DNA methylation profiles of cancer-related fatigue associated with markers of inflammation and immunometabolism.

Cancer patients are commonly affected by fatigue. Herein, we sought to examine epigenetic modifications (i.e., DNA methylation) related to fatigue in peripheral blood among patients during and after treatment for head and neck cancer (HNC). Further, we determined whether these modifications were associated with gene expression and inflammatory protein markers, which we have previously linked to fatigue in HNC. This prospective, longitudinal study enrolled eligible patients with data collected at pre-radiotherapy, end of radiotherapy, and six months and one-year post-radiotherapy. Fatigue data were reported by patients using the Multidimensional Fatigue Inventory (MFI)-20. DNA methylation (Illumina MethylationEPIC) and gene expression (Applied Biosystems Clariom S) arrays and assays for seven inflammatory markers (R&D Systems multiplex) were performed. Mixed models and enrichment analyses were applied to establish the associations. A total of 386 methylation loci were associated with fatigue among 145 patients (False Discovery Rate [FDR] < 0.05). Enrichment analyses showed the involvement of genes related to immune and inflammatory responses, insulin and lipid metabolism, neuropsychological disorders, and tumors. We further identified 16 methylation-gene expression pairs (FDR < 0.05), which were linked to immune and inflammatory responses and lipid metabolism. Ninety-one percent (351) of the 386 methylation loci were also significantly associated with inflammatory markers (e.g., interleukin 6, c-reactive protein; FDR < 0.05), which further mediated the association between methylation and fatigue (FDR < 0.05). These data suggest that epigenetic modifications associated with inflammation and immunometabolism, in conjunction with relevant gene expression and protein markers, are potential targets for treating fatigue in HNC patients. The findings also merit future prospective studies in other cancer populations as well as interventional investigations.

Single-cell analysis identified PDIA3 as regulator of malignant characteristics and macrophage function in human cancers.

Protein disulfide isomerase A3 (PDIA3) is an endoplasmic reticulum (ER) protein. It has different functions including glycoprotein folding in the ER. The unfavorable prognosis of cancer patients was related to the abnormal PDIA3 expression level. However, it is unclear how PDIA3 correlates with the malignant characteristics of different tumors and its impact on tumor immunity. Pan-cancer data were downloaded from several databases for large-scale bioinformatics analysis. The immunological functions of PDIA3 were systematically explored at the single-cell sequencing level, including cell communication, cell metabolism, cell evolution and epigenetic modification. We performed immunofluorescence staining to visualize PDIA3 expression and infiltration of macrophages in pan-cancer samples. Further, we performed a loss-of-function assay of PDIA3 in vitro. The CCK8 assay, clone formation assay, and transwell assay were performed. M2 macrophages were co-cultured with different cell lines before the transwell assay was performed. The immunofluorescence staining of pan-cancer samples presented a higher expression of PDIA3 than those of the paired normal tissues. According to single-cell sequencing analysis, expression of PDIA3 was closely associated with cell communication, cell metabolism, cell evolution and epigenetic modification. The knockdown of PDIA3 in tumor cells inhibited cell proliferation and invasion, and restrained cocultured M2 macrophage migration. Furthermore, PDIA3 displayed predictive value in immunotherapy response in human cancer cohorts, indicating a potential therapeutic target. Our study showed that PDIA3 was associated with tumor malignant characteristics and could mediate the migration of M2 macrophages in various tumor types. PDIA3 could be a promising target to achieve tumor control and improve the immune response on a pan-cancer scale.

Operando Spectroscopy Observation of Mo Clusters-Ti3 C2 TX Catalyst/Support Interface's Dynamic Evolution in Hydrogen Evolution Reaction.

The interaction between catalyst and support plays an important role in electrocatalytic hydrogen evolution (HER), which may explain the improvement in performance by phase transition or structural remodeling. However, the intrinsic behavior of these catalysts (dynamic evolution of the interface under bias, structural/morphological transformation, stability) has not been clearly monitored, while the operando technology does well in capturing the dynamic changes in the reaction process in real time to determine the actual active site. In this paper, nitrogen-doped molybdenum atom-clusters on Ti3 C2 TX (MoACs /N-Ti3 C2 TX ) is used as a model catalyst to reveal the dynamic evolution of MoAcs on Ti3 C2 TX during the HER process. Operando X-ray absorption structure (XAS) theoretical calculation and in situ Raman spectroscopy showed that the Mo cluster structure evolves to a 6-coordinated monatomic Mo structure under working conditions, exposing more active sites and thus improving the catalytic performance. It shows excellent HER performance comparable to that of commercial Pt/C, including an overpotential of 60 mV at 10 mA cm-2 , a small Tafel slope (56 mV dec-1 ), and high activity and durability. This study provides a unique perspective for investigating the evolution of species, interfacial migration mechanisms, and sources of activity-enhancing compounds in the process of electroreduction.

Posterior circulation ischemic stroke: radiomics-based machine learning approach to identify onset time from magnetic resonance imaging.

PURPOSE: Posterior circulation ischemic stroke (PCIS) possesses unique features. However, previous studies have primarily or exclusively relied on anterior circulation stroke cases to build machine learning (ML) models for predicting onset time. To date, there is no research reporting the effectiveness and stability of ML in identifying PCIS onset time. We aimed to build diffusion-weighted imaging-based ML models to identify the onset time of PCIS patients. METHODS: Consecutive PCIS patients within 24 h of definite symptom onset were included (112 in the training set and 49 in the independent test set). Images were processed as follows: volume of interest segmentation, image feature extraction, and feature selection. Five ML models, naïve Bayes, logistic regression, tree ensemble, k-nearest neighbor, and random forest, were built based on the training set to estimate the stroke onset time (binary classification: ≤ 4.5 h or > 4.5 h). Relative standard deviations (RSD), receiver operating characteristic (ROC) curves, and the calibration plot was performed to evaluate the stability and performance of the five models. RESULTS: The random forest model had the best performance in the test set, with the highest area under the curve (AUC, 0.840; 95% CI: 0.706, 0.974). This model also achieved the highest accuracy, sensitivity, specificity, positive predictive value, and negative predictive value (83.7%, 64.3%, 91.4%, 75.0%, and 86.5%, respectively). Furthermore, the model had high stability (RSD = 0.0094). CONCLUSION: The PCIS case-based ML model was effective for estimating the symptom onset time and achieved considerably high specificity and stability.

The development of audiovisual speech perception in Mandarin-speaking children: Evidence from the McGurk paradigm.

The developmental trajectory of audiovisual speech perception in Mandarin-speaking children remains understudied. This cross-sectional study in Mandarin-speaking 3- to 4-year-old, 5- to 6-year-old, 7- to 8-year-old children, and adults from Xiamen, China (n = 87, 44 males) investigated this issue using the McGurk paradigm with three levels of auditory noise. For the identification of congruent stimuli, 3- to 4-year-olds underperformed older groups whose performances were comparable. For the perception of the incongruent stimuli, a developmental shift was observed as 3- to 4-year-olds made significantly more audio-dominant but fewer audiovisual-integrated responses to incongruent stimuli than older groups. With increasing auditory noise, the difference between children and adults widened in identifying congruent stimuli but narrowed in perceiving incongruent ones. The findings regarding noise effects agree with the statistically optimal hypothesis.

Compact, remote optical waveguide magnetic field sensing using double-pass Faraday rotation-induced optical attenuation.

Compact, magnetic field, B sensing is proposed and demonstrated by combining the two Faraday rotation elements and beam displacement crystals within a micro-optical fiber circulator with a fiber reflector and ferromagnets to allow high contrast attenuation in an optical fiber arm. Low optical noise sensing is measured at λ=1550n m as a change in attenuation, α, of optical light propagating through the rotators and back. The circulator's double-pass configuration, using a gold mirror as a reflector, achieves a magnetic field sensitivity s=Δ α/Δ B=(0.26±0.02)d B/m T with a resolution of Δ B=0.01m T, over a detection range B=0-89m T. The circulator as a platform provides direct connectivity to the Internet, allowing remote sensing to occur. The method described here is amenable to multisensor combinations, including with other sensor technologies, particularly in future integrated waveguide Faraday optical circuits and devices, extending its utility beyond point magnetic field sensing applications.

Effects of a UV absorber in silica-loaded resin on DLP silica fiber preform fabrication.

3D printing technologies have distinguished advantages in manufacturing arbitrary shapes and complex structures that have attracted us to use digital light processing (DLP) technology for specialty silica optical fiber preforms. One of the main tasks is to develop an appropriate recipe for DLP resin that is UV sensitive and loaded with silica nanoparticles. In this work, the effects of a UV absorber in highly silica-loaded resin on DLP printing are experimentally investigated. Spot tests and DLP printing are carried out on resins with varying dosages of a typical UV absorber, Sudan Orange G. Based on the experimental results, the UV absorber can significantly improve the resolution of DLP printed green bodies while requiring a larger exposure dose.

Maternal Childhood Adversity and Infant Epigenetic Aging: Moderation by Restless Sleep During Pregnancy.

Maternal exposure to childhood adversity is associated with detrimental health outcomes throughout the lifespan and may have implications for offspring. Evidence links maternal adverse childhood experiences (ACEs) to detrimental birth outcomes, yet the impact on the infant's epigenome is unclear. Moreover, maternal sleep habits during pregnancy may influence this association. Here, we explore whether restless sleep during pregnancy moderates the association between exposure to maternal childhood adversity and infant epigenetic age acceleration in 332 mother-infant dyads (56% female; 39% Black; 25% Hispanic). During the 2nd trimester, mothers self-reported childhood adversity and past-week restless sleep; DNA methylation from umbilical vein endothelial cells was used to estimate five epigenetic clocks. Multivariable linear regression was used to test study hypotheses. Despite no evidence of main effects, there was evidence of an interaction between maternal ACEs and restless sleep in predicting infant epigenetic age acceleration using the EPIC Gestational Age clock. Only infants whose mothers reported exposure to both ACEs and restless sleep demonstrated accelerated epigenetic aging. Results provide preliminary evidence that maternal childhood adversity and sleep may influence the infant epigenome.

Recent Advances in Trajectory Planning and Object Recognition for Robot Sensing and Control.

Nowadays, trajectory planning and control technology has been extensively utilized in industry, agriculture, service, construction, infrastructure inspection, military reconnaissance, disaster management, and other areas [...].

Diphosphine Ligand-Enabled Nickel-Catalyzed Chelate-Assisted Inner-Selective Migratory Hydroarylation of Alkenes.

The precise control of the regioselectivity in the transition metal-catalyzed migratory hydrofunctionalization of alkenes remains a big challenge. With a transient ketimine directing group, the nickel-catalyzed migratory ß-selective hydroarylation and hydroalkenylation of alkenyl ketones has been realized with aryl boronic acids using alkyl halide as the mild hydride source for the first time. The key to this success is the use of a diphosphine ligand, which is capable of the generation of a Ni(II)-H species in the presence of alkyl bromide, and enabling the efficient migratory insertion of alkene into Ni(II)-H species and the sequent rapid chain walking process. The present approach diminishes organosilanes reductant, tolerates a wide array of complex functionalities with excellent regioselective control. Moreover, this catalytic system could also be applied to the migratory hydroarylation of alkenyl azahetereoarenes, thus providing a general approach for the preparation of 1,2-aryl heteroaryl motifs with wide potential applications in pharmaceutical discovery.

Proprotein convertase furina is required for heart development in zebrafish.

Cardiac looping and trabeculation are key processes during cardiac chamber maturation. However, the underlying mechanisms remain incompletely understood. Here, we report the isolation, cloning and characterization of the proprotein convertase furina from the cardiovascular mutant loft in zebrafish. loft is an ethylnitrosourea-induced mutant and has evident defects in the cardiac outflow tract, heart looping and trabeculation, the craniofacial region and pharyngeal arch arteries. Positional cloning revealed that furina mRNA was barely detectable in loft mutants, and loft failed to complement the TALEN-induced furina mutant pku338, confirming that furina is responsible for the loft mutant phenotypes. Mechanistic studies demonstrated that Notch reporter Tg(tp1:mCherry) signals were largely eliminated in mutant hearts, and overexpression of the Notch intracellular domain partially rescued the mutant phenotypes, probably due to the lack of Furina-mediated cleavage processing of Notch1b proteins, the only Notch receptor expressed in the heart. Together, our data suggest a potential post-translational modification of Notch1b proteins via the proprotein convertase Furina in the heart, and unveil the function of the Furina-Notch1b axis in cardiac looping and trabeculation in zebrafish, and possibly in other organisms.

PD-1+ mast cell enhanced by PD-1 blocking therapy associated with resistance to immunotherapy.

BACKGROUND: Programmed cell death protein 1 (PD-1) antibody has been approved for a variety of tumors, but its effective rate is unsatisfactory. New evidence suggests that mast cells are an important component of the tumor microenvironment and are associated with resistance to immunotherapy, but the underlying mechanism is not clear. METHODS: Bioinformatics analysis of patients with melanoma in TCGA-SKCM and GSE91061 was used to determine the prognostic value of mast cells and their association with anti-PD-1 immunotherapy. HMC-1 cells (mast cell line) and bone marrow-derived mast cells (BMMCs) were used to verify the effect of PD-1 antibody and cromolyn sodium in vitro. The mouse subcutaneous melanoma model was used to verify the effect of the PD-1 antibody on mast cells in vivo. RESULTS: Bioinformatics analysis showed that mast cells were a poor prognostic factor associated with resistance to anti-PD-1 immunotherapy. PD-1 was expressed on the mast cell membrane. The PD-1 antibody promoted the release of histamine and cytokines from mast cells via the PI3K/AKT pathway and calcium signaling pathway. The activation of mast cells induced by PD-1 antibody could be partially inhibited by cromolyn sodium. In vivo, cromolyn sodium increased the efficacy of PD-1 antibody and decreased the infiltration of mast cells and the density of microvessels. CONCLUSION: PD-1+ mast cell activated by PD-1 antibody plays a negative role in the tumor microenvironment via the enhanced function of releasing histamine and cytokines. Inhibition of mast cell may provide a new solution to solve the low response rate of anti-PD-1 immunotherapy.

Voltage, thermal and magnetic field fiber sensors based on magnetic nanoparticles-doped photonic liquid crystal fibers.

In this article, highly sensitive voltage, thermal and magnetic field fiber sensors were obtained in magnetic nanoparticles-doped E7 liquid crystals filled into photonic crystal fibers (PLCF). The voltage and temperature sensitivity reached at 12.598 nm/V and -3.874 nm/°C, respectively. The minimum voltage response time is 48.2 ms. The phase transition temperature Tc of liquid crystal with magnetic dopant was reduced from 60 °C to 46 °C. The magnetic field sensor based on magnetic nanoparticles-doped PLCF were obtained with sensitivity of 118.2 pm/mT from 400 to 460 mT.

Circulating short chain fatty acids and fatigue in patients with head and neck cancer: A longitudinal prospective study.

Fatigue among patients with head and neck cancer (HNC) has been associated with higher inflammation. Short-chain fatty acids (SCFAs) have been shown to have anti-inflammatory and immunoregulatory effects. Therefore, this study aimed to examine the association between SCFAs and fatigue among patients with HNC undergoing treatment with radiotherapy with or without concurrent chemotherapy. Plasma SCFAs and the Multidimensional Fatigue Inventory-20 were collected prior to and one month after the completion of treatment in 59 HNC patients. The genome-wide gene expression profile was obtained from blood leukocytes prior to treatment. Lower butyrate concentrations were significantly associated with higher fatigue (p = 0.013) independent of time of assessment, controlling for covariates. A similar relationship was observed for iso/valerate (p = 0.025). Comparison of gene expression in individuals with the top and bottom 33% of butyrate or iso/valerate concentrations prior to radiotherapy revealed 1,088 and 881 significantly differentially expressed genes, respectively (raw p < 0.05). The top 10 Gene Ontology terms from the enrichment analyses revealed the involvement of pathways related to cytokines and lipid and fatty acid biosynthesis. These findings suggest that SCFAs may regulate inflammatory and immunometabolic responses and, thereby, reduce inflammatory-related symptoms, such as fatigue.

Validation of a targeted metabolomics panel for improved second-tier newborn screening.

Improved second-tier assays are needed to reduce the number of false positives in newborn screening (NBS) for inherited metabolic disorders including those on the Recommended Uniform Screening Panel (RUSP). We developed an expanded metabolite panel for second-tier testing of dried blood spot (DBS) samples from screen-positive cases reported by the California NBS program, consisting of true- and false-positives from four disorders: glutaric acidemia type I (GA1), methylmalonic acidemia (MMA), ornithine transcarbamylase deficiency (OTCD), and very long-chain acyl-CoA dehydrogenase deficiency (VLCADD). This panel was assembled from known disease markers and new features discovered by untargeted metabolomics and applied to second-tier analysis of single DBS punches using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in a 3-min run. Additionally, we trained a Random Forest (RF) machine learning classifier to improve separation of true- and false positive cases. Targeted metabolomic analysis of 121 analytes from DBS extracts in combination with RF classification at a sensitivity of 100% reduced false positives for GA1 by 83%, MMA by 84%, OTCD by 100%, and VLCADD by 51%. This performance was driven by a combination of known disease markers (3-hydroxyglutaric acid, methylmalonic acid, citrulline, and C14:1), other amino acids and acylcarnitines, and novel metabolites identified to be isobaric to several long-chain acylcarnitine and hydroxy-acylcarnitine species. These findings establish the effectiveness of this second-tier test to improve screening for these four conditions and demonstrate the utility of supervised machine learning in reducing false-positives for conditions lacking clearly discriminating markers, with future studies aimed at optimizing and expanding the panel to additional disease targets.

Resveratrol Attenuates Ankylosing Spondylitis in Mice by Inhibiting the TLR4/NF-κB/NLRP3 Pathway and Regulating Gut Microbiota.

Ankylosing spondylitis (AS) is an autoimmune disease associated with disturbed gut microbiota. Currently, the treatments and outcomes of AS are not satisfactory. It is reported that resveratrol (RES) is a major phytoalexin with anti-inflammatory, antibacterial and some other pharmacological effects. However, there are no studies on the role of RES in AS. Therefore, this study aimed to explore the effect and mechanism of RES on AS. Proteoglycan and complete freund's adjuvant were used to conduct an AS mouse model, and then the AS mice were gavaged with RES (20 mg/kg and 50 mg/kg) daily for 4 weeks. Subsequently, the effect of RES on AS mice was assessed by detecting disease severity, inflammatory cytokines, NLRP3 inflammasome, TLR4/NF-κB pathway, intestinal mucosal barrier function, intestinal microbial barrier function. The assessment results indicated that RES could significantly relieve progression and severity of AS, inhibit the expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, interleukin-17A, interferon-γ), and promote the expression of anti-inflammatory cytokines (interleukin-4). RES intervention caused the inhibition of NLRP3 inflammasome and TLR4/NF-κB pathway. In terms of intestinal barrier function, experimental results found RES increased zonula occludens-1 and occludin expression, and additionally, changed the composition of the gut microbiota by increasing levels of Lactobacillus and Bifidobacterium and reducing levels of Enterococcus faecalis and Escherichia coli. Collectively, RES protects PG-induced AS mice by inhibiting inflammatory responses and TLR4/NF-κB/NLRP3 pathway, restoring intestinal mucosal barrier function, and regulating the composition of the gut microbiota. In other words, RES is a potential candidate for the treatment of AS.

Development of categorical speech perception in Mandarin-speaking children and adolescents.

Although children develop categorical speech perception at a very young age, the maturation process remains unclear. A cross-sectional study in Mandarin-speaking 4-, 6-, and 10-year-old children, 14-year-old adolescents, and adults (n = 104, 56 males, all Asians from mainland China) was conducted to investigate the development of categorical perception of four Mandarin phonemic contrasts: lexical tone contrast Tone 1-2, vowel contrast /u/-/i/, consonant aspiration contrast /p/-/ph /, and consonant formant transition contrast /p/-/t/. The results indicated that different types of phonemic contrasts, and even the identification and discrimination of the same phonemic contrast, matured asynchronously. The observation that tone and vowel perception are achieved earlier than consonant perception supports the phonological saliency hypothesis.

Correlation between Mean Platelet Volume and Gensini Score in Patients with Coronary Heart Disease in Different Diabetic States.

SUBJECT: To investigate the correlation between mean platelet volume (MPV) levels and Gensini scores in stable coronary heart disease (CHD) patients with or without diabetes. METHODS: A retrospective analysis was conducted on 2525 patients with stable CHD in Zhongshan Hospital, Fudan University. There were 1274 in the low MPV group and 1251 in the high MPV group, divided by a median MPV level of 10.9 fL. In the total population, 1605 patients were non-diabetic and 920 were diabetic. The severity of coronary artery disease was quantified using the Gensini score. RESULTS: The Gensini score was significantly higher in the high MPV group than in the low MPV group (p < 0.001). MPV levels increased significantly with the number of stenotic (>50%) coronary vessels (p < 0.001). The Spearman analysis showed a positive correlation between MPV and Gensini score (r = 0.189, p < 0.001), which was more significant in the diabetic subgroup (r = 0.232, p < 0.001). Receiver operating characteristic (ROC) curves were employed to assess the predictive value of MPV for high Gensini scores, using the median value of 32 points as the cutoff. MPV levels in the diabetes cohort exhibited a higher predictive value for high Gensini scores (area under the curve: 0.635 [0.614-0.657], p < 0.001). Multivariate linear regression analysis showed that diabetes and MPV were independently associated with Gensini scores. CONCLUSION: MPV levels in stable CHD patients can predict the severity of coronary artery stenosis. This correlation is more significant in the presence of diabetes.

Timing and Frequency Synchronization Using CAZAC Sequences for OFDM Systems.

Since orthogonal frequency division multiplexing (OFDM) systems are very susceptible to symbol timing offset (STO) and carrier frequency offset (CFO), which cause inter-symbol interference (ISI) and inter-carrier interference (ICI), accurate STO and CFO estimations are very important. In this study, first, a new preamble structure based on the Zadoff-Chu (ZC) sequences was designed. On this basis, we proposed a new timing synchronization algorithm, called the continuous correlation peak detection (CCPD) algorithm, and its improved algorithm: the accumulated correlation peak detection (ACPD) algorithm. Next, the correlation peaks that were obtained during the timing synchronization were used for the frequency offset estimation. For this, the quadratic interpolation algorithm was adopted as the frequency offset estimation algorithm, which was better than the fast Fourier transform (FFT) algorithm. The simulation results showed that when the correct timing probability reached 100%, under the parameters of m = 8 and N = 512, the performance of the CCPD algorithm was 4 dB higher than that of Du's algorithm, and that of the ACPD algorithm was 7 dB. Under the same parameters, the quadratic interpolation algorithm also had a great performance improvement in both small and large frequency offsets, when compared with the FFT algorithm.

Reprojection Error Analysis and Algorithm Optimization of Hand-Eye Calibration for Manipulator System.

The Euclidean distance error of calibration results cannot be calculated during the hand-eye calibration process of a manipulator because the true values of the hand-eye conversion matrix cannot be obtained. In this study, a new method for error analysis and algorithm optimization is presented. An error analysis of the method is carried out using a priori knowledge that the location of the augmented reality markers is fixed during the calibration process. The coordinates of the AR marker center point are reprojected onto the pixel coordinate system and then compared with the true pixel coordinates of the AR marker center point obtained by corner detection or manual labeling to obtain the Euclidean distance between the two coordinates as the basis for the error analysis. We then fine-tune the results of the hand-eye calibration algorithm to obtain the smallest reprojection error, thereby obtaining higher-precision calibration results. The experimental results show that, compared with the Tsai-Lenz algorithm, the optimized algorithm in this study reduces the average reprojection error by 44.43% and the average visual positioning error by 50.63%. Therefore, the proposed optimization method can significantly improve the accuracy of hand-eye calibration results.