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Abstract Background The efficiency of medical services directly impacts the economic burden of healthcare, making it crucial to analyze the input-output efficiency of various types of medical institutions. However, while hospitals had been extensively analyzed for their efficiency, other types of medical institutions had received limited attention in this regard. Methods In this study, we employed data envelopment analysis (DEA) methods based on time series and internal benchmarks to autonomously assess the efficiency of 18 distinct categories of healthcare facilities in China over the past decade. The verification was conducted through the utilization of the critical incident technique (CIT). Additionally, we utilized the Delphi process (AHP) method to evaluate suppliers of medical consumables, implemented a multi-population genetic algorithm for managing these consumethod and analytic hierarchymables efficiently, and applied stakeholder theory to manage medical personnel efficiency. Results Our findings indicated that medical institutions capable of providing clinical services exhibited higher levels of efficiency compared to those unable to do so. Multiple indicators suggested redundancy within these institutions. Notably, comprehensive benefit evaluation revealed that clinical laboratory had performed poorly over the past decade. We selected an inefficient medical institution for intervention in reagent management and the work efficiency of medical staff. After implementing the Delphi method and multi-population genetic algorithm for consumable replenishment, the reagent cost was reduced by 40%, 39% and 31% respectively in each of the three experimental groups, compared to the control group. By applying stakeholder theory and process reengineering methods, we were able to shorten quality control management time for medical staff in the experimental group by 41 min per day, reduce clinical service time by 25 min per day, and extend rest time by 70 min per day, while the quality indicators were all meeting the targets. Conclusion By employing various mathematical models as described above, we were able to reduce costs associated with medical consumables and enhance medical personnel work efficiency without compromising quality objectives.

Owing to their rich color, excellent mechanical properties, and favorable biocompatibility, colored zirconia ceramics have been widely used in intelligent terminals, dental restoration, colored decorations, and other potential fields. This paper starts with the challenges faced by colored zirconia ceramics, followed by a summary of the application market of colored zirconia ceramics. Herein, we review various types of colorants and their mechanism of color development, summarize coloring methods, and analyze their advantages and disadvantages. Finally, the research progress on zirconia ceramics with red, blue, black, and other common colors is summarized, and future development directions are proposed in this review.

With globalization accelerating, films, as unique cultural products, are increasingly crossing borders and forming global trade networks. This network is a significant research focus in film geography. An in-depth analysis of the global film trade network helps illuminates its spatial and temporal patterns, offering both academic insight and practical value for the expansion of the Chinese film market overseas and the implementing cultural power strategies. Based on data from the United Nations Commodity Trade Statistics Database, this study uses complex network analysis methods to explore the evolution of the spatial and temporal characteristics of the global film trade network from 2004 to 2019. The findings reveal four key trends: first, the continuous expansion, seen in the growing number of nodes and trade flows indicates that the film trade relations between countries are becoming closer, creating a highly interconnected international cultural market. This reflects a growing decentralization of global cultural products, particularly with an increased in participation from Asian countries. Second, the trade network's topology has shifted from a dual-core model centered on Europe and America to a multipolar structure centered on Europe, Asia, and the United States, highlighting the increasingly important role of Asian countries, especially China, in the global film trade. Third, the distinction between the network's core and periphery has become more pronounced, revealing an increasing hierarchy in the film trade. This hierarchy may exacerbate market imbalances, giving stronger countries more influence over film production and distribution, whereas smaller cultural markets face more severe challenges. Finally, community detection analysis shows that the global film trade network exhibits significant community distribution characteristics, with these communities being relatively geographically concentrated, fostering stable exchange and cooperation of cultural products. This study examines the spatial and temporal evolution of the global film trade network from a macro perspective, focusing on the overall characteristics, topological structure, spatial evolution, and community formation. The research found that film geography emphasizes the role of films as a social practice, revealing cultural exchanges and their global dissemination among different countries and regions. Economic power continues to play a crucial role in the global film distribution. Despite the increasingly interconnected global film trade, the diversification of trade partners were not decentralized; rather, it has reinforced connections among countries within regions, reflecting a complementary relationship between regionalization and globalization. Economically developed countries dominate regional groups, highlighting the critical role of economic power in the global film trade. Despite stable trade cooperation, cultural imperialism remains a persistent issue as the dominance of American films in the global market promotes cultural homogenization. The study highlights the interplay of economic and cultural forces in shaping global film product flows, with the film network intersecting with other global networks. This calls for a critical analysis of power dynamics and sociocultural significance within these structures. As globalization advances, more nations are integrating into the global film trade, with China emerging as a key player. However, there is still a need to optimize trade structures, actively expand markets, and foster collaboration with countries involved in the Belt and Road Initiative to strengthen China's s position in the global film trade network.

Terbium aluminum garnet (Tb3Al5O12; TAG) ceramics are among the most promising magneto–optical materials owing to their outstanding comprehensive performance. Many works have focused on improving the optical quality of TAG ceramics. A key point for improving optical quality is ensuring the accuracy of the stoichiometric ratio and avoiding secondary phases. In this work, 0, 2, 4, or 6 wt% Sc2O3 was added to the TAG ceramics to increase the solid solubility. The effects of Sc substitution on the crystal structure, sintering process, microstructure, optical transmittance, and magneto–optical properties of (Tb1−xScx)3(Al1−yScy)2Al3O12 (TSAG) ceramics are studied in detail. 4 wt% Sc2O3:TAG ceramics with an in-line transmittance of 82.2% at 1064 nm and 81.2% at 633 nm were successfully fabricated, and the Verdet constant was 164.4 rad·T−1·m−1 at 633 nm. Anti-site defects (ADs) and Sc replacement in TAG are further studied via first-principles calculations to determine the working mechanism of Sc. Both the experimental and calculation results show that the introduction of Sc can effectively increase the solid solubility of TAG ceramics, suppress secondary phases, and hence improve the optical transmittance.

Abstract Cisplatin is a commonly used chemotherapy agent with a nearly universal side effect of sensorineural hearing loss. The cellular mechanisms underlying cisplatin ototoxicity are poorly understood. Efforts in drug development to prevent or reverse cisplatin ototoxicity have largely focused on pathways of oxidative stress and apoptosis. An effective treatment for cisplatin ototoxicity, sodium thiosulfate (STS), while beneficial when used in standard risk hepatoblastoma, is associated with reduced survival in disseminated pediatric malignancy, highlighting the need for more specific drugs without potential tumor protective effects. The unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways have been shown to be involved in the pathogenesis of noise-induced hearing loss and cochlear synaptopathy in vivo, and these pathways have been implicated broadly in cisplatin cytotoxicity. This study sought to determine whether the UPR can be targeted to prevent cisplatin ototoxicity. Neonatal cochlear cultures and HEK cells were exposed to cisplatin, and UPR marker gene expression and cell death measured. Treatment with ISRIB (Integrated Stress Response InhIBitor), a drug that activates eif2B and downregulates the pro-apoptotic PERK/CHOP pathway of the UPR, was tested for its ability to reduce apoptosis in HEK cells, hair-cell death in cochlear cultures, and hearing loss using an in vivo mouse model of cisplatin ototoxicity. Finally, to evaluate whether ISRIB might interfere with cisplatin chemoeffectiveness, we tested it in head and neck squamous cell carcinoma (HNSCC) cell-based assays of cisplatin cytotoxicity. Cisplatin exhibited a biphasic, non-linear dose–response of cell death and apoptosis that correlated with different patterns of UPR marker gene expression in HEK cells and cochlear cultures. ISRIB treatment protected against cisplatin-induced hearing loss and hair-cell death, but did not impact cisplatin’s cytotoxic effects on HNSCC cell viability, unlike STS. These findings demonstrate that targeting the pro-apoptotic PERK/CHOP pathway with ISRIB can mitigate cisplatin ototoxicity without reducing anti-cancer cell effects, suggesting that this may be a viable strategy for drug development.

Gastric cancer (GC) is one of the most commonly diagnosed malignancies, threatening millions of lives worldwide each year. Importantly, GC is a heterogeneous disease, posing a significant challenge to the selection of patients for more optimized therapy. Over the last decades, extensive community effort has been spent on dissecting the heterogeneity of GC, leading to the identification of distinct molecular subtypes that are clinically relevant. However, so far, no tool is publicly available for GC subtype prediction, hindering the research into GC subtype-specific biological mechanisms, the design of novel targeted agents, and potential clinical applications. To address the unmet need, we developed an R package GCclassifier for predicting GC molecular subtypes based on gene expression profiles. To facilitate the use by non-bioinformaticians, we also provide an interactive, user-friendly web server implementing the major functionalities of GCclassifier. The predictive performance of GCclassifier was demonstrated using case studies on multiple independent datasets.

Yb:CaF2 transparent ceramics represent a promising laser gain medium for ultra-short lasers due to their characteristics: low phonon energy, relatively high thermal conductivity, negative thermo-optical coefficient, and low refractive index. Compared to single crystals, Yb:CaF2 ceramics offer superior mechanical properties, lower cost, and it is easier to obtain large-sized samples with proper shape and uniform Yb3+ doping at high concentrations. The combination of air pre-sintering and Hot Isostatic Pressing (HIP) emerges as a viable strategy for achieving high optical quality and fine-grained structure of ceramics at lower sintering temperatures. The properties of the powders used in ceramic fabrication critically influence both optical quality and laser performance of Yb:CaF2 ceramics. In this study, the 5 atomic percentage (at.%) Yb:CaF2 transparent ceramics were fabricated by air pre-sintering and hot isostatic pressing (HIP) using nano-powders synthesized through the co-precipitation method. The co-precipitated powders were optimized by studying air calcination temperature (from 350 to 550 °C). The influence of calcination temperature on the microstructure and laser performance of Yb:CaF2 ceramics was studied in detail. The 5 at.% Yb:CaF2 transparent ceramics air pre-sintered at 625 °C from powders air calcined at 400 °C and HIP post-treated at 600 °C exhibited the highest in-line transmittance of 91.5% at 1200 nm (3.0 mm thickness) and the best laser performance. Specifically, a maximum output power of 0.47 W with a maximum slope efficiency of 9.2% at 1029 nm under quasi-CW (QCW) pumping was measured.

Abstract Endothelial progenitor cells (EPCs) play a crucial role in maintaining vascular health and aiding in the repair of damaged blood vessels. However, the specific impact of EPCs-derived exosomes on vascular endothelial cell injury caused by lipopolysaccharide (LPS) remains inadequately understood. This study aims to explore the potential benefits of EPC-exosomes in mitigating LPS-induced vascular injury and to elucidate the underlying mechanism. Initially, EPCs were isolated from mouse peripheral blood, and their identity was confirmed through flow cytometry and immunocytochemistry. Subsequently, the exosomes derived from EPCs were identified using transmission electron microscopy (TEM) and western blot analysis. A sepsis model was induced by subjecting brain microvascular endothelial cells (BMECs) to LPS-induced injury. Both EPC and their exosomes demonstrated a significant increase in BMECs proliferation, reduced apoptosis, decreased levels of pro-inflammatory factors (TNF-α, IL-6, and caspase-3), and enhanced sprouting and angiogenesis of BMECs. Notable, the Exosomes demonstrated a more pronounced impact on these parameters. Furthermore, both EPCs and Exosomes exhibited significantly increased levels of miR-126a-5p, with the Exosomes showing a more substantial enhancement. These findings suggest that supplementing exosomal miR-126a-5p from EPCs can provide protective effects on BMECs, offering a potential therapeutic option for treating sepsis-induced microvascular endothelial cell injury.

Abstract Dental pulp stem cells (DPSC) have shown osteogenic and bone regenerative potential. Improving the in situ bone regeneration potential of DPSC is crucial for their application as seed cells during bone defect reconstruction in clinics. This study aimed to develop DPSC-derived organoid-like microspheroids as effective seeds for bone tissue engineering applications. DPSC osteogenic microspheroids (70 μm diameter) were cultured in a polydimethylsiloxane-mold-based agarose-gel microwell-culture-system with or without cannabidiol (CBD)-treatment. Results of in vitro studies showed higher osteogenic differentiation potential of microspheroids compared with 2D-cultured-DPSC. CBD treatment further improved the osteogenic differentiation potential of microspheroids. The effect of CBD treatment in the osteogenic differentiation of microspheroids was more pronounced compared with that of CBD-treated 2D-cultured-DPSC. Microspheroids showed a higher degree of bone regeneration in nude mice calvarial bone defect compared to 2D-cultured-DPSC. CBD-treated microspheroids showed the most robust in situ bone regenerative potential compared with microspheroids or CBD-treated 2D-cultured-DPSC. According to mRNA sequencing, bioinformatic analysis, and confirmation study, the higher osteogenic potential of CBD-treated microspheroids was mainly attributed to WNT6 upregulation. Taken together, DPSC microspheroids have robust osteogenic potential and can effectively translate the effect of in vitro osteoinductive stimulation during in situ bone regeneration, indicating their application potential during bone defect reconstruction in clinics.

Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine (TCM) for over 13 centuries. However, the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear welfare. Here, we present a new approach for creating artificial bear bile (ABB) as a high-quality and sustainable alternative to natural bear bile. This study addresses the scientific challenges of creating bear bile alternatives through interdisciplinary collaborations across various fields, including resources, chemistry, biology, medicine, pharmacology, and TCM. A comprehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been established, allowing for the systematic screening of therapeutic constituents. Through the utilization of chemical synthesis and enzyme engineering technologies, our research has achieved the environmentally friendly, large-scale production of bear bile therapeutic compounds, as well as the optimization and recomposition of ABB formulations. The resulting ABB not only closely resembles natural bear bile in its composition but also offers advantages such as consistent product quality, availability of raw materials, and independence from threatened or wild resources. Comprehensive preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from commercially available drained bear bile (DBB). Furthermore, preclinical toxicological assessment and phase I clinical trials show that the safety of ABB is on par with that of the currently used DBB. This innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs, thereby strengthening the integrity and sustainability of TCM.

Objective Estimating the joint roughness coefficient (JRC) is essential for evaluating the mechanical properties of a rock mass. Due to the limitation of a single statistical parameter for characterizing morphology, JRC values estimation by a single statistical parameter may produce a sufficiently unreliable result. Methods To address the existing challenges in determining JRC values, a model based on Gaussian process regression (GPR) combined with principal component analysis (PCA) was proposed for the quantitative evaluation of JRC. Notably, eight parameters were selected as indicators for the comprehensive expression of the rock joint roughness. To analyse the model's performance, a publicly available dataset of 112 rock joint profiles was used as an example, of which 95 were chosen as training samples and 17 were chosen as validation samples. The reliability of the model was verified by comparing the predicted results with the measured JRC values. Results The results show that the derived GPR model demonstrates promising performance (R2=0.972, MSE =0.517) for estimation of JRC values, indicating the high applicability of the model in constructing implicit relationships between multiple statistical parameters and JRC values even under small sample conditions. Conclusion In general, the GPR model may provide a new way of estimating JRC values with artificial intelligence.

Abstract Background Oral squamous cell carcinoma (OSCC) causes significant mortality and morbidity worldwide. Surgical resection with adjuvant radiotherapy remains the standard treatment for locally advanced resectable OSCC. Results from landmark trials have established postoperative concurrent cisplatin-radiotherapy (Cis-RT) as the standard treatment for OSCC patients with high-risk pathologic features. However, cisplatin-related toxicity limits usage in clinical practice. Given the need for effective but less toxic alternatives, we previously conducted a single-arm trial showing favorable safety profiles and promising efficacy of concurrent docetaxel-radiotherapy (Doc-RT). Methods In this randomized phase 2 trial, we aimed to compare Doc-RT with the standard Cis-RT in postoperative OSCC patients. Eligible patients had AJCC stage III–IV resectable OSCC with high-risk pathologic features. Two hundred twenty-four patients were enrolled and randomly assigned to receive concurrent Doc-RT or Cis-RT. The primary endpoint was 2-year disease-free survival (DFS). Secondary endpoints included overall survival (OS), locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), and adverse events (AEs). Integrin β1 (ITGB1) expression was analyzed as a biomarker for efficacy. Results After a median 28.8-month follow-up, 2-year DFS rates were 63.7% for Doc-RT arm and 56.1% for Cis-RT arm (p = 0.55). Meanwhile, Doc-RT demonstrated comparable efficacy to Cis-RT in OS, LRFS, and DMFS. Doc-RT resulted in fewer grade 3 or 4 hematological AEs. Low ITGB1 was associated with improved Doc-RT efficacy versus Cis-RT. Conclusions This randomized trial directly compared Doc-RT with Cis-RT for high-risk postoperative OSCC patients, with comparable efficacy and less toxicity. ITGB1 merits further validation as a predictive biomarker to identify OSCC patients most likely to benefit from Doc-RT. Findings indicate docetaxel may be considered as a concurrent chemoradiation option in this setting. Trial registration www.ClinicalTrials.gov . NCT02923258 (date of registration: October 4, 2016)

Abstract PIWI-interacting RNA (piRNA) is the most abundant small non-coding RNA in animal cells, typically 26–31 nucleotides in length and it binds with PIWI proteins, a subfamily of Argonaute proteins. Initially discovered in germ cells, piRNA is well known for its role in silencing transposons and maintaining genome integrity. However, piRNA is also present in somatic cells as well as in extracellular vesicles and exosomes. While piRNA has been extensively studied in various diseases, particular cancer, its function in immune diseases remains unclear. In this review, we summarize current research on piRNA in immune diseases. We first introduce the basic characteristics, biogenesis and functions of piRNA. Then, we review the association of piRNA with different types of immune diseases, including autoimmune diseases, immunodeficiency diseases, infectious diseases, and other immune-related diseases. piRNA is considered a promising biomarker for diseases, highlighting the need for further research into its potential mechanisms in disease pathogenesis.

Abstract Single gamete cell sequencing together with long-read sequencing can reliably produce chromosome-level phased genomes. In this study, we employed PacBio HiFi and Hi-C sequencing on a male Landrace pig, coupled with single-sperm sequencing of its 102 sperm cells. A haplotype assembly method was developed based on long-read sequencing and sperm-phased markers. The chromosome-level phased assembly showed higher phasing accuracy than methods that rely only on HiFi reads. The use of single-sperm sequencing data enabled the construction of a genetic map, successfully mapping the sperm motility trait to a specific region on chromosome 1 (105.40–110.70 Mb). Furthermore, with the assistance of Y chromosome-bearing sperm data, 26.16 Mb Y chromosome sequences were assembled. We report a reliable approach for assembling chromosome-level phased genomes and reveal the potential of sperm population in basic biology research and sperm phenotype research.

Carnosine dipeptidase 1 (CNDP1), an enzyme integral to the hydrolysis of dipeptides containing histidine, plays an indispensable role in myriad physiological processes, including hydrolysis of proteins, maturation of specific biochemical functionalities within proteins, tissue regeneration, and regulation of cell cycle. However, the implications of CNDP1 in oncogenesis and its prognostic value are not yet fully elucidated. Initially, we procured the GSE40367 dataset from the Gene Expression Omnibus and established a protein–protein interaction network. Thereafter, we conducted functional and pathway enrichment analyses utilizing GO, KEGG, and GSEA. Moreover, we undertook an association analysis concerning the expression of CNDP1 with immune infiltration, along with survival analysis across various cancers and specifically in hepatocellular carcinoma (HCC). Our study uncovered a total of 2,248 differentially expressed genes, with a down-regulation of CNDP1 in HCC and other cancers. Our explorations into the relationship between CNDP1 and immune infiltration disclosed a negative correlation between CNDP1 expression and the presence of immune cells in HCC. Survival analyses revealed that diminished expression of CNDP1 correlates with an adverse prognosis in HCC and several other types of cancer. These observations intimate that CNDP1 holds promise as a novel prognostic biomarker for both pan-cancer and HCC.

Cyclosporine A, a cyclic polypeptide, exhibits potent immunosuppressive activity and exerts its effects through various mechanisms including immunosuppression, anti-inflammatory, inhibition of apoptosis, promotion of epithelial healing and goblet cell function recovery, enhancement of tear secretion, and close association with ocular surface disease repair. Owing to its significant efficacy, inhibition of disease recurrence and few side effects, the clinical application of cyclosporine A in the management of ocular surface diseases, including dry eye, corneal graft rejection following penetrating keratoplasty, vernal keratoconjunctivitis, noninfective keratitis and herpes simplex virus keratitis, has witnessed a substantial rise in recent years. Nevertheless, variations exist in the management of ocular surface inflammatory diseases when utilizing distinct concentrations and dosage forms of cyclosporine A. Therefore, the paper provides an overview of impacts of cyclosporine A on ocular surface diseases.

The mechanisms underlying pathological changes in the central nervous system (CNS) following Coxsackievirus A16 (CV-A16) infection have not yet been elucidated. IFN-γ-inducible protein-10 (IP-10) is often used as a predictive factor to monitor early virus infection. It has also been reported that IP-10 plays a pivotal role in neuroinflammation. In this study, we aimed to explore the role of IP-10 in the neuropathogenesis of CV-A16 infection. We observed that the level of IP-10, as well as the TLR3-TRIF-TRAF3-TBK1-NF-κB and RIG-I/MDA5-MAVS-TRAFS-TBK1-NF-κB pathways, which are the upstream of IP-10, were significantly elevated during the course of CV-A16 infection. This increase was accompanied by an increase in a series of inflammatory cytokines at different time-points during CV-A16 infection. To determine whether IP-10 influences BBB integrity, we examined junctional complexes. Our results revealed that the expression levels of Claudin5, Occludin, ZO-1 and VE-Cadherin were notably decreased in CV-A16-infected HUVECs, but these indicators were restored in CV-A16-infected HUVECs with Eldelumab treatment. Nevertheless, IP-10 is only a chemokine that primarily traffics CXCR3-positive immune cells to inflammatory sites or promotes the production of inflammatory cytokines. Therefore, the interactions between IP-10 and inflammatory cytokines were evaluated. Our data revealed that IP-10 mediated the production of TNF-α, which was also observed to change the junctional complexes. Moreover, in a suckling mouse model, IP-10 and TNF-α treatments exacerbated clinical symptoms, mortality and pathological changes in the brain of CV-A16-infected mice, but Anti-IP-10 and Anti-TNF-α treatments alleviated these changes. Our data also revealed that IP-10 may be detected early in CV-A16 infection, whereas TNF-α was detected late in CV-A16 infection, and the production of TNF-α was also found to be positively correlated with IP-10. In addition, IP-10 and TNF-α were observed to reduce junctional complexes and enhance virus entry into the CNS. Taken together, this study provides the first evidence that CV-A16 activates the IP-10/TNF-α regulatory axis to cause BBB damage and accelerate the formation of neuroinflammation in infected hosts, which not only provides a new understanding of the neuropathogenesis caused by CV-A16, but also offers a promising target for the development of CV-A16 antiviral drugs.

Distribution network topology identification (DNTI) is an important prerequisite for distribution system operation. Frequent topology changes and limited measurement equipment make identifying the correct topology unavoidably challenging. To this end, this paper proposes a state estimation method for distribution network topology identification using a small amount of phasor measurement unit (PMU) measurement data. Firstly, this paper introduces the application of the structural equation model (SEM) in distribution networks and explains the relationship between branch currents and topology. Then, auxiliary variables are introduced for the feasible domain problem present in the algorithm, which improves the solvability of the algorithm. In addition, this paper reconsiders the operation mode constraints in terms of nodes from the perspective of distribution network operation mode. The Structural Equation Modeling-based Mixed Integer Programming (SEM-MIP) method proposed in this paper can be solved using existing commercial solvers, and its effectiveness has been verified by simulation in IEEE 33-node test system and IEEE 123-node test system.

Objectives: Physical frailty has been found to increase the risk of multiple adverse outcomes including cardiovascular disease (CVD) in diabetic patients, but whether this could be modified by traditional risk factor control remains unknown. We aimed to explore the joint and interaction effects of frailty and traditional risk factor control on the risk of CVD. Design: A population-based cohort study. Setting and participants: We included 15,753 participants with type 2 diabetes at baseline from UK Biobank. Measurements: Physical frailty was assessed by Fried criteria’s frailty phenotype. The degree of risk factor control was determined by the numbers of the following factors controlled within the target range, including glycated hemoglobin, blood pressure, low-density lipoprotein cholesterol, smoking, and kidney condition. Incident CVD included coronary heart disease, stroke, or heart failure. Cox proportional hazard models were used to assess the individual and joint effects of frailty and risk factor control on the risk of CVD. Results: After a median follow-up of 13.5 years, 1129 incident CVD events were observed. Compared with non-frailty, both prefrailty and frailty were significantly associated with increased risk of CVD (HR 1.22, 95% CI [1.13, 1.31] for pre-frailty and 1.70 [1.53, 1.90] for frailty). For the joint effects, participants with frailty and a low degree of risk factor control (control of 0−1 risk factors) had the highest risk of CVD (2.92 [2.04, 4.17]) compared to those with non-frailty and optimal risk factor control (control of 4−5 risk factors). Moreover, a significant additive interaction between frailty and risk factor control was observed, with around 3.8% of CVD risk attributed to the interactive effects. Conclusions: Both prefrailty and frailty were associated with a higher risk of CVD in participants with type 2 diabetes. Moreover, physical frailty could interact with the degree of risk factor control in an additive manner to increase the CVD risk.

BackgroundThis retrospective cohort study and meta-analysis aims to explore the association between microvascular invasion (MVI) and clinicopathologiccal features, as well as survival outcomes of patients with renal cell carcinoma (RCC).Material and methodsThe retrospective cohort study included 30 RCC patients with positive MVI and another 75 patients with negative MVI as controls. Clinicopathological features and follow-up data were compiled. The meta-analysis conducted searches on PubMed, Cochrane Library, Web of Science, Embase, and WanFang Data from the beginning to 30 September 2023, for comparative studies relevant to MVI patients. The Newcastle-Ottawa Scale and Egger Test were used to assess the risk of biases and certainty of evidence in the included studies.ResultsThe cohort study showed that MVI was associated with advanced primary tumor stage, high pathological grades, high tumor size, high clinical symptoms and lymph node invasion (P 0.05). The meta-analysis part included 11 cohort studies. The results confirmed that patients with MVI positive had worse 12 and 60 mo CSS rates (HR12mo = 0.86, 95%CI 0.80–0.92; HR60mo = 0.63, 95% CI 0.55–0.72; P < 0.00001). Moreover, the meta-analysis also confirmed that MVI group was associated with higher rate of advanced tumor stage, pathological grades, tumor size diameter, higher rate of clinical symptoms and lymph node invasion (P

Aeromonas hydrophila is a widespread fish pathogen. However, due to the extensive use of antibiotics in aquaculture, this bacterium has developed drug resistance. In recent years, tea tree oil, extracted from Melaleuca alternifolia, has gained widespread application in antibacterial research. Nevertheless, the underlying mechanism of action of tea tree oil on A. hydrophila remains unclear. In this study, the inhibitory effect of tea tree oil on A. hydrophila was analyzed, and its mechanism of action was elucidated through a combination of transcriptome and proteome analyses. In the current work, tea tree oil (0.039 mg/mL) significantly inhibited the growth of A. hydrophila and changed the permeability of the cell membrane. A total of 109 differentially expressed genes (DEGs) were identified by the combined analysis of the transcriptome and the proteome, of which 46 were upregulated and 63 were downregulated. These co-regulated DEGs were primarily enriched in metabolic pathways such as bacterial chemotaxis, pyrimidine metabolism, and the two-component system. Simultaneously, it was found that the target proteins of tea tree oil, such as secB, yajC, rpsP, rplL, and rpsT were significantly downregulated. These findings suggested that the potential of tea tree oil as an alternative to antibiotics in inhibiting the growth of A. hydrophila. It provides new insights into the molecular mechanisms underlying the antimicrobial activity of tea tree oil against A. hydrophila.

3D printing of flexible piezoelectric composites (3D-FPCs) is increasingly attracting the attention due to its unique advantage for customized smart applications. However, current research mainly focuses on the 0–3 piezoelectric composites, in which the piezoelectric ceramics are embedded in polymer matrix in the form of particles. The poor connectivity between particles much reduces the conduction of strain and charge in the composites, seriously limiting its application in actuation. In this work, a continuous lead zirconate titanate (PZT) double-layer ceramic scaffold was prepared by 3D printing and assembled with epoxy resin and interdigital electrodes together to manufacture a multifunctional device. The 3D-FPCs exhibit a free strain of 1830 ​ppm in actuating and are able to actuate a stainless-steel cantilever beam to produce a tip displacement of 5.71 ​mm. Additionally, the devices exhibit a sensitivity of 26.81V/g in sensing applications. Furthermore, 3D-FPCs are demonstrated as actuators for mobile small robots and wearable sensors for sensing joint activities.

Background: Identification of individuals with prediabetes who are at high risk of developing diabetes allows for precise interventions. We aimed to determine the role of nuclear magnetic resonance (NMR)-based metabolomic signature in predicting the progression from prediabetes to diabetes. Methods: This prospective study included 13,489 participants with prediabetes who had metabolomic data from the UK Biobank. Circulating metabolites were quantified via NMR spectroscopy. Cox proportional hazard (CPH) models were performed to estimate the associations between metabolites and diabetes risk. Supporting vector machine, random forest, and extreme gradient boosting were used to select the optimal metabolite panel for prediction. CPH and random survival forest (RSF) models were utilized to validate the predictive ability of the metabolites. Results: During a median follow-up of 13.6 years, 2525 participants developed diabetes. After adjusting for covariates, 94 of 168 metabolites were associated with risk of progression to diabetes. A panel of nine metabolites, selected by all three machine-learning algorithms, was found to significantly improve diabetes risk prediction beyond conventional risk factors in the CPH model (area under the receiver-operating characteristic curve, 1 year: 0.823 for risk factors + metabolites vs 0.759 for risk factors, 5 years: 0.830 vs 0.798, 10 years: 0.801 vs 0.776, all p < 0.05). Similar results were observed from the RSF model. Categorization of participants according to the predicted value thresholds revealed distinct cumulative risk of diabetes. Conclusions: Our study lends support for use of the metabolite markers to help determine individuals with prediabetes who are at high risk of progressing to diabetes and inform targeted and efficient interventions. Funding: Shanghai Municipal Health Commission (2022XD017). Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZDCX20212501). Shanghai Municipal Human Resources and Social Security Bureau (2020074). Clinical Research Plan of Shanghai Hospital Development Center (SHDC2020CR4006). Science and Technology Commission of Shanghai Municipality (22015810500).

Background: Cardiovascular disease (CVD) is the leading cause of death in the United States, and rates of CVD incidence vary widely by race and ethnicity. Cigarette smoking is associated with increased risk of CVD. The purpose of the study was: 1) to examine smoking prevalence over time across Asian and Pacific Islander (API) and multi-race API subgroups; 2) to determine whether the CVD risk associated with smoking differed among these subgroups. Methods: We identified patients belonging to 7 single race/ethnicity groups, 4 multi-race/ethnicity groups, and a non-Hispanic White (NHW) comparison group at two large health systems in Hawaii and California. We estimated annual smoking prevalence from 2011 through 2018 by group and gender. We examined incidence of CVD events by smoking status and race/ethnicity, and computed hazard ratios for CVD events by age, gender, race/ethnicity, census block median household income, census block college degree, and study site using Cox regression. Results: Of the 12 groups studied, the Asian Indian and Chinese American groups had the lowest smoking prevalence, and the Asian + Pacific Islander multiracial group had the highest smoking prevalence. The prevalence of smoking decreased from 2011 to 2018 for all groups. Multi-race/ethnicity groups had higher risk of CVD than the NHW group. There was no significant interaction between race/ethnicity and smoking in models predicting CVD, but the association between race/ethnicity and CVD incidence was attenuated after adjusting for smoking status. Conclusions: There is considerable heterogeneity in smoking prevalence and the risk of CVD among API subgroups.

Objective: The aim of this study was to elucidate the effects of fermented hawthorn extract on high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in rats, and explore the possible underlying mechanisms. Methods: A total of 42 male adult Sprague-Dawley rats were randomly divided into five groups: normal control group (given a normal feed diet and distilled water by gavage), NAFLD model (given HFD and distilled water by gavage), low-, medium-, and high-dose fermented hawthorn extract treatment groups (given HFD and different doses of fermented hawthorn extract by gavage). After 12 weeks of gavage administration, changes in body weight, liver/body weight ratio, serum liver enzymes, as well as triglyceride (TG) content and oxidative stress levels in rat liver tissueswere detected. Histological evaluation was performed to observe the degree of fat accumulation (steatosis). qRT-PCR and western blotting were performed to detect the mRNA and protein expression of cytochrome P4502E1 (CYP2E1, a key enzyme associated with lipid peroxidation), and lipogenic factors (sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS)) in rat liver tissues. Results: Fermented hawthorn extract significantly reduced the body weight, decreased the levels of liver enzymes, improved hepatic steatosis, and exhibited obvious antioxidant effects. Fermented hawthorn extract also significantly down-regulated the mRNA and protein expression levels of CYP2E1, SREBP-1c and FAS. Conclusion: Our findings suggested that fermented hawthorn extract can markedly reduce body weight, ameliorate HFD-induced NAFLD in rats, and exhibits significant antioxidant effects. Its underlying mechanism may depend on the inhibition of CYP2E1, SREBP-1c, and FAS expression.

Magneto-optical and thermo-optical characteristics of transparent Tb2Ti2O7 ceramics were investigated. The dependence of the index of refraction on the wavelength in the 0.29–2 μm range, the wavelength and temperature dependence of the Verdet constant, as well as the dependence of thermally induced depolarization on laser radiation power were measured. The value of the Verdet constant in Tb2Ti2O7 surpasses that in Tb3Ga5O12 by more than 1.68 times. The thermo-optical characteristic Qeff was estimated to be (1.8–3.7)∙10−8 1/K, which is record small compared to Qeff of the known magneto-optical materials. The small value of Qeff makes Tb2Ti2O7 a highly promising magneto-optical material for Faraday isolators and rotators for high average power lasers.

Filling the cyan gap is the key element in achieving full-spectrum illumination using violet chip to excite red, green and blue phosphors. However, designing cyan phosphors suitable for violet light excitation with excellent performance remains challenging. Herein, a novel cyan phosphor Ba9Lu2-x-nSi6O24:xCe (n-BLS:Ce) with multiple crystal sites of Ba2+ and Lu3+ for Ce3+ ions was designed and prepared via crystal-site engineering. The Ce3+ ions at Ba2+ sites emit ultraviolet light at 385 nm under 325 nm ultraviolet light excitation, and the Ce3+ ions at Lu3+ sites emit cyan light at 485 nm under 395 nm violet light excitation. The favorable occupation of Ce3+ ions at Lu3+ sites could be realized by introducing Lu vacancies. Significantly, the cyan light emission intensity of Ba9Lu1.4Si6O24:0.3Ce (n0.3-BLS:Ce) with Lu vacancies is effectively improved by 47 % compared to Ba9Lu1.7Si6O24:0.3Ce (n0-BLS:Ce) without Lu vacancies. And the emission intensity at 150 °C retains 96 % of that at room temperature. The color rendering index increases from 87.9 to 94.5 after supplementing Ba9Lu2-x-nSi6O24:xCe cyan phosphor in w-LEDs devices combining commercial red, green, and blue phosphors with a violet chip, indicating its potential practical application in full-spectrum lighting. This work also provides new ideas for the design and development of new and efficient high-quality light-emitting materials.

BackgroundPrimary hepatic neuroendocrine tumors (PHNETs) are an utterly rare entity. The diagnosis of PHNETs could legitimize when an extrahepatic primary NET must always be excluded. PHNETs can achieve a high survival rate after complete surgical resection, however, most patients still have an 18% risk of recurrence within 5 years after surgery. In our case, the recurrence occurred 8 years after the first hepatectomy, which is relatively rare in the current literature. Therefore, rigorous postoperative follow-up is necessary for early detection and timely treatment of recurrent PHNETs.Case informationWe report a case of PHNET in a 24-year-old previously healthy female patient who relapsed 8 years after hepatectomy. This case focuses on the importance of diagnosis of primary and recurrent PHNETS in young patients, rare pathological types, and post-operative follow-up.ConclusionThis case report detailed the rare pathological morphology and characteristic immunohistochemical markers in our case for PHNETS, which enhanced the new understanding of the diagnosis of this entity. In addition, we also highlighted the variable duration of recurrence after treatment of PHNETs. The 8-year recurrent period in our case suggests the importance of regular examination in patients with PHNETs by following the doctor’s instructions.

BackgroundDespite advancements in diabetes treatment, the management of Painful Diabetic Neuropathy (PDN) remains challenging. Our previous research indicated a significant correlation between the expression and distribution of Aquaporin-4 (AQP4) in the spinal glymphatic system and PDN. However, the potential role and mechanism of liquiritin in PDN treatment remain uncertain.MethodsThis study established a rat model of PDN using a combination of low-dose Streptozotocin (STZ) and a high-fat, high-sugar diet. Rats were treated with liquiritin and MCC950 (an NLRP3 inhibitor). We monitored fasting blood glucose, body weight, and mechanical allodynia periodically. The glymphatic system’s clearance function was evaluated using Magnetic Resonance Imaging (MRI), and changes in proteins including NLRP3, MMP-9, and AQP4 were detected through immunofluorescence and Western blot techniques.ResultsThe rats with painful diabetic neuropathy (PDN) demonstrated several physiological changes, including heightened mechanical allodynia, compromised clearance function within the spinal glymphatic system, altered distribution of AQP4, increased count of activated astrocytes, elevated expression levels of NLRP3 and MMP-9, and decreased expression of AQP4. However, following treatment with liquiritin and MCC950, these rats exhibited notable improvements.ConclusionLiquiritin may promote the restoration of AQP4 polarity by inhibiting NLRP3 and MMP-9, thereby enhancing the clearance functions of the spinal cord glymphatic system in PDN rats, alleviating the progression of PDN.

Background: Lipid accumulation product (LAP), visceral adiposity index (VAI) and Chinese visceral adiposity index (CVAI) are proposed indices of visceral adipose accumulation. This study aimed to explore their relationship and temporal changes with hyperuricemia (HUA) development in a Chinese population. Methods: A total of 4268 participants aged ≥45 years from the baseline survey of the China Health and Retirement Longitudinal Study were followed up for 4 years (from 2011 to 2015). The relationships among VAI, LAP, CVAI and HUA were analyzed using logistic regression. The predictive abilities of the VAI, LAP and CVAI for HUA were compared using receiver operating characteristic curves. Nonlinear relationships between the indices and HUA were analyzed using restricted cubic spline regression. Results: During the four-year follow-up, 415 (9.72 %) patients experienced incident HUA . Elevated baseline VAI (odds ratio (OR): 1.19 (95 % confidence interval (95 %CI: 1.10, 1.29)), LAP (OR: 1.21 (95 % CI: 1.09, 1.34)) and CVAI (OR: 1.19 (95 % CI: 1.02, 1.40)) were significantly correlated with increased HUA risk (all P < 0.05). Compared to individuals with consistently low VAI,CVAIor LAP levels, those with elevated or consistently high levels of these indicators are more likely to have HUA. The area under curve (AUC) was slightly greater and more significant for the CVAI (AUC=0.641) than for the VAI (AUC=0.604) and LAP (AUC=0.628) (P < 0.05). Conclusion: VAI, LAP and CVAI can predict HUA, with CVAI more efficient than VAI and LAP. Early management can lessen the burden of HUA in Chinese people aged 45 years or older with elevated CVAI levels.

Hyperuricemia is with growing incidence and of high risk to develop into gout and other metabolic diseases. The key enzyme catalyzing uric acid synthesis, xanthine oxidoreductase (XOR) is a vital target for anti-hyperuricemic drugs, while XOR inhibitors characterized as both potent and safe are currently in urgent need. In this study, a novel small molecule compound, CC15009, was identified as a specific XOR inhibitor. CC15009 exerted strongest in vitro XOR inhibitory activity among current XOR inhibitors. It also showed favorable dose-dependent uric acid-lowering effects in two different XOR substrate-induced hyperuricemic mouse models, which was significantly superior than the current first-line drug, allopurinol. Mechanically, the direct binding of CC15009 against XOR was confirmed by molecular docking and SPR analysis. The inhibition mode was competitive and reversible. Besides, the potential antioxidant activity of CC15009 was indicated by its strong inhibitory activity against the oxidized isoform of XOR, which reduced ROS generation as the byproduct. Regarding the safety concerns of current XOR inhibitors, especially in cardiovascular risks, the safety of CC15009 was comprehensively evaluated. No significant abnormality was observed in the acute, subacute toxicity tests and mini-AMES test. Notably, there was no obvious inhibition of CC15009 against cardiac ion channels, including hERG, Nav1.5, Cav1.2 at the concentration of 30 μM, indicating its lower cardiovascular risk. Taken together, our results supported CC15009 as a candidate of high efficacy and safety profile to treat hyperuricemia through direct XOR inhibition.

Abstract Background Mucosal melanoma (MM) is a rare but devastating subtype of melanoma. Our previous studies have demonstrated robust anti-tumor effects of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors in head and neck MM (HNMM) patient-derived xenograft models with CDK4 amplification. Herein, we aimed to investigate the efficacy and safety of dalpiciclib (SHR6390), a CDK4/6 inhibitor, in HNMM patients harboring CDK4 amplification. Methods The anti-tumor efficacy of dalpiciclib was assessed by HNMM patient-derived xenograft (PDX) models and patient-derived tumor cells (PDC) in vivo and in vitro. Immunohistochemical analyses and western blot were then performed to assess the markers of cell proliferation and CDK4/6 signaling pathway. For the clinical trial, advanced recurrent and/or metastatic HNMM patients with CDK4 amplification were treated with dalpiciclib 125 mg once daily for 21 consecutive days in 28-day cycles. The primary endpoint was disease control rate (DCR). Secondary endpoints included safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results Dalpiciclib profoundly suppressed growth of HNMM-PDX and PDC with CDK4 amplification, whereas it showed relatively weak suppression in those with CDK4 wild type compared with vehicle. And dalpiciclib resulted in a remarkable reduction in the expression levels of Ki-67 and phosphorylated Rb compared with control group. In the clinical trial, a total of 17 patients were enrolled, and 16 patients were evaluable. The ORR was 6.3%, and the DCR was 81.3%. The estimated median PFS was 9.9 months (95% CI, 4.8-NA), and the median OS was not reached. The rate of OS at 12 months and 24 months was 68.8% (95% CI, 0.494–0.957) and 51.6% (95% CI, 0.307–0.866), respectively. The most frequent adverse events were neutrophil count decrease, white blood cell count decrease, and fatigue. Conclusions Dalpiciclib was well-tolerated and displayed a durable benefit for HNMM patients with CDK4 amplification in this study. Further studies on CDK4 inhibitors and its combination strategy for MM are worth further exploration. Trial registration ChiCTR2000031608.

Corona virus disease 2019 (COVID-19) has exerted a profound adverse impact on human health. Studies have demonstrated that aerosol transmission is one of the major transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pathogenic microorganisms such as SARS-CoV-2 can survive in the air and cause widespread infection among people. Early monitoring of pathogenic microorganism transmission in the atmosphere and accurate epidemic prediction are the frontier guarantee for preventing large-scale epidemic outbreaks. Monitoring of pathogenic microorganisms in the air, especially in densely populated areas, may raise the possibility to detect viruses before people are widely infected and contain the epidemic at an earlier stage. The multi-scale coupled accurate epidemic prediction system can provide support for governments to analyze the epidemic situation, allocate health resources, and formulate epidemic response policies. This review first elaborates on the effects of the atmospheric environment on pathogenic microorganism transmission, which lays a theoretical foundation for the monitoring and prediction of epidemic development. Secondly, the monitoring technique development and the necessity of monitoring pathogenic microorganisms in the atmosphere are summarized and emphasized. Subsequently, this review introduces the major epidemic prediction methods and highlights the significance to realize a multi-scale coupled epidemic prediction system by strengthening the multidisciplinary cooperation of epidemiology, atmospheric sciences, environmental sciences, sociology, demography, etc. By summarizing the achievements and challenges in monitoring and prediction of pathogenic microorganism transmission in the atmosphere, this review proposes suggestions for epidemic response, namely, the establishment of an integrated monitoring and prediction platform for pathogenic microorganism transmission in the atmosphere.

The sudden onset of the coronavirus disease 2019 (COVID-19) in January 2020 has affected essential global health services. Cancer-screening services that can reduce cancer mortality are strongly affected. However, the specific role of COVID-19 in cancer screening is not fully understood. This study aimed to assess the efficiency of global cancer screening programs before and during the COVID-19 pandemic and to promote potential cancer-screening strategies for the next pandemic. Electronic searches in PubMed, Embase, and Web of Science, and manual searches were performed between January 1, 2020 and March 1, 2023. Cohort studies that reported the number of participants who underwent cancer screening before and during the COVID-19 pandemic were included. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Differences in cancer-screening rates were estimated using the incidence rate ratio (IRR). Fifty-five cohort studies were included in this meta-analysis. The screening rates of colorectal cancer using invasive screening methods (Pooled IRR = 0.52, 95% CI: 0.42 to 0.65, p < 0.01), cervical cancer (Pooled IRR = 0.56, 95% CI: 0.47 to 0.67, p < 0.01), breast cancer (Pooled IRR = 0.57, 95% CI: 0.49 to 0.66, p < 0.01) and prostate cancer (Pooled IRR = 0.71, 95% CI: 0.56 to 0.90, p < 0.01) during the COVID-19 pandemic were significantly lower than those before the COVID-19 pandemic. The screening rates of lung cancer (Pooled IRR = 0.77, 95% CI: 0.58 to 1.03, p = 0.08) and colorectal cancer using noninvasive screening methods (Pooled IRR = 0.74, 95% CI: 0.50 to 1.09, p = 0.13) were reduced with no statistical differences. The subgroup analyses revealed that the reduction in cancer-screening rates varied across economies. Our results suggest that the COVID-19 pandemic has had a noteworthy impact on colorectal, cervical, breast, and prostate cancer screening. Developing innovative cancer-screening technologies is important to promote the efficiency of cancer-screening services in the post-COVID-19 era and prepare for the next pandemic.

ABSTRACT Aim This study aims to investigate the association of glycemia risk index (GRI), a novel composite metric derived from continuous glucose monitoring (CGM), with arterial stiffness in patients with type 2 diabetes. Materials and Methods A total of 342 adults with type 2 diabetes were enrolled between April and June 2023 from 11 communities in Shanghai, China. Medical examinations, including measurements of anthropometric parameters, blood pressure, and venous blood samples were conducted. Brachial‐ankle pulse wave velocity (baPWV) was examined to evaluate arterial stiffness. All the participants underwent a 14 day CGM recording and GRI was calculated from the CGM data. Results The mean age was 70.3 ± 6.8 years, and 162 (47.4%) were male. Participants with a higher baPWV had significantly higher levels of GRI and hyperglycemia component (both P for trend

The neutron tube is the core component of the controllable neutron source logging instrument. Its working stability, temperature resistance, neutron yield and other indicators have an important impact on the working performance of instrument. At present, with the requirement of deep logging, the neutron tube used in logging is supposed to improve neutron yield, temperature resistance, operating life and working stability. In this paper, the structure, materials and manufacturing process of drive-in target neutron tube are designed and optimized to reduce power consumption and improve operating time. The temperature resistance, operating life, and neutron yield of sample tube have tested to estimate the performance of ENT2465 with an outer diameter of 25 millimeters. Place the sample tube in the oil tank of the neutron testing platform and connect the cable. Record the temperature, cumulative working time, neutron yield, target voltage, target current and anode current during the work of the sample tube. The results show that under the target voltage of 80 kV and target current less than 60 μA, the accumulated operating life of the sample tube exceeds 1 000 hours, including 23 hours of continuous operation at 175℃ and more than 500 hours of accumulated operation, and 36 hours of continuous operation at room temperature. The neutron yield only decreases by 5.3 % after 1 000 hours under the same target voltage and current.

Faraday isolators can prevent the front-end system from disturbance and damage caused by a back-reflected beam, so they are important elements in laser systems. As magneto-optical materials are the most important component in Faraday isolators, the studies on magneto-optical materials have attracted much attention these years. Tb3Al5O12 (TAG) ceramics are considered to be one of the most promising magneto-optical materials for visible to near-infrared wavelength band application because of their outstanding comprehensive magneto-optical performance. However, the optical quality of TAG ceramics needs further optimization to meet the application requirements. In this work, high optical quality (Tb1−xYx)3Al5O12 (x = 0, 0.05, 0.1, 0.2, and 0.3) magneto-optical ceramics were fabricated successfully by solid-state reaction sintering combined with hot isostatic pressing (HIP) post-treatment. All the ceramics obtained showed a single garnet phase for different values of x in the range studied. The addition of Y2O3 was found to suppress the secondary phase and improve optical quality significantly. The ceramic samples obtained had clear grain boundaries and possessed the in-line transmittance values of 82.9% at 1064 nm and 82.2% at 633 nm, respectively. The Verdet constants of (Tb1−xYx)3Al5O12 ceramics with x = 0, 0.05, 0.1, 0.2, and 0.3 were −188.1, −175.4, −168.5, −143.0, and −119.9 rad/(T·m), respectively. The thermal conductivity of TAG ceramics was found to be 5.23 W/(m·K) at 25 ℃, and when 20% Y was substituted in place of Tb, the thermal conductivity decreased by only 9.4%.

Objective: Previously, our group screened a strain of Lactobacillus casei YZU01 that could efficiently remove patulin from apple juice. This article aimed to study the effect of L. casei YZU01 on the quality of apple juice during the removal of patulin from apple juice. Methods: The quality parameters of apple juice, including organic acids (citric acid, tartaric acid, fumaric acid, acetic acid and L-malic acid) and sugar content (glucose and galactose), acidity, non-enzymatic browning index, light transmittance, and color parameter, were assessed in three groups: commercial apple juice (CAJ), apple juice supplemented with patulin (CAJ-Patulin), and apple juice supplemented with patulin after degradation by L. casei YZU01 (CAJ-Patulin-L. casei YZU01). This analysis was conducted using high performance liquid chromatography (HPLC), pH meter, UV spectrophotometer, and colorimeter. Results: The content of citric acid, tartaric acid, fumaric acid and acetic acid in the group of CAJ-Patulin-L. casei YZU01 was increased from 0.18, 2.3, 0.12, and 0.00 g/kg to 2.11, 3.4, 0.15, and 0.66 g/kg, respectively. However, the content of L-malic acid, glucose and galactose in the group of CAJ-Patulin-L. casei YZU01 was decreased from 7.31, 38.59, and 67.55 g/kg to 5.26, 1.59 and 28.37 g/kg, respectively. The change of sugar and acid contents in the group of CAJ-Patulin-L. casei YZU01 had little effect on the acidity of apple juice. Furthermore, L. casei YZU01 treatment would not cause non-enzymatic browning reaction and had not adverse effects on the color of apple juice, but it would cause a fluctuation in light transmittance. In addition, after 72 hours of degradation, L. casei YZU01 had little effect on the L* and b* value of apple juice, but slightly increased the a* value, which represented that the green color of apple juice became lighter. In conclusion, the sugar and acid contents of apple juice were changed after treatment with L. casei YZU01, but no non-enzymatic browning reaction and color change was observed.

Acoustic metamaterials (AMs) composed of periodic artificial structures have extraordinary sound wave manipulation capabilities compared with traditional acoustic materials, and they have attracted widespread research attention. The sound insulation performance of thin-walled structures commonly used in engineering applications with restricted space, for example, vehicles’ body structures, and the latest studies on the sound insulation of thin-walled metamaterial structures, are comprehensively discussed in this paper. First, the definition and math law of sound insulation are introduced, alongside the primary methods of sound insulation testing of specimens. Secondly, the main sound insulation acoustic metamaterial structures are summarized and classified, including membrane-type, plate-type, and smart-material-type sound insulation metamaterials, boundaries, and temperature effects, as well as the sound insulation research on composite structures combined with metamaterial structures. Finally, the research status, challenges, and trends of sound insulation metamaterial structures are summarized. It was found that combining the advantages of metamaterial and various composite panel structures with optimization methods considering lightweight and proper wide frequency band single evaluator has the potential to improve the sound insulation performance of composite metamaterials in the full frequency range. Relative review results provide a comprehensive reference for the sound insulation metamaterial design and application.

Abstract Extrachromosomal circular DNA (eccDNA) refers to a distinct class of circular DNA molecules that exist independently from linear chromosomal DNA. Extensive evidence has firmly established the significant involvement of eccDNA in cancer initiation, progression, and evolutionary processes. However, the relationship between eccDNA and brain aging remains elusive. Here, we employed extrachromosomal circular DNA sequencing (Circle-seq) to generate a comprehensive dataset of eccDNA from six brain structures of both young and naturally-aged mice, including the olfactory bulb, medial prefrontal cortex, nucleus accumbens, caudate putamen, hippocampus, and cerebellum. Furthermore, through database annotation, we characterized the properties of mouse brain eccDNA, thereby gaining insights into the potential functions of eccDNA in the mouse brain. In conclusion, our study addresses a previously unexplored area by providing a comprehensive molecular characterization of eccDNA in brain tissues. The data presented in the study can be used as a fundamental resource to associate the molecular phenotypes of eccDNA with brain aging and gain deep insights into the biological role of eccDNA in mammalian brain aging.

Abstract Background Vitamin D may help to alleviate asthma exacerbation because of its anti-inflammation effect, but the evidence is inconsistent in childhood asthma. MiRNAs are important mediators in asthma pathogenesis and also excellent non-invasive biomarkers. We hypothesized that circulating miRNAs are associated with asthma exacerbation and modified by vitamin D levels. Methods We sequenced baseline serum miRNAs from 461 participants in the Childhood Asthma Management Program (CAMP). Logistic regression was used to associate miRNA expression with asthma exacerbation through interaction analysis first and then stratified by vitamin D insufficient and sufficient groups. Microarray from lymphoblastoid B-cells (LCLs) treated by vitamin D or sham of 43 subjects in CAMP were used for validation in vitro. The function of miRNAs was associated with gene modules by weighted gene co-expression network analysis (WGCNA). Results We identified eleven miRNAs associated with asthma exacerbation with vitamin D effect modification. Of which, five were significant in vitamin D insufficient group and nine were significant in vitamin D sufficient group. Six miRNAs, including hsa-miR-143-3p, hsa-miR-192-5p, hsa-miR-151a-5p, hsa-miR-24-3p, hsa-miR-22-3p and hsa-miR-451a were significantly associated with gene modules of immune-related functions, implying miRNAs may mediate vitamin D effect on asthma exacerbation through immune pathways. In addition, hsa-miR-143-3p and hsa-miR-451a are potential predictors of childhood asthma exacerbation at different vitamin D levels. Conclusions miRNAs are potential mediators of asthma exacerbation and their effects are directly impacted by vitamin D levels.

Abstract Background The key role of thrombospondin 1 (THBS1) in the pathogenesis of acute-on-chronic liver failure (ACLF) is unclear. Here, we present a transcriptome approach to evaluate THBS1 as a potential biomarker in ACLF disease pathogenesis. Methods Biobanked peripheral blood mononuclear cells (PBMCs) from 330 subjects with hepatitis B virus (HBV)-related etiologies, including HBV-ACLF, liver cirrhosis (LC), and chronic hepatitis B (CHB), and normal controls (NC) randomly selected from the Chinese Group on the Study of Severe Hepatitis B (COSSH) prospective multicenter cohort underwent transcriptome analyses (ACLF = 20; LC = 10; CHB = 10; NC = 15); the findings were externally validated in participants from COSSH cohort, an ACLF rat model and hepatocyte-specific THBS1 knockout mice. Results THBS1 was the top significantly differentially expressed gene in the PBMC transcriptome, with the most significant upregulation in ACLF, and quantitative polymerase chain reaction (ACLF = 110; LC = 60; CHB = 60; NC = 45) was used to verify that THBS1 expression corresponded to ACLF disease severity outcome, including inflammation and hepatocellular apoptosis. THBS1 showed good predictive ability for ACLF short-term mortality, with an area under the receiver operating characteristic curve (AUROC) of 0.8438 and 0.7778 at 28 and 90 days, respectively. Enzyme-linked immunosorbent assay validation of the plasma THBS1 using an expanded COSSH cohort subjects (ACLF = 198; LC = 50; CHB = 50; NC = 50) showed significant correlation between THBS1 with ALT and γ-GT (P = 0.01), and offered a similarly good prognostication predictive ability (AUROC = 0.7445 and 0.7175) at 28 and 90 days, respectively. ACLF patients with high-risk short-term mortality were identified based on plasma THBS1 optimal cut-off value (

Viscoelastic damping materials (VDMs) are valued for their high damping characteristics in vibration and noise control. However, they typically underperform at lower frequencies and add substantial mass to structures. This study introduces an innovative approach by embedding an acoustic black hole (ABH) structure within VDMs (ABH-VDM) to achieve lightweight and broadband vibration damping. Firstly, a finite element method-based vibration model is developed to analyse the propagation and attenuation characteristics of vibrations in a plate strip embedded with ABH-VDM. This analysis provides insights into the dynamic behaviour and damping effectiveness of the proposed structure. Secondly, the study investigates the vibration reduction capabilities and mass implications of ABH-VDM on large-scale plate structures. The influence of ABH structural parameters, including the power exponent, cut-off thickness, and array configuration, is systematically investigated to optimize damping performance. Finally, experimental validation confirms that ABH-VDM achieves an additional 1.4 dB reduction in vibration across the entire frequency spectrum, with a bandwidth extension of 900 Hz. Moreover, ABH-VDM reduces mass by 8.6 %, demonstrating its potential for lightweight vibration control in structural applications. This research contributes valuable insights into advancing lightweight and broadband damping solutions for enhanced vibration management in engineering systems.

Marine associated-bacteria is an excellent source for novel enzymes. The quest to find new agarases with unique properties for industrial application is continually growing. Agarase hydrolyzed agar to oligoagar for broader applications. Herein, we report the production of β-agarase from Alteromonas macleodii BC7.1, a marine sediment bacteria collected in Barra Cadi Island, South Sulawesi, Indonesia. The enzyme production was optimal using a medium containing 0.4 % of agar after 48 h incubation. The enzyme has an optimum activity at 45 °C, pH 7–8 and was stable for 12 h incubation. Agarase BC7.1 (Aga-BC7.1) was resistant to most ions (except Zn and Mn), denaturing agents and chemicals. The Km and Vmax values were 18 mg/mL and 100 U/mg, respectively. The molecular size of agarase in its native condition was 220 kDa. Based on α-glucosidase inhibition activity indicated that oligosaccharides can be produced within 8–24 hours using 0.3–0.5 % (w/v) substrate, at 30–37 °C, with 50 mM Tris-HCl buffer at pH 7.0 and various types of agar. The HPLC analyses of the hydrolysis products confirmed the presence of neoagarooligosaccharides (NAOS), neoagaro-biose (NA2), -tetraose (NA4), and -hexose (NA6). A mixture of oligosaccharides with a major content of NA2 exhibits the highest α-glucosidase inhibition activity compared to crude oligosaccharides and other fractions. This study thus highlights the potency of β-agarase from A. macleodii for industrial application.

IntroductionTraumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery.MethodsIn this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6–12 months (6–12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis.ResultsOur key findings include: (1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. (2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. (3) The increase in the ALPS index from acute (14Day) to the chronic (6–12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information.ConclusionePVS burden and ALPS index offers distinct values in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.

Coxsackievirus A16 (CV-A16) and coxsackievirus A10 (CV-A10), more commonly etiological agents of hand, foot and mouth disease (HFMD), are capable of causing severe neurological syndromes with high fatalities, but their neuropathogenesis has rarely been studied. Mounting evidence indicated that pyroptosis is an inflammatory form of cell death that might be widely involved in the pathogenic mechanisms of neurotropic viruses. Our study was designed to examine the effects of NLRP3-mediated pyroptosis in CV-A16- and CV-A10-induced inflammatory neuropathologic formation. In this work, it was showed that SH-SY5Y cells were susceptible to CV-A16 and CV-A10, and meanwhile their infections could result in a decreasing cell viability and an increasing LDH release as well as Caspase1 activation. Moreover, CV-A16 and CV-A10 infections triggered NLRP3-mediated pyroptosis and promoted the release of inflammatory cytokines. Additionally, activated NLRP3 accelerated the pyroptosis formation and aggravated the inflammatory response, but inhibited NLRP3 had a dampening effect on the above situation. Finally, it was further revealed that NLRP3 agonist enhanced the viral replication, but NLRP3 inhibitor suppressed the viral replication, suggesting that NLRP3-driven pyroptosis might support CV-A16 and CV-A10 production in SH-SY5Y cells. Together, our findings demonstrated a mechanism by which CV-A16 and CV-A10 induce inflammatory responses by evoking NLRP3 inflammasome-regulated pyroptosis, which in turn further stimulated the viral replication, providing novel insights into the pathogenesis of CV-A16 and CV-A10 infections.

Ramp events caused by intermittent wind power are increasingly intensifying, seriously threatening the stability and economy of power systems. This paper proposes a novel event-based optimization (EBO) method to smooth the impact of ramp events by balancing energy between wind farms and pumped storage power stations. Firstly, ramp events in wind farms are modeled by using discretization energy within given intervals, which is suitable for the EBO framework. Then, a value function is defined to search the discrete smoothing strategy with event constraints, such as switching operation conditions, the storage capacity of pumped storage, etc. The event-based Q-factor, composed of value functions, is used to search the optimal actions with complicated constraints under a single-stage and multi-stage framework. Finally, a simulation example is developed according to the operation data of an actual wind farm, and the smoothing effect of the strategy is verified by comparing it with the dynamic programming algorithm. Simulation results show that the proposed EBO method can smooth the impact of ramp events by flexibly combining the features of wind farms and pumped storage power stations.