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This study aimed to propose a method to predict yarn unevenness grounded on the generalized regression neural network and traditional neural network model to further improve the prediction accuracy. The yarn unevenness model was constructed. Under this model, a three-layer neural network, a four-layer neural network, a five-layer neural network, and a generalized regression neural network were designed. Finally, Python was used for training and simulation. The training parameters and the three network models data were made consistent to ensure the comparability of the results. The results showed that using the yarn unevenness model, the average relative error of the four-layer neural network to cut down 0.87% compared with that of the three-layer neural network. Compared with the five-layer neural network, the four-layer neural network performance was not much different, but the running speed was increased by 46.05%. Compared with the four-layer neural network, the average relative error of the generalized regression neural network was reduced by 0.57%, the mean square error was reduced by 0.98%, he root mean square error was reduced by 4.76%, and the running speed was increased by 74.70%. &nbsp

Background: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is increasingly recognized as a manifestation preceding the α-synucleinopathies like Parkinson’s disease (PD). Neurofilament light chain (NfL) have been reported to be higher in synucleinopathies as a sign of neurodegeneration. Objective: To evaluate whether plasma NfL is valuable in reflecting cognitive and motor status in iRBD and PD with a premorbid history of RBD (PDRBD), and predicting disease progression in iRBD. Methods: Thirty-one patients with iRBD, 30 with PDRBD, and 18 healthy controls were included in the cross-sectional and prospective study. Another cohort from the Parkinson’s Progression Markers Initiative (PPMI) dataset was enrolled for verification analysis. All patients received evaluations of cognitive, motor, and autonomic function by a battery of clinical tests at baseline and follow-up. Blood NfL was measured by the Quanterix Simoa HD-1. Results: In our cohort, 26 patients with iRBD completed the follow-up evaluations, among whom eight (30.8%) patients displayed phenoconversion. Baseline plasma NfL cutoff value of 22.93 pg/mL performed best in distinguishing the iRBD converters from non-converters (sensitivity: 75.0%, specificity: 83.3%, area under the curve: 0.84). Cognitive and motor function were significantly correlated with NfL levels in PDRBD (correlation coefficients: –0.379, 0.399; respectively). Higher baseline NfL levels in iRBD were significantly associated with higher risks for cognitive, motor, autonomic function progression, and phenoconversion at follow-up (hazard ratios: 1.069, 1.065, 1.170, 1.065; respectively). The findings were supported by the PPMI dataset. Conclusion: Plasma NfL is valuable in reflecting disease severity of PDRBD and predicting disease progression and phenoconversion in iRBD.

Cell-free DNA (cfDNA) analysis holds promise for early detection of lung cancer and benefits patients with higher survival. However, the detection sensitivity of previous cfDNA-based studies was still low to suffice the clinical use, especially for early-stage tumors.Establish an accurate and affordable approach for early-stage lung cancer detection by integrating cfDNA fragmentomics and machine learning models.This study included 350 non-cancer and 432 cancer participants. The participants' plasma cfDNA samples were profiled by whole-genome sequencing. Multiple cfDNA features and machine learning models were compared in the training cohort to achieve an optimal model. Model performance was evaluated in three validation cohorts.A stacked ensemble model integrating five cfDNA features and five machine learning algorithms constructed in the training cohort (cancer: 113, healthy: 113) outperformed all the models built on individual feature-algorithm combinations. This integrated model yielded superior sensitivities of 91.4% at 95.7% specificity for Cohort Validation I [Area Under the Curve (AUC): 0.984], 84.7% at 98.6% specificity for Validation II (AUC: 0.987), and 92.5% at 94.2% specificity for Additional Validation (AUC: 0.974), respectively. The model's high performance remained consistent when sequencing depth was down to 0.5× (AUC: 0.966-0.971). Furthermore, our model is sensitive to identifying early pathological features (83.2% sensitivity for stage I, 85.0% sensitivity for1cm tumor at the 0.66 cutoff).We have established a stacked ensemble model using cfDNA fragmentomics features and achieved superior sensitivity for detecting early-stage lung cancer, which could promote early diagnosis and benefit more patients. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Several attempts have been made to enhance N-methyl-D-aspartate (NMDA) receptor function in schizophrenia, but they have yielded mixed results. Luvadaxistat, a D-amino acid oxidase (DAAO) inhibitor that increases the glutamate co-agonist D-serine levels, is being developed for the treatment of cognitive impairment associated with schizophrenia. We conducted a biomarker study in patients, assessing several endpoints related to physiological outcomes of NMDA receptor modulation to determine whether luvadaxistat affects neural circuitry biomarkers relevant to NMDA receptor function and schizophrenia. This was a randomized, placebo-controlled, double-blind, two-period crossover phase 2a study assessing luvadaxistat 50 mg and 500 mg for 8 days in 31 patients with schizophrenia. There were no treatment effects of luvadaxistat at either dose in eyeblink conditioning, a cerebellar-dependent learning measure, compared with placebo. We observed a nominally significant improvement in mismatch negativity (MMN) and a statistical trend to improvement for auditory steady-state response at 40 Hz, in both cases with 50 mg, but not with 500 mg, compared with placebo. Although the data should be interpreted cautiously owing to the small sample size, they suggest that luvadaxistat can improve an illness-related circuitry biomarker at doses associated with partial DAAO inhibition. These results are consistent with 50 mg, but not higher doses, showing a signal of efficacy in cognitive endpoints in a larger phase 2, 12-week study conducted in parallel. Thus, MMN responses after a short treatment period may predict cognitive function improvement. MMN and ASSR should be considered as biomarkers in early trials addressing NMDA receptor hypofunction.

Capacitive electrocardiography (cECG) has been proposed for ambulatory cardiac health monitoring. However, due to the high sensitivity of capacitive electrodes to various noise sources, particularly the power-line interference (PLI) and motion artifacts (MA), the existing capacitive systems are only verified in terms of RR interval. The aim of the present study is to explore the feasibility of using cECG for morphological analysis, and thus to extract clinical meaningful parameters.A capacitive electrode with active guarding is realized. A phase-locked-loop (PLL) based adaptive canceller is employed to remove PLI from the cECG. Wavelet analysis is adopted to cancel other noises. The developed capacitive system and algorithms are evaluated by real ECG measurements on 7 volunteers using 3-lead configuration. The correlation coefficient (CC) between the processed cECG and the wet ECG is calculated in two different conditions: with and without the QRS complex. Several frequently used diagnostic parameters, i.e., RR interval, QRS interval, P segment, T segment, ST segment, are extracted and compared with that obtained from the wet ECG.High CCs are observed between the cECG and the wet ECG in both conditions, i.e., 0.97±0.03 with the QRS complex and 0.92±0.07 without the QRS complex. Besides, RR interval extracted from the two different ECG signals are identical for each subject. Other diagnostic parameters are quite similar.Our results suggest cECG to be reliable for ambulatory heart rate monitoring. The results also indicate the feasibility of using cECG for clinical diagnosis.

This study was aimed at investigating the adaptive changes in myocardial work (MyW) during normal pregnancy. Sequential 2D standard and speckle-tracking echocardiography was performed on 41 pregnant women in each gestational trimester and 4 to 11 mo after delivery. Thirty-eight age-matched, healthy, non-pregnant women served as controls. Four components of MyW-global myocardial work index (GWI), constructive work (GCW), wasted work (GWW) and work efficiency (GWE)-were calculated. GWI began to decline early in the first trimester and remained at a low level until delivery; GCW gradually decreased with gestational progression and reached its lowest level in the third trimester. When compared with the values for non-pregnant women and those postpartum, GWE and GWW remained unchanged in gestation. This study provides normal ranges of MyW during pregnancy. Despite the adapted decrease in GWI and GCW, the myocardium manages to work efficiently in the healthy pregnancy with drastic hemodynamic alternations.

This research aims to reinforce the hand-feeling and washing fastness of anti-pilling and antistatic cashmere textiles based on a traditional “addition” technique. The technical proposal that effectively controls the distribution of polymer on cashmere textiles, based on foaming micro-coating technology, is studied and compared to prevent the superabundant polymer being fixed in the gaps between yarns/fibers and to ensure the graphene is semi-embedded in the membrane of “Table coating.” A couple of flexible hydrophilic anionic polyurethanes are used in micro-coating processing of cashmere purposefully. The effects of different coating technique on pilling, static, anti-ultraviolet, and washing resistance of coated cashmere textiles are studied. The results show that the semi-embedded graphene in the table coating membrane is meaningful to the static resistance. The pilling resistance of cashmere textile covered by polymer membranes is enhanced from grade 1–2 to grade 4–5 when the weight gain rate of “Bottom coating” polyurethane reaches 1.5% (o.w.f.), and its static voltage half-life decreases from 170 s to less than 2 s. In addition, the ultraviolet protection factor (UPF) value of coated cashmere is doubled, and anti-pilling and anti-static effects can withstand five washings.

Objective. During orthodontic treatment, a higher caries risk has been reported, so fluorides and other remineralizing compounds have been proposed. Currently, fluoride varnish is commonly available in conventional and light-curable forms. This in vitro study was performed to evaluate the effectiveness of two different materials, Clinpro™ XT (light-curable forms) and Duraphat (conventional forms) varnish, whose main active principle according to their manufacturers is fluoride in preventing tooth discoloration during orthodontic treatment with appliances attached with metal brackets or resin. Materials and Methods. This study included 120 premolars free of white spot lesions and caries that were randomly divided into the following six groups (n = 20): resin control (RCTR), resin Clinpro (RC), resin Duraphat (RD), bracket control (BCTR), bracket Clinpro (BC), and bracket Duraphat (BD). All the samples were exposed to 180 ml of coffee (4 times × 5 min/day) for 7 or 28 days. When not immersed in coffee, the teeth were stored in artificial saliva, which was replaced every day. The lightness ( L ∗ ), red/green axis ( a ∗ ), and yellow/blue axis ( b ∗ ) values were recorded with a dental spectrophotometer (Easy shade Advance 4.0) on days 0 (baseline), 7, and 28. The color difference ( Δ E ∗ ) on days 7 and 28 was also calculated. Results. The data were statistically analyzed using one-way ANOVA and Bonferroni’s test (α = 0.05). Significant differences were observed between the Δ E ∗ , L ∗ , a ∗ , and b ∗ values of the Clinpro™ XT and Duraphat groups and those of the control groups after 7 and 28 days regardless of the attachment type ( P P

The development of wearable artificial livers was restricted to device miniaturization and bleeding risk with water-soluble anticoagulants. Herein, a double-deck column filled with solid anticoagulant microspheres and Kevlar porous microspheres (KPMs, bilirubin adsorbents) was connected with the principle machine of wearable artificial liver (approximately 9 kg) to treat hyperbilirubinemia beagles for the first time. With the initial normal dose of heparin, the double-deck column could afford 3 h hemoperfusion in whole blood without thrombus formation. The removal efficiency of the double-deck column for total bilirubin (TBIL) was 31.4%. Interestingly, the excessive amounts of hepatocyte metabolites were also decreased by approximately 25%. The "anticoagulant + column" realized safe and effective whole blood hemoperfusion without the plasma separation system and heparin pump; however, the proposed principle machine of wearable artificial liver and "anticoagulant + column" cannot completely replace the bio-liver now. The intelligence of the device and the versatility of the adsorbent need to be improved; moreover, advanced experimental techniques need to be developed to validate the survival rates in animals. Overall, this study is a meaningful trial for the development of wearable artificial livers in the future.

Diabetic wounds are challenging to heal due to complex pathogenic abnormalities. Routine treatment with acid fibroblast growth factor (aFGF) is widely used for diabetic wounds but hardly offers a satisfying outcome due to its instability. Despite the emergence of various nanoparticle-based protein delivery approaches, it remains challenging to engineer a versatile delivery system capable of enhancing protein stability without the need for complex preparation. Herein, a polyphenol-driven facile assembly of nanosized coacervates (AE-NPs) composed of aFGF and Epigallocatechin-3-gallate (EGCG) was constructed and applied in the healing of diabetic wounds. First, the binding patterns of EGCG and aFGF were predicted by molecular docking analysis. Then, the characterizations demonstrated that AE-NPs displayed higher stability in hostile conditions than free aFGF by enhancing the binding activity of aFGF to cell surface receptors. Meanwhile, the AE-NPs also had a powerful ability to scavenge reactive oxygen species (ROS) and promote angiogenesis, which significantly accelerated full-thickness excisional wound healing in diabetic mice. Besides, the AE-NPs suppressed the early scar formation by improving collagen remodeling and the mechanism was associated with the TGF-β/Smad signaling pathway. Conclusively, AE-NPs might be a potential and facile strategy for stabilizing protein drugs and achieving the scar-free healing of diabetic wounds. STATEMENT OF SIGNIFICANCE: Diabetic chronic wound is among the serious complications of diabetes that eventually cause the amputation of limbs. Herein, a polyphenol-driven facile assembly of nanosized coacervates (AE-NPs) composed of aFGF and EGCG was constructed. The EGCG not only acted as a carrier but also possessed a therapeutic effect of ROS scavenging. The AE-NPs enhanced the binding activity of aFGF to cell surface receptors on the cell surface, which improved the stability of aFGF in hostile conditions. Moreover, AE-NPs significantly accelerated wound healing and improved collagen remodeling by regulating the TGF-β/Smad signaling pathway. Our results bring new insights into the field of polyphenol-containing nanoparticles, showing their potential as drug delivery systems of macromolecules to treat diabetic wounds.

Itch is an uncomfortable and complex sensation that elicits the desire to scratch. The nucleus accumbens (NAc) activity is important in driving sensation, motivation, and emotion. Excitatory afferents from the medial prefrontal cortex (mPFC), amygdala, and hippocampus are crucial in tuning the activity of dopamine receptor D1-expressing and D2-expressing medium spiny neurons (Drd1-MSN and Drd2-MSN) in the NAc. However, a cell-type and neural circuity-based mechanism of the NAc underlying acute itch remains unclear. We found that acute itch induced by compound 48/80 (C48/80) decreased the intrinsic membrane excitability in Drd1-MSNs, but not in Drd2-MSNs, in the NAc core of male mice. Chemogenetic activation of Drd1-MSNs alleviated C48/80-induced scratching behaviors but not itch-related anxiety-like behaviors. In addition, C48/80 enhanced the frequency of spontaneous EPSCs (sEPSCs) and reduced the paired-pulse ratio (PPR) of electrical stimulation-evoked EPSCs in Drd1-MSNs. Furthermore, C48/80 increased excitatory synaptic afferents to Drd1-MSNs from the mPFC, not from the basolateral amygdala (BLA) or ventral hippocampus (vHipp). Consistently, the intrinsic excitability of mPFC-NAc projecting pyramidal neurons was increased after C48/80 treatment. Chemogenetic inhibition of mPFC-NAc excitatory synaptic afferents relieved the scratching behaviors. Moreover, pharmacological activation of κ opioid receptor (KOR) in the NAc core suppressed C48/80-induced scratching behaviors, and the modulation of KOR activity in the NAc resulted in the changes of presynaptic excitatory inputs to Drd1-MSNs in C48/80-treated mice. Together, these results reveal the neural plasticity in synapses of NAc Drd1-MSNs from the mPFC underlying acute itch and indicate the modulatory role of the KOR in itch-related scratching behaviors.SIGNIFICANCE STATEMENTItch stimuli cause strongly scratching desire and anxiety in patients. However, the related neural mechanisms remain largely unclear. In the present study, we demonstrated that the pruritogen compound 48/80 (C48/80) shapes the excitability of dopamine receptor D1-expressing medium spiny neurons (Drd1-MSNs) in the nucleus accumbens (NAc) core and the glutamatergic synaptic afferents from medial prefrontal cortex (mPFC) to these neurons. Chemogenetic activation of Drd1-MSNs or inhibition of mPFC-NAc excitatory synaptic afferents relieves the scratching behaviors. In addition, pharmacological activation of κ opioid receptor (KOR) in the NAc core alleviates C48/80-induced itch. Thus, targeting mPFC-NAc Drd1-MSNs or KOR may provide effective treatments for itch.

CRISPR-Cas9 gene editing is emerging as a prospective therapy for genomic mutations. However, current editing approaches are directed primarily toward relatively small cohorts of patients with specific mutations. Here, we describe a cardioprotective strategy potentially applicable to a broad range of patients with heart disease. We used base editing to ablate the oxidative activation sites of CaMKIIδ, a primary driver of cardiac disease. We show in cardiomyocytes derived from human induced pluripotent stem cells that editing the CaMKIIδ gene to eliminate oxidation-sensitive methionine residues confers protection from ischemia/reperfusion (IR) injury. Moreover, CaMKIIδ editing in mice at the time of IR enables the heart to recover function from otherwise severe damage. CaMKIIδ gene editing may thus represent a permanent and advanced strategy for heart disease therapy.

Background Endotoxin tolerance (ET) is a protective mechanism in the process of sepsis, septic shock, and their sequelae including uncontrolled inflammation. Accumulating evidence has shown that peripheral T cells contribute to the induction of ET. However, what and how T-cell development contributes to ET inductions remain unclear. Methods Mice were intraperitoneally injected with LPS at a concentration of 5 mg/kg to establish an LPS tolerance model and were divided into two groups: a group examined 72 h after LPS injection (72-h group) and a group examined 8 days after LPS injection (8-day group). Injection of PBS was used as a control. We performed high-throughput sequencing to analyze the characteristics and changes of CD4+SP TCRβ CDR3 repertoires with respect to V direct to J rearrangement during the ET induction. Moreover, the proportion and proliferation, as well as surface molecules such as CD80 and CD86, of F4/80+ macrophages were analyzed using FCM. Furthermore, ACT assay was designed and administered by the tail vein into murine LPS-induced mouse model to evaluate the role of F4/80+ macrophages on the development of CD4+SP thymocytes in ET condition. Results We found that the frequency and characteristics of the TCRβ chain CDR3 changed obviously under condition of ET, indicating the occurrence of TCR rearrangement and thymocyte diversification. Moreover, the absolute numbers of F4/80+ macrophages, but not other APCs, were increased in thymic medulla at 72-h group, accompanied by the elevated function-related molecules of F4/80+ macrophages. Furthermore, adoptively transferred OVA332-339 peptide-loaded macrophages into Rag-1−/− mice induced the clone deletion of OVA-specific CD4+SP, thereby ameliorating the pathology in lung tissue in LPS challenge. Conclusions These data reveal that the frequency and characteristics of the TCRβ chain CDR3 undergo dynamic programming under conditions of LPS tolerance. Furthermore, the peripheral macrophages may be a key factor which carry peripheral antigen to thymic medulla and affect the negative selection of T-cell population, thereby contributing to the formation of ET. These results suggest that the clone selection in thymus in ET may confer protection against microbial sepsis.