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HighlightsDerived from silica photonic crystals, inverse opal microspheres have a regularly connected porous structure and inherit structural color properties.Combined with the stable scaffold and the photothermal phase-transition of the secondary filling material, the inverse opal composite microspheres are endowed with self-healing properties and the ability for controllable drug release.Inverse opal microspheres were significantly treated for diabetic wound, via promoting tissue regeneration, collagen deposition and angiogenesis. Meanwhile, the release of drugs could be monitored by the structural color characteristic.Chronic diabetic wounds confront a significant medical challenge because of increasing prevalence and difficult-healing circumstances. It is vital to develop multifunctional hydrogel dressings, with well-designed morphology and structure to enhance flexibility and effectiveness in wound management. To achieve these, we propose a self-healing hydrogel dressing based on structural color microspheres for wound management. The microsphere comprised a photothermal-responsive inverse opal framework, which was constructed by hyaluronic acid methacryloyl, silk fibroin methacryloyl and black phosphorus quantum dots (BPQDs), and was further re-filled with a dynamic hydrogel. The dynamic hydrogel filler was formed by Knoevenagel condensation reaction between cyanoacetate and benzaldehyde-functionalized dextran (DEX-CA and DEX-BA). Notably, the composite microspheres can be applied arbitrarily, and they can adhere together upon near-infrared irradiation by leveraging the BPQDs-mediated photothermal effect and the thermoreversible stiffness change of dynamic hydrogel. Additionally, eumenitin and vascular endothelial growth factor were co-loaded in the microspheres and their release behavior can be regulated by the same mechanism. Moreover, effective monitoring of the drug release process can be achieved through visual color variations. The microsphere system has demonstrated desired capabilities of controllable drug release and efficient wound management. These characteristics suggest broad prospects for the proposed composite microspheres in clinical applications.

Video description is challenging due to the high complexity of translating visual content into language. In most popular attention‐based pipelines for this task, visual features and previously generated words are usually concatenated as a vector to predict the current word. However, the errors caused by the inaccuracy of the predicted words may be accumulated, and the gap between visual features and language features may bring noises into the description model. Facing these problems, a variant of recurrent neural network is designed in this work, and a novel framework is developed to enhance the visual clues for video description. Moreover, a multi‐objective reinforcement learning strategy is implemented to build a more comprehensive reward with multiple metrics to improve the consistency and semantics of the generated description sentence. The experiments on the benchmark MSR‐VTT2016 and MSVD datasets demonstrate the effectiveness of the proposed approach.

The circadian rhythm is an evolutionarily conserved mechanism with translational regulation increasingly recognized as pivotal in its modulation. In this study, we found that upstream open reading frames (uORFs) are enriched in Drosophila circadian rhythm genes, with particularly conserved uORFs present in core circadian clock genes. We demonstrate evidence that the uORFs of the core clock gene, Clock ( Clk ), rhythmically and substantially attenuate CLK protein translation in Drosophila , with pronounced suppression occurring during daylight hours. Eliminating Clk uORFs leads to increased CLK protein levels during the day and results in a shortened circadian cycle, along with a broad shift in clock gene expression rhythms. Notably, Clk uORF deletion also augments morning sleep by reducing dopaminergic activity. Beyond daily circadian adjustments, Clk uORFs play a role in modulating sleep patterns in response to seasonal daylight variations. Furthermore, the Clk uORFs act as an important regulator to shape the rhythmic expression of a vast array of genes and influence multifaceted physiological outcomes. Collectively, our research sheds light on the intricate ways uORFs dynamically adjust downstream coding sequences to acclimate to environmental shifts.

Proteostasis is fundamental for maintaining organismal health. However, the mechanisms underlying its dynamic regulation and how its disruptions lead to diseases are largely unclear. Here, we conduct in-depth propionylomic profiling in Drosophila , and develop a small-sample learning framework to prioritize the propionylation at lysine 17 of H2B (H2BK17pr) to be functionally important. Mutating H2BK17 which eliminates propionylation leads to elevated total protein level in vivo. Further analyses reveal that H2BK17pr modulates the expression of 14.7–16.3% of genes in the proteostasis network, and determines global protein level by regulating the expression of genes involved in the ubiquitin-proteasome system. In addition, H2BK17pr exhibits daily oscillation, mediating the influences of feeding/fasting cycles to drive rhythmic expression of proteasomal genes. Our study not only reveals a role of lysine propionylation in regulating proteostasis, but also implements a generally applicable method which can be extended to other issues with little prior knowledge. The development of a new smallsample learning framework, KprFunc, leads to the discovery of an important role for lysine propionylation in determining global protein homeostasis, mediated by a critical propionylation site on histone H2B, H2BK17pr.

Anaerobic ammonium oxidation (anammox) bacteria significantly improve the efficiency and reduce cost of nitrogen removal in wastewater treatment plants. However, their slow growth and vulnerable activity limit the application of anammox technology. In this paper, the enhancement of biotin on the nitrogen removal activity of anammox bacteria in short-term batch experiments was studied. We found that biotin played a significant role in promoting anammox activity within a biotin concentration range of 0.1–1.5 mg/L. At a biotin concentration of 1.0 mg/L, the total nitrogen removal rate (NRR) increased by 112%, extracellular polymeric substance (EPS) secretion and heme production significantly improved, and anammox bacterial biomass increased to maximum levels. Moreover, the predominant genus of anammox bacteria was Candidatus Brocadia .

Bean dregs can be prepared into organic fertilizer by microbial fermentation. Geobacillus toebii GT-02, which has promoting effect on bean dregs fermentation, was isolated from horse dung and it grows within a range of 40–75 °C and pH 6.50–9.50. The effectiveness of GT-02 addition on composition transformations and the microbial community in bean dregs thermophilic fermentation at 70 °C for 5 days was investigated (T1). Fermentation of bean dregs without GT-02 served as control (CK). The results showed that T1 (the germination index (GI) = 95.06%) and CK (GI = 86.42%) reached maturity (defined by GI ≥ 85%) on day 3 and day 5, respectively. In addition, the total nitrogen loss of T1 (18.46%) on day 3 was lower than that in CK (24.12%). After thermophilic fermentation, the total organic carbon and dry matter loss of T1 (53.51% and 54.16%) was higher than that in CK (41.72% and 42.82%). The mean microbial number in T1 was 4.94 × 10 7 CFUs/g dry matter, which was 5.37 times higher than that in CK. 16S rDNA sequencing identified Bacillus , Geobacillus and Thermobacillus as dominant in CK, while Bacillus , Ammoniibacillus and Geobacillus were dominant in T1. A canonical correspondence analysis showed that Geobacillus and Ammoniibacillus were positively correlated with the GI. Thus, thermophilic fermentation with GT-02 can promote the maturity of bean dregs, which indicated the potential application value of GT-02 in thermophilic fermentation.

Background The severity of tics may influence executive function in children and adolescents diagnosed with tic disorders. The underlying mechanism is still inadequately researched. This study investigates the mediating role of premonitory urges in the relationship between tic severity and executive functioning, alongside the moderating effect of comorbidities. Methods A total of 154 children and adolescents, aged 6 to 15 years, diagnosed with tic disorders, were recruited from Fujian, China. The Yale Global Tic Severity Scale (YGTSS), Premonitory Urges for Tics Scale (PUTS), and Behavior Rating Inventory of Executive Function (BRIEF) were utilized to evaluate tic severity, premonitory urges, and executive functioning. R software version 4.4.3 was used for descriptive statistics and Pearson correlation studies. The moderated mediator models were tested using Bayesian Structural Equation Modeling (BSEM). Results A Bayesian simple mediation model revealed that the premonitory urge fully mediated the association between tic severity and executive functioning. Additionally, comorbidity was found to independently predict both the premonitory urge and executive functioning. In the context of a moderated mediation model, comorbidity intensified the association between tic severity and the premonitory urge, resulting in more pronounced indirect effects on behavioral regulation (BRI) and metacognition (MI). The Index of Moderated Mediation was significant for both BRI and MI, thereby confirming the enhancement of the mediation pathway driven by comorbidity. Conclusions This study is the first application of BSEM to clarify the mediating mechanism through which tic severity affects executive functioning via the premonitory urge, while concurrently validating the moderating effect of comorbidities. This finding supports the optimization of clinical assessment and intervention strategies.

Cardiovascular disease is the main cause of death worldwide, and traditional cardiovascular risk factors cannot fully explain the occurrence of the disease. In recent years, the relationship between gut microbiota and its metabolites and cardiovascular disease has been a hot study topic. The changes in gut microbiota and its metabolites are related to the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. The mechanisms by which gut microbiota and its metabolites influence cardiovascular disease have been reported, although not comprehensively. Additionally, following ingestion, flavonoids are decomposed into phenolic acids that are more easily absorbed by the body after being processed by enzymes produced by intestinal microorganisms, which increases flavonoid bioavailability and activity, consequently affecting the onset of cardiovascular disease. However, flavonoids can also inhibit the growth of harmful microorganisms, promote the proliferation of beneficial microorganisms, and maintain the balance of gut microbiota. Hence, it is important to study the relationship between gut microbiota and flavonoids to elucidate the protective effects of flavonoids in cardiovascular diseases. This article will review the role and mechanism of gut microbiota and its metabolites in the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. It also discusses the potential value of flavonoids in the prevention and treatment of cardiovascular disease following their transformation through gut microbiota metabolism.

Background Prostate cancer (PCa) is a globally prevalent malignancy in males and is imposing an increasing epidemiological burden. The androgen receptor (AR) signalling axis is fundamentally implicated in PCa tumorigenesis and disease progression. Although androgen deprivation therapy (ADT) elicits transient therapeutic responses in the majority of cases, progression to castration-resistant prostate cancer (CRPC) remains an almost universal clinical trajectory. Dysregulated lipid homeostasis, manifesting as intracellular lipid deposition, has been mechanistically linked to CRPC pathogenesis and therapeutic failure under enzalutamide regimens. However, effective strategies to mitigate lipid accumulation in PCa remain elusive. Methods STARD4, a key gene involved in lipid metabolism, was identified as functionally significant in PCa through integrated bioinformatics analysis of public databases. RT‒qPCR, western blot analysis, and IHC staining were performed to evaluate STARD4 expression, while Kaplan–Meier survival analysis, Gleason score, and tumor stage were performed to assess its clinical significance in PCa. The biological functions of STARD4 and its contribution to enzalutamide resistance were elucidated through in vitro and in vivo experiments. The effect of STARD4 on abnormal lipid accumulation in PCa cells was evaluated by Oil Red O (ORO) staining, while its impact on endoplasmic reticulum (ER) stress was assessed through ER-tracking imaging and transmission electron microscopy (TEM). Mechanistic exploration involves a combination of techniques, including RNA-seq analysis, Gene ontology analysis, coimmunoprecipitation (Co-IP), and GST pull-down assay, to analyse the interactions and potential mechanisms involving STARD4, AR, and E3 ubiquitin ligase UBE4B. Results In this study, we observed that STARD4 expression was markedly reduced in PCa tissues and was correlated with an adverse prognosis. STARD4 overexpression inhibited PCa cell proliferation, migration, and lipid accumulation while promoting apoptosis through ER stress. Mechanistically, STARD4 enhanced the interaction between UBE4B and AR, facilitating AR ubiquitination and degradation and thus suppressing AR signalling. Additionally, the upregulation of STARD4 expression enhanced sensitivity to enzalutamide in resistant cells by diminishing lipid accumulation and inhibiting the AR signalling pathway. In summary, STARD4 functions as a tumour suppressor in PCa by regulating cholesterol metabolism and modulating AR signalling. Conclusions Our findings identify STARD4 as a promising therapeutic target for reversing enzalutamide resistance in PCa while also providing novel insights for future research on lipid metabolism within the tumour microenvironment. Graphical abstract

The incidence of thyroid cancer is increasing worldwide. Fine-needle aspiration (FNA) cytology is widely applied with the use of extracted biological cell samples, but current FNA cytology is labor-intensive, time-consuming, and can lead to the risk of false-negative results. Surface-enhanced Raman spectroscopy (SERS) combined with machine learning algorithms holds promise for cancer diagnosis. In this study, we develop a label-free SERS liquid biopsy method with machine learning for the rapid and accurate diagnosis of thyroid cancer by using thyroid FNA washout fluids. These liquid supernatants are mixed with silver nanoparticle colloids, and dispersed in quartz capillary for SERS measurements to discriminate between healthy and malignant samples. We collect Raman spectra of 36 thyroid FNA samples (18 malignant and 18 benign) and compare four classification models: Principal Component Analysis–Linear Discriminant Analysis (PCA-LDA), Random Forest (RF), Support Vector Machine (SVM), and Convolutional Neural Network (CNN). The results show that the CNN algorithm is the most precise, with a high accuracy of 88.1%, sensitivity of 87.8%, and the area under the receiver operating characteristic curve of 0.953. Our approach is simple, convenient, and cost-effective. This study indicates that label-free SERS liquid biopsy assisted by deep learning models holds great promise for the early detection and screening of thyroid cancer.