Identification of cuproptosis-related genes related to the progression of ankylosing spondylitis by integrated bioinformatics analysis.

Ankylosing spondylitis (AS) is an autoimmune disease, and the relationship between copper death and AS is not clear. The aim of this study was to analyze and identify potential cuprosis-related genes associated with the onset of AS by bioinformatics methods. We obtained the AS gene expression profile GSE25101 from the Gene Expression Omnibus (GEO) database, which consists of blood samples from 16 active AS patients and 16 sex-and age-matched controls. After analyzing the data, we utilized the WGCNA method to identify genes that exhibited significant differential expression. In order to assess the prognostic and predictive power of these genes, we constructed receiver operating characteristic (ROC) curves. To further validate our predictions, we employed nomograms, calibration curves, decision curve analysis, and external datasets. Lastly, we conducted an analysis on immune infiltration and explored the correlation between key genes and immune response. Three genes, namely INPP5E, CYB5R1, and HGD, have been identified through analysis to be associated with AS. The diagnosis of patients using these genes has been found to possess a high level of accuracy. The area under the ROC curve is reported to be 0.816 for INPP5E, 0.879 for CYB5R1, and also 0.879 for HGD. Furthermore, the nomogram demonstrates an excellent predictive power, and it has been calibrated using a Calibration curve. Its clinical usefulness and net benefit have been thoroughly analyzed and estimated through the use of a DCA curve. Moreover, INPP5E, CYB5R1, and HGD are found to be associated with various types of immune cells. In conclusion, the systematic analysis of cuprosis-related genes may aid in the identification of mechanisms related to copper-induced cell death in AS and offer valuable biomarkers for the diagnosis and treatment of AS.

From the perspective of perceptual speech quality: The robustness of frequency bands to noise.

Speech quality is one of the main foci of speech-related research, where it is frequently studied with speech intelligibility, another essential measurement. Band-level perceptual speech intelligibility, however, has been studied frequently, whereas speech quality has not been thoroughly analyzed. In this paper, a Multiple Stimuli With Hidden Reference and Anchor (MUSHRA) inspired approach was proposed to study the individual robustness of frequency bands to noise with perceptual speech quality as the measure. Speech signals were filtered into thirty-two frequency bands with compromising real-world noise employed at different signal-to-noise ratios. Robustness to noise indices of individual frequency bands was calculated based on the human-rated perceptual quality scores assigned to the reconstructed noisy speech signals. Trends in the results suggest the mid-frequency region appeared less robust to noise in terms of perceptual speech quality. These findings suggest future research aiming at improving speech quality should pay more attention to the mid-frequency region of the speech signals accordingly.

Expectations Come True: The Placebo Effect of Exercise on Affective Responses.

Objective: This study investigated the placebo and nocebo effects of habitual and induced expectations. Methods: In Study 1, 95 participants (Mage = 19.65 ± 2.21 years, MBMI = 21.94 ± 2.55) were grouped according to habitual expectations (positive, neutral, or negative) and completed a 30-min moderate-intensity aerobic exercise, and their affective response, rating of perceived exertion (RPE), and heart rate variability (HRV) were measured before, during, and after the exercise. In Study 2, the participants from Study 1 were grouped according to induced expectations (control, positive, or negative) and completed a 30-min moderate-intensity aerobic exercise. Affective response, RPE, and HRV were measured before, during, and after exercise. Results: In Study 1, positive habitual expectations increased affective response during and after exercise [F(2, 92) = 2.959, p = .057, ηp2 = .060], and negative habitual expectations increased RPE during exercise [F(2, 92) = 5.174, p = .007, ηp2 = .101]. In Study 2, positive induced expectation increased affective response during [F(2, 86) = 5.492, p = .006, ηp2 = .113] and after exercise [F(2, 86) = 6.096, p = .003, ηp2 = .124] and was not affected by habitual expectation. Conclusion: The affective response during and after exercise is influenced by habitual and induced expectations. Positive expectations enhance affective benefits, while negative expectations reduce affective benefits.

THERMOSENSITIVE BARREN PANICLE (TAP) is required for rice panicle and spikelet development at high ambient temperature.

In cereal plants, the size of the panicle (inflorescence) is a critical factor for yield. Panicle size is determined by a complex interplay of genetic and environmental factors, but the mechanisms underlying adaptations to temperature stress during panicle development remain largely unknown. We identify the rice THERMOSENSITIVE BARREN PANICLE (TAP) gene, which encodes a transposase-derived FAR1-RELATED SEQUENCE (FRS) protein and is responsible for regulating panicle and spikelet development at high ambient temperature. The tap mutants display high temperature-dependent reproductive abnormalities, including compromised secondary branch and spikelet initiation and pleiotropic floral organ defects. Consistent with its thermosensitive phenotype, TAP expression is induced by high temperature. TAP directly promotes the expression of OsYABBY3 (OsYAB3), OsYAB4, and OsYAB5, which encode key transcriptional regulators in panicle and spikelet development. In addition, TAP physically interacts with OsYAB4 and OsYAB5 proteins; phenotypic analysis of osyab4 tap-1 and osyab5 tap-1 double mutants indicates that TAP-OsYAB4/OsYAB5 complexes act to maintain normal panicle and spikelet development. Taken together, our study reveals the novel role of a TE-derived transcription factor in controlling rice panicle development under high ambient temperatures, shedding light on the molecular mechanism underlying the adaptation of cereal crops to increasing environmental temperatures.

Dual-path transformer-based network with equalization-generation components prediction for flexible vibrational sensor speech enhancement in the time domain.

The flexible vibrational sensor (FVS) has the potential to become a popular wearable communication device because of its natural noise shielding characteristics and soft materials. However, FVS speech faces a severe loss of frequency components. To improve speech quality, a time-domain neural network model based on the dual-path transformer combined with equalization-generation components prediction (DPT-EGNet) is proposed. More specifically, the DPT-EGNet consists of five modules, namely the pre-processing module, dual-path transformer module, equalization module, generation module, and post-processing module. The dual-path transformer module is leveraged to extract the local and global contextual relationship of long-term speech sequences, which is extremely beneficial for inferring the missing components. The equalization and generation modules are designed according to the characteristics of FVS speech, which further improve the speech quality by simulating the inversion process of the speech distortion. The experimental results demonstrate that the proposed model effectively improves the quality of FVS speech; the average perceptual evaluation of speech quality (PESQ), short-time objective intelligibility (STOI), and composite measure for overall speech quality (COVL) scores of three males and three females are relatively increased by 64.19%, 29.63%, and 101.37%, which is superior to other baseline models developed in different domains. The proposed model also has significantly lower complexity than the others.

A rice single cell transcriptomic atlas defines the developmental trajectories of rice floret and inflorescence meristems.

Rice inflorescence development determines yield and relies on the activity of axillary meristems (AMs); however, high-resolution analysis of its early development is lacking. Here, we have used high-throughput single-cell RNA sequencing to profile 37 571 rice inflorescence cells and constructed a genome-scale gene expression resource covering the inflorescence-to-floret transition during early reproductive development. The differentiation trajectories of florets and AMs were reconstructed, and discrete cell types and groups of regulators in the highly heterogeneous young inflorescence were identified and then validated by in situ hybridization and with fluorescent marker lines. Our data demonstrate that a WOX transcription factor, DWARF TILLER1, regulates flower meristem activity, and provide evidence for the role of auxin in rice inflorescence branching by exploring the expression and biological role of the auxin importer OsAUX1. Our comprehensive transcriptomic atlas of early rice inflorescence development, supported by genetic evidence, provides single-cell-level insights into AM differentiation and floret development.

Engineered mesenchymal stem cell-derived exosomes with high CXCR4 levels for targeted siRNA gene therapy against cancer.

Gene therapy has been used in a variety of diseases and shows brilliant anticancer or cancer suppression effects. Gene therapy is gradually evolving as the most compelling frontier hotspot in the field of cancer therapy. The current vehicles used in gene therapy have poor safety and low delivery efficiency, and thus, it is urgent to develop novel delivery vehicles for gene therapy. Due to the excellent stability and biosafety of exosomes, their use as drug carriers for novel nucleic acid therapy is in full swing, revealing huge prospects for clinical application. Mesenchymal stem cells (MSCs) have a natural homing property and can spontaneously accumulate at injury sites, inflammation sites, and even tumour sites. This feature is attributed to a variety of tropism factors expressed on their surface; for example, CXC chemokine receptor type 4 (CXCR4) can specifically bind to the highly expressed stromal cell derived factor-1 (SDF-1) on the tumour surface, which is essential for accumulation of MSCs at the tumour site. The mesenchymal stem cells used in this study were genetically engineered to obtain exosomes with high CXCR4 expression as carriers for targeted gene-drug delivery, and then, the Survivin gene was loaded via electrotransformation to construct a brand-new gene-drug delivery system (CXCR4high Exo/si-Survivin). Finally, related in vivo and in vitro experiments were conducted. We observed that the new delivery system can efficiently aggregate at the tumour site and release siRNA into tumour cells, knocking down the Survivin gene in tumour cells in vivo and thereby inhibiting tumour growth. This new gene-drug delivery system has tremendous clinical transformation value and provides a new strategy for clinical treatment of tumours.

Minimum-monitor-unit optimization via a stochastic coordinate descent method.

Objective. Deliverable proton spots are subject to the minimum monitor-unit (MMU) constraint. The MMU optimization problem with relatively large MMU threshold remains mathematically challenging due to its strong nonconvexity. However, the MMU optimization is fundamental to proton radiotherapy (RT), including efficient IMPT and proton arc delivery (ARC). This work aims to develop a new optimization algorithm that is effective in solving the MMU problem.Approach.Our new algorithm is primarily based on stochastic coordinate decent (SCD) method. It involves three major steps: first to decouple the determination of active sets for dose-volume-histogram (DVH) planning constraints from the MMU problem via iterative convex relaxation method; second to handle the nonconvexity of the MMU constraint via SCD to localize the index set of nonzero spots; third to solve convex subproblems projected to this convex set of nonzero spots via projected gradient descent method.Main results.Our new method SCD is validated and compared with alternating direction method of multipliers (ADMM) for IMPT and ARC. The results suggest SCD had better plan quality than ADMM, e.g. the improvement of conformal index (CI) from 0.56 to 0.69 during IMPT, and from 0.28 to 0.80 during ARC for the lung case. Moreover, SCD successfully handled the nonconvexity from large MMU threshold that ADMM failed to handle, in the sense that (1) the plan quality from ARC was worse than IMPT (e.g. CI was 0.28 with IMPT and 0.56 with ARC for the lung case), when ADMM was used; (2) in contrast, with SCD, ARC achieved better plan quality than IMPT (e.g. CI was 0.69 with IMPT and 0.80 with ARC for the lung case), which is compatible with more optimization degrees of freedom from ARC compared to IMPT.Significance. To the best of our knowledge, our new MMU optimization method via SCD can effectively handle the nonconvexity from large MMU threshold that none of the current methods can solve. Therefore, we have developed a unique MMU optimization algorithm via SCD that can be used for efficient IMPT, proton ARC, and other particle RT applications where large MMU threshold is desirable (e.g. for the delivery of high dose rates or/and a large number of spots).

Shyness Weakens the Agreeableness-Prosociality Association via Social Self-Efficacy: A Moderated-Mediation Study of Chinese Undergraduates.

Using a sample of 1383 undergraduate students (M age = 20.06, N female = 817), this study tested a moderated mediation model in which shyness moderated the association between agreeableness and prosocial behavior, as well as the relation between agreeableness and social self-efficacy (SSE). Results showed (when gender, age, and family socio-economic status were controlled) that agreeableness exerted a positive effect on prosocial behavior (PSB) toward three types of recipients (i.e., family members, friends/acquaintances, strangers), and this effect was mediated by SSE and moderated by shyness. The relationships between agreeableness and PSB were more positive under low shyness than that under high shyness condition. In addition, shyness also moderated the first stage of mediation model (i.e., the agreeableness-SSE association), showing that the relation between agreeableness and SSE was more positive under low shyness than that under high shyness condition. Identifying the moderation effect of shyness provides evidence that personality traits may operate in an interactive manner. This may shed new light on why there are inconsistent findings regarding the agreeableness-prosociality association.