Functional composites by programming entropy-driven nanosheet growth.

Nanomaterials must be systematically designed to be technologically viable1-5. Driven by optimizing intermolecular interactions, current designs are too rigid to plug in new chemical functionalities and cannot mitigate condition differences during integration6,7. Despite extensive optimization of building blocks and treatments, accessing nanostructures with the required feature sizes and chemistries is difficult. Programming their growth across the nano-to-macro hierarchy also remains challenging, if not impossible8-13. To address these limitations, we should shift to entropy-driven assemblies to gain design flexibility, as seen in high-entropy alloys, and program nanomaterial growth to kinetically match target feature sizes to the mobility of the system during processing14-17. Here, following a micro-then-nano growth sequence in ternary composite blends composed of block-copolymer-based supramolecules, small molecules and nanoparticles, we successfully fabricate high-performance barrier materials composed of more than 200 stacked nanosheets (125 nm sheet thickness) with a defect density less than 0.056 µm-2 and about 98% efficiency in controlling the defect type. Contrary to common perception, polymer-chain entanglements are advantageous to realize long-range order, accelerate the fabrication process (<30 min) and satisfy specific requirements to advance multilayered film technology3,4,18. This study showcases the feasibility, necessity and unlimited opportunities to transform laboratory nanoscience into nanotechnology through systems engineering of self-assembly.

DNA-Programmed Four-Bit Quaternary Fluorescence Encoding (FLUCO) Enables 51-Colored Bioimaging Analysis.

Color encoding plays a crucial role in painting, digital photography, and spectral analysis. Achieving accurate, target-responsive color encoding at the molecular level has the potential to revolutionize scientific research and technological innovation, but significant challenges persist. Here, we propose a multibit DNA self-assembly system based on computer-aided design (CAD) technology, enabling accurate, target-responsive, amplified color encoding at the molecular level, termed fluorescence encoding (FLUCO). As a model, we establish a quaternary FLUCO system using four-bit DNA self-assembly, which can accurately encode 51 colors, presenting immense potential in applications such as spatial proteomic imaging and multitarget analysis. Notably, FLUCO enables the simultaneous imaging of multiple targets exceeding the limitations of channels using conventional imaging equipment, and marks the integration of computer science for molecular encoding and decoding. Overall, our work paves the way for target-responsive, controllable molecular encoding, facilitating spatial omics analysis, exfoliated cell analysis, and high-throughput liquid biopsy.

Enzyme Reaction-Assisted Programmable Transcriptional Switches for Bioactive Molecule Detection.

Bioactive molecules are highly worthwhile to recognize and explore the latent pathogenic mechanism. Conventional methods for bioactive molecule detection, including mass spectrometry and fluorescent probe imaging, are limited due to the complex processing and signal interference. Here, we designed enzyme-reaction-assisted programmable transcriptional switches for the detection of bioactive molecules. The approach is based on the use of programmable enzyme site-specific cleavage-assisted DNA triplex-based conformational switches that, upon responding to bioactive molecules, can trigger the transcription of fluorescent light-up aptamers. Thanks to the programmable nature of the sensing platform, the method can be adapted to different bioactive molecules, and we demonstrated the enzyme-small molecule catalytic reaction combination of myeloperoxidase (MPO)-hydrogen peroxide (H2O2) as a model that transcriptional switches was capable of detecting H2O2 and possessed the specificity and anti-interference ability in vitro. Furthermore, we successfully applied the switches into cells to observe the detection feasibility in vivo, and dynamically monitored changes of H2O2 in cellular oxidative stress levels. Therefore, we attempt to amalgamate the advantages of enzyme reaction with the pluripotency of programmable transcriptional switches, which can take both fields a step further, which may promote the research of biostimuli and the construction of DNA molecular devices.

Models of mild cognitive deficits in risk assessment in early psychosis.

BACKGROUND: Mild cognitive deficits (MCD) emerge before the first episode of psychosis (FEP) and persist in the clinical high-risk (CHR) stage. This study aims to refine risk prediction by developing MCD models optimized for specific early psychosis stages and target populations. METHODS: A comprehensive neuropsychological battery assessed 1059 individuals with FEP, 794 CHR, and 774 matched healthy controls (HCs). CHR subjects, followed up for 2 years, were categorized into converters (CHR-C) and non-converters (CHR-NC). The MATRICS Consensus Cognitive Battery standardized neurocognitive tests were employed. RESULTS: Both the CHR and FEP groups exhibited significantly poorer performance compared to the HC group across all neurocognitive tests (all p < 0.001). The CHR-C group demonstrated poorer performance compared to the CHR-NC group on three sub-tests: visuospatial memory (p < 0.001), mazes (p = 0.005), and symbol coding (p = 0.023) tests. Upon adjusting for sex and age, the performance of the MCD model was excellent in differentiating FEP from HC, as evidenced by an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.895 (p < 0.001). However, when applied in the CHR group for predicting CHR-C (AUC = 0.581, p = 0.008), the performance was not satisfactory. To optimize the efficiency of psychotic risk assessment, three distinct MCD models were developed to distinguish FEP from HC, predict CHR-C from CHR-NC, and identify CHR from HC, achieving accuracies of 89.3%, 65.6%, and 80.2%, respectively. CONCLUSIONS: The MCD exhibits variations in domains, patterns, and weights across different stages of early psychosis and diverse target populations. Emphasizing precise risk assessment, our findings highlight the importance of tailored MCD models for different stages and risk levels.

Correlative relationship between body mass index and heart rate variability in psychiatric disorders.

OBJECTIVE: Indicators of heart rate variability (HRV) have been used to assess the autonomic activity. However, the influence of obesity on HRV in these patients remains to be determined. This study aimed to examine how obesity (measured with the body mass index [BMI]) affects HRV and determine whether the effect varies among different psychiatric disorders. We recruited 3159 consecutive patients, including 1744 with schizophrenia, 966 with mood disorders, and 449 with anxiety disorders. Patients were divided into four groups based on BMI: underweight (< 18.5), normal weight (18.5-23.9), overweight (24-27.9), and obese (≥ 28). The cardiovascular status was assessed using several time- and frequency-based HRV indicators, measured via electrocardiogram signals recorded for 5 min. The mean BMI of the participants was 23.6 ± 4.0. The patients in the overweight and obese groups were 29.4% and 13.6% of the total, respectively. The HRV indicators were higher in underweight and normal-weight patients than in the overweight and obese ones. After stratification based on the psychiatric diagnosis, the patients with mood disorders showed lower HRV than those with schizophrenia or anxiety disorder in the normal-weight group. In contrast, in the overweight and obese groups the patients with mood disorders showed higher HRV than those with the other disorders. The HRV variables were significantly associated with BMI, and higher BMI was associated with higher heart rates and lower HRV. These results indicate that weight gain in psychiatric disorders is associated with an imbalance in autonomic nerve activity. However, the relationship between autonomic activity, weight gain, and psychiatric disorders warrants further investigation.

Association between serum cytokines and timeframe for conversion from clinical high-risk to psychosis.

AIM: Although many studies have explored the link between inflammatory markers and psychosis, there is a paucity of research investigating the temporal progression in individuals at clinical high-risk (CHR) who eventually develop full psychosis. To address this gap, we investigated the correlation between serum cytokine levels and Timeframe for Conversion to Psychosis (TCP) in individuals with CHR. METHODS: We enrolled 53 individuals with CHR who completed a 5-year follow-up with a confirmed conversion to psychosis. Granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-1ß, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) levels were measured at baseline and 1-year. Correlation and quantile regression analyses were performed. RESULTS: The median TCP duration was 14 months. A significantly shorter TCP was associated with higher levels of TNF-α (P = 0.022) and VEGF (P = 0.016). A negative correlation was observed between TCP and TNF-α level (P = 0.006) and VEGF level (P = 0.04). Quantile regression indicated negative associations between TCP and GM-CSF levels below the 0.5 quantile, IL-10 levels below the 0.3 quantile, IL-2 levels below the 0.25 quantile, IL-6 levels between the 0.65 and 0.75 quantiles, TNF-α levels below the 0.8 quantile, and VEGF levels below the 0.7 quantile. A mixed linear effects model identified significant time effects for IL-10 and IL-2, and significant group effects for changes in IL-2 and TNF-α. CONCLUSIONS: Our findings underscore that a more pronounced baseline inflammatory state is associated with faster progression of psychosis in individuals with CHR. This highlights the importance of considering individual inflammatory profiles during early intervention and of tailoring preventive measures for risk profiles.

Proximity-Enhanced Functional Imaging Analysis of Engineered Tumors.

Functional imaging (FI) techniques have revolutionized tumor imaging by providing information on specific tumor functions, such as glycometabolism. However, tumor cells lack unique molecular characteristics at the molecular level and metabolic pathways, resulting in limited metabolic differences compared to normal cells and increased background signals from FI. To address this limitation, we developed a novel imaging technique termed proximity-enhanced functional imaging (PEFI) for accurate visualization of tumors. By using "two adjacent chemically labeled glycoproteins" as output signals, we significantly enhance the metabolic differences between tumor and normal cells by PEFI, thereby reducing the background signals for analysis and improving the accuracy of tumor functional imaging. Our results demonstrate that PEFI can accurately identify tumors at the cellular, tissue, and animal level, and has potential value in clinical identification and analysis of tumor cells and tissues, as well as in the guidance of clinical tumor resection surgery.

Effects of polygenic risk of schizophrenia on interhemispheric callosal white matter integrity and frontotemporal functional connectivity in first-episode schizophrenia.

BACKGROUND: Schizophrenia is a severely debilitating psychiatric disorder with high heritability and polygenic architecture. A higher polygenic risk score for schizophrenia (SzPRS) has been associated with smaller gray matter volume, lower activation, and decreased functional connectivity (FC). However, the effect of polygenic inheritance on the brain white matter microstructure has only been sparsely reported. METHODS: Eighty-four patients with first-episode schizophrenia (FES) patients and ninety-three healthy controls (HC) with genetics, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI) data were included in our study. We investigated impaired white matter integrity as measured by fractional anisotropy (FA) in the FES group, further examined the effect of SzPRS on white matter FA and FC in the regions connected by SzPRS-related white matter tracts. RESULTS: Decreased FA was observed in FES in many commonly identified regions. Among these regions, we observed that in the FES group, but not the HC group, SzPRS was negatively associated with the mean FA in the genu and body of corpus callosum, right anterior corona radiata, and right superior corona radiata. Higher SzPRS was also associated with lower FCs between the left inferior frontal gyrus (IFG)-left inferior temporal gyrus (ITG), right IFG-left ITG, right IFG-left middle frontal gyrus (MFG), and right IFG-right MFG in the FES group. CONCLUSION: Higher polygenic risks are linked with disrupted white matter integrity and FC in patients with schizophrenia. These correlations are strongly driven by the interhemispheric callosal fibers and the connections between frontotemporal regions.

Serum angioneurin levels following electroconvulsive therapy for mood disorders.

OBJECTIVES: The efficacy of electroconvulsive therapy (ECT) in treating mood disorders (MDs) is hypothesized to be mediated by the induction of neurotrophic factors (denoted "angioneurins") that trigger neuronal plasticity. This study aimed to assess the effects of ECT on serum angioneurin levels in patients with MD. METHODS: A total of 110 patients with MDs including 30 with unipolar depression, 25 with bipolar depression (BD), 55 with bipolar mania (BM), and 50 healthy controls were included in the study. Patients were subdivided into two groups: those who received ECT + medication (12 ECT sessions) and those who received only medication (no-ECT). Depressive and manic symptom assessments and measurements of vascular endothelial growth factor (VEGF), fibroblast growth factor-2, nerve growth factor (NGF), and insulin-like growth factor-1 levels in blood samples were performed at baseline and week 8. RESULTS: Patients in the ECT group, specifically those with BD and BM, had significantly increased levels of VEGF compared to their baseline VEGF levels (p = 0.002). No significant changes in angioneurin levels were observed in the no-ECT group. Serum NGF levels were significantly associated with a reduction in depressive symptoms. Angioneurin levels were not associated with manic symptom reduction. CONCLUSIONS: This study hints that ECT may increase VEGF levels with angiogenic mechanisms that amplify NGF signaling to promote neurogenesis. It may also contribute to changes in brain function and emotional regulation. However, further animal experiments and clinical validation are needed.

Changes in Inflammatory Markers in Clinical High Risk of Developing Psychosis.

INTRODUCTION: Immune alterations are associated with the progression of psychosis. However, there are few studies designed to longitudinally measure inflammatory biomarkers during psychotic episodes. We aimed to assess changes in biomarkers from the prodromal phase to psychotic episodes in individuals with clinical high risk (CHR) of psychosis and compare converters and non-converters to psychosis as well as healthy controls (HCs). METHODS: We enrolled 394 individuals with CHR and 100 HCs. A total of 263 individuals with CHR completed the 1-year follow-up, and 47 had converted to psychosis. Interleukin (IL)-1ß, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor levels were measured at baseline and 1 year after completion of the clinical assessment. RESULTS: The baseline serum levels of IL-10, IL-2, and IL-6 were significantly lower in the conversion group than in the non-conversion group (IL-10, p = 0.010; IL-2, p = 0.023; IL-6, p = 0.012) and HC (IL-6: p = 0.034). Self-controlled comparisons showed that IL-2 changed significantly (p = 0.028), and IL-6 levels tended toward significance (p = 0.088) in the conversion group. In the non-conversion group, serum levels of TNF-α (p = 0.017) and VEGF (p = 0.037) changed significantly. Repeated measures analysis of variance revealed a significant time effect related to TNF-α (F = 4.502, p = 0.037, effect size (η2) = 0.051), a group effect related to IL-1ß (F = 4.590, p = 0.036, η2 = 0.062), and IL-2 (F = 7.521, p = 0.011, η2 = 0.212), but no time × group effect. DISCUSSION: Alterations in the serum levels of inflammatory cytokines were found to precede the first episode of psychosis in the CHR population, particularly for those who later converted to psychosis. Longitudinal analysis supports the varied roles of cytokines in individuals with CHR with later psychotic conversion or non-conversion outcomes.

Remediation of Thirdhand Tobacco Smoke with Ozone: Probing Deep Reservoirs in Carpets.

We assessed the efficacy of ozonation as an indoor remediation strategy by evaluating how a carpet serves as a sink and long-term source of thirdhand tobacco smoke (THS) while protecting contaminants absorbed in deep reservoirs by scavenging ozone. Specimens from unused carpet that was exposed to smoke in the lab ("fresh THS") and contaminated carpets retrieved from smokers' homes ("aged THS") were treated with 1000 ppb ozone in bench-scale tests. Nicotine was partially removed from fresh THS specimens by volatilization and oxidation, but it was not significantly eliminated from aged THS samples. By contrast, most of the 24 polycyclic aromatic hydrocarbons detected in both samples were partially removed by ozone. One of the home-aged carpets was installed in an 18 m3 room-sized chamber, where its nicotine emission rate was 950 ng day-1 m-2. In a typical home, such daily emissions could amount to a non-negligible fraction of the nicotine released by smoking one cigarette. The operation of a commercial ozone generator for a total duration of 156 min, reaching concentrations up to 10,000 ppb, did not significantly reduce the carpet nicotine loading (26-122 mg m-2). Ozone reacted primarily with carpet fibers, rather than with THS, leading to short-term emissions of aldehydes and aerosol particles. Hence, by being absorbed deeply into carpet fibers, THS constituents can be partially shielded from ozonation.

Attenuated niacin response is associated with a subtype of first-episode drug-naïve psychosis characterized as serious negative symptoms.

Although the phenomenon of attenuated niacin response (ANR) has been widely replicated in some patients with first-episode psychosis (FEP), its relevance to the negative symptoms (NS) of psychosis remains unclear. Total of 240 patients with drug-naïve FEP and 101 healthy controls (HCs) were recruited, and 209 were followed up for 1 year. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and niacin-induced responses were measured using laser Doppler flowmetry. We calculated the log-transform EC50 [concentration of methyl nicotinate required to elicit a half-maximal blood flow (MBF) response] and MBF values. Core-NS was generated by factor analysis of the PANSS-NS subscale and cluster analysis to produce subtypes. Significant differences were found in the log10 (EC50) values between the FEP and HC groups (p < 0.001), supporting the ANR in patients with FEP. A higher NS severity was found in the ANR subgroup than that in other patients. Factor analysis determined that a two-dimensional model included core NS and rigidity of thinking. The log10 (EC50) value was significantly associated with only the core NS. Cluster analysis revealed three subtypes-36.7% (cluster-1, n = 88), 16.7% (cluster-2, n = 40), and 46.7% (cluster-3, n = 112). Cluster-2 characterized by extensive NS appeared to have a more remarkable ANR and less symptomatic improvement than those with other clusters during follow-up. No significant changes were found in the niacin response trajectories between the baseline and follow-up. Our findings indicate a significant correlation between ANR and core NS in patients with FEP. ANR may be a potential biomarker for certain subtypes with NS-dominated characteristics and poor symptomatic remission.

Eye movement indices as predictors of conversion to psychosis in individuals at clinical high risk.

Eye movement abnormalities have been established as an "endophenotype" of schizophrenia. However, less is known about the possibility of these abnormalities as biomarkers for psychosis conversion among clinical high risk (CHR) populations. In the present study, 108 CHR individuals and 70 healthy controls (HC) underwent clinical assessments and eye-tracking tests, comprising fixation stability and free-viewing tasks. According to three-year follow-up outcomes, CHR participants were further stratified into CHR-converter (CHR-C; n = 21) and CHR-nonconverter (CHR-NC; n = 87) subgroups. Prediction models were constructed using Cox regression and logistic regression. The CHR-C group showed more saccades of the fixation stability test (no distractor) and a reduced saccade amplitude of the free-viewing test than HC. Moreover, the CHR-NC group exhibited excessive saccades and an increased saccade amplitude of the fixation stability test (no distractor; with distractor) compared with HC. Furthermore, two indices could effectively discriminate CHR-C from CHR-NC with an area under the receiver-operating characteristic (ROC) curve of 0.80, including the saccade number of the fixation stability test (no distractor) and the saccade amplitude of the free-viewing test. Combined with negative symptom scores of the Scale of Prodromal Symptoms, the area was 0.81. These findings support that eye movement alterations might emerge before the onset of clinically overt psychosis and could assist in predicting psychosis transition among CHR populations.

Policy-relevant differences between secondhand and thirdhand smoke: strengthening protections from involuntary exposure to tobacco smoke pollutants.

Starting in the 1970s, individuals, businesses and the public have increasingly benefited from policies prohibiting smoking indoors, saving thousands of lives and billions of dollars in healthcare expenditures. Smokefree policies to protect against secondhand smoke exposure, however, do not fully protect the public from the persistent and toxic chemical residues from tobacco smoke (also known as thirdhand smoke) that linger in indoor environments for years after smoking stops. Nor do these policies address the economic costs that individuals, businesses and the public bear in their attempts to remediate this toxic residue. We discuss policy-relevant differences between secondhand smoke and thirdhand smoke exposure: persistent pollutant reservoirs, pollutant transport, routes of exposure, the time gap between initial cause and effect, and remediation and disposal. We examine four policy considerations to better protect the public from involuntary exposure to tobacco smoke pollutants from all sources. We call for (a) redefining smokefree as free of tobacco smoke pollutants from secondhand and thirdhand smoke; (b) eliminating exemptions to comprehensive smoking bans; (c) identifying indoor environments with significant thirdhand smoke reservoirs; and (d) remediating thirdhand smoke. We use the case of California as an example of how secondhand smoke-protective laws may be strengthened to encompass thirdhand smoke protections. The health risks and economic costs of thirdhand smoke require that smokefree policies, environmental protections, real estate and rental disclosure policies, tenant protections, and consumer protection laws be strengthened to ensure that the public is fully protected from and informed about the risks of thirdhand smoke exposure.

Uncovering the global task-modulated brain network in chunk decomposition with Chinese characters.

Chunk decomposition, which requires the mental representation transformation in accordance with behavioral goals, is of vital importance to problem solving and creative thinking. Previous studies have identified that the frontal, parietal, and occipital cortex in the cognitive control network selectively activated in response to chunk tightness, however, functional localization strategy may overlook the interaction brain regions. Based on the notion of a global brain network, we proposed that multiple specialized regions have to be interconnected to maintain goal representation during the course of chunk decomposition. Therefore, the present study applied a beta-series correlation method to investigate interregional functional connectivity in the event-related design of chunk decomposition tasks using Chinese characters, which would highlight critical nodes irrespective to chunk tightness. The results reveal a network of functional hubs with highly within or between module connections, including the orbitofrontal cortex, superior/inferior parietal lobule, hippocampus, and thalamus. We speculate that the thalamus integrates information across modular as an integrative hub while the orbitofrontal cortex tracks the mental states of chunk decomposition on a moment-to-moment basis. The superior and inferior parietal lobule collaborate to manipulate the mental representation of chunk decomposition and the hippocampus associates the relationship between elements in the question and solution phase. Furthermore, the tightness of chunks is not only associated with different processors in visual systems but also leads to increased intermodular connections in right superior frontal gyrus and left precentral gyrus. To summary up, the present study first reveals the task-modulated brain network of chunk decomposition in addition to the tightness-related nodes in the frontal and occipital cortex.

Automatic auditory processing features in distinct subtypes of patients at clinical high risk for psychosis: Forecasting remission with mismatch negativity.

Individuals at clinical high risk (CHR) for psychosis exhibit a compromised mismatch negativity (MMN) response, which indicates dysfunction of pre-attentive deviance processing. Event-related potential and time-frequency (TF) information, in combination with clinical and cognitive profiles, may provide insight into the pathophysiology and psychopathology of the CHR stage and predict the prognosis of CHR individuals. A total of 92 individuals with CHR were recruited and followed up regularly for up to 3 years. Individuals with CHR were classified into three clinical subtypes demonstrated previously, specifically 28 from Cluster 1 (characterized by extensive negative symptoms and cognitive deficits), 31 from Cluster 2 (characterized by thought and behavioral disorganization, with moderate cognitive impairment), and 33 from Cluster 3 (characterized by the mildest symptoms and cognitive deficits). Auditory MMN to frequency and duration deviants was assessed. The event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) were acquired using TF analysis. Predictive indices for remission were identified using logistic regression analyses. As expected, reduced frequency MMN (fMMN) and duration MMN (dMMN) responses were noted in Cluster 1 relative to the other two clusters. In the TF analysis, Cluster 1 showed decreased theta and alpha ITC in response to deviant stimuli. The regression analyses revealed that dMMN latency and alpha ERSP to duration deviants, theta ITC to frequency deviants and alpha ERSP to frequency deviants, and fMMN latency were significant MMN predictors of remission for the three clusters. MMN variables outperformed behavioral variables in predicting remission of Clusters 1 and 2. Our findings indicate relatively disrupted automatic auditory processing in a certain CHR subtype and a close affinity between these electrophysiological indexes and clinical profiles within different clusters. Furthermore, MMN indexes may serve as predictors of subsequent remission from the CHR state. These findings suggest that the auditory MMN response is a potential neurophysiological marker for distinct clinical subtypes of CHR.

Thirdhand Exposures to Tobacco-Specific Nitrosamines through Inhalation, Dust Ingestion, Dermal Uptake, and Epidermal Chemistry.

Tobacco-specific nitrosamines (TSNAs) are emitted during smoking and form indoors by nitrosation of nicotine. Two of them, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are human carcinogens with No Significant Risk Levels (NSRLs) of 500 and 14 ng day-1, respectively. Another TSNA, 4-(methylnitrosamino)-4-(3-pyridyl) butanal (NNA), shows genotoxic and mutagenic activity in vitro. Here, we present additional evidence of genotoxicity of NNA, an assessment of TSNA dermal uptake, and predicted exposure risks through different pathways. Dermal uptake was investigated by evaluating the penetration of NNK and nicotine through mice skin. Comparable mouse urine metabolite profiles suggested that both compounds were absorbed and metabolized via similar mechanisms. We then investigated the effects of skin constituents on the reaction of adsorbed nicotine with nitrous acid (epidermal chemistry). Higher TSNA concentrations were formed on cellulose and cotton substrates that were precoated with human skin oils and sweat compared to clean substrates. These results were combined with reported air, dust, and surface concentrations to assess NNK intake. Five different exposure pathways exceeded the NSRL under realistic scenarios, including inhalation, dust ingestion, direct dermal contact, gas-to-skin deposition, and epidermal nitrosation of nicotine. These results illustrate potential long-term health risks for nonsmokers in homes contaminated with thirdhand tobacco smoke.

Understanding of the interactions between azole-anion-based ionic liquids and 2-methyl-3-butyn-2-ol from the experimental perspective: the cage effect.

The interactions between azole-anion-based ionic liquids (AILs) and 2-methyl-3-butyn-2-ol (MBY) play an important role in AIL-promoted carboxylative cyclization of MBY with CO2. To better understand the interactions between AILs ([P66614][Im], [P66614][4-MeIm], and [P66614][4-BrIm]) and MBY, a detailed investigation from the experimental perspective has been carried out in this study. The results show that the derivative of viscosity (η) with the mole fraction of AIL (xAIL) of AIL + MBY mixtures appears to have the maximum value when xAIL ≈ 0.3, while 1H NMR chemical shifts of P-CH2 of [P66614]+ reach the minimum value at xAIL ≈ 0.3, indicating that [P66614]+ of AILs tend to self-aggregate. The interaction parameters (gji-gii) of the systems obtained from η by the Eyring-UNIQUAC equation are positive, and the difference between the bulk and local composition (xi-xii) is always negative, indicating that AILs can interact with MBY. Moreover, excess molar volumes and isentropic compressibility deviations are all negative deviations and become more negative as the temperature increases, reaching a minimum value at xAIL ≈ 0.30, indicating that azole-based anions can form H-bonds with MBY, and MBY molecules tend to enter the aggregates formed by AILs. Consequently, the cage effect is proposed to describe the interactions between AILs and MBY: MBY first enters the cage formed by the aggregation of [P66614]+, and then forms H-bonds with azole-based anions. Finally, the sizes of the particles of the [P66614][Im] + MBY mixture from dynamic light scattering increase first and then decrease with xAIL, with the maximum of 122 nm at xAIL ≈ 0.25, which confirms the rationality of the cage effect.

Further evidence that antipsychotic medication does not prevent long-term psychosis in higher-risk individuals.

OBJECTIVE: Although existing guidelines have discouraged use of antipsychotics for general clinical high-risk (CHR) individuals, it is unclear if antipsychotics can prevent psychosis in higher-risk population. We aimed to study the comparative real-world effectiveness of antipsychotic treatments for preventing psychosis in higher-risk CHR individuals. METHODS: A total of 300 CHR individuals were identified using the structured interview for prodromal syndromes (SIPS) and followed the participants for 3 years. In total, 228(76.0%) individuals completed baseline assessments using the NAPLS-2 risk calculator (NAPLS-2-RC), and 210(92.1%) completed the follow-up. The sample was further stratified according to risk level. "Higher-risk" was defined based on the NAPLS-2-RC risk score (≥ 20%) and SIPS positive symptom total scores (≥ 10). The main outcome was conversion to psychosis and poor functional outcomes, defined as a global assessment of function (GAF) score lower than 60 at follow-up. RESULTS: In higher-risk CHR individuals, we found no significant difference in the rate of conversion to psychosis or poor functional outcomes between the antipsychotic and no-antipsychotic groups. Low-risk individuals treated with antipsychotic drugs were more likely exhibit poor functional outcomes compared with the no-antipsychotics group(NAPLS-2-RC estimated risk: χ2 = 8.330, p = 0.004; Positive symptom severity: χ2 = 12.997, p < 0.001). No significant effective factors were identified for prevention of the conversion to psychosis; conversely, CHR individuals who were treated with high dose antipsychotics (olanzapine, aripiprazole) showed a significantly increased risk of poor functional outcomes. CONCLUSIONS: In CHR individuals, antipsychotic treatment should be provided with caution because of the risk of poor functional outcomes. Further, antipsychotic treatment does not appear to prevent onset of psychosis in real-world settings.

Temporal and time-frequency features of auditory oddball response in distinct subtypes of patients at clinical high risk for psychosis.

Individuals at clinical high risk (CHR) for psychosis exhibit a reduced P300 oddball response, which indicates deficits in attention and working memory processes. Previous studies have mainly researched these responses in the temporal domain; hence, non-phase-locked or induced neural activities may have been ignored. Event-related potential (ERP) and time-frequency (TF) information, combined with clinical and cognitive profiles, may provide an insight into the pathophysiology and psychopathology of the CHR stage. The 104 CHR individuals who completed cognitive assessments and ERP tests were recruited and followed up between 2016 and 2018. Individuals with CHR were classified by three clinical subtypes demonstrated before, specifically 32 from Cluster-1 (characterized by extensive negative symptoms and cognitive deficits, at the highest risk for conversion to psychosis), 34 from Cluster-2 (characterized by thought and behavioral disorganization, with moderate cognitive impairment), and 38 from Cluster-3 (characterized by the mildest symptoms and cognitive deficits). Electroencephalograms were recorded during the auditory oddball paradigm. The P300 ERPs were analyzed in the temporal domain. The event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) were acquired by TF analysis. A reduced P300 response to target tones was noted in Cluster-1 relative to the other two clusters. Moreover, the P300 amplitude of Cluster-1 was associated with speed of processing (SoP) scores. Furthermore, the P300 amplitude of Cluster-3 was significantly correlated with verbal and visual learning scores. In the TF analysis, decreased delta ERSP and ITC were observed in Cluster-1; delta ITC was associated with SoP scores in Cluster-3. The results indicate relatively disrupted oddball responses in a certain CHR subtype and a close affinity between these electrophysiological indexes and attention, working memory, and declarative memory within different CHR clusters. These findings suggest that the auditory oddball response is a potential neurophysiological marker for distinct clinical subtypes of CHR.