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Abstract Background Myocardial fibrosis, a hallmark of heart disease, is closely associated with macrophages, yet the genetic pathophysiology remains incompletely understood. In this study, we utilized integrated single-cell transcriptomics and bulk RNA-seq analysis to investigate the relationship between macrophages and myocardial fibrosis across omics integration. Methods We examined and curated existing single-cell data from dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), myocardial infarction (MI), and heart failure (HF), and analyzed the integrated data using cell communication, transcription factor identification, high dimensional weighted gene co-expression network analysis (hdWGCNA), and functional enrichment to elucidate the drivers of macrophage polarization and the macrophage-to-myofibroblast transition (MMT). Additionally, we assessed the accuracy of single-cell data from the perspective of driving factors, cell typing, anti-fibrosis performance of left ventricular assist device (LVAD). Candidate drugs were screened using L1000FWD. Results All four heart diseases exhibit myocardial fibrosis, with only MI showing an increase in macrophage proportions. Macrophages participate in myocardial fibrosis through various fibrogenic molecules, especially evident in DCM and MI. Abnormal RNA metabolism and dysregulated transcription are significant drivers of macrophage-mediated fibrosis. Furthermore, profibrotic macrophages exhibit M1 polarization and increased MMT. In HF patients, those responding to LVAD therapy showed a significant decrease in driver gene expression, M1 polarization, and MMT. Drug repurposing identified cinobufagin as a potential therapeutic agent. Conclusion Using integrated single-cell transcriptomics, we identified the drivers of macrophage-mediated myocardial fibrosis in four heart diseases and confirmed the therapeutic effect of LVAD on improving HF with single-cell accuracy, providing novel insights into the diagnosis and treatment of myocardial fibrosis.

Abstract Macrophages may acquire a reparative phenotype that supports tissue repair and remodeling in response to tissue injury. However, the metabolic requirements underpinning this process are incompletely understood. Here, we show that posttranslational modification (PTM) of PPARγ regulates lipid synthesis in response to wound microenvironmental cues and that metabolic rewiring orchestrates function of reparative macrophages. In injured tissues, repair signaling leads to decreased macrophage PPARγ threonine 166 (T166) phosphorylation, which results in a partially active PPARγ transcriptional program comprised of increased binding activity to the regulator regions of lipid synthesis-associated genes, thereby increased lipogenesis. The accumulated lipids serve as signaling molecules, triggering STAT3-mediated growth factor expression, and supporting the synthesis of phospholipids for the expansion of the endoplasmic reticulum (ER), which is required for protein secretion. Genetic or pharmacological inhibition of PPARγ T166 phosphorylation promotes the reparative function of macrophages and facilitates tissue regeneration. In summary, our work identifies PPARγ T166-regulated lipid biosynthesis as an essential pathway for meeting the anabolic demands of the activation and function of macrophages and provides a rationale for potential therapeutic targeting of tissue repair.

Triboelectrification （TE） is a physical phenomenon that exists on the surface of almost all materials， and the TE of semiconductor materials is different from the electrification of dielectric materials.At the dynamic interface between one semiconductor and another semiconductor or a metal， mechanical friction causes the continuous breaking and rebuilding of chemical bonding between atoms at the interfaces， which could release a quantized energy that is the binding energy of two atoms （or called as bindington） to excite non-equilibrium electron-hole pairs.These electrons and holes can be separated by the built-in electric field formed at the p-n junctions （or Schottky junction， semiconductor heterojunction）， so as to output direct-current （DC） electricity in the external circuits. This phenomenon is defined as the tribovoltaic effect. It is similar to the photovoltaic effect， but the difference is the exciting energy sources. In the tribovoltaic effect， electron-hole pairs are excited by the energy released by the instantaneous transition of atoms at the interface or the energy released when new bonds are formed at the interface； while the photovoltaic effect is excited by photo energy.This article reviews the research progress of DC nanogenerators based on the tribovoltaic effect， including mechanism research， material and device design， surface modification enhancement strategies， etc. We also discuss the possible applications of tribovoltaic devices as flexible DC power sources for wearable electronics， with emphases on their device design， performance optimization，and potential application scenarios.

Abstract Accurate, fast and lightweight dense target detection methods are highly important for precision agriculture. To detect dense apricot flowers using drones, we propose an improved dense target detection method based on YOLOv8, named D-YOLOv8. First, we introduce the Dense Feature Pyramid Networks (D-FPN) to enhance the model’s ability to extract dense features and Dense Attention Layer (DAL) to focus on dense target areas, which enhances the feature extraction ability of dense areas, suppresses features in irrelevant areas, and improves dense target detection accuracy. Finally, RAW data are used to enhance the dataset, which introduces additional original data into RAW images, further enriching the feature input of dense objects. We perform validation on the CARPK challenge dataset and constructed a dataset. The experimental results show that our proposed D-YOLOv8m achieved 98.37% AP, while the model parameters were only 13.2 million. The improved network can effectively support any task of dense target detection.

Under the pressures of global climate change and human activities, the carrying capacity of water and soil resources in agricultural lands has decreased, and the traditional models of agricultural development are no longer sustainable. Land degradation, groundwater quality reduction and ecosystem instability are the consequences of agricultural development without considering sustainability indicators. This article aims to investigate the use of variable relationship analysis and Bayesian network methods to analyze and investigate the relationship between irrigation in agriculture and the sustainability of the groundwater ecosystem. Descriptive statistics of agriculture including cultivation pattern, time, precipitation, irrigation, and land slope were analyzed and combined with the simulated characteristics of groundwater including specific yield, hydraulic conductivity and hydrodynamic diffusion coefficients. Five crops of wheat, barley, paddy, alfalfa, and potato were studied to evaluate the effect of plants on the pattern of nitrate release due to irrigation and fertilization in agriculture. The results showed that managing the amount of fertilizer and the volume of irrigation can positively affect the nitrate distribution pattern in the groundwater even in a short period of time. HIGHLIGHTS The relationships between variables are used to build a logical model for analysis.; The quantity and quality of irrigation water is incorporated into the system for estimating the nitrate concentration in groundwater.;

Abstract Mitochondria are central to endothelial cell activation and angiogenesis, with the RNA polymerase mitochondrial (POLRMT) serving as a key protein in regulating mitochondrial transcription and oxidative phosphorylation. In our study, we examined the impact of POLRMT on angiogenesis and found that its silencing or knockout (KO) in human umbilical vein endothelial cells (HUVECs) and other endothelial cells resulted in robust anti-angiogenic effects, impeding cell proliferation, migration, and capillary tube formation. Depletion of POLRMT led to impaired mitochondrial function, characterized by mitochondrial depolarization, oxidative stress, lipid oxidation, DNA damage, and reduced ATP production, along with significant apoptosis activation. Conversely, overexpressing POLRMT promoted angiogenic activity in the endothelial cells. In vivo experiments demonstrated that endothelial knockdown of POLRMT, by intravitreous injection of endothelial specific POLRMT shRNA adeno-associated virus, inhibited retinal angiogenesis. In addition, inhibiting POLRMT with a first-in-class inhibitor IMT1 exerted significant anti-angiogenic impact in vitro and in vivo. Significantly elevated expression of POLRMT was observed in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. POLRMT endothelial knockdown inhibited pathological retinal angiogenesis and mitigated retinal ganglion cell (RGC) degeneration in DR mice. At last, POLRMT expression exhibited a substantial increase in the retinal proliferative membrane tissues of human DR patients. These findings collectively establish the indispensable role of POLRMT in angiogenesis, both in vitro and in vivo.

Abstract Background The aim of this study was to investigate the association between systemic immune‐inflammation index (SII) and all‐cause mortality in individuals with chronic kidney disease (CKD). Patients and Methods This prospective cohort study was carried out among 9303 participants with CKD from the National Health and Nutrition Examination Survey cycles spanning 1999 to 2018. The mortality data were ascertained by linking participant records to the National Death Index up to December 31, 2019. Complex sampling‐weighted multivariate Cox proportional hazards models were employed to estimate the association between SII level and all‐cause mortality, providing hazard ratios (HR) and 95% confidence intervals (CI). A restricted cubic spline analysis was conducted to explore potential nonlinear correlation. Subgroup analyses and sensitivity analyses were also conducted. Results During a median follow‐up period of 86 months, 3400 (36.54%) all‐cause deaths were documented. A distinctive “J”‐shaped relationship between SII level and all‐cause mortality was discerned among individuals with CKD, with the nadir observed at an SII level of 478.93 within the second quartile. After adjusting for potential covariates, the risk of all‐cause mortality escalated by 13% per increment of one standard deviation of SII, once SII exceeded 478.93 (HR = 1.13; 95% CI = 1.08–1.18). An elevated SII was associated with an increased risk of all‐cause mortality among patients with CKD (Q4 vs. Q2: HR = 1.23; 95% CI = 1.01–1.48). Subgroup analyses indicated that the correlation between SII and CKD mortality was particularly pronounced among participants over 60 years old and individuals with diabetes. Sensitivity analyses revealed a linear positive association between SII and all‐cause mortality after removing the extreme 5% outliers of SII. Conclusions A distinctive “J”‐shaped relationship between SII level and all‐cause mortality was identified among individuals with CKD. Further research is warranted to validate and expand upon these findings.

IntroductionApplying biochar (BC) to reduce toxic substance accumulation in soil, either through direct adsorption or modulation of the microbial community, has received considerable attention. However, a knowledge gap exists regarding how BC regulates microbial community structure and functions to mitigate toxic substance accumulation.MethodsWe previously identified p-coumaric acid (p-CA) as a representative autotoxin in tobacco rhizosphere soil. On this basis, this study simulated a soil environment with p-CA accumulation to investigate the impacts of BC on p-CA, soil physicochemical properties, and microbial community structure and function.ResultsThe results showed that p-CA could be directly adsorbed onto BC, which followed the pseudo-second-order kinetic model (R2 = 0.996). A pot experiment revealed that BC significantly reduced soil p-CA, altered soil microbial composition, and enhanced bacterial community diversity. A weighted correlation network analysis showed a close association between taxon 1 in the microbial network and p-CA, suggesting a pivotal role for this taxon in reducing p-CA, with Devosia and Nocardioides identified as potential key contributors to this process. The prediction of possible keystone taxa functions showed that BC increased the relative abundances of aromatic compound degraders. Mantel tests indicated that soil organic matter exerted the greatest influence on keystone taxa functions and hub genera.DiscussionThese findings suggest that BC may either directly chemisorb p-CA or indirectly facilitate p-CA degradation by regulating the functioning of keystone taxa. The results of this study provide a novel perspective for further investigation of the mechanisms through which BC reduces the accumulation of toxic substances in soil.

Abstract Treatment of bone defects remains crucial challenge for successful bone healing, which arouses great interests in designing and fabricating ideal biomaterials. In this regard, the present study focuses on developing a novel fluffy scaffold of poly Lactide-co-glycolide (PLGA) composites with hydroxyapatite (HA) scaffold used in bone defect repair in rabbits. This fluffy PLGA/HA composite scaffold was fabricated by using multi-electro-spinning combined with biomineralization technology. In vitro analysis of human bone marrow mesenchymal stem cells (BMSCs) seeded onto fluffy PLGA/HA composite scaffold showed their ability to adhere, proliferate and cell viability. Transplant of fluffy PLGA/HA composite scaffold in a rabbit model showed a significant increase in mineralized tissue production compared to conventional and fluffy PLGA/HA composite scaffold. These findings are promising for fluffy PLGA/HA composite scaffolds used in bone defects. Graphical Abstract

Background Systemic Immune-Inflammation Index (SII) is a novel inflammatory biomarker closely associated with the inflammatory response and chronic kidney disease. Klotho is implicated as a pathogenic factor in the progression of kidney disease, and supplementation of Klotho may delay the progression of chronic kidney disease by inhibiting the inflammatory response. Our aim is to investigate the potential relationship between SII and Klotho in adult patients in the United States and explore the differences in the populations with and without albuminuria.Methods We conducted a cross-sectional study recruiting adult participants with complete data on SII, Klotho, and urine albumin-to-creatinine ratio (ACR) from the National Health and Nutrition Examination Survey from 2007 to 2016. SII was calculated as platelet count × neutrophil count/lymphocyte count, with abnormal elevation defined as values exceeding 330 × 10^9/L. Albuminuria was defined as ACR >30 mg/g. Weighted multivariable regression analysis and subgroup analysis were employed to explore the independent relationship between SII and Klotho.Results Our study included a total of 10,592 individuals. In all populations, non-albuminuria population, and proteinuria population with ACR ≥ 30, participants with abnormally elevated SII levels, as compared to those with SII less than 330 × 10^9/L, showed a negative correlation between elevated SII levels and increased Klotho, which persisted after adjusting for covariates.Conclusions There is a negative correlation between SII and Klotho in adult patients in the United States. This finding complements previous research but requires further analysis through large prospective studies.

Background Renal impairment has been previously linked to peripheral eosinophil count (PEC), prompting an investigation into its potential relationship with chronic kidney disease (CKD). This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES 1999–2018) to comprehensively explore the association between PEC and CKD.Methods Survey-weighted generalized multivariate linear regression was employed to evaluate the associations between PEC, urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), with meticulous adjustment for potential covariates. To assess non-linear correlations, a restricted cubic spline analysis was conducted. Sensitivity analysis was performed to test the stability of results.Results The study included a total of 9224 participants with non-dialysis CKD. In the multivariate linear regression model, after comprehensive adjustment for potential covariates, PEC showed a negative association with eGFR (β per 100 cells/uL increase in PEC, −0.71; 95% CI, −1.04, −0.37), while demonstrating a positive trend with UACR (β per 100 cells/uL increase in PEC, 10.21; 95% CI, 1.37, 19.06). The restrictive cubic spline curve analysis suggested that these associations occurred within the range of 0 to 400 cells/uL for PEC. Sensitivity analysis supported the stability of the observed results.Conclusions Circulating eosinophil levels are negatively correlated with eGFR and demonstrate a positive trend with UACR, when PEC falls within the range of less than 400 cells/uL among adults with CKD. Further research is warranted to validate these findings.

As Wolbachia pipientis is more widely being released into field populations of Aedes aegypti for disease control, the ability to select the appropriate strain for differing environments is increasingly important. A previous study revealed that longer-term quiescence in the egg phase reduced the fertility of mosquitoes, especially those harboring the wAlbB Wolbachia strain. This infertility was also associated with a greater biting rate. Here, we attempt to quantify the effect of this heightened biting behavior on the transmission potential of the dengue virus using a combination of assays for fitness, probing behavior, and vector competence, allowing repeat feeding, and incorporate these effects in a model of R0. We show that Wolbachia-infected infertile mosquitoes are more interested in feeding almost immediately after an initial blood meal relative to wild type and Wolbachia-infected fertile mosquitoes and that these differences continue for up to 8 days over the period we measured. As a result, the infertile Wolbachia mosquitoes have higher virus prevalence and loads than Wolbachia-fertile mosquitoes. We saw limited evidence of Wolbachia-mediated blocking in the disseminated tissue (legs) in terms of prevalence but did see reduced viral loads. Using a previously published estimate of the extrinsic incubation period, we demonstrate that the effect of repeat feeding/infertility is insufficient to overcome the effects of Wolbachia-mediated blocking on R0. These estimates are very conservative, however, and we posit that future studies should empirically measure EIP under a repeat feeding model. Our findings echo previous work where periods of extensive egg quiescence affected the reproductive success of Wolbachia-infected Ae. aegypti. Additionally, we show that increased biting behavior in association with this infertility in Wolbachia-infected mosquitoes may drive greater vector competence. These relationships require further exploration, given their ability to affect the success of field releases of Wolbachia for human disease reduction in drier climates where longer egg quiescence periods are expected.

ObjectiveAlthough urinary extracellular vesicles (uEVs) have been extensively studied in various cancers, their involvement in breast cancer (BC) remains largely unexplored. The non-invasive nature of urine as a biofluid and its abundant protein content offer considerable potential for the early detection of breast cancer.MethodsThis study analyzed the proteomic profiles of uEVs from BC patients and healthy controls (HC). The dysregulation of ECM1 and ANXA1 in the uEVs was validated in a larger cohort of 128 BC patients, 25 HC and 25 benign breast nodules (BBN) by chemiluminescence assay (CLIA). The expression levels of ECM1 and ANXA1 were also confirmed in the uEVs of MMTV-PyMT transgenic breast cancer mouse models.ResultsLC-MS/MS analysis identified 571 dysregulated proteins in the uEVs of BC patients. ECM1 and ANXA1 were selected for validation in 128 BC patients, 25 HC and 25 BBN using CLIA, as their fold change showed a significant difference of more than 10 with p-value

Objective: It's crucial to identify an easily detectable biomarker that is specific to radiation injury in order to effectively classify injured individuals in the early stage in large-scale nuclear accidents. Methods: C57BL/6J mice were subjected to whole-body and partial-body γ irradiation, as well as whole-body X-ray irradiation to explore the response of serum sSelectin-L to radiation injury. Then, it was compared with its response to lipopolysaccharide-induced acute infection and doxorubicin-induced DNA damage to study the specificity of sSelectin-L response to radiation. Furthermore, it was further evaluated in serum samples from nasopharyngeal carcinoma patients before and after radiotherapy. Simulated rescue experiments using Amifostine or bone marrow transplantation were conducted in mice with acute radiation syndrome to determine the potential for establishing sSelectin-L as a prognostic marker. The levels of sSelectin-L were dynamically measured using the ELISA method. Results: Selectin-L is mainly expressed in hematopoietic tissues and lymphatic tissues. Mouse sSelectin-L showed a dose-dependent decrease from 1 day after irradiation and exhibited a positive correlation with lymphocyte counts. Furthermore, the level of sSelectin-L reflected the degree of radiation injury in partial-body irradiation mice and in nasopharyngeal carcinoma patients. sSelectin-L was closely related to the total dose of γ or X ray. There was no significant change in the sSelectin-L levels in mice intraperitoneal injected with lipopolysaccharide or doxorubicin. The sSelectin-L was decreased slower and recovered faster than lymphocyte count in acute radiation syndrome mice treated with Amifostine or bone marrow transplantation. Conclusions: Our study shows that sSelectin-L has the potential to be an early biomarker to classify injured individuals after radiation accidents, and to be a prognostic indicator of successful rescue of radiation victims.

Abstract Anesthetics can affect temperature regulation when administered to an anesthetized individual, which can be tracked by measuring the core body temperature. This is useful in assessing the depth and consistency of the anesthesia, as well as its effect on temperature control. In this study, a temperature probe measurement system is created with a remarkable sensitivity of 685.3 Ω °C−1, a high resolution of 0.01 °C, and a fast response rate of 0.16 s °C−1. This ultrafine and biocompatible probe is composed of a single carbon fiber with a diameter of 5.4 µm, encased in a 0.7 mm needle. The system is reliable and provides faster temperature measurements than existing technologies. By inserting the probe beneath the scapula to measure core body temperature in real‐time, a linear correlation can be seen between the duration of anesthesia, the minimum core body temperature, and the respiratory rate when different doses of tribromoethanol anesthetic are administered. This can improve the effectiveness and safety of clinical practice, accelerate the progress and utilization of anesthetic drugs, and give a better comprehension of the physiological mechanisms of anesthesia.

Abstract Background Chamomile (Matricaria recutita L.) is an important economic crop after tobacco (Nicotiana tabacum L.) cultivation. The nicotine released into the soil during tobacco cultivation has an impact on various aspects of chamomile growth, including plant height, flowering period, flower yield, and flower quality. We aimed to examine the effects of physiological and metabolic response of chamomile under different concentrations of nicotine stress. Results The study revealed that chamomile growth was positively influenced by nicotine concentrations of 1.0 μg/g (N-1) and 10.0 μg/g (N-10). However, higher nicotine concentrations of 100.0 μg/g (N-100) and 500.0 μg/g (N-500) were found to induce stress as the highest levels of antioxidant enzyme activities and malondialdehyde (MDA) levels were observed under this treatment. In addition, it was observed that nicotine was transported from the roots to other organs during the entire growth period of chamomile and the nicotine levels reached saturation under N-100 treatment. A total of 1096 metabolites were detected by ultra-high-performance liquid chromatography-coupled tandem mass spectrometry (UHPLC–MS/MS) analysis, and 48 differentially expressed metabolites (DEMs) were identified among the groups via widely targeted metabolomics studies. The response of chamomile flowers to nicotine stress is associated with the presence of flavonoids, phenolic acids, organic acids, and other substances. Metabolic regulation under nicotine stress primarily involves processes, such as aminoacyl-tRNA biosynthesis, ABC (ATP-binding cassette) transporter activity, glyoxylate and dicarboxylate metabolism and pyrimidine metabolism. Conclusions This report presents the first findings on how nicotine affects the metabolism of chamomile. It also provides a comprehensive understanding of how crops can resist nicotine stress from a metabolic perspective. Graphical Abstract

The adoption of brown fermented milk in the normal diet and daily beverages is accompanied by significant sugar intake and a high public health burden. To reduce the sugar content in dairy products while maintaining optimal nutritional properties, a novel low-calorie, lactose-free brown fermented milk was developed through enzymatic hydrolysis and the Maillard reaction. The optimal product was achieved using low-temperature lactase, where the lactose and glucose content were reduced 33-fold and 2.4-fold to 0.06 g/100 g and 13.32 g/L, respectively, meeting the criteria for being lactose-free (