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Abstract Background Acinetobacter pittii, belongs to the genus Acinetobacter, has a special pathogenesis and is commonly known as nosocomial pathogen; community infections are rare. Objective To present a case study of community-acquired pneumonia and septic shock resulting from infection with Acinetobacter pittii and to investigate the diagnosis, clinical features and treatment of Acinetobacter pittii infection. Methods The clinical features and prognosis of patients with Acinetobacter pittii, infection were analyzed retrospectively. Results The sepsis caused by Acinetobacter pittii, was improved after treatment. Discussion and conclusion Pneumonia caused by fully sensitive hypervirulent Acinetobacter pittii is rare, usually with acute course, severe illness and high mortality. It is necessary to identify the infectious agent as soon as possible, and early treatment can improve the success rate of treatment.

The prevalence and spread of antibiotic resistance genes (ARGs) have been a significant concern for global public health in recent years. Small rural watersheds are the smallest units of factor mobility for agricultural production in China, and their ARG profiles are the best scale of the contamination status, but the mapping and the distribution and diffusion of ARGs in the water and soil of small rural watersheds are inadequate. In this study, based on microbial metagenomics, we invested prevalence maps of 209 ARGs corresponding to typical commonly used antibiotics (including multidrug, aminoglycoside, macrolide-lincosamide-streptogramin B (MLSB), and β-Lactamase) in water and soil in different agricultural types, as well as within water-soil interfaces in small rural watersheds in Southwest China. The results revealed that the most abundant ARGs in water and soil were consistent, but different in subtypes, and anthropogenic activities affect the transport of ARGs between water and soils. Livestock wastewater discharges influenced the diversity and abundance of ARGs in water, while in soil it is planting type and fertilizer management, and thus interfered with the co-occurrence patterns between bacteria and ARGs. Co-occurrence analysis revealed that Proteobacteria, Actinobacteria, and Bacteroidetes were the predominant ARG hosts in water and soil, but soil exhibited a more intricate ARG-bacterial association. Overall, this study provides integrated profiles of ARGs in water and soil influenced by anthropogenic activities at the small watershed scale in a typical rural area and provides a baseline for comparisons of ARGs.

In many countries, the urban–rural income inequality affects healthy and sustainable economic development and is a pressing issue that requires immediate attention. As a new industrial development model, rural industrial convergence can provide new ideas and impetus for alleviating the urban–rural income inequality. This study, drawing on provincial panel data from China spanning 2010 to 2022, used the entropy method and Theil index to measure the rural industrial convergence and the urban–rural income inequality, respectively, and empirically tested the effect and mechanism of rural industrial convergence on the urban–rural income inequality. The results showed the following: (1) Rural industrial convergence had a notable impact on alleviating the urban–rural income inequality. (2) Rural industrial convergence could help reduce the urban–rural income inequality by increasing the scale of land operation. (3) The government attention to green development could positively moderate the impact of rural industrial convergence on the urban–rural income inequality; the deeper the government attention to green development, the greater the role rural industrial convergence played in alleviating the urban–rural income inequality. (4) There was a threshold effect in the alleviating effect of rural industrial convergence on the urban–rural income inequality, which was gradually strengthened when the growth of the digital economy and the enhancement of the business environment were beyond the threshold point. (5) Rural industrial convergence also had significant spatial spillover effects on adjacent regions. Overall, the findings of this study enrich the research on the impact of rural industrial convergence on the urban–rural income inequality and provide insights for other similar countries.

Abstract Background The role of pyroptosis in kidney disease is limited and incomplete. Quercetin, a flavonoid compound present in a variety of fruits, vegetables, and plants, has shown antioxidant and anti-inflammatory properties. This study was designed to validate the importance of pyroptosis in an experimental model of folic acid nephropathy and to explore the effect of quercetin in protecting against pyroptosis. Methods Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were used to establish the correlation between pyroptosis and folic acid nephropathy. Immune cell infiltration, network pharmacology and single-cell RNA sequencing analysis were utilized to ascertain the specific target of quercetin in relation to pyroptosis. Finally, quercetin’s role was verified in vivo and in vitro. Results The GSEA analysis revealed a significant correlation between pyroptosis and folic acid nephropathy (NES = 1.764, P = 0.004). The hub genes identified through WGCNA were closely associated with inflammation. Molecular docking demonstrated a strong binding affinity between quercetin and caspase-1, a protein known to be involved in macrophage function, as confirmed by immune cell infiltration and single-cell analysis. Quercetin demonstrated a significant amelioration of kidney injury and reduction in macrophage infiltration in the animal model. Furthermore, quercetin exhibited a significant inhibition of caspase-1 expression, subsequently leading to the inhibition of pro-inflammatory cytokines expression, such as IL-1β, IL-18, TNF-α, and IL-6. The inhibitory effect of quercetin on macrophage pyroptosis was also confirmed in RAW264.7 cells. Conclusion This study contributes substantial evidence to support the significant role of pyroptosis in the development of folic acid nephropathy, and highlights the ability of quercetin to downregulate caspase-1 in macrophages as a protective mechanism against pyroptosis.

The expansion and intensification of human activities have resulted in excessive nitrogen (N) in rivers, causing worldwide concern. To effectively manage agricultural non-point source pollution and ensure a safe drinking water supply in watersheds, it is crucial to trace and quantify the primary sources and spatial distribution patterns of N. In response to the challenge of unclear sources and agricultural non-point source pollution, this study utilised the Bayesian isotope mixing model and Soil and Water Assessment Toolmodel to identify the dominant nitrate sources and transformation processes. These models were employed to quantify N retention by the mainstream and tributaries in the Bai River Basin, which directly impacts the safety of drinking water in Beijing. Total N (TN) concentrations in the Yunzhou Reservoir (4.22 ± 0.04 mg.L˗1) and Miyun Reservoir (2.88 ± 0.62 mg.L˗1) inlets in autumn and winter were V class (2 mg.L˗1) category as per GB 3838–2002 standards. This implies higher risks of eutrophication and algal blooms exceeding the standards at individual points and seasons in the Bai River. Fertilisers were the main nitrate source in the Bai River Basin, contributing 44.6% during the dry season and 62.9% during the wet season, suggesting that nitrate is more susceptible to leaching and runoff during rainy periods. Rainfall was not a major contributor, with only 3.2% and 2.9% originating from the Hebei and Beijing areas of the Bai River, respectively. Annually, the Bai River Basin exports loads of approximately 629.3 t.a˗1 of TN and 433.7 t.a˗1 of organic N (Org-N) from the Bai River Basin land to the river. The TN and Org-N loads at the final destination in the Miyun Reservoir were 521.3 t.a˗1 and 100.3 t.a˗1, respectively. Of the exported TN and Org-N, 17.16% and 76.87%, respectively, were retained in the river network. Consequently, N transformation occurred in the Bai River, with nitrification–denitrification being particularly dominant. Nitrification was more evident in the nitrate-enriched river.

The Olsen phosphorus (P) concentration of a soil is a key index that can be used to evaluate the P supply capacity of the soil and to estimate the optimal P fertilization rate. A study of the relationship between the soil Olsen P concentration and the P balance (P input minus P output) and their variations among different fertilization patterns will help to provide useful information for proper management of P fertilization. In this paper, the two investigated long-term experiments were established on black soils in the northeast region of China. Six fertilization treatments were selected: (1) unfertilized (CK); (2) nitrogen only (N); (3) nitrogen and potassium (NK); (4) nitrogen and phosphorus (NP); (5) nitrogen, phosphorus, and potassium (NPK); and (6) nitrogen, phosphorus, potassium and manure (NPKM). The results showed that the average Olsen P concentrations in the black soils at Gongzhuling and Harbin (16- and 31-year study periods, respectively), decreased by 0.49 and 0.56 mg kg-1 a-1, respectively, without P addition and increased by 3.17 and 1.78 mg kg-1 a-1, respectively, with P fertilization. The changes in soil Olsen P concentrations were significantly (P

Abstract Background Little evidence on the association between geriatric nutritional risk index (GNRI) with prognosis and postoperative complications was observed. This study examined the potential prognostic value of GNRI in elderly patients undergoing non-cardiac surgery. Methods This retrospective analysis was data retried from the Chinese elderly patients’ perioperative database (CEPPD), a multicenter registry, from June 1st, 2012 to August 15th, 2019. Patients were categorized into at-risk group (GNRI ≤ 98) and no-risk group (GNRI > 98). Kaplan–Meier analysis and multivariate Cox proportional hazard regression were used to explore the association between GNRI and overall survival (OS). Multivariate logistic regression and linear regression were used to explore the association of the GNRI with postoperative complications. A propensity score matching (PSM) analysis was also conducted at a 1:1 ratio using the greedy nearest-neighbor method. Results The final analysis included 28,762 elderly patients undergoing non-cardiac surgery. The PSM cohort included 7,063 patients in each group. The 1-year OS rate was 90.2% in the at-risk group vs. 96.3% in the no-risk group (P

Fatal familial insomnia (FFI) is a rare autosomal dominant genetic neurodegenerative disease. Generally, FFI patients will develop rapidly progressive dementia, sleep disturbance, autonomic dysfunction, and so on. Cerebrospinal fluid examination of FFI patients normally shows no obvious abnormalities. Here, we report a young male patient who was diagnosed with FFI during the COVID-19 epidemic. Clinical symptoms include psychobehavioral abnormality, cognitive decline, sleep disturbance, and autonomic dysfunction. No abnormalities were found in routine examinations after admission. However, the number of white blood cells in the cerebrospinal fluid increased. Though the patient was treated with anti-infection and immunotherapy, the symptoms were not relieved. A lumbar puncture was performed again, and it was found that the total Tau protein in the cerebrospinal fluid was elevated, and PET results showed that brain metabolism decreased. Finally, a genetic test was used to confirm the diagnosis of FFI. This case suggests that patients with FFI may also have elevated white blood cells in cerebrospinal fluid and timely detection of Tau protein in cerebrospinal fluid is helpful for early identification of FFI. And precise diagnosis relies on genetic testing.

Tartary buckwheat was used as raw material to extract tartary buckwheat protein, and the enzymatic hydrolysis conditions of tartary buckwheat protein lipid-lowering peptides were screened by single factor and response surface optimization experiments using the inhibition rate of pancreatic lipase as index. The amino acid composition and lipid lowering activity of lipid-lowering peptides were studied. The results showed that the lipid-lowering peptides obtained from tartary buckwheat protein with bromelain had higher inhibitory activity on pancreatic lipase. The optimal enzymatic hydrolysis conditions were hydrolysis time 2.1 h, hydrolysis temperature 62.0 ℃, substrate concentration 3.23%, pH7.0 and enzyme substrate ratio 0.4%. Under these conditions, the inhibitory rate of pancreatic lipase was 81.22%±0.16%. Amino acid analysis showed that essential amino acids, hydrophobic amino acids and acidic amino acids accounted for 27.82%, 32.11%, 35.86%, and the ratio of arginine to lysine was 2.28. The EC50/IC50 values of sodium taurine cholic acid binding rate, cholesterol esterase inhibition rate and pancreatic lipase inhibition rate were 9.136, 3.902 and 0.051 mg/mL, respectively. The results provided a new idea and theoretical basis for the high-value utilization of tartary buckwheat resources and the development of tartary buckwheat protein active peptides.

Abstract Background Organic phosphate flame retardants (OPFRs) and phthalate acid esters (PAEs) are common endocrine-disrupting chemicals that cause metabolic disorders. This study aimed to assess the association between joint exposure to OPFRs and PAEs during early pregnancy in women with gestational diabetes mellitus (GDM). Methods Seven OPFRs and five PAEs were detected in the urine of 65 GDM patients and 100 controls using gas chromatography-tandem triple quadrupole mass spectrometry (GC-MS). The association of OPFRs and PAEs with GDM was assessed using logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. Results Levels of dibutyl phthalate (DBP), di-2-ethylhexyl phthalate (DEHP), diethyl phthalate (DEP), dimethyl phthalate (DMP), tris (2-butoxyethyl) phosphate (TBEP), tributyl phosphate (TBP), tris (2-chloroethyl) phosphate (TCEP), tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tri-ortho-cresyl phosphate (TOCP), and triphenyl phosphate (TPHP) increased in the GDM group, and the OPFRs and PAEs, except for BBP and TMCP, were associated with GDM in the logistic regression analysis. In the WQS model, the mixture of OPFRs and PAEs was significantly positively associated with GDM (OR = 3.29, 95%CI = 1.27–8.51, P = 0.014), with TDCPP having the highest WQS index weight. BKMR analysis reinforced these results, showing that the overall association of joint exposure to the OPFRs and PAEs with GDM increased at exposure levels of the 55th to 75th percentiles. Independent exposure to TDCPP (OR = 1.42, 95%CI = 1.09–1.86, P = 0.011) and TBEP (OR = 1.29, 95%CI = 1.04–1.60, P = 0.023) were associated with an increased risk of GDM. Conclusions Environmental exposure to OPFRs and PAEs is significantly associated with GDM. These findings provide evidence for the adverse effects of exposure to OPFRs and PAEs on the health of pregnant women.

Abstract Aiming at the problems of inaccuracy in detecting the α phase contour of TB6 titanium alloy. By combining computer vision technology with human vision mechanisms, the spatial characteristics of the α phase can be simulated to obtain the contour accurately. Therefore, an algorithm for α phase contour detection of TB6 titanium alloy fused with multi-scale fretting features is proposed. Firstly, through the response of the classical receptive field model based on fretting and the suppression of new non-classical receptive field model based on fretting, the information maps of the α phase contour of the TB6 titanium alloy at different scales are obtained; then the information map of the smallest scale contour is used as a benchmark, the neighborhood is constructed to judge the deviation of other scale contour information, and the corresponding weight value is calculated; finally, Gaussian function is used to weight and fuse the deviation information, and the contour detection result of TB6 titanium alloy α phase is obtained. In the Visual Studio 2013 environment, 484 metallographic images with different temperatures, strain rates, and magnifications were tested. The results show that the performance evaluation F value of the proposed algorithm is 0.915, which can effectively improve the accuracy of α phase contour detection of TB6 titanium alloy.

Abstract The role of the compromised immune microenvironment, including immune checkpoints, in myelodysplastic syndromes (MDS) has been identified as critical This study aimed to investigate the expression patterns of immune checkpoints, particularly soluble PD-1/PD-L1 (sPD-1/sPD-L1) as well as PD-1 on effector T cell subsets, and assess their prognostic value and potential regulatory roles in MDS. 161 MDS patients were enrolled, including 129 patients were primarily diagnosed with de novo MDS, together with 59 MDS patients who underwent hypomethylating agents (HMAs) therapy. Plasma sPD-L1 level was elevated in newly diagnosed MDS patients, which was also found to be associated with MDS disease progression that further increase in higher IPSS-R score group. Patients with increased sPD-L1 expression at diagnosis exhibited notably poorer overall survival, and multivariate Cox analysis indicated that elevated sPD-L1 was an independent risk factor. Furthermore, the levels of multiple cytokines and membrane-bound PD-1 on T cells were found to correlate with sPD-1/sPD-L1 levels in plasma. Importantly, we also found sPD-L1 levels significantly increased in MDS patients who showed progression of disease following HMAs therapy. In conclusion, we found elevated plasma sPD-L1 levels in MDS patients are associated with disease progression and poorer overall survival. This study showed that sPD-L1 is a potential biomarker for prognosis and a target for immunotherapy in MDS.

Abstract Iron metabolism disorder has been identified as a contributor to the pathogenesis and progression of multiple cognitive dysfunction-related diseases, including postoperative delirium. However, the association between preoperative iron reserves and postoperative delirium risk remains elusive. This retrospective cohort study aimed to explore the impact of preoperative serum ferritin levels on the risk of postoperative delirium in elderly patients undergoing non-neurosurgical and non-cardiac procedures. Conducted at the Chinese PLA General Hospital between January 2014 and December 2021, the study finally included 12,841 patients aged 65 years and above. Preoperative serum ferritin levels were assessed within 30 days before surgery, and postoperative delirium occurrence within the first seven days after surgery was determined through medical chart review. The analyses revealed that both low and high levels of serum ferritin were associated with an increased risk of postoperative delirium. Patients in the lowest quintile of serum ferritin exhibited an 81% increased risk, while those in the highest quintile faced a 91% increased risk compared to those in the second quintile. Furthermore, mediation analyses indicated that the direct effect of preoperative serum ferritin on postoperative delirium contradicted its indirect effect mediated by hemoglobin levels. These findings suggest that maintaining serum ferritin within moderate range preoperatively could be beneficial for managing postoperative delirium risk among elderly patients.

ObjectiveCirculating regulatory T cells (Tregs) are closely related to immune tolerance and maintenance of immune homeostasis. Perhaps, there is a unique immune cell phenotype for difficult-to-treat rheumatoid arthritis (D2T RA). Low-dose interleukin-2 (IL-2) has been considered for the treatment of autoimmune diseases. This study focused on the uniqueness of D2T RA lymphocyte subsets and the feasibility of low-dose IL-2 therapy.MethodsParticipants included 1,042 RA patients who were divided into three groups according to the presence or absence of treatment and their response to treatment in the last 6 months—new group, treated group, and D2T group—and 339 healthy controls (HCs). A total of 381 patients—107, 151, and 123 in each of the three experimental groups—received low-dose IL-2 treatment [0.5 million international units (MIU) per day, subcutaneous injection from day 1 to day 5]. The absolute numbers of peripheral blood lymphocyte subsets were detected by flow cytometry (FCM) and serum cytokine levels were detected by flow cytometry bead array (CBA).ResultsThe absolute number of T, CD4+ T, and Treg cells in the D2T RA group was lower than that in the HC, new, and treated RA groups. Compared with the HC and new RA group, the ratio of Th17/Treg cells in the D2T RA group increased. The new, treated, and D2T RA groups had higher cytokine levels than the HC. The number of Treg cells in RA patients was negatively correlated with the disease activity index. Treg cells in the new, treated, and D2T RA groups could be increased by low-dose IL-2 therapy without any side effects.ConclusionsThe number of lymphocytes and subsets in D2T RA patients was reduced, especially Treg cells, resulting in a shift in the balance of effector T cells/Treg cells toward effector T cells, which is ameliorated by low-dose IL-2 without obvious side effects.

IntroductionDairy products are an important source of high-quality protein, calcium, vitamin A, and other nutrients, and they are a crucial part of a balanced diet for children. However, the daily intake of dairy products among school-age children in China is significantly inadequate. Considering school lunches as a vital pathway for children to obtain nutrients, this study aims to develop school lunch dishes incorporating mozzarella cheese and to assess the acceptance of these dishes among school-age children.MethodsThis study was carried out in a primary school which has a self-run canteen in Nanjing. We innovatively integrated cheese with traditional Chinese food, and conducted a 3-month pilot study to develop dishes that meet the nutritional needs and sensory experience of students. 121 students with an average age of 9.8 years were invited to assess each dishes’ appearance, aroma, taste and overall liking, by using a 5-point Likert Scale. Focus group discussions were conducted after the project to further discover students’ attitude toward cheese dishes and canteen cooks’ experience in improving cheese dishes.ResultsDuring the program, 16 cheese dishes were made, including 3 steamed dishes, 2 ready-to-eat foods (only heating required), and 11 stir-fried dishes. The overall liking’ results showed that ready-to-eat foods were the most popular among students, and steamed dishes ranked higher than stir-fried dishes (P < 0.001). Among the stir-fried dishes, students’ liking scores differed for cheese dishes made from different raw materials, pure meat food was more popular than vegetable food (P = 0.003), meat and vegetable food (P = 0.012). Additionally, focus group discussions found that students gave more positive ratings to and ready-to-eat foods and steamed dishes.ConclusionCheese can be well combined with traditional Chinese ingredients and be accepted, especially steamed or combined with meat. Introducing cheese in school lunches not only helps cultivate a habit of consuming cheese among children and adolescents from a young age, but also aids in closing the gap between their dairy consumption and dietary guidelines.

BackgroundSepsis, a life-threatening organ dysfunction caused by a dysregulated immune response to infection, remains a significant global health challenge. Phosphoglycerate kinase 1 (PGK1) has been implicated in regulating inflammation and immune cell infiltration in inflammatory conditions. However, the role of PGK1 in sepsis remains largely unexplored.MethodsFour microarray datasets and a high throughput sequencing dataset were acquired from GEO database to reveal the PGK1 expression in patients of sepsis. Quantitative real-time PCR and western blotting was then used to validate the PGK1 level. Additionally, microarray and single-cell RNA sequencing data integration, including gene set enrichment analysis (GSEA), KEGG and GO functional enrichment analysis, immune infiltration analysis, and single-cell sequencing analysis, were performed to elucidate the role of PGK1 in sepsis.ResultsOur results revealed a significant upregulation of PGK1 in sepsis patients, with the area under the ROC curve (AUC) exceeding 0.9 across multiple datasets, indicating PGK1’s strong potential as a diagnostic biomarker. Notably, PGK1 was enriched in key immune-related pathways, including the TNF signaling pathways, and leukocyte transendothelial migration, suggesting its involvement in immune regulation. Furthermore, PGK1 expression showed a positive correlation with the levels of inflammatory mediators CXCL1, CXCL16, and the chemokine receptor CCR1. In terms of immune cell infiltration, PGK1 was positively correlated with naive B cells, resting memory CD4 T cell, gamma delta T cells, M0 macrophages, eosinophils and negatively correlated with plasma cells, CD8 T cells, activated memory CD4 T cell, Tregs, activated dendritic cells.ConclusionsThis study concluded that PGK1 served as a novel diagnostic biomarker for sepsis, with potential implications for prognosis and immune regulation. The significant upregulation of PGK1 in sepsis patients and its association with immune-related pathways and cell types highlight its potential role in the pathogenesis of sepsis.

Summary: Tumor-associated macrophages (TAMs) are a critical component of the immunosuppressive tumor microenvironment, comprising monocyte-derived macrophages (MDM-TAMs) and tissue-resident macrophages (TRM-TAMs). Here, we discovered that TRM-TAMs mediate the pro-tumor effects of interleukin (IL)-17A and that IL-17A-driven tumor progression requires tumor cell production of osteopontin (OPN). Mechanistically, we identified CEBPβ as a transcription factor downstream of IL-17A in tumor cells and LYVE-1 as an OPN receptor on TRM-TAMs. IL-17A stimulates tumor cell production of OPN, and OPN/LYVE-1 signaling activates the JNK/c-Jun pathway, leading to the proliferation of immunosuppressive LYVE-1+ TRM-TAMs. Unlike its effect on LYVE-1+ TRM-TAMs, OPN interacts with α4β1 to promote the chemotaxis of LYVE-1− MDM-TAMs toward tumors. IL-17A neutralization, OPN inactivation in tumor cells, or LYVE-1 deletion in macrophages inhibited TAMs and enhanced anti-tumor immune responses and anti-PDL1 therapy. Thus, the IL-17A/CEBPβ/OPN/LYVE-1 axis offers a mechanism suppressing anti-tumor immune responses and, hence, an effective therapeutic target for cancer.

Abstract With the rapid development of modern science and technology, navigation technology provides great convenience for people's life, but the problem of inaccurate localization in complex environments has always been a challenge that navigation technology needs to be solved urgently. To address this challenge, this paper proposes an augmented reality navigation method that combines image segmentation and multi-sensor fusion tracking registration. The method optimizes the image processing process through the GA-OTSU-Canny algorithm and combines high-precision multi-sensor information in order to achieve accurate tracking of positioning and guidance in complex environments. Experimental results show that the GA-OTSU-Canny algorithm has a faster image edge segmentation rate, and the fastest start speed is only 1.8 s, and the fastest intersection selection time is 1.2 s. The navigation system combining the image segmentation and sensor tracking and registration techniques has a highly efficient performance in real-world navigation, and its building recognition rates are all above 99%. The augmented reality navigation system not only improves the navigation accuracy in high-rise and urban canyon environments, but also significantly outperforms traditional navigation solutions in terms of navigation startup time and target building recognition accuracy. In summary, this research not only provides a new framework for the theoretical integration of image processing and multi-sensor data, but also brings innovative technical solutions for the development and application of practical navigation systems.

Abstract Background PD-1/PD-L1 blockade has become a powerful method to treat malignant tumors. However, a large proportion of patients still do not benefit from this treatment, due to low tumor immunogenicity and low tumor penetration of the agents. Recently, neutrophil elastase has been shown to induce robust tumor immunogenicity, while the insufficient enzyme activity at the tumor site restricted its anti-tumor application. Here, we designed polyethyleneimine-modified neutrophil elastase (PEI-elastase) loaded with PD-L1small interfering RNA (PD-L1 siRNA) for improving enzymatic activity and delivering siRNA to tumor, which was expected to solve the above-mentioned problems. Results We first demonstrated that PEI-elastase possessed high enzymatic activity, which was also identified as an excellent gene-delivery material. Then, we synthesized anti-tumor lipopolymer (P-E/S Lip) by encapsulating PEI-elastase and PD-L1siRNA with pH-responsive anionic liposomes. The P-E/S Lip could be rapidly cleaved in tumor acidic environment, leading to exposure of the PEI-elastase/PD-L1 siRNA. Consequently, PEI-elastase induced powerful tumor immunogenicity upon direct tumor killing with minimal toxicity to normal cells. In parallel, PEI-elastase delivered PD-L1siRNA into the tumor and reduced PD-L1 expression. Orthotopic tumor administration of P-E/S Lip not only attenuated primary tumor growth, but also produced systemic anti-tumor immune response to inhibit growth of distant tumors and metastasis. Moreover, intravenous administration of P-E/S Lip into mice bearing subcutaneous tumors leaded to an effective inhibition of established B16-F10 tumor and 4T1 tumor, with histological analyses indicating an absence of detectable toxicity. Conclusions In our study, a protease-based nanoplatform was used to cooperatively provoke robust tumor immunogenicity and down-regulate PD-L1 expression, which exhibited great potential as a combination therapy for precisely treating solid tumors. Graphical Abstract

Plant seed oils are rich in unsaturated fatty acids and lipid-soluble active ingredients, which have become a hot spot of research in recent years. In this study, a novel low-temperature continuous phase transition extraction device was utilized to extract passion fruit seed oil and its lipid composition, quality properties and hypolipidemic activity were investigated. The extraction rate of passion fruit seed oil by low-temperature continuous phase transition extraction was 20.37 %, which was about twice as much as that of solvent extraction (10.80 %). The contents of unsaturated fatty acids, vitamin E and β-carotene in passion fruit seed oil extracted by low-temperature continuous phase transition were 84.00 %, 21.03 μg/g and 6.28 μg/g, respectively, which were significantly better than those of solvent extraction. The acid value, peroxide value and saponification value of the resulting passion fruit seed oil were 0.275 mg/g, 0.034 g/100g and 185.175 mg/g, respectively. Passion fruit seed oil exhibited good hypolipidemic activity, and the IC50 of its inhibitory effect on pancreatic lipase and cholesterol esterase were 97.19 μg/mL and 48.08 μg/mL, respectively. Further 3T3-L1 cell experiments concluded that passion fruit seed oil not only reduces lipid production in cells, but also reduces triglyceride, total cholesterol, and low-density lipoprotein cholesterol content in cells, while elevating high-density lipoprotein cholesterol content. This study provides a theoretical basis for the development and utilization of passion fruit seed oil as a functional lipid.

This article conducts experimental research on the influencing factors of the anti-skid performance testing system SCRIM for asphalt pavement. Studied the distribution pattern of anti-skid performance test results of the testing system under different testing speeds, test tires, temperature, water film thickness, test wheel position, tire wear degree, and other factors. Revealed the influence law of various influencing factors on the anti-skid performance of asphalt pavement. The test results indicate that the SFC test value decreases with the increase of vehicle speed. The test results of tires made of different materials vary greatly, and tires with wear exceeding 3 mm cannot be used for testing. The influence of water film thickness on the measured values varies depending on the SFC level. The SFC measurement value of the normal trajectory of the vehicle’s driving wheel track is the smallest, and the measurement value of the left trajectory is greater than that of the right trajectory. The SFC measurement decreases as the tire wear increases.

Background Passion fruit (Passiflora edulis) is loved for its delicious flavor and nutritious juice. Although studies have delved into the cultivation and enhancement of passion fruit varieties, the underlying factors contributing to the fruit’s appealing aroma remain unclear. Methods This study analyzed the full-length transcriptomes of two passion fruit cultivars with different flavor profiles: “Tainong 1” (TN1), known for its superior fruit flavor, and “Guihan 1” (GH1), noted for its strong environmental resilience but lackluster taste. Utilizing PacBio Iso-Seq and Illumina RNA-Seq technologies, we discovered terpene synthase (TPS) genes implicated in fruit ripening that may help explain the flavor disparities. Results We generated 15,913 isoforms, with N50 lengths of 1,500 and 1,648 bp, and mean lengths of 1,319 and 1,463 bp for TN1 and GH1, respectively. Transcript and isoform lengths ranged from a maximum of 7,779 bp to a minimum of 200 and 209 bp. We identified 14,822 putative coding DNA sequences (CDSs) averaging 1,063 bp, classified 1,007 transcription factors (TFs) into 84 families. Additionally, differential expression analysis of ripening fruit from both cultivars revealed 314 upregulated and 43 downregulated unigenes in TN1 compared to GH1. The top 10 significantly enriched Gene Ontology (GO) terms for the differentially expressed genes (DEGs) indicated that TN1’s upregulated genes were primarily involved in nutrient transport, whereas GH1’s up-regulated genes were associated with resistance mechanisms. Meanwhile, 17 PeTPS genes were identified in P. edulis and 13 of them were TPS-b members. A comparative analysis when compared PeTPS with AtTPS highlighted an expansion of the PeTPS-b subfamily in P. edulis, suggesting a role in its fruit flavor profile. Conclusion Our findings explain that the formation of fruit flavor is attributed to the upregulation of essential genes in synthetic pathway, in particular the expansion of TPS-b subfamily involved in terpenoid synthesis. This finding will also provide a foundational genetic basis for understanding the nuanced flavor differences in this species.

Abstract Background Bawei Chenxiang Wan (BCW) is among the most effective and widely used therapies for coronary heart disease and angina pectoris in Tibet. However, whether it confers protection through a right-ventricle (RV) myocardial metabolic mechanism is unknown. Methods Male Sprague–Dawley rats were orally administrated with BCW, which was injected concurrently with a bolus of Sugen5416, and subjected to hypoxia exposure (SuHx; 5000 m altitude) for 4 weeks. Right ventricular hypertrophy (RVH) in high-altitude heart disease (HAHD) was assessed using Fulton’s index (FI; ratio of RV to left ventricle + septum weights) and heart-weight-to-body-weight ratio (HW/BW). The effect of therapeutic administration of BCW on the RVH hemodynamics was assessed through catheterization (mean right ventricular pressure and mean pulmonary artery pressure (mRVP and mPAP, respectively)). Tissue samples were used to perform histological staining, and confirmatory analyses of mRNA and protein levels were conducted to detect alterations in the mechanisms of RVH in HAHD. The protective mechanism of BCW was further verified via cell culture. Results BCW considerably reduced SuHx-associated RVH, as indicated by macro morphology, HW/BW ratio, FI, mPAP, mRVP, hypertrophy markers, heart function, pathological structure, and myocardial enzymes. Moreover, BCW can alleviate the disorder of glucose and fatty acid metabolism through upregulation of carnitine palmitoyltransferase1ɑ, citrate synthase, and acetyl-CoA and downregulation of glucose transport-4, phosphofructokinase, and pyruvate, which resulted in the reduced levels of free fatty acid and lactic acid and increased aerobic oxidation. This process may be mediated via the regulation of sirtuin 3 (SIRT3)-hypoxia-inducible factor 1α (HIF1α)-pyruvate dehydrogenase kinase (PDK)/pyruvate dehydrogenase (PDH) signaling pathway. Subsequently, the inhibition of SIRT3 expression by 3-TYP (a selective inhibitor of SIRT3) can reverse substantially the anti-RVH effect of BCW in HAHD, as indicated by hypertrophy marker and serum myocardial enzyme levels. Conclusions BCW prevented SuHx-induced RVH in HAHD via the SIRT3-HIF1ɑ-PDK/PDH signaling pathway to alleviate the disturbance in fatty acid and glucose metabolism. Therefore, BCW can be used as an alternative drug for the treatment of RVH in HAHD.

Abstract Background Myocardial injury after non-cardiac surgery (MINS) is a common and insidious postoperative complication. This study aimed to evaluate the relationship between the triglyceride-glucose index (TyG) and MINS in advanced-age patients. Methods We performed a single-center retrospective study including patients ≥ 65 years of age who underwent non-cardiac surgery. The relationship between TyG and MINS was investigated using univariate and multivariate logistic regression analyses. Multivariate logistic regression analysis involved three models: Model I adjusted for preoperative factors, Model II adjusted for surgery-related factors, and Model III adjusted for both preoperative and surgery-related factors. Propensity score matching (PSM) was used to reduce the confounding effects of covariates. Subgroup analyses were then performed to evaluate the relationship between TyG and MINS in various subsamples. Results A total of 7789 patients were studied, among whom 481 (6.2%) developed MINS. A cut-off value of TyG of 8.57 was determined using a receiver operating characteristic (ROC) curve to be associated with the best predictive performance. Participants with TyG ≥ 8.57 were at a higher risk of developing MINS than those with TyG

Abstract Developmental delay (DD), or intellectual disability (ID) is a very large group of early onset disorders that affects 1–2% of children worldwide, which have diverse genetic causes that should be identified. Genetic studies can elucidate the pathogenesis underlying DD/ID. In this study, whole-exome sequencing (WES) was performed on 225 Chinese DD/ID children (208 cases were sequenced as proband-parent trio) who were classified into seven phenotype subgroups. The phenotype and genomic data of patients with DD/ID were further retrospectively analyzed. There were 96/225 (42.67%; 95% confidence interval [CI] 36.15–49.18%) patients were found to have causative single nucleotide variants (SNVs) and small insertions/deletions (Indels) associated with DD/ID based on WES data. The diagnostic yields among the seven subgroups ranged from 31.25 to 71.43%. Three specific clinical features, hearing loss, visual loss, and facial dysmorphism, can significantly increase the diagnostic yield of WES in patients with DD/ID (P = 0.005, P = 0.005, and P = 0.039, respectively). Of note, hearing loss (odds ratio [OR] = 1.86%; 95% CI = 1.00-3.46, P = 0.046) or abnormal brainstem auditory evoked potential (BAEP) (OR = 1.91, 95% CI = 1.02–3.50, P = 0.042) was independently associated with causative genetic variants in DD/ID children. Our findings enrich the variation spectrums of SNVs/Indels associated with DD/ID, highlight the value genetic testing for DD/ID children, stress the importance of BAEP screen in DD/ID children, and help to facilitate early diagnose, clinical management and reproductive decisions, improve therapeutic response to medical treatment.

In order to further clarify the influence of multistage pulse ultrasound on the characteristics of gas desorption in water-bearing coal, the ultrasonic stimulation test system of gas-containing coal is used to analyze the pore structure and gas desorption of coal under the condition of continuous ultrasonic stimulation of coal with different moisture contents and multistage pulse stimulation of water-saturated coal, and the mechanism of multistage pulse stimulation of water-bearing coal is revealed. The results show that the average pore diameter, specific surface area and total pore volume of coal increase with the increase of ultrasonic power and water saturation degree. When ultrasonic power is 1000 W, compared with dry coal, the increase of specific surface area and total pore volume of coal increases from 4.369% and 3.504% of 25% moisture content to 7.699% and 8.992% of 100% moisture content, respectively. There is a Langmuir-type relationship between coal gas desorption and time, and coal gas desorption amount and desorption rate are positively correlated with ultrasonic power and water saturation degree of coal. Compared with dry coal, the gas desorption capacity and desorption rate increase linearly with the increase of water saturation degree of coal, and ultrasonic stimulation has the best effect on the pore reconstruction and gas desorption of water saturated coal. With the increase of ultrasonic multistage pulse times, the specific surface area, total pore volume, gas desorption capacity and desorption rate of water-saturated coal increase. Compared with the 1000 W ultrasonic excitation, the increase of specific surface area and total pore volume of coal is a positive power function of the number of multistage pulses. The increase of gas desorption amount and desorption rate of coal increases from 2.745% and 4.598% of the first multistage pulse to 27.222% and 11.106% of the third multistage pulse, respectively, which is in a positive linear relationship with the number of multistage pulses. The combined effect of vibration and cavitation generated by multi-stage pulse ultrasonic stimulation of water-bearing coal causes fatigue damage to the coal matrix, strengthens the pore transformation of coal, and increases the molecular kinetic energy of gas, thus promoting gas desorption in coal. On site, the gas extraction in coal seam can be enhanced through the development of multi-stage pulse ultrasonic emitter combined with hydraulic technology.

Abstract Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease. UC confronts with severe challenges including the unclear pathogenesis and lack of specific diagnostic markers, demanding for identifying predictive biomarkers for UC diagnosis and treatment. We perform immune infiltration and weighted gene co-expression network analysis on gene expression profiles of active UC, inactive UC, and normal controls to identify UC related immune cell and hub genes. Neutrophils, M1 macrophages, activated dendritic cells, and activated mast cells are significantly enriched in active UC. MMP-9, CHI3L1, CXCL9, CXCL10, CXCR2 and S100A9 are identified as hub genes in active UC. Specifically, S100A9 is significantly overexpressed in mice with colitis. The receiver operating characteristic curve demonstrates the excellent performance of S100A9 expression in diagnosing active UC. Inhibition of S100A9 expression reduces DSS-induced colonic inflammation. These identified biomarkers associated with activity in UC patients enlighten the new insights of UC diagnosis and treatment.

Abstract Although there are many methods to improve the fault ride‐through (FRT) capability of doubly‐fed induction generator (DFIG) systems at present, each method has its shortcomings, especially the applicability under different voltage dips (VDs), so an improved system structure with a dynamic switching topology and a corresponding control scheme is proposed. Based on the mechanism analysis that the series impedance of the stator can effectively reduce the overcurrent on the rotor side, and considering the feasibility of the FRT scheme in engineering, the dynamic switching topology is designed. The selection of theoretical parameters in different cases is also analysed and designed. Simultaneously, to cooperate with the hardware measures, the control scheme of the rotor side converter (RSC) under different conditions is also improved. The RSC can use the control scheme of active flux attenuation to effectively and quickly reduce the overcurrent on the rotor side, and use reactive power support to accelerate the voltage recovery. The novelty of the FRT scheme is that the scheme can dynamically adjust the topology structure and control scheme under different voltage dips. Thus, its ride‐through performance during fault is better under different conditions. A simulation model of the improved system structure and control scheme is built on the MATLAB/Simulink platform. Through the comparison of simulation data, the validity and correctness of the proposed FRT scheme are verified.

As AI applications become increasingly integrated into daily life, protecting user privacy while enabling collaborative model training has become a crucial challenge, especially in decentralized edge computing environments. Traditional federated learning (FL) approaches, which rely on centralized model aggregation, struggle in such settings due to bandwidth limitations, data heterogeneity, and varying device capabilities among edge nodes. To address these issues, we propose PearFL, a decentralized FL framework that enhances collaboration and model generalization by introducing prototype exchange mechanisms. PearFL allows each client to share lightweight prototype information with its neighbors, minimizing communication overhead and improving model consistency across distributed devices. Experimental evaluations on benchmark datasets, including MNIST, CIFAR-10, and CIFAR-100, demonstrate that PearFL achieves superior communication efficiency, convergence speed, and accuracy compared to conventional FL methods. These results confirm PearFL’s efficacy as a scalable solution for decentralized learning in heterogeneous and resource-constrained environments.

China, the world’s largest egg producer, faces challenges of protein feed shortages and nitrogen pollution from manure. Low-protein diets (LPDs) offer potential solutions, but their adoption by small-scale farmers is uncertain. This study used surveys, meta-analysis, life-cycle assessment, and life-cost analysis to address these gaps. A field survey in Quzhou County (a typical representative of small- and medium-scale farmers in China’s egg farming industry) found that 84% of egg farmers were unfamiliar with LPDs and believed higher protein levels were better. On average, pre-laying and late-laying diets exceeded national LPD recommendations by 0.3% and 0.5% crude protein (CP), respectively. The main barriers to LPD adoption were perceived low quality, lack of veterinary recommendations, and limited technical support. A meta-analysis of 30 studies (published before July 2024) showed that reducing CP by less than 1% did not compromise productivity. Local LPD demonstrations and training improved farmer confidence. Results indicated a 10% reduction in the nitrogen footprint and a 115% increase in earnings for LPD-demonstration farmers. The study suggests a coupled pathway integrating research and technology diffusion, highlighting the need for collaboration among scientists, feed companies, and technical experts to overcome misconceptions and promote LPD adoption. This integrated framework offers valuable insights for sustainable agricultural development in China and other resource-limited countries.

Abstract Precise diagnostic biomarkers of anticitrullination protein antibody (ACPA)‐negative and early‐stage RA are still to be improved. We aimed to screen autoantibodies in ACPA‐negative patients and evaluated their diagnostic performance. The human genome‐wide protein arrays (HuProt arrays) were used to define specific autoantibodies from the sera of 182 RA patients and 261 disease and healthy controls. Statistical analysis was performed with SPSS 17.0. In Phase I study, 51 out of 19,275 recombinant proteins covering the whole human genome were selected. In Phase II validation study, anti‐ANAPC15 (anaphase promoting complex subunit 15) exhibited 41.8% sensitivity and 91.5% specificity among total RA patients. There were five autoantibodies increased in ACPA‐negative RA, including anti‐ANAPC15, anti‐LSP1, anti‐APBB1, anti‐parathymosin, and anti‐UBL7. Anti‐parathymosin showed the highest prevalence of 46.2% (p = 0.016) in ACPA‐negative early stage (