Search

Abstract Background Despite remarkable achievements in applying chimeric antigen receptor (CAR)-T cells to treat hematological malignancies, they remain much less effective against solid tumors, facing several challenges affecting their clinical use. We previously showed that multichain DNAX-activating protein (DAP) CAR structures could enhance the safety and efficacy of CAR-T cells when used against solid tumors. In particular, mesothelin (MSLN)-targeted CAR-T cell therapy has therapeutic potential in MSLN-positive solid tumors, including ovarian cancer and mesothelioma. Methods In vitro cell killing assays and xenograft model were utilized to determine the anti-tumor efficacy of MSLN targeting DAP-CAR-T cells and other CAR-T cells. ELISA and flow cytometry analysis were used to assess the cytokine secretion capacity and proliferation ability. Eight patients with MSLN expression were enrolled to evaluate the safety and efficacy of MSLN-DAP CAR-T cell therapy. Single-cell sequencing was performed to explore the dynamics of immune cells in patients during treatment and to identify the transcriptomic signatures associated with efficacy and toxicity. Results We found that multichain DAP-CAR formed by combining a natural killer cell immunoglobulin-like receptor truncator and DAP12 exhibited better cytotoxicity and tumor-killing capacity than other natural killer cell-activated receptors associated with DAP12, DAP10, or CD3Z. The safety and efficacy of MSLN-DAP CAR-T cell therapy in patients with ovarian cancer and mesothelioma were evaluated in a single-arm, open-label clinical trial (ChiCTR2100046544); two patients achieved partial response, while four patients had a stable disease status. Furthermore, single-cell sequencing analysis indicated that KT032 CAR-T cell infusion could recruit more immune cells and temporarily remodel the TME. Conclusions Our study highlights the safety and therapeutic efficacy of multiple-chain DAP-CAR-T cell therapy targeting MSLN to treat patients with ovarian cancer and mesothelioma. Trial registration ChiCTR.org.cn, ChiCTR2100046544 . May 21, 2021.

To solve the problem of poor thermal stability of the current D-allulose 3-epimerase (DAEase), the ancestor sequences of DAEase with different catalytic domains were reconstructed by big data mining, reasonable modification and ancestor sequence reconstruction (ASR) strategy under the guidance of phylogenetic information. The expression vectors of the ancestor sequences were constructed, and DAEase A13 with significantly enhanced thermal stability was screened by recombinant expression and molecular docking, and its enzymatic properties were characterized. In addition, the molecular mechanism of thermal stability enhancement of DAEase A13 was revealed based on structural analysis and molecular dynamics. The results showed that the half-life of A13 constructed based on ASR strategy could reach 8.4 h at 70 ℃, indicating that its thermal stability was significantly enhanced compared with that of wild-type (WT) enzyme. The maximum conversion rate of A13 reached 31%, indicating that the catalytic activity of A13 was slightly higher than that of WT enzyme. The structural and molecular dynamics analysis revealed that the increase in hydrogen bonding and hydrophobic interaction in ASR A13 was the main factor responsible for maintaining the stability of the enzyme's molecular structure at high temperatures. The results showed that ASR strategy could modify DAEases to enhance the stability, activity or hybridity, which could provide superior biocatalyst sources for various industrial applications of functional sugars.

Abstract Background The phenylalanine ammonia-lyase (PAL) gene, a well-studied plant defense gene, is crucial for growth, development, and stress resistance. The PAL gene family has been studied in many plants. Citrus is among the most vital cash crops worldwide. However, the PAL gene family has not been comprehensively studied in most Citrus species, and the biological functions and specific underlying mechanisms are unclear. Results We identified 41 PAL genes from nine Citrus species and revealed different patterns of evolution among the PAL genes in different Citrus species. Gene duplication was found to be a vital mechanism for the expansion of the PAL gene family in citrus. In addition, there was a strong correlation between the ability of PAL genes to respond to stress and their evolutionary duration in citrus. PAL genes with shorter evolutionary times were involved in more multiple stress responses, and these PAL genes with broad-spectrum resistance were all single-copy genes. By further integrating the lignin and flavonoid synthesis pathways in citrus, we observed that PAL genes contribute to the synthesis of lignin and flavonoids, which enhance the physical defense and ROS scavenging ability of citrus plants, thereby helping them withstand stress. Conclusions This study provides a comprehensive framework of the PAL gene family in citrus, and we propose a hypothetical model for the stress resistance mechanism in citrus. This study provides a foundation for further investigations into the biological functions of PAL genes in the growth, development, and response to various stresses in citrus.

Abstract Recent research has explored the potential of the demethylating drug 5-azacytidine (Aza) as therapy for a range of diseases. However, the therapeutic efficacy of Aza for patients of atherosclerosis remains unclear. This study investigates the therapeutic application of Aza to atherosclerosis in order to elucidate the underlying mechanisms. We generated induced Tregs (iTregs) from CD4+ T cells by using Aza in vitro, and this was followed by the intravenous infusion of iTregs for the treatment of atherosclerosis. The adoptive transfer of Aza-iTreg significantly increased peripheral blood Treg cells, suppressed inflammation, and attenuated atherosclerosis in ApoE−/− mice. Furthermore, we observed a notable demethylation of the Forkhead box P3 (Foxp3)-regulatory T cell-specific demethylated region (TSDR) and an upregulation of Foxp3 expression in the CD4+ T cells in the spleen of the ApoE−/− mice following the transfer of Aza- iTregs. We also demonstrated that Aza converted naive CD4+ T cells into Tregs by DNA methyltransferase 1 (Dnmt1)-mediated Foxp3-TSDR demethylation and the upregulation of Foxp3 expression. Conversely, the overexpression of Dnmt1 in the CD4+ T cells attenuated the Aza-induced Foxp3-TSDR demethylation and upregulation of Foxp3 expression. Our results reveal that Aza converts naive CD4+ T cells into functional Tregs by inhibiting Dnmt1, and the transfer of Aza-iTregs suppresses atherosclerosis in mice.

Abstract Background This research aims to assess the demographic characteristics, prevalence, outcomes, and complications in chronic kidney disease (CKD) patients following mandible fractures in the United States using a nationally representative database. Methods We analyzed data from the National Inpatient Sample from 2010 to 2019 in the United States. Patients with mandible fractures were categorized into three groups based on the International Classification of Diseases, Ninth and Tenth Revisions (ICD-9-CM and ICD-10-CM): end-stage renal disease (ESRD), non-ESRD CKD, and healthy kidney function. Chi-squared tests and analysis of variance (ANOVA) were used to compare these groups. Additionally, multivariate regression analysis was performed to determine whether CKD is an independent risk factor for complications in patients with mandible fractures. Results A total of 38,481 patients in the United States were estimated to have experienced mandible fractures between 2010 and 2019. The incidence rate of non-ESRD CKD in patients with mandible fractures significantly increased over time, while the prevalence of ESRD remained stable during the ten-year period. Compared to the healthy kidney function group, patients with chronic kidney disease exhibited higher hospital costs, longer hospitalization durations, and higher in-hospital mortality rates. Additionally, they had greater odds ratios for most of the investigated complications. Conclusions This study revealed a steady annual increase in the morbidity rate of non-ESRD CKD among patients with mandible fractures, while ESRD prevalence remained stable over ten years. We observed a close association between chronic kidney disease and the prognosis of patients with mandible fractures. Clinicians should prioritize preventive measures and appropriate management of mandibular fractures in patients with CKD.

Walnut kernels, selected as the raw material, underwent hydrolysis with protein-glutaminase (PG) following pulping. This process laid the foundation for producing set-type walnut yogurt, involving steps such as blending, homogenization, sterilization, and fermentation. The study investigated the impact of protein-glutaminase and five distinct starter cultures labeled I~V on the quality of walnut yogurt. This was evaluated by examining the yogurt's fermentation characteristics, physicochemical indicators, and microstructure. Furthermore, walnut yogurt developed under these optimal conditions was compared to traditional milk yogurt to assess its quality and characteristics. The findings revealed a significant improvement in the fermentation characteristics and textural parameters of yogurt fermented by walnut milk following enzymatic hydrolysis compared to non-enzymatic walnut milk. The optimal conditions were identified as 0.2% enzyme concentration and a 40-minute reaction time, with the pH, acidity, hardness, and consistency of walnut yogurt being 4.3, 55°T, 85.30 g, and 583.96 g·s, respectively. Walnut yogurt developed using starter culture I exhibited the highest acidity level, maintaining minimal fluctuation over a 21-day storage period. In contrast, yogurts prepared with alternative starter cultures demonstrated varying degrees of stratification and sedimentation. The yogurt fermented with culture I showed superior viscoelastic properties, presenting a denser gel network. Conversely, yogurts fermented with cultures IV and V displayed reduced apparent viscosity, lower values of G' (storage modulus), and G'' (loss modulus), along with a looser gel structure. Additionally, walnut yogurt produced with starter culture I maintained bacterial counts exceeding 106 CFU/mL throughout the storage duration. Despite walnut yogurt requiring further refinement in aspects such as consistency, water-holding capacity, and whey release rate compared to milk yogurt, the overall impact of PG was positive, enhancing the gelation quality of walnut yogurt. The yogurt prepared with starter culture I (Lactobacillus bulgaricus and Streptococcus thermophilus) was notably improved, receiving favorable overall assessments.

Abstract Background ‘Hongyang’ kiwifruit (Actinidia chinensis cv ‘Hongyang’) is a high-quality variety of A. chinensis with the advantages of high yield, early ripening, and high stress tolerance. Studies have confirmed that the Shaker K+ genes family is involved in plant uptake and distribution of potassium (K+). Results Twenty-eight Shaker genes were identified and analyzed from the ‘Hongyang’ kiwifruit (A. chinensis cv ‘Hongyang’) genome. Subcellular localization results showed that more than one-third of the AcShaker genes were on the cell membrane. Phylogenetic analysis indicated that the AcShaker genes were divided into six subfamilies (I-VI). Conservative model, gene structure, and structural domain analyses showed that AcShaker genes of the same subfamily have similar sequence features and structure. The promoter cis-elements of the AcShaker genes were classified into hormone-associated cis-elements and environmentally stress-associated cis-elements. The results of chromosomal localization and duplicated gene analysis demonstrated that AcShaker genes were distributed on 18 chromosomes, and segmental duplication was the prime mode of gene duplication in the AcShaker family. GO enrichment analysis manifested that the ion-conducting pathway of the AcShaker family plays a crucial role in regulating plant growth and development and adversity stress. Compared with the transcriptome data of the control group, all AcShaker genes were expressed under low-K+stress, and the expression differences of three genes (AcShaker15, AcShaker17, and AcShaker22) were highly significant. The qRT-PCR results showed a high correlation with the transcriptome data, which indicated that these three differentially expressed genes could regulate low-K+ stress and reduce K+ damage in kiwifruit plants, thus improving the resistance to low-K+ stress. Comparison between the salt stress and control transcriptomic data revealed that the expression of AcShaker11 and AcShaker18 genes was significantly different and lower under salt stress, indicating that both genes could be involved in salt stress resistance in kiwifruit. Conclusion The results showed that 28 AcShaker genes were identified and all expressed under low K+ stress, among which AcShaker22 was differentially and significantly upregulated. The AcShaker22 gene can be used as a candidate gene to cultivate new varieties of kiwifruit resistant to low K+ and provide a reference for exploring more properties and functions of the AcShaker genes.

Indica and Japonica rice were selected as test materials to investigate the difference formation in textural perception, particle size, water content, leakage solid content and reducing sugar content of rice bolus during chewing process were analyzed by using in vivo oral masticatory properties as a reference and setting salivary addition amounts, chewing times in vitro. The results showed that the three types of rice were similar in composition, but their gelatinization characteristics and crystalline structures were different. Monitoring the dynamic textural perception of rice, it was found that the force worked on rice decreased from 44~66 N to 20~21 N, Daohuaxiang No.2 rice had a higher chewiness and adhesiveness, while Yexiangyoulisi rice had a lower adhesiveness and loose texture perception during in vitro chewing. Through analyzing the characteristics of rice bolus in simulated chewing process, results indicated that the moisture content of rice bolus of Yexiangyoulisi rice increased by 1.84%, significantly higher than the other Japonica rice (P

China is the largest aquaculture country in the world, with mariculture production accounting for more than 50% of the total production in the world. In 2021, the production of shellfish in China increased to 1.546 × 107 tons, accounting for approximately 70% of the mariculture production. Filter-feeding bivalves such as oysters and clams are the main species of mariculture in China. In addition to the important economic values, filter-feeding bivalves influence ecosystem nutrient cycling through feeding, metabolism, and biodeposition and play roles in increasing the water transparency, preventing harmful algal blooms, controlling eutrophication, and promoting carbon storage. The physiological activities of filter-feeding bivalves, especially ingestion and metabolism, form the link between planktonic and benthic ecosystems, and their physiological indicators are the basic parameters for evaluating the energy budget and carrying capacity. However, although researchers have conducted a series of studies on the physiological activities of filter-feeding bivalves, some limitations in monitoring and the subsequent data processing remain. Therefore, it is urgent to improve the measurement of the physiological activities of filter-feeding bivalves, including the accuracy of data collection and the rigorousness of data processing, to ensure the accuracy of the experimental results.Mudflats are located in the interaction zone between the land and sea and are important areas for the habitat, growth, and reproduction of several macrobenthic organisms. As the dominant species of macrobenthic communities, mudflat-buried shellfish play a crucial role in the material and energy flows of a mudflat ecosystem. However, recently, with the expansion of shellfish aquaculture, the mudflat environment has been deteriorating accompanied by a series of ecological problems, such as high mortality and slow growth rates and alteration in the structure of phytoplankton community, which has led to significant losses to the shellfish aquaculture industry. Therefore, the ability of the ecosystem to support shellfish production must be evaluated, and its carrying capacity must be estimated. Generally, numerical methods for estimating the carrying capacity of shellfish based on food limiting indicators include physical-biological ecosystem modelling, trophodynamic modeling, and energy balance modeling. Current methodologies for estimating shellfish carrying capacity are divided into two main categories: dynamic and static modellings. Compared with the dynamic estimation model, static estimation methods are based on the environment of the target area and the key physiological parameters of shellfish and have been widely applied in some aquaculture areas such as Sanggou Bay, Jiaozhou Bay, and Zhangzidao in China.Here, to explore the energy budget and carrying capacity of the surf clam, Mactra veneriformis, and the estuarine clam, Potamocorbula laevis, in Geligang, Liaodong Bay, a portable particle counter and a continuous oxygen monitoring system were used in combination with flow-through chambers to detect the feeding and metabolic parameters of M. veneriformis and P. laevis. Furthermore, the carrying capacity of two mudflat-buried bivalves in Liaodong Bay was estimated based on the organic carbon supply-demand balance model. The results indicated that 1) the clearance rates of M. veneriformis and P. laevis were (4.87±0.85) L/(h·g) and (6.46±2.25) L/(h·g), respectively, and the oxygen consumption rates were (0.94±0.45) mg/(h·g) and (0.22±0.14) mg/(h·g), respectively. The energy absorption of M. veneriformis and P. laevis ranged from 748.97 to 1 333.52 J/(h·g), and 931.55 to 1 647.08 J/(h·g), respectively. 2) Using organic carbon supply-demand balance model combined with the primary productivity and shellfish clearance rate, we found that the carrying capacity of M. veneriformis in Geligang, Liaodong Bay, was 57, 47, and 34 ind./m2 for age-1 (total wet weight 6.7 g), age-2 (total wet weight 9.3 g) and age-3 (total wet weight 14.6 g), respectively; and the carrying capacity of P. laevis was 346, 143, and 99 ind./m2 for age-1 (total wet weight 0.14 g), age-2 (total wet weight 0.69 g), and age-3 (total wet weight 1.25 g), respectively. These results provide basic data for the rational exploitation and utilization of shellfish resources and the conservation of biodiversity in a mudflat ecosystem.

To enhance the scientific rigor of design decisions and develop new rosewood furniture that aligns with user emotions, this study integrates the strengths of the Hesitant Fuzzy Analytic Hierarchy Process (HFAHP) and Hesitant Fuzzy Quality Function Deployment (HFQFD) within the framework of Kansei Engineering (KE). This method accurately translates Consumer Requirements (CRs) into Engineering Characteristics (ECs). First, the KJ Method was used to screen and categorize Kansei words, create product sample images, and deconstruct the form of rosewood furniture using morphological analysis. Second, after collecting valid questionnaires using a 7-point Likert scale, Factor Analysis (FA) was employed to extract three key Kansei factors. Third, HFAHP was utilized to calculate the weights of the Kansei words. Fourth, HFQFD was applied to construct a hesitant fuzzy correlation matrix between CRs and ECs, determining the priority of design elements for rosewood furniture. Finally, using a square table as an example in the design practice, the optimal Scheme No. 9, which highly meets consumer emotional needs and features harmonious form combinations, was selected. This study enhances the emotional value of rosewood furniture, optimizes the design decision-making process, and improves contemporary consumer satisfaction.

Psychological and physiological cognitive measurements were combined with Kansei engineering theory to study the shape of the traditional Chinese official-hat chair, a kind of Ming-style chairs, while investigating people’s perceptual cognitive process. This work employed focus groups to obtain 5 groups of representative words and 22 typical samples for evaluation experiments. After data preprocessing, principal component analysis (PCA) was used to extract three main components: "Concise-Ornate", "Soft-Strong", and "Elegant-Vulgar". In terms of component weight calculation, the analytic hierarchy process (AHP) was initially used to calculate the subjective cognitive weight of different components, and then eye-tracking technology was used to assist in calculating the physiological cognitive weight. Finally, combining the subjective and objective weights, the weights of the components were determined as: backrest (41.02%) > stretcher (18.29%) > handrail (11.64%) > top rail (11.14%) > outside stick (8.64%) > inside stick (5.32%) > foot rail (3.95%). The four main components—backrest, stretcher, handrail, and top rail—along with perceptual image evaluations, were selected to establish a multivariate linear regression equation, thereby constructing a mathematical mapping relationship between perceptual image and main design elements. This provides theoretical support for designers in creating different perceptual images.

Abstract Objective The objective of this study was to develop and evaluate the performance of machine learning models for predicting the possibility of systemic inflammatory response syndrome (SIRS) following percutaneous nephrolithotomy (PCNL). Methods We retrospectively reviewed the clinical data of 337 patients who received PCNL between May 2020 and June 2022. In our study, 80% of the data were used as the training set, and the remaining data were used as the testing set. Separate prediction models based on the six machine learning algorithms were created using the training set. The predictive performance of each machine learning model was determined by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity using the testing set. We used coefficients to interpret the contribution of each variable to the predictive performance. Results Among the six machine learning algorithms, the support vector machine (SVM) delivered the best performance with accuracy of 0.868, AUC of 0.942 (95% CI 0.890–0.994) in the testing set. Further analysis using the SVM model showed that prealbumin contributed the most to the prediction of the outcome, followed by preoperative urine culture, systemic immune-inflammation (SII), neutrophil to lymphocyte ratio (NLR), staghorn stones, fibrinogen, operation time, preoperative urine white blood cell (WBC), preoperative urea nitrogen, hydronephrosis, stone burden, sex and preoperative lymphocyte count. Conclusion Machine learning-based prediction models can accurately predict the possibility of SIRS after PCNL in advance by learning patient clinical data, and should be used to guide surgeons in clinical decision-making.

The anti-detection capabilities of adversarial malware examples have drawn the attention of antivirus vendors and researchers. In black-box scenarios where internal information of the target model cannot be accessed, with the ability of the reinforcement learning (RL) agents to adjust strategies based on the feedback from the environment, existing RL-based methods enable evasion of Windows PE malware detectors. However, obtaining evasion rewards as positive feedback in the black-box setting proves challenging, resulting in low training efficiency. To address this issue, we introduce the intrinsic curiosity reward into the framework to motivate the agent to explore unknown state spaces and learn effective evasion strategies. Additionally, we employ the generative adversarial network (GAN) to obtain varying synthetic data, which replaces random or benign bytes as adversarial payloads for the agent's action content, improving attack capabilities and reducing the risk of hard-coded adversarial perturbations being anchored. We compare the attack performance with other RL-based baseline methods, and experimental results show that our framework is more flexible and effective, achieving a 63%-85% attack success rate against EMBER, FireEye and MalConv. Even if defensive measures are taken, the proposed method still has a certain attack capability, and the success rate remains between 48%-67%.

The mortise and tenon structure is a pivotal component of ancient Chinese architecture and furniture, encapsulating a rich history of evolution, cultural shifts, and productivity developments. Engaging modern individuals with this historical context through innovative product design provides a way to advance the cultural and creative industries and promote the sustainable development of mortise and tenon culture. This study conducted sentiment analysis on consumer reviews of three types of mortise and tenon cultural and creative products in the Chinese market, revealing consumer needs and expectations regarding functionality, quality, and design. Utilizing Norman's Emotional Design Theory, the study analyzed the design elements of mortise and tenon cultural and creative products across the instinctive, behavioral, and reflective levels. A systematic design model was put together, providing both theoretical support and practical guidance for the future design of these products, thereby offering inspiration and aid for the modernization and transformation of traditional culture.

Abstract Background Lymph node metastasis (LNM) is associated with worse prognosis in bladder urothelial carcinoma (BUC) patients. This study aimed to develop and validate machine learning (ML) models to preoperatively predict LNM in BUC patients treated with radical cystectomy (RC). Methods We retrospectively collected demographic, pathological, imaging, and laboratory information of BUC patients who underwent RC and bilateral lymphadenectomy in our institution. Patients were randomly categorized into training set and testing set. Five ML algorithms were utilized to establish prediction models. The performance of each model was assessed by the area under the receiver operating characteristic curve (AUC) and accuracy. Finally, we calculated the corresponding variable coefficients based on the optimal model to reveal the contribution of each variable to LNM. Results A total of 524 and 131 BUC patients were finally enrolled into training set and testing set, respectively. We identified that the support vector machine (SVM) model had the best prediction ability with an AUC of 0.934 (95% confidence interval [CI]: 0.903–0.964) and accuracy of 0.916 in the training set, and an AUC of 0.855 (95%CI: 0.777–0.933) and accuracy of 0.809 in the testing set. The SVM model contained 14 predictors, and positive lymph node in imaging contributed the most to the prediction of LNM in BUC patients. Conclusions We developed and validated the ML models to preoperatively predict LNM in BUC patients treated with RC, and identified that the SVM model with 14 variables had the best performance and high levels of clinical applicability.

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported. Methods and design The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers. Conclusions As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH. Registration Number in ClinicalTrials.gov NCT05311072.

The objective of this study was to optimize the extraction process of total sterols from wild Pyracantha fortuneana leaves (WPFL), and explore their antioxidant and whitening activities. The yield of total sterols (WPFLTPS) was used as indicator, and the single factor experiment was used to investigate the effects of extraction solvent, solid-liquid ratio, ultrasonic temperature and ultrasonic time on the yield of WPFLTPS. Based on this, the orthogonal experimental design was used to optimize the extraction conditions. The DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] and nitrite methods were used to evaluate the antioxidant activity of WPFLTPS in vitro. The whitening activity was evaluated by the inhibitory effect on tyrosinase. The results showed that for optimal extraction process of WPFLTPS, the extraction solvent was absolute ethanol, ultrasonic temperature was 50 ℃, solid-liquid ratio was 1:16 g/mL, and ultrasonic time was 25 minutes. Under these conditions, the yield of WPFLTPS was (11.00±0.03) mg/g. In the range of 0.5~5 mg/mL, WPFLTPS had strong scavenging effects on DPPH radicals, ABTS+ radicals and nitrite ions, as well as a strong inhibitory effect on tyrosinase, demonstrating a good dose-response relationship. This extraction process was stable and reliable for extracting WPFLTPS. The WPFLTPS can be used as a new, natural antioxidant and tyrosinase inhibitor in functional foods.

BackgroundParkinson’s disease psychosis (PDP) is one of the most severe and disabling non-motor symptoms in the progression of Parkinson’s disease (PD), significantly impacting the prognosis of PD patients. In recent years, there has been an increase in literature on PDP. However, bibliometrics has rarely been applied to PDP research. This study provides an overview of the current state of PDP research and predicts future trends in this field.MethodsThe literature search was conducted using the Web of Science Core Collection, with the search terms (Parkinson* AND (psychotic* OR hallucination* OR illusion* OR delusion* OR misperception* OR psychosis OR psychoses)). VOSviewer and CiteSpace software were employed to perform bibliometric analysis and visual representation of the search results.ResultsA total of 603 articles were effectively included. Since 2017, there has been a significant upward trend in publications related to PDP. The United States, the United Kingdom, and Canada were the top three contributing countries in terms of publication volume, with France also having a strong influence in this field. Movement Disorders and King’s College London included and published the most articles on PDP. The paper titled “Hallucinations in Parkinson’s Disease: Prevalence, Phenomenology, and Risk Factors” received the highest number of citations and average citations. Cluster analysis results identified brain, prevalence, connectivity, and atypical antipsychotics as key hotspots in this field. High-frequency keywords were grouped into three themes: neurobiology, therapeutic strategies, and symptom research. Among them, pimavanserin, risk, and functional connectivity have been the most studied areas in the past 7 years and are likely to remain key topics in future research.ConclusionResearch on PDP has garnered increasing attention. This study visualizes PDP research over the past 25 years to analyze global hotspots and trends. It offers researchers a valuable perspective for identifying key topics and understanding research trajectories in this expanding field.

IntroductionPorcine circovirus type 2 (PCV2) and Porcine epidemic diarrhea virus (PEDV) are highly prevalent in Sichuan, significantly affecting the swine industry’s development. PCV2, known for its immunosuppressive effects, can compromise pigs’ immune systems, while PEDV typically causes diarrhea in piglets, leading to high mortality rates. Despite their impact, recent studies on the epidemiology and genetic diversity of PCV2 and PEDV within Sichuan Province remain limited.MethodsThis study examines clinical samples from 352 diarrheal piglets across 63 pig farms in 17 regions of Sichuan Province, revealing positivity rates of 42.33% (149/352) for PCV2 and 50.28% (177/352) for PEDV, with a co-infection rate of 27.56% (97/352). Notably, the highest positivity rates were observed in Ziyang for PCV2 at 61.90% (13/21), and in Meishan for PEDV at 73.81% (31/42), both regions also reported the highest co-infection rates of 47.62%.Results and discussionSeasonal analysis indicated that PEDV infections peaked during winter, whereas PCV2 showed no significant seasonal trends. Phylogenetic analysis identified 14 PCV2 strains, categorizing 2 as PCV2b (14.29%), 10 as PCV2d (71.43%), and 2 as PCV2e (14.29%). Among the 16 PEDV strains, 2 were classified as G1a (12.5%) and 14 as G2a (87.5%), with PCV2d and PEDV G2a identified as the predominant strains in the region. The study also highlights a high mutation rate at the antigenic sites of both viruses, potentially affecting vaccine efficacy. These findings underscore the need for ongoing surveillance and vaccine development tailored to the prevalent strains to improve control measures within the province.

BackgroundPsoriasis is closely associated with cardiovascular disease (CVD). However, the current evidence on the correlation between Life’s Essential 8 and Psoriasis is insufficient. Our aim was to investigate the relationship between Life’s Essential 8 (LE8), a measure of cardiovascular health (CVH), and psoriasis.ObjectiveThis study aimed to clarify the impact of Life’s Essential 8 on Psoriasis and explore its implications.MethodsThis population-based cross-sectional study included 9,876 US adults aged 20 to 59 years from the National Health and Nutrition Examination Survey (NHANES) 2003–2006 and 2009–2014 cycles. The LE8 score comprises 8 metrics and was categorized into low, moderate, and high CVH. Logistic regression and restricted cubic splines (RCS) were used to assess the association between LE8 score and psoriasis.ResultsAmong the 9,876 participants, those with moderate and high CVH had higher risks of psoriasis compared to low CVH. Additionally, every 10-point increase in the LE8 score was associated with a 10% reduced risk of psoriasis. Interaction was observed between gender, age, education level, race/ethnicity, marital status, and PIR.ConclusionLE8 and its subscale scores were strongly negatively related to the risk of psoriasis. Encouraging optimal CVH levels may be advantageous in reducing the incidence of psoriasis.

Abstract In plantae, basic leucine zipper (bZIP) transcription factors (TFs) are widespread and regulate a variety of biological processes under abiotic stress. However, it has not been extensively studied in Rosaceae, and the functional effects of bZIP on Eriobotrya japonica under salt stress are still unknown. Therefore, in this study, the bZIP TF family of 12 species of Rosaceae was analyzed by bioinformatics method, and the expression profile and quantitative real‐time polymerase chain reaction of E. japonica under salt stress were analyzed. The results showed that a total of 869 bZIP TFs were identified in 12 species of Rosaceae and divided into nine subfamilies. Differences in promoter cis‐elements between subfamilies vary depending on their role. Species belonging to the same subfamily have a similar number of chromosomes and the number of genes contained on each chromosome. Gene duplication analysis has found segmental duplication to be a prime force in the evolution of Rosaceae species. In addition, nine EjbZIPs were significantly different, including seven up‐regulated and two down‐regulated in E. japonica under salt stress. Especially, EjbZIP13 was involved in the expression of SA‐responsive proteins by binding to the NPR1 gene. EjbZIP27, EjbZIP30, and EjbZIP38 were highly expressed in E. japonica under salt stress, thus improving the salt tolerance capacity of the plants. These results can provide a theoretical basis for exploring the characteristics and functions of the bZIP TF family in more species and breeding salt‐tolerant E. japonica varieties. It also provides a reference for resolving the response mechanism of bZIP TF in 12 Rosaceae species under salt stress.

Habitat fragmentation is an important factor affecting biodiversity conservation, and few studies have discussed the relationship between the overall pattern of wetlands and biological ecological functions. Based on this, this study proposed the construction of wetland biodiversity conservation Ecological Networks (ENs) from the perspective of connectivity, and proposed a comprehensive framework for the construction of wetland ENs. Firstly, the key species were identified, and the habitat patches suitable for egret migration were analyzed by Morphological Spatial Pattern Analysis (MSPA) and landscape connectivity index, and the ecological sources were determined based on the policy influence. The Minimum Cumulative Resistance (MCR) model was used to extract the wetland ENs, and the network evaluation index, gravity model and Hydrological analysis model were used to analyze the “network − corridor − node” respectively. The results showed that: (1) The wetland patches in Haikou City were relatively trivial, and the connectivity between and within the patches was insufficient. There were 13 potential sources suitable for egret habitat and 17 ecological sources for comprehensive extraction; (2) The wetland ENs tends to be east of Nandu River, the network tightness is 0.038, and the network connectivity is low; (3) There are 45 important corridors and 8 important ecological sources, mainly concentrated in the east of Nandu River; (4) Identify 115, 50 and 66 ecological pinpoints, obstacle points and break points of wetland network, and propose protection, optimization and restoration strategies respectively. Comprehensive identification of ecological sources and the progressive wetland ENs analysis model of “network − corridor − node” will promote the further systematization of wetland biological protection research.

Abstract Background We describe a case in which bilateral optic nerve infiltration and leukemic retinopathy were the initial signs of disease relapse in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL) with central nervous system (CNS) involvement. Case presentation A 65-year-old Asian female with Ph+-ALL in complete remission presented at our institution with symptoms of visual disturbance, central scotoma and pain with eye movement in both eyes for a 1-month duration. Ophthalmic examination revealed remarkable optic disc swelling with multiple flame-shaped peripapillary hemorrhages, retinal venous dilation and retinal hemorrhages in both eyes. She was subsequently referred to the treating oncologist and diagnosed with Ph+-ALL relapse with multiple relapsed diseases involving the bone marrow and CNS. After intrathecal (IT) therapy, her visual acuity dramatically improved, and her leukemic infiltrates decreased. Conclusions To the best of our knowledge, this is the first case report of ALL relapse with CNS involvement presenting as bilateral optic nerve infiltration and leukemic retinopathy in an adult. Hence, we highlight the priority and sensitivity of ophthalmic examinations, as they are noninvasive methods for detecting leukemia relapse.

Abstract Background Hepatic stellate cells (HSCs) play a crucial role in the development of fibrosis in non-alcoholic fatty liver disease (NAFLD). Small extracellular vesicles (sEV) act as mediators for intercellular information transfer, delivering various fibrotic factors that impact the function of HSCs in liver fibrosis. In this study, we investigated the role of lipotoxic hepatocyte derived sEV (LTH-sEV) in HSCs activation and its intrinsic mechanisms. Methods High-fat diet (HFD) mice model was constructed to confirm the expression of LIMA1. The relationship between LIMA1-enriched LTH-sEV and LX2 activation was evaluated by measurement of fibrotic markers and related genes. Levels of mitophagy were detected using mt-keima lentivirus. The interaction between LIMA1 and PINK1 was discovered through database prediction and molecular docking. Finally, sEV was injected to investigate whether LIMA1 can accelerate HFD induced liver fibrosis in mice. Results LIMA1 expression was upregulated in lipotoxic hepatocytes and was found to be positively associated with the expression of the HSCs activation marker α-SMA. Lipotoxicity induced by OPA led to an increase in both the level of LIMA1 protein in LTH-sEV and the release of LTH-sEV. When HSCs were treated with LTH-sEV, LIMA1 was observed to hinder LX2 mitophagy while facilitating LX2 activation. Further investigation revealed that LIMA1 derived from LTH-sEV may inhibit PINK1-Parkin-mediated mitophagy, consequently promoting HSCs activation. Knocking down LIMA1 significantly attenuates the inhibitory effects of LTH-sEV on mitophagy and the promotion of HSCs activation. Conclusions Lipotoxic hepatocyte-derived LIMA1-enriched sEVs play a crucial role in promoting HSCs activation in NAFLD-related liver fibrosis by negatively regulating PINK1 mediated mitophagy. These findings provide new insights into the pathological mechanisms involved in the development of fibrosis in NAFLD. Graphical Abstract

Abstract Background Plant-specific TIFY proteins are widely found in terrestrial plants and play important roles in plant adversity responses. Although the genome of loquat at the chromosome level has been published, studies on the TIFY family in loquat are lacking. Therefore, the EjTIFY gene family was bioinformatically analyzed by constructing a phylogenetic tree, chromosomal localization, gene structure, and adversity expression profiling in this study. Results Twenty-six EjTIFY genes were identified and categorized into four subfamilies (ZML, JAZ, PPD, and TIFY) based on their structural domains. Twenty-four EjTIFY genes were irregularly distributed on 11 of the 17 chromosomes, and the remaining two genes were distributed in fragments. We identified 15 covariate TIFY gene pairs in the loquat genome, 13 of which were involved in large-scale interchromosomal segmental duplication events, and two of which were involved in tandem duplication events. Many abiotic stress cis-elements were widely present in the promoter region. Analysis of the Ka/Ks ratio showed that the paralogous homologs of the EjTIFY family were mainly subjected to purifying selection. Analysis of the RNA-seq data revealed that a total of five differentially expressed genes (DEGs) were expressed in the shoots under gibberellin treatment, whereas only one gene was significantly differentially expressed in the leaves; under both low-temperature and high-temperature stresses, there were significantly differentially expressed genes, and the EjJAZ15 gene was significantly upregulated under both low- and high-temperature stress. RNA-seq and qRT-PCR expression analysis under salt stress conditions revealed that EjJAZ2, EjJAZ4, and EjJAZ9 responded to salt stress in loquat plants, which promoted resistance to salt stress through the JA pathway. The response model of the TIFY genes in the jasmonic acid pathway under salt stress in loquat was systematically summarized. Conclusions These results provide a theoretical basis for exploring the characteristics and functions of additional EjTIFY genes in the future. This study also provides a theoretical basis for further research on breeding for salt stress resistance in loquat. RT-qPCR analysis revealed that the expression of one of the three EjTIFY genes increased and the expression of two decreased under salt stress conditions, suggesting that EjTIFY exhibited different expression patterns under salt stress conditions.

To compare the volatile flavor characteristics of red jujube from different origins, volatile aroma components of jujube fruit from five origins (Xinzheng, Lingbao, Yulin, Hotan and Dezhou) were analyzed by headspace solid-phase microextraction combined with gas chromatography mass spectrometry. The results showed that a total of 51 compounds were identified, among which the most volatile compounds were contained in Xinjiang Hotan jujube. Combined with multivariate statistical analysis, the differences in the overall volatile flavor substances of red jujube from different origins could be well distinguished. Under the conditions of satisfying the variable importance in projection>1 and P

This research was to assess the dietary copper (Cu) requirement of broiler chickens fed a practical corn-soybean meal diet during 22–42 d of age. A total of 288 numbered Arbor Acres male broilers at 22 d of age were randomly allotted 6 treatments with 8 replicate cages (6 broilers per cage) per treatment. Broilers were fed a Cu-unsupplemented corn-soybean meal basal diet (control, containing 7.36 mg Cu/kg) or the basal diet added with 3, 6, 9, 12, or 15 mg Cu/kg from CuSO4·5H2O for 21 d. Quadratic, asymptotic and broken-line models were fitted and the best fitted models were selected to determine dietary Cu requirements. The results revealed that the contents of Cu in serum and liver, mRNA expression levels of Cu- and zinc-containing superoxide dismutase (CuZnSOD) in liver and monoamine oxidase b (MAO B) in heart, as well as protein expression level of CuZnSOD in liver were affected (P

Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly contagious disease that threatens the global swine industry. Recent studies have focused on the damage that PRRSV causes to the reproductive system of male pigs, although pathological research is lacking. Therefore, we examined the pathogenic mechanisms in male piglets infected with PRRSV. Gross and histopathological changes indicated that PRRSV affected the entire reproductive system, as confirmed via immunohistochemical analysis. PRRSV infected Sertoli cells and spermatogonia. To test the new hypothesis that PRRSV infection in piglets impairs blood – testis barrier (BTB) development, we investigated the pathology of PRRSV damage in the BTB. PRRSV infection significantly decreased the quantity and proliferative capacity of Sertoli cells constituting the BTB. Zonula occludens-1 and β-catenin were downregulated in cell – cell junctions. Transcriptome analysis revealed that several crucial genes and signalling pathways involved in the growth and development of Leydig cells, Sertoli cells, and tight junctions in the testes were downregulated. Apoptosis, necroptosis, inflammatory, and oxidative stress-related pathways were activated, whereas hormone secretion-related pathways were inhibited. Many Sertoli cells and spermatogonia underwent apoptosis during early differentiation. Infected piglets exhibited disrupted androgen secretion, leading to significantly reduced testosterone and anti-Müllerian hormone levels. A cytokine storm occurred, notably upregulating cytokines such as tumour necrosis factor-α and interleukin-6. Markers of oxidative-stress damage (i.e. H2O2, malondialdehyde, and glutathione) were upregulated, whereas antioxidant-enzyme activities (i.e. superoxide dismutase, total antioxidant capacity, and catalase) were downregulated. Our results demonstrated that PRRSV infected multiple organs in the male reproductive system, which impaired growth in the BTB.

Polyphenols are phytochemicals commonly found in plant-based diets which have demonstrated immunomodulatory and anti-inflammatory properties. However, the interplay between polyphenols and pathogens at mucosal barrier surfaces has not yet been elucidated in detail. Here, we show that proanthocyanidin (PAC) polyphenols interact with gut parasites to influence immune function and gut microbial-derived metabolites in mice. PAC intake inhibited mastocytosis during infection with the small intestinal roundworm Heligmosomoides polygyrus, and altered the host tissue transcriptome at the site of infection with the large intestinal whipworm Trichuris muris, with a notable enhancement of type-1 inflammatory and interferon-driven gene pathways. In the absence of infection, PAC intake promoted the expansion of Turicibacter within the gut microbiota, increased fecal short chain fatty acids, and enriched phenolic metabolites such as phenyl-γ-valerolactones in the cecum. However, these putatively beneficial effects were reduced in PAC-fed mice infected with T. muris, suggesting concomitant parasite infection can attenuate gut microbial-mediated PAC catabolism. Collectively, our results suggest an inter-relationship between a phytonutrient and infection, whereby PAC may augment parasite-induced inflammation (most prominently with the cecum dwelling T. muris), and infection may abrogate the beneficial effects of health-promoting phytochemicals.

Pseudorabies virus is a major pathogen in the pig industry, causing substantial economic losses. The emergence of pseudorabies virus variant strains in China has led to extensive spread, raising concerns about their potential impact. However, the differences in pathogenicity between the classical strains and the variant strains of genotype II are not well understood. In this study, we isolated three pseudorabies virus strains to evaluate their replication characteristics and to examine the differences in virulence genes among various subgenotypes strains. Additionally, a piglet infection model was utilized to investigate the clinical features of infection, tissue tropism, and the inflammatory responses induced by these strains. Our results showed that the genotype II variant strains (MS, XJ, LS, and CZ) had significantly larger plaque sizes and higher replication capacities than the genotype II classical strain Fa. The animal experiments revealed significant differences in pathogenicity among the pseudorabies virus subgenotype strains, with the variant strains showing higher mortality rates, more severe clinical symptoms, increased nasal virus shedding, and a more robust inflammatory response compared to the genotype II classical strain. There were also notable differences in tissue tropism among the strains. In terms of tissue viral loads, the genotype II variant strains did not exhibit a significant advantage over the genotype I classical strain. Furthermore, our findings indicate that antibodies against the genotype II classical strains have a reduced neutralizing capacity against the genotype II variant strains. On the other hand, antibodies against the genotype II variant strains displayed similar neutralizing abilities against both classical and variant strains. Overall, these findings offer important insights into the distinctions among pseudorabies virus subgenotypes and their implications for the clinical control of pseudorabies virus infections in pig farming.

Porcine circovirus 4 (PCV4) was first identified in 2019, categorized within the genus Circovirus in the family Circoviridae. To date, the virus has not been isolated from clinical samples. Meanwhile, many aspects of the biology and pathogenic mechanisms of PCV4 infection remain unknown. In this study, PCV4 was successfully rescued from an infectious clone. We utilized a PCV4 virus stock derived from this infectious clone to intranasally inoculate 4-week-old specific-pathogen-free piglets to evaluate PCV4 pathogenesis. The rescued PCV4 was capable of replicating in both PK-15 cells and piglets, with the virus detectable in nearly all collected samples from the challenge groups. Pathological lesions and PCV4-specific antigens were observed in various tissues and organs, including the lungs, kidneys, lymph nodes, spleen, and liver, in the inoculated piglets. Additionally, the levels of pro-inflammatory cytokines in the serum of the PCV4-inoculated group were significantly elevated compared to the control group, indicating that the induced inflammatory response may contribute to tissue damage associated with PCV4 infection. These findings offer new insights into the pathogenesis and inflammatory responses associated with PCV4-related diseases.

Primary familial brain calcification (PFBC), also known as Fahr’s disease, is a central nervous system calcium deposition disorder with symmetrical basal ganglia calcification. Most PFBC cases are caused by SLC20A2 gene variant. We report a Chinese female patient with PFBC and dopamine-responsive parkinsonism who had motor fluctuations and dyskinesia and recovered effectively after symptomatic medication adjustment. A novel heterozygous missense variant was found by whole-exome sequencing and proven harmful by family validation and genetic analysis. This example expands the phenotype of SLC20A2-associated PFBC patients and shows the clinical efficacy of dopaminergic replacement treatment.

BackgroundAngiotensin II receptor blockers (ARBs) are utilized for the management of hypertension and diabetes. Previous meta-analyses suggested that azilsartan medoxomil (AZL-M) improved blood pressure (BP) reduction, but there were no safety findings or suggestions for patients with hypertension or diabetes.MethodsWe performed an efficacy and safety meta-analysis of randomized controlled trials (RCTs) evaluating AZL-M therapy for reducing BP in patients with hypertension. Patients with hypertension complicated by diabetes were analyzed. The relevant literature was searched in English and Chinese databases for RCTs involving AZL-M in hypertension. Efficacy variables included the change from baseline in the 24-h mean systolic/diastolic BP measured by ambulatory BP monitoring, the change from baseline in clinic systolic/diastolic BP, and responder rates. Safety variables included total adverse events (AEs), serious AEs, AEs leading to discontinuation, and AEs related to the study drug. The raw data from the included studies were utilized to calculate the odds ratio (OR) for dichotomous data and the mean difference (MD) for continuous data, accompanied by 95% confidence intervals (CIs). Statistical analysis was performed using R software.ResultsA total of 11 RCTs met the inclusion criteria, representing 7,608 patients, 5 of whom had diabetes. Pooled analysis suggested a reduction in BP among patients randomized to 40 mg of AZL-M vs. control therapy [24-h ambulatory blood pressure monitoring (ABPM) mean systolic blood pressure (SBP) (MD: −2.85 mmHg), clinic SBP (MD: −3.48 mmHg), and clinic diastolic blood pressure (DBP) (MD: −1.96 mmHg)] and for 80 mg of AZL-M vs. control therapy [24-h ABPM mean SBP (MD: −3.59 mmHg), 24-h ABPM mean DBP (MD: −2.62 mmHg), clinic SBP (MD: −4.42 mmHg), clinic DBP (MD: −3.09 mmHg), and responder rate (OR: 1.46)]. There was no difference in the reduction of risks, except for dizziness (OR: 1.56) in the 80-mg AZL-M group or urinary tract infection (OR: 1.82) in the 40-mg AZL-M group. Analysis of patients with diabetes revealed that AZL-M can provide superior management, while safety and tolerability were similar to those of control therapy.ConclusionsAZL-M appears to reduce BP to a greater extent than dose-control therapy and does not increase the risk of adverse events in patients with hypertension and diabetes compared with placebo.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=464284, identifier PROSPERO CRD42023464284.

In recent years, the epidemiological profile of Getah virus (GETV) has become increasingly serious, posing a huge threat to animal and public health in China. GETV can cause multi-species infection, including horses, pigs, rats, cattle, kangaroos, reptiles and birds. However, there were few reports on the efficiency of the virus entering the host via routes of different systems. In the present study, a GETV strain (SC201807) was obtained from a piglet's blood in 2018 in Sichuan, China. First, we established a quantitative real-time polymerase chain reaction (qRT-PCR) SYBR assay specific to GETV. Then, we evaluated the infection efficiency of different routes using mouse animal model. 108 male mice were randomly divided into four groups as follows: intramuscular, intraoral and intranasal infection routes, and negative control. All mice in the experimental group were inoculated with 4 × 102.85 TCID50 GETV virus. Tissue tropism experiments show that GETV has a wide range of tissue distribution, and intramuscular infection is the first to infect all tissues of the body, and suggest that oral infection may be a new GETV transmission route. Histopathological examination results showed that intramuscular injection of GETV mainly caused different degrees of pathological damage to the tissues, and could rapidly induce a large amount of inflammatory regulatory factors such as IL-6 and TNF-α. Our data may help us to evaluate the risk of transmission of Porcine Getah virus and provide an experimental basis for the prevention and control of Porcine Getah virus.

In the development of chronic liver disease, the hepatic stellate cell (HSC) plays a pivotal role in increasing intrahepatic vascular resistance (IHVR) and inducing portal hypertension (PH) in cirrhosis. Our research demonstrated that HSC contraction, prompted by angiotensin II (Ang II), significantly contributed to the elevation of type I collagen (COL1A1) expression. This increase was intimately associated with enhanced cell tension and YAP nuclear translocation, mediated through α-smooth muscle actin (α-SMA) expression, microfilaments (MF) polymerization, and stress fibers (SF) assembly. Further investigation revealed that the Rho/ROCK signaling pathway regulated MF polymerization and SF assembly by facilitating the phosphorylation of cofilin and MLC, while Ca2+ chiefly governed SF assembly via MLC. Inhibiting α-SMA-MF-SF assembly changed Ang II-induced cell contraction, YAP nuclear translocation, and COL1A1 expression, findings corroborated in cirrhotic mice models. Overall, our study offers insights into mitigating IHVR and PH through cell mechanics, heralding potential breakthroughs.

Abstract Patients with Type 2 Diabetes Mellitus are increasingly susceptible to atherosclerotic plaque vulnerability, leading to severe cardiovascular events. In this study, we demonstrate that elevated serum levels of palmitic acid, a type of saturated fatty acid, are significantly linked to this enhanced vulnerability in patients with Type 2 Diabetes Mellitus. Through a combination of human cohort studies and animal models, our research identifies a key mechanistic pathway: palmitic acid induces macrophage Delta-like ligand 4 signaling, which in turn triggers senescence in vascular smooth muscle cells. This process is critical for plaque instability due to reduced collagen synthesis and deposition. Importantly, our findings reveal that macrophage-specific knockout of Delta-like ligand 4 in atherosclerotic mice leads to reduced plaque burden and improved stability, highlighting the potential of targeting this pathway. These insights offer a promising direction for developing therapeutic strategies to mitigate cardiovascular risks in patients with Type 2 Diabetes Mellitus.

Abstract Background Thyroid eye disease (TED) is highly correlated with dysregulated immunoendocrine status. The insular cortex was found to regulate peripheral inflammation and immunomodulation in mice. This study aimed to explore whether the insular cortex in patients with TED played a modulatory role including the aberrant brain functional alteration and its association with immunoendocrine status. Methods This study included 34 active patients (AP), 30 inactive patients (IP) with TED, and 45 healthy controls (HC) matched for age, sex, and educational level. Comprehensive clinical details (especially immunoendocrine markers) and resting-state functional magnetic resonance imaging data were collected from each participant. The amplitude of low-frequency fluctuation (ALFF) was used to probe the aberrant alterations of local neural activity. The seed-based functional connectivity (FC) analysis was used to explore the relationship between the insular cortex and each voxel throughout the whole brain. The correlation analysis was conducted to assess the association between insular neurobiomarkers and immunoendocrine parameters. Results When compared with the IP and HC groups, the AP group displayed significantly higher ALFF values in the right insular cortex (INS.R) and lower FC values between the INS.R and the bilateral cerebellum. None of the neurobiomarkers differed between the IP and HC groups. Besides, correlations between insular neurobiomarkers and immunoendocrine markers (free thyroxine, the proportion of T cells, and natural killer cells) were identified in both AP and IP groups. Conclusions This study was novel in reporting that the dysregulation of the insular cortex activity in TED was associated with abnormal peripheral immunoendocrine status. The insular cortex might play a key role in central–peripheral system interaction in TED. Further research is crucial to enhance our understanding of the central–peripheral system interaction mechanisms involved in autoimmune diseases.

Abstract Background and aims Flavonoids are a class of secondary plant metabolites that have been shown to have multiple health benefits, including antioxidant and anti-inflammatory. This study was to explore the association between dietary flavonoid consumption and the prevalence of chronic respiratory diseases (CRDs) in adults. Methods and results The six main types of flavonoids, including isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols, were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007–2010 and 2017–2018 by the two 24-h recall interviews. The prevalence of CRDs, including asthma, emphysema, and chronic bronchitis, was determined through a self-administered questionnaire. The analysis included 15,753 participants aged 18 years or older who had completed a diet history interview. After adjustment for potential confounders, the inverse link was found with total flavonoids, anthocyanidins, flavanones, and flavones, with an OR (95%CI) of 0.86 (0.75–0.98), 0.84 (0.72–0.97), 0.80(0.69–0.92), and 0.85(0.73–0.98) for the highest group compared to the lowest group. WQS regression revealed that the mixture of flavonoids was negatively linked with the prevalence of CRDs (OR = 0.88 [0.82–0.95], P

The advent of plant-based yogurt provides a beneficial option for individuals having cow milk protein allergies, high cholesterol, as well as those who prioritize animal welfare and environmental sustainability. Despite this, plant-based yogurt has experienced a decline in consumer preference owing to factors such as whey separation, unpleasant odor, and insufficient acidity. Consequently, enhancing the quality of plant-based yogurt carries immense relevance for extending the commercial utilization of plant-derived food products. In this review, a summary of nutritional, flavor, and textural quality issues associated with plant-based yogurts derived from various sources was presented. Subsequently, a detailed explanation of different regulatory techniques for plant-based yogurt quality was provided, including the action modes and impacts of improving the formula, processing condition, and fermentation method. The mechanisms involved in stabilizing the plant-based yogurt system, boosting the solubility of plant-based proteins, facilitating the cross-linking of gel network and other related aspects were discussed. It is important to note that the effects of different regulatory techniques on the quality of plant-based yogurt vary with each method presenting unique strengths and weaknesses. Occasionally, a combination of methods might be necessary to optimize the enhancement of plant-based yogurt quality. Lastly, the potential measures for controlling the quality of plant-based yogurt were proposed. Our review aimed at offering valuable guidance for the production of high-quality plant-based yogurts.

Mactra veneriformis is a common economic benthic shellfish with high nutritional value and is widely distributed in the Shandong and Liaoning provinces. Geligang is located in the northern part of Liaodong Bay. It is formed by the water impact of Shuangtaizi and Liaohe River. It has an area of approximately 10 000 hm2 with a fertile substrate. It is an important habitat of beach shellfish, such as M. veneriformis. Studies on the influencing factors of wild population quality traits and their correlation with morphological traits are helpful for developing genetic breeding of marine shellfish. To analyze the effects of morphological traits on quality traits of M. veneriformis at different ages in Geligang, the shell length (SL), shell width (SW), shell height (SH), body weight (BW), and soft tissue wet weight (RW) of 1–3 years old M. veneriformis were analyzed using correlation analysis, path analysis, and multiple regression analysis. The M. veneriformis used in the experiment was obtained from the Geliang in Liaodong Bay in September 2022. A total of 80 1-year-old, 104 2-year-old, and 168 3-year-old M. veneriformis were obtained. The results showed that the morphological traits of M. veneriformis at different growth stages had different contributions to quality traits, and there were significant differences (P < 0.01). SW had the greatest direct effect on the BW of 1–3 year-old M. veneriformis, but had different effects on the RW; SW had the greatest direct effect on 1-year-old M. veneriformis; and SL had the greatest effect on 2- and 3-year-old M. veneriformis. The direct path coefficient of SH to the BW and RW of 2-year-old M. veneriformis did not reach significant level (P > 0.05) and was eliminated. The optimal regression equation of quantitative traits to qualitative traits of 1–3 year-old M. veneriformis was established. The results showed that when BW was the target trait, SW was the main selection trait and SL was the auxiliary selection trait for 1–3 year-old M. veneriformis. When RW was the target trait, SW should be the main selection trait for 1-year-old M. veneriformis, supplemented by SL. The SL should be the main selection trait for both 2- and 3-year-old M. veneriformis, but the SW was the auxiliary selection trait for 2-year-old M. veneriformis, while the SH was for 3-year-old M. veneriformis. In this study, correlation analysis, path analysis, and multiple regression analysis were performed on the morphological traits and quality traits of 1–3 years old M. veneriformis to determine the key morphological traits affecting the quality traits of M. veneriformis at different ages. In this study, the R2 values of the morphological traits of 1- and 2-year-old M. veneriformis (0.898 and 0.859, respectively) were greater than 0.850, indicating that the main factors affecting the body weight of living M. veneriformis were found. However, the R2 value of the morphological traits of 3-year-old M. veneriformis (0.815) was below 0.850, indicating that there may be other influencing traits in addition to the traits analyzed in this study. The reason may be that with the growth of M. veneriformis, the thickness of the shell and the effect on the weight of the living body gradually increase. In this study, the R2 values of morphological traits of 1–3 years old M. veneriformis (0.738, 0.648, and 0.538, respectively) on the wet weight of soft tissue were all below 0.850, indicating that there were other key factors affecting the wet weight of soft tissue. The age of sexual maturity of the M. veneriformis is at 1 year. The development of the gonad in the soft part may be closely related to the size of the wet weight of the soft tissue. The sampling period is mainly in the proliferation to depletion period of the gonad development of M. veneriformis. The gonad development is simultaneously affected by the environment. These results can provide reference for breeding M. veneriformis and the selection of parent shellfish.

This document tackles the issue of distributed adaptive tracking control for generic linear multi-agent systems. Specifically, the focus is on linear systems with non-zero control inputs from the leader, which are not directly accessible to the follower. Unlike existing literature limited to fixed topologies, this study tackles the challenge of switching topologies. A distributed discontinuous adaptive tracking controller uses Riccati inequalities and based on the state errors between neighboring agents. This controller adaptively adjusts the coupling weights between adjacent agents and ensures that switching communication topologies does not affect follower agent communication and remains undirected, allowing the leader to reach all followers via a directed path in the joint graph. This paper also examines stable multi-agent systems using fixed and dynamic network configurations. A communication graph in which the leader is bound by their control inputs is shown to be able to demonstrate such behavior, provided that the graph is jointly connected. A description of the followers’ states will effectively approach and converge on the leader’s state. An additional simulation experiment confirms its effectiveness and robustness of suggested method.

Abstract Background GRAS is a family of plant-specific transcription factors (TFs) that play a vital role in plant growth and development and response to adversity stress. However, systematic studies of the GRAS TF family in kiwifruit have not been reported. Results In this study, we used a bioinformatics approach to identify eighty-six AcGRAS TFs located on twenty-six chromosomes and phylogenetic analysis classified them into ten subfamilies. It was found that the gene structure is relatively conserved for these genes and that fragmental duplication is the prime force for the evolution of AcGRAS genes. However, the promoter region of the AcGRAS genes mainly contains cis-acting elements related to hormones and environmental stresses, similar to the results of GO and KEGG enrichment analysis, suggesting that hormone signaling pathways of the AcGRAS family play a vital role in regulating plant growth and development and adversity stress. Protein interaction network analysis showed that the AcGRAS51 protein is a relational protein linking DELLA, SCR, and SHR subfamily proteins. The results demonstrated that 81 genes were expressed in kiwifruit AcGRAS under salt stress, including 17 differentially expressed genes, 13 upregulated, and four downregulated. This indicates that the upregulated AcGRAS55 , AcGRAS69, AcGRAS86 and other GRAS genes can reduce the salt damage caused by kiwifruit plants by positively regulating salt stress, thus improving the salt tolerance of the plants. Conclusions These results provide a theoretical basis for future exploration of the characteristics and functions of more AcGRAS genes. This study provides a basis for further research on kiwifruit breeding for resistance to salt stress. RT-qPCR analysis showed that the expression of 3 AcGRAS genes was elevated under salt stress, indicating that AcGRAS exhibited a specific expression pattern under salt stress conditions.

Abstract Background Wilson’s disease (WD) is an inherited disorder of copper metabolism. Agenesis of the corpus callosum is the complete or partial absence of the major united fiber bundles connecting the cerebral hemispheres. Intracranial lipoma is an adipose tissue tumor resulting from an abnormal embryonic development of the central nervous system. The simultaneous occurrence of these three disorders is rare and has not been reported. This report focuses on the pathogenesis and association between the three disorders and highlights the importance of recognizing and effectively managing their coexistence. Case presentation The purpose of this study was to present a patient with coexisting WD, intracranial lipoma, and corpus callosum dysplasia. We reviewed a female patient hospitalized in 2023 with clinical manifestations of elevated aminotransferases and decreased ceruloplasmin, as well as genetic testing for an initial diagnosis of Wilson’s disease. Subsequently, a cranial MRI showed corpus callosum dysplasia with short T1 signal changes in the cerebral falx, leading to a final diagnosis of Wilson’s disease combined with intracranial lipoma and corpus callosum dysplasia. The patient’s WD is currently stable after treatment with sodium dimercaptosulfonamide (DMPS) and penicillamine, and the patient’s abnormal copper metabolism may promote the growth of intracranial lipoma. Conclusion The pathogenesis of WD combined with intracranial lipoma and corpus callosum dysplasia is complex and clinically rare. The growth of intracranial lipomas may be associated with abnormal copper metabolism in WD. Abnormal copper metabolism affects lipid metabolism and triggers inflammatory responses. Therefore, early diagnosis and treatment are beneficial for improvement. Each new case of this rare co-morbidity is important as it allows for a better assessment and understanding of these cases’ more characteristic clinical manifestations, which can help estimate the course of the disease and possible therapeutic options.

Abstract Background Our previous studies demonstrated that divalent organic iron (Fe) proteinate sources with higher complexation or chelation strengths as expressed by the greater quotient of formation (Qf) values displayed higher Fe bioavailabilities for broilers. Sodium iron ethylenediaminetetraacetate (NaFeEDTA) is a trivalent organic Fe source with the strongest chelating ligand EDTA. However, the bioavailability of Fe when administered as NaFeEDTA in broilers and other agricultural animals remains untested. Herein, the chemical characteristics of 12 NaFeEDTA products were determined. Of these, one feed grade NaFeEDTA (Qf = 2.07 × 108), one food grade NaFeEDTA (Qf = 3.31 × 108), and one Fe proteinate with an extremely strong chelation strength (Fe-Prot ES, Qf value = 8,590) were selected. Their bioavailabilities relative to Fe sulfate (FeSO4·7H2O) for broilers fed with a conventional corn-soybean meal diet were evaluated during d 1 to 21 by investigating the effects of the above Fe sources and added Fe levels on the growth performance, hematological indices, Fe contents, activities and gene expressions of Fe-containing enzymes in various tissues of broilers. Results NaFeEDTA sources varied greatly in their chemical characteristics. Plasma Fe concentration (PI), transferrin saturation (TS), liver Fe content, succinate dehydrogenase (SDH) activities in liver, heart, and kidney, catalase (CAT) activity in liver, and SDH mRNA expressions in liver and kidney increased linearly (P

Abstract Background Radiomics analysis of orbital magnetic resonance imaging (MRI) shows preliminary potential for intravenous glucocorticoid (IVGC) response prediction of thyroid eye disease (TED). The current region of interest segmentation contains only a single organ as extraocular muscles (EOMs). It would be of great value to consider all orbital soft tissues and construct a better prediction model. Methods In this retrospective study, we enrolled 127 patients with TED that received 4·5 g IVGC therapy and had complete follow-up examinations. Pre-treatment orbital T2-weighted imaging (T2WI) was acquired for all subjects. Using multi-organ segmentation (MOS) strategy, we contoured the EOMs, lacrimal gland (LG), orbital fat (OF), and optic nerve (ON), respectively. By fused-organ segmentation (FOS), we contoured the aforementioned structures as a cohesive unit. Whole-orbit radiomics (WOR) models consisting of a multi-regional radiomics (MRR) model and a fused-regional radiomics (FRR) model were further constructed using six machine learning (ML) algorithms. Results The support vector machine (SVM) classifier had the best performance on the MRR model (AUC = 0·961). The MRR model outperformed the single-regional radiomics (SRR) models (highest AUC = 0·766, XGBoost on EOMs, or LR on OF) and conventional semiquantitative imaging model (highest AUC = 0·760, NaiveBayes). The application of different ML algorithms for the comparison between the MRR model and the FRR model (highest AUC = 0·916, LR) led to different conclusions. Conclusions The WOR models achieved a satisfactory result in IVGC response prediction of TED. It would be beneficial to include more orbital structures and implement ML algorithms while constructing radiomics models. The selection of separate or overall segmentation of orbital soft tissues has not yet attained its final optimal result.

ObjectivesThe springback is the main factor affecting the forming quality of hull plates in the cold forming process. To improve the forming quality, it is necessary to investigate springback prediction, obtain the appropriate springback control method and further guide the die design.MethodsA fully convolutional network (FCN) is used to perform pixel-level calculations and regression calculation on the springback image so as to achieve springback prediction for each forming position on the sheet. In this study, a finite element (FE) model is established using ABAQUS 2019, and the numerical results are validated by the experimental results. The verified model is then applied to obtain the training sample set. The workpiece geometric information is used as the input of the neural network to retain all the information of the image, and the TensorFlow Core V2.2.0 platform is used to build the FCN based on different convolutional neural network models. Finally, the pros and cons of different neural networks are compared, and the optimal network is applied to the die design.ResultsThe results show that the maximum error of the predicted springback is 8.49%, where the constructed FCN32 has the highest accuracy. The proposed model can also realize one-time mould design with a calculation time of only 0.5 seconds and a maximum error of only 1.00%, significantly improving calculation efficiency.ConclusionsThe FCN-based algorithm proposed herein provides a springback prediction method for strips with high accuracy and efficiency, as well as offering a new approach to quick mould design.

Abstract Brown seaweeds have a rich bioactive content known to modulate biological processes, including the mucosal immune response and microbiota function, and may therefore have the potential to control enteric pathogens. Here, we tested if dietary seaweed (Saccharina latissima) supplementation could modulate pig gut health with a specific focus on parasitic helminth burdens, gut microbiota composition, and host immune response during a five week feeding period in pigs co-infected with the helminths Ascaris suum and Oesophagostomum dentatum. We found that inclusion of fermented S. latissima (Fer-SL) at 8% of the diet increased gut microbiota α-diversity with higher relative abundances of Firmicutes, Tenericutes, Verrucomicrobia, Spirochaetes and Elusimicrobia, and lower abundance of Prevotella copri. In the absence of helminth infection, transcription of immune-related genes in the intestine was only moderately influenced by dietary seaweed. However, Fer-SL modulated the transcriptional response to infection in a site-specific manner in the gut, with an attenuation of infection-induced gene expression in the jejunum and an amplification of gene expression in the colon. Effects on systemic immune parameters (e.g. blood lymphocyte populations) were limited, indicating the effects of Fer-SL were mainly localized to the intestinal tissues. Despite previously documented in vitro anti-parasitic activity against pig helminths, Fer-SL inclusion did not significantly affect parasite egg excretion or worm establishment. Collectively, our results show that although Fer-SL inclusion did not reduce parasite burdens, it may modify the gut environment during enteric parasite infection, which encourages continued investigations into the use of seaweeds or related products as novel tools to improve gut health.

Abstract Aim This study aimed to undertake a bibliometric analysis to provide comprehensive information in demonstrating the current status and outline the overall trends in the area of readiness for hospital discharge (RHD). Design A bibliometric and visual analysis of RHD literature was undertaken. Methods Articles were retrieved from the Web of Science network from 2002 to 2021. VOSviewer was used to identify the co‐authorship network of countries/institutions, co‐authorship and co‐citation analysis of authors, and co‐citation analysis of references and citation analysis of documents. CiteSpace was used to identify the keyword co‐occurrence network and perform cluster analysis, detecting the keywords with citation bursts and speculated frontiers in this research field. Results A total of 512 articles were included in the final analysis. Key findings are: (1) There has been a continuous but somewhat fluctuating rise in the number of publications. (2) 56.05% of publications come from the USA with Marquette University making the highest contribution. (3) Most publications (17, 3.32%) in RHD research were from the Journal of Clinical Nursing, and Anaesthesia and Analgesia had the highest number of citations (584 citations). (4) Weiss ME (25, 4.88%) was the most productive author whose articles have been the most highly cited (646 citations). (5) Cited references from Weiss ME (2007) also made the largest contribution to co‐citations, and the most cited reference was from Jack BW (2009) (1022 citations). (6) The 20 most frequent keywords and keywords with the strongest citation bursts were retrieved. There were seven research hotspots, and three emerging research frontiers were explored. Conclusions The bibliometric analysis of material published in the last 20 years indicates that there have been statistically significant gains in comprehensive information on RHD, including the knowledge mapping of the countries, institutions, authors, references and keywords. The hotspots and frontiers, which have been explored can give guidance to researchers as to new angles and directions to take. Implications for Nursing Management The effects of the implementation of ERAS on RHD‐related risk for adverse post‐discharge outcomes in surgical patients will be of increasing concern for healthcare professionals. It is important for patients and their relatives to be confident that on discharge they are sufficiently ready for hospital discharge to enable them to safely and smoothly make the transition to home. Improving the level of RHD in discharged patients can help nurse managers and researchers measure the effectiveness of discharge planning services.

Perilla (Perilla frutescens) seeds are emerging as a valuable resource for functional foods and medicines owing to their rich oil and protein content with diverse nutritional and health benefits. Perilla seed oil (PSO) possesses a high level of a-linolenic acid (ALA), a favorable ratio of unsaturated to saturated fatty acids, and other active ingredients such as tocopherols and phytosterols, which contribute to its antioxidant, anti-inflammatory, and cardiovascular protective effects. The balanced amino acid ratio and good functional properties of perilla seed protein make it suitable for a variety of food applications. The chemical composition, health benefits, and potential applications of PSO as well as the structural characterization, functional properties, modification methods, bioactivities, and application scenarios of perilla seed protein are comprehensively presented in this paper. Furthermore, the challenges as well as future prospects and research focus of PSO and perilla seed protein are discussed. The growing interest in plant-based diets and functional foods has made PSO and perilla seed protein promising ingredients for the development of novel foods and health products. The purpose of this paper is to highlight implications for future research and development utilizing these two untapped resources to improve human health and nutrition.