Association between Personal Abiotic Airborne Exposures and Body Composition Changes among Healthy Adults (60-69 Years Old): A Combined Exposome-Wide and Lipidome Mediation Approach from the China BAPE Study.

BACKGROUND: Evidence suggested that abiotic airborne exposures may be associated with changes in body composition. However, more evidence is needed to identify key pollutants linked to adverse health effects and their underlying biomolecular mechanisms, particularly in sensitive older adults. OBJECTIVES: Our research aimed to systematically assess the relationship between abiotic airborne exposures and changes in body composition among healthy older adults, as well as the potential mediating mechanisms through the serum lipidome. METHODS: From September 2018 to January 2019, we conducted a monthly survey among 76 healthy adults (60-69 years old) in the China Biomarkers of Air Pollutant Exposure (BAPE) study, measuring their personal exposures to 632 abiotic airborne pollutions using MicroPEM and the Fresh Air wristband, 18 body composition indicators from the InBody 770 device, and lipidomics from venous blood samples. We used an exposome-wide association study (ExWAS) and deletion/substitution/addition (DSA) model to unravel complex associations between exposure to contaminant mixtures and body composition, a Bayesian kernel machine regression (BKMR) model to assess the overall effect of key exposures on body composition, and mediation analysis to identify lipid intermediators. RESULTS: The ExWAS and DSA model identified that 2,4,5-T methyl ester (2,4,5-TME), 9,10-Anthracenedione (ATQ), 4b,8-dimethyl-2-isopropylphenanthrene, and 4b,5,6,7,8,8a,9,10-octahydro-(DMIP) were associated with increased body fat mass (BFM), fat mass indicators (FMI), percent body fat (PBF), and visceral fat area (VFA) in healthy older adults [Bonferroni-Hochberg false discovery rate (FDRBH)<0.05]. The BKMR model demonstrated a positive correlation between contaminants (anthracene, ATQ, copaene, di-epi-α-cedrene, and DMIP) with VFA. Mediation analysis revealed that phosphatidylcholine [PC, PC(16:1e/18:1), PC(16:2e/18:0)] and sphingolipid [SM, SM(d18:2/24:1)] mediated a significant portion, ranging from 12.27% to 26.03% (p-value <0.05), of the observed increase in VFA. DISCUSSION: Based on the evidence from multiple model results, ATQ and DMIP were statistically significantly associated with the increased VFA levels of healthy older adults, potentially regulated through lipid intermediators. These findings may have important implications for identifying potentially harmful environmental chemicals and developing targeted strategies for the control and prevention of chronic diseases in the future, particularly as the global population is rapidly aging. https://doi.org/10.1289/EHP13865.

Study of the Preparation and Performance of TiO2-Based Magnetic Regenerative Adsorbent.

Against the backdrop of "carbon neutrality", the green treatment of dye wastewater is particularly important. Currently, the adsorption method shows strong application prospects. Therefore, selecting efficient and recyclable adsorbents is of significant importance. TiO2 is an excellent adsorbent, but its difficult recovery often leads to secondary pollution. γ-Fe2O3-modified coal-series kaolin exhibits both excellent adsorption properties and rapid separation through magnetic separation technology. By utilizing the synergistic effects of both, TiO2/-γFe2O3 coal-series kaolin, magnetic adsorbent regeneration materials were prepared using coprecipitation method and characterized. The influencing factors of this functional material on the adsorption of Congo red dye and its regeneration performance are discussed. The experimental results indicated that the specific surface area, pore volume and Ms value of this functional material are 127.5 m2/g, 0.38 cm3/g, and 13.4 emu/g, respectively. It exhibits excellent adsorption characteristics towards Congo red, with an adsorption rate reaching 96.8% within 10 min, conforming to the pseudo-second-order kinetic model, and demonstrating Langmuir IV-type monolayer adsorption. After the adsorption of Congo red, magnetic separation shows superior efficiency. Furthermore, treatment of the adsorbed composite with EDTA allows for recycling, with adsorption rates still above 91% after three cycles, indicating an excellent regeneration capability.

Personal exposure to airborne organic pollutants and lung function changes among healthy older adults.

Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants' pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution.

Inhalation of ferrate-disinfected Escherichia coli caused lung injury via endotoxin-induced oxidative stress and inflammation response.

Ferrate (Fe(VI)) is an environmentally friendly disinfectant that is widely used to eradicate microbes in reclaimed water. However, the potential health risks associated with inhalation of Fe(VI)-treated bacteria-laden reclaimed water remains uncertain. We aimed to explore the inhalation hazards and potential mechanisms of K2FeO4-treated Escherichia coli (E. coli, ATCC 25922). Our findings indicated that Fe(VI) disinfection induced a dose- and time-dependent E. coli inactivation, accompanied by a rapid release of the bacterial endotoxin, lipopolysaccharide (LPS). Scanning electron microscopy (SEM) observations indicate that Fe(VI)-induced endotoxin production consists of at least two stages: initial binding of endotoxin to bacteria and subsequent dissociation to release free endotoxin. Furthermore, Fe(VI) disinfection was not able to effectively eliminate pure or E. coli-derived endotoxins. The E. coli strain used in this study lacks lung infection capability, thus the inhalation of bacteria alone failed to induce severe lung injury. However, mice inhaled exposure to Fe(VI)-treated E. coli showed severe impairment of lung structure and function. Moreover, we observed an accumulation of neutrophil/macrophage recruitment, cell apoptosis, and ROS generation in the lung tissue of mice subjected to Fe(VI)-treated E. coli. RNA sequencing (RNA-seq) and PCR results revealed that genes involved with endotoxin stimuli, cell apoptosis, antioxidant defence, inflammation response, chemokines and their receptors were upregulated in response to Fe(VI)-treated E. coli. In conclusion, Fe(VI) is ineffective in eliminating endotoxins and can trigger secondary hazards owing to endotoxin release from inactivated bacteria. Aerosol exposure to Fe(VI)-treated E. coli causes considerable damage to lung tissue by inducing oxidative stress and inflammatory responses.

Safety and Efficacy of Dry Eye Intelligent Therapeutic Device in the Treatment of Meibomian Gland Dysfunction in Rabbits.

PURPOSE: To assess the safety and efficacy of the dry eye intelligent therapeutic device in rabbits with meibomian gland dysfunction. METHODS: The meibomian gland dysfunction-afflicted rabbits were subjected to treatment using the dry eye intelligent therapeutic device. Various parameters, including eyelid margin, meibomian gland opening, redness, meibomian gland area, keratoconjunctival fluorescence staining, and intraocular pressure, were examined and analyzed using an ocular surface comprehensive examination instrument, slit lamp, and tonometer at corresponding times points. Hematoxylin and eosin staining was performed to examine the mucosal epithelium and meibomian gland. RESULTS: In this study, eyelid margin congestion and meibomian gland opening obstruction were significantly improved after 3 weeks and 4 weeks of treatment, respectively (p < .01, p < .05). The treatment group showed a significant increase in tear meniscus height after 2 weeks, 3 weeks and 4 weeks of treatment (p < .001, p < .01, p < .05). No significant changes were noted in meibomian gland area, redness, intraocular pressure, and keratoconjunctival fluorescence staining of rabbits before and after treatment. Hematoxylin and eosin staining revealed a complete structure of mucosal epithelium and meibomian gland in the treatment group and that the expansion of the blocked meibomian gland duct was reduced. CONCLUSION: The utilization of the dry eye intelligent therapeutic device in treating meibomian gland dysfunction-afflicted rabbits exhibits potential promising safety, efficacy, and overall benefits, thereby offering a novel alternative for managing meibomian gland dysfunction patients in clinical settings.

Depth-Aware Unpaired Video Dehazing.

This paper investigates a novel unpaired video dehazing framework, which can be a good candidate in practice by relieving pressure from collecting paired data. In such a paradigm, two key issues including 1) temporal consistency uninvolved in single image dehazing, and 2) better dehazing ability need to be considered for satisfied performance. To handle the mentioned problems, we alternatively resort to introducing depth information to construct additional regularization and supervision. Specifically, we attempt to synthesize realistic motions with depth information to improve the effectiveness and applicability of traditional temporal losses, and thus better regularizing the spatiotemporal consistency. Moreover, the depth information is also considered in terms of adversarial learning. For haze removal, the depth information guides the local discriminator to focus on regions where haze residuals are more likely to exist. The dehazing performance is consequently improved by more pertinent guidance from our depth-aware local discriminator. Extensive experiments are conducted to validate our effectiveness and superiority over other competitors. To the best of our knowledge, this study is the initial foray into the task of unpaired video dehazing. Our code is available at https://github.com/YaN9-Y/DUVD.

Isolation and characterization of rabbit limbal niche cells.

Limbal niche cells (LNCs) are one of the most important supporting cells for corneal epithelial stem cells (CES), however, research on LNCs has been mostly limited to humans and rats previously. To expand the research work into the rabbit animal model, one of the most often used animals in stem cell study, this study was carried out for the in vitro isolation and identification of rabbit LNCs. Rabbit LNCs were isolated by collagenase A digestion method and single cells were obtained, the cells were then seeded on 5% Matrigel-coated plastic surface and cultured in modified embryonic stem cell medium (MESCM). Three biological replicates of the isolating and characterization were recorded from New Zealand White rabbits aged from 2.5 months to 5 months. LNC markers (VIM/CD90/CD105/SCF/PDGFRß) were analyzed using tyramide signal amplification (TSA) staining, immunohistochemical staining (IHC), western blotting (WB), and real-time reverse transcription polymerase chain reaction (qPCR). TSA staining suggested that VIM was highly expressed in rabbit limbus stroma, which was confirmed by WB, and P63α was expressed in the basal limbus epithelium. Pan-CK and CK12 were highly expressed in the central corneal epithelium but lightly expressed in the limbal epithelium. The WB result indicated that PDGFRß and VIM expressions in rabbit-LNCs P4 were higher than in P1 and P7. In addition, rabbit corneal epithelium highly expressed Paired Box 6 (PAX6) and Epidermal growth factor-like domain 6(EGFL6). For the three repeat experiments, the cell expansion activity of rabbit-LNC was highest at P4. Rabbit-LNCs were passaged from P0 to P7, and the number of cell doublings (NCD) of P4 for the three repeat experiments was 2.816, 2.737, and 2.849. qPCR showed that high mRNA expression levels of VIM, CD90, CD105, SCF, and PDGFRß in rabbit-LNCs P4. In conclusion, rabbit-LNCs could be successfully isolated by the collagenase A digestion method as used in human tissue. There were similar characteristics between rabbit and human LNCs (VIM+/CD90+/CD105+/SCF+/PAX6+/PDGFRß+).

Pain Characteristics of Patients With Fibromyalgia: A Comparison Between Gender and Different Emotional States.

BACKGROUND: Generalized pain is the core symptom of fibromyalgia (FM). Few studies have described FM's different pain characteristics under various conditions. OBJECTIVE: To explore the pain characteristics of patients with FM of different gender and emotional states. STUDY DESIGN: A cross-sectional study. SETTING: A medical center in Beijing, People's Republic of China. METHODS: A total of 197 patients with FM were recruited from an outpatient clinic. Three distinct instruments were used to assess their pain characteristics: the Numeric Rating Scale (NRS-11) to assess pain severity, the Widespread Pain Index (WPI) to assess the number of pain regions, and the Short Form-McGill Pain Questionnaire-2 (SF-MPQ-2) to assess pain qualities. The Zung Self-Rating Anxiety Scale and Zung Self-Rating Depression Scale were used to assess patients' emotional states. An independent 2-sample t test, chi-squared test, and Mann-Whitney U test were used to analyze gender pain characteristics differences and different emotional states (with/without anxiety, with/without depression). RESULTS: Pain severity on the NRS-11 was 7 (5-8), the number of pain regions determined by WPI was 13 (10-16), and the total score of different pain qualities from the SF-MPQ-2 was 2.36 (1.68-3.73) in all patients with FM. The most frequently reported regions of pain were the right shoulder girdle (89.34%), left shoulder girdle (88.32%), upper back (85.28%), and neck (81.73%). The most frequently reported pain qualities were tiredness/exhaustion (97.46%), aching pain (94.42%), numbness (78.68%), cold/freezing pain (75.63%), and tenderness (75.13%). Women patients reported more severe pain and numbness, less frequent chest pain, and shooting pain than men patients did. Patients with FM and anxiety experienced more frequent and more severe feelings of punishing/cruel thoughts, fearfulness, sickening, and tenderness; more frequent jaw pain and cold-freezing pain; more severe pain caused by light touch and tiredness/exhaustion; less frequent lower leg pain than those without anxiety did. Patients with FM and depression reported more frequent and more severe pain caused by light touch; more frequent tenderness; more severe feelings of tiredness/exhaustion, sickening,fearfulness, and punishing/cruel thoughts; and less frequent and less severe piercing pain than those without depression did. LIMITATIONS: The limitations of this study are its single-center design and lack of objective pain indicators. CONCLUSION: Gender significantly affected pain severity, chest pain, numbness, and shooting pain. Jaw pain, lower leg pain, cold/freezing pain, tenderness, pain caused by light touch, piercing pain, and pain-affective descriptors are closely related to emotional states in FM. A comprehensive understanding of pain characteristics in patients with FM would be helpful for disease education, diagnosis, and treatment.

Feasibility for High-Temperature Graphitization of Deformed Meager Coal.

The flattening of nanoscale pores is a crucial step in the process of anthracite graphitization, which primarily occurs due to lithostatic pressure or tectonic stress. Anthracite, a highly metamorphosed form of carbonaceous material, is a primary component of artificial graphite, but its availability is limited in China. Therefore, it is necessary to investigate the graphitization of low metamorphic coal. Note that the pores of deformed coal are substantially compressed, and the evolution of macromolecular structure is accelerated owing to strong tectonic extrusion and shearing action. Herein, the feasibility analysis of coal-based graphite at temperatures of 2200 and 2600 °C was investigated using mylonitized meager coal (YA-M; Ro,max = 2.34%), which exhibits the most intense deformation intensity, and it was compared with undeformed coal (YA-U; Ro,max = 1.87%) from the same coal seam. Results indicate that YA-U primarily consists of cylindrical pores with an average pore diameter of 10 nm, while YA-M exhibits extensive fine bottleneck and parallel plate pores with an average pore size of ∼4 nm. Additionally, interlayer spacing decreases from 0.3592 nm in YA-U to 0.3575 nm in YA-M, while crystallite height increases from 1.9633 nm in YA-U to 2.1424 nm in YA-M. The undeformed coal YA-U exhibits short and disordered aromatic fringes with a localized turbostratic structure that hinders graphitization. In contrast, YA-M exhibits more and longer localized fringe pairs arranged in parallel with improved structural ordering, indicating a favorable environment for graphitization. Ductile deformation narrows the pore diameter distribution, causing deformation pores on the mylonitic granules' surface to close, shrink directionally, collapse, or connect, resulting in obvious flattening characteristics of nanoscale. Based on these results, the graphitization degree of the graphitized products YA-GM-2200 and YA-GM-2600 was 80.23% and 88.37%, respectively, with interlayer spacings of 0.3371 and 0.3364 nm, indicating that these products have entered the semigraphite (medium graphitization) and graphite range, respectively. In contrast, the graphitization degree of YA-GU-2200 and YA-GU-2600 was only 51.16% and 56.98%, respectively, indicating that they have only progressed from anthracite to meta-anthracite (the preliminary graphitization stage). These findings confirm the view that the shear stress generated by the geological age flattens the pores of mylonitized meager coal and optimizes the aromatic lattice arrangement and orientation, facilitating graphitization and lowering the graphitization temperature (from 2800 to 2200 °C). Deformed coal is soft and can be easily crushed into powdered form using the human hand, making it less suitable for transportation. Additionally, owing to the unfavorable separation of minerals and lower hydrocarbon-generating potential, deformed coal application potential and price are consistently lower than those of undeformed coal. However, deformed coal is widely distributed in various coal measures in China, making these research findings valuable in promoting the high value-added utilization of low-rank deformed coal resources and expanding the carbon source of coal-based graphite materials.

Functional reorganization of brain activity in children with attention-deficit/hyperactivity disorder: Evidence from the modulatory effect of cognitive demand during visuospatial attention task.

Previous studies reported that the inferior parietal lobule (IPL) had lower activation during visuospatial attention in children with attention-deficit/hyperactivity disorder (ADHD), while the functional connectivity (FC) between the IPL and other brain regions and how cognitive demand might modulate IPL's FC remain unclear. We performed a functional magnetic resonance imaging experiment recruiting two task conditions with relatively low and high cognitive demand of visuospatial attention. Forty-four children with ADHD and 36 age- and sex-matched healthy controls were included. IPL's regional activation and FC intensities were compared between groups and correlated with clinical measurements. We found that the IPL had significantly reduced activation in children with ADHD compared to healthy controls and this abnormal activation was not modulated by the cognitive demand of visuospatial attention. Importantly, further analysis revealed that the functional connectivity between IPL and inferior frontal gyrus was modulated by the cognitive demand of visuospatial attention in children with ADHD. These results revealed a modulatory effect of cognitive demand of visuospatial attention on IPL's functional connectivity but not IPL's activation in children with ADHD. More generally, these results highlight the functional reorganization of the brain activity as a possible compensatory strategy in response to the symptoms of ADHD.

Exploring the Potential "Brain-Cognition-Behavior" Relationship in Children With ADHD Based on Resting-State Brain Local Activation and Functional Connectivity.

OBJECTIVE: Exploring how abnormal brain function in children with ADHD affects executive function and ultimately leads to behavioral impairment provides a theoretical basis for clinically targeted neurotherapy and cognitive training. METHOD: Amplitude of low frequency fluctuations (ALFF), regional homogeneity (ReHo), and seed-based FC were analyzed in 53 ADHD and 52 healthy controls. The "brain-cognition-behavior" relationship was further explored using mediation analysis. RESULTS: ADHD showed abnormal local activation in the middle temporal gyrus (MTG), inferior occipital gyrus and inferior frontal gyrus (IFG) and reduced FC between the IFG and the cerebellum. ADHD diagnosis may affect ALFF of MTG and further modulate shift and finally affect inattentive symptoms. It may also affect the total symptoms through the FC of the IFG with the cerebellum. CONCLUSION: ADHD showed extensive spontaneous activity abnormalities and frontal-cerebellar FC impairments. Localized functional abnormalities in the MTG may affect the shift in EF, resulting in attention deficit behavior.

Symptom-guided multimodal neuroimage fusion patterns in children with attention-deficit/hyperactivity disorder and its potential "brain structure-function-cognition-behavior" pathological pathways.

The "brain-cognition-behavior" process is an important pathological pathway in children with attention-deficit/hyperactivity disorder (ADHD). Symptom guided multimodal neuroimaging fusion can capture behaviorally relevant and intrinsically linked structural and functional features, which can help to construct a systematic model of the pathology. Analyzing the multimodal neuroimage fusion pattern and exploring how these brain features affect executive function (EF) and leads to behavioral impairment is the focus of this study. Based on gray matter volume (GMV) and fractional amplitude of low frequency fluctuation (fALFF) for 152 ADHD and 102 healthy controls (HC), the total symptom score (TO) was set as a reference to identify co-varying components. Based on the correlation between the identified co-varying components and EF, further mediation analysis was used to explore the relationship between brain image features, EF and clinical symptoms. This study found that the abnormalities of GMV and fALFF in ADHD are mainly located in the default mode network (DMN) and prefrontal-striatal-cerebellar circuits, respectively. GMV in ADHD influences the TO through Metacognition Index, while fALFF in HC mediates the TO through behavior regulation index (BRI). Further analysis revealed that GMV in HC influences fALFF, which further modulates BRI and subsequently affects hyperactivity-impulsivity score. To conclude, structural brain abnormalities in the DMN in ADHD may affect local brain function in the prefrontal-striatal-cerebellar circuit, making it difficult to regulate EF in terms of inhibit, shift, and emotional control, and ultimately leading to hyperactive-impulsive behavior.

Purely nonlinear amplified ultralow-noise transmission using hybrid second-order DRA and PPLN-based PSA.

We report ultralow-noise transmission over a 102-km single-mode fiber using a purely nonlinear amplification scheme consisting of a second-order distributed Raman amplifier (DRA) and a phase-sensitive amplifier (PSA) based on periodically poled LiNbO3 waveguides. The hybrid DRA/PSA features a broadband gain over the C and L bands and an ultralow-noise advantage, with a less than -6.3 dB effective noise figure in the DRA stage and a 1.6 dB optical signal-to-noise ratio (OSNR) improvement in the PSA stage. Compared with the unamplified link, the OSNR is improved by 10.2 dB for a 20-Gbaud 16QAM signal in the C band, resulting in error-free detection (a bit-error rate of less than 3.8 × 10-3) for the signal with a low link input power of -25 dBm. Mitigation of nonlinear distortion is also achieved by the proposed nonlinear amplified system due to the subsequent PSA.

Deep-learning-based biomarker of spinal cartilage endplate health using ultra-short echo time magnetic resonance imaging.

Background: T2* relaxation times in the spinal cartilage endplate (CEP) measured using ultra-short echo time magnetic resonance imaging (UTE MRI) reflect aspects of biochemical composition that influence the CEP's permeability to nutrients. Deficits in CEP composition measured using T2* biomarkers from UTE MRI are associated with more severe intervertebral disc degeneration in patients with chronic low back pain (cLBP). The goal of this study was to develop an objective, accurate, and efficient deep-learning-based method for calculating biomarkers of CEP health using UTE images. Methods: Multi-echo UTE MRI of the lumbar spine was acquired from a prospectively enrolled cross-sectional and consecutive cohort of 83 subjects spanning a wide range of ages and cLBP-related conditions. CEPs from the L4-S1 levels were manually segmented on 6,972 UTE images and used to train neural networks utilizing the u-net architecture. CEP segmentations and mean CEP T2* values derived from manually- and model-generated segmentations were compared using Dice scores, sensitivity, specificity, Bland-Altman, and receiver-operator characteristic (ROC) analysis. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated and related to model performance. Results: Compared with manual CEP segmentations, model-generated segmentations achieved sensitives of 0.80-0.91, specificities of 0.99, Dice scores of 0.77-0.85, area under the receiver-operating characteristic curve values of 0.99, and precision-recall (PR) AUC values of 0.56-0.77, depending on spinal level and sagittal image position. Mean CEP T2* values and principal CEP angles derived from the model-predicted segmentations had low bias in an unseen test dataset (T2* bias =0.33±2.37 ms, angle bias =0.36±2.65°). To simulate a hypothetical clinical scenario, the predicted segmentations were used to stratify CEPs into high, medium, and low T2* groups. Group predictions had diagnostic sensitivities of 0.77-0.86 and specificities of 0.86-0.95. Model performance was positively associated with image SNR and CNR. Conclusions: The trained deep learning models enable accurate, automated CEP segmentations and T2* biomarker computations that are statistically similar to those from manual segmentations. These models address limitations with inefficiency and subjectivity associated with manual methods. Such techniques could be used to elucidate the role of CEP composition in disc degeneration etiology and guide emerging therapies for cLBP.

Irisin drives macrophage anti-inflammatory differentiation via JAK2-STAT6-dependent activation of PPARγ and Nrf2 signaling.

Irisin is an exercise-induced myokine that alleviates inflammation and obesity. The induction of anti-inflammatory (M2) macrophage is facilitated for treatment of sepsis and associated lung damage. However, whether irisin drives macrophage M2 polarization remains unclear. Here, we found that irisin induced-macrophage anti-inflammatory differentiation in vivo using an LPS-induced septic mice model and in vitro using RAW64.7 cells and bone marrow-derived macrophages (BMDMs). Irisin also promoted the expression, phosphorylation, and nuclear translocation of peroxisome proliferator-activated receptor gamma (PPAR-γ) and nuclear factor-erythroid 2-related factor 2 (Nrf2). Inhibition or knockdown of PPAR-γ and Nrf2 abolished irisin-induced accumulation of M2 macrophage markers, such as interleukin (IL)-10 and Arginase 1. Furthermore, dual-luciferase reporter and chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) assays confirmed that STAT6 boosts PPAR-γ and Nrf2 transcription by binding to their DNA promoters in irisin-stimulated macrophages. In contrast, STAT6 shRNA blocked the irisin-induced activation of Pparγ, Nrf2, and related downstream genes. Moreover, the interaction of irisin with its ligand integrin αVß5 remarkably promoted Janus kinase 2 (JAK2) phosphorylation, while inhibition or knockdown of integrin αVß5 and JAK2 attenuated the activation of STAT6, PPAR-γ, and Nrf2 signaling. Interestingly, co-immunoprecipitation (Co-IP) assay also revealed that the binding between JAK2 and integrin αVß5 is critical for irisin-induced macrophage anti-inflammatory differentiation by enhancing the activation of the JAK2-STAT6 pathway. In conclusion, irisin boosted M2 macrophage differentiation by inducing JAK2-STAT6-dependent transcriptional activation of the PPAR-γ-related anti-inflammatory system and Nrf2-related antioxidant genes. The findings of this study suggest that the administration of irisin is a novel and promising therapeutic strategy for infectious and inflammatory diseases.

Cross-cultural adaptation and validation of the Chinese version of the short-form of the Central Sensitization Inventory (CSI-9) in patients with chronic pain: A single-center study.

Chronic pain affects more than 30% of the general population. The 9-item Central Sensitization Inventory (CSI-9) is a shortened version of the CSI-25, which is a patient-reported instrument used to screen people at risk of central sensitization (CS). The aim of this study was to cross-culturally adapt and validate a Chinese version of the CSI-9. The Chinese CSI-9 was generated by translation of the original English version, back-translation, cultural adaptation, and revision using the Delphi method. The Chinese CSI-9 was administered to 235 patients with chronic pain and 55 healthy controls. Structural validity (confirmatory factor analysis), construct validity (correlations with other scales), test-retest reliability (intraclass correlation coefficient, ICC), and internal consistency (Cronbach's α) were evaluated. Confirmatory factor analysis was performed using one factor. The Chinese CSI-9 score was positively correlated with the Pain Catastrophic Scale (PCS) total score (r = 0.463), PCS subscale scores (r = 0.347-0.463), Brief Pain Inventory (BPI) mean item score (r = 0.524), BPI total score (r = 0.773), and the number of painful sites (r = 0.451). The Chinese CSI-9 had excellent test-retest reliability (ICC = 0.958) and excellent internal consistency (Cronbach's α = 0.902 in the overall sample and 0.828 in the chronic pain population). The optimal cut-off value for the Chinese CSI-9 was 18 points. The Chinese CSI-9 had excellent test-retest reliability and satisfactory structural validity and construct validity. The CSI-9 could potentially be utilized in China as a self-report questionnaire in both clinical practice and research settings.

First donor haemovigilance system at a national level in China: Establishment and improvement.

BACKGROUND AND OBJECTIVES: No systematic study has measured the incidence of adverse reactions (ARs) to blood donation at the national level in China before 2019. The objective of this study was to establish an effective reporting system to collect information on ARs to blood donation in China. MATERIALS AND METHODS: The status of donor haemovigilance (DHV) in blood collection facilities in China was evaluated, and an online DHV system was established to collect data on ARs to blood donation in July 2019. The definitions of ARs were based on the International Society of Blood Transfusion (ISBT) standards. The prevalence and data quality of ARs from 2019 to 2021 were analysed. RESULTS: A standard online reporting system has been established for ARs to blood donation. In total, 61, 62 and 81 participating sites were included in this pilot study in 2019, 2020 and 2021, respectively. From July 2019 to December 2021, 21,502 cases of whole-blood-related ARs and 1114 cases of apheresis platelet-related ARs were reported, with an incidence of 3.8‰ and 2.2‰, respectively. Data completeness for key reporting elements improved from 41.7% (15/36) in 2019 to 74.4% (29/39) in 2020. Data quality analysis for the year 2021 yielded similar results as for 2020. CONCLUSION: The construction and continuous improvement of the blood donor safety monitoring system prompted the establishment of the DHV system. Improvements have been made to the DHV system in China, with a significant increase in sentinels and higher data quality.

ISSLS Prize in Bioengineering Science 2023: Age- and sex-related differences in lumbar intervertebral disc degeneration between patients with chronic low back pain and asymptomatic controls.

PURPOSE: Clinical management of disc degeneration in patients with chronic low back pain (cLBP) is hampered by the challenge of distinguishing pathologic changes relating to pain from physiologic changes related to aging. The goal of this study was to use imaging biomarkers of disc biochemical composition to distinguish degenerative changes associated with cLBP from normal aging. METHODS: T1ρ MRI data were acquired from 133 prospectively enrolled subjects for this observational study (80 cLBP, 53 controls; mean ± SD age = 43.9 ± 13.4 years; 61 females, 72 males). The mean T1ρ relaxation time in the nucleus pulposus (NP-T1ρ; n = 650 discs) was used as a quantitative biomarker of disc biochemical composition. Linear regression was used to assess associations between NP-T1ρ and age, sex, spinal level, and study group, and their interactions. RESULTS: NP-T1ρ values were lower in cLBP patients than controls (70.8 ± 22.8 vs. 76.4 ± 22.2 ms, p = 0.009). Group differences were largest at L5-S1 (ΔT1ρcLBP-control = -11.3 ms, p < 0.0001), representing biochemical deterioration typically observed over a 9-12 year period (NP-T1ρ declined by 0.8-1.1 ms per year [95% CI]). Group differences were large in younger patients and diminished with age. Finally, the age-dependence of disc degeneration was stronger in controls than cLBP patients. CONCLUSION: Aging effects on the biochemical composition of the L5-S1 disc may involve a relatively uniform set of factors from which many cLBP patients deviate. NP-T1ρ values at L5-S1 may be highly relevant to clinical phenotyping, particularly in younger individuals.

Deep Graph Translation.

Deep generative models for graphs have recently achieved great successes in modeling and generating graphs for studying networks in biology, engineering, and social sciences. However, they are typically unconditioned generative models that have no control over the target graphs given a source graph. In this article, we propose a novel graph-translation-generative-adversarial-nets (GT-GAN) model that transforms the source graphs into their target output graphs. GT-GAN consists of a graph translator equipped with innovative graph convolution and deconvolution layers to learn the translation mapping considering both global and local features. A new conditional graph discriminator is proposed to classify the target graphs by conditioning on source graphs while training. Extensive experiments on multiple synthetic and real-world datasets in the domain of cybernetworks, the Internet of Things, and neuroscience demonstrate that the proposed GT-GAN model significantly outperforms other baseline methods in terms of both effectiveness and scalability. For instance, GT-GAN outperforms the classical state-of-the-art (SOTA) methods in functional connectivity (FC) prediction of brain networks by at least 32.5%.

A randomized controlled study of remote computerized cognitive, neurofeedback, and combined training in the treatment of children with attention-deficit/hyperactivity disorder.

There is an increasing interest in non-pharmacological treatments for children with attention-deficit/hyperactivity disorder (AD/HD), especially digital techniques that can be remotely delivered, such as neurofeedback (NFT) and computerized cognitive training (CCT). In this study, a randomized controlled design was used to compare training outcomes between remotely delivered NFT, CCT, and combined NFT/CCT training approaches. A total of 121 children with AD/HD were randomly assigned to the NFT, CCT, or NFT/CCT training groups, with 80 children completing the training program. Pre- and post-training symptoms (primary outcome), executive and daily functions were measured using questionnaires as well as resting EEG during eyes-closed (EC) and eyes-open (EO) conditions. After 3 months of training, the inattentive and hyperactive/impulsive symptoms, inhibition, working memory, learning and life skills of the three groups of children were significantly improved. The objective EEG activity showed a consistent increase in the relative alpha power in the EO condition among the three training groups. Training differences were not observed between groups. There was a positive correlation between pre-training EO relative alpha power and symptom improvement scores of inattention and hyperactivity/impulsivity, as well as a negative correlation between pre-training inattention scores and change in EO relative alpha. This study verified the training effects of NFT, CCT, and combined NFT/CCT training in children with AD/HD and revealed an objective therapeutic role for individual relative alpha activity. The verified feasibility and effectiveness of home-based digital training support promotion and application of digital remote training.