and proposes in-memory computing capabilities for artificial neural networks using SOI-based charge-trapping synaptic transistors.

A CRISPR activation screen identifies MUC-21 as critical for resistance to NK and T cell-mediated cytotoxicity.

BACKGROUND: Immunotherapy has significantly advanced cancer treatments, but many patients do not respond to it, partly due to immunosuppressive mechanisms used by tumor cells. These cells employ immunosuppressive ligands to evade detection and elimination by the immune system. Therefore, the discovery and characterization of novel immunosuppressive ligands that facilitate immune evasion are crucial for developing more potent anti-cancer therapies. METHODS: We conducted gain-of-function screens using a CRISPRa (CRISPR activation) library that covered the entire human transmembrane sub-genome to identify surface molecules capable of hindering NK-mediated cytotoxicity. The immunosuppressive role and mechanism of MUC21 were validated using NK and T cell mediated cytotoxicity assays. Bioinformatics tools were employed to assess the clinical implications of mucin-21 (MUC21) in cancer cell immunity. RESULTS: Our genetic screens revealed that MUC21 expression on cancer cell surfaces inhibits both the cytotoxic activity of NK cells and antibody-dependent cellular cytotoxicity, but not affecting complement-dependent cytotoxicity. Additionally, MUC21 expression hinders T cell activation by impeding antigen recognition, thereby diminishing the effectiveness of the immune checkpoint inhibitor, anti-PD-L1. Moreover, MUC21 expression suppress the antitumor function of both CAR-T cells and CAR-NK cells. Mechanistically, MUC21 facilitates immune evasion by creating steric hindrance, preventing interactions between cancer and immune cells. Bioinformatics analysis revealed elevated MUC21 expression in lung cancer, which correlated with reduced infiltration and activation of cytotoxic immune cells. Intriguingly, MUC21 expression was higher in non-small cell lung cancer (NSCLC) tumors that were non-responsive to anti-PD-(L)1 treatment compared to responsive tumors. CONCLUSIONS: These findings indicate that surface MUC21 serves as a potent immunosuppressive ligand, shielding cancer cells from NK and CD8+T cell attacks. This suggests that inhibiting MUC21 could be a promising strategy to improve cancer immunotherapy.

Enhanced Synaptic Behaviors in Chitosan Electrolyte-Based Electric-Double-Layer Transistors with Poly-Si Nanowire Channel Structures.

In this study, we enhance the synaptic behavior of artificial synaptic transistors by utilizing nanowire (NW)-type polysilicon channel structures. The high surface-to-volume ratio of the NW channels enables efficient modulation of the channel conductance, which is interpreted as the synaptic weight. As a result, NW-type synaptic transistors exhibit a larger hysteresis window compared to film-type synaptic transistors, even within the same gate voltage sweeping range. Moreover, NW-type synaptic transistors demonstrate superior short-term facilitation and long-term memory transition compared with film-type ones, as evidenced by the measured paired-pulse facilitation and excitatory post-synaptic current characteristics at varying frequencies and pulse numbers. Additionally, we observed gradual potentiation/depression characteristics, making these artificial synapses applicable to artificial neural networks. Furthermore, the NW-type synaptic transistors exhibit improved Modified National Institute of Standards and Technology pattern recognition rate of 91.2%. In conclusion, NW structure channels are expected to be a promising technology for next-generation artificial intelligence (AI) semiconductors, and the integration of NW structure channels has significant potential to advance AI semiconductor technology.

Solid-State Structural Transformation in Zn(II) Metal-Organic Frameworks in a Single-Crystal-to-Single-Crystal Fashion.

Solid-state structural transformation is an interesting methodology used to prepare various metal-organic frameworks (MOFs) that are challenging to prepare in direct synthetic procedures. On the other hand, solid-state [2 + 2] photoreactions are distinctive methodologies used for light-driven solid-state transformations. Meanwhile, most of these photoreactions explored are quantitative in nature, in addition to them being stereo-selective and regio-specific in manner. In this work, we successfully synthesized two photoreactive novel binuclear Zn(II) MOFs, [Zn2(spy)2(tdc)2] (1) and [Zn2(spy)4(tdc)2] (2) (where spy = 4-styrylpyridine and tdc = 2,5-thiophenedicarboxylate) with different secondary building units. Both MOFs are interdigitated in nature and are 2D and 1D frameworks, respectively. Both the compounds showed 100% and 50% photoreaction upon UV irradiation, as estimated from the structural analysis for 1 and 2, respectively. This light-driven transformation resulted in the formation of 3D, [Zn2(rctt-ppcb)(tdc)2] (3), and 2D, [Zn2(spy)2(rctt-ppcb)(tdc)2] (4) (where rctt = regio, cis, trans, trans; ppcb = 1,3-bis(4'-pyridyl)-2,4-bis(phenyl)cyclobutane), respectively. These solid-state structural transformations were observed as an interesting post-synthetic modification. Overall, we successfully transformed novel lower-dimensional frameworks into higher-dimensional materials using a solid-state [2 + 2] photocycloaddition reaction.

Implementation of Highly Stable Memristive Characteristics in an Organic-Inorganic Hybrid Resistive Switching Layer of Chitosan-Titanium Oxide with Microwave-Assisted Oxidation.

This study proposes a high-performance organic-inorganic hybrid memristor for the development of neuromorphic devices in the memristor-based artificial synapse. The memristor consists of a solid polymer electrolyte (SPE) chitosan layer and a titanium oxide (TiOx) layer grown with a low-thermal-budget, microwave-assisted oxidation. The fabricated Ti/SPE-chitosan/TiOx/Pt-structured memristor exhibited steady bipolar resistive switching (BRS) characteristics and demonstrated excellent endurance in 100-cycle repetition tests. Compared to SPE-chitosan memristors without a TiOx layer, the proposed organic-inorganic hybrid memristor demonstrated a higher dynamic range and a higher response to pre-synaptic stimuli such as short-term plasticity via paired-pulse facilitation. The effect of adding the TiOx layer on the BRS properties was examined, and the results showed that the TiOx layer improved the chemical and electrical superiority of the proposed memristor synaptic device. The proposed SPE-chitosan organic-inorganic hybrid memristor also exhibited a stable spike-timing-dependent plasticity, which closely mimics long-term plasticity. The potentiation and depression behaviors that modulate synaptic weights operated stably via repeated spike cycle tests. Therefore, the proposed SPE-chitosan organic-inorganic hybrid memristor is a promising candidate for the development of neuromorphic devices in memristor-based artificial synapses owing to its excellent stability, high dynamic range, and superior response to pre-synaptic stimuli.

Insect immune resolution with EpOME/DiHOME and its dysregulation by their analogs leading to pathogen hypersensitivity.

Epoxyoctadecamonoenoic acids (EpOMEs) are epoxide derivatives of linoleic acid (9,12-octadecadienoic acid: LA). They are metabolized into dihydroxyoctadecamonoenoic acids (DiHOMEs) in mammals. Unlike in mammals where they act as adipokines or lipokines, EpOMEs act as immunosuppressants in insects. However, the functional link between EpOMEs and pro-immune mediators such as PGE2 is not known. In addition, the physiological significance of DiHOMEs is not clear in insects. This study analyzed the physiological role of these C18 oxylipins using a lepidopteran insect pest, Spodoptera exigua. Immune challenge of S. exigua rapidly upregulated the expression of the phospholipase A2 gene to trigger C20 oxylipin biosynthesis, followed by the upregulation of genes encoding EpOME synthase (SE51385) and a soluble epoxide hydrolase (Se-sEH). The sequential gene expression resulted in the upregulations of the corresponding gene products such as PGE2, EpOMEs, and DiHOMEs. Interestingly, only PGE2 injection without the immune challenge significantly upregulated the gene expression of SE51825 and Se-sEH. The elevated levels of EpOMEs acted as immunosuppressants by inhibiting cellular and humoral immune responses induced by the bacterial challenge, in which 12,13-EpOME was more potent than 9,10-EpOME. However, DiHOMEs did not inhibit the cellular immune responses but upregulated the expression of antimicrobial peptides selectively suppressed by EpOMEs. The negative regulation of insect immunity by EpOMEs and their inactive DiHOMEs were further validated by synthetic analogs of the linoleate epoxide and corresponding diol. Furthermore, inhibitors specific to Se-sEH used to prevent EpOME degradation significantly suppressed the immune responses. The data suggest a physiological role of C18 oxylipins in resolving insect immune response. Any immune dysregulation induced by EpOME analogs or sEH inhibitors significantly enhanced insect susceptibility to the entomopathogen, Bacillus thuringiensis.

Enhancement of Non-Linear Deep Learning Model by Adjusting Confounding Variables for Bone Age Estimation in Pediatric Hand X-rays.

In medicine, confounding variables in a generalized linear model are often adjusted; however, these variables have not yet been exploited in a non-linear deep learning model. Sex plays important role in bone age estimation, and non-linear deep learning model reported their performances comparable to human experts. Therefore, we investigate the properties of using confounding variables in a non-linear deep learning model for bone age estimation in pediatric hand X-rays. The RSNA Pediatric Bone Age Challenge (2017) dataset is used to train deep learning models. The RSNA test dataset is used for internal validation, and 227 pediatric hand X-ray images with bone age, chronological age, and sex information from Asan Medical Center (AMC) for external validation. U-Net based autoencoder, U-Net multi-task learning (MTL), and auxiliary-accelerated MTL (AA-MTL) models are chosen. Bone age estimations adjusted by input, output prediction, and without adjusting the confounding variables are compared. Additionally, ablation studies for model size, auxiliary task hierarchy, and multiple tasks are conducted. Correlation and Bland-Altman plots between ground truth and model-predicted bone ages are evaluated. Averaged saliency maps based on image registration are superimposed on representative images according to puberty stage. In the RSNA test dataset, adjusting by input shows the best performances regardless of model size, with mean average errors (MAEs) of 5.740, 5.478, and 5.434 months for the U-Net backbone, U-Net MTL, and AA-MTL models, respectively. However, in the AMC dataset, the AA-MTL model that adjusts the confounding variable by prediction shows the best performance with an MAE of 8.190 months, whereas the other models show the best performances by adjusting the confounding variables by input. Ablation studies of task hierarchy reveal no significant differences in the results of the RSNA dataset. However, predicting the confounding variable in the second encoder layer and estimating bone age in the bottleneck layer shows the best performance in the AMC dataset. Ablations studies of multiple tasks reveal that leveraging confounding variables plays an important role regardless of multiple tasks. To estimate bone age in pediatric X-rays, the clinical setting and balance between model size, task hierarchy, and confounding adjustment method play important roles in performance and generalizability; therefore, proper adjusting methods of confounding variables to train deep learning-based models are required for improved models.

Predictable Factors of People with Asymmetrical Hearing Loss Wearing a Hearing Aid in the Worse Ear Only.

In patients with bilateral asymmetrical hearing loss (AHL), where only one hearing aid is available, it is difficult to decide which ear to amplify. The aim of this study was to evaluate the outcomes of hearing aid use for AHL patients fitted with a hearing aid in their worse ear only. One-hundred-two adults with asymmetrical-mixed or sensorineural hearing loss were retrospectively included. AHL was classified into three subgroups: unilateral hearing loss (UHL) and AHL type 1 (AHL1) and type 2 (AHL2). The main outcome measures were (1) the time spent wearing a hearing aid, (2) the hearing in a noise test (HINT), (3) the sound localization test and (4) the Korean version of the International Outcome Inventory for Hearing Aids (IOI-HA). The 1 kHz-hearing threshold of the better ear was significantly better in the successful users than in the intermittent users for UHL. Younger age was associated with significantly better outcomes than older for AHL1 and AHL2. Among the etiologies of AHL, sudden hearing loss was associated with significantly better outcomes of hearing aid use for AHL, UHL and AHL1 patients. In this study, the success rate and usage rates were 43.1% and 67.6% in AHL patients wearing a hearing aid in the worse ear. This study identified the hearing threshold of 1 kHz from the better ear, age and etiology of sudden hearing loss as audiometric and non-audiometric factors that affected the outcomes of hearing aid use.

Synaptic Transistors Based on PVA: Chitosan Biopolymer Blended Electric-Double-Layer with High Ionic Conductivity.

This study proposed a biocompatible polymeric organic material-based synaptic transistor gated with a biopolymer electrolyte. A polyvinyl alcohol (PVA):chitosan (CS) biopolymer blended electrolyte with high ionic conductivity was used as an electrical double layer (EDL). It served as a gate insulator with a key function as an artificial synaptic transistor. The frequency-dependent capacitance characteristics of PVA:CS-based biopolymer EDL were evaluated using an EDL capacitor (Al/PVA: CS blended electrolyte-based EDL/Pt configuration). Consequently, the PVA:CS blended electrolyte behaved as an EDL owing to high capacitance (1.53 µF/cm2) at 100 Hz and internal mobile protonic ions. Electronic synaptic transistors fabricated using the PVA:CS blended electrolyte-based EDL membrane demonstrated basic artificial synaptic behaviors such as excitatory post-synaptic current modulation, paired-pulse facilitation, and dynamic signal-filtering functions by pre-synaptic spikes. In addition, the spike-timing-dependent plasticity was evaluated using synaptic spikes. The synaptic weight modulation was stable during repetitive spike cycles for potentiation and depression. Pattern recognition was conducted through a learning simulation for artificial neural networks (ANNs) using Modified National Institute of Standards and Technology datasheets to examine the neuromorphic computing system capability (high recognition rate of 92%). Therefore, the proposed synaptic transistor is suitable for ANNs and shows potential for biological and eco-friendly neuromorphic systems.

Manipulation of GameXPeptide synthetase gene expression by a promoter exchange alters the virulence of an entomopathogenic bacterium, Photorhabdus temperata temperata, by modulating insect immune responses.

An entomopathogenic bacterium, Photorhabdus temperata subsp. temperata, is mutualistic to its host nematode, Heterorhabditis megidis. The infective juvenile nematodes enter target insects through natural openings and release the symbiotic bacteria into the insect hemocoel. The released bacteria suppress the insect immune responses and cause septicemia through their secondary metabolites. GameXPeptide (GXP) is one of the common secondary metabolites of most Photorhabdus species and is produced by the catalytic activity of a specific non-ribosomal peptide synthetase called GxpS encoded by the gxpS gene. This study confirmed gxpS to be encoded in the P. temperata temperata genome and analyzed its expression during bacterial growth. LC-MS/MS analysis of the bacterial culture broth contained at least four different GXPs (GXP-A to GXP-D), in which GXP-A was the most abundant. To investigate GXP synthesis following gxpS expression, the gxpS promoter of P. temperata temperata was replaced with an inducible arabinose promoter by homologous recombination. The gxpS transcript levels in the mutant were altered by the addition of l-arabinose. Without the inducer, the gxpS transcript level was significantly lower compared to the wild type and produced significantly lower amounts of the four GXPs. The addition of the inducer to the mutant significantly increased gxpS expression and produced significantly higher levels of the four GXPs compared to the wild type. The metabolite extracts obtained from wild-type and mutant bacteria showed differential immunosuppressive activities according to their GXP contents against the cellular and humoral immune responses of a lepidopteran insect, Spodoptera exigua. Interestingly, the gxpS-mutant bacteria showed less insecticidal activity compared to the wild type, whereas the addition of GXP to the mutant significantly restored insecticidal activity. These results suggest that the gxpS gene encoded in P. temperata temperata is responsible for the production of at least four different GXPs, which play crucial roles in bacterial virulence.

Unexpected Solvent-Dependent Self-Assembly of Alkali Metal Complexes of Calix[6]-mono-crown-4: Dinuclear Bowls, a Pseudo-Capsule, and a One-Dimensional Polymer.

1,4-Bridged calix[6]-mono-crown-4 (H4L) capable of metal binding was employed, and the influence of solvent variations on the formation of alkali metal complexes (1-6) was investigated. In the crystal, the bowl-shaped H4L host contains one water molecule in a good-fit fashion via H-bonds. When the H4L host was reacted with alkali metal hydroxides (M = Na, K, Rb, and Cs) in chloroform/methanol (solvent A), anion-free dinuclear bowl-shaped complexes of type [M2(H2L)] were isolated regardless of the metal ions. In the dinuclear bowl complexes 1-4, two metal ions (M1 and M2) show different binding behaviors: one (M1) locates inside the pocket like an "egg-in-nest", and the other (M2) positions above the M1 interacting with the calix rim. When chloroform/acetonitrile (solvent B) was used in potassium(I) complexation, interestingly, an elegant pseudo-capsule-type quadrunuclear complex 5 was isolated. In 5, two dipotassium(I) bowls in a rim-to-rim arrangement are triply bridged by one water and two acetonitrile molecules like a magic glue. However, in dichloromethane/methanol (solvent C), cesium(I) yielded an infinite product 6 in which dicesium(I) bowls are linked by cation-π interactions, giving rise to a one-dimensional zigzag coordination polymer. Taken collectively, all products share a dinuclear bowl unit, some of which are further extended to the pseudo-capsule or polymeric array, depending on the solvents. The results suggest the solvent variation as a versatile engineering tool and present a perspective on the metallosupramolecules of calix[6]-mono-crowns with monomer, dimer (e.g., pseudo-capsule), and polymer topologies.

Protective Effect of Delta-Like 1 Homolog Against Muscular Atrophy in a Mouse Model.

BACKGRUOUND: Muscle atrophy is caused by an imbalance between muscle growth and wasting. Delta-like 1 homolog (DLK1), a protein that modulates adipogenesis and muscle development, is a crucial regulator of myogenic programming. Thus, we investigated the effect of exogenous DLK1 on muscular atrophy. METHODS: We used muscular atrophy mouse model induced by dexamethasone (Dex). The mice were randomly divided into three groups: (1) control group, (2) Dex-induced muscle atrophy group, and (3) Dex-induced muscle atrophy group treated with DLK1. The effects of DLK1 were also investigated in an in vitro model using C2C12 myotubes. RESULTS: Dex-induced muscular atrophy in mice was associated with increased expression of muscle atrophy markers and decreased expression of muscle differentiation markers, while DLK1 treatment attenuated these degenerative changes together with reduced expression of the muscle growth inhibitor, myostatin. In addition, electron microscopy revealed that DLK1 treatment improved mitochondrial dynamics in the Dex-induced atrophy model. In the in vitro model of muscle atrophy, normalized expression of muscle differentiation markers by DLK1 treatment was mitigated by myostatin knockdown, implying that DLK1 attenuates muscle atrophy through the myostatin pathway. CONCLUSION: DLK1 treatment inhibited muscular atrophy by suppressing myostatin-driven signaling and improving mitochondrial biogenesis. Thus, DLK1 might be a promising candidate to treat sarcopenia, characterized by muscle atrophy and degeneration.

Hemp-Derived Nanovesicles Protect Leaky Gut and Liver Injury in Dextran Sodium Sulfate-Induced Colitis.

Hemp (Cannabis sativa L.) is used for medicinal purposes owing to its anti-inflammatory and antioxidant activities. We evaluated the protective effect of nanovesicles isolated from hemp plant parts (root, seed, hemp sprout, and leaf) in dextran sulfate sodium (DSS)-induced colitis in mice. The particle sizes of root-derived nanovesicles (RNVs), seed-derived nanovesicles (SNVs), hemp sprout-derived nanovesicles (HSNVs), and leaf-derived nanovesicles (LNVs) were within the range of 100-200 nm as measured by nanoparticle tracking analysis. Acute colitis was induced in C57BL/N mice by 5% DSS in water provided for 7 days. RNVs were administered orally once a day, leading to the recovery of both the small intestine and colon lengths. RNVs, SNVs, and HSNVs restored the tight (ZO-1, claudin-4, occludin) and adherent junctions (E-cadherin and α-tubulin) in DSS-induced small intestine and colon injury. Additionally, RNVs markedly reduced NF-κB activation and oxidative stress proteins in DSS-induced small intestine and colon injury. Tight junction protein expression and epithelial cell permeability were elevated in RNV-, SNV-, and HSNV-treated T84 colon cells exposed to 2% DSS. Interestedly, RNVs, SNVs, HSNVs, and LNVs reduced ALT activity and liver regeneration marker proteins in DSS-induced liver injury. These results showed for the first time that hemp-derived nanovesicles (HNVs) exhibited a protective effect on DSS-induced gut leaky and liver injury through the gut-liver axis by inhibiting oxidative stress marker proteins.