Transforming layered 2D mats into multiphasic 3D nanofiber scaffolds with tailored gradient features for tissue regeneration.

Multiphasic scaffolds with tailored gradient features hold significant promise for tissue regeneration applications. Herein, this work reports the transformation of two-dimensional (2D) layered fiber mats into three dimensional (3D) multiphasic scaffolds using a 'solids-of-revolution' inspired gas-foaming expansion technology. These scaffolds feature precise control over fiber alignment, pore size, and regional structure. Manipulating nanofiber mat layers and Pluronic F127 concentrations allows further customization of pore size and fiber alignment within different scaffold regions. The cellular response to multiphasic scaffolds demonstrates the number of cells migrated and proliferated onto the scaffolds are mainly dependent on the pore size rather than fiber alignment. In vivo subcutaneous implantation of multiphasic scaffolds to rats reveals substantial cell infiltration, neo tissue formation, collagen deposition, and new vessel formation within scaffolds, greatly surpassing the capabilities of traditional nanofiber mats. Histological examination indicates the importance of optimizing pore size and fiber alignment for promotion of cell infiltration and tissue regeneration. Overall, these scaffolds have potential applications in tissue modeling, studying tissue-tissue interactions, interface tissue engineering, and high-throughput screening for optimized tissue regeneration.

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.

Does source matter? Examining the effects of health experts, friends, and social media influencers on young adult perceptions of Instagram e-cigarette education messages.

PURPOSE: Young adults' e-cigarette use is a leading public health concern. Using messages from credible sources can help improve message acceptance, yet little research has examined the role of source credibility on young adults' responses to e-cigarette education messages. METHODS: We examined the impact of source on young adults' perceptions of e-cigarette education messages and e-cigarettes. In July 2022, we conducted an experimental study using an online sample of young adults (N=459, Mage=24.6) who were randomized to one of three source conditions: expert, friend, or influencer, and viewed e-cigarette education messages. We used one-way ANOVA to estimate the association between the conditions and outcomes (perceived source credibility, message trust, curiosity, use interests, perceived message effectiveness, beliefs, harm perceptions, and intentions to refrain). RESULTS: The expert condition was associated with significantly higher perceived source credibility (vs. friend, influencer; p<0.001), message trust (vs. friend, influencer; p<0.001), and curiosity (vs. influencer; p's<0.05). CONCLUSIONS: Public health campaigns may leverage health experts to deliver e-cigarette education messages targeting young adults to improve effectiveness of the messages.

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.

Impact of Financial Disclosures and Health Warnings on Youth and Young Adult Perceptions of Pro-E-cigarette Instagram Posts.

INTRODUCTION: We examined the impact of financial disclosures and warning labels on pro-e-cigarette Instagram posts and their association with attitudes toward the ad and product among youth and young adults. METHODS: During March to May 2021, we conducted a factorial experiment using an online convenience sample of youth and young adults (N = 1687, Mage = 21.54). Participants were randomized to one of four conditions: pro-e-cigarette Instagram posts with only a financial disclosure, only a warning label, both a financial disclosure + warning label, or no financial disclosure or warning label. After viewing the posts, participants answered questions regarding their attitude toward the ad and the product. We used one-way ANOVA to estimate the association of condition on outcomes controlling for demographics. RESULTS: Young adults who viewed Instagram posts with only a financial disclosure reported more positive attitudes toward the ad than those who viewed posts with both a financial disclosure + warning label (p < .05). Young adults who viewed posts with only a financial disclosure reported more positive attitudes toward the product than those who viewed posts with only a warning label, both a financial disclosure + warning label, and without either (ps < .05). Differences were not statistically significant for youth. E-cigarette use status was associated with increased positive attitudes toward the ad (p < .001) and product (p < .001) for all participants. CONCLUSIONS: Our results can inform policy interventions to mitigate the effects of e-cigarette social media marketing among youth and young adults. Including financial disclosures may not decrease appeal of e-cigarettes compared to posts without either. IMPLICATIONS: Findings from the study suggest that a warning label may be more effective in reducing the effects of pro-e-cigarette social media posts than a financial disclosure among young adults. Public health officials should examine additional strategies beyond financial disclosures and warning labels (eg, social media peer mentoring program) to offset the persuasive effects of pro-e-cigarette social media marketing posts on young people. Additional policy interventional efforts are needed to limit the impact of e-cigarette social media marketing.

N-cadherin and ß1 integrin coordinately regulate growth plate cartilage architecture.

Spatial and temporal regulation of chondrocyte maturation in the growth plate drives growth of many bones. One essential event to generate the ordered cell array characterizing growth plate cartilage is the formation of chondrocyte columns in the proliferative zone via 90-degree rotation of daughter cells to align with the long axis of the bone. Previous studies have suggested crucial roles for cadherins and integrin ß1 in column formation. The purpose of this study was to determine the relative contributions of cadherin- and integrin-mediated cell adhesion in column formation. Here we present new mechanistic insights generated by application of live time-lapse confocal microscopy of cranial base explant cultures, robust genetic mouse models, and new quantitative methods to analyze cell behavior. We show that conditional deletion of either the cell-cell adhesion molecule Cdh2 or the cell-matrix adhesion molecule Itgb1 disrupts column formation. Compound mutants were used to determine a potential reciprocal regulatory interaction between the two adhesion surfaces and identified that defective chondrocyte rotation in a N-cadherin mutant was restored by a heterozygous loss of integrin ß1. Our results support a model for which integrin ß1, and not N-cadherin, drives chondrocyte rotation and for which N-cadherin is a potential negative regulator of integrin ß1 function.

The Combined Effects on Human Dental Pulp Stem Cells of Fast-Set or Premixed Hydraulic Calcium Silicate Cements and Secretome Regarding Biocompatibility and Osteogenic Differentiation.

An important part of regenerative endodontic procedures involving immature permanent teeth is the regeneration of the pulp-dentin complex with continuous root development. Hydraulic calcium silicate cements (HCSCs) are introduced for the pulpal treatment of immature permanent teeth. The stem-cell-derived secretome recently has been applied for the treatment of various damaged tissues. Here, we evaluated the biocompatibility and osteogenic differentiation of HCSCs combined with secretome on human dental pulp stem cells. In the Cell Counting Kit-8 test and wound healing assays, significantly higher cell viability was observed with secretome application. In alkaline phosphatase analysis, the activity was significantly higher with secretome application in all groups, except for RetroMTA on day 2 and Endocem MTA Premixed on day 4. In an Alizarin Red S staining analysis, all groups with secretome application had significantly higher staining values. Quantitative real-time polymerase chain reaction results showed that the day 7 expression of OSX significantly increased with secretome application in all groups. SMAD1 and DSPP expression also increased significantly with secretome addition in all groups except for Biodentine. In conclusion, HCSCs showed favorable biocompatibility and osteogenic ability and are predicted to demonstrate greater synergy with the addition of secretome during regenerative endodontic procedures involving immature permanent teeth.

A Facile Strategy for the Fabrication of Cell-laden Porous Alginate Hydrogels Based on Two-phase Aqueous Emulsions.

Porous alginate hydrogels possess many advantages as cell carriers. However, current pore generation methods require either complex or harsh fabrication processes, toxic components, or extra purification steps, limiting the feasibility and affecting the cellular survival and function. In this study, a simple and cell-friendly approach to generate highly porous cell-laden alginate hydrogels based on two-phase aqueous emulsions is reported. The pre-gel solutions, which contain two immiscible aqueous phases of alginate and caseinate, are crosslinked by calcium ions. The porous structure of the hydrogel construct is formed by subsequently removing the caseinate phase from the ion-crosslinked alginate hydrogel. Those porous alginate hydrogels possess heterogeneous pores around 100 µm and interconnected paths. Human white adipose progenitors (WAPs) encapsulated in these hydrogels self-organize into spheroids and show enhanced viability, proliferation, and adipogenic differentiation, compared to non-porous constructs. As a proof of concept, this porous alginate hydrogel platform is employed to prepare core-shell spheres for coculture of WAPs and colon cancer cells, with WAP clusters distributed around cancer cell aggregates, to investigate cellular crosstalk. This efficacious approach is believed to provide a robust and versatile platform for engineering porous-structured alginate hydrogels for applications as cell carriers and in disease modeling.

Developing Mood-Based Computer-Tailored Health Communication for Smoking Cessation: Feasibility Randomized Controlled Trial.

BACKGROUND: Computer-tailored health communication (CTHC), a widely used strategy to increase the effectiveness of smoking cessation interventions, is focused on selecting the best messages for an individual. More recently, CTHC interventions have been tested using contextual information such as participants' current stress or location to adapt message selection. However, mood has not yet been used in CTCH interventions and may increase their effectiveness. OBJECTIVE: This study aims to examine the association of mood and smoking cessation message effectiveness among adults who currently smoke cigarettes. METHODS: In January 2022, we recruited a web-based convenience sample of adults who smoke cigarettes (N=615; mean age 41.13 y). Participants were randomized to 1 of 3 mood conditions (positive, negative, or neutral) and viewed pictures selected from the International Affective Picture System to induce an emotional state within the assigned condition. Participants then viewed smoking cessation messages with topics covering five themes: (1) financial costs or rewards, (2) health, (3) quality of life, (4) challenges of quitting, and (5) motivation or reasons to quit. Following each message, participants completed questions on 3 constructs: message receptivity, perceived relevance, and their motivation to quit. The process was repeated 30 times. We used 1-way ANOVA to estimate the association of the mood condition on these constructs, controlling for demographics, cigarettes per day, and motivation to quit measured during the pretest. We also estimated the association between mood and outcomes for each of the 5 smoking message theme categories. RESULTS: There was an overall statistically significant effect of the mood condition on the motivation to quit outcome (P=.02) but not on the message receptivity (P=.16) and perceived relevance (P=.86) outcomes. Participants in the positive mood condition reported significantly greater motivation to quit compared with those in the negative mood condition (P=.005). Participants in the positive mood condition reported higher motivation to quit after viewing smoking cessation messages in the financial (P=.03), health (P=.01), quality of life (P=.04), and challenges of quitting (P=.03) theme categories. We also compared each mood condition and found that participants in the positive mood condition reported significantly greater motivation to quit after seeing messages in the financial (P=.01), health (P=.003), quality of life (P=.01), and challenges of quitting (P=.01) theme categories than those in the negative mood condition. CONCLUSIONS: Our findings suggest that considering mood may be important for future CTHC interventions. Because those in the positive mood state at the time of message exposure were more likely to have greater quitting motivations, smoking cessation CTHC interventions may consider strategies to help improve participants' mood when delivering these messages. For those in neutral and negative mood states, focusing on certain message themes (health and motivation to quit) may be more effective than other message themes.

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.

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.

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.

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.

Sexual orientation and gender identity differences in perceptions and product appeal in response to e-cigarette advertising.

INTRODUCTION: E-cigarette use is disparately high among sexual minoritized populations. As e-cigarette advertising may influence product appeal, this study tested sexual orientation- and gender-based differences in response to e-cigarette advertisement exposure on advertisement perceptions and product appeal. METHODS: We recruited 497 adults (mean age=31.9 years, 45.1% women, 54.3% heterosexual, 71.2% Non-Hispanic White) living in the United States via the crowdsourcing platform Prolific. Participants viewed two randomly selected e-cigarette advertisements (from n=173 advertisements). Post-exposure, participants rated the perceived advertisement effectiveness, relevance, and product use intention. Associations between sexual orientation and outcomes were estimated using multivariable linear mixed-effects models. We tested interaction effects between sexual orientation, gender, and advertisement feature (e.g. presence of humans, flavors, and product packaging), and ran Tukey post hoc tests for pairwise comparisons. RESULTS: Post-exposure, heterosexual women, sexual minoritized men, and sexual minoritized women (reference group: heterosexual men) rated perceived advertisement effectiveness and relevance lower after viewing advertisements featuring flavors (vs no flavors; all p<0.001). Sexual minoritized men and sexual minoritized women rated perceived advertisement relevance lower after viewing advertisements featuring humans (all p<0.001) or fruit (all p<0.001). Heterosexual women, sexual minoritized men, and sexual minoritized women reported lower product use intention after viewing advertisements featuring an e-liquid bottle (vs no e-liquid bottle; all p<0.05). CONCLUSIONS: Sexual minoritized women and men reported lower e-cigarette advertisement appeal and product use intentions than heterosexual men. More evidence is needed to understand advertisement perceptions and product appeal in this group to inform e-cigarette advertising regulations and anti-tobacco messaging campaigns that aim to reduce tobacco-related health inequities.

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.

Benzo[d]imidazole-pyrrolo[1,2-a]pyrazine Hybrids Ameliorate Amyloid Aggregates in the Brain of Alzheimer Transgenic Mice.

Abnormal assembly of amyloid ß (Aß) in the brain is implicated in Alzheimer's disease (AD) and is associated with cognitive impairments. Since Aß accumulation occurs in advance of the onset of clinical symptoms, identifying preventable drug candidates regulating Aß accumulation is regarded as a promising approach in AD therapeutic. Herein, we synthesized eight Yonsei Institute of pharmaceutical sciences Alzheimer's Drug (YIAD) compounds based on 5-benzyl-6-phenylbenzo[4,5]imidazo[1,2-a]pyrrolo[2,1-c]pyrazine structures. Subsequently, YIAD-0203 and YIAD-0205 were selected as effective candidates via thioflavin T assays and gel electrophoresis. The potential therapeutic effect of YIAD-0203 and YIAD-0205 on Aß aggregates was investigated through an AD transgenic mouse model with five familial AD mutations (5XFAD) by oral gavage. Significant amounts of Aß plaque and oligomer reduction were observed in the hippocampus region of both 4.3-month-old (early stage of AD) and 6.0-month-old (mid stage of AD) YIAD-0205-treated 5XFAD mice brains when compared to the nontreated brains. The ability of YIAD-0205 to ameliorate Aß aggregates in the early and mid stages of AD progression supports the notion that YIAD-0205 could be utilized as a reliable scaffold for the development of preventive AD drug candidates.

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.

Albumin-coated copper nanoparticles for photothermal cancer therapy: Synthesis and in vitro characterization.

Copper nanoparticles (CuNPs) have attracted great interest in various biomedical research fields due to their superior optical and plasmonic properties. In the present study, we synthesized bovine serum albumin (BSA)-coated CuNPs (BSA-CuNPs) by adopting the aqueous reduction method in 2-step procedures. The prepared BSA-CuNPs were characterized in vitro for their physical characteristics and photothermal activity. The successful synthesis of BSA-CuNPs was verified through transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), dynamic light scattering (DLS), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and ultraviolet-visible (UV-VIS) light spectroscopy. The prepared BSA-CuNPs revealed a great light-to-heat conversion capacity and good photothermal stability. Notably, accompanied by laser irradiation, the BSA-CuNPs elicited significantly higher cytotoxicity on tumor cells than the control group. Preliminary animal studies to determine the biosafety and pharmacokinetics (PK) profiles exhibited that the BSA-CuNPs have a maximum tolerable dose (MTD) of 16 mgCu/kg and a relatively long plasma half-life of 1.98 h. Overall, our findings demonstrated that BSA-CuNPs might be a potential photothermal therapeutic agent for cancer treatment.

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.

Pharmaceutical Strategies to Improve Druggability of Potential Drug Candidates in Nonalcoholic Fatty Liver Disease Therapy.

Nonalcoholic fatty liver disease (NAFLD) has become globally prevalent and is the leading cause of chronic liver disease. Although NAFLD is reversible without medical intervention in the early stage, the condition could be sequentially worsened to nonalcoholic steatohepatitis (NASH) and, eventually, cirrhosis and hepatic cancer. The progression of NAFLD is related to various factors such as genetics, pre-disposed metabolic disorders, and immunologic factors. Thankfully, to date, there have been accumulating research efforts and, as a result, different classes of potent drug candidates have been discovered. In addition, there have also been various attempts to explore pharmaceutical strategies to improve the druggability of drug candidates. In this review, we provided a brief overview of the drug candidates that have undergone clinical trials. In the latter part, strategies for developing better drugs are discussed.