Photochromism from wavelength-selective colloidal phase segregation.

Phase segregation is ubiquitously observed in immiscible mixtures, such as oil and water, in which the mixing entropy is overcome by the segregation enthalpy1-3. In monodispersed colloidal systems, however, the colloidal-colloidal interactions are usually non-specific and short-ranged, which leads to negligible segregation enthalpy4. The recently developed photoactive colloidal particles show long-range phoretic interactions, which can be readily tuned with incident light, suggesting an ideal model for studying phase behaviour and structure evolution kinetics5,6. In this work, we design a simple spectral selective active colloidal system, in which TiO2 colloidal species were coded with spectral distinctive dyes to form a photochromic colloidal swarm. In this system, the particle-particle interactions can be programmed by combining incident light with various wavelengths and intensities to enable controllable colloidal gelation and segregation. Furthermore, by mixing the cyan, magenta and yellow colloids, a dynamic photochromic colloidal swarm is formulated. On illumination of coloured light, the colloidal swarm adapts the appearance of incident light due to layered phase segregation, presenting a facile approach towards coloured electronic paper and self-powered optical camouflage.

Bipolar Photoelectrochemistry for Phase-Modulated Optoelectronic Hybrid Nanomotor.

Complex micro/nanorobots may be constructed by integrating several independent, controlled nanomotors for high degrees of freedom of maneuvering and manipulation. However, designing nanomotors with distinctive responses to the same global stimuli is challenging due to the nanomotors' simple structure and limited material composition. In this work, we demonstrate that a nanomotor can be designed with the same principles of electronic circuits, where the motion of semiconductor particles can be controlled with synchronized electric and optical signals. This technique relies on transient bipolar photoelectrochemistry in semiconductor microparticles, where the reaction site selectivity is realized by modulating the light pulse in the time domain. Due to the microparticles' intrinsic resistance and surface capacitance, the nanomotors can be designed as an electronic circuit, enabling distinctive responses to the global electric/optical field and achieving the desired movement or deflection/rotation. This work gives new insight into the manipulation technique for independent and untethered nanomotor control. Ultimately, it exploits the potential for particle sorting based on geometry in time and frequency domain modulation.

SCD1 sustains brown fat sympathetic innervation and thermogenesis during the long-term cold exposure.

Brown fat adipose tissue (BAT) is a therapeutic potential target to improve obesity, diabetes and cold acclimation in mammals. During the long-term cold exposure, the hyperplastic sympathetic network is crucial for BAT the maintain the highly thermogenic status. It has been proved that the sympathetic nervous drives the thermogenic activity of BAT via the release of norepinephrine. However, it is still unclear that how the thermogenic BAT affects the remodeling of the hyperplastic sympathetic network, especially during the long-term cold exposure. Here, we showed that following long-term cold exposure, SCD1-mediated monounsaturated fatty acid biosynthesis pathway was enriched, and the ratios of monounsaturated/saturated fatty acids were significantly up-regulated in BAT. And SCD1-deficiency in BAT decreased the capacity of cold acclimation, and suppressed long-term cold mediated BAT thermogenic activation. Furthermore, by using thermoneutral exposure and sympathetic nerve excision models, we disclosed that SCD1-deficiency in BAT affected the thermogenic activity, depended on sympathetic nerve. In mechanism, SCD1-deficiency resulted in the unbalanced ratio of palmitic acid (PA)/palmitoleic acid (PO), with obviously higher level of PA and lower level of PO. And PO supplement efficiently reversed the inhibitory role of SCD1-deficiency on BAT thermogenesis and the hyperplastic sympathetic network. Thus, our data provided insight into the role of SCD1-mediated monounsaturated fatty acids metabolism to the interaction between thermogenic activity BAT and hyperplastic sympathetic networks, and illustrated the critical role of monounsaturated fatty acids biosynthetic pathway in cold acclimation during the long-term cold exposure.

Discovery of anticancer function of Febrifugine: Inhibition of cell proliferation, induction of apoptosis and suppression steroid synthesis in bladder cancer cells.

Bladder cancer is a prevalent malignancy affecting the urinary system, which presents a significant global health concern. Although there are many treatments for bladder cancer, identifying more effective drugs and methods remains an urgent problem. As a pivotal component of contemporary medical practice, traditional Chinese medicine (TCM) assumes a crucial role in the realm of anti-tumor therapy, especially with the identification of active ingredients and successful exploration of pharmacological effects. Febrifugine, identified as a quinazoline-type alkaloid compound extracted from the Cytidiaceae family plant Huangchangshan, exhibits heightened sensitivity to bladder cancer cells in comparison to control cells (non-cancer cells) group. The proliferation growth of bladder cancer cells T24 and SW780 was effectively inhibited by Febrifugine, and the IC50 was 0.02 and 0.018 µM respectively. Febrifugine inhibits cell proliferation by suppressing DNA synthesis and induces cell death by reducing steroidogenesis and promoting apoptosis. Combined with transcriptome analysis, Febrifugine was found to downregulate low density lipoprotein receptor-associated protein, lanosterol synthase, cholesterol biosynthesis second rate-limiting enzyme, 7-dehydrocholesterol reductase, flavin adenine dinucleotide dependent oxidoreductase and other factors to inhibit the production of intracellular steroids in bladder cancer T24 cells. The results of animal experiments showed that Febrifugine could inhibit tumor growth. In summary, the effect of Febrifugine on bladder cancer is mainly through reducing steroid production and apoptosis. Therefore, this study contributes to the elucidation of Febrifugine's potential as an inhibitor of bladder cancer and establishes a solid foundation for the future development of novel therapeutic agents targeting bladder cancer.

PET-MRI Applications and Future Prospects in Psychiatry.

This article reviews the synergistic application of positron emission tomography-magnetic resonance imaging (PET-MRI) in neuroscience with relevance for psychiatry, particularly examining neurotransmission, epigenetics, and dynamic imaging methodologies. We begin by discussing the complementary insights that PET and MRI modalities provide into neuroreceptor systems, with a focus on dopamine, opioids, and serotonin receptors, and their implications for understanding and treating psychiatric disorders. We further highlight recent PET-MRI studies using a radioligand that enables the quantification of epigenetic enzymes, specifically histone deacetylases, in the brain in vivo. Imaging epigenetics is used to exemplify the impact the quantification of novel molecular targets may have, including new treatment approaches for psychiatric disorders. Finally, we discuss innovative designs involving functional PET using [18F]FDG (fPET-FDG), which provides detailed information regarding dynamic changes in glucose metabolism. Concurrent acquisitions of fPET-FDG and functional MRI provide a time-resolved approach to studying brain function, yielding simultaneous metabolic and hemodynamic information and thereby opening new avenues for psychiatric research. Collectively, the review underscores the potential of a multimodal PET-MRI approach to advance our understanding of brain structure and function in health and disease, which could improve clinical care based on objective neurobiological features and treatment response monitoring. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Trends in research on cochlear implantation with inner ear malformation: a bibliometric and visualization analysis from 1986 to 2024.

OBJECTIVE: The aim of this study was to conduct a bibliometric and visualization analysis of research on cochlear implantation (CI) for inner ear malformations (IEMs) from 1986 to 2024. METHODS: A comprehensive literature search was performed using the Web of Science Core Collection Database, resulting in the identification of 431 relevant publications. Various data analysis and visualization tools, including VOSviewer, CiteSpace, and Bibliometrix, were utilized to analyze annual publication outputs, countries/regions and institutions, authors, journals and studies, keywords, and theme evolution. RESULTS: The study revealed an overall increasing trend in research output on CI for IEMs, with significant contributions from countries such as the United States, China, Turkey, Germany, and Italy. The analysis also identified key authors, research teams, journals, and studies that have made substantial contributions to the field. Furthermore, the study highlighted important research hotspots and trends, such as the classification of IEMs, outcomes of CI for IEMs, and the management of pediatric patients with IEMs. CONCLUSION: The findings of this study provide a comprehensive overview of the research landscape surrounding CI for IEMs. The results serve as a basis for future research topic selection and emphasize the need for enhanced international collaboration and the publication of high-impact research to further advance this field.

Machine learning-based prediction of the outcomes of cochlear implantation in patients with inner ear malformation.

OBJECTIVE: The objectives of this study are twofold: first, to visualize the structure of malformed cochleae through image reconstruction; and second, to develop a predictive model for postoperative outcomes of cochlear implantation (CI) in patients diagnosed with cochlear hypoplasia (CH) and incomplete partition (IP) malformation. METHODS: The clinical data from patients diagnosed with cochlear hypoplasia (CH) and incomplete partition (IP) malformation who underwent cochlear implantation (CI) at Beijing Tongren Hospital between January 2016 and August 2020 were collected. Radiological features were analyzed through 3D segmentation of the cochlea. Postoperative auditory speech rehabilitation outcomes were evaluated using the Categories of Auditory Performance (CAP) and the Speech Intelligibility Rating (SIR). This study aimed to investigate the relationship between cochlear parameters and postoperative outcomes. Additionally, a predictive model for postoperative outcomes was developed using the K-nearest neighbors (KNN) algorithm. RESULTS: In our study, we conducted feature selection by using patients' imaging and audiological attributes. This process involved methods such as the removal of missing values, correlation analysis, and chi-square tests. The findings indicated that two specific features, cochlear volume (V) and cochlear canal length (CDL), significantly contributed to predicting the outcomes of hearing and speech rehabilitation for patients with inner ear malformations. In terms of hearing rehabilitation, the KNN classification achieved an accuracy of 93.3%. Likewise, for speech rehabilitation, the KNN classification demonstrated an accuracy of 86.7%. CONCLUSION: The measurements obtained from the 3D reconstruction model hold significant clinical relevance. Despite the considerable variability in cochlear morphology across individuals, radiological features remain effective in predicting cochlear implantation (CI) prognosis for patients with inner ear malformations. The utilization of 3D segmentation techniques and the developed predictive model can assist surgeons in conducting preoperative cochlear structural measurements for patients with inner ear malformations. This, in turn, can offer a more informed perspective on the anticipated outcomes of cochlear implantation.

Enhanced Magnetoimpedance Effect in Co-Based Micron Composite CoFeNiSiB Ribbon Strips Coated by Carbon and FeCoGa Nanofilms for Sensing Applications.

Quenched Co-based ribbon strips are widely used in the fields of magnetic amplifier, magnetic head material, magnetic shield, electric reactor, inductance core, sensor core, anti-theft system label, and so on. In this study, Co-based composite CoFeNiSiB ribbon strips with a micron width were fabricated by micro-electro-mechanical systems (MEMS) technology. The carbon and FeCoGa nanofilms were deposited for surface modification. The effect of carbon and FeCoGa nanofilm coatings on the crystal structure, surface morphology, magnetic properties, and magnetoimpedance (MI) effect of composite ribbon strips were systematically investigated. The results show that the surface roughness and coercivity of the composite ribbon strips are minimum at a thickness of the carbon coating of 60 nm. The maximum value of MI effect is 41% at 2 MHz, which is approximately 2.4 times greater than plain ribbon and 1.6 times greater than FeCoGa-coated composite ribbon strip. The addition of a carbon layer provides a conductive path for high frequency currents, which effectively reduces the characteristic frequency of the composite ribbon strip. The FeCoGa coating is able to close the flux path and reduce the coercivity, which, in turn, increases the transverse permeability and improves the MI effect. The findings indicate that a successful combination of carbon layer and magnetostrictive FeCoGa nanofilm layer can improve the MI effect and magnetic field sensitivity of the ribbon strips, demonstrating the potential of the composite strips for local and micro area field sensing applications.

Colloidal Self-Assembly: From Passive to Active Systems.

Self-assembly fundamentally implies the organization of small sub-units into large structures or patterns without the intervention of specific local interactions. This process is commonly observed in nature, occurring at various scales ranging from atomic/molecular assembly to the formation of complex biological structures. Colloidal particles may serve as micrometer-scale surrogates for studying assembly, particularly for the poorly understood kinetic and dynamic processes at the atomic scale. Recent advances in colloidal self-assembly have enabled the programmable creation of novel materials with tailored properties. We here provide an overview and comparison of both passive and active colloidal self-assembly, with a discussion on the energy landscape and interactions governing both types. In the realm of passive colloidal assembly, many impressive and important structures have been realized, including colloidal molecules, one-dimensional chains, two-dimensional lattices, and three-dimensional crystals. In contrast, active colloidal self-assembly, driven by optical, electric, chemical, or other fields, involves more intricate dynamic processes, offering more flexibility and potential new applications. A comparative analysis underscores the critical distinctions between passive and active colloidal assemblies, highlighting the unique collective behaviors emerging in active systems. These behaviors encompass collective motion, motility-induced phase segregation, and exotic properties arising from out-of-equilibrium thermodynamics. Through this comparison, we aim to identify the future opportunities in active assembly research, which may suggest new application domains.

Tunable Self-Thermophoretic Nanomotors with Polymeric Coating.

Thermophoretic micro/nanomotors (MNMs) generate self-propulsion without a chemical reaction. Intrinsically, this promises excellent biocompatibility and is thus suitable for biomedical applications. However, their propulsion efficiency is severely limited due to the poor understanding of the thermophoretic process, which dominates the conversion from thermal energy into mechanical movement. We here developed a series of self-thermophoresis light-powered MNMs with variable surface coatings and discovered obvious self-thermophoresis propulsion enhancement of the polymeric layer. An intrinsically negative self-thermophoretic movement is also observed for the first time in the MNM system. We propose that enthalpic contributions from polymer-solvent interactions should play a fundamental role in the self-thermophoretic MNMs. Quantitative microcalorimetry and molecular dynamics simulations are performed to support our hypothesis. The polymer solvation enthalpy and coating thickness influences on self-thermophoresis are investigated, further highlighting the essential enthalpy contributions to thermophoresis. Our work indicates that surface grafting would be important in designing high-efficiency thermally driven nanorobotic systems for biomedical applications.

Characterizing systemic physiological effects on the blood oxygen level dependent signal of resting-state fMRI in time-frequency space using wavelets.

Systemic physiological dynamics, such as heart rate variability (HRV) and respiration volume per time (RVT), are known to account for significant variance in the blood oxygen level dependent (BOLD) signal of resting-state functional magnetic resonance imaging (rsfMRI). However, synchrony between these cardiorespiratory changes and the BOLD signal could be due to neuronal (i.e., autonomic activity inducing changes in heart rate and respiration) or vascular (i.e., cardiorespiratory activity facilitating hemodynamic changes and thus the BOLD signal) effects and the contributions of these effects may differ spatially, temporally, and spectrally. In this study, we characterize these brain-body dynamics using a wavelet analysis in rapidly sampled rsfMRI data with simultaneous pulse oximetry and respiratory monitoring of the Human Connectome Project. Our time-frequency analysis across resting-state networks (RSNs) revealed differences in the coherence of the BOLD signal and heartbeat interval (HBI)/RVT dynamics across frequencies, with unique profiles per network. Somatomotor (SMN), visual (VN), and salience (VAN) networks demonstrated the greatest synchrony with both systemic physiological signals when compared to other networks; however, significant coherence was observed in all RSNs regardless of direct autonomic involvement. Our phase analysis revealed distinct frequency profiles of percentage of time with significant coherence between BOLD and systemic physiological signals for different phase offsets across RSNs, suggesting that the phase offset and temporal order of signals varies by frequency. Lastly, our analysis of temporal variability of coherence provides insight on potential influence of autonomic state on brain-body communication. Overall, the novel wavelet analysis enables an efficient characterization of the dynamic relationship between cardiorespiratory activity and the BOLD signal in spatial, temporal, and spectral dimensions to inform our understanding of autonomic states and improve our interpretation of the BOLD signal.

Integrated multi-omics analyses reveal Jorunnamycin A as a novel suppressor for muscle-invasive bladder cancer by targeting FASN and TOP1.

BACKGROUND: Bladder cancer is a urological carcinoma with high incidence, among which muscle invasive bladder cancer (MIBC) is a malignant carcinoma with high mortality. There is an urgent need to develop new drugs with low toxicity and high efficiency for MIBC because existing medication has defects, such as high toxicity, poor efficacy, and side effects. Jorunnamycin A (JorA), a natural marine compound, has been found to have a high efficiency anticancer effect, but its anticancer function and mechanism on bladder cancer have not been studied. METHODS: To examine the anticancer effect of JorA on MIBC, Cell Counting Kit 8, EdU staining, and colony formation analyses were performed. Moreover, a xenograft mouse model was used to verify the anticancer effect in vivo. To investigate the pharmacological mechanism of JorA, high-throughput quantitative proteomics, transcriptomics, RT-qPCR, western blotting, immunofluorescence staining, flow cytometry, pulldown assays, and molecular docking were performed. RESULTS: JorA inhibited the proliferation of MIBC cells, and the IC50 of T24 and UM-UC-3 was 0.054 and 0.084 µM, respectively. JorA-induced significantly changed proteins were enriched in "cancer-related pathways" and "EGFR-related signaling pathways", which mainly manifested by inhibiting cell proliferation and promoting cell apoptosis. Specifically, JorA dampened the DNA synthesis rate, induced phosphatidylserine eversion, and inhibited cell migration. Furthermore, it was discovered that fatty acid synthase (FASN) and topoisomerase 1 (TOP1) are the JorA interaction proteins. Using DockThor software, the 3D docking structures of JorA binding to FASN and TOP1 were obtained (the binding affinities were - 8.153 and - 7.264 kcal/mol, respectively). CONCLUSIONS: The marine compound JorA was discovered to have a specific inhibitory effect on MIBC, and its potential pharmacological mechanism was revealed for the first time. This discovery makes an important contribution to the development of new high efficiency and low toxicity drugs for bladder cancer therapy.

Susceptibility of Eucalyptus trees to defoliation by the Eucalyptus snout beetle, Gonipterus sp. n. 2, is enhanced by high foliar contents of 1,8-cineole, oxalic acid and sucrose and low contents of palmitic and shikimic acid.

Gonipterus sp. n. 2 (Coleoptera, Curculionidae) is an invasive, commercially important weevil that causes large-scale defoliation of Eucalyptus trees. The weevil specifically feeds on young leaves and new shoots, thus reducing tree growth. The weevil displays a very strong preference for certain Eucalyptus genotypes, however, this behaviour and the chemistry underlying it is poorly understood, thereby complicating the selection of resistant trees. To elucidate the feeding preference of Gonipterus sp. n. 2, we assessed the relative levels of susceptibility of 62 Eucalyptus genotypes from 23 species using a laboratory choice assay. This revealed large intraspecific variation in susceptibility to weevil feeding, which for certain species, exceeded the interspecific variation. A semiquantitative metabolite profile analysis on 13 genotypes revealed strong correlations of 10 metabolites to feeding damage. The behavioural effects of the identified compounds were assessed through an in vitro feeding preference assay using artificial diets as well as under field conditions. This revealed three phagostimulants (1,8-cineole, oxalic acid and sucrose) and two feeding deterrent compounds (shikimic acid and palmitic acid) for Gonipterus sp. n. 2. These chemical markers can be applied to tree breeding programmes for the selection of resistant genotypes to reduce damage caused by Gonipterus weevils.

A prospective CSFV-PCV2 bivalent vaccine effectively protects against classical swine fever virus and porcine circovirus type 2 dual challenge and prevents horizontal transmission.

Classical swine fever virus (CSFV) infection leading to CSF outbreaks is among the most devastating swine diseases in the pig industry. Porcine circovirus type 2 (PCV2) infection, resulting in porcine circovirus-associated disease (PCVAD), is also a highly contagious disease affecting pig health worldwide. To prevent and control disease occurrence, multiple-vaccine immunization is necessary in contaminated areas or countries. In this study, a novel CSFV-PCV2 bivalent vaccine was constructed and demonstrated to be capable of eliciting humoral and cellular immune responses against CSFV and PCV2, respectively. Moreover, a CSFV-PCV2 dual-challenge trial was conducted on specific-pathogen-free (SPF) pigs to evaluate vaccine efficacy. All of the vaccinated pigs survived and showed no clinical signs of infection throughout the experimental period. In contrast, placebo-vaccinated pigs exhibited severe clinical signs of infection and steeply increased viremia levels of CSFV and PCV2 after virus challenge. Additionally, neither clinical signs nor viral detections were noted in the sentinel pigs when cohabitated with vaccinated-challenged pigs at three days post-inoculation of CSFV, indicating that the CSFV-PCV2 bivalent vaccine completely prevents horizontal transmission of CSFV. Furthermore, conventional pigs were utilized to evaluate the application of the CSFV-PCV2 bivalent vaccine in field farms. An adequate CSFV antibody response and a significant decrease in PCV2 viral load in the peripheral lymph nodes were observed in immunized conventional pigs, suggesting its potential for clinical application. Overall, this study demonstrated that the CSFV-PCV2 bivalent vaccine effectively elicited protective immune responses and the ability to prevent horizontal transmission, which could be a prospective strategy for controlling both CSF and PCVAD in commercial herds.

Cluster analysis of patients with chronic rhinosinusitis and asthma after endoscopic sinus surgery.

BACKGROUND: Patients with chronic rhinosinusitis with nasal polyps and asthma (CRSwAS) are highly heterogenous in severity and prognosis. The clinical phenotypes and inflammatory endotypes of CRSwAS and their association with outcomes of endoscopic sinus surgery (ESS) have not been fully studied yet. OBJECTIVE: We aimed to find out the clinical phenotypes of CRSwAS and explore their relationship with ESS outcomes using cluster analysis. METHODS: We recruited 103 consecutive adult patients with CRSwAS who had undergone ESS and been followed up for more than 1 year. For cluster analysis, we collected the data from 63 variables pertaining to demographic characteristics, preoperative disease status, surgical techniques, postoperative medical treatment, and outcomes. Eosinophilic CRS was defined as greater than or equal to 10 eosinophils/high-power field, and sinus computed tomography was evaluated by Lund-Mackay sinus computed tomography score (LM score). RESULTS: We screened 92 eligible patients and 13 preoperative variables for balanced iterative reducing and clustering using hierarchies cluster analysis. Patients with CRSwAS were divided into 4 clusters with distinct ESS outcomes: (1) cluster 1, characterized by aspirin-exacerbated respiratory disease, eosinophilic CRS, high preoperative LM score, moderate-to-severe asthma, and uncontrolled CRS after ESS; (2) cluster 2, characterized as having female dominance (66.67%), non-aspirin-exacerbated respiratory disease, eosinophilic CRS, high preoperative LM score, moderate-to-severe asthma, and uncontrolled CRS after ESS; (3) cluster 3, characterized as having female dominance (95.83%), noneosinophilic CRS, low preoperative LM score, moderate asthma, and controlled CRS after ESS; and (4) cluster 4, characterized as men-only, smoker, noneosinophilic CRS, low preoperative LM score, mild asthma, and controlled CRS after ESS. CONCLUSION: CRSwAS has distinct clusters, each corresponding to unique clinical and inflammatory characteristics and ESS outcomes.

Cochlear Implant Facilitates the Use of Talker Sex and Spatial Cues to Segregate Competing Speech in Unilaterally Deaf Listeners.

OBJECTIVES: Talker sex and spatial cues can facilitate segregation of competing speech. However, the spectrotemporal degradation associated with cochlear implants (CIs) can limit the benefit of talker sex and spatial cues. Acoustic hearing in the nonimplanted ear can improve access to talker sex cues in CI users. However, it's unclear whether the CI can improve segregation of competing speech when maskers are symmetrically placed around the target (i.e., when spatial cues are available), compared with acoustic hearing alone. The aim of this study was to investigate whether a CI can improve segregation of competing speech by individuals with unilateral hearing loss. DESIGN: Speech recognition thresholds (SRTs) for competing speech were measured in 16 normal-hearing (NH) adults and 16 unilaterally deaf CI users. All participants were native speakers of Mandarin Chinese. CI users were divided into two groups according to thresholds in the nonimplanted ear: (1) single-sided deaf (SSD); pure-tone thresholds <25 dB HL at all audiometric frequencies, and (2) Asymmetric hearing loss (AHL; one or more thresholds > 25 dB HL). SRTs were measured for target sentences produced by a male talker in the presence of two masker talkers (different male or female talkers). The target sentence was always presented via loudspeaker directly in front of the listener (0°), and the maskers were either colocated with the target (0°) or spatially separated from the target at ±90°. Three segregation cue conditions were tested to measure masking release (MR) relative to the baseline condition: (1) Talker sex, (2) Spatial, and (3) Talker sex + Spatial. For CI users, SRTs were measured with the CI on or off. RESULTS: Binaural MR was significantly better for the NH group than for the AHL or SSD groups ( P < 0.001 in all cases). For the NH group, mean MR was largest with the Talker sex + spatial cues (18.8 dB) and smallest for the Talker sex cues (10.7 dB). In contrast, mean MR for the SSD group was largest with the Talker sex + spatial cues (14.7 dB), and smallest with the Spatial cues (4.8 dB). For the AHL group, mean MR was largest with the Talker sex + spatial cues (7.8 dB) and smallest with the Talker sex (4.8 dB) and the Spatial cues (4.8 dB). MR was significantly better with the CI on than off for both the AHL ( P = 0.014) and SSD groups ( P < 0.001). Across all unilaterally deaf CI users, monaural (acoustic ear alone) and binaural MR were significantly correlated with unaided pure-tone average thresholds in the nonimplanted ear for the Talker sex and Talker sex + spatial conditions ( P < 0.001 in both cases) but not for the Spatial condition. CONCLUSION: Although the CI benefitted unilaterally deaf listeners' segregation of competing speech, MR was much poorer than that observed in NH listeners. Different from previous findings with steady noise maskers, the CI benefit for segregation of competing speech from a different talker sex was greater in the SSD group than in the AHL group.

Thromboxane-Prostanoid Receptor Signaling Drives Persistent Fibroblast Activation in Pulmonary Fibrosis.

Rationale: Although persistent fibroblast activation is a hallmark of idiopathic pulmonary fibrosis (IPF), mechanisms regulating persistent fibroblast activation in the lungs have not been fully elucidated. Objectives: On the basis of our observation that lung fibroblasts express TBXA2R (thromboxane-prostanoid receptor) during fibrosis, we investigated the role of TBXA2R signaling in fibrotic remodeling. Methods: We identified TBXA2R expression in lungs of patients with IPF and mice and studied primary mouse and human lung fibroblasts to determine the impact of TBXA2R signaling on fibroblast activation. We used TBXA2R-deficient mice and small-molecule inhibitors to investigate TBXA2R signaling in preclinical lung fibrosis models. Measurements and Main Results: TBXA2R expression was upregulated in fibroblasts in the lungs of patients with IPF and in mouse lungs during experimental lung fibrosis. Genetic deletion of TBXA2R, but not inhibition of thromboxane synthase, protected mice from bleomycin-induced lung fibrosis, thereby suggesting that an alternative ligand activates profibrotic TBXA2R signaling. In contrast to thromboxane, F2-isoprostanes, which are nonenzymatic products of arachidonic acid induced by reactive oxygen species, were persistently elevated during fibrosis. F2-isoprostanes induced TBXA2R signaling in fibroblasts and mediated a myofibroblast activation profile due, at least in part, to potentiation of TGF-ß (transforming growth factor-ß) signaling. In vivo treatment with the TBXA2R antagonist ifetroban reduced profibrotic signaling in the lungs, protected mice from lung fibrosis in three preclinical models (bleomycin, Hermansky-Pudlak mice, and radiation-induced fibrosis), and markedly enhanced fibrotic resolution after bleomycin treatment. Conclusions: TBXA2R links oxidative stress to fibroblast activation during lung fibrosis. TBXA2R antagonists could have utility in treating pulmonary fibrosis.

Effect of multidisciplinary team (MDT) centred on pregnant women with pulmonary hypertension on treatment and outcomes of pregnancy.

BACKGROUND: The importance of multidisciplinary team (MDT) centred on pregnant women with pulmonary hypertension (PH) has been highlighted. However, rare studies have explored its effects on pregnancy outcomes. This study seeks to investigate whether and how the MDT has an effect on the treatment and outcomes of PH pregnant women. METHODS: A pre- and post-intervention study was conducted based on an interrupted time series design to compare the treatment and outcomes of patients with PH before (pre-MDT) and after (post-MDT) implementation of the MDT. PH was defined as pulmonary artery systolic pressure (sPAP) ≥ 35 mmHg measured by echocardiography or right heart catheterization and sPAP at 35-60 mmHg and over 60 mmHg was defined as mild and severe PH, respectively. All results were analyzed by T-tests, Chi square tests or Fisher exact test and two-sided p value < 0.05 was set to be statistically significant. RESULTS: 149 pregnancies were found in 143 women with PH. Overall, 46 pregnancies were elective abortions, remaining 49 and 54 pregnancies completing delivery in the pre-MDT group and post-MDT group, respectively. Five (10.2%) mother and seven (8.6%) neonatal died in the former, while no maternal deaths but 1.9% neonatal death occurred in the latter. In subgroup analysis, maternal and fetal/neonatal complications were higher in patients with severe PH and World Health Organization functional class (WHO FC) III/IV and all maternal deaths occurred in class III/IV women. In pre-MDT and post-MDT groups, there were 8 and 22 pregnant women receiving the pulmonary-specific therapy and completing delivery, respectively. The percentage of heart failure and urgent cesarean of pre-MDT group was higher than the post-MDT group (30.6% vs. 12.9%, p = 0.02; 40.8% vs. 14.8%, p = 0.01, respectively). CONCLUSION: Implementing the MDT decreased the rate of urgent caesarean section and heart failure in patients with PH and no maternal deaths occurred in the post-MDT group. Pregnant women with severe PH and WHO FC III/IV might have a poor prognosis, whereas the use of pulmonary-specific therapy might improve outcomes of pregnancy.

NLRP3 deficiency protects against hypobaric hypoxia induced neuroinflammation and cognitive dysfunction.

As increasing number of people migrated to high altitude, highland encephalopathy and hypoxia-induced cognitive impairment arouse public attention. Yet, its underlying mechanisms remain unclear. Emerging evidence has implied neuroinflammation and neuronal loss may be involved. In the present study, we investigated the neuroinflammation and neuronal loss in mice after hypoxic insult. Our reports showed hypobaric hypoxia exposure for 3 weeks led to impaired spatial exploration and short-term memory in mice, concomitant with neuron loss. In addition, hypoxia induced neuroinflammation and NLRP3 inflammasome activation. Besides, to explore the role of the inflammasome in hypoxia-induced cognitive dysfunction, NLRP3 knockout mice were applied and the results showed that NLRP3 could negatively regulate GPX4 to modify antioxidant capacity. In summary, our work demonstrated that hypoxia exposure led to neuroinflammation and neuronal-deletion, which may be the key events in the process of hypoxia induced cognitive impairment. NLRP3 inflammasome promoted antioxidant deficiency by negatively regulating GPX4.

Analysis of relationship between P wave dispersion and diagnosis of pulmonary arterial hypertension and risk stratification.

BACKGROUND: The aim of this study was to measure the P-wave dispersion(PWD) in the ECG of patients with pulmonary arterial hypertension(PAH). METHODS: A total of 103 PAH patients were collected, including 55 patients related with congenital heart disease(CHD) and 44 patients with idiopathic pulmonary arterial hypertension(IPAH). In addition, 30 CHD patients without PAH (nPAH-CHD group) and 30 healthy controls (HCG group) were collected as control. Patients in the PAH group were categorized into the low-risk group (30 cases), moderate-risk group (53 cases) and high-risk group (20 cases), followed by comparison of PWD difference between groups. The ROC curve was used to evaluate the diagnostic efficacy of PWD on PAH-CHD and IPAH. RESULTS: The levels of PWD and maximum P wave duration(Pmax) in PAH-CHD and IPAH group were significantly higher than those in nPAH-CHD and HCG group (P < 0.05). PWD level was positively correlated with right ventricular end-diastolic diameter(RVD), right atrial end-systolic diameter(RAS), mean pulmonary arterial pressure(mPAP), pulmonary vascular resistance(PVR)(r = 0.407, 0.470, 0.477, 0.423, P < 0.001), and was negatively correlated with systolic displacement of tricuspid valve annulus(TAPSE) level (r = -0.551, P < 0.001). After risk quantification in 103 PAH patients, we found that PWD was significantly different among the low-risk, moderate-risk and high-risk groups (43.89 ± 9.91 vs. 51.29 ± 6.61, 62.15 ± 10.44, P < 0.001). CHD-PAH and IPAH were identified by PWD with a cut off value of 41.5 ms (P < 0.001), and a cut off value of 41.45 ms (P < 0.001), respectively. CONCLUSIONS: PWD might be an effective ECG indicator for PAH, which might be used as a relatively economical indicator for PAH patients to assist in early diagnosis, disease severity assessment and prognosis evaluation.