Grey modelling and real-time forecasting for the approximate non-homogeneous white exponential law BDS clock bias sequences.

Precise forecasting of satellite clock bias is crucial for ensuring service quality and enhancing the efficiency of real-time precise point positioning (PPP).The grey model with many benefits is an excellent choice for predicting real-time clock bias. However, the absolute prediction error of a small number of satellites is very high in actual forecasting process. In order to address this issue, a non-homogeneous white exponential law grey model has been constructed specifically for predicting clock bias sequences with non-homogeneous class ratio approximating constants. Considering that any model is difficult to apply to different kinds of satellite clocks and clock bias signals, an adaptive selection strategy for forecast model is proposed to ensure more excellent prediction accuracy. Afterwards, a prediction scenario based on the observed products of the BeiDou satellite navigation system (BDS) is created to demonstrate the effectiveness of the approach described in this article. The outcomes of the method are then compared with those of a single grey model and the ultra-rapid predicted products. The outcomes demonstrate that this strategy's prediction accuracy is less than 1 ns/day and that its prediction uncertainty is much decreased, which may improve data selection for real-time applications like real-time kinematics (RTK) and PPP.

Introducing enzymatic cleavage features and transfer learning realizes accurate peptide half-life prediction across species and organs.

Peptide drugs are becoming star drug agents with high efficiency and selectivity which open up new therapeutic avenues for various diseases. However, the sensitivity to hydrolase and the relatively short half-life have severely hindered their development. In this study, a new generation artificial intelligence-based system for accurate prediction of peptide half-life was proposed, which realized the half-life prediction of both natural and modified peptides and successfully bridged the evaluation possibility between two important species (human, mouse) and two organs (blood, intestine). To achieve this, enzymatic cleavage descriptors were integrated with traditional peptide descriptors to construct a better representation. Then, robust models with accurate performance were established by comparing traditional machine learning and transfer learning, systematically. Results indicated that enzymatic cleavage features could certainly enhance model performance. The deep learning model integrating transfer learning significantly improved predictive accuracy, achieving remarkable R2 values: 0.84 for natural peptides and 0.90 for modified peptides in human blood, 0.984 for natural peptides and 0.93 for modified peptides in mouse blood, and 0.94 for modified peptides in mouse intestine on the test set, respectively. These models not only successfully composed the above-mentioned system but also improved by approximately 15% in terms of correlation compared to related works. This study is expected to provide powerful solutions for peptide half-life evaluation and boost peptide drug development.

Comparison of "framework Shuffling" and "CDR Grafting" in humanization of a PD-1 murine antibody.

Introduction: Humanization is typically adopted to reduce the immunogenicity of murine antibodies generated by hybridoma technology when used in humans. Methods: Two different strategies of antibody humanization are popularly employed, including "complementarity determining region (CDR) grafting" and "framework (FR) shuffling" to humanize a murine antibody against human programmed death-1 (PD-1), XM PD1. In CDR-grafting humanization, the CDRs of XM PD-1, were grafted into the human FR regions with high homology to the murine FR counterparts, and back mutations of key residues were performed to retain the antigen-binding affinities. While in FR-shuffling humanization, a combinatorial library of the six murine CDRs in-frame of XM PD-1 was constructed to a pool of human germline FRs for high-throughput screening for the most favorable variants. We evaluated many aspects which were important during antibody development of the molecules obtained by the two methods, including antibody purity, thermal stability, binding efficacy, predicted humanness, and immunogenicity, along with T cell epitope prediction for the humanized antibodies. Results: While the ideal molecule was not achieved through CDR grafting in this particular instance, FR-shuffling proved successful in identifying a suitable candidate. The study highlights FR-shuffling as an effective complementary approach that potentially increases the success rate of antibody humanization. It is particularly noted for its accessibility to those with a biological rather than a computational background. Discussion: The insights from this comparison are intended to assist other researchers in selecting appropriate humanization strategies for drug development, contributing to broader application and understanding in the field.

Predicting Peptide Permeability Across Diverse Barriers: A Systematic Investigation.

Peptide-based therapeutics hold immense promise for the treatment of various diseases. However, their effectiveness is often hampered by poor cell membrane permeability, hindering targeted intracellular delivery and oral drug development. This study addressed this challenge by introducing a novel graph neural network (GNN) framework and advanced machine learning algorithms to build predictive models for peptide permeability. Our models offer systematic evaluation across diverse peptides (natural, modified, linear and cyclic) and cell lines [Caco-2, Ralph Russ canine kidney (RRCK) and parallel artificial membrane permeability assay (PAMPA)]. The predictive models for linear and cyclic peptides in Caco-2 and RRCK cell lines were constructed for the first time, with an impressive coefficient of determination (R2) of 0.708, 0.484, 0.553, and 0.528 in the test set, respectively. Notably, the GNN framework behaved better in permeability prediction with larger data sets and improved the accuracy of cyclic peptide prediction in the PAMPA cell line. The R2 increased by about 0.32 compared with the reported models. Furthermore, the important molecular structural features that contribute to good permeability were interpreted; the influence of cell lines, peptide modification, and cyclization on permeability were successfully revealed. To facilitate broader use, we deployed these models on the user-friendly KNIME platform (https://github.com/ifyoungnet/PharmPapp). This work provides a rapid and reliable strategy for systematically assessing peptide permeability, aiding researchers in drug delivery optimization, peptide preselection during drug discovery, and potentially the design of targeted peptide-based materials.

Malignant Melanoma of the Sphenoid Sinus: Case Report and Literature Review.

Malignant melanoma originating from the sphenoid sinus is an extremely rare but aggressive tumor of the head and neck. A 57-year-old man had a 1 month history of headache, right trigeminal paresthesias, and upper lid ptosis. Magnetic resonance imaging showed a large mass in the right sphenoid sinus and an invasion of the right cavernous sinus and clivus. The patient underwent endoscopic endonasal transsphenoidal surgery, and pathologically revealed malignant melanoma. One month after the operation, the patient was treated with radiation therapy. Unfortunately, the patient died of distant metastasis 2 years later. Due to its rarity, there is still no effective treatment strategy and no way to assess the progression of malignant melanoma.

Investigating the active chemical constituents and pharmacology of Nanocnide lobata in the treatment of burn and scald injuries.

OBJECTIVE: To identify the most effective fraction of Nanocnide lobata in the treatment of burn and scald injuries and determine its bioactive constituents. METHODS: Chemical identification methods were used to analyze solutions extracted from Nanocnide lobata using petroleum ether, ethyl acetate, n-butanol using a variety of color reactions. The chemical constituents of the extracts were identified by ultra-performance liquid chromatography (UPLC)-mass spectrometry (MS). A total of 60 female mice were randomly divided into the following 6 groups: the petroleum ether extract-treated group; the ethyl acetate extract-treated group; the n-butanol extract-treated group; the model group; the control group; and the positive drug group. The burn/scald model was established using Stevenson's method. At 24 hours after modeling, 0.1 g of the corresponding ointment was evenly applied to the wound in each group. Mice in the model group did not undergo treatment, while those in the control group received 0.1 g of Vaseline. Wound characteristics, including color, secretions, hardness, and swelling, were observed and recorded. Photos were taken and the wound area calculated on the 1st, 5th, 8th, 12th, 15th, 18th and 21st days. Hematoxylin-eosin (HE) staining was utilized to observe the wound tissue of mice on the 7th, 14th, and 21st days. An enzyme-linked immunosorbent assay (ELISA) kit was used to measure the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-10, vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-ß1. RESULTS: The chemical constituents of Nanocnide lobata mainly include volatile oils, coumarins, and lactones. UPLC-MS analysis revealed 39 main compounds in the Nanocnide lobata extract. Among them, ferulic acid, kaempferitrin, caffeic acid, and salicylic acid have been confirmed to exhibit anti-inflammatory and antioxidant activity related to the treatment of burns and scalds. HE staining revealed a gradual decrease in the number of inflammatory cells and healing of the wounds with increasing time after Nanocnide lobata extract administration. Compared with the model group, the petroleum ether extract-treated group showed significant differences in the levels of TNF-α (161.67±4.93, 106.33±3.21, 77.67±4.04 pg/mL) and IL-10 (291.77±4.93, 185.09±9.54, 141.33±1.53 pg/mL) on the 7th, 14th, and 21st days; a significant difference in the content of TGF-ß1 (75.68±3.06 pg/mL) on the 21st day; and a significant difference in the level of VEGF (266.67±4.73, 311.33±10.50 pg/mL) on the 7th and 14th days respectively. CONCLUSION: Petroleum ether Nanocnide lobata extract and the volatile oil compounds of Nanocnide lobata might be effective drugs in the treatment of burn and scald injuries, as they exhibited a protective effect on burns and scalds by reducing the expression of TNF-α, IL-10 and TGF-ß1 and increasing the expression of VEGF. In addition, these compounds may also exert pharmacological effects that promote wound tissue repair, accelerate wound healing, and reduce scar tissue proliferation, inflammation and pain.

Comparison of supraorbital keyhole approach and extended transsphenoidal approach in endoscopic surgery for tuberculum sellae meningioma: A case series.

The endoscope-assisted supraorbital keyhole approach and extended transsphenoidal approach have been widely used in the treatment of tuberculum sellae meningiomas (TSMs). The purpose of the present study was to retrospectively analyze and compare the characteristics and efficacy of the two surgical approaches under the endoscope in the resection of TSMs. In the present study, 36 patients with TSMs who underwent surgical resection are presented, including one group of 17 cases with an endoscopic supraorbital keyhole approach and the other group of 19 cases with an endoscopic extended transsphenoidal approach. The clinical characteristics, diagnosis, treatment process and treatment effect of the two groups were analyzed retrospectively, and the two surgical approaches were also compared. The gross total resection rates of the two groups were similar, reaching 94.5 and 94.7%, respectively. The postoperative visual acuity recovery showed that in the endoscopic supraorbital keyhole approach group, 23 eyes were improved, 8 eyes were maintained and 3 eyes deteriorated, and the visual recovery was 67.6%. In the endoscopic extended transsphenoidal approach group, 32 eyes were improved, 4 eyes were maintained and 2 eyes deteriorated, and the visual recovery was 84.2%. In the supraorbital keyhole approach group, there was no cerebrospinal fluid leakage, while in the extended transsphenoidal approach group, cerebrospinal fluid leakage occurred in 3 cases (15.8%). In these two groups, no tumor recurrence was revealed during the follow-up of ~5 years. Both the endoscope-assisted supraorbital keyhole approach and the extended transsphenoidal approach were effective and safe. The endoscopic supraorbital keyhole approach treated TSMs with lateral extension, but it was not enough to protect the optic nerve. The endoscopic extended transsphenoidal approach protected the optic nerve, but the risk of cerebrospinal fluid leakage was increased. In conclusion, these two surgical methods have their own advantages and limitations.

Endoscopic endonasal surgery for non-invasive pituitary neuroendocrinology tumors with incomplete pseudocapsule.

Background: Pituitary neuroendocrinology tumors (PitNETs) with pseudocapsule can be effectively removed by the pseudocapsule-based extracapsular resection technique. In the areas without pseudocapsule, the tumor cells can spread into the adjacent tissues at the cellular level, which brings a great challenge to achieving total tumor resection. Methods: Our surgical strategy for PitNETs with an incomplete pseudocapsule is to combine the pseudocapsule-based extracapsular resection technique with the intensive excision technique for the removal of the tumor. Specifically, the pseudocapsule-based extracapsular resection technique is applied in the areas with pseudocapsule, while in the areas without pseudocapsule, the intensive excision technique bounded by adjacent normal structures is adopted. Moreover, a pathological examination was performed to determine the situations of pseudocapsule and tumor cell remnant. Results: All growth hormone-secreting PitNETs achieved biochemical remission after surgery. There was no deterioration of pituitary functions postoperatively, and the preoperative hypopituitarism had improved in all patients postoperatively. In total, two cases suffered a transient diabetes insipidus, and intraoperative cerebrospinal fluid leakage was observed in two cases but no postoperative cerebrospinal fluid leakage in all cases. There was no recurrence during the follow-up. The fragmental pseudocapsule and small tumor remnants were found in the majority of suspicious tissues by histological staining. Conclusion: The effectiveness and safety of the surgical strategy were preliminarily explored for removing PitNETs without incomplete pseudocapsules. In overview, the pseudocapsule-based extracapsular resection technique is applied in areas with pseudocapsule, while the intensive excision bounded by adjacent normal structures is adopted in other areas.

Successful multidisciplinary therapy for a patient with liver metastasis from ascending colon adenocarcinoma: A case report and review of literature.

BACKGROUND: Liver metastasis is the most common form of distant metastasis in colorectal cancer, and the only possible curative treatment for patients with colorectal liver metastases (CRLM) is hepatectomy. However, approximately 25% of patients with CRLM have indications for liver resection at the initial diagnosis. Strategies aimed at downstaging large or multifocal tumors to enable curative resection are appealing. CASE SUMMARY: A 42-year-old man was diagnosed with ascending colon cancer and liver metastases. Due to the huge lesion size and compression of the right portal vein, the liver metastases were initially diagnosed as unresectable lesions. The patient was treated with preoperative transcatheter arterial chemoembolization (TACE) consisting of 5-fluorouracil/Leucovorin/oxaliplatin/Endostar®. After four courses, radical right-sided colectomy and ileum transverse colon anastomosis were performed. Postoperatively, the pathological analysis revealed moderately differentiated adenocarcinoma with necrosis and negative margins. Thereafter, S7/S8 partial hepatectomy was performed after two courses of neoadjuvant chemotherapy. Pathological examination of the resected specimen revealed a pathologically complete response (pCR). Intrahepatic recurrence was detected more than two months after the operation, and the patient was then treated with TACE consisting of irinotecan/Leucovorin/fluorouracil therapy plus Endostar®. Subsequently, the patient was treated with a γ-knife to enhance local control. Notably, a pCR was reached, and the patient's overall survival time was > 9 years. CONCLUSION: Multidisciplinary treatment can promote the conversion of initially unresectable colorectal liver metastasis and facilitate complete pathological remission of liver lesions.

Pure endoscopic minimally invasive surgery with a non­expandable tubular retractor for intradural extramedullary spinal tumors.

Minimally invasive spinal surgery (MISS) for intradural extramedullary (IDEM) spinal tumors is a safe and effective surgical strategy. Currently, various tubular retractors are widely used in the MISS of IDEM spinal tumors, primarily relying on microscopic visualization. To the best of the authors' knowledge, there is no report of pure endoscopic surgery with parallel non-expandable tubular retractors for IDEM spinal lesions. The present study reports a case series of IDEM spinal tumors that were treated via pure endoscopic MISS with a parallel non-expandable tubular retractor. The extent of tumor resection was evaluated by comparing preoperative and postoperative magnetic resonance imaging (MRI). The initial and follow-up clinical conditions were assessed according to the visual analog scale for pain and the modified McCormick scale for neurological status. Postoperative MRI demonstrated that all cases had achieved a gross total resection. After the operation, the clinical symptoms of all patients were significantly improved and there were no serious postoperative complications. At the initial follow-up, the pain experienced by the patients was significantly reduced or had even disappeared, and the neurological deficit was improved by at least one grade on the modified McCormick scale. The present report indicates that pure endoscopic MISS with a parallel non-expandable tubular retractor may be an effective and safe surgical strategy for IDEM spinal tumor resection.

A radiobiological perspective on radioresistance or/and radiosensitivity of head and neck squamous cell carcinoma.

Background: This article aimed to compile and summarize clinically relevant literature in radiation therapy, and to discuss the potential in radioresistant and radiosensitive head and neck cancer. Study Design: Narrative review. Materials and methods: Google Scholar, PubMed and the Cochrane Library were retrieved using combined key words such as "radiotherapy" and "head and neck cancer". Search strings additionally queried were "radioresistant", "radiosensitive", "head and neck region", "squamous cell carcinoma", in combination with Boolean Operators 'AND' and 'OR'. Subsequently, the resulting publications were included for review of the full text. Results: Radiotherapeutic response currently in clinical observation referred to HNSCC scoping were selected into this review. The compiled mechanisms were then detailed concerning on the clinical significance, biological characteristics, and molecular function. Conclusions: Brachytherapy or/and external-beam radiotherapy are crucial for treating HNSCC, especially the early stage patients, but in patients with locally advanced tumors, their outcome with radiation therapy is poor due to obvious radioresistance. The curative effects mainly depend on the response of radiation therapy, so an updated review is needed to optimize further applications in HNSCC radiotherapy.

Enzyme-linked immunosorbent assays for quantification of MMAE-conjugated ADCs and total antibodies in cynomolgus monkey sera.

Antibody-drug conjugates (ADCs) are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies. In this study, we report the generation of a monoclonal antibody against monomethyl auristatin E (MMAE) and the development, validation, and application of sensitive and high-throughput enzyme-linked immunosorbent assays (ELISA) to measure the concentrations of MMAE-conjugated ADCs and total antibodies (tAb, antibodies in ADC plus unconjugated antibodies) in cynomolgus monkey sera. These assays were successfully applied to in vitro plasma stability and pharmacokinetic (PK) studies of SMADC001, an MMAE-conjugated ADC against trophoblast cell surface antigen 2 (TROP-2). The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit, Lys (m-dPEG24)-Cit, and Val-Cit linkers. The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation between serum concentrations and the OD450 values, with R 2 at 1.000, and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL, respectively; the intra- and inter-assay accuracy bias% ranged from -12.2% to -5.2%, precision ranged from -12.4% to -1.4%, and the relative standard deviation (RSD) was less than 6.6% and 8.7%, respectively. The total error was less than 20.4%. The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters, which suggested that these can be applied to quantify MMAE-conjugated ADCs, as well as in PK studies. Furthermore, these assays can be easily adopted for development of other similar immunoassays.

Case report: Fully endoscopic microvascular decompression for glossopharyngeal neuralgia.

With the advances in endoscopic technology, endoscopy is widely used in many neurosurgical procedures, such as microvascular decompression, which is an effective method to treat glossopharyngeal neuralgia, trigeminal neuralgia, and facial spasm. The purpose of this study was to determine the efficacy of fully endoscopic microvascular decompression in the treatment of glossopharyngeal neuralgia. We managed a patient with glossopharyngeal neuralgia in our department, whose main clinical manifestation was recurrent left ear and facial pain for 3 years. The patient underwent a fully endoscopic microvascular decompression. The pain in the left ear and face was significantly relieved postoperatively, and there was no recurrence at the 6-month follow-up evaluation. We describe a case of glossopharyngeal neuralgia that was successfully treated by fully endoscopic microvascular decompression, which showed that endoscopy has advantages in microvascular decompression, and fully endoscopic microvascular decompression is an effective method for glossopharyngeal neuralgia.

Case report: Fully endoscopic microvascular decompression for trigeminal neuralgia.

Microvascular decompression is safe, effective, and micro-invasive. Due to these advantages, it has become the mainstream treatment for trigeminal neuralgia, glossopharyngeal neuralgia, and hemifacial spasm. Initially, microvascular decompression was performed under a microscope, which limited the light source and visualization capabilities. With the development of endoscopic technology, the endoscope has been used in microvascular decompression, which further improved the visualization range and light source properties. The purpose of the present study was to investigate the efficacy of fully endoscopic microvascular decompression for the treatment of trigeminal neuralgia. In total, three patients with trigeminal neuralgia who underwent fully endoscopic microvascular decompression were evaluated. After surgery, the facial pain of all patients was significantly relieved. In addition, there were no obvious postoperative complications and no recurrence after 6 months of follow-up. These excellent surgical outcomes indicate that fully endoscopic microvascular decompression is an effective and safe method for the treatment of trigeminal neuralgia. Furthermore, it also shows that the endoscope presents advantages for use in microvascular decompression.

Enzyme-linked immunosorbent assays for quantification of MMMAE-conjugated ADCs and total antibodies in cynomolgus monkey sera / 药物分析学报

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

Optical fiber time transmission technology based on a double-fiber round-trip method.

In this paper, an optical fiber time transmission technology based on a double-fiber round-trip method is provided. In the system, the one-way transmission delay from the master station to the slave station can be calculated directly through the measurement of three time interval counters and their ratio relationship. The method eliminates the influence of fiber length expansion and round-trip transmission delay fluctuation, which is caused by ambient temperature change. The master and slave stations are connected by 100 km and 80 km optical fibers, respectively, and the temperature of the optical fiber link varies from -20∘C to 40°C. Compared with the single-fiber round-trip method, the time interval error of a double-fiber round-trip method is reduced from 1.4 ns to 80 ps when the wavelength is 1310-1550 nm, and from 320 to 80 ps when the wavelength is 1490-1550 nm.

Mitophagy Improves Ethanol Tolerance in Yeast: Regulation by Mitochondrial Reactive Oxygen Species in Saccharomyces cerevisiae.

Ethanol often accumulates during the process of wine fermentation, and mitophagy has critical role in ethanol output. However, the relationship between mitophagy and ethanol stress is still unclear. In this study, the expression of ATG11 and ATG32 genes exposed to ethanol stress was accessed by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The result indicated that ethanol stress induced expression of the ATG11 and ATG32 genes. The colony sizes and the alcohol yield of atg11 and atg32 were also smaller and lower than those of wild type strain under ethanol whereas the mortality of mutants is higher. Furthermore, compared with wild type, the membrane integrity and the mitochondrial membrane potential of atg11 and atg32 exhibited greater damage following ethanol stress. In addition, a greater proportion of mutant cells were arrested at the G1/G0 cell cycle. There was more aggregation of peroxide hydrogen (H2O2) and superoxide anion (O2•-) in mutants. These changes in H2O2 and O2•- in yeasts were altered by reductants or inhibitors of scavenging enzyme by means of regulating the expression of ATG11 and ATG32 genes. Inhibitors of the mitochondrial electron transport chain (mtETC) also increased production of H2O2 and O2•- by enhancing expression of the ATG11 and ATG32 genes. Further results showed that activator or inhibitor of autophagy also activated or inhibited mitophagy by altering production of H2O2 and O2•. Therefore, ethanol stress induces mitophagy which improves yeast the tolerance to ethanol and the level of mitophagy during ethanol stress is regulated by ROS derived from mtETC.

Secreted Monocyte miR-27a, via Mesenteric Arterial Mas Receptor-eNOS Pathway, Causes Hypertension.

BACKGROUND: Essential hypertension is associated with increased plasma concentrations of extracellular vesicles (EVs). We aimed to determine the role of monocyte miR-27a in EVs on arterial Mas receptor expression, and its involvement in the pathogenesis of hypertension. METHODS: THP-1 cells were transfected with miR-27a mimic and miR-27a inhibitor, and EVs were collected. Mas receptor expression and endothelial nitric oxide synthase (eNOS) phosphorylation were determined by immunoblotting. Sprague-Dawley (SD) rats received EVs via tail-vein injection. Blood pressure (BP) was measured with the tail-cuff method. The vasodilatory response of mesenteric arteries was measured using a small vessel myograph. RESULTS: EVs from THP-1 cells increased rat BP by impairing Ang-(1-7)-mediated vasodilation in mesenteric arteries, which was further exaggerated by EVs from lipopolysaccharides-treated THP-1 cells. As the receptor and key signaling of Ang-(1-7), next experiments found that Mas receptor expression and eNOS phosphorylation were decreased in mesenteric arteries from EVs-treated SD rats. Screening studies found miR-27a in EVs may be involved in this process. Through transfection with miR-27a inhibitor or miR-27a mimic, we found that miR-27a downregulates Mas receptor expression in endothelial cells. Injection of EVs from miR-27a-transfected HEK-293 cells decreased Mas receptor and eNOS phosphorylation in mesenteric arteries, impaired Ang-(1-7)-mediated vasodilation and increased BP. Earlier effects were reversed using cells with downregulation of miR-27 in EVs. CONCLUSIONS: Monocyte miR-27a in EVs decreases Mas receptor expression and eNOS phosphorylation in endothelium, impairs Ang-(1-7)-mediated vasodilation, and causes hypertension. Understanding the contributions of EVs in the pathogenesis of hypertension may facilitate their use as a diagnostic biomarker.