Genetically Engineered CLDN18.2 CAR-T Cells Expressing Synthetic PD1/CD28 Fusion Receptors Produced Using a Lentiviral Vector.

This study aimed to develop synthetic Claudin18.2 (CLDN18.2) chimeric antigen receptor (CAR)-T (CAR-T) cells as a treatment for advanced gastric cancer using lentiviral vector genetic engineering technology that targets the CLDN18.2 antigen and simultaneously overcomes the immunosuppressive environment caused by programmed cell death protein 1 (PD-1). Synthetic CAR T cells are a promising approach in cancer immunotherapy but face many challenges in solid tumors. One of the major problems is immunosuppression caused by PD-1. CLDN18.2, a gastric-specific membrane protein, is considered a potential therapeutic target for gastric and other cancers. In our study, CLDN18.2 CAR was a second-generation CAR with inducible T-cell costimulatory (CD278), and CLDN18.2-PD1/CD28 CAR was a third-generation CAR, wherein the synthetic PD1/CD28 chimeric-switch receptor (CSR) was added to the second-generation CAR. In vitro, we detected the secretion levels of different cytokines and the killing ability of CAR-T cells. We found that the secretion of cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) secreted by three types of CAR-T cells was increased, and the killing ability against CLDN18.2-positive GC cells was enhanced. In vivo, we established a xenograft GC model and observed the antitumor effects and off-target toxicity of CAR-T cells. These results support that synthetic anti-CLDN18.2 CAR-T cells have antitumor effect and anti-CLDN18.2-PD1/CD28 CAR could provide a promising design strategy to improve the efficacy of CAR-T cells in advanced gastric cancer.

A water-soluble label for food products prevents packaging waste and counterfeiting.

Sustainability, humidity sensing and product origin are important features of food packaging. While waste generated from labelling and packaging causes environmental destruction, humidity can result in food spoilage during delivery and counterfeit-prone labelling undermines consumer trust. Here we introduce a food label based on a water-soluble nanocomposite ink with a high refractive index that addresses these issues. By patterning the nanocomposite ink using nanoimprint lithography, the resultant metasurface shows bright and vivid structural colours. This method makes it possible to quickly and inexpensively create patterns on large surfaces. A QR code is also developed that can provide up-to-date information on food products. Microprinting hidden in the QR code protects against counterfeiting, cannot be physically detached or replicated and may be used as a humidity indicator. Our proposed food label can reduce waste while ensuring customers receive accurate product information.

Causal dynamics of sleep, circadian rhythm, and mood symptoms in patients with major depression and bipolar disorder: insights from longitudinal wearable device data.

BACKGROUND: Sleep and circadian rhythm disruptions are common in patients with mood disorders. The intricate relationship between these disruptions and mood has been investigated, but their causal dynamics remain unknown. METHODS: We analysed data from 139 patients (76 female, mean age = 23.5 ± 3.64 years) with mood disorders who participated in a prospective observational study in South Korea. The patients wore wearable devices to monitor sleep and engaged in smartphone-delivered ecological momentary assessment of mood symptoms. Using a mathematical model, we estimated their daily circadian phase based on sleep data. Subsequently, we obtained daily time series for sleep/circadian phase estimates and mood symptoms spanning >40,000 days. We analysed the causal relationship between the time series using transfer entropy, a non-linear causal inference method. FINDINGS: The transfer entropy analysis suggested causality from circadian phase disturbance to mood symptoms in both patients with MDD (n = 45) and BD type I (n = 35), as 66.7% and 85.7% of the patients with a large dataset (>600 days) showed causality, but not in patients with BD type II (n = 59). Surprisingly, no causal relationship was suggested between sleep phase disturbances and mood symptoms. INTERPRETATION: Our findings suggest that in patients with mood disorders, circadian phase disturbances directly precede mood symptoms. This underscores the potential of targeting circadian rhythms in digital medicine, such as sleep or light exposure interventions, to restore circadian phase and thereby manage mood disorders effectively. FUNDING: Institute for Basic Science, the Human Frontiers Science Program Organization, the National Research Foundation of Korea, and the Ministry of Health & Welfare of South Korea.

Identifying predictive factors for mood recurrence in early-onset major mood disorders: A 4-year, multicenter, prospective cohort study.

We investigate the predictive factors of the mood recurrence in patients with early-onset major mood disorders from a prospective observational cohort study from July 2015 to December 2019. A total of 495 patients were classified into three groups according to recurrence during the cohort observation period: recurrence group with (hypo)manic or mixed features (MMR), recurrence group with only depressive features (ODR), and no recurrence group (NR). As a result, the baseline diagnosis of bipolar disorder type 1 (BDI) and bipolar disorder type 2 (BDII), along with a familial history of BD, are strong predictors of the MMR. The discrepancies in wake-up times between weekdays and weekends, along with disrupted circadian rhythms, are identified as a notable predictor of ODR. Our findings confirm that we need to be aware of different predictors for each form of mood recurrences in patients with early-onset mood disorders. In clinical practice, we expect that information obtained from the initial assessment of patients with mood disorders, such as mood disorder type, family history of BD, regularity of wake-up time, and disruption of circadian rhythms, can help predict the risk of recurrence for each patient, allowing for early detection and timely intervention.

Multi-domain automated patterning of DNA-functionalized hydrogels.

DNA-functionalized hydrogels are capable of sensing oligonucleotides, proteins, and small molecules, and specific DNA sequences sensed in the hydrogels' environment can induce changes in these hydrogels' shape and fluorescence. Fabricating DNA-functionalized hydrogel architectures with multiple domains could make it possible to sense multiple molecules and undergo more complicated macroscopic changes, such as changing fluorescence or changing the shapes of regions of the hydrogel architecture. However, automatically fabricating multi-domain DNA-functionalized hydrogel architectures, capable of enabling the construction of hydrogel architectures with tens to hundreds of different domains, presents a significant challenge. We describe a platform for fabricating multi-domain DNA-functionalized hydrogels automatically at the micron scale, where reaction and diffusion processes can be coupled to program material behavior. Using this platform, the hydrogels' material properties, such as shape and fluorescence, can be programmed, and the fabricated hydrogels can sense their environment. DNA-functionalized hydrogel architectures with domain sizes as small as 10 microns and with up to 4 different types of domains can be automatically fabricated using ink volumes as low as 50 µL. We also demonstrate that hydrogels fabricated using this platform exhibit responses similar to those of DNA-functionalized hydrogels fabricated using other methods by demonstrating that DNA sequences can hybridize within them and that they can undergo DNA sequence-induced shape change.

Smart building block with colored radiative cooling devices and quantum dot light emitting diodes.

In this study, we design a smart building block with quantum-dot light-emitting diode (QLED) and colored radiative cooling devices. A smart light-emitting building block is fabricated using a bottom-inverted QLED that emits green light, an insulating layer, and a top radiative cooling structure that emits mid-infrared light. The heat generated during QLED operation is measured and analyzed to investigate the correlation between heat and QLED degradation. The top cooling part is designed to have no impact on the QLED's performance and utilizes Ag-polydimethylsiloxane as a visible-light reflector and mid-infrared absorber/emitter. For the colored cooling part, white radiative cooling paint is used instead of Ag-polydimethylsiloxane to improve cooling performance, and red and yellow paints are employed to realize vivid red and yellow colors, respectively. We demonstrate a smart imitation house system with a smart light-emitting building block as the roof and analyze the cooling of the heat generated during QLED operation. A maximum cooling effect of up to 9.6 °C is observed compared to the imitation house system without the smart light-emitting building block, effectively dissipating heat generated during QLED operation. The smart light-emitting building block presented in this study opens new avenues in the fields of lighting and cooling systems.

Differential effect of cancer-associated fibroblast-derived extracellular vesicles on cisplatin resistance in oral squamous cell carcinoma via miR-876-3p.

Rationale: Platinum-based chemotherapy is commonly used for treating solid tumors, but drug resistance often limits its effectiveness. Cancer-associated fibroblast (CAF)-derived extracellular vesicle (EV), which carry various miRNAs, have been implicated in chemotherapy resistance. However, the molecular mechanism through which CAFs modulate cisplatin resistance in oral squamous cell carcinoma (OSCC) is not well understood. We employed two distinct primary CAF types with differential impacts on cancer progression: CAF-P, representing a more aggressive cancer-promoting category, and CAF-D, characterized by properties that moderately delay cancer progression. Consequently, we sought to investigate whether the two CAF types differentially affect cisplatin sensitivity and the underlying molecular mechanism. Methods: The secretion profile was examined by utilizing an antibody microarray with conditioned medium obtained from the co-culture of OSCC cells and two types of primary CAFs. The effect of CAF-dependent factors on cisplatin resistance was investigated by utilizing conditioned media (CM) and extracellular vesicle (EVs) derived from CAFs. The impacts of candidate genes were confirmed using gain- and loss-of-function analyses in spheroids and organoids, and a mouse xenograft. Lastly, we compared the expression pattern of the candidate genes in tissues from OSCC patients exhibiting different responses to cisplatin. Results: When OSCC cells were cultured with conditioned media (CM) from the two different CAF groups, cisplatin resistance increased only under CAF-P CM. OSCC cells specifically expressed insulin-like growth factor binding protein 3 (IGFBP3) after co-culture with CAF-D. Meanwhile, IGFBP3-knockdown OSCC cells acquired cisplatin resistance in CAF-D CM. IGFBP3 expression was promoted by GATA-binding protein 1 (GATA1), a transcription factor targeted by miR-876-3p, which was enriched only in CAF-P-derived EV. Treatment with CAF-P EV carrying miR-876-3p antagomir decreased cisplatin resistance compared to control miRNA-carrying CAF-P EV. On comparing the staining intensity between cisplatin-sensitive and -insensitive tissues from OSCC patients, there was a positive correlation between IGFBP3 and GATA1 expression and cisplatin sensitivity in OSCC tissues from patients. Conclusion: These results provide insights for overcoming cisplatin resistance, especially concerning EVs within the tumor microenvironment. Furthermore, it is anticipated that the expression levels of GATA1 and miR-876-3p, along with IGFBP3, could aid in the prediction of cisplatin resistance.

Effects of a Rice-Farming Simulation Video Game on Nature Relatedness, Nutritional Status, and Psychological State in Urban-Dwelling Adults During the COVID-19 Pandemic: Randomized Waitlist Controlled Trial.

BACKGROUND: During the COVID-19 pandemic, urban inhabitants faced significant challenges in maintaining connections with nature, adhering to nutritional guidelines, and managing mental well-being. OBJECTIVE: Recognizing the urgent need for innovative approaches, this study was designed to explore the potential benefits of a specific digital intervention, the rice-farming simulation game Sakuna: Of Rice and Ruin, for nature relatedness, nutritional behaviors, and psychological well-being. METHODS: A total of 66 adults without any prior major psychiatric disorders residing in an urban area were recruited for the study. They were randomly assigned to 2 groups through block randomization: the immediate intervention group (IIG; 34/66, 52%) and the waitlist group (32/66, 48%). Participants in the IIG were instructed to play the game for at least 4 days per week for 3 weeks, with each session lasting from 30 minutes to 3 hours. Assessments were performed at baseline, week 1, and week 3. The Nature Relatedness Scale (NR) and Nutrition Quotient Scale were used to evaluate nature relatedness and nutritional state, respectively. Furthermore, psychological state was assessed using the World Health Organization Quality of Life-Brief Version (WHOQOL-BREF), Brief Fear of Negative Evaluation Scale, Social Avoidance and Distress Scale, Toronto Alexithymia Scale, State-Trait Anxiety Inventory, Center for Epidemiologic Studies Depression Scale Revised, and Korean Resilience Quotient. RESULTS: This study's results revealed significant time interactions between the IIG and waitlist group for both the total NR score (P=.001) and the score of the self subdomain of NR (P<.001), indicating an impact of the game on nature relatedness. No group×time interactions were found for the total Nutrition Quotient Scale and subdomain scores, although both groups showed increases from baseline. For psychological state, a significant group×time interaction was observed in the total WHOQOL-BREF score (P=.049), suggesting an impact of the game on quality of life. The psychological (P=.01), social (P=.003), and environmental (P=.04) subdomains of the WHOQOL-BREF showed only a significant time effect. Other psychological scales did not display any significant changes (all P>.05). CONCLUSIONS: Our findings suggest that the rice-farming game intervention might have positive effects on nature relatedness, nature-friendly dietary behaviors, quality of life, anxiety, depression, interpersonal relationships, and resilience among urban adults during the COVID-19 pandemic. The impact of pronature games in confined urban environments provides valuable evidence of how digital technologies can be used to enhance urban residents' affinity for nature and psychological well-being. This understanding can be extended in the future to other digital platforms, such as metaverses. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0007657; http://tinyurl.com/yck7zxp7.

Vivid Colored Cooling Structure Managing Full Solar Spectrum via Near-Infrared Reflection and Photoluminescence.

Colored radiative cooling (CRC) offers an attractive alternative for surface and space cooling, while preserving the aesthetics of an object. However, there has been no study on the CRC using phosphors in regard to vivid coloration, sophisticated performance investigation, retention of properties, functionality, and structural flexibility all at once. Thus, to manage the entire solar spectrum, a colored cooling structure comprising a near-infrared (NIR)-reflective bottom layer and a top colored layer with a phosphor-embedded polymer matrix is proposed. The structure is paintable, vividly colored, hydrophobic, and ultraviolet (UV) and water resistant. In the daytime outdoor measurement, the structure with red, orange, and yellow colors exhibited lower temperature than a control group using commercial white paint by 4.7 °C, 7.2 °C, and 7.4 °C, respectively. After precise theoretical and experimental time-tracing temperature validation, the CRC performance enhancement from NIR reflection and photoluminescence effects was thoroughly analyzed, and a temperature reduction of up to 16.1 °C was achieved for the orange-colored structure. Furthermore, experiments of hydrophobicity infusion and exposure to UV and deionized water verified the durability of the colored cooling structure. In addition, flexible-film-type colored cooling structures were demonstrated using different bottom reflective layers, such as a silver thin film and porous aluminum oxide particle-embedded poly(vinylidene fluoride-co-hexafluoropropylene), suggesting the potential applicability of these colored cooling structures for vivid-colored, functional, and durable CRC.

Ensemble Approach to Combining Episode Prediction Models Using Sequential Circadian Rhythm Sensor Data from Mental Health Patients.

Managing mood disorders poses challenges in counseling and drug treatment, owing to limitations. Counseling is the most effective during hospital visits, and the side effects of drugs can be burdensome. Patient empowerment is crucial for understanding and managing these triggers. The daily monitoring of mental health and the utilization of episode prediction tools can enable self-management and provide doctors with insights into worsening lifestyle patterns. In this study, we test and validate whether the prediction of future depressive episodes in individuals with depression can be achieved by using lifelog sequence data collected from digital device sensors. Diverse models such as random forest, hidden Markov model, and recurrent neural network were used to analyze the time-series data and make predictions about the occurrence of depressive episodes in the near future. The models were then combined into a hybrid model. The prediction accuracy of the hybrid model was 0.78; especially in the prediction of rare episode events, the F1-score performance was approximately 1.88 times higher than that of the dummy model. We explored factors such as data sequence size, train-to-test data ratio, and class-labeling time slots that can affect the model performance to determine the combinations of parameters that optimize the model performance. Our findings are especially valuable because they are experimental results derived from large-scale participant data analyzed over a long period of time.

Periodontitis promotes bacterial extracellular vesicle-induced neuroinflammation in the brain and trigeminal ganglion.

Gram-negative bacteria derived extracellular vesicles (EVs), also known as outer membrane vesicles, have attracted significant attention due to their pathogenic roles in various inflammatory diseases. We recently demonstrated that EVs secreted by the periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) can cross the blood-brain barrier (BBB) and that their extracellular RNA cargo can promote the secretion of proinflammatory cytokines, such as IL-6 and TNF-α, in the brain. To gain more insight into the relationship between periodontal disease (PD) and neuroinflammatory diseases, we investigated the effect of Aa EVs in a mouse model of ligature-induced PD. When EVs were administered through intragingival injection or EV-soaked gel, proinflammatory cytokines were strongly induced in the brains of PD mice. The use of TLR (Toll-like receptor)-reporter cell lines and MyD88 knockout mice confirmed that the increased release of cytokines was triggered by Aa EVs via TLR4 and TLR8 signaling pathways and their downstream MyD88 pathway. Furthermore, the injection of EVs through the epidermis and gingiva resulted in the direct retrograde transfer of Aa EVs from axon terminals to the cell bodies of trigeminal ganglion (TG) neurons and the subsequent activation of TG neurons. We also found that the Aa EVs changed the action potential of TG neurons. These findings suggest that EVs derived from periodontopathogens such as Aa might be involved in pathogenic pathways for neuroinflammatory diseases, neuropathic pain, and other systemic inflammatory symptoms as a comorbidity of periodontitis.

Potential effectiveness of digital therapeutics specialized in executive functions as adjunctive treatment for clinical symptoms of attention-deficit/hyperactivity disorder: a feasibility study.

Introduction: The role of digital therapeutics (DTx) in the effective management of attention deficit/hyperactivity disorder (ADHD) is beginning to gain clinical attention. Therefore, it is essential to verify their potential efficacy. Method: We aimed to investigate the improvement in the clinical symptoms of ADHD by using DTx AimDT01 (NUROW) (AIMMED Co., Ltd., Seoul, Korea) specialized in executive functions. NUROW, which consists of Go/No-go Task- and N-Back/Updating-based training modules and a personalized adaptive algorithm system that adjusts the difficulty level according to the user's performance, was implemented on 30 Korean children with ADHD aged 6 to 12 years. The children were instructed to use the DTx for 15 min daily for 4 weeks. The Comprehensive attention test (CAT) and Childhood Behavior Checklist (CBCL) were used to assess the children at baseline and endpoint. In contrast, the ADHD-Rating Scale (ARS) and PsyToolkit were used weekly and followed up at 1 month, for any sustained effect. Repeated measures ANOVA was used to identify differences between the participants during visits, while t-tests and Wilcoxon signed-rank tests were used to identify changes before and after the DTx. Results: We included 27 participants with ADHD in this analysis. The ARS inattention (F = 4.080, p = 0.010), hyperactivity (F = 5.998. p < 0.001), and sum (F = 5.902, p < 0.001) significantly improved. After applying NUROW, internalized (t = -3.557, p = 0.001, 95% CI = -3.682--0.985), other (Z = -3.434, p = 0.001, effect size = -0.661), and sum scores (t = -3.081, p = 0.005, 95% CI = -10.126--2.022) were significantly changed in the CBCL. The overall effect was confirmed in the ARS sustained effect analysis even after 1 month of discontinuing the DTx intervention. Discussion: According to caregivers, the findings indicate that DTx holds potential effect as an adjunctive treatment in children with ADHD, especially in subjective clinical symptoms. Future studies will require detailed development and application targeting specific clinical domains using DTx with sufficient sample sizes.Clinical trial registration: KCT0007579.

Association between Plasma Metabolic Profiles of the Antidepressant Escitalopram and Clinical Response in Subjects with Depression.

Liquid chromatography/electrospray ionization-mass spectrometry revealed plasma metabolic profiles for the antidepressant drug escitalopram (ECTP) and associated clinical responses in subjects with major depressive disorder (MDD). Metabolic profiles contribute to variations in responses to drug treatment of depression. To assess clinical responses and treatment outcomes, we quantified the levels of metabolites, including those of the parent drug, in plasma samples collected at different time points (days 0, 7, 14, and 42) during treatment of seven patients with MDD. Results showed that mean plasma levels of key metabolites and ECTP at day 7 were significantly associated with the clinical response at 42 days after treatment. Statistical analyses, including principal component analysis, of key metabolites and ECTP samples at different time points clearly distinguished the clinical responders from non-responder subjects. Although further validation with a larger cohort is necessary, our results indicate that early improvement and plasma levels of key metabolites and ECTP are predictive of therapeutic treatment outcomes and thus can be used to guide the use of ECTP.

Acetate controls endothelial-to-mesenchymal transition.

Endothelial-to-mesenchymal transition (EndMT), a process initiated by activation of endothelial TGF-ß signaling, underlies numerous chronic vascular diseases and fibrotic states. Once induced, EndMT leads to a further increase in TGF-ß signaling, thus establishing a positive-feedback loop with EndMT leading to more EndMT. Although EndMT is understood at the cellular level, the molecular basis of TGF-ß-driven EndMT induction and persistence remains largely unknown. Here, we show that metabolic modulation of the endothelium, triggered by atypical production of acetate from glucose, underlies TGF-ß-driven EndMT. Induction of EndMT suppresses the expression of the enzyme PDK4, which leads to an increase in ACSS2-dependent Ac-CoA synthesis from pyruvate-derived acetate. This increased Ac-CoA production results in acetylation of the TGF-ß receptor ALK5 and SMADs 2 and 4 leading to activation and long-term stabilization of TGF-ß signaling. Our results establish the metabolic basis of EndMT persistence and unveil novel targets, such as ACSS2, for the potential treatment of chronic vascular diseases.

Lyotropic Boron Nitride Nanotube Liquid Crystals: Preparation, Characterization, and Wet-Spinning for Fabrication of Composite Fiber.

Microfiber fabrication via wet-spinning of lyotropic liquid crystals (LCs) with anisotropic nanomaterials has gained increased attention due to the microfibers' excellent physical/chemical properties originating from the unidirectional alignment of anisotropic nanomaterials along the fiber axis with high packing density. For wet-spinning of the microfibers, however, preparing lyotropic LCs by achieving high colloidal stability of anisotropic nanomaterials, even at high concentrations, has been a critically unmet prerequisite, especially for recently emerging nanomaterials. Here, we propose a cationically charged polymeric stabilizer that can efficiently be adsorbed on the surface of boron nitride nanotubes (BNNTs), which provide steric hindrance in combination with Coulombic repulsion leading to high colloidal stability of BNNTs up to 22 wt %. The BNNT LCs prepared from the dispersions with various stabilizers were systematically compared using optical and rheological analysis to optimize the phase behavior and rheological properties for wet-spinning of the BNNT LCs. Systematic optical and mechanical characterizations of the BNNT microfibers with aligned BNNTs along the fiber axis revealed that properties of the microfibers, such as their tensile strength, packing density, and degree of BNNT alignment, were highly dependent on the quality of BNNT LCs directly related to the types of stabilizers.

Three years of wastewater surveillance for new psychoactive substances from 16 countries.

The proliferation of new psychoactive substances (NPS) over recent years has made their surveillance complex. The analysis of raw municipal influent wastewater can allow a broader insight into community consumption patterns of NPS. This study examines data from an international wastewater surveillance program that collected and analysed influent wastewater samples from up to 47 sites in 16 countries between 2019 and 2022. Influent wastewater samples were collected over the New Year period and analysed using validated liquid chromatography - mass spectrometry methods. Over the three years, a total of 18 NPS were found in at least one site. Synthetic cathinones were the most found class followed by phenethylamines and designer benzodiazepines. Furthermore, two ketamine analogues, one plant based NPS (mitragynine) and methiopropamine were also quantified across the three years. This work demonstrates that NPS are used across different continents and countries with the use of some more evident in particular regions. For example, mitragynine has highest mass loads in sites in the United States, while eutylone and 3-methylmethcathinone increased considerably in New Zealand and in several European countries, respectively. Moreover, 2F-deschloroketamine, an analogue of ketamine, has emerged more recently and could be quantified in several sites, including one in China, where it is considered as one of the drugs of most concern. Finally, some NPS were detected in specific regions during the initial sampling campaigns and spread to additional sites by the third campaign. Hence, wastewater surveillance can provide an insight into temporal and spatial trends of NPS use.

High-resolution visualization of pial surface vessels by flattened whole mount staining.

Understanding development of the cerebral vasculature is essential for the central nervous system (CNS) research and therapeutic developments. Here, we developed a simple, convenient, and fast method-the flattened cortex whole mount (FCWM) technique-for imaging of pial cerebral vessels. FCWM involves dissection of the whole cerebral cortex followed by flattening, sectioning and application of CLARITY technology. Compared to conventional methods, FCWM offers several advantages including (1) high-resolution visualization of the whole cortex pial surface vessel structures and distributions; (2) precise localization of a particular blood vessel, allowing observations of a desired blood vessel during normal development or in disease settings; (3) compatibility with confocal imaging. Application of FCWM for examination of cerebral vasculature during postnatal development or in stroke settings allowed us to demonstrate that cerebral blood vessels manifest type-specific maturation and remodeling which are linked to the rate of endothelial proliferation.

Target and suspect screening of (new) psychoactive substances in South Korean wastewater by LC-HRMS.

New psychoactive substances (NPS) are a type of abused drug designed to mimic the effects of the currently known illicit drugs, whose structures are constantly changing to escape surveillance. The quick identification of NPS use in the community therefore demands immediate action. This study aimed to develop a target and suspect screening method using LC-HRMS to identify NPS in wastewater samples. An in-house database of 95 traditional and NPS was built using the reference standards, and an analytical method was developed. Wastewater samples were collected from 29 wastewater treatment plants (WWTP) across South Korea, representing 50 % of the total population. The psychoactive substances in waste water samples were screened using in-house database and developed analytical methods. A total of 14 substances were detected in the target analysis, including three NPS (N-methyl-2-AI, 25E-NBOMe, and 25D-NBOMe) and 11 traditional psychoactive substances and their metabolites (zolpidem phenyl-4-COOH, ephedrine, ritalinic acid, tramadol, phenmetrazine, phendimetrazine, phentermine, methamphetamine, codeine, morphine, and ketamine). Out of these, N-methyl-2-AI, zolpidem phenyl-4-COOH, ephedrine, ritalinic acid, tramadol, phenmetrazine, and phendimetrazine were detected with a detection frequency of over 50 %. Primarily, N-methyl-2-Al was detected in all the wastewater samples. Additionally, four NPSs (amphetamine-N-propyl, benzydamine, isoethcathinone, methoxyphenamine) were tentatively identified at level 2b in a suspect screening analysis. This is the most comprehensive study to investigate NPS using target and suspect analysis methods at the national level. This study raises a need for continuous monitoring of NPS in South Korea.

One-step printable platform for high-efficiency metasurfaces down to the deep-ultraviolet region.

A single-step printable platform for ultraviolet (UV) metasurfaces is introduced to overcome both the scarcity of low-loss UV materials and manufacturing limitations of high cost and low throughput. By dispersing zirconium dioxide (ZrO2) nanoparticles in a UV-curable resin, ZrO2 nanoparticle-embedded-resin (nano-PER) is developed as a printable material which has a high refractive index and low extinction coefficient from near-UV to deep-UV. In ZrO2 nano-PER, the UV-curable resin enables direct pattern transfer and ZrO2 nanoparticles increase the refractive index of the composite while maintaining a large bandgap. With this concept, UV metasurfaces can be fabricated in a single step by nanoimprint lithography. As a proof of concept, UV metaholograms operating in near-UV and deep-UV are experimentally demonstrated with vivid and clear holographic images. The proposed method enables repeat and rapid manufacturing of UV metasurfaces, and thus will bring UV metasurfaces more close to real life.