A facile and smart strategy to enhance bone regeneration with efficient vitamin D3 delivery through sterosome technology.

The spontaneous healing of critical-sized bone defects is often limited, posing an increased risk of complications and suboptimal outcomes. Osteogenesis, a complex process central to bone formation, relies significantly on the pivotal role of osteoblasts. Despite the well-established osteogenic properties of vitamin D3 (VD3), its lipophilic nature confines administration to oral or muscle injection routes. Therefore, a strategic therapeutic approach involves designing a multifunctional carrier to enhance efficacy, potentially incorporating it into the delivery system. Here, we introduce an innovative sterosome-based delivery system, utilizing palmitic acid (PA) and VD3, aimed at promoting osteogenic differentiation and facilitating post-defect bone regeneration. The delivery system exhibited robust physical characteristics, including excellent stability, loading efficiency, sustained drug release and high cellular uptake efficiency. Furthermore, comprehensive investigations demonstrated outstanding biocompatibility and osteogenic potential in both 2D and 3D in vitro settings. A critical-sized calvarial defect model in mice recapitulated the notable osteogenic effects of the sterosomes in vivo. Collectively, our research proposes a clinically applicable strategy for bone healing, leveraging PA/VD3 sterosomes as an efficient carrier to deliver VD3 and enhance bone regenerative effects.

Telitacicept Treatment Refractory Lupus Nephritis: A Case Report.

Introduction: Refractory lupus nephritis (LN) causes kidney disease progression and increases the risk of loss of renal function. Due to the high specificity and few side effects of biological agents, they are recommended for the treatment of systemic lupus erythematosus. There are few data on telitacicept for the treatment of refractory LN. Case Presentation: Here, we report the efficacy and safety of telitacicept in the treatment of refractory LN in a 25-year-old female patient. This patient with refractory lupus developed Pneumocystis jirovecii pneumonia while using multitargeted therapy, and the patient's urine protein was rapidly relieved after telitacicept combination with low-dose mycophenolate mofetil (MMF). Conclusion: This result suggests that telitacicept has a positive effect on refractory LN with no significant side effects. Further reports and a registry are necessary to confirm that telitacicept with low-dose MMF should be preferred in refractory LN.

Effect of a Simulated Coal Mine Environment on Polyurethane Grouting Material and a Proposed Polyurethane Strengthening Method.

When it comes to grouting in coal mines, polyurethane (PU) is often utilized. However, it is of vital importance to consistently improve the mineral PU, considering the significant amount of environmental deterioration to which it is prone. Laboratory experiments were used to model various coal mine conditions. Additionally, a workable technique for PU strengthening using ultrasonic waves was proposed. Compression tests and scanning electron microscopy (SEM) were used to describe the PU-gangue material's induration characteristics. The results showed that ultrasound has a positive impact on PU's mechanical strength. The final strength of the PU was significantly impacted by the size of the coal gangue particles, the amount of dust, and the amount of water. The induration made of gangue and PU with the same mass but differing particle sizes was noticeably different in its compressive strength. The strengthening mechanism showed that the average size of the rigid foam after the ultrasound treatment was smaller, and the 'honeycomb'-structured space in the inner section was more compact, resulting in the rigid PU foam having a higher compressive strength after ultrasound treatment. Furthermore, the dust content and water content of coal mines need to be controlled within a specific range to ensure the effective use of PU grouting materials.

Exploring the translational potential of PLGA nanoparticles for intra-articular rapamycin delivery in osteoarthritis therapy.

Osteoarthritis (OA) is a prevalent joint disease that affects all the tissues within the joint and currently lacks disease-modifying treatments in clinical practice. Despite the potential of rapamycin for OA disease alleviation, its clinical application is hindered by the challenge of achieving therapeutic concentrations, which necessitates multiple injections per week. To address this issue, rapamycin was loaded into poly(lactic-co-glycolic acid) nanoparticles (RNPs), which are nontoxic, have a high encapsulation efficiency and exhibit sustained release properties for OA treatment. The RNPs were found to promote chondrogenic differentiation of ATDC5 cells and prevent senescence caused by oxidative stress in primary mouse articular chondrocytes. Moreover, RNPs were capable to alleviate metabolism homeostatic imbalance of primary mouse articular chondrocytes in both monolayer and 3D cultures under inflammatory or oxidative stress. In the mouse destabilization of the medial meniscus (DMM) model, intra-articular injection of RNPs effectively mitigated joint cartilage destruction, osteophyte formation, chondrocytes hypertrophy, synovial inflammation, and pain. Our study demonstrates the feasibility of using RNPs as a potential clinically translational therapy to prevent the progression of post-traumatic OA.

Main-Chain Cationic Bile Acid Polymers Mimicking Facially Amphiphilic Antimicrobial Peptides.

Antibiotic-resistant bacterial infections have led to an increased demand for antibacterial agents that do not contribute to antimicrobial resistance. Antimicrobial peptides (AMPs) with the facially amphiphilic structures have demonstrated remarkable effectiveness, including the ability to suppress antibiotic resistance during bacterial treatment. Herein, inspired by the facially amphiphilic structure of AMPs, the facially amphiphilic skeletons of bile acids (BAs) are utilized as building blocks to create a main-chain cationic bile acid polymer (MCBAP) with macromolecular facial amphiphilicity via polycondensation and a subsequent quaternization. The optimal MCBAP displays an effective activity against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli, fast killing efficacy, superior bactericidal stability in vitro, and potent anti-infectious performance in vivo using the MRSA-infected wound model. MCBAP shows the low possibility to develop drug-resistant bacteria after repeated exposure, which may ascribe to the macromolecular facial amphiphilicity promoting bacterial membrane disruption and the generation of reactive oxygen species. The easy synthesis and low cost of MCBAP, the superior antimicrobial performance, and the therapeutic potential in treating MRSA infection altogether demonstrate that BAs are a promising group of building blocks to mimic the facially amphiphilic structure of AMPs in treating MRSA infection and alleviating antibiotic resistance.

Validation of metagenomic next-generation sequencing of bronchoalveolar lavage fluid for diagnosis of suspected pulmonary infections in patients with systemic autoimmune rheumatic diseases receiving immunosuppressant therapy.

Background: The accuracy and sensitivity of conventional microbiological tests (CMTs) are insufficient to identify opportunistic pathogens in patients with systemic autoimmune rheumatic diseases (SARDs). The study aimed to assess the usefulness of metagenomic next-generation sequencing (mNGS) vs. CMTs for the diagnosis of pulmonary infections in patients with SARDs receiving immunosuppressant therapy. Methods: The medical records of 40 patients with pulmonary infections and SARDs treated with immunosuppressants or corticosteroids were reviewed retrospectively. Bronchoalveolar lavage fluid (BALF) samples were collected from all patients and examined by mNGS and CMTs. Diagnostic values of the CMTs and mNGS were compared with the clinical composite diagnosis as the reference standard. Results: Of the 40 patients included for analysis, 37 (92.5%) were diagnosed with pulmonary infections and 3 (7.5%) with non-infectious diseases, of which two were considered primary diseases and one an asthma attack. In total, 15 pathogens (7 bacteria, 5 fungi, and 3 viruses) were detected by CMTs as compared to 58 (36 bacteria, 12 fungi, and 10 viruses) by mNGS. Diagnostic accuracy of mNGS was superior to that of the CMTs for the detection of co-infections with bacteria and fungi (95 vs. 53%, respectively, p < 0.01), and for the detection of single infections with fungi (97.5 vs. 55%, respectively, p < 0.01). Of the 31 patients diagnosed with co-infections, 4 (12.9%) were positive for two pathogens and 27 (87.1%) for three or more. The detection rate of co-infection was significantly higher for mNGS than CMTs (95 vs. 16%, respectively, p < 0.01). Conclusion: The accuracy of mNGS was superior to that of the CMTs for the diagnosis of pulmonary infections in patients with SARDs treated with immunosuppressants. The rapid diagnosis by mNGS can ensure timely adjustment of treatment regimens to improve diagnosis and outcomes.

Liverwort bHLH transcription factors and the origin of stomata in plants.

Stomata are distributed in nearly all major groups of land plants, with the only exception being liverworts. Instead of having stomata on sporophytes, many complex thalloid liverworts possess air pores in their gametophytes. At present, whether stomata in land plants are derived from a common origin remains under debate.1,2,3 In Arabidopsis thaliana, a core regulatory module for stomatal development comprises members of the bHLH transcription factor (TF) family, including AtSPCH, AtMUTE, and AtFAMA of subfamily Ia and AtSCRM1/2 of subfamily IIIb. Specifically, AtSPCH, AtMUTE, and AtFAMA each successively form heterodimers with AtSCRM1/2, which in turn regulate the entry, division, and differentiation of stomatal lineages.4,5,6,7 In the moss Physcomitrium patens, two SMF (SPCH, MUTE and FAMA) orthologs have been characterized, one of which is functionally conserved in regulating stomatal development.8,9 We here provide experimental evidence that orthologous bHLH TFs in the liverwort Marchantia polymorpha affect air pore spacing as well as the development of the epidermis and gametangiophores. We found that the bHLH Ia and IIIb heterodimeric module is highly conserved in plants. Genetic complementation experiments showed that liverwort SCRM and SMF genes weakly restored a stomata phenotype in atscrm1, atmute, and atfama mutant backgrounds in A. thaliana. In addition, homologs of stomatal development regulators FLP and MYB88 also exist in liverworts and weakly rescued the stomatal phenotype of atflp/myb88 double mutant. These results provide evidence not only for a common origin of all stomata in extant plants but also for relatively simple stomata in the ancestral plant.

Flot2 acts as a novel mediator of podocyte injury in proteinuric kidney disease.

Podocyte injury is a common hallmark of chronic kidney disease (CKD). The podocin-nephrin complex localized in lipid rafts of podocyte is vital to reduce podocyte injury and proteinuria, however, the mechanism underlying its localization remains unclear. This study uncovers an important role of Flot2 in stabilizing the podocin-nephrin complex localized in lipid rafts. We first confirmed that Flot2 was expressed in podocyte and demenstrated that podocyte-specific Flot2 deletion worsen albuminuria, podocyte injury and glomerular pathology in LPS/ADR-induced nephropathy mouse models. Meanwhile, podocyte injury, albuminuria and pathologic aberrance were prevented in podocyte-specific Flot2 overexpression transgenic mice when challenged with LPS or ADR. Further found that Flot2 was vital to recruit podocin and nephrin into rafts and ameliorated podocyte injury. Flot2 and podocin directly interacted with each other via their SPFH domain. Meanwhile, we also showed that Flot-2 is a direct target of Krüppel-like factor (KLF15). Importanly, we observed that Flot2 was downregulated in renal biopsies from patients with podocytopathies and its expression negatively correlated with proteinuria and positively correlated with eGFR, indicating that Flot2 may be a novel therapeutic target for proteinuric kidney disease.

Intrinsic antibacterial and osteoinductive sterosomes promote infected bone healing.

Open fractures and internal fixation implants are often accompanied by bacterial infection, leading to osteomyelitis, characterized by intractable bone infection and sequestrum formation, and can result in lifelong disability or fatal sepsis. As common clinical treatment strategies, high-dose antibiotic application and autologous bone transplantation face the risk of recurrence and donor site injury. Herein, we designed and prepared a novel drug delivery system by rational selection of the antibacterial single-chain amphiphile (cetylpyridinium chloride, CPC) and osteoinductive sterol (20S-hydroxycholesterol, Oxy) to formulate CPC/Oxy sterosomes. We demonstrate their excellent biocompatibility and antibacterial ability through 2D and 3D settings in vitro. In addition, the osteogenic differentiation of bone marrow mesenchymal stem cells was investigated in cell monolayers and a hydrogel environment. Moreover, a rat infected critical-sized calvarial defect model was employed to illustrate the effects of antibacterial and osteogenic CPC/Oxy sterosomes in vivo. Our results showed that CPC/Oxy sterosomes not only exterminated bacterial infections, but also enhanced calvarial healing without additional antibiotics, bone formation promoters or exogenous cells. This research provides a promising and effective multifunctional sterosomal platform for the treatment of infected bone defects, with the potential to be combined with therapeutic genes, and small molecule drugs.

Parallel evolution of two AIM24 protein subfamilies and their conserved functions in ER stress tolerance in land plants.

Despite decades of efforts in genome sequencing and functional characterization, some important protein families remain poorly understood. In this study, we report the classification, evolution, and functions of the largely uncharacterized AIM24 protein family in plants, including the identification of a novel subfamily. We show that two AIM24 subfamilies (AIM24-A and AIM24-B) are commonly distributed in major plant groups. These two subfamilies not only have modest sequence similarities and different gene structures but also are of independent bacterial ancestry. We performed comparative functional investigations on the two AIM24 subfamilies using three model plants: the moss Physcomitrium patens, the liverwort Marchantia polymorpha, and the flowering plant Arabidopsis thaliana. Intriguingly, despite their significant differences in sequence and gene structure, both AIM24 subfamilies are involved in ER stress tolerance and the unfolded protein response (UPR). In addition, transformation of the AIM24-A gene from P. patens into the AIM24-B null mutant of A. thaliana could at least partially rescue ER stress tolerance and the UPR. We also discuss the role of AIM24 genes in plant development and other cellular activities. This study provides a unique example of parallel evolution in molecular functions and can serve as a foundation for further investigation of the AIM24 family in plants.

Somatic mutations during rapid clonal domestication of Populus alba var. pyramidalis.

For many clonally propagated species, the accumulation of somatic mutations is the principal driver of declines in yield and quality. However, somatic mutations may also promote genetic diversification. Thus, elucidating somatic mutation rates and patterns is important to understand the genetic basis undergirding the emergence of commercially valuable traits and developmental processes. In this study, we studied the effect of short-time clonal domestication of Populus alba var. pyramidalis, a species that has been propagated by cutting for the last 67 years. We found that: (1) the somatic mutation rate for P. alba var. pyramidalis is 9.24 × 10-9, which is higher than rates observed in related species; (2) there were more mutations near heterozygous regions, and a larger proportion of CpG and CHG sites were associated with somatic mutations, which may be related to the blocking of DNA repair by methylation; and (3) deleterious mutations were not shared by multiple individuals, and all occurred in heterozygous states, demonstrating the strong selective pressures that act against deleterious mutations. Taken together, the results of our study provide a global view of somatic mutation that will aid efforts to understand the genetic basis of commercially valuable traits and to improve clonally breeding species.

The Cycas genome and the early evolution of seed plants.

Cycads represent one of the most ancient lineages of living seed plants. Identifying genomic features uniquely shared by cycads and other extant seed plants, but not non-seed-producing plants, may shed light on the origin of key innovations, as well as the early diversification of seed plants. Here, we report the 10.5-Gb reference genome of Cycas panzhihuaensis, complemented by the transcriptomes of 339 cycad species. Nuclear and plastid phylogenomic analyses strongly suggest that cycads and Ginkgo form a clade sister to all other living gymnosperms, in contrast to mitochondrial data, which place cycads alone in this position. We found evidence for an ancient whole-genome duplication in the common ancestor of extant gymnosperms. The Cycas genome contains four homologues of the fitD gene family that were likely acquired via horizontal gene transfer from fungi, and these genes confer herbivore resistance in cycads. The male-specific region of the Y chromosome of C. panzhihuaensis contains a MADS-box transcription factor expressed exclusively in male cones that is similar to a system reported in Ginkgo, suggesting that a sex determination mechanism controlled by MADS-box genes may have originated in the common ancestor of cycads and Ginkgo. The C. panzhihuaensis genome provides an important new resource of broad utility for biologists.

Effects of predilution hemodiafiltration-induced intradialytic left ventricular systolic dysfunction compared to high-flux hemodialysis.

PURPOSE: Hemodialysis (HD)-induced myocardial ischemia may lead to left ventricular (LV) dysfunction after normal perfusion returns. This study aimed to assess the short-term influence of predilution hemodiafiltration (HDF) and high-flux hemodialysis (HD) on intradialytic LV systolic function, and hematologic and biochemical risk factors. METHODS: This cross-over clinical trial enrolled 38 dialysis patients who were randomized equally into one of two treatment sequences: 1-week predilution HDF treatment followed by 1-week high-flux HD, and vice versa. LV systolic function was assessed by echocardiography before and after the mid-week dialysis session. Hematologic and biochemical parameters were also measured. Replacement fluid volume for all patients was 24.2 ± 1.3 L/session. RESULTS: Subjects' mean age was 53.3 ± 11.8 years and 24 were males. LV ejection fraction (LVEF) decreased from 61.31 ± 9.96 to 59.03 ± 10.37% after HDF (P = 0.016), and increased from 61.69 ± 11.08 to 62.72 ± 11.26% after high-flux HD (P = 0.190). Average of peak LV systolic tissue velocity increased from 6.74 ± 1.23 to 6.98 ± 1.56 cm/s after HDF (P = 0.246), and increased from 6.71 ± 1.34 to 7.44 ± 2.18 cm/s (P = 0.039) after high-flux HD. The ratio between peak LV early diastolic mitral inflow velocity and peak LV early diastolic tissue velocity (E/E') at the septal mitral annulus decreased to 18 ± 9 from 21 ± 11 (P = 0.147) after HDF, and to 17 ± 8 from 20 ± 8 (P = 0.037) after high-flux HD. ß2-microglobulin was reduced more during HDF than during high-flux HD (70.7 ± 5.3 vs. 67.7 ± 3.9%, P < 0.001). CONCLUSION: Predilution HDF decreases intradialytic LV systolic function more than high-flux HD. Randomized controlled trials with a larger multi-center sample and long-term follow-up are required to demonstrate the potential mechanisms of predilution HDF effecting on ventricular function.

Major episodes of horizontal gene transfer drove the evolution of land plants.

How horizontal gene transfer (HGT) has contributed to the evolution of animals and plants remains a major puzzle. Despite recent progress, defining the overall scale and pattern of HGT events in land plants has been largely elusive. In this study, we performed systematic analyses for acquired genes in different plant groups and throughout land plant evolution. We found that relatively recent HGT events occurred in charophytes and all major land plant groups, but their frequency declined rapidly in seed plants. Two major episodes of HGT events occurred in land plant evolution, corresponding to the early evolution of streptophytes and the origin of land plants, respectively. Importantly, a vast majority of the genes acquired in the two episodes have been retained in descendant groups, affecting numerous activities and processes of land plants. We analyzed some of the acquired genes involved in stress responses, ion and metabolite transport, growth and development, and specialized metabolism, and further assessed the cumulative effects of HGT in land plants.

The maize single-nucleus transcriptome comprehensively describes signaling networks governing movement and development of grass stomata.

The unique morphology of grass stomata enables rapid responses to environmental changes. Deciphering the basis for these responses is critical for improving food security. We have developed a planta platform of single-nucleus RNA-sequencing by combined fluorescence-activated nuclei flow sorting, and used it to identify cell types in mature and developing stomata from 33,098 nuclei of the maize epidermis-enriched tissues. Guard cells (GCs) and subsidiary cells (SCs) displayed differential expression of genes, besides those encoding transporters, involved in the abscisic acid, CO2, Ca2+, starch metabolism, and blue light signaling pathways, implicating coordinated signal integration in speedy stomatal responses, and of genes affecting cell wall plasticity, implying a more sophisticated relationship between GCs and SCs in stomatal development and dumbbell-shaped guard cell formation. The trajectory of stomatal development identified in young tissues, and by comparison to the bulk RNA-seq data of the MUTE defective mutant in stomatal development, confirmed known features, and shed light on key participants in stomatal development. Our study provides a valuable, comprehensive, and fundamental foundation for further insights into grass stomatal function.

Roxadustat Improves Erythropoietin Antibody-Mediated Pure Red Cell Aplasia in a Patient with Hemodialysis.

Anemia is a common complication of chronic kidney disease (CKD). Recombinant human erythropoietin (rHu-EPO) is used extensively in patients with CKD. However, anti-erythropoietin (anti-EPO) antibody has been reported during rHu-EPO treatment, which causes pure red cell aplasia (PRCA). We presented a case of 75-year-old man, who underwent hemodialysis for 2 years. He developed PRCA during rHu-EPO treatment. The rHu-EPO was immediately discontinued, and the patient was given roxadustat treatment. After 6 months of roxadustat treatment, the anti-EPO antibody was disappeared, and hemoglobin recovered normal range. The results suggest that roxadustat can be used to treat patients with anti-EPO antibody-mediated PRCA without immunosuppressive therapy.

Pharmacokinetics and Pharmacodynamics of Sacubitril/Valsartan in Maintenance Hemodialysis Patients with Heart Failure.

BACKGROUND: Heart failure (HF) is one of the main comorbidities in patients receiving maintenance hemodialysis (HD). Sacubitril/valsartan (SAC/VAL) is widely used in HF patients with reduced ejection fraction (HFrEF) or HF mid-range ejection fraction (HFmrEF). However, the pharmacokinetic (PK) and pharmacodynamic properties of SAC/VAL in HD patients with HF remain uncertain. OBJECTIVES: This study aimed to analyze the efficacy and PK properties of SAC/VAL in HD patients with HFrEF or HFmrEF. METHODS: HD patients with HFrEF or HFmrEF were treated with SAC/VAL 50 or 100 mg twice a day (BID) and the concentrations of valsartan and LBQ657 (active metabolite of SAC) were determined by high-performance liquid chromatography-tandem mass spectrometry during HD and on the days between HD sessions (interval days). N-terminal-pro B-type natriuretic peptide and high-sensitivity troponin T were measured, and left ventricular ejection fraction (LVEF) was evaluated by echocardiography. RESULTS: The mean maximum plasma concentrations (Cmax) of LBQ657 and VAL on the interval days were 15.46 ± 6.01 and 2.57 ± 1.23 mg/L, respectively. Compared with previous values in patients with severe renal impairment and healthy volunteers, these levels both remained within the safe concentration ranges during treatment with SAC/VAL 100 mg BID. Moreover, SAC/VAL significantly improved LVEF in HD patients with HFrEF or HFmrEF (p < 0.05). CONCLUSIONS: HD did not remove the SAC metabolite LBQ657 or VAL in patients with HF. However, SAC/VAL 100 mg BID was safe and effective in patients undergoing HD.

GAP-43 ameliorates Podocyte injury by decreasing nuclear NFATc1 expression.

Podocyte injury is sufficient to cause glomerulosclerosis and proteinuria, eventually leading to kidney failure. Previous studies found that podocytes and neurons had similar biological characteristics. Growth-associated protein-43 (GAP-43) is a growth cone protein in neurons, and a marker of axonal and synaptic growth. However, it is not known whether GAP-43 is expressed in podocytes. Compared with normal glomerular podocytes, GAP-43 was significantly reduced in patients with glomerular diseases. GAP-43 also significantly reduced in lipopolysaccharide (LPS)-treated podocytes. We found that the decreased expression of nephrin, the cell marker of the podocyte, was significantly recovered with GAP-43 overexpression. In contrast, the migration ability in LPS-treated podocyte was reduction after GAP-43 overexpressing. Moreover, overexpression of GAP-43 attenuated podocyte apoptosis by up-regulating the ratio of Bcl-2/Bax with LPS treatment. Finally, Plaue and Rcan1 which are downstream target gene of NFATc1 decreased with overexpression of GAP-43 podocytes. We concluded that GAP-43 attenuated podocyte injury by inhibiting calcineurin/NFATc1 signaling. The findings may provide a promising treatment for podocyte injury-related diseases.

OsANN4 modulates ROS production and mediates Ca2+ influx in response to ABA.

BACKGROUND: Plant annexins are calcium- and lipid-binding proteins that have multiple functions, and a significant amount of research on plant annexins has been reported in recent years. However, the functions of annexins in diverse biological processes in rice are largely unclear. RESULTS: Herein, we report that OsANN4, a calcium-binding rice annexin protein, was induced by abscisic acid (ABA). Under ABA treatment, the plants in which OsANN4 was knocked down by RNA interference showed some visible phenotypic changes compared to the wild type, such as a lower rooting rate and shorter shoot and root lengths. Moreover, the superoxide dismutase (SOD) and catalase (CAT) activities of the RNAi lines were significantly lower and further resulted in higher accumulation of O2.- and H2O2 than those of the wild-type. A Non-invasive Micro-test Technology (NMT) assay showed that ABA-induced net Ca2+ influx was inhibited in OsANN4 knockdown plants. Interestingly, the phenotypic differences caused by ABA were eliminated in the presence of LaCl3 (Ca2+ channel inhibitor). Apart from this, we demonstrated that OsCDPK24 interacted with and phosphorylated OsANN4. When the phosphorylated serine residue of OsANN4 was substituted by alanine, the interaction between OsANN4 and OsCDPK24 was still observed, however, both the conformation of OsANN4 and its binding activity with Ca2+ might be changed. CONCLUSIONS: OsANN4 plays a crucial role in the ABA response, partially by modulating ROS production, mediating Ca2+ influx or interacting with OsCDPK24.

Thromboxane A2 is involved in the development of hypertension in chronic kidney disease rats.

Hypertension is one of the most common complications of chronic kidney disease (CKD). Some research has indicated that changes in large artery function especially caused by thromboxane A2 (TXA2) may be a novel factor acting to induce hypertension in CKD. We studied the 5/6 nephrectomy rat model and measured serum levels of creatinine (Cr), calcium (Ca), phosphorus (P), TXA2-stable metabolites (thromboxane B2, TXB2), and caudal artery pressure after nephrectomy. The tension variations in thoracic aortas were measured after stimulating by vasoconstrictor/vasodilator using the cumulative concentration administration method and then tested the expression of TXA2 receptors in the thoracic aortas through western blots. The CKD rats developed uremia, electrolyte imbalances，and hypertension. They also exhibited a significant increase in TXB2 concentration. The aortic rings of CKD rats showed an increased contraction response to U46619 (a TXA2 analogue) and the expression of TXA2 receptors also enhanced. In the meanwhile, the diastolic function decreased in the CKD group. Our results demonstrate that the impairment of artery contractile function caused by the increase of TXA2 receptors on the wall of aortic rings may be involved in hypertension in CKD rats.