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Abstract Heavy flavour production in proton-proton (pp) collisions provides insights into the fundamental properties of Quantum Chromodynamics (QCD). Beauty hadron production measurements are widely performed through indirect approaches based on their inclusive decay modes. A Bayesian unfolding data-driven analysis of the ALICE and LHCb data was performed in this study, which recovers the full kinematic information of the beauty hadrons via different inclusive decay channels. The corresponding beauty hadron production cross sections obtained after the Bayesian unfolding are found to be consistent within their uncertainties. The weighted average open beauty production cross sections are presented as a function of the transverse momentum and rapidity in pp collisions at s $$ \sqrt{s} $$ = 5.02 TeV and s $$ \sqrt{s} $$ = 13 TeV, respectively. The p T-integrated open beauty production dσ/dy and the total b b ¯ $$ \textrm{b}\overline{\textrm{b}} $$ cross section σ b b ¯ $$ {\sigma}_{\textrm{b}\overline{\textrm{b}}} $$ are also reported. The precision of these results significantly improves upon worldwide measurements, providing valuable validation and constraints on mechanisms of heavy flavour production in pp collisions at the LHC energies.

Abstract Circularly polarized luminescence materials with broad color tunability are highly valuable for applications in 3D display and photonic technologies. Here we show that incorporating intermolecular charge-transfer complexation into chiral supramolecular polymers is an efficient strategy to achieve this objective. Adjusting the charge-transfer strength between triphenylamine donors and naphthalenemonoimide acceptors enables tunable circularly polarized luminescence signals across the visible light spectrum. This includes blue-colored emission for the supramolecular donor polymers, as well as green, yellow, orange and red-colored emission for supramolecular donor–acceptor polymers. The donor–acceptor packing modes are further influenced by the presence or absence of acetylene linkages on the triphenylamine donors, resulting in ground- or excited-state charge transfer with varying luminescent lifetimes. Additionally, white-light circularly polarized luminescence is achieved by encapsulating blue- and orange-emitting species into surfactant-based micelles in a compartmentalized manner. Overall, manipulating charge-transfer complexation in supramolecular polymers provides an effective approach to wide-range tunable circularly polarized luminescence materials.

Renal unilateral ischemia-reperfusion injury (UIRI) constitutes a significant global health challenge, with poor recovery leading to chronic kidney disease and subsequent renal fibrosis. Extracellular vesicles (EVs) present substantial potential benefits for renal diseases. However, the limited yield and efficacy of EVs produced through traditional methodologies (2D-EVs) severely restrict their widespread application. Moreover, the efficient and effective strategies for using EVs in UIRI treatment and their mechanisms remain largely unexplored. In this study, we propose an innovative approach by integrating bioprinted mesenchymal stem cell microfiber extracellular vesicles production technology (3D-EVs) with a tail vein injection method, introducing a novel treatment strategy for UIRI. Our comparison of the biological functions of 2D-EVs and 3D-EVs, both in vitro and in vivo, reveals that 3D-EVs significantly outperform 2D-EVs. Specifically, in vitro, 3D-EVs demonstrate a superior capacity to enhance the proliferation and migration of NRK-52E cells and mitigate hypoxia/reoxygenation (H/R)-induced injuries by reducing epithelial-mesenchymal transformation, extracellular matrix deposition, and ferroptosis. In vivo, 3D-EVs exhibit enhanced therapeutic effects, as evidenced by improved renal function and decreased collagen deposition in UIRI mouse kidneys. We further elucidate the mechanism by which 3D-EVs derived from KLF15 ameliorate UIRI-induced tubular epithelial cells (TECs) ferroptosis through the modulation of SLC7A11 and GPX4 expression. Our findings suggest that bioprinted mesenchymal stem cells microfiber-derived EVs significantly ameliorate renal UIRI, opening new avenues for effective and efficient EV-based therapies in UIRI treatment.

Abstract Researchers have investigated the potential of leveraging pre-trained language models, such as CodeBERT, to enhance source code-related tasks. Previous methodologies have relied on CodeBERT’s ‘[CLS]’ token as the embedding representation of input sequences for task performance, necessitating additional neural network layers to enhance feature representation, which in turn increases computational expenses. These approaches have also failed to fully leverage the comprehensive knowledge inherent within the source code and its associated text, potentially limiting classification efficacy. We propose CodeClassPrompt, a text classification technique that harnesses prompt learning to extract rich knowledge associated with input sequences from pre-trained models, thereby eliminating the need for additional layers and lowering computational costs. By applying an attention mechanism, we synthesize multi-layered knowledge into task-specific features, enhancing classification accuracy. Our comprehensive experimentation across four distinct source code-related tasks reveals that CodeClassPrompt achieves competitive performance while significantly reducing computational overhead.

Abstract Rheumatoid arthritis (RA) and arthrofibrosis (AF) are both chronic synovial hyperplasia diseases that result in joint stiffness and contractures. They shared similar symptoms and many common features in pathogenesis. Our study aims to perform a comprehensive analysis between RA and AF and identify novel drugs for clinical use. Based on the text mining approaches, we performed a correlation analysis of 12 common joint diseases including arthrofibrosis, gouty arthritis, infectious arthritis, juvenile idiopathic arthritis, osteoarthritis, post infectious arthropathies, post traumatic osteoarthritis, psoriatic arthritis, reactive arthritis, rheumatoid arthritis, septic arthritis, and transient arthritis. 5 bulk sequencing datasets and 4 single-cell sequencing datasets of RA and AF were integrated and analyzed. A novel drug repositioning method was found for drug screening, and text mining approaches were used to verify the identified drugs. RA and AF performed the highest gene similarity (0.77) and functional ontology similarity (0.84) among all 12 joint diseases. We figured out that they share the same key pathogenic cell including CD34 + sublining fibroblasts (CD34-SLF) and DKK3 + sublining fibroblasts (DKK3-SLF). Potential therapeutic target database (PTTD) was established with the differential expressed genes (DEGs) of these key pathogenic cells. Based on the PTTD, 15 potential drugs for AF and 16 potential drugs for RA were identified. This work provides a new perspective on AF and RA study which enhances our understanding of their pathogenesis. It also shed light on their underlying mechanism and open new avenues for drug repositioning studies.

Abstract Ge–Sb–Se–Te chalcogenides, namely Se-substituted Ge–Sb–Te, have been developed as an alternative optical phase change material (PCM) with a high figure-of-merit. A need for the integration of such new PCMs onto a variety of photonic platforms has necessitated the development of fabrication processes compatible with diverse material compositions as well as substrates of varying material types, shapes, and sizes. This study explores the application of chemical solution deposition as a method capable of creating conformally coated layers and delves into the resulting modifications in the structural and optical properties of Ge–Sb–Se–Te PCMs. Specifically, we detail the solution-based deposition of Ge–Sb–Se–Te layers and present a comparative analysis with those deposited via thermal evaporation. We also discuss our ongoing endeavor to improve available choice of processing-material combinations and how to realize solution-derived high figure-of-merit optical PCM layers, which will enable a new era for the development of reconfigurable photonic devices.

Due to the huge capacities of computing and storage resources, wide-area distributed computing environment has become important infrastructures supporting computing power and data interconnection.In wide-area distributed computing environment, matching of tasks and resources is important to improve system performance.However, the diversity of tasks and resources and the geographical dispersion of resources increase the complexity of matching problems.To solve the problems of high response delay and low matching efficiency, a dynamic bidirectional matching method of tasks and resources oriented to wide-area distributed computing environments is proposed.The matching process is simplified and the response delay is mitigated by building a unified task requirement model and resource capability model.Moreover, the task-oriented and resource-oriented matching degrees are defined to express the preference of task-perspective and resource-perspective; the two-side comprehensive matching degree of tasks and resources is defined by the trade-off of the task-oriented and resource-oriented matching degree.The two-side comprehensive matching degrees are dynamically calculated for each task group and the resources to improve the matching quality.The experimental results show that the proposed method can effectively promoting the matching quality and significantly reduce the response delay compared with the existing methods.

In the existing large-scale distributed environments, there is still much room for improvement in the performance and computational efficiency of big data applications.However, performance analysis and optimization in large-scale environments requires a large number of human resources from domain experts.This paper proposes a general lowperformance query statement detection and optimization process for performance optimization in big data applications, summarizes four types of low-performance behaviors that significantly affect the performance of big data applications, and proposes specific optimization strategies for each type of low-performance behavior.Finally, through experimental evaluation, the effectiveness of the optimization scheme in actual large-scale cluster is verified.

【Objective】Caladium bicolor is a foliage plant in the Araceae family, characterized by rich colors and diverse patterns on its leaves, making it widely used for indoor and outdoor ornamental purposes and possessing good economic value. C. bicolor is often cultivated in greenhouses without additional lighting measures, which limits the quality and efficiency of seedling production due to weather conditions, making it difficult to guarantee the production efficiency and standardization of commercial seedlings. Light is an important factor in the growth and pigment accumulation of C. bicolor. The study aims to explore suitable types of light quality for tissue-cultured C. bicolor seedlings, providing a theoretical basis for improving the production efficiency and seedling quality of C. bicolor plants.【Method】We used white fluorescent light as a control and employed 7 different light quality types including LED white light, LED red light, LED blue light, LED red-blue-white 1:1:1, LED red-blue-green 1:1:1 and LED red-blue-white-green 1:1:1:1 light to treat tissue-cultured regenerated plants of C. bicolor. Various growth indicators such as leaf size, leaf thickness, plant height, number of roots, and pigment content of C. bicolor after different light quality treatments were measured to evaluate and select effective light qualities that could enhance the quality of commercial C. bicolor seedlings.【Result】Compared to fluorescent light, LED red light treatment was detrimental to the increase in the number of leaves and the thickness of petioles in C. bicolor, which were 5.3 pieces and 3.42 mm, respectively; it hindered the accumulation of total chlorophyll content and relative anthocyanin content on the leaf surface, which were 2.0 mg/g and 1.0 U/g respectively; and it was also unfavorable for the maximum photochemical efficiency of PSII (Fv/Fm) and the actual quantum yield of photosystem II〔Y(II)〕, with values of only 0.64 and 0.60, respectively. LED blue light treatment promoted the increase in plant height, petiole thickness and accumulation of relative anthocyanin content in C. bicolor, which were 21 cm, 4.6 mm and 6.1 U/g, respectively. However, it was not beneficial for the increase in the number of roots in C. bicolor. For the light combination treatment, LED red blue white green 1:1:1:1 was beneficial for the increase of leaf area, reaching 98.8 cm2. The relative anthocyanin content on the leaf surface was highest under this treatment, reaching 8.23 U/g. LED red blue green 1:1:1 treatment was not conducive to increasing plant height, petiole thickness and leaf thickness, which were 10.6 cm, 3.9 mm, and 0.70 mm, respectively. The relative anthocyanin content on the petioles of C. bicolor under LED red blue white 1:1:1, LED red blue green 1:1:1, and LED red blue white green 1:1:1:1 treatments was significantly lower than that under white fluorescent lamp light treatment.【Conclusion】Different light qualities influence the growth and pigment accumulation of regenerated plants of C. bicolor. LED blue light treatment is the most effective in increasing plant height, petiole thickness and relative anthocyanin content in C. bicolor. LED red blue white green 1:1:1:1 treatment is the most effective in increasing leaf area and relative anthocyanin content on the leaf surface. By selecting the appropriate light quality ratio based on actual conditions in production, the efficiency of standardized production of C. bicolor seedlings can be effectively improved.

Abstract Heavy quarks, produced at early stages of heavy-ion collisions, are an excellent probe of the Quark-Gluon Plasma (QGP) also created in these collisions. Electrons from open heavy-flavor hadron decays (HFE) are good proxies for heavy quarks, and have been measured extensively in the last two decades to study QGP properties. These measurements are traditionally carried out by subtracting all known background sources from the inclusive electron sample. More recently, a significant enhancement of $$e^+e^-$$ e + e - pair production at very low transverse momenta was observed in peripheral heavy-ion collisions. The production characteristics is consistent with coherent photon–photon interactions, which should also constitute a background source to the HFE measurements. In this article, we provide theoretical predictions for the contribution of coherent electron production to HFEs as a function of transverse momentum, centrality and collision energy in Au+Au and Pb+Pb collisions.

Abstract Nucleotides, such as uridine 5′‐monophosphate (5′‐UMP) and cytidine 5′‐monophosphate (5′‐CMP), are heavily demanded as food additives, dietary supplements, and medicinal intermediates. Although enzymatic phosphorylation is an effective approach to producing these nucleosides, its practical application is challenging due to the need for the expensive enzymes and coenzyme guanosine‐5′‐triphosphate (GTP). Here we prepared biocompatible calcium‐based nanoflowers incorporated with cascade enzymes, uridine‐cytidine kinase (UCK) and acetate kinase (ACK), for the production of nucleotides. The spatial distribution of these enzymes was optimized to maximize their catalytic performances. The most active nanoflowers (Ca3(PO4)2& ACK)& UCK that display the rate‐limiting enzyme UCK on the outer layer were used in a packed‐bed reactor for continuous synthesis of 5′‐UMP and 5′‐CMP. The catalytic performance of the catalyst retained over 80% within 10 h, showing good operational stability.

Abstract Introduction The prognostic value of multifocality in paediatric papillary thyroid carcinoma (PTC) patients remains a subject of debate. This study aimed to explore the clinical significance and prognostic value of multifocality in children and adolescents with PTC. Methods This study retrospectively analysed the clinicopathological characteristics and postoperative follow-up data of 338 PTC patients aged ≤ 20 years from May 2012 to July 2022. The clinical and pathological characteristics of 205 patients with unifocal lesions and 133 patients with multifocal lesions were compared. A logistic regression model evaluated the relationship between multifocal lesions and disease recurrence/persistence in children and adolescents with PTC. Based on the median follow-up time of children with multifocal PTC, 114 patients with multifocal PTC older than 20 years were added, and the clinicopathological characteristics were compared between the 133. paediatric/adolescent patients and 114 adult patients with multifocal PTC. Results Among the paediatric and adolescent patients, over a median follow-up time of 49 months, 133 had multifocal disease and 205 had unifocal disease. Multifocal PTC patients exhibited stronger invasiveness in the form of extrathyroidal extension, tumour diameter, lymph node metastasis, and distant metastasis. Multifocality (OR 2.68; p = 0.017), lateral lymph node metastasis (OR 2.85; p = 0.036), and distant metastasis (OR 4.28; p = 0.010) were identified as independent predictive factors for the recurrence/persistence of disease. Comparing the paediatric/adolescent vs. adult multifocal patients, the former demonstrated greater tumour invasiveness. Lateral lymph node metastasis (OR 6.36; P = 0.012) and distant metastasis (OR 3.70; P = 0.027) were independent predictive factors for recurrence/persistence of disease in multifocal patients, while age was not (OR 0.95; P = 0.455). Conclusion Tumour multifocality independently predicts persistent/recurrent disease in paediatric and adolescent PTC patients.

AimsOur study, employing a multi-omics approach, aimed to delineate the distinct gut microbiota and metabolic characteristics in individuals under 30 with unclassified diabetes, thus shedding light on the underlying pathophysiological mechanismsMethodsThis age- and sex-matched case-control study involved 18 patients with unclassified diabetes, 18 patients with classic type 1 diabetes, 13 patients with type 2 diabetes, and 18 healthy individuals. Metagenomics facilitated the profiling of the gut microbiota, while untargeted liquid chromatography-mass spectrometry was used to quantify the serum lipids and metabolites.ResultsOur findings revealed a unique gut microbiota composition in unclassified diabetes patients, marked by a depletion of Butyrivibrio proteoclasticus and Clostridium and an increase in Ruminococcus torques and Lachnospiraceae bacterium 8_1_57FAA. Comparative analysis identified the combined marker panel of five bacterial species, seven serum biomarkers, and three clinical parameters could differentiate patients with UDM from HCs with an AUC of 0.94 (95% CI 0.85–1). Notably, the gut microbiota structure of patients with unclassified diabetes resembled that of type 2 diabetes patients, especially regarding disrupted lipid and branched-chain amino acid metabolism.ConclusionsDespite sharing certain metabolic features with type 2 diabetes, unclassified diabetes presents unique features. The distinct microbiota and metabolites in unclassified diabetes patients suggest a significant role in modulating glucose, lipid, and amino acid metabolism, potentially influencing disease progression. Further longitudinal studies are essential to explore therapeutic strategies targeting the gut microbiota and metabolites to modify the disease trajectory.

BackgroundDNA damage induced by chemotherapy has duality. It affects the efficacy of chemotherapy and constrains its application. An increasing number of studies have shown that traditional Chinese medicine (TCM) is highly effective in reducing side-effects induced by chemotherapy due to its natural, non-toxic and many sourced from food. Recent advancements have demonstrated survival rates are improved attributable to effective chemotherapy. DNA damage is the principal mechanism underlying chemotherapy. However, not all instances of DNA damage are beneficial. Chemotherapy induces DNA damage in normal cells, leading to side effects. It affects the efficacy of chemotherapy and constrains its application.ObjectivesThis review aims to summarize the dual nature of DNA damage induced by chemotherapy and explore how TCM can mitigate chemotherapy-induced side effects.ResultsThe review summarized the latest research progress in DNA damage caused by chemotherapy and the effect of alleviating side effects by TCM. It focused on advantages and disadvantages of chemotherapy, the mechanism of drugs and providing insights for rational and effective clinical treatment and serving as a basis for experiment. In this review, we described the mechanisms of DNA damage, associated chemotherapeutics, and their toxicity. Furthermore, we explored Chinese herb that can alleviate chemotherapy-induced side-effects.ConclusionWe highlight key mechanisms of DNA damage caused by chemotherapeutics and discuss specific TCM herbs that have shown potential in reducing these side effects. It can provide reference for clinical and basic research.

IntroductionThyroid cancer (THCA) is the most common endocrine tumor. Coagulation may be associated with the development of cancer, but its role in THCA patients is not yet clear.MethodsIn this study, we determined the predictive value of coagulation biomarker D-dimer for THCA patient lateral lymph node metastasis (LLNM) through receiver operating characteristics (ROC) analysis and logistic regression analysis. Subsequently, this study used the TCGA database to identify coagulation-related molecular subtypes through consensus clustering analysis and compared their prognosis. We identified coagulation-related genes (CRGs) associated with prognosis in thyroid cancer through gene expression data and clinical information, and constructed a prognostic model by selecting the prognostic CRGs using LASSO regression. Patients were divided into high-risk and low-risk groups based on the median score. Subsequently, prognosis, clinical characteristics, gene mutation occurrence, immune infiltration, function, and drug sensitivity of the two groups were analyzed. We also constructed a nomogram combining the model and clinical features. Finally, the expression of the prognostic CRGs was validated by RT-qPCR.ResultsD-dimers had better performance in predicting LLNM(the area under the curve was 0.656 (95% CI 0.580-0.733), with a cut-off value of 0.065 mg/l), and D-dimer>0.065mg/l was an independent predictor of LLNM. Then, we selected 8 prognostic CRGs to construct a predictive model. The prognosis of low-risk group patients was significantly better than that of high-risk group (P

Background In the realm of wheat seed germination, abiotic stresses such as salinity and high temperature have been shown to hinder the process. These stresses can lead to the production of reactive oxygen species, which, within a certain concentration range, may actually facilitate seed germination. γ-aminobutyric acid (GABA), a non-protein amino acid, serves as a crucial signaling molecule in the promotion of seed germination. Nevertheless, the potential of GABA to regulate seed germination under the simultaneous stress of heat and salinity remains unexplored in current literature. Methods This study employed observational methods to assess seed germination rate (GR), physiological methods to measure H2O2 content, and the activities of glutamate decarboxylase (GAD), NADPH oxidase (NOX), superoxide dismutase (SOD), and catalase (CAT). The levels of ABA and GABA were quantified using high-performance liquid chromatography technology. Furthermore, quantitative real-time PCR technology was utilized to analyze the expression levels of two genes encoding antioxidant enzymes, MnSOD and CAT. Results The findings indicated that combined stress (30 °C + 50 mM NaCl) decreased the GR of wheat seeds to about 21%, while treatment with 2 mM GABA increased the GR to about 48%. However, the stimulatory effect of GABA was mitigated by the presence of ABA, dimethylthiourea, and NOX inhibitor, but was strengthened by H2O2, antioxidant enzyme inhibitor, fluridone, and gibberellin. In comparison to the control group (20 °C + 0 mM NaCl), this combined stress led to elevated levels of ABA, reduced GAD and NOX activity, and a decrease in H2O2 and GABA content. Further investigation revealed that this combined stress significantly suppressed the activity of superoxide dismutase (SOD) and catalase (CAT), as well as downregulated the gene expression levels of MnSOD and CAT. However, the study demonstrates that exogenous GABA effectively reversed the inhibitory effects of combined stress on wheat seed germination. These findings suggest that GABA-induced NOX-mediated H2O2 signalling plays a crucial role in mitigating the adverse impact of combined stress on wheat seed germination. This research holds significant theoretical and practical implications for the regulation of crop seed germination by GABA under conditions of combined stress.

BackgroundNumerous studies have recently examined the impact of dietary factors such as high-fat diets on fatigue. Our study aims to investigate whether high-fat diet (HFD) alone or combined with alternate-day fasting (ADF) can lead to the central fatigue symptoms and to investigate the potential integration of dietary and sleep variables in the development of central fatigue models.MethodsSeventy-five male Wistar rats were divided into five groups: control, HFD, HFD + ADF, modified multiple platform method (MMPM), and MMPM+HFD + ADF. Each group underwent a 21-day modeling period according to their respective protocol. Their behavioral characteristics, fatigue biochemical markers, hippocampal pathological changes, mitochondrial ultrastructure, and oxidative stress damage were analyzed.ResultsOur findings demonstrate that using only HFD did not cause central fatigue, but combining it with ADF did. This combination led to reduced exercise endurance, decreased locomotor activity, impaired learning and memory abilities, along with alterations in serum levels of alanine aminotransferase (ALT), creatine kinase (CK), and lactate (LAC), as well as hippocampal pathological damage and other central fatigue symptoms. Moreover, the MMPM+HFD + ADF method led to the most obvious central fatigue symptoms in rats, including a variety of behavioral changes, alterations in fatigue-related biochemical metabolic markers, prominent pathological changes in hippocampal tissue, severe damage to the ultrastructure of mitochondria in hippocampal regions, changes in neurotransmitters, and evident oxidative stress damage. Additionally, it was observed that rats subjected to HFD + ADF, MMPM, and MMPM+HFD + ADF modeling method exhibited significant brain oxidative stress damage.ConclusionWe have demonstrated the promotive role of dietary factors in the development of central fatigue and have successfully established a more stable and clinically relevant animal model of central fatigue by integrating dietary and sleep factors.

Background: AGBL2's role in tumorigenesis and cancer progression has been reported in several cancer studies, and it is closely associated with α-tubulin detyrosination. The roles of AGBL2 and α-tubulin detyrosination in renal cell carcinoma (RCC) pathogenesis remain unclear and require further investigation. Methods: In this study, we conducted an analysis of AGBL2 expression differences between renal clear cell carcinoma tissues and normal tissues using data from The Cancer Genome Atlas (TCGA). We performed a comprehensive prognostic analysis of AGBL2 in Kidney Renal Clear Cell Carcinoma (KIRC) using univariate and multivariate Cox regression. Based on the results of the Cox analysis, we constructed a prognostic model to assess its predictive capabilities. Receiver Operating Characteristic (ROC) analysis confirmed the diagnostic value of AGBL2 in renal cancer. We conducted further validation by analyzing cancer tissue samples and renal cancer cell lines, which confirmed the role of AGBL2 in promoting RCC cell proliferation and migration through in vitro experiments. Additionally, we verified the impact of AGBL2's detyrosination on α-tubulin using the tubulin carboxypeptidase (TCP) inhibitor parthenolide. Finally, we performed sequencing analysis on AGBL2 knockdown 786-O cells to investigate the correlation between AGBL2, immune infiltration, and AKT phosphorylation. Moreover, we experimentally demonstrated the enhancing effect of AGBL2 on AKT phosphorylation. Results: TCGA analysis revealed a significant increase in AGBL2 expression in RCC patients, which was correlated with poorer overall survival (OS), disease-specific survival (DSS), and progression-free intervals (PFI). According to the analysis results, we constructed column-line plots to predict the 1-, 3-, and 5-year survival outcomes in RCC patients. Additionally, the calibration plots assessing the model's performance exhibited favorable agreement with the predicted outcomes. And the ROC curves showed that AGBL2 showed good diagnostic performance in KIRC (AUC = 0.836)). Cell phenotyping assays revealed that AGBL2 knockdown in RCC cells significantly inhibited cell proliferation and migration. Conversely, overexpression of AGBL2 resulted in increased cell proliferation and migration in RCC cells. We observed that AGBL2 is predominantly located in the nucleus and can elevate the detyrosination level of α-tubulin in RCC cells. Moreover, the enhancement of RCC cell proliferation and migration by AGBL2 was partially inhibited after treatment with the TCP inhibitor parthenolide. Analysis of the sequencing data revealed that AGBL2 is associated with a diverse array of biological processes, encompassing signal transduction and immune infiltration. Interestingly, AGBL2 expression exhibited a negative correlation with the majority of immune cell infiltrations. Additionally, AGBL2 was found to enhance the phosphorylation of AKT in RCC cells. Conclusion: Our study suggests that AGBL2 fosters RCC cell proliferation and migration by enhancing α-tubulin detyrosination. Moreover, elevated AGBL2 expression increases phosphorylation of AKT in RCC cells.

IntroductionMicrobial pathogens invade various human organs, including the oral cavity. Candida albicans (C.a) and Streptococcus mutans (S.m) served respectively as representative oral pathogenic fungi and bacteria to stimulate dental pulp stem cells (DPSCs) and to screen the DPSC subcluster that specifically responded to fungal infection.MethodsDPSCs were obtained from the impacted third molars of six healthy subjects. Then, cells were mixed and divided into three samples, two of which were stimulated with C.a and S.m, respectively; the third sample was exposed to cell medium only (Ctrl). Single-cell mRNA sequencing analysis of treated DPSCs was performed.ResultsDPSCs were composed of four major clusters of which one, DPSC.7, exhibited unique changes compared to those of other subclusters. The DPSC.7 cell percentage of the C.a sample was twice those of the Ctrl and S.m samples. DPSC.7 cells expressed genes associated with the response to reactive oxygen species (ROS) response. DPSC.7 subgroup cells established characteristic aggregation under the stimulation of different pathogens in UMAP. The MAPK/ERK1/2 and NF-κB pathways were up-regulated, DUSP1/5/6 expressions were suppressed, FOS synthesis was activated, the immune-related pathway was induced, and the levels of cytokines, including IL-6 and CCL2, were up-regulated in DPSC.7 cells when stimulated with C.a.ConclusionsOur study analyzed the cellular and molecular properties of DPSCs infected by oral fungi and bacteria with single-cell RNA sequencing. A subcluster of DPSCs responded specifically to infections with different pathogens, activating the MAPK and NF-κB pathways to induce immune responses via the ROS pathway. This suggests novel treatment strategies for fungal infections.

Objectives: IGF-binding protein 1 (IGFBP1) is a key regulator of insulin-like growth factors, impacting biological processes, including cancer progression and prognosis. Materials and methods: This study investigates genetic alterations affecting IGFBP1 expression in tumors using data from The Cancer Genome Atlas (TCGA) PanCancer Atlas via cBioPortal. We analyzed samples from 32 cancer types for mutation sites, including deep deletions, amplifications, and mutations. RNA-seq data were normalized using log2(value + 1). Statistical analyses, including survival outcomes, were conducted using R packages like ggplot2, stats, and car. Kaplan-Meier survival curves and log-rank tests assessed overall survival (OS) and progression-free survival (PFS). Univariate Cox regression was used to develop nomogram models for OS. Functional consequences of IGFBP1 mutations were explored through protein structure, stability, and IGF interaction analyses. Protein-protein interaction networks and functional enrichment were analyzed using GEPIA2, STRING, and Cytoscape. Gene Ontology (GO), KEGG, and Gene Set Enrichment Analysis (GSEA) provided insights into affected biological pathways. Results: Pan-cancer analysis revealed diverse expression patterns, including significant upregulation in cutaneous melanoma (SKCM) and downregulation in lung adenocarcinoma (LUAD) and stomach adenocarcinoma (STAD). Specifically, elevated IGFBP1 expression in SKCM patients led to a 25 % improvement in 5-year survival. In contrast, higher IGFBP1 levels in LUAD and OV patients resulted in a 30 % and 20 % decrease in survival, respectively. Elevated IGFBP1 levels are significantly linked to advanced tumor stage and grade in OV and LUAD, affecting prognostic outcomes. Nomogram models for OV, SKCM, LUAD, and STAD showed IGFBP1's predictive strength with AUC values ranging from 0.70 to 0.85, indicating its diagnostic potential. Genetic analyses revealed mutations in IGFBP1 in 12 % of STAD cases and 10 % of UCEC cases, indicating significant genetic variation. Immune analysis showed that high IGFBP1 expression significantly influenced immune cell infiltration, particularly macrophages and CD8+ T cells, thereby affecting survival in LUAD and OV. Functional enrichment and gene set enrichment analysis identified IGFBP1 involvement in crucial pathways, such as cell cycle regulation, immune response, and PD-1 signaling, highlighting its biological impact. Additionally, IGFBP1 expression delineates distinct molecular and immune subtypes, correlating with specific cancer behaviors and immune patterns. Conclusions: These findings highlight IGFBP1's potential as a biomarker and therapeutic target, particularly for immunoregulation and cancer subtype stratification.

BackgroundEarly childhood caries (ECC) are a prevalent chronic disease in young children. However, there has been limited research on the microbiota in different tissue levels of the same tooth in children with ECC. This study aimed to investigate the dynamic changes in bacterial diversity during the progression of Severe Early Childhood Caries (S-ECC) within the same tooth, from the tooth surface to the root canal, by collecting tissue samples from different areas of the affected tooth.MethodsTwenty primary teeth with periapical periodontitis were selected from 20 children aged 3–5 years, with 100 samples collected from the different layers: uncavitated buccal enamel surface without white spot lesion (surface), the outermost layer of the dentin carious lesion (superficial), the inner layer of carious dentin (deep), necrotic pulp tissue (pulp), and root exudate (exudate). The taxonomy of each OTU representative sequence was analyzed against the 16S rRNA database. Comparisons of alpha diversity between groups were performed. The number of shared and unique genera between groups counted. Beta diversity was contrasted to evaluate differences in bacterial community composition, and the relationships between the microbiota and samples were analyzed. The heatmap analysis of the 30 most abundant genera was used, which highlighted their relative distribution and abundance. The significantly abundant taxa (phylum to genera) of bacteria among the different groups were identified. The differences of relative abundance between bacterial genera among the five groups were analyzed. Significant Spearman correlations were noted, and visualization of the co-occurrence network was conducted.ResultsBacterial 16S rRNA gene sequencing showed that most genera were present in all layers, with the number of shared genera increasing as the disease advanced. The bacterial communities and core genera in the co-occurrence network changed with progression to severe ECC.ConclusionAn increase in both the quantity and complexity of bacterial interactions was observed. This study emphasized the importance of paying attention to the relationship between microbial species rather than just checking changes in bacterial species structure when investigating the role of bacteria in disease progression.

The fatigue crack propagation (FCP) behavior of a new Al–Cu–Li alloy under different aging treatments including T3, T8, and non-isothermal aging (NIA) was investigated. It was detected that the T8-24h sample exhibited the highest FCP resistance and the best mechanical performance. Compared with the T3-40D sample, the crack paths of the T8-24h sample and the C150 (non-isothermal peak-aged) sample were more tortuous and the crack width was narrower. Furthermore, the T8-24 sample had the lowest decreased FCP rate by an order of magnitude at the stress intensity factor (ΔK) of 30 MPa·m1/2. A large number of nano-scale T1 phases were precipitated in the T8-24h sample and their number density was also increased compared with the other sample. The presence of the tiny T1 phase plays a crucial role in impeding crack propagation as it can be sheared by dislocations without accumulating damage. This resulted in a substantial improvement both in the mechanical and fatigue properties of the alloy. Moreover, in the Paris stage of FCP, factors such as the size and concentration of precipitates within the grain and grain boundary play a vital role in determining the extent of crack growth. The results of transmission electron microscopy (TEM) bright field images on grain boundaries (GBs) analysis show that the variations in strength between the grain boundary and intragranular regions have a direct influence on the alloy's susceptibility to fatigue and corrosion resistance.

Abstract Considering the high recrudescence and the long-lasting unhealed large-sized wound that affect the aesthetics and cause dysfunction after resection of maxillofacial malignant skin tumors, a groundbreaking strategy is urgently needed. Photothermal therapy (PTT), which has become a complementary treatment of tumors, however, is powerless in tissue defect regeneration. Therefore, a novel multifunctional sodium nitroprusside and Fe2+ ions loaded microneedles (SNP-Fe@MNs) platform was fabricated by accomplishing desirable NIR-responsive photothermal effect while burst releasing nitric oxide (NO) after the ultraviolet radiation for the ablation of melanoma. Moreover, the steady releasing of NO in the long term by the platform can exert its angiogenic effects via upregulating multiple related pathways to promote tissue regeneration. Thus, the therapeutic dilemma caused by postoperative maxillofacial skin malignancies could be conquered through promoting tumor cell apoptosis via synergistic PTT—gas therapy and subsequent regeneration process in one step. The bio-application of SNP-Fe@MNs could be further popularized based on its ideal bioactivity and appealing features as a strategy for synergistic therapy of other tumors occurred in skin. Graphical Abstract

In order to explore the antioxidant ability of different solvent extracts of Ge-riched Auricularia auricular mycelium in vitro, the Ge-riched A. auricular mycelium was extracted by water, 70% ethanol and ethyl acetate. The scavenging ability of different extracts on superoxide anion free radical, hydroxyl free radical and DPPH free radical were compared. The comprehensive antioxidant capacity of different solvent extracts was evaluated by subordinate function value, and the correlation between substance content and antioxidant capacity were analyzed. The results showed that the content of organic Ge in Ge-riched A. auricular mycelium was 542.83 μg/g. The extraction rate and substance content of different solvent extracts were different, the extraction rate of water extract and ethanol extract was higher, the polysaccharide content of water extract was the highest, and the polyphenol and flavonoid content of ethyl acetate extract was the highest. Different solvent extracts had certain scavenging ability on free radicals，and the extract concentration increased with the increase. Water extract had the strongest scavenging rate of superoxide anion free radical，when the extract concentration was 9 mg/mL, the highest clearance rate was 43.32%. 70% ethanol extract had the best scavenging effect on hydroxyl free radical and DPPH free radical. When the extract concentration was 9 mg/mL, the scavenging rate was 70.10% and 76.99%, respectively. Polysaccharides, polyphenols and flavonoids all played different roles in scavenging free radicals, and ethanol extract had the strongest comprehensive antioxidant capacity. The contents of polysaccharides, polyphenols and flavonoids were significant (P

Abstract The Amur tiger is currently confronted with challenges of anthropogenic development, leading to its population becoming fragmented into two geographically isolated groups: smaller and larger ones. Small and isolated populations frequently face a greater extinction risk, yet the small tiger population’s genetic status and survival potential have not been assessed. Here, a total of 210 samples of suspected Amur tiger feces were collected from this small population, and the genetic background and population survival potentials were assessed by using 14 microsatellite loci. Our results demonstrated that the mean number of alleles in all loci was 3.7 and expected heterozygosity was 0.6, indicating a comparatively lower level of population genetic diversity compared to previously reported studies on other subspecies. The genetic estimates of effective population size (Ne) and the Ne/N ratio were merely 7.6 and 0.152, respectively, representing lower values in comparison to the Amur tiger population in Sikhote-Alin (the larger group). However, multiple methods have indicated the possibility of genetic divergence within our isolated population under study. Meanwhile, the maximum kinship recorded was 0.441, and the mean inbreeding coefficient stood at 0.0868, both of which are higher than those observed in other endangered species, such as the African lion and the grey wolf. Additionally, we have identified a significant risk of future extinction if the lethal equivalents were to reach 6.26, which is higher than that of other large carnivores. Further, our simulation results indicated that an increase in the number of breeding females would enhance the prospects of this population. In summary, our findings provide a critical theoretical basis for further bailout strategies concerning Amur tigers.

Abstract Background Atrial septal defect (ASD) is a common form of congenital heart disease. Although several genes related to ASD have been found, the genetic factors of ASD remain unclear. This study aimed to evaluate the correlation between 10 candidate single nucleotide polymorphisms (SNPs) and sporadic atrial septal defects. Methods Based on the results of 34 individual whole exome sequences, 10 candidate SNPs were selected. In total, 489 ASD samples and 420 normal samples were collected. The 10 SNPs in the case group and the control group were identified through Snapshot genotyping technology. The χ2-test and unconditional regression model were used to evaluate the relationship between ASD and each candidate SNP. Haploview software was used to perform linkage disequilibrium and haplotype analysis. Results The χ2 results showed that the FLT4 rs383985 (P = 0.003, OR = 1.115–1.773), HYDIN rs7198975 (P = 0.04621, OR = 1.003–1.461), and HYDIN rs1774266 (P = 0.04621, OR = 1.003–1.461) alleles were significantly different between the control group and the case group (P

Abstract Background Prior studies reported that elevated asprosin level was associated with obesity in adults and animal models. However, the relationship between asprosin level and children with obeisty remains controversial. The aim of our analysis was to systematically review available literatures linking asprosin and children with obesity for a comprehensive understanding of the relationship between circulating asprosin level and obesity in children. Methods Eight databases were gleaned for studies published up to January 2024. Standard mean difference with 95% confidence interval (CI) and Fisher’s Z transformation was calculated to evaluate the relationship between asprosin level and children with obesity using the Review Manager 5.4 Software. Other indicators were measured via mean difference with 95% CI. Results Six observational studies were included both in systematic review and meta-analysis. The current evidence indicated that no significant difference was observed in the level of circulating asprosin between the children with and without obesity (SMD = 0.37; 95% CI:—0.22–0.95, p = 0.22). However, Fisher’s Z transformation suggested the positive association of circulating asprosin levels and clinical index measuring the degree of obesity: total cholesterol (Fisher’s Z: 0.11, 95% CI: 0.02–0.20, p = 0.02). Conclusions Circulating asprosin level was not independently related to childhood obesity currently. More rigorous longitudinal researches were required to disentangle the causations. However, the positive association of asprosin levels and total cholesterol indicated that asprosin might get involved in the lipid-metabolism of childhood obesity, asprosin might be a prospective bio-index and targeted treatment of total cholesterol metabolism besides the role of glucogenic and orexigenic. Trial registration Prospero ID: CRD42023426476.

Cover cropping has the potential to generate private economic benefits to farm operations as well as larger-scale environmental benefits to the broader community. However, cover crop adoption remains limited in the United States (US) (i.e., 4.7 % in 2022 (USDA-NASS, 2024)), primarily due to uncertainty in economic outcomes, with several studies showing potentially negative net returns from cover crop use in the short-term (1–3 years). This study investigates the medium-term (5–7 years) economic impact of cover crop adoption using plot-level data from field experiments in the state of Maryland. The empirical analysis employs ordinary least squares (OLS) statistical models and partial budgeting techniques to achieve the study objective. Our results show that cover crops do not have a statistically significant effect on crop yield, fertilizer costs, or pesticide costs, but we find that cover crop use statistically increases field operation and seed expenses. As a result, the private net return from cover crop adoption in the medium term is generally negative based on the Maryland field trial data used in the analysis. Specifically, the average net return per acre with cover crops is approximately $60-$90 lower for corn and around $60 lower for soybeans compared to fields without cover crops. This empirical finding suggests that public support through incentive payments may help further incentivize cover crop adoption in the US, which can then provide environmental and ecosystem services that are of benefit to the general public.

Significant energy transition would be needed in China under the carbon neutrality target. Since it would have important impacts on water resource through increased usage, understanding the water demand under specific climate change targets could enable better policy-making for the energy transition. In order to quantitatively analyze the impacts, this study proposed a methodology that combines CO2 emissions, energy transition, and water demand. An energy-water integrated assessment model was built, to simulate the future energy and CO2 emissions pathways up to 2050 in China. The water demand of energy systems under both policy scenario (PS) and two mitigation scenarios (2C and 1.5C) are calculated. The key influencing factors of water demand are analysed in two low-water-demand mitigation scenarios (2C-LW and 1.5C-LW). The results showed that China’s future energy system and CO2 emissions pathways change significantly under mitigation scenarios. The timing of the CO2 emissions peak advances from around 2030 under the PS scenario to between 2020 and 2025 in the mitigation scenarios. Near-zero emissions are achieved by 2050 under the 1.5C scenario. However, with no further water-saving measures, water consumption in energy sector would continue to increase under both the policy scenario and mitigation scenarios. This pressure is compounded by certain mitigation technologies, such as inland nuclear power, biomass energy, and CCS technologies. As such, the potential for water conservation in energy system under climate mitigation targets is studied. The results showed that water-saving measures can significantly reduce long-term water demand in the energy system.

Cache plays a crucial role in improving system response time, alleviating server pressure, and achieving load balancing in various aspects of modern information systems. The data prefetch and cache replacement algorithms are significant factors influencing caching performance. Due to the inability to learn user interests and preferences accurately, existing rule-based and data mining caching algorithms fail to capture the unique features of the user access behavior sequence, resulting in low cache hit rates. In this article, we introduce BERT4Cache, an end-to-end bidirectional Transformer model with attention for data prefetch in cache. BERT4Cache enhances cache hit rates and ultimately improves cache performance by predicting the user’s imminent future requested objects and prefetching them into the cache. In our thorough experiments, we show that BERT4Cache achieves superior results in hit rates and other metrics compared to generic reactive and advanced proactive caching strategies.

BackgroundThe WFS1 gene encodes the protein wolframin, which is crucial for maintaining endoplasmic reticulum homeostasis. Variants in this gene are predominantly associated with Wolfram syndrome and have been implicated in other disorders such as diabetes mellitus and psychiatric diseases, which increases the rate of clinical misdiagnosis.MethodsPatients were diagnosed with early-onset unclassified diabetes according to their clinical and laboratory data. We performed whole-exome sequencing (WES) in 165 patients, interpreting variants according to the American College of Medical Genetics/Association for Molecular Pathology (ACMG/AMP) 2015 guidelines. Variant verification was done by Sanger sequencing. In vitro experiments were conducted to evaluate the effects of WFS1 compound heterozygous variants.ResultsWe identified WFS1 compound heterozygous variants (p.A214fs*74/p.F329I and p.I427S/p.I304T) in two patients with Wolfram Syndrome-Like disorders (WSLD). Both WFS1 compound heterozygous variants were associated with increased ER stress, reduced cell viability, and decreased SERCA2b mRNA levels. Additionally, pathogenic or likely pathogenic WFS1 heterozygous variants were identified in the other three patients.ConclusionOur results underscore the importance of early genetic testing for diagnosing young-onset diabetes and highlight the clinical relevance of WFS1 variants in increasing ER stress and reducing cell viability. Incorporating these genetic insights into clinical practice can reduce misdiagnoses and improve treatment strategies for related disorders.

Under a full straw returning system, the relationship between soil bacterial community diversity and straw decomposition, yield, and the combined application of slow-release nitrogen and urea remains unclear. To evaluate these effects and provide an effective strategy for sustainable agricultural production, a 2-year field positioning trial was conducted using maize as the research object. Six experimental treatments were set up: straw returning + no nitrogen fertilizer (S1N0), straw returning + slow-release nitrogen fertilizer:urea = 0:100% (S1N1), straw returning + slow-release nitrogen fertilizer:urea = 30%:70% (S1N2), straw returning + slow-release nitrogen fertilizer:urea = 60%:40% (S1N3), straw returning + slow-release nitrogen fertilizer:urea = 90%:10% (S1N4), and straw removal + slow-release nitrogen fertilizer:urea = 30%:70% (S0N2). Significant differences (p

Central fatigue is a common pathological state characterized by psychological loss of drive, lack of appetite, drowsiness, and decreased psychic alertness. The mechanism underlying central fatigue is still unclear, and there is no widely accepted successful animal model that fully represents human characteristics. We aimed to construct a more clinically relevant and comprehensive animal model of central fatigue. In this study, we utilized the Modified Multiple Platform Method (MMPM) combined with alternate-day fasting (ADF) to create the animal model. The model group rats are placed on a stationary water environment platform for sleep deprivation at a fixed time each day, and they were subjected to ADF treatment. On non-fasting days, the rats were allowed unrestricted access to food. This process was sustained over a period of 21 days. We evaluated the model using behavioral assessments such as open field test, elevated plus maze test, tail suspension test, Morris water maze test, grip strength test, and forced swimming test, as well as serum biochemical laboratory indices. Additionally, we conducted pathological observations of the hippocampus and quadriceps muscle tissues, transmission electron microscope observation of mitochondrial ultrastructure, and assessment of mitochondrial energy metabolism and oxidative stress-related markers. The results revealed that the model rats displayed emotional anomalies resembling symptoms of depression and anxiety, decreased exploratory behavior, decline in learning and memory function, and signs of skeletal muscle fatigue, successfully replicating human features of negative emotions, cognitive decline, and physical fatigue. Pathological damage and mitochondrial ultrastructural alterations were observed in the hippocampus and quadriceps muscle tissues, accompanied by abnormal mitochondrial energy metabolism and oxidative stress in the form of decreased ATP and increased ROS levels. In conclusion, our ADF+MMPM model comprehensively replicated the features of human central fatigue and is a promising platform for preclinical research. Furthermore, the pivotal role of mitochondrial energy metabolism and oxidative stress damage in the occurrence of central fatigue in the hippocampus and skeletal muscle tissues was corroborated.

Abstract Researchers usually detect insider threats by analyzing user behavior. The time information of user behavior is an important concern in internal threat detection. Existing works on insider threat detection fail to make full use of the time information, which leads to their poor detection performance. In this paper, we propose a novel behavioral feature extraction scheme: we implicitly encode absolute time information in the behavioral feature sequences and use a feature sequence construction method taking covariance into account to make our scheme adaptive to users. We select Stacked Bidirectional LSTM and Feedforward Neural Network to build a deep learning-based insider threat detection model: Behavior Rhythm Insider Threat Detection (BRITD). BRITD is universally applicable to various insider threat scenarios, and it has good insider threat detection performance: it achieves an AUC of 0.9730 and a precision of 0.8072 with the CMU CERT dataset, which exceeds all baselines. Graphical Abstract

Abstract Background Some studies have assessed the predictive role of the atherogenic index of plasma (AIP) for macrovascular diseases. This prospective investigation aimed to elucidate whether AIP is associated with diabetic kidney disease (DKD) and diabetic retinopathy (DR) incidence. Methods The data were extracted from 4831 participants, of whom 2943 and 3360 participants with type 2 diabetes (T2D) were included in the DKD and DR follow-up analyses, respectively. Cox regression models were performed to test the relationships of AIP value at baseline with the risk of incident DKD and DR. Group-based trajectory modelling was utilized to discern AIP trajectories during the follow-up period. Subsequently, logistic regressions were applied to ascertain the influence of AIP trajectories on the incidence of DKD and DR. Results During the follow-up period, 709 (24.1%) and 193 (5.7%) participants developed DKD and DR, respectively. The median (interquartile range) follow-up time was 24.2 (26.3) months for DKD and 25.7 (27.0) months for DR. According to the multivariate Cox regression models, baseline AIP was positively and linearly related to the occurrence of DKD, with a hazard ratio of 1.75 (95% confidence interval [CI] 1.36–2.26). Three distinct trajectories of AIP were identified throughout the follow-up time: Low (31.4%), Median (50.2%), and High (18.3%). Compared to participants with the Low AIP trajectory, those with High and Median AIP trajectories presented 117% (95% CI: 1.62–2.91) and 84% (95% CI 1.46–2.32) greater odds of developing DKD, respectively. However, neither baseline levels nor trajectories of AIP were shown to be related to DR after adjusting for confounding factors. Conclusions Baseline levels and trajectories of AIP were independently related to elevated DKD risk, indicating that AIP could be used as a predictor for identifying T2D participants at higher risk of DKD. No association between AIP and DR was detected.

Abstract Background Oral cancer is considered one of the most malignant types of tumors and is known for its high likelihood of recurrence and metastasis. During clinical treatment, patients with oral cancer often develop resistance to chemotherapy, making the treatment process challenging. The purpose of this study was to investigate the genes related to chemotherapy resistance and their mechanisms in oral cancer patients. Methods The “limma” package was used to identify the differentially expressed genes between tumor and normal tissues from TCGA dataset. Subsequently, the “WGCNA” package was utilized to discover genes associated with chemoresistance. Cisplatin-resistant oral cancer cell lines were obtained through exposure to gradually increasing doses of cisplatin. SiRNA was used to knock down the MT3 and YAP1 genes to validate their functions. Finally, the therapeutic efficacy of combining a YAP1 inhibitor with cisplatin was confirmed by inoculating an oral cancer cell line in mice. Results In our study, we analyzed 43 OSCC samples and identified 724 different genes using the weighted gene coexpression network analysis (WGCNA) method. Among these genes, MT3 stood out as strongly associated with chemotherapy resistance. Patients with high MT3 expression had worse prognoses, and MT3 levels were elevated in drug-resistant patients. Knocking down MT3 reversed tumor cell chemoresistance. We also observed that MT3 increased the expression of YAP1, potentially contributing to chemotherapy resistance by inducing tumor stemness through YAP1. In animal models, using YAP1 inhibitors improved the effectiveness of cisplatin in treating chemoresistant oral cancer. Conclusions MT3 is related to chemotherapy resistance, which may be caused by its promotion of YAP1 expression and induction of tumor cell stemness. Inhibiting the activity of MT3 and YAP1 is helpful for increasing chemotherapy sensitivity.

Prior studies demonstrated an equivocal conclusion about the association between the level of retinol-binding protein 4 (RBP4)/visfatin and periodontitis patients with obesity. The aim of our study (Prospero ID: CRD42023469058) was to systematically review the available articles linking the biofluid levels of RBP4/visfatin to the comorbidity of periodontitis and obesity. Clinical trials were screened in accordance with specific inclusion criteria from seven databases up to November 2023. A quality assessment was performed with the Newcastle–Ottawa Scale and ROBINS-I tools for observational and interventional trials, respectively. The standard mean difference (SMD) with a 95% confidence interval (CI) related to the RBP4 level was recorded; the other indicators related to the visfatin level were measured via the mean difference (MD) with the corresponding 95% CI, and Fisher’s Z transformation was measured to reveal the association using Review Manager 5.4. The current evidence was based on five observational studies and two interventional studies. All of them were included in the systematic review, and six of them were in the meta-analysis. Statistical analysis indicated that there was no significant difference in the circulating levels of RBP4 in the periodontitis patients with obesity or without, who were labeled as OP or NP, respectively (155 OP-107 NP: SMD = 1.38; 95% CI: −0.18–2.94, p = 0.08), as well as the periodontal healthy patients with a normal weight, who were labelled as NnP (116 OP-79 NnP: SMD = 6.76; 95% CI: −5.34–18.87, p = 0.27). Meanwhile, a significant higher level of serum visfatin was found in the OP patients than that of the NP (86 OP-45 NP: MD = 4.21; 95% CI: 2.65–5.77, p < 0.00001)/NnP (164 OP-88 NnP: MD = 13.02; 95% CI: 7.34–18.70, p < 0.00001) group. In addition, a positive association was observed between the serum RBP4 and body mass index/clinical attachment loss (CAL). And, then, there was a positive association between the serum visfatin and periodontal parameters, including the probing depth, CAL, and plaque index, as well as metabolic parameters, including the total cholesterol, triglycerides, fasting blood glucose, and low-density lipoprotein cholesterol. Here, the circulating RBP4 level was not independently related to the comorbidity of periodontitis and obesity, while serum visfatin was significantly associated with periodontitis and obesity. Notably, the positive association between circulating RBP4/visfatin and the periodontal parameters/metabolic parameters firmly suggested that the higher severity of the obese or periodontal status was associated with an elevated level of serum visfatin or RBP4 in the OP group. With more rigorous longitudinal research, the exact causations between RBP4/visfatin and the patients affected by obesity and periodontitis could be disentangled. RBP4 and visfatin might be novel, enlightening prospective bio-indexes for the targeted treatment of comorbidities.

Mixed matrix lithium adsorbents have attracted much interest for lithium recovery from brine. However, the absence of an interfacial interaction between the inorganic lithium-ion sieves (LISs) and the organic polymer matrix resulted in the poor structural stability and attenuated lithium adsorption efficiency. Here, a novel hollow hemispherical mixed matrix lithium adsorbent (H-LIS) with high interfacial compatibility was constructed based on mussel-bioinspired surface chemistry using a solvent evaporation induced phase transition method. The effects of types of functional modifiers, LIS loading amount, adsorption temperature and pH on their structural stability and lithium adsorption performance were systematically investigated. The optimized H-LIS adsorbent with the LIS loading amount of 50 wt.% possessed the structural merit that the LIS functionally modified by dopamine exposed on both the inner and outer surfaces of the hollow hemispheres. At the best adsorption pH of 12.0, it showed a comparable lithium adsorption capacity of 25.68 mg·g−1 to the powdery LIS within 4 h, favorable adsorption selectivity of Mg/Li and good reusability that could maintain over 90% of lithium adsorption capacity after the LiCl adsorption—0.25 M HCl pickling-DI water cleaning cycling processes for three times. The interfacial interaction mechanism of H-LIS for lithium adsorption was innovatively explored via advanced microcalorimetry technology. It suggested the nature of the Li+ adsorption process was exothermic and dopamine modification could reduce the activation energy for lithium adsorption from 15.68 kJ·mol−1 to 13.83 kJ·mol−1 and trigger a faster response to Li+ by strengthening the Li+-H+ exchange rate, which established the thermodynamic relationship between the structure and Li+ adsorption performance of H-LIS. This work will provide a technical support for the structural regulation of functional materials for lithium extraction from brine.

The small brown planthopper (SBPH), Laodelphax striatellus (Fallén) (Hemiptera: Delphacidae), is an increasing threat to Gramineae crops, posing significant risks to both the environment and food safety. β-asarone, as a promising green alternative to chemical insecticides, possesses wide application prospects in the crop protection field. To enhance the insecticidal activity of β-asarone, a series of derivatives were prepared through an active substructure splicing strategy, and their insecticidal activities against SBPH were evaluated. Among the 7 commercial compounds with chemical structures similar to β-asarone and 12 structural derivatives of β-asarone, compound 10, which incorporates the 2-chloropyridine functional group from flupyrimin, exhibited the most potent insecticidal activity against SBPH, with an 8.31-fold increase in insecticidal activity compared to β-asarone. Furthermore, transcriptome analysis showed that among the selected genes that may play important roles in insecticidal activity, an ABC transporter gene, MDR49, was most significantly down-regulated. MDR49 was highly expressed in the 4th-instar nymphs, with the highest expression level in the fat body, midgut, and abdomen. RNA interference (RNAi) against MDR49 significantly reduced susceptibility to compound 10 in SBPH, which revealed that MDR49 may be the candidate insecticidal target of compound 10. Additionally, the insecticidal spectrum revealed that compound 10 showed excellent efficacy against Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) and Tetranychus cinnabarinus (Boisduval) (Acarina: Tetranychidae). This study indicates that compound 10 could be further developed as a novel eco-friendly pesticide.

Propagation of cuttings is the primary method of rose multiplication. Aux/IAA, early response genes to auxin, play an important role in regulating the process of adventitious root formation in plants. However, systematic research on the identification of RhAux/IAA genes and their role in adventitious root formation in roses is lacking. In this study, 34 RhAux/IAA genes were identified by screening the rose genome, distributed on seven chromosomes, and classified into three clades based on the evolutionary tree. An analysis of the cis-acting elements in the promoters of RhAux/IAA genes revealed the presence of numerous elements related to plant hormones, the light signal response, the growth and development of plants, and abiotic stress. RNA-seq analysis identified a key RhIAA25 gene that may play an important role in the generation of adventitious roots in roses. Subcellular localization, yeast self-activation, and tissue-specific expression experiments indicated that RhIAA25 encoded a nuclear protein, had no yeast self-activated activity, and was highly expressed in the stem. The overexpression of RhIAA25 promoted the elongation of the primary root in Arabidopsis but inhibited adventitious root formation. This study systematically identified and analyzed the RhAux/IAA gene family and identified a key gene, RhIAA25, that regulates adventitious root generation in roses. This study offers a valuable genetic resource for investigating the regulatory mechanism of adventitious root formation in roses.

Plasmonic intragap nanostructures (PINs) have garnered intensive attention in Raman-related analysis due to their exceptional ability to enhance light–matter interactions. Although diverse synthetic strategies have been employed to create these nanostructures, the emphasis has largely been on PINs with simple configurations, which often fall short in achieving effective near-field focusing. Three-dimensional (3D) complex PINs, distinguished by their intricate networks of internal gaps and voids, are emerging as superior structures for effective light trapping. These structures facilitate the generation of hot spots and hot zones that are essential for enhanced near-field focusing. Nevertheless, the synthesis techniques for these complex structures and their specific impacts on near-field focusing are not well-documented. This review discusses the recent advancements in the synthesis of 3D complex PINs and their applications in surface-enhanced Raman scattering (SERS). We begin by describing the foundational methods for fabricating simple PINs, followed by a discussion on the rational design strategies aimed at developing 3D complex PINs with superior near-field focusing capabilities. We also evaluate the SERS performance of various 3D complex PINs, emphasizing their advanced sensing capabilities. Lastly, we explore the future perspective of 3D complex PINs in SERS applications.

Autogenous arteriovenous fistula (AVF) is the preferred dialysis access for receiving hemodialysis treatment in end-stage renal disease patients. After AVF is established, vascular remodeling occurs in order to adapt to hemodynamic changes. Uremia toxins, surgical injury, blood flow changes and other factors can induce inflammatory response, immune microenvironment changes, and play an important role in the maintenance of AVF vascular remodeling. This process involves the infiltration of pro-inflammatory and anti-inflammatory immune cells and the secretion of cytokines. Pro-inflammatory and anti-inflammatory immune cells include neutrophil (NEUT), dendritic cell (DC), T lymphocyte, macrophage (Mφ), etc. This article reviews the latest research progress and focuses on the role of immune microenvironment changes in vascular remodeling of AVF, in order to provide a new theoretical basis for the prevention and treatment of AVF failure.

BackgroundThe psychological status of Chinese postgraduate students majoring in stomatology after the COVID-19 restrictions still remains unclear. The objective of this study is to evaluate the mental status through a cross-sectional survey and gather related theoretical evidence for psychological intervention on postgraduate students majoring in stomatology.MethodsAn online survey was administered, and subjective well-being, anxiety, stress and depression symptoms were assessed using the 5-item World Health Organization Well-Being Index (WHO-5), item Generalized Anxiety Disorder Scale (GAD-7), 10-item Perceived Stress Scale (PSS-10), and Patient Health Questionnaire-9 (PHQ-9), respectively, wherein suicidal ideation and sleep-related problems were measured with PHQ-9 and Insomnia Severity Index (ISI).ResultsA total of 208 participants who completed one questionnaire were considered as valid. It was found that female respondents generally exhibited significantly higher levels of PSS-10, PHQ-9, and GAD-7 scores and shorter physical activity hours than male students. Students from rural areas demonstrated significantly higher levels of PHQ-9, suicidal ideation, and less portion of good or fair family economic support. Additionally, individuals from only-child families reported increased levels of activity hours (1.78 ± 2.07, p = 0.045) and a higher portion (55.10%, p = 0.007) of having clear future plan as compared with multiple-child families. The risk factors for anxiety symptoms (GAD-7 score) were higher scores of PSS-10 (OR = 1.15, 95% CI = 1.09–1.22), PHQ-9 (OR = 1.35, 95% CI = 1.22–1.49), and ISI-7 (OR = 1.14, 95% CI = 1.06–1.23), while owning a clear graduation plan was the protective factor (OR = 0.55, 95% CI = 0.31–0.98). Moreover, the risk factors for depressive symptoms (PHQ-9) included PSS-10 (OR = 1.10, 95% CI = 1.04–1.16), GAD-7 (OR = 1.38, 95% CI = 1.25–1.52), suicidal ideation (OR = 5.66, 95% CI = 3.37–9.51), and ISI-7 (OR = 1.17, 95% CI = 1.09–1.25). Approximately 98.08% of Chinese postgraduates studying stomatology reported experiencing at least moderate stress after the COVID-19 restrictions.ConclusionWithin the limitations of this study, senior students were more inclined to stress, while anxiety symptoms were related to severer levels of stress, depression, and insomnia. Depressive symptoms were associated with higher levels of stress, anxiety, insomnia, suicidal ideation, and lower levels of self-reported well-being. Thus, psychological interventions for postgraduates should be timely and appropriately implemented by strengthening well-being, reasonably planning for the future, and good physique, thereby mitigating the psychological issues after COVID-19 restrictions.

In light of contemporary energy and environmental objectives, a pivotal transformation of the energy system, encompassing biomass energy, is imperative. A notable challenge in biomass energy facility layout planning is the trade-off between high-efficiency production and the associated investment costs. To harmonize energy efficiency with economy viability, a hybrid layout with the simultaneous construction of centralized and decentralized biomass energy facilities has emerged as a crucial strategic solution. However, the delineation methods for these two layouts lack explicit data support. This study established a population density threshold (PDT) suitable for selecting the distributed layout and employed population density as the criterion for delineating the two layouts. Taking Fuxin City as an example, hybrid layout planning schemes were generated under different PDTs, and a cost and energy benefit analysis framework was developed for these schemes. The results indicated that the scheme with a PDT of 145 person/km2 exhibited the highest energy and economic comprehensive benefits. Compared to a single layout, the planning strategy proposed in this study could achieve nearly the same energy surplus level while saving an investment cost ranging from 2403.9 million CNY to 25,000.23 million CNY. The findings are applicable to other regions with similar conditions, and the analysis framework proposed in this study can be utilized in formulating biomass development strategies for other countries and regions.

Herein, we constructed innovative reduction-sensitive and targeted gelatin-based micelles for doxorubicin (DOX) delivery in tumor therapy. AS1411 aptamer-modified gelatin-ss-tocopherol succinate (AGSST) and the control GSST without AS1411 modification were synthesized and characterized. Antitumor drug DOX-containing AGSST (AGSST-D) and GSST-D nanoparticles were prepared, and their shapes were almost spherical. Reduction-responsive characteristics of DOX release in vitro were revealed in AGSST-D and GSST-D. Compared with non-targeted GSST-D, AGSST-D demonstrated better intracellular uptake and stronger cytotoxicity against nucleolin-overexpressed A549 cells. Importantly, AGSST-D micelles showed more effective killing activity in A549-bearing mice than GSST-D and DOX⋅HCl. It was revealed that AGSST-D micelles had no obvious systemic toxicity. Overall, AGSST micelles would have the potential to be an effective drug carrier for targeted tumor therapy.

This case describes the benefits of perioperative chemo-immunotherapy for advanced gastric cancer and incomplete pyloric obstruction, supplemented with nutritional support. Early parenteral nutrition to stabilize nutritional status and mitigate nutrition impact symptoms, and in addition, throughout the chemo-immunotherapy perioperative period also maintained oral nutrition support and a tailored dietary plan. Above nutritional support maintained the patient’s physical condition during immunotherapy. Eventually, this combination therapy plan leads to a partial response. On the other hand, a combination of therapies that focus more on immune checkpoint inhibitor may be able to mitigate the side effects of chemotherapy. Such findings may yield novel prospects for patients with advanced gastric cancer and incomplete pyloric obstruction, enabling them to achieve better outcomes.

Renal cell carcinoma (RCC) is a frequent urological malignancy characterized by a high rate of metastasis and lethality. The treatment strategy for advanced RCC has moved through multiple iterations over the past three decades. Initially, cytokine treatment was the only systemic treatment option for patients with RCC. With the development of medicine, antiangiogenic agents targeting vascular endothelial growth factor and mammalian target of rapamycin and immunotherapy, immune checkpoint inhibitors (ICIs) have emerged and received several achievements in the therapeutics of advanced RCC. However, ICIs have still not brought completely satisfactory results due to drug resistance and undesirable side effects. For the past years, the interests form researchers have been attracted by the combination of ICIs and targeted therapy for advanced RCC and the angiogenesis and immunogenic tumor microenvironmental variations in RCC. Therefore, we emphasize the potential principle and the clinical progress of ICIs combined with targeted treatment of advanced RCC, and summarize the future direction.

In this work, a four-port directional filter (DF) with a broad passband and low reflection is proposed at the W-band, which comprises three unit filters at 92, 95, and 97 GHz, cascaded in series. Each unit consists of two microstrip lines in the top circuit layer for signal input and output, two pairs of apertures in the middle ground layer for directional coupling, and one square loop in the bottom layer as a selective resonator. By sweeping the working frequencies of the three units and optimizing the phase delays between them, the proposed filter achieves a 3-dB bandwidth as broad as 16%, an insertion loss of 2.5 dB at 95 GHz, and an out-of-band rejection of −28 and −23 dB at 80 and 110 GHz, respectively. The corresponding reflection attenuation is larger than 9.6 dB from 60 to 105 GHz. To verify our design, a prototype is fabricated and characterized, and its experimental data are consistent with the simulation. This work significantly expands the bandwidth of DFs and may find many applications in frequency division multiplexing and high-gain wireless systems.