Investigation of spatiotemporal distribution and formation mechanisms of ozone pollution in eastern Chinese cities applying convolutional neural network.

Severe ground-level ozone (O3) pollution over major Chinese cities has become one of the most challenging problems, which have deleterious effects on human health and the sustainability of society. This study explored the spatiotemporal distribution characteristics of ground-level O3 and its precursors based on conventional pollutant and meteorological monitoring data in Zhejiang Province from 2016 to 2021. Then, a high-performance convolutional neural network (CNN) model was established by expanding the moment and the concentration variations to general factors. Finally, the response mechanism of O3 to the variation with crucial influencing factors is explored by controlling variables and interpolating target variables. The results indicated that the annual average MDA8-90th concentrations in Zhejiang Province are higher in the northern and lower in the southern. When the wind direction (WD) ranges from east to southwest and the wind speed (WS) ranges between 2 and 3 m/sec, higher O3 concentration prone to occur. At different temperatures (T), the O3 concentration showed a trend of first increasing and subsequently decreasing with increasing NO2 concentration, peaks at the NO2 concentration around 0.02 mg/m3. The sensitivity of NO2 to O3 formation is not easily affected by temperature, barometric pressure and dew point temperature. Additionally, there is a minimum [Formula: see text] at each temperature when the NO2 concentration is 0.03 mg/m3, and this minimum [Formula: see text] decreases with increasing temperature. The study explores the response mechanism of O3 with the change of driving variables, which can provide a scientific foundation and methodological support for the targeted management of O3 pollution.

Emission characteristics of biogenic volatile organic compounds in a subtropical pristine forest of southern China.

Emission characteristics of biogenic volatile organic compounds (BVOCs) from dominant tree species in the subtropical pristine forests of China are extremely limited. Here we conducted in situ field measurements of BVOCs emissions from representative mature evergreen trees by using dynamic branch enclosures at four altitude gradients (600-1690 m a.s.l.) in the Nanling Mountains of southern China. Composition characteristics as well as seasonal and altitudinal variations were analyzed. Standardized emission rates and canopy-scale emission factors were then calculated. Results showed that BVOCs emission intensities in the wet season were generally higher than those in the dry season. Monoterpenes were the dominant BVOCs emitted from most broad-leaved trees, accounting for over 70% of the total. Schima superba, Yushania basihirsuta and Altingia chinensis had relatively high emission intensities and secondary pollutant formation potentials. The localized emission factors of isoprene were comparable to the defaults in the Model of Emissions of Gases and Aerosols from Nature (MEGAN), while emission factors of monoterpenes and sesquiterpenes were 2 to 58 times of those in the model. Our results can be used to update the current BVOCs emission inventory in MEGAN, thereby reducing the uncertainties of BVOCs emission estimations in forested regions of southern China.

Emission characteristics, environmental impacts and health risk assessment of volatile organic compounds from the typical chemical industry in China.

To study the volatile organic compounds (VOCs) emission characteristics of industrial enterprises in China, 6 typical chemical industries in Yuncheng City were selected as research objects, including the modern coal chemical industry (MCC), pharmaceutical industry (PM), pesticide industry (PE), coking industry (CO) and organic chemical industry (OC). The chemical composition of 91 VOCs was quantitatively analyzed. The results showed that the emission concentration of VOCs in the chemical industry ranged from 1.16 to 155.59 mg/m3. Alkanes were the main emission components of MCC (62.0%), PE (55.1%), and OC (58.5%). Alkenes (46.5%) were important components of PM, followed by alkanes (23.8%) and oxygenated volatile organic compounds (OVOCs) (21.2%). Halocarbons (8.6%-71.1%), OVOCs (9.7%-37.6%) and alkanes (11.2%-27.0%) were characteristic components of CO. The largest contributor to OFP was alkenes (0.6%-81.7%), followed by alkanes (9.3%-45.9%), and the lowest one was alkyne (0%-0.5%). Aromatics (66.9%-85.4%) were the largest contributing components to SOA generation, followed by alkanes (2.6%-28.5%), and the lowest one was alkenes (0%-4.1%). Ethylene and BTEX were the key active species in various chemical industries. The human health risk assessment showed workers long-term exposed to the air in the chemical industrial zone had a high cancer and non-cancer risk during work, and BTEX and dichloromethane were the largest contributors.

Examining the moderating effects of anger expression style on the association between facets of trait anger and cardiovascular responses to acute psychological stress.

OBJECTIVE: The current study aims to (1) examine the association between measures of trait anger (i.e., anger temperament and anger reaction) and cardiovascular reactivity to acute psychological stress, and (2) to identify if anger expression styles moderate the association between trait anger and cardiovascular reactivity. METHODS: A sample of 669 participants completed a standardized cardiovascular reactivity protocol consisting of resting baseline and stressor phase (mental arithmetic and Stroop), with systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) monitored throughout. Participants also completed measures of trait anger including anger temperament and anger reaction, as well as measures assessing anger expression styles including anger-in, anger-out and anger control. RESULTS: Anger temperament was significantly associated with blunted cardiovascular reactivity, as well as increased levels of subjective stress. Moreover, the association between anger temperament and cardiovascular reactivity was significantly moderated by anger-in, with associations observed only amongst those who reported an increased tendency to suppress their anger. The association between anger reaction and cardiovascular reactivity was moderated by both anger-out and anger control. CONCLUSION: While blunted cardiovascular responses may be mechanism linking facets of trait anger to adverse health outcomes, the current findings accentuate the importance of considering expression styles when examining the association between anger experience and cardiovascular reactivity.

Prediction of craving across studies: A commentary on conceptual and methodological considerations when using data-driven methods.

Craving is a central feature of substance use disorders and disorders due to addictive behaviors. Considerable research has investigated neural mechanisms involved in the development and processing of craving. Recently, connectome-based predictive modeling, a data-driven method, has been used in four studies aiming to predict craving related to substance use, addictive behaviors, and food. Studies differed in methods, samples, and conceptualizations of craving. Within the commentary we aim to compare, contrast and consolidate findings across studies by considering conceptual and methodological features of the studies. We derive a theoretical model on the functional connectivity-craving relationships across studies.

Regulation of Skeletal Muscle Resistance Arteriolar Tone: Temporal Variability in Vascular Responses.

INTRODUCTION: A full understanding of the integration of the mechanisms of vascular tone regulation requires an interrogation of the temporal behavior of arterioles across vasoactive challenges. Building on previous work, the purpose of the present study was to start to interrogate the temporal nature of arteriolar tone regulation with physiological stimuli. METHODS: We determined the response rate of ex vivo proximal and in situ distal resistance arterioles when challenged by one-, two-, and three-parameter combinations of five major physiological stimuli (norepinephrine, intravascular pressure, oxygen, adenosine [metabolism], and intralumenal flow). Predictive machine learning models determined which factors were most influential in controlling the rate of arteriolar responses. RESULTS: Results indicate that vascular response rate is dependent on the intensity of the stimulus used and can be severely hindered by altered environments, caused by application of secondary or tertiary stimuli. Advanced analytics suggest that adrenergic influences were dominant in predicting proximal arteriolar response rate compared to metabolic influences in distal arterioles. CONCLUSION: These data suggest that the vascular response rate to physiologic stimuli can be strongly influenced by the local environment. Translating how these effects impact vascular networks is imperative for understanding how the microcirculation appropriately perfuses tissue across conditions.

Physiological provocation compared to acetazolamide in the assessment of cerebral hemodynamics: a case report.

BACKGROUND: Severe large vessel disease may lead to cerebral hemodynamic failure that critically impairs cerebral blood flow (CBF) regulation elevating the risk of ischemic events. Assessment of the condition is often based on changes in CBF during vasodilatation; however, pharmacologically induced vasodilation does not reflect the physiological condition during an ischemic event caused by hemodynamic failure. We compared a [15O]H2O PET brain scan during vasodilation to a [99mTc]HMPAO SPECT brain scan during an ongoing transient ischemic attack (TIA). CASE PRESENTATION: A single patient presenting with limb-shaking TIA underwent CT, Digital Subtraction Angiography, and two different modalities of cerebral perfusion scans: [15O]H2O PET and [99mTc]HMPAO SPECT. Acetazolamide was used in the PET scan to induce vasodilatation, and during the SPECT scan physiological stress, standing up rapidly, was used to induce limb-shaking TIA. CT-angiography and Digital Subtraction Angiography revealed an occlusion in the distal part of the right A2 segment of the anterior cerebral artery, with a corresponding infarction in the watershed area. Collaterals supplied the main vascular territory of the anterior cerebral artery. During rest, neither perfusion modalities demonstrated reduced perfusion outside of the ischemic core. However, we found a pronounced difference between the PET utilizing acetazolamide and the SPECT during the TIA. The PET scan demonstrated relative hypoperfusion in vascular territory supplied by collaterals, while the area around the ischemic core was not affected. Contrary, the SPECT had only minor relative hypoperfusion in the collateral-supplied area, whereas the watershed area proximal to the infarct core had pronounced relative hypoperfusion. CONCLUSIONS: The observed discrepancy in compromised areas during physiological provocation compared to pharmacological induced vasodilation questions the use of an unphysiological stressor for assessment of cerebrovascular hemodynamics. A physiological provocation test may achieve more clinically relevant evaluation.

The first in-human study to evaluate the antiplatelet properties of the clopidogrel conjugate DT-678 in acute coronary syndrome patients and healthy volunteers.

BACKGROUND AND PURPOSE: DT-678 is a novel antiplatelet prodrug, capable of releasing the antiplatelet active metabolite of clopidogrel (AM) upon exposure to glutathione. In this study, we investigated factors responsible for clopidogrel high on-treatment platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients and evaluated the capacity of DT-678 to overcome HTPR. EXPERIMENTAL APPROACH: A total of 300 consecutive ACS patients naive to P2Y12 receptor inhibitors were recruited and genotyped for CYP2C19 alleles. Blood samples were drawn before and after administration of 600-mg clopidogrel. Platelet reactivity index (PRI) and plasma AM concentrations were determined and grouped according to their CYP2C19 genotypes. DT-678 was applied ex vivo to whole blood samples to examine its inhibitory effects. To further examine the antiplatelet effectiveness of DT-678 in vivo, 20 healthy human subjects were recruited in a Phase I clinical trial, and each received a single dose of either 3-mg DT-678 or 75-mg clopidogrel. The pharmacokinetics and pharmacodynamics in different CYP2C19 genotype groups were compared. KEY RESULTS: Statistical analyses revealed that CYP2C19 genotype, body mass index, hyperuricaemia, and baseline PRI were significantly associated with a higher risk of clopidogrel HTPR in ACS patients. The addition of DT-678 ex vivo decreased baseline PRI regardless of CYP2C19 genotypes, overcoming clopidogrel HTPR. This observation was further confirmed in healthy volunteers receiving 3 mg of DT-678. CONCLUSION AND IMPLICATIONS: These results suggest that DT-678 effectively overcomes clopidogrel HTPR resulting from genetic and/or clinical factors in Chinese ACS patients, demonstrating its potential to improve antiplatelet therapy.

Childhood trauma and social anxiety in adolescents: Mediating role of cardiovascular response to social stress.

Adolescents exposed to childhood trauma are at an elevated risk for social anxiety. However, the physiological mechanisms linking childhood trauma and adolescents' social anxiety remain poorly understood. This study examined whether cardiovascular reactivity to acute social stress was a mechanism underlying this association. Participants were Chinese adolescents (N = 172; Mage = 12.95). They first reported their childhood trauma and social anxiety using the Childhood Trauma Questionnaire and the Social Interaction Anxiety Scale. They then participated in a social stress task, during which their cardiovascular data [heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP)] were monitored. The results showed that high levels of childhood trauma were associated with blunted HR, SBP, and DBP reactivity, which in turn were associated with high levels of social anxiety. Mediation analysis indicated that childhood trauma was indirectly associated with social anxiety via blunted cardiovascular reactivity. The findings suggest that blunted cardiovascular reactivity may serve as a physiological pathway linking childhood trauma and adolescents' social anxiety.

Cannabis cue-reactivity in cannabis use disorder: Diverging evidence in two distinct cannabis cultures.

BACKGROUND: Cannabis policies and attitudes play a role in the development and presentation of cannabis use disorder (CUD), but it is unclear how these factors are related to biomarkers of addiction. The current study examined cross-cultural differences in cannabis attitudes, cannabis cue-reactivity in the brain and its associations with cannabis use measures and cannabis attitudes. DESIGN: Cross-sectional fMRI study. SETTING: The Netherlands (NL) and Texas (TX), USA. PARTICIPANTS: 104 cannabis users with CUD (44% female; NL-CUD = 54, TX-CUD = 50) and 83 non-using controls (52% female; NL-CON = 50, TX-CON = 33). MEASUREMENTS: Self-reported positive (perceived benefits) and negative (perceived harms) cannabis attitudes and tactile cannabis cue-reactivity assessed using a 3T MRI scanner. FINDINGS: While the CUD group overall was more positive and less negative about cannabis and reported higher craving, the TX-CUD group reported significantly more positive and less negative attitudes and less craving than the NL-CUD group. Cannabis cue-reactivity was observed in the CUD group in clusters including the precuneus, lateral occipital cortex, frontal medial cortex, nucleus accumbens, and thalamus. In the TX-CUD group, a positive association was observed between symptom severity and cue-induced craving and cannabis cue-reactivity in precuneus and occipital cortex clusters, while a negative association was observed in the NL-CUD group. In these clusters, individuals with more positive attitudes exhibited a positive association between craving and cue-reactivity and those with less positive attitudes exhibited a negative association. No associations with quantity of use were observed. CONCLUSIONS: Cue-induced craving might be deferentially associated with cannabis cue-reactivity across distinct cannabis use environments.

Tuning a Bioengineered Hydrogel for Studying Astrocyte Reactivity in Glioblastoma.

Astrocytes play many essential roles in the central nervous system (CNS) and are altered significantly in disease. These reactive astrocytes contribute to neuroinflammation and disease progression in many pathologies, including glioblastoma (GB), an aggressive form of brain cancer. Current in vitro platforms do not allow for accurate modeling of reactive astrocytes. In this study, we sought to engineer a simple bioengineered hydrogel platform that would support the growth of primary human astrocytes and allow for accurate analysis of various reactive states. After validating this platform using morphological analysis and qPCR, we then used the platform to begin investigating how astrocytes respond to GB derived extracellular vesicles (EVs) and soluble factors (SF). These studies reveal that EVs and SFs induce distinct astrocytic states. In future studies, this platform can be used to study how astrocytes transform the tumor microenvironment in GB and other diseases of the CNS. STATEMENT OF SIGNIFICANCE: Recent work has shown that astrocytes help maintain brain homeostasis and may contribute to disease progression in diseases such as glioblastoma (GB), a deadly primary brain cancer. In vitro models allow researchers to study basic mechanisms of astrocyte biology in healthy and diseased conditions, however current in vitro systems do not accurately mimic the native brain microenvironment. In this study, we shown that our hydrogel system supports primary human astrocyte culture with an accurate phenotype and allows us to study how astrocytes change in response to a variety of inflammatory signals in GB. This platform could be used further investigate astrocyte behavior and possible therapeutics that target reactive astrocytes in GB and other brain diseases.

Electronic structure, global reactivity descriptors and nonlinear optical properties of glycine interacted with ZnO, MgO and CaO for bacterial detection.

Modern laboratory medicine relies on analytical instruments for bacterial detection, focusing on biosensors and optical sensors for early disease diagnosis and treatment. Thus, Density Functional Theory (DFT) was utilized to study the reactivity of glycine interacted with metal oxides (ZnO, MgO, and CaO) for bacterial detection. Total dipole moment (TDM), frontier molecular orbitals (FMOs), FTIR spectroscopic data, electronic transition states, chemical reactivity descriptors, nonlinear optical (NLO) characteristics, and molecular electrostatic potential (MESP) were all investigated at the B3LYP/6-31G(d, p) level using DFT and Time-Dependent DFT (TD-DFT). The Coulomb-attenuating approach (CAM-B3LYP) was utilized to obtain theoretical electronic absorption spectra with the 6-31G(d, p) basis set to be more accurate than alternative quantum chemical calculation approaches, showing good agreement with the experimental data. The TDM and FMO investigation showed that glycine/CaO model has the highest TDM (10.129Debye) and lowest band gap (1.643 eV). The DFT computed IR and the experimental FTIR are consistent. The calculated UV-vis spectra showed a red shift with an increase in polarity following an increase in the absorption wavelength due to the interaction with ZnO, MgO, and CaO. Among the five solvents of water, methanol, ethanol, DMSO and acetone, the water and DMSO enhances the UV-Vis absorption. Glycine/CaO model showed high linear polarizability (14.629 × 10-24esu) and first hyperpolarizability (23.117 × 10-30esu), indicating its potential for nonlinear optical applications. The results showed that all model molecules, particularly glycine/CaO, contribute significantly to the development of materials with potential NLO features for sensor and optoelectronic applications. Additionally, MESP confirmed the increased electronegativity of the studied structures. Additionally, glycine/ZnO nanocomposite was synthesized and characterized using IR and UV-visible spectroscopy to determine their structural and spectroscopic features. It was discovered that there was good agreement between the DFT computed findings and the related experimental data. The antibacterial activity of glycine/ZnO nanocomposites against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa were studied in terms of concentration and time. The results showed that increasing the concentration of glycine/ZnO nanocomposite significantly enhanced its antibacterial efficacy by lowering optical density. Notably, Pseudomonas aeruginosa exhibited lower susceptibility to the nanocomposite compared to S. aureus, requiring higher concentrations for effective bactericidal action. In summary, this study contributes novel insights into the dual functionality of glycine-metal oxide complexes, with significant implications as optical biosensor for microbial detection.

Unfolding the empathic insights and tendencies among medical students of two gulf institutions using interpersonal reactivity index.

BACKGROUND: Empathy is an essential core competency for future doctors. Unfortunately, the medical curriculum is infamously known to burn out aspiring doctors, which may potentially lead to a decline in empathy among medical students. This research was planned to understand the evolution of empathic approaches among students across the curriculum using the Interpersonal reactivity index (IRI) as a benchmark at the Royal College of Surgeons in Ireland - Medical University of Bahrain (RCSI-MUB) and University of Sharjah (UoS). METHODS: We adopted a cross-sectional design and administered an online survey to the medical students of RCSI-MUB and UoS using a modified version of the IRI along with its three subscales of empathic concern (EC), perspective taking (PT), and personal distress (PD). To identify intra- and inter-institutional variations in empathy scores, the Analysis of Variance (ANOVA) was performed separately for each institution and with both institutions combined. A two-way ANOVA was conducted for the comparison between years and institutions. For the subscale analysis of EC, PT, and PD, we used one-way ANOVA for significant differences between years at both institutions. For the gender-effect analysis, t-test was performed to examine the differences in total IRI scores at both institutions combined and at each institution separately. Additionally, an Analysis of Covariance (ANCOVA) was done to identify the influence of gender on empathy scores. RESULTS: A total of 140 students from both institutions participated in this study. We found a fluctuating pattern of empathy scores without a clear trend across the years. The sub-scales of EC, PD, and PT across academic years at both institutions showed significant differences within the EC at RCSI-MUB (p = 0.003). No significant differences were identified across other years from both institutions. There were significant differences between empathy scores from RCSI-MUB and UoS for EC (p = 0.011). Additionally, a pronounced interaction effect between year and institution was observed for PT (p = 0.032). The gender-wise analysis showed that female students had higher empathy scores than males (p = 0.004). The ANCOVA for IRI score results revealed a p-value of 0.023, indicating that gender plays a crucial role in empathy levels among medical students. The ANCOVA results revealed a p-value of 0.022 in the EC subscale. CONCLUSION: Our study unveiled intricate patterns in empathy development among medical students across years and genders at RCSI-MUB and UoS. These congruences and dissimilarities in empathy scores signal a subjective understanding of empathy by medical students. The disparities in understanding may encourage medical educators to embed empathy in standard medical curricula for better healthcare outcomes.

Development of Sustainable Construction Materials from Inert Waste Mixtures Using the Mechanosynthesis Process.

This research investigates the potential of mechanosynthesis to transform inert waste mixtures into sustainable construction materials. Three waste streams were employed: recycled glass, recycled concrete, and excavated soils. Two alternative material formulations, F1 (50% recycled concrete, 30% recycled glass, 20% excavated soil) and F2 (60% excavated soil, 20% recycled concrete, 20% recycled glass), were developed. Cement pastes were produced by partially substituting cement (CEM I) with 50% of either F1 or F2. Characterization techniques, including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (ATR-FTIR), and mechanical testing, were performed. Cement pastes incorporating milled waste materials exhibited significantly enhanced compressive strength compared to their unmilled counterparts. At 28 curing days, compressive strengths reached 44, 47, 45, and 49.7 MPa, and at 90 curing days, they increased to 47.5, 50, 55, and 61 MPa for milling conditions of 200 rpm for 5 min, 200 rpm for 15 min, 400 rpm for 5 min, and 400 rpm for 15 min, respectively. In addition, F1 formulations showed higher compressive strengths than the reference CEM II and CEM III pastes. These results highlight the efficacy of mechanosynthesis in valorizing construction waste, mitigating CO2 emissions, and creating environmentally friendly construction materials.

Pollen-Food Allergy Syndrome: From Food Avoidance to Deciphering the Potential Cross-Reactivity between Pru p 3 and Ole e 7.

BACKGROUND: Cross-reactivity between nonspecific lipid transfer proteins could cause anaphylaxis, further influencing food avoidance and nutrient deficiencies. The one affecting olive pollen (Ole e 7) and peach (Pru p 3) may underlie a variety of pollen-food syndromes, though a deep molecular analysis is necessary. METHODS: Three Ole e 7-monosensitised patients (MON_OLE), three Pru p 3-monosensitised patients (MON_PRU) and three bisensitised patients (BI) were selected. For epitope mapping, both digested proteins were incubated with patient sera, and the captured IgE-bound peptides were characterised by LC-MS. RESULTS: The analysis revealed two Ole e 7 epitopes and the three Pru p 3 epitopes previously described. Interestingly, the "KSALALVGNKV" Ole e 7 peptide was recognised by MON_OLE, BI and MON_PRU patients. Conversely, all patients recognised the "ISASTNCATVK" Pru p 3 peptide. Although complete sequence alignment between both proteins revealed 32.6% identity, local alignment considering seven residue fragments showed 50 and 57% identity when comparing "ISASTNCATVK" with Ole e 7 and "KSALALVGNKV" with Pru p 3. CONCLUSIONS: This study mapped sIgE-Ole e 7-binding epitopes, paving the way for more precise diagnostic tools. Assuming non-significant sequence similarity, structural homology and shared key residues may underlie the potential cross-reactivity between Ole e 7 and Pru p 3 nsLTPs.

On the link between the reaction force constant and conceptual DFT.

CONTEXT: The reaction force constant ( κ ), introduced by Professor Alejandro Toro-Labbé, plays a pivotal role in characterizing the reaction pathway by assessing the curvature of the potential energy profile along the intrinsic reaction coordinate. This study establishes a novel link between κ and the reactivity descriptors of conceptual density functional theory (c-DFT). Specifically, we derive expressions that relate the reaction force constant to nuclear softness and variations in chemical potential. Our findings indicate that regions of the reaction pathway where κ is negative match with significant electronic structure rearrangements, while positive κ regions match mostly with geometric rearrangements. This correlation between κ and c-DFT reactivity descriptors enhances our understanding of the underlying forces driving chemical reactions and offers new perspectives for analyzing reaction mechanisms. METHODS: The internal reaction path for the proton transfer in SNOH, chemical potential, and nuclear softness were computed using DFT with B3LYP exchange-correlation functional and 6-311++G(d,2p) basis set.

Dual-assist heterologous antigens screening: An effective strategy to improve the sensitivity of lateral flow immunoassay.

Heterologous strategy has promising applications in improving the sensitivity of competitive immunoassay. In this study, the potential heterologous coating antigens (HEA) were screened from eight imidacloprid (IMI) structural analogs based on the cross-reactivity (CR) of a prepared antibody. Computer-aided molecular modeling was used to predict the optimal HEA. Compared with the homologous coating antigen (HOA), the predicted HEA prepared from acetamiprid (CR = 0.23 %) increased the detection sensitivity of the enzyme-linked immunoassay and colloidal gold nanoparticle-based lateral flow immunoassay (HOA-Au-LFIA) by 5.6 and 4.1 times, respectively. Subsequently, the HEA and aggregation-induced emission fluorescent labels were integrated into a lateral flow immunoassay platform (HEA-AIE-LFIA). The limit of detection was 0.12 ng mL-1 for HEA-AIE-LFIA, which was 7.7-fold lower than that of HOA-Au-LFIA. Furthermore, HEA-AIE-LFIA was applied to detect IMI in food samples with excellent recoveries (86.41 %-111.25 %). Overall, this strategy of screening for superior HEA has great potential for improving LFIA sensitivity.

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma.

Adoptive cell therapy (ACT) using in vitro expanded tumor-infiltrating lymphocytes (TILs) has inconsistent clinical responses. To better understand determinants of therapeutic success, we tracked TIL clonotypes from baseline tumors to ACT products and post-ACT blood and tumor samples in melanoma patients using single-cell RNA and T cell receptor (TCR) sequencing. Patients with clinical responses had baseline tumors enriched in tumor-reactive TILs, and these were more effectively mobilized upon in vitro expansion, yielding products enriched in tumor-specific CD8+ cells that preferentially infiltrated tumors post-ACT. Conversely, lack of clinical responses was associated with tumors devoid of tumor-reactive resident clonotypes and with cell products mostly composed of blood-borne clonotypes that persisted in blood but not in tumors post-ACT. Upon expansion, tumor-specific TILs lost tumor-associated transcriptional signatures, including exhaustion, and responders exhibited an intermediate exhausted effector state after TIL engraftment in the tumor, suggesting functional reinvigoration. Our findings provide insight into the nature and dynamics of tumor-specific clonotypes associated with clinical response to TIL-ACT, with implications for treatment optimization.

Blunted reward-related activation to food scenes distinguishes individuals with alcohol use disorder in a pilot case-control fMRI pilot study.

BACKGROUND: Alcohol use disorder (AUD) is thought to bias the neurocircuitry underlying reward processing and motivation to preferentially attend to conditioned alcohol cues over natural rewards. The present case-control pilot study evaluated this hypothesis using novel natural reward paradigms. METHODS: Twenty-eight participants (AUD, n = 14, light drinkers, n = 14) were recruited-AUD participants reported 44.0% heavy drinking days (%HDD) and 4.67 drinks/day over the preceding 90 days. Functional magnetic resonance imaging (fMRI) data were acquired during the administration of three separate picture-viewing paradigms of alcohol cues, food scenes, and social reward, respectively. Independent samples t-tests were performed to compare groups' fMRI data and exploratory correlation analyses were performed to examine associations with clinical characteristics of AUD. RESULTS: Food scenes elicited abnormally low reward-related activation, within the superior frontal gyrus and caudate bilaterally, among AUD participants. Lower activation to food scenes within the superior frontal gyrus was, in turn, associated with higher levels of past-month %HDD among AUD participants, specifically, along with craving and alcohol dependence severity when examined across the full sample. Contrasting reward types (e.g., alcohol cues vs. food scenes) did not reveal "preferential" activation to differentiate groups. CONCLUSIONS: Heavy drinking appears associated with reduced responsivity to natural rewards, specifically food rather than social cues. Neural mechanisms underlying the high prevalence of malnutrition among individuals with AUD may involve some combination of blunted approach-related affect and reduced craving-related motivation to eat when food is present, resulting in limited engagement of cortico-striato-thalamic motor circuitry supporting food acquisition. However, given the preliminary nature of this pilot study, such formulations remain tentative until larger follow-up studies can be conducted. From a potential translational standpoint, the ability of promising therapeutics to demonstrate increased responsivity to natural rewards, specifically nutritive reward may serve as a valuable complementary efficacy indicator for future clinical neuroimaging trials in AUD.

Exploring the Utility of a Functional Magnetic Resonance Imaging (fMRI) Cannabis Cue-Reactivity Paradigm in Treatment Seeking Adults with Cannabis Use Disorder.

BACKGROUND: Functional magnetic resonance imaging (fMRI) studies examining cue-reactivity in cannabis use disorder (CUD) have either had small sample sizes or involved non-treatment-seeking participants. As a secondary analysis, we administered an fMRI cue-reactivity task to CUD participants entering two separate clinical trials (varenicline or repetitive Transcranial Magnetic Stimulation-rTMS) to determine the task activation patterns for treatment-seeking participants with CUD. We aimed to determine the activation patterns for the total sample and determined behavioral correlates. We additionally compared studies to determine if patterns were consistent. METHODS: Treatment-seeking participants with moderate or severe CUD had behavioral craving measured at baseline via the short form of the Marijuana Craving Questionnaire (MCQ-SF) and completed a visual cannabis cue-reactivity task during fMRI (measuring the Blood-Oxygen-Level-Dependent-BOLD response) following 24-hours of cannabis-abstinence. RESULTS: Sixty-five participants were included (37-varenicline, 28-rTMS; 32% female; mean-age 30.4±9.9SD). When contrasting cannabis-images vs. matched-neutral-images, participants showed greater BOLD response in bilateral ventromedial-prefrontal, dorsolateral-prefrontal, anterior cingulate, and visual cortices, as well as the striatum. There was stronger task-based functional-connectivity (tbFC) between the medial prefrontal cortex and both the amygdala and the visual cortex. Craving negatively correlated with BOLD response in the left ventral striatum (R2=-0.32; p=0.01) in the full sample. There were no significant differences in either activation or tbFC between studies. DISCUSSION: Among two separate treatment-seeking groups with CUD, there was increased cannabis cue-reactivity and tbFC in regions related to executive function and reward processing. Cannabis-craving was negatively associated with cue-reactivity in the left ventral striatum.