Potential and application of abortive transcripts as a novel molecular marker of cancers.

Abortive transcript (AT) is a 2-19 nt long non-coding RNA that is produced in the abortive initiation stage. Abortive initiation was found to be closely related to RNA polymerase through in vitro experiments. Therefore, the distribution of AT length and the scale of abortive initiation are correlated to the promoter, discriminator, and transcription initiation sequence, and can be affected by transcription elongation factors. AT plays an important role in the occurrence and development of various diseases. Here we summarize the discovery of AT, the factors responsible for AT formation, the detection methods and biological functions of AT, to provide new clues for finding potential targets in the early diagnosis and treatment of cancers.

Generation of a competing endogenous RNA network and validation of BNIP1 expression in the lung of irradiated mice.

BACKGROUND: Radiation-induced lung injury (RILI) is a serious complication of radiation therapy, and it is mediated by long non-coding RNAs (lncRNAs). STUDY DESIGN AND METHODS: Mouse lung tissues were examined using RNA-Seq and RNA-Seq libraries 72 h after the administration of 6 Gy of X-ray irradiation. The target mRNAs were functionally annotated and the target lncRNA-based miRNAs and target miRNA-based mRNAs were predicted after irradiation to establish the lncRNA-miRNA-mRNA ceRNA axis. RESULTS: The analyses showed that relative to unirradiated controls, 323 mRNAs, 114 miRNAs, and 472 lncRNAs were significantly up-regulated following irradiation, whereas 1907 mRNAs, 77 miRNAs, and 1572 lncRNAs were significantly down-regulated following irradiation. Voltage-gated ion channels, trans-membrane receptor protein tyrosine kinases, and vascular endothelial growth factor have all been associated with dysregulated miRNA-mRNA relationships. KEGG pathway analysis of the dysregulated miRNA-mRNA targets revealed involvement in pathways associated with the hedgehog signaling pathway-fly, ErbB signaling, VEGF signaling, axon guidance, and focal adhesion. KEGG analysis of differentially expressed showed enrichment of mRNAs in primary immunodeficiency, the intestinal immune axis for IgA production, hematopoietic cell lineages, systemic lupus erythematosus, and Th1 and Th2 cell differentiation. Finally, the ceRNA network revealed that BNIP1 was a critical mRNA modulated by the most significant upregulation of lncRNA E230013L22Rik. CONCLUSION: In summary, the lncRNA-miRNA-mRNA ceRNA axis of RILI was constructed following irradiation in a mouse model. RNA dysregulation in the early stage of RILI may lead to severe complications at a later stage, with BNIP1 contributing to radiation-induced cellular apoptosis in RILI.

Impacts of spatial symmetries on stimulated Brillouin scatterings in nanoscale silicon waveguides: a theoretical and numerical study considering material anisotropies.

Fully considering the mechanical and photoelastic anisotropies of monocrystalline silicon, the impacts of spatial symmetries on the stimulated Brillouin scatterings (SBSs) in nanoscale suspended silicon waveguides are studied theoretically and numerically based on group theory. First, starting from an assumption that the principal material coordinate system can be arbitrarily orientated in a waveguide with fixed geometry, the silicon waveguides are systematically classified into a number of point groups according to their spatial symmetry features. Thereafter, the symmetry characteristics of physical fields and SBS opto-mechanical coupling characteristics in the silicon waveguides belonging to different point groups are further examined, and the major new findings can be summarized as follows: The SBS opto-mechanical couplings in several kinds of silicon waveguides with certain nontrivial symmetry features exhibit relatively predictable behaviors in that the opto-mechanical coupling coefficients can be deterministically vanishing or nonvanishing under very few constraints, which can thus serve as general symmetry selection rules for SBSs in suspended silicon waveguides. The results obtained in the present study could be a useful theoretical reference for the design of novel SBS-active silicon photonic devices.

Complete chloroplast genome sequence of Pinus tabuliformis var. henryi (Mast.) C.T.Kuan 1983 (Pinaceae).

Pinus tabuliformis var. henryi (Mast.) C.T.Kuan 1983 is an endemic and rare subtropical pine, mainly distributed in central China. In this study, we sequenced the complete chloroplast (cp) genome of P. tabuliformis var. henryi and reported it for the first time. The cp genome was 119,634 base pairs (bp) in total length, including two inverted repeats (IRs, 495 bp), separated by a large single-copy region (LSC, 65,600 bp) and a small single-copy region (SSC, 53,044 bp). There are 114 different genes in the cp genome of P. tabuliformis var. henryi, including 74 protein-coding genes, 36 transfer RNA genes, and four ribosomal RNA genes. The overall GC content of the cp genome was 38.5%. Our phylogenetic analysis of P. tabuliformis var. henryi demonstrated that it was closely related to P. tabuliformis and could be used to identify and analyze its genetic diversity, which was expected to provide new data for taxonomic and phylogenetic studies of Pinus.

Vitamin D binding protein (VDBP) hijacks twist1 to inhibit vasculogenic mimicry in hepatocellular carcinoma.

Rationale: Vitamin D (VD) has been suggested to have antitumor effects, however, research on the role of its transporter vitamin D-binding protein (VDBP, gene name as GC) in tumors is limited. In this study, we demonstrated the mechanism underlying the inhibition of vasculogenic mimicry (VM) by VDBP in hepatocellular carcinoma (HCC) and proposed an anti-tumor strategy of combining anti-PD-1 therapy with VD. Methods: Three-dimensional cell culture models and mice with hepatocyte-specific GC deletion were utilized to study the correlation between VDBP expression and VM. A patient-derived tumor xenograft (PDX) model was further applied to validate the therapeutic efficacy of VD in combination with an anti-PD-1 drug. Results: The study revealed that VDBP expression is negatively correlated with VM in HCC patients and elevated VDBP expression is associated with a favorable prognosis. The mechanism studies suggested VDBP hindered the binding of Twist1 on the promoter of VE-cadherin by interacting with its helix-loop-helix DNA binding domain, ultimately leading to the inhibition of VM. Furthermore, VD facilitated the translocation of the vitamin D receptor (VDR) into the nucleus where VDR interacts with Yin Yang 1 (YY1), leading to the transcriptional activation of VDBP. We further demonstrated that the combination of VD and anti-PD-1 led to an improvement in the anti-tumor efficacy of an anti-PD-1 drug. Conclusion: Collectively, we identified VDBP as an important prognostic biomarker in HCC patients and uncovered it as a therapeutic target for enhancing the efficacy of immune therapy.

A nomogram for predicting hospital mortality of critical ill patients with sepsis and cancer: a retrospective cohort study based on MIMIC-IV and eICU-CRD.

OBJECTIVE: Sepsis remains a high cause of death, particularly in immunocompromised patients with cancer. The study was to develop a model to predict hospital mortality of septic patients with cancer in intensive care unit (ICU). DESIGN: Retrospective observational study. SETTING: Medical Information Mart for Intensive Care IV (MIMIC IV) and eICU Collaborative Research Database (eICU-CRD). PARTICIPANTS: A total of 3796 patients in MIMIC IV and 549 patients in eICU-CRD were included. PRIMARY OUTCOME MEASURES: The model was developed based on MIMIC IV. The internal validation and external validation were based on MIMIC IV and eICU-CRD, respectively. Candidate factors were processed with the least absolute shrinkage and selection operator regression and cross-validation. Hospital mortality was predicted by the multivariable logistical regression and visualised by the nomogram. The model was assessed by the area under the curve (AUC), calibration curve and decision curve analysis curve. RESULTS: The model exhibited favourable discrimination (AUC: 0.726 (95% CI: 0.709 to 0.744) and 0.756 (95% CI: 0.712 to 0.801)) in the internal and external validation sets, respectively, and better calibration capacity than Acute Physiology and Chronic Health Evaluation IV in external validation. CONCLUSIONS: Despite that the predicted model was based on a retrospective study, it may also be helpful to predict the hospital morality of patients with solid cancer and sepsis.

Expert Consensus on Acute Respiratory Failure in Critically Ill Cancer Patients (2023).

Objective This consensus aims to provide evidence-based recommendations on common questions in the diagnosis and treatment of acute respiratory failure (ARF) for critically ill cancer patients.Methods We developed six clinical questions using the PICO (Population, Intervention, Comparison, and Outcome) principle in diagnosis and treatment for critical ill cancer patients with ARF. Based on literature searching and meta-analyses, recommendations were devised. The GRADE (Grading of Recommendation Assessment, Development and Evaluation) method was applied to each question to reach consensus in the expert panel. Results The panel makes strong recommendations in favor of (1) metagenomic next-generation sequencing (mNGS) tests may aid clinicians in rapid diagnosis in critically ill cancer patients suspected of pulmonary infections; (2) extracorporeal membrane oxygenation (ECMO) therapy should not be used as a routine rescue therapy for acute respiratory distress syndrome in critically ill cancer patients but may benefit highly selected patients after multi-disciplinary consultations; (3) cancer patients who have received immune checkpoint inhibitor therapy have an increased incidence of pneumonitis compared with standard chemotherapy; (4) critically ill cancer patients who are on invasive mechanical ventilation and estimated to be extubated after 14 days may benefit from early tracheotomy; and (5) high-flow nasal oxygen and noninvasive ventilation therapy can be used as a first-line oxygen strategy for critically ill cancer patients with ARFs. A weak recommendation is: (6) for critically ill cancer patients with ARF caused by tumor compression, urgent chemotherapy may be considered as a rescue therapy only in patients determined to be potentially sensitive to the anticancer therapy after multidisciplinary consultations. Conclusions The recommendations based on the available evidence can guide diagnosis and treatment in critically ill cancer patients with acute respiratory failure and improve outcomes.

Factors affecting the primary patency of native arteriovenous fistulas after ultrasound-guided percutaneous transluminal angioplasty.

OBJECTIVE: By analyzing the clinical history, laboratory test indexes, and intraoperative ultrasound imaging data of patients receiving ultrasound-guided percutaneous transluminal angioplasty (UG-PTA) for the first time, the application value of UG-PTA in the treatment of peripheral stenosis of autogenous arteriovenous fistula (AVF) and the related factors affecting postoperative patency were investigated. METHODS: A total of 381 patients with dysfunction of radio-cephalic AVF were treated with UG-PTA from June 2017 to September 2019. According to the inclusion and exclusion criteria, 199 patients were included in this study. Baseline characteristics of patients, including demographic, clinical, and laboratory data, were collected. Kaplan-Meier's survival curve was used to demonstrate the cumulative primary patency rate of UG-PTA. Univariate and multivariate Cox regression analysis was performed on clinical, anatomic, biochemical, and medication variables to identify the predictors of postintervention primary patency. RESULTS: The early technical success rate of UG-PTA was 98.4% (375/381). One hundred and ninety-nine patients, with an average age of 52.9 years, were analyzed, 97 of whom were males (48.7%). The median follow-up duration was 21 months. No major complication was observed. Postintervention primary patency rates were 87.7%, 75.8%, and 60.0% at 6, 12, and 24 months, respectively. A previously failed AVF (HR, 1.935, 95% CI 1.071-3.494; p = .029) and an increased level of parathyroid hormone (HR per 100 pg/mL increase, 1.105; 95% CI 1.014-1.203; p = .004) were identified as independent negative predictors of primary patency of UG-PTA. CONCLUSIONS: UG-PTA is a safe and effective method for the treatment of peripheral stenosis of AVF. Previously failed AVF and elevated parathyroid hormone levels are associated with lower primary patency rate.

The chemistry and activity-orientedcharacterization of isoflavones difference between roots of Pueraria lobata and P. thomsonii guided by feature-based molecular networking.

Isoflavones are important chemical components in Pueraria species with various biological activities. This study proposed an integrated strategy combining feature-based molecular networking (FBMN), chemometrics and activity evaluation for isoflavone analysis in the roots of P. lobate (PLR) and P. thomsonii (PTR). Based on the strategy, a total of 68 isoflavones were annotated in the two Pueraria species, and 11 significant difference isoflavones between PLR and PTR were identified by chemometric methods. Additionally, the correlation coefficient between the characteristic isoflavones and hypoglycemic activity were calculated, and 7 isoflavones were further confirmed as bioactive marker compounds. This approach provided guidance for the discovery of active markers among different products.

The role of intercellular junction proteins in the penetration resistance of Drosophila larvae to avermectin.

Insecticide resistance has become an increasingly serious challenge for agriculture in the world. To reveal the mechanisms of insecticide resistance, majority of studies have been carried out on the insensitivity of insecticide targets and the metabolism of insecticides. However, the mechanism of the insecticide penetration resistance in insects remains unclear. This study aimed to reveal the mechanism underlying the penetration resistance of Drosophila larvae to insecticide avermectin (AVM). Levels of intercellular junction proteins (IJPs) in the larvae were determined by Western blotting analysis and immunofluorescence assay. The result showed that the expression of IJPs septate junction and adherens junction proteins increased in the AVM-resistant insects compared with those in the AVM-susceptible ones, and the upregulation of the IJPs was mediated by the activation of protein kinase C (PKC) pathway. That AVM induced the activation of PKC was found not only in the Drosophila larvae but also in Drosophila S2 cells. These findings revealed that AVM could activate PKC pathway in Drosophila larvae, which mediated the upregulation of the IJPs and then led to the resistance to AVM, suggesting that the chemicals that can disrupt PKC activation may potentially be used to circumvent the resistance to AVM in insects.

Identification of wheat seedling varieties based on MssiapNet.

Introduction: In the actual planting of wheat, there are often shortages of seedlings and broken seedlings on long ridges in the field, thus affecting grain yield and indirectly causing economic losses. Variety identification of wheat seedlings using physical methods timeliness and is unsuitable for universal dissemination. Recognition of wheat seedling varieties using deep learning models has high timeliness and accuracy, but fewer researchers exist. Therefore, in this paper, a lightweight wheat seedling variety recognition model, MssiapNet, is proposed. Methods: The model is based on the MobileVit-XS and increases the model's sensitivity to subtle differences between different varieties by introducing the scSE attention mechanism in the MV2 module, so the recognition accuracy is improved. In addition, this paper proposes the IAP module to fuse the identified feature information. Subsequently, training was performed on a self-constructed real dataset, which included 29,020 photographs of wheat seedlings of 29 varieties. Results: The recognition accuracy of this model is 96.85%, which is higher than the other nine mainstream classification models. Although it is only 0.06 higher than the Resnet34 model, the number of parameters is only 1/3 of that. The number of parameters required for MssiapNet is 29.70MB, and the single image Execution time and the single image Delay time are 0.16s and 0.05s. The MssiapNet was visualized, and the heat map showed that the model was superior for wheat seedling variety identification compared with MobileVit-XS. Discussion: The proposed model has a good recognition effect on wheat seedling varieties and uses a few parameters with fast inference speed, which makes it easy to be subsequently deployed on mobile terminals for practical performance testing.

Circle-Seq reveals genomic and disease-specific hallmarks in urinary cell-free extrachromosomal circular DNAs.

BACKGROUND: Extrachromosomal circular deoxyribonucleic acid (eccDNA) is evolving as a valuable biomarker, while little is known about its presence in urine. METHODS: Here, we report the discovery and analysis of urinary cell-free eccDNAs (ucf-eccDNAs) in healthy controls and patients with advanced chronic kidney disease (CKD) by Circle-Seq. RESULTS: Millions of unique ucf-eccDNAs were identified and comprehensively characterised. The ucf-eccDNAs are GC-rich. Most ucf-eccDNAs are less than 1000 bp and are enriched in four pronounced peaks at 207, 358, 553 and 732 bp. Analysis of the genomic distribution of ucf-eccDNAs shows that eccDNAs are found on all chromosomes but enriched on chromosomes 17, 19 and 20 with a high density of protein-coding genes, CpG islands, short interspersed transposable elements (SINEs) and simple repeat elements. Analysis of eccDNA junction sequences further suggests that microhomology and palindromic repeats might be involved in eccDNA formation. The ucf-eccDNAs in CKD patients are significantly higher than those in healthy controls. Moreover, eccDNA with miRNA genes is highly enriched in CKD ucf-eccDNA. CONCLUSIONS: This work discovers and provides the first deep characterisation of ucf-eccDNAs and suggests ucf-eccDNA as a valuable noninnvasive biomarker for urogenital disorder diagnosis and monitoring.

Oxidative phosphorylation promotes vascular calcification in chronic kidney disease.

Metabolism has been reported to associate with the progression of vascular diseases. However, how vascular calcification in chronic kidney disease (CKD) is regulated by metabolic status remains poorly understood. Using a model of 5/6 nephrectomy, we demonstrated that the aortic tissues of CKD mice had a preference for using oxidative phosphorylation (OXPHOS). Both high phosphate and human uremic serum-stimulated vascular smooth muscle cells (VSMCs) had enhanced mitochondrial respiration capacity, while the glycolysis level was not significantly different. Besides, 2-deoxy-d-glucose (2-DG) exacerbated vascular calcification by upregulating OXPHOS. The activity of cytochrome c oxidase (COX) was higher in the aortic tissue of CKD mice than those of sham-operated mice. Moreover, the expression levels of COX15 were higher in CKD patients with aortic arch calcification (AAC) than those without AAC, and the AAC scores were correlated with the expression level of COX15. Suppressing COX sufficiently attenuated vascular calcification. Our findings verify the relationship between OXPHOS and calcification, and may provide potential therapeutic approaches for vascular calcification in CKD.

Short- and medium-term survival of critically ill patients with solid cancer admitted to the intensive care unit.

BACKGROUND: A great increase in the number of patients needs critical care to the intensive care unit (ICU) due to improvements in oncology. The aim of the study was to explore risk factors affecting survival of critically ill patients with solid cancers in ICU. METHODS: The study retrospectively reviewed patients between 2001 and 2012, which were collected by Medical Information Mart for Intensive Care III (MIMIC-III) from the Beth Israel Deaconess Medical Center in Boston, MA, USA. RESULTS: A total of 38,508 adult patients, who were admitted to ICUs and 8,308 (21.6%) were diagnosed as an underlying malignancy; 1,671 and 3,165 adult patients with sold cancer were admitted to surgical ICU (SICU) and medical ICU (MICU), respectively. Patients in SICU had a higher survival rate at the point of 28-, 90-day, and 1-, 3-year than patients in MICU (P<0.001 for all). Multivariate analysis demonstrated that age ≥70, emergency admission, the presence of metastases, Oxford Acute Severity of Illness Score (OASIS) ≥30 and sepsis were independent risk factors affecting 28-day survival in SICU. In MICU, emergency admission, metastatic disease, Sequential Organ Failure Assessment (SOFA) ≥3, Simplified Acute Physiology Score II (SAPS II) ≥39, Acute Physiology Score III (APS III) ≥40, Oxford Acute Severity of Illness Score (OASIS) ≥30, Elixhauser comorbidity index ≥9 and sepsis were independent risk factors for 28-day survival rate. The area under curve (AUC) of the OASIS for predicting ICU mortality was 0.824 [95% confidence interval (CI): 0.805-0.842], which was obviously higher than other scores in SICU. The AUC of the SAPS II for predicting ICU mortality was 0.820 (95% CI: 0.806-0.833), which was slightly higher than other scores in MICU. CONCLUSIONS: Patients with cancer in SICU have longer survival time than patients with cancer in MICU. The prediction of prognosis of critically ill cancer patients can guide treatment and optimize medical resources.

Enhancement of methane production from waste activated sludge using hybrid microbial electrolysis cells-anaerobic digestion (MEC-AD) process - A review.

Hybrid microbial electrolysis cells-anaerobic digestion (MEC-AD) was proved to increase methane productivity and methane yield of waste activated sludge (WAS) by establishing direct interspecies electron transfer method and enriching functional microorganisms. This review first summarized the pretreatment methods of WAS for MEC-AD and then reviewed the reactor configurations, operation parameters, and the economic benefit of MEC-AD. Furthermore, the enhancement mechanisms of MEC-AD were reviewed based on the analysis of thermodynamics and microbial community. It was found that the decrease of hydrogen partial pressure due to the hydrogenotrophic methanogens enriched in cathodic biofilm and direct interspecies electron transfer between exoelectrogens and anode were the core mechanisms for improving acidogenesis, acetogenesis, and methanogenesis. Finally, the potentially technological issues that need to be addressed to increase energy efficiency in large-scale MEC-AD processes were discussed.

[Synergistic Control of Nitrogenous Disinfection By-products and Opportunistic Pathogens in Drinking Water by Iron-Modified Quartz Sand Filtration].

The main function of quartz sand in drinking water treatment has been to remove turbidity, while the microbial effect of its solid-liquid interface has been ignored. In order to solve the limitations of control of the disinfection by-products (DBPs) and opportunistic pathogens (OPs) in common quartz sand, the common quartz sand was modified to iron sand. The maximum DBPs formation potential of typical nitrogenous disinfection by-products (N-DBPs) and carbonaceous disinfection by-products was determined using gas chromatography-ECD. Compared with those of sand, the inhibition effects of halonitromethanes, haloacetamides, and haloacetonitriles by the Fe-sand were increased by 51.51%, 43.66%, and 90.6%, respectively. In addition, the gene copy numbers of Hartmanella vermiformis, Legionella spp., Mycobacterium spp., M. avium, and Naegleria spp. were detected via quantitative qPCR, and the results indicated that the Fe-sand did have a similar significant inhibitory effect on OPs. The Fe-sand had limited ability to enhance the removal of NOM. However, the Fe-sand effectively inhibited the continuous contribution of biofilm to N-DBPs and opportunistic pathogens. The distribution of biofilms on the surface of the Fe-sand filter media was uniform, not likely to fall off, and more stable; however, the suspended biofilms in the effluent were more difficult to aggregate. In addition, the α-helix of the secondary structure in the extracellular protein disappeared in the effluent of the Fe-sand. Therefore, the whole suspended biofilm was easily penetrated by chlorine. The Fe-sand solid-liquid interface did significantly change the microbial community structure and suspended biofilm characteristics, which provides a new concept to ensure the safety of drinking water quality and plays a good theoretical supporting role in the improvement and transformation of the existing process in drinking water treatment plants.

Ultrasound-guided percutaneous transluminal angioplasty for the treatment of cephalic arch stenosis in hemodialysis arteriovenous fistulas.

OBJECTIVES: Cephalic arch stenosis (CAS) is a common cause that leads to the failure of hemodialysis arteriovenous fistulas (AVFs). Patients with CAS are primarily treated with fluoroscopy-guided angioplasty. Here, seven patients with de novo cephalic arch stenosis who underwent office-based UG-PTA were. METHODS: Retrospectively analyzed the total of 321 patients with AVF dysfunction in the nephrology departmnet between July 2017 and October 2018. Among them, seven patients with de novo CAS were included in this study and followed up every 2 months for more than a year. RESULTS: No significant complications were seen from the operations, and the primary patency rates at 6 and 12 months were found to be 100% and 42.8%, respectively. CONCLUSIONS: The office-based UG-PTA is probably safe, effective, and feasible in the management of CAS and can be used as a substitute for fluoroscopy-guided PTA.

Why are Drosophila larvae more sensitive to avermectin than adults?

The insects have different physiological and morphological characteristics in various developmental stages. The difference in the characteristics may be related to the different sensitivity of insects to insecticides. In avermectin resistant strain screening assay, we found that the Drosophila larvae displayed a higher sensitivity to the insecticidal effect of avermectin, compared with adults. In this study, we found that the Drosophila larvae have relatively thicker chitin layer, faster avermectin metabolism and lower P-glycoprotein (P-gp) level, when compared with the adults. Besides, the expression levels of the molecular targets of avermectin, glutamate-gated chloride channel and γ-aminobutyric acid (GABA)-gated chloride channel, are lower in the larval stage than the adult. These results suggested that lower P-gp level in the body especially in brain may be the major reason for the higher sensitivity of Drosophila larvae to the insecticide. In summary, these results shed new light on the concept that different developmental stages of insects display different sensitivity to the same insecticide, which also provided a physiological explanation of the relevant mechanism of the difference of sensitivity of insect at its larval and adult stages to insecticide.

High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease.

Although macrophage infiltration has been proven to increase calcified artery media in chronic kidney disease (CKD) patients, the mechanism by which macrophages are involved in vascular calcification (VC) progression remains unclear. Taking advantage of miRNA-seq, RNA-seq, dual-luciferase reporter assay, qRT-PCR, and arteries from CKD patients as well as CKD mouse models, we identified that high-phosphate-stimulated macrophage-derived exosomes (Mexo-P) suppressed let-7b-5p expression in VSMCs, which further upregulated TGFBR1. Moreover, gain-and-loss-of-function assays were used to determine the regulatory effects and downstream mechanism of let-7b-5p and TGFBR1 on VC. Mechanically, Mexo-P induced VSMC TGFBR1 upregulation by suppressing let-7b-5p, which further amplifies SMAD3/RUNX2 signaling and thereby contributes to VC. Our findings indicate that macrophage-derived exosomes promote CKD-associated VC through the let-7b-5p/TGFBR1 axis in high-phosphate conditions. Our study provides insight into macrophages associated with VC, which might be potential therapeutical targets for VC.