Ultrasonic humidifier aerosols: Observed high heavy metal enrichment and a new emission control method.

Ultrasonic humidifiers are commonly used in households to maintain indoor humidity and generate a large number of droplets or spray aerosols. However, there have been various health concerns associated with humidifier use, largely due to aerosols generated during operation. Here, we investigated the size distribution, chemical composition, and charged fraction of aerosol particles emitted from commercial ultrasonic humidifiers. Heavy metals in water used for humidifiers were found to be highly enriched in the ultrasonic humidifier aerosols (UHA), with the enrichment factors ranging from 102 to 107. This enrichment may pose health concerns for the building occupants, as UHA concentrations of up to 106 particles/cm3 or 3 mg/m3 were observed. Furthermore, approximately 90% of UHA were observed to be electrically charged, for the first time according to our knowledge. Based on this discovery, we proposed and tested a new method to remove UHA by using a simple electrical field. The designed electrical field in this work can efficiently remove 81.4% of UHA. Therefore, applying this electrical field could be an effective method to significantly reduce the health risks by UHA.

Combustion aerosols and suspended dust with controlled processes in Lhasa: Elemental analysis and size distribution characteristics.

To explore air contamination resulting from special biomass combustion and suspended dust in Lhasa, the present study focused on the size distribution and chemical characteristics of particulate matter (PM) emission resulting from 7 types of non-fossil pollution sources. We investigated the concentration and size distribution of trace elements from 7 pollution sources collected in Lhasa. Combining Lhasa's atmospheric particulate matter data, enrichment factors (EFs) have been calculated to examine the potential impact of those pollution sources on the atmosphere quality of Lhasa. The highest mass concentration of total elements of biomass combustion appeared at PM0.4, and the second highest concentration existed in the size fraction 0.4-1 µm; the higher proportion (12 %) of toxic metals was produced by biomass combustion. The elemental composition of suspended dust and atmospheric particulate matter was close (except for As and Cd); the highest concentration of elements was all noted in PM2.5-10 (PM3-10). Potassium was found to be one of the main biomass markers. The proportion of Cu in suspended dust is significantly lower than that of atmospheric particulate matter (0.53 % and 3.75 %), which indicates that there are other anthropogenic sources. The EFs analysis showed that the Cr, Cu, Zn, and Pb produced by biomass combustion were highly enriched (EFs > 100) in all particle sizes. The EFs of most trace elements increased with decreasing particle size, indicating the greater influence of humanfactors on smaller particles.

Source-free collaborative domain adaptation via multi-perspective feature enrichment for functional MRI analysis.

Resting-state functional MRI (rs-fMRI) is increasingly employed in multi-site research to analyze neurological disorders, but there exists cross-site/domain data heterogeneity caused by site effects such as differences in scanners/protocols. Existing domain adaptation methods that reduce fMRI heterogeneity generally require accessing source domain data, which is challenging due to privacy concerns and/or data storage burdens. To this end, we propose a source-free collaborative domain adaptation (SCDA) framework using only a pretrained source model and unlabeled target data. Specifically, a multi-perspective feature enrichment method (MFE) is developed to dynamically exploit target fMRIs from multiple views. To facilitate efficient source-to-target knowledge transfer without accessing source data, we initialize MFE using parameters of a pretrained source model. We also introduce an unsupervised pretraining strategy using 3,806 unlabeled fMRIs from three large-scale auxiliary databases. Experimental results on three public and one private datasets show the efficacy of our method in cross-scanner and cross-study prediction.

Genetic structure and selective sweeps in Kirghiz sheep using SNP50K bead chip.

The objective of this study is to analyze environmental genetic selection signals in large-scale sheep populations with conflicting environmental adaptations, aiming to identify and isolate genes associated with environmental adaptations in sheep populations. Kirghiz sheep, which inhabit high-altitude environments year-round, demonstrate the ability to adapt to extreme conditions. In this study, 42 Kirghiz sheep, 24 Tien-Shan in Kyrgyzstan sheep, 189 Qira black sheep, and 160 Chinese Merino sheep were genotyped using Illumina Ovine SNP50K chip. Regions exhibiting a selection signal threshold of 5%, as well as PI analysis and haplotype statistical scanning gene data were annotated, and intersecting genes were identified as candidate genes. Through Fst and haplotype statistical analysis revealed the key gene PDGFD and its vicinity's impact on fat deposition in sheep tails. Additionally, Fst and PI analysis uncovered genes related to high-altitude adaptation as well as those linked to animal growth and reproduction.Further GO and KEGG enrichment pathway analyses unveiled pathways associated with high-altitude adaptation such as negative regulation of peptidyl-tyrosine phosphorylation and xenobiotic metabolism processes.This investigation into the adaptability of Kirghiz sheep provides theoretical support and practical guidance for the conservation and genetic enhancement of Kirghiz sheep germplasm resources.

Analysis of microRNAs and the microRNA-messengerRNA regulatory network in chronic alcohol exposure.

Introduction: Chronic alcoholism is one of the most common neurological diseases in modern society. However, the key mechanisms underlying learning and memory impairments caused by chronic alcohol exposure remain unclear. In this study, a microRNA-messenger RNA (miRNA-mRNA) network was constructed to explore the potential function of key genes in chronic alcohol exposure, their effects on the hippocampus, and their mechanisms which facilitate brain injury in mice. Methods: The Morris water maze test was used to assess the learning ability of mice in each group. Mitochondrial ATPase activity and H2S levels in the hippocampi of mice were determined. Differentially expressed miRNAs and mRNAs in the mouse hippocampus were identified using second-generation sequencing. Using the TargetScan, miRTarBase, and miRDB databases, we predicted miRNA target genes and constructed a miRNA-mRNA regulatory network. Furthermore, using the Gene Ontology and KEGG databases we performed functional enrichment and protein-protein interaction analyses. Real-time quantitative polymerase chain reaction (qPCR) and other methods were employed to verify the mRNA expression of related genes. Results: The Morris water maze test revealed that mice exposed to chronic alcohol exhibited a significantly reduced learning ability compared to the control group (p < 0.05). Compared with the control group, the activity of mitochondrial ATPase in the hippocampal tissue of alcohol-treated mice was significantly decreased (p < 0.01), suggesting brain injury. In the model group, H2S significantly increased in the mice hippocampi (p < 0.01), indicating that chronic alcohol exposure could activate cystathionineß-synthase (CBS) and catalyze the mass formation of H2S, suggesting brain injury. A total of 208 differentially expressed miRNAs and 377 differentially expressed mRNAs were screened through bioinformatic analysis. Enrichment analysis indicated that the main pathways were involved in neurodegeneration and regulation of the Wnt signaling pathway. The PCR detected a significant downregulation in the expressions of FOS and EGR1 genes. Discussion: Consequently, chronic alcohol exposure may regulate the expression of FOS and EGR1 in the hippocampus through miR-222-3p, miR-132-3p, miR-212-3p, and miR-191-5p, reduce the activity of hippocampal mitochondrial ATPase, activate CBS, catalyze the large amount of H2S formation, and destroy the mitochondrial structure, resulting in decreased learning ability. Our findings revealed valuable genes and miRNAs for the study of chronic alcohol exposure.

Ion adsorption-enrichment effect and its driving mechanism for nano-dots lithography with SPM probe on water-soluble crystal surfaces.

HYPOTHESIS: Water-soluble KDP (KH2PO4) crystals possess excellent optical properties and are employed as frequency converters in clean fusion energy. To improve their performances, there is an immediate necessity to lithograph surface nano-patterns on them. Although the Scanning Probe Microscope (SPM) provides a promising way to achieve this purpose through the water menisci, the driving mechanisms of the lithographic behaviors have not yet been revealed. SIMULATIONS AND EXPERIMENTS: Multi-scale investigations are constructed to explore the underlying driving mechanisms. The SPM probe-induced ion diffusion-transport behaviors are investigated by molecular dynamics. The ion adsorption-enrichment mechanisms are revealed by 18 adsorption models via the ab initio. The SPM probe-induced self-assembly experiments are performed to prove the local heavy concentration. A comprehensive model is developed to describe the lithography mechanisms of the probe-induced self-assembly nano-dots on water-soluble substrates. FINDINGS: It is interestingly found that the KDP growth units (H2PO4-) exhibit obvious adsorption-enrichment effect at 3.16 Å from the probe surface, causing local heavy concentration. The H2PO4- would spontaneously adsorb onto the probe surface, which is dominated by the Si-O bonding reactions. The nano-dots with the height of 27 âˆ¼ 48 nm and diameter of 2.0 âˆ¼ 2.7 µm are lithographed on the KDP substrate. The proposed model further confirms that the lithography processes are driven by the solution supersaturation, solute diffusion, and surface free energy.

Dechlorane plus in dust, hair and urine: Exposure, excretion and level change.

Dechlorane plus (DP) has been detected in a variety of environmental media and in human. Measurement of DPs in hair, urine, and house dust across different habitats allows for the assessment of short-term spatial changes in human exposure to DPs, as well as their excretion in urine. This offers a significant reference point for further research on the behavior of persistent pollutants within organisms. We measured and analyzed the concentrations of DP in the hair and urine of 32 students from a university in Beijing during school and home phases, and in indoor dust from dormitories and some home environments. The results indicated that the concentrations of DP in three types of samples were higher during the home phase compared to the school phase. We compared the fanti values and identified selective enrichment of syn-DP in hair, along with selective excretion of syn-DP in urine. Utilizing molecular docking technique, we simulated the binding effect between DP and the Megalin protein. The results demonstrated that the binding energy of anti-DP to Megalin was higher than that of syn-DP, suggesting that anti-DP has a greater propensity to bind to Megalin and be reabsorbed. This results in higher levels of syn-DP excretion in urine. Finally, we categorized students based on their participation in the organic exposure experiment and their BMI. The results indicated that the concentrations of DP in hair and urine were higher in the exposed group compared to the non-exposed group during the school year. After excluding the effect of exposure, habitat changes were more likely to affect the accumulation and excretion of DP in normal-weight students (BMI ≤24 kg/m2, n = 28), while overweight students (BMI >24 kg/m2, n = 4) were less affected by the effect of habitat because of their higher body fat percentage and their greater ability to accumulate DP.

Calcium enrichment activity initiates extracellular calcium influx-dependent inflammatory response of biologically-derived hydroxyapatite.

Biologically-derived hydroxyapatite is a widely used biomaterial in various clinical applications including bone augmentation. However, the osteogenic application of biological hydroxyapatite is limited by inflammatory responses, and the underlying mechanism remains unknown. The current study aimed to elucidate the molecular mechanisms underlying the inflammatory response to biological hydroxyapatite. Porcine-derived hydroxyapatite (PHA) with two sintering temperatures (800 and 1600 °C), PHA800 and PHA1600, respectively, were prepared. A PHA/macrophage co-culture model was established. Transcriptome, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) analyses were used to determine the inflammatory effects and the main pathways activated by PHA800 and PHA1600. Intracellular calcium level, PHA-induced calcium enrichment, and related biological effects were used to determine the molecular mechanism at the PHA-cell interface. PHA800 significantly upregulated a TLR4 mediated inflammatory pathway in a calcium influx-dependent manner, and the calcium enrichment activity on the surface of PHA800 promoted calcium influx. In contrast, the calcium enrichment activity on the surfaces of the PHA1600 and PHA800 pretreated groups was attenuated, resulting in decreased calcium influx and mild inflammatory effects. Our results provide a fundamental basis for the development of novel bone substitutes that elicit low levels of inflammation response.

Genetic effect of thyroid function-related diseases on acute respiratory distress syndrome: a Mendelian randomization study.

BACKGROUND: Previous studies have shown an association between acute respiratory distress syndrome (ARDS) and thyroid function. However, their causal relationship remains unspecified. Therefore, this study aims to explore the causal relationship between ARDS and thyroid function-related diseases with Mendelian Randomization (MR) analysis. METHODS: ARDS dataset finn-b-J10_ARDS, finn-b-E4_THYROID dataset of disorders of the thyroid gland (DTG) and finn-b-E4_HYTHYNAS of hypothyroidism were acquired from public database. In univariate MR (UVMR), causal effects between DTG, hypothyroidism and ARDS were investigated using 5 types of algorithms, and reliability was validated by sensitivity analysis. Moreover, multivariate MR (MVMR), enrichment and interaction network analyses of genes corresponding to SNPs of DTG and hypothyroidism were carried out. Significant level was chosen as p<0.05. RESULTS: UVMR identified DTG and hypothyroidism (P < 0.05, OR > 1) as risk factors, and were causally related to ARDS. Reliability of UVMR results was confirmed through sensitivity analysis, and results were stable and reliable. However, DTG and hypothyroidism had no effect on ARDS in MVMR, possibly because these factors had independent effects on ARDS. Ultimately, 96 and 113 genes corresponding to SNPs of DTG and hypothyroidism were found closely related to immune-related pathways. CONCLUSIONS: UVMR and MVMR analysis revealed a causal connection between DTG and hypothyroidism as risk factors with ARDS, providing robust evidence for investigation into relationship of hypothyroidism on ARDS and between DTG and ARDS.

Enhancing Patient Selection in Sepsis Clinical Trials Design Through an AI Enrichment Strategy: Algorithm Development and Validation.

BACKGROUND: Sepsis is a heterogeneous syndrome, and enrollment of more homogeneous patients is essential to improve the efficiency of clinical trials. Artificial intelligence (AI) has facilitated the identification of homogeneous subgroups, but how to estimate the uncertainty of the model outputs when applying AI to clinical decision-making remains unknown. OBJECTIVE: We aimed to design an AI-based model for purposeful patient enrollment, ensuring that a patient with sepsis recruited into a trial would still be persistently ill by the time the proposed therapy could impact patient outcome. We also expected that the model could provide interpretable factors and estimate the uncertainty of the model outputs at a customized confidence level. METHODS: In this retrospective study, 9135 patients with sepsis requiring vasopressor treatment within 24 hours after sepsis onset were enrolled from Beth Israel Deaconess Medical Center. This cohort was used for model development, and 10-fold cross-validation with 50 repeats was used for internal validation. In total, 3743 patients with sepsis from the eICU Collaborative Research Database were used as the external validation cohort. All included patients with sepsis were stratified based on disease progression trajectories: rapid death, recovery, and persistent ill. A total of 148 variables were selected for predicting the 3 trajectories. Four machine learning algorithms with 3 different setups were used. We estimated the uncertainty of the model outputs using conformal prediction (CP). The Shapley Additive Explanations method was used to explain the model. RESULTS: The multiclass gradient boosting machine was identified as the best-performing model with good discrimination and calibration performance in both validation cohorts. The mean area under the receiver operating characteristic curve with SD was 0.906 (0.018) for rapid death, 0.843 (0.008) for recovery, and 0.807 (0.010) for persistent ill in the internal validation cohort. In the external validation cohort, the mean area under the receiver operating characteristic curve (SD) was 0.878 (0.003) for rapid death, 0.764 (0.008) for recovery, and 0.696 (0.007) for persistent ill. The maximum norepinephrine equivalence, total urine output, Acute Physiology Score III, mean systolic blood pressure, and the coefficient of variation of oxygen saturation contributed the most. Compared to the model without CP, using the model with CP at a mixed confidence approach reduced overall prediction errors by 27.6% (n=62) and 30.7% (n=412) in the internal and external validation cohorts, respectively, as well as enabled the identification of more potentially persistent ill patients. CONCLUSIONS: The implementation of our model has the potential to reduce heterogeneity and enroll more homogeneous patients in sepsis clinical trials. The use of CP for estimating the uncertainty of the model outputs allows for a more comprehensive understanding of the model's reliability and assists in making informed decisions based on the predicted outcomes.

Rapid Characterization of Phospholipids from Biological Matrix Enabled by Indium Tin Oxide (ITO) Coated Slide Assisted Enrichment MALDI Mass Spectrometry.

Lipidomic analysis of human serum is essential to monitor the individual's health status. Herein, we develop a facile strategy for rapid characterization of phospholipids in human serum via indium tin oxide (ITO) coated glass slide solid phase extraction MALDI mass spectrometry (ITO-SPE-MALDI-MS). Phospholipid species are retained on ITO slide via solid phase extraction owing to the unique property of the ITO material; the measurement of phospholipid species from 1 µl human serum within 2 min is achievable. A comparison of ITO-SPE strategy with conventional extraction methods was further carried out using liquid chromatography-mass spectrometry (LC-MS) and ion-mobility mass spectrometry (IM-MS), resulting in a comparable enrichment performance for the phospholipid analysis. Furthermore, rapid lipidomic profiling of serum samples from human colorectal cancer patients and cell lines was demonstrated. Our results indicate that ITO-SPE-MALDI-MS provides a higher throughput strategy for the analysis of phospholipid species in complex biological mixtures, showcasing its potential for applications in the analysis of clinical biofluids.

Deep and unbiased proteomics, pathway enrichment analysis, and protein-protein interaction of biomarker signatures in migraine.

Background: Currently, there are no biomarkers for migraine. Objectives: We aimed to identify proteomic biomarker signatures for diagnosing, subclassifying, and predicting treatment response in migraine. Design: This is a cross-sectional and longitudinal study of untargeted serum and cerebrospinal fluid (CSF) proteomics in episodic migraine (EM; n = 26), chronic migraine (CM; n = 26), and healthy controls (HC; n = 26). Methods: We developed classification models for biomarker identification and natural clusters through unsupervised classification using agglomerative hierarchical clustering (AHC). Pathway analysis of differentially expressed proteins was performed. Results: Of 405 CSF proteins, the top five proteins that discriminated between migraine patients and HC were angiotensinogen, cell adhesion molecule 3, immunoglobulin heavy variable (IGHV) V-III region JON, insulin-like growth factor binding protein 6 (IGFBP-6), and IGFBP-7. The top-performing classifier demonstrated 100% sensitivity and 75% specificity in differentiating the two groups. Of 229 serum proteins, the top five proteins in classifying patients with migraine were immunoglobulin heavy variable 3-74 (IGHV 3-74), proteoglycan 4, immunoglobulin kappa variable 3D-15, zinc finger protein (ZFP)-814, and mediator of RNA polymerase II transcription subunit 12. The best-performing classifier exhibited 94% sensitivity and 92% specificity. AHC separated EM, CM, and HC into distinct clusters with 90% success. Migraine patients exhibited increased ZFP-814 and calcium voltage-gated channel subunit alpha 1F (CACNA1F) levels, while IGHV 3-74 levels decreased in both cross-sectional and longitudinal serum analyses. ZFP-814 remained upregulated during the CM-to-EM reversion but was suppressed when CM persisted. CACNA1F was pronounced in CM persistence. Pathway analysis revealed immune, coagulation, glucose metabolism, erythrocyte oxygen and carbon dioxide exchange, and insulin-like growth factor regulation pathways. Conclusion: Our data-driven study provides evidence for identifying novel proteomic biomarker signatures to diagnose, subclassify, and predict treatment responses for migraine. The dysregulated biomolecules affect multiple pathways, leading to cortical spreading depression, trigeminal nociceptor sensitization, oxidative stress, blood-brain barrier disruption, immune response, and coagulation cascades. Trial registration: NCT03231241, ClincialTrials.gov.

Identification of biological markers for migraine using proteins found in the cerebrospinal fluid and blood The diagnosis of migraine currently relies on self-reported symptoms. Inaccurate reporting by patients and inadequate interviewing by diagnosticians can result in misdiagnosis and subsequent mistreatment. Our study investigated the disparity in protein levels in the cerebrospinal fluid (CSF) and serum between individuals with migraine and healthy individuals. Our study provides evidence for identifying novel protein biomarkers and biological pathways that can assist in diagnosing, subclassifying, and predicting treatment responses for migraine.

GOTermViewer: Visualization of Gene Ontology Enrichment in Multiple Differential Gene Expression Analyses.

Gene ontology phrases are a widely used set of hierarchical terms that describe the biological properties of genes. These terms are then used to annotate individual genes, making it possible to determine the likely physiological properties of groups of genes such as a list of differentially expressed genes. Consequently, their ability to predict changes in biological features and functions based on alterations in gene expression has made gene ontology terms popular in the wide range of bioinformatic fields, such as differential gene expression and evolutionary biology. However, while they make the analysis easier, it is seldom easy to convey the results in a readily understandable manner. A number of applications have been developed to visualize gene ontology (GO) term enrichment; however, these solutions tend to focus on the display of aggregated results from a single analysis, making them unsuitable for the analysis of a series of experiments such as a time course or response to different drug treatments. As multiple pair wise comparisons are becoming a common feature of RNA profiling experiments, the absence of a mechanism to easily compare them is a significant problem. Consequently, to overcome this obstacle, we have developed GOTermViewer, an application that displays GO term enrichment data as determined by GOstats such that changes in physiological response across a number of individual analyses across a time course or range of drug treatments can be visualized.

Work-family enrichment among parent nurses: a cross-sectional scale development and validation study.

BACKGROUND: Work-family enrichment refers to the extent to which experiences in one role improve the quality of life in another role, and the bidirectionality indicates that benefits derived from work can be applied to family and vice versa. Parent nurses, that is, female nurses who are raising preschool children, play a major role at work and in the family. Thus, work-family enrichment is significant for them. The Work-Family Enrichment Scale cannot be generalized to parent nurses. This study was aimed at developing and psychometrically validating a draft Work-Family Enrichment Scale for Parent Nurses. METHODS: A questionnaire survey was conducted among 1,090 parent nurses who were randomly sampled from hospitals with more than 200 beds in Japan. The survey evaluated (1) a draft Work-Family Enrichment Scale for Parent Nurses, (2) the Japanese version of the Work-Family Enrichment Scale, and (3) the Positive Spillover Scale. The scales were psychometrically evaluated for internal consistency, construct validity, and criterion-related validity. RESULTS: Data from 503 participants (age, mean ± standard deviation [range] 35.5 ± 4.96 [23-47] years) were analyzed. Results of exploratory factor analysis, the work to family enrichment direction yielded five factors for 23 items: "emotional fulfillment," "efficiency," "ability to lead," "displaying industriousness," and "self-growth." Cronbach's alpha coefficients ranged from 0.862 to 0.914. In the family-to-work enrichment direction, there were five factors for 28 items: "help-seeking," "receptiveness," "expansion of one's horizon," "efficiency," and "emotional fulfillment." Cronbach's alpha coefficients ranged from 0.790 to 0.907. Additionally, the correlation coefficients reporting criterion-related validity were 0.685 and 0.619 with regard to the Japanese version of the Work-Family Enrichment Scale and 0.596 and 0.534 with the Positive Spillover Scale for the Work-to-Family Enrichment Scale and the Family-to-Work Enrichment Scale for Parent Nurses, respectively. CONCLUSIONS: The Work-Family Enrichment Scale for Parent Nurses has adequate reliability and validity and can be used as an effective measure to assess the positive aspects of work and family roles among female parent nurses.

Feuerstein Instrumental Enrichment Program for People With Schizophrenia After the First Episode of Psychosis: Protocol for an Open-Label Intervention Study.

BACKGROUND: Schizophrenia is a disorder associated with neurocognitive deficits that adversely affect daily functioning and impose an economic burden. Cognitive rehabilitation interventions, particularly during the early phases of illness, have been shown to improve cognition, functionality, and quality of life. The Feuerstein Instrumental Enrichment (FIE) program, based on the Mediated Learning Experience and the Structural Cognitive Modifiability theory, has been applied in various disorders, but its applicability in schizophrenia has not yet been clarified. OBJECTIVE: This study aims to investigate the effects of the FIE program on the functionality of patients with first-episode schizophrenia. METHODS: In total, 17 patients will be recruited for an open-label intervention consisting of twice-weekly sessions for 10 weeks. The primary outcome measure will be changes in the Goal Achievement Scale score. Maze task performance from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery will serve as a secondary outcome measure. At the same time, changes in Positive and Negative Syndrome Scale scores and other MATRICS domains will be analyzed as exploratory outcomes. Assessments will be administered before and after the intervention, with a follow-up period of 6 months. RESULTS: This trial was preregistered in The Brazilian Registry of Clinical Trials (RBR-4gzhy4s). By February 2024, 11 participants were enrolled in the training. Recruitment is expected to be completed by May 2024. Data analysis will be conducted between May and September 2024. The results are expected to be published in January 2025. CONCLUSIONS: This study may establish a protocol for the FIE program that uses mediation techniques for individuals in the early stages of schizophrenia. The results will add to the knowledge about strategies to promote cognitive skills and functional impairment in daily life. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57031.

Long-lasting behavioral and neurochemical effects of early-life environmental enrichment in rats submitted to neonatal morphine administration.

The present study examined the medium- and long-term effects of early environmental enrichment (EE) on neuromotor, nociceptive, cognitive, behavioral, and neurochemical parameters in newborn rats repeatedly exposed to morphine. The study employed 90 Wistar rats: 10 adult nulliparous females and 80 male pups. Litter was split into standard and EE housing. Following, half of each litter received saline (S) or morphine (M) injections, resulting in four groups: SC + S, EE + S, SC + M, and EE + M. EE was applied from PND1 to PND21, while morphine or saline was given daily (5 µg/s.c.) from PND8 to PND14. Neuromotor development was similar between groups. In the OF test, morphine reduced outer and total crossings, whereas EE increased inner crossings and rearings. Adult rats showed a decrease in outer and total crossings and grooming and an increase in rearing. EE increased the number of protected and unprotected head dipping. Adult rats showed an increase in protected head dipping. Adult rats showed a lower recognition index, and, when exposed to EE, a lower anxiety index and analgesia. EE increased brainstem and hippocampal BDNF levels. Adult rats had increased hypothalamus, spinal cord, and brainstem BDNF levels, an increase in the spinal cord, and decreased hypothalamus TNF-α levels. This study demonstrated that early-life EE raises BDNF levels in the brainstem and hippocampus of rats and modifies their behaviors (such as nociception, exploration, and anxiety) in a state-dependent manner (morphine and age).

High-resolution spiral microfluidic channel integrated electrochemical device for isolation and detection of extracellular vesicles without lipoprotein contamination.

Recent studies have indicated significant correlation between the concentration of immune checkpoint markers borne by extracellular vesicles (EVs) and the efficacy of immunotherapy. This study introduces a high-resolution spiral microfluidic channel-integrated electrochemical device (HiMEc), which is designed to isolate and detect EVs carrying the immune checkpoint markers programmed death ligand 1 (PD-L1) and programmed death protein 1 (PD-1), devoid of plasma-abundant lipoprotein contamination. Antigen-antibody reactions were applied to immobilize the lipoproteins on bead surfaces within the plasma, establishing a size differential with EVs. A plasma sample was then introduced into the spiral microfluidic channel, which facilitated the acquisition of nanometer-sized EVs and the elimination of micrometer-sized lipoprotein-bead complexes, along with the isolation and quantification of EVs using HiMEc. PD-L1 and PD-1 expression on EVs was evaluated in 30 plasma samples (10 from healthy donors, 20 from lung cancer patients) using HiMEc and compared to the results obtained from standard tissue-based PD-L1 testing, noting that HiMEc could be utilized to select further potential candidates. The obtained results are expected to contribute positively to the clinical assessment of potential immunotherapy beneficiaries.

Gene regulatory mechanisms of T cell exhaustion in diffuse large B cell lymphoma based on single-cell transcriptome data.

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous and aggressive B cell malignancy that accounts for about 30 % of non-Hodgkin lymphomas. The current standard treatment for DLBCL is rituximab plus chemotherapy, but many patients are refractory or relapse, indicating the need for improved understanding of its molecular pathology. T cell exhaustion is a state of dysfunction or impairment that occurs in chronic infections or cancers, and is associated with poor prognosis in DLBCL. However, the molecular mechanisms of T cell exhaustion in DLBCL are poorly understood. In this study, we performed a comprehensive analysis of T cell exhaustion in DLBCL using public single-cell transcriptome data. We identified different subtypes of T cells and characterized their gene expression features. We found that DLBCL had a significantly higher proportion of exhausted T cells than normal tonsil, and that exhausted T cells had distinct gene expression signatures from non-exhausted T cells. These signatures included genes related to inhibitory receptors, cytokines, transcription factors and metabolic enzymes. We also found that ID3 gene was significantly upregulated in exhausted T cells in DLBCL, which may play a key role in T cell exhaustion. We constructed a protein-protein interaction network, identifying major hub proteins involved in T cell exhaustion or migration. We also performed KEGG and GO enrichment analysis for the differentially expressed genes between exhausted and non-exhausted T cells, and found important signaling pathways related to T cell exhaustion in DLBCL. Our results provide new insights into the molecular mechanisms underlying T cell exhaustion and offer novel therapeutic targets for this complex disease.

Polymorphisms in miRNA Genes Targeting the AMPK Signaling Pathway are Associated with Cervical Cancer Susceptibility in a Han Chinese Population.

Purpose: Cervical cancer (CC) poses a significant threat to women's health worldwide, and multiple signaling pathways have been confirmed to be involved in its development. The AMPK signaling pathway plays a central role in maintaining energy homeostasis, and its dysregulation is closely associated with the occurrence of CC. Changes in microRNA (miRNA) expression levels might be related to the AMPK signaling pathway. Single nucleotide polymorphisms (SNPs) can affect the function of miRNA and result in the development of CC. To investigate the association between the SNPs of AMPK pathway-associated miRNAs and CC in a Han Chinese population, we selected eight miRNA genes located in the AMPK pathway and analyzed nine SNP loci within these genes to explore whether they are associated with genetic susceptibility to cervical intraepithelial neoplasia (CIN) and CC. Methods: A total of 2,220 subjects were included in this study, including 928 healthy controls, 421 CIN patients, and 871 CC patients. Nine candidate SNPs (rs895819 in miR-27a, rs10061133 in miR-449b, rs41291179 in miR-216a, rs76481776 in miR-182, rs10406069 in miR-5196, rs12803915 and rs550894 in miR-612, rs66683138 in miR-3622b, and rs2620381 in miR-627) were genotyped using the TaqMan method. Results: The results showed significant differences in the allele distribution of rs41291179 and rs12803915 between the control group and the CIN group, as well as between the control group and the CC group (all P values < 0.005). The A allele of rs41291179 and the G allele of rs12803915 were associated with decreased risk of CIN (OR = 0.05, 95% CI: 0.01-0.39; OR = 0.61, 95% CI: 0.49-0.76) and CC (OR = 0.08, 95% CI: 0.01-0.66; OR = 0.71, 95% CI: 0.59-0.86), respectively. Conclusion: Our results suggest that polymorphisms in miRNA genes of the AMPK signaling pathway are associated with the development of CC.

Environmental enrichment and sex, but not n-acetylcysteine, alter extended-access amphetamine self-administration and cue-seeking.

There are no approved therapeutics for psychostimulant use and recurrence of psychostimulant use. However, in preclinical rodent models environmental enrichment can decrease psychostimulant self-administration of low unit doses and cue-induced amphetamine seeking. We have previously demonstrated that glutamate-dependent therapeutics are able to alter amphetamine seeking to amphetamine-associated cues only in enriched rats. In the current experiment, we will determine if enrichment can attenuate responding and cue-induced amphetamine seeking during extended access to a high dose of intravenous amphetamine. We will also determine if N-acetylcysteine (NAC), a glutamate dependent therapeutic, can attenuate amphetamine seeking in differentially reared rats. Female and male Sprague-Dawley rats were reared in enriched, isolated, or standard conditions from postnatal day 21 to 51. Rats were trained to self-administer intravenous amphetamine (0.1mg/kg/infusion) during twelve 6-hour sessions. During the abstinence period, NAC (100mg/kg) or saline was administered daily. Following a cue-induced amphetamine-seeking test, astrocyte densities within regions of the medial prefrontal cortex (mPFC) and nucleus accumbens (ACb) were quantified using immunohistochemistry. Environmental enrichment decreased responding for amphetamine and during the cue-induced amphetamine-seeking test. NAC did not attenuate cue-induced amphetamine seeking or alter astrocyte density. Across all groups, female rats self-administered less amphetamine but responded more during cue-induced amphetamine seeking than male rats. While amphetamine increased astrocyte densities within the ACb and mPFC, it did not alter mPFC astrocyte densities in female rats. The results suggest that enrichment can attenuate responding during extended access to a high dose of amphetamine and the associated cues. Sex alters amphetamine-induced changes to astrocyte densities in a regionally specific matter.