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OBJECTIVE: We describe a rare case of uterine mesothelial cysts mimicking ovarian cysts in a primipara patient with a history of Cesarean section. CASE REPORT: A 39-year-old female patient with history of Cesarean section presented with dysmenorrhea. Sonography revealed that a hypoechoic and anechoic multicystic complex, which was located on the right side of the pelvic cavity, had infiltrated the adjacent posterior wall of the uterus, and it was preoperatively misdiagnosed as ovarian cysts with suspected endometrioma. Laparoscopic surgery revealed multiple cystic lesions filled with clear yellow fluid on the posterior uterine wall instead of the adnexa. Laparoscopic uterine cystectomy was performed, and the patient's recovery was uneventful. Pathohistological and immunohistochemical examinations confirmed the diagnosis of uterine mesothelial cysts. CONCLUSION: Uterine mesothelial cysts should be considered in the differential diagnosis of pelvic lesions. Increasing the awareness of this rare disease can contribute to improved evaluation, decision-making, and disease management.

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There are limited therapeutic options for patients with advanced prostate cancer (PCa). We previously found that heat shock factor 1 (HSF1) expression is increased in PCa and is an actionable target. In this manuscript, we identify that HSF1 regulates the conversion of homocysteine to cystathionine in the transsulfuration pathway by altering levels of cystathionine-ß-synthase (CBS). We find that HSF1 directly binds the CBS gene and upregulates CBS mRNA levels. Targeting CBS decreases PCa growth and induces tumor cell death while benign prostate cells are largely unaffected. Combined inhibition of HSF1 and CBS results in more pronounced inhibition of PCa cell proliferation and reduction of transsulfuration pathway metabolites. Combination of HSF1 and CBS knockout decreases tumor size for a small cell PCa xenograft mouse model. Our study thus provides new insights into the molecular mechanism of HSF1 function and an effective therapeutic strategy against advanced PCa.

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Objective:To explore the inhibitory mechanism of herb cake-partitioned moxibustion on tumor growth in colitis-associated colorectal cancer(CAC)based on histone lysine demethylase 4D(KDM4D). Methods:Inbred male Sprague-Dawley rats were randomly divided into a normal group,a CAC group,a herb cake-partitioned moxibustion group,and an inhibitor group.Except the normal group,rats in the other three groups were treated with azoxymethane(AOM)combined with dextran sulfate sodium(DSS)to make CAC rat models.Rats in the normal group and the CAC group did not receive interventions;rats in the herb cake-partitioned moxibustion group received moxibustion at Qihai(CV6)and bilateral Tianshu(ST25),2 cones for one point each time,once a day for 30 d with 1-day rest every week;rats in the inhibitor group received intraperitoneal injection of KDM4D inhibitor,5-chloro-8-hydroxyquinoline(5-c-8HQ),once a day for 30 d.After intervention,the general condition,colon length,tumor number and volume,and histopathological colon changes were observed.The expression of adenomatous polyposis coli(APC),axis inhibitor(Axin),cyclin D1,matrix metalloproteinase(MMP)-7 and MMP-9 mRNAs were detected by real-time quantitative polymerase chain reaction.The proliferating cell nuclear antigen(PCNA),cleaved caspase3,KDM4D,APC,and Axin proteins were detected by immunohistochemistry. Results:Compared with the normal group,the general condition was poor,the colon length was significantly shortened(P<0.01),the number and volume of colonic tumors were increased(P<0.01),the structure of glandular duct was obviously disordered with"back-to-back"and cowall phenomenon,and also high-grade adenocarcinoma formed;the protein expression levels of PCNA and KDM4D were significantly increased(P<0.01),while cleaved caspase3,APC,and Axin were significantly reduced(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were significantly increased(P<0.01),while APC and Axin were significantly reduced(P<0.01)in the CAC group.Compared with the CAC group,the general condition was improved,the length of colon was significantly increased(P<0.01),the number and volume of the colonic tumors were reduced(P<0.05),and the colon tissues showed epithelial cell proliferation with enlarged and deep staining nuclei,dysplasia and inflammatory cell infiltration;the protein expression levels of PCNA and KDM4D were significantly reduced(P<0.01),while the cleaved caspase3,APC,and Axin were significantly increased(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were reduced(P<0.05),while the APC and Axin were increased(P<0.05)in the colon tissues of rats in the herb cake-partitioned moxibustion group and the inhibitor group. Conclusion:Herb cake-partitioned moxibustion regulated abnormally expressed KDM4D in CAC rats,activated APC and Axin,the upstream molecules of Wnt/β-catenin pathway,inhibited abnormally activated downstream molecules of Wnt/β-catenin pathway.This may be a key mechanism of herb cake-partitioned moxibustion in inhibiting CAC tumor growth.

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This study examined treatment outcomes, including preserved fertility, menstrual regularity, and pregnancy outcomes, in patients with stage I epithelial ovarian cancer (EOC) or borderline ovarian tumors (BOTs) who underwent fertility-sparing surgery (FSS). Patients with stage I EOC and BOTs who were aged 18-45 years and underwent FSS between 2007 and 2022 were retrospectively reviewed. Significant differences between various subgroups in terms of disease recurrence, menstrual irregularity due to the disease, and pregnancy outcomes were analyzed. A total of 71 patients with BOTs and 33 patients with EOC were included. In the BOT group, the median age was 30 (range, 19-44) years. Recurrence occurred in eight patients, with one case exhibiting a malignant transformation into mucinous EOC. Among the 35 married patients with BOTs, 20 successfully conceived, resulting in 23 live births and 3 spontaneous abortions. A higher pregnancy rate was observed in those without prior childbirth (82.4%) than in those who had prior childbirth (33.3%). In the EOC group, the median age was 34 (range, 22-42) years. Recurrence occurred in one patient. Menstrual regularity was maintained in 69.7% of the patients. Among the 14 married patients in this group, 12 achieved a total of 15 pregnancies (including 2 twin pregnancies), 16 live births, and 1 spontaneous abortion. The results of the study confirmed that FSS is a favorable surgical option for young women with early-stage BOTs or EOC who wish to preserve their fertility. However, additional investigations are needed to validate these findings.

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Acute myeloid leukemia (AML) is the second most common hematologic malignancy in children. The incidence of childhood AML is much lower than acute lymphoblastic leukemia (ALL), which makes childhood AML a rare disease in children. The role of genetic abnormalities in AML classification, management, and prognosis prediction is much more important than before. Disease classifications and risk group classifications, such as the WHO classification, the international consensus classification (ICC), and the European LeukemiaNet (ELN) classification, were revised in 2022. The application of the new information in childhood AML will be upcoming in the next few years. The frequency of each genetic abnormality in adult and childhood AML is different; therefore, in this review, we emphasize well-known genetic subtypes in childhood AML, including core-binding factor AML (CBF AML), KMT2Ar (KMT2A/11q23 rearrangement) AML, normal karyotype AML with somatic mutations, unbalanced cytogenetic abnormalities AML, NUP98 11p15/NUP09 rearrangement AML, and acute promyelocytic leukemia (APL). Current risk group classification, the management algorithm in childhood AML, and novel treatment modalities such as targeted therapy, immune therapy, and chimeric antigen receptor (CAR) T-cell therapy are reviewed. Finally, the indications of hematopoietic stem cell transplantation (HSCT) in AML are discussed.

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The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor governs a variety of biological processes, including metabolism, by acting on distinct molecular targets in different subcellular compartments. In the cytosol, inactive PTEN can be recruited to the plasma membrane where it dimerizes and functions as a lipid phosphatase to regulate metabolic processes mediated by the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin complex 1 (mTORC1) pathway. However, the metabolic regulation of PTEN in the nucleus remains undefined. Here, using a gain-of-function approach to targeting PTEN to the plasma membrane and nucleus, we show that nuclear PTEN contributes to pyrimidine metabolism, in particular de novo thymidylate (dTMP) biosynthesis. PTEN appears to regulate dTMP biosynthesis through interaction with methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), a key enzyme that generates 5,10-methylenetetrahydrofolate, a cofactor required for thymidylate synthase (TYMS) to catalyze deoxyuridylate (dUMP) into dTMP. Our findings reveal a nuclear function for PTEN in controlling dTMP biosynthesis and may also have implications for targeting nuclear-excluded PTEN prostate cancer cells with antifolate drugs.

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Recent developments in sequencing technologies have greatly improved our knowledge of phylogenetic relationships and genomic architectures throughout the tree of life. Spiralia, a diverse clade within Protostomia, is essential for understanding the evolutionary history of parasitism, gene conversion, nervous systems and animal body plans. In this review, we focus on the current hypotheses of spiralian phylogeny and investigate the impact of long-read sequencing on the quality of genome assemblies. We examine chromosome-level assemblies to highlight key genomic features that have driven spiralian evolution, including karyotype, synteny and the Hox gene organization. In addition, we show how chromosome rearrangement has influenced spiralian genomic structures. Although spiralian genomes have undergone substantial changes, they exhibit both conserved and lineage-specific features. We recommend increasing sequencing efforts and expanding functional genomics research to deepen insights into spiralian biology.

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Pathogenic root/wood rot fungal species infect multiple urban tree species in Singapore. There is a need for sustainable and environmentally friendly mitigation. We report the local Trichoderma strains as potential biocontrol agents (BCAs) for pathogenic wood rot fungal species such as Phellinus noxius, Rigidoporus microporus, and Fulvifomes siamensis. Isolated Trichoderma strains were DNA-barcoded for their molecular identities and assessed for their potential as a BCA by their rate of growth in culture and effectiveness in inhibiting the pathogenic fungi in in vitro dual culture assays. Trichoderma harzianum strain CE92 was the most effective in inhibiting the growth of the pathogenic fungi tested. Preliminary results suggested both volatile organic compound (VOC) production and direct hyphal contact contributed to inhibition. SPME GC-MS identified known fungal inhibitory volatiles. Trichoderma harzianum strain CE92 hyphae were found to coil around Phellinus noxius and Lasiodiplodia theobromae upon contact in vitro and were possibly a part of the mycoparasitism. In summary, the work provides insight into Trichoderma inhibition of pathogenic fungi and identifies local strains with good potential for broad-spectrum BCAs against root/wood rot fungi in Singapore.

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Inactivation of the RB1 tumor suppressor gene is common in several types of therapy-resistant cancers, including metastatic castration-resistant prostate cancer, and predicts poor clinical outcomes. Effective therapeutic strategies against RB1-deficient cancers remain elusive. Here, we showed that RB1 loss/E2F activation sensitized cancer cells to ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, by upregulating expression of ACSL4 and enriching ACSL4-dependent arachidonic acid-containing phospholipids, which are key components of ferroptosis execution. ACSL4 appeared to be a direct E2F target gene and was critical to RB1 loss-induced sensitization to ferroptosis. Importantly, using cell line-derived xenografts and genetically engineered tumor models, we demonstrated that induction of ferroptosis in vivo by JKE-1674, a highly selective and stable GPX4 inhibitor, blocked RB1-deficient prostate tumor growth and metastasis and led to improved survival of the mice. Thus, our findings uncover an RB/E2F/ACSL4 molecular axis that governs ferroptosis and also suggest a promising approach for the treatment of RB1-deficient malignancies.

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Neuroendocrine (NE) cells comprise ~1% of epithelial cells in benign prostate and prostatic adenocarcinoma (PCa). However, they become enriched in hormonally treated and castration-resistant PCa (CRPC). In addition, close to 20% of hormonally treated tumors recur as small cell NE carcinoma (SCNC), composed entirely of NE cells, which may be the result of clonal expansion or lineage plasticity. Since NE cells do not express androgen receptors (ARs), they are resistant to hormonal therapy and contribute to therapy failure. Here, we describe the identification of glypican-3 (GPC3) as an oncofetal cell surface protein specific to NE cells in prostate cancer. Functional studies revealed that GPC3 is critical to the viability of NE tumor cells and tumors displaying NE differentiation and that it regulates calcium homeostasis and signaling. Since our results demonstrate that GPC3 is specifically expressed by NE cells, patients with confirmed SCNC may qualify for GPC3-targeted therapy which has been developed in the context of liver cancer and displays minimal toxicity due to its tumor-specific expression. © 2023 The Pathological Society of Great Britain and Ireland.

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Currently colorectal cancer (CRC) is the third most prevalent cancer worldwide. Body mass index (BMI) is frequently used in CRC screening and risk assessment to quantitatively evaluate weight. However, the impact of BMI on clinical strategies for CRC has received little attention. Within the framework of the predictive, preventive, and personalized medicine (3PM/PPPM), we hypothesized that BMI stratification would affect the primary, secondary, and tertiary care options for CRC and we conducted a critical evidence-based review. BMI dynamically influences CRC outcomes, which helps avoiding adverse treatment effects. The outcome of surgical and radiation treatment is adversely affected by overweight (BMI ≥ 30) or underweight (BMI < 20). A number of interventions, such as enhanced recovery after surgery and robotic surgery, can be applied to CRC at all levels of BMI. BMI-controlling modalities such as exercise, diet control, nutritional therapy, and medications may be potentially beneficial for patients with CRC. Patients with overweight are advised to lose weight through diet, medication, and physical activity while patients suffering of underweight require more focus on nutrition. BMI assists patients with CRC in better managing their weight, which decreases the incidence of adverse prognostic events during treatment. BMI is accessible, noninvasive, and highly predictive of clinical outcomes in CRC. The cost-benefit of the PPPM paradigm in developing countries can be advanced, and the clinical benefit for patients can be improved with the promotion of BMI-based clinical strategy models for CRC.

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Point cloud data are extensively used in various applications, such as autonomous driving and augmented reality since it can provide both detailed and realistic depictions of 3D scenes or objects. Meanwhile, 3D point clouds generally occupy a large amount of storage space that is a big burden for efficient communication. However, it is difficult to efficiently compress such sparse, disordered, non-uniform and high dimensional data. Therefore, this work proposes a novel deep-learning framework for point cloud geometric compression based on an autoencoder architecture. Specifically, a multi-layer residual module is designed on a sparse convolution-based autoencoders that progressively down-samples the input point clouds and reconstructs the point clouds in a hierarchically way. It effectively constrains the accuracy of the sampling process at the encoder side, which significantly preserves the feature information with a decrease in the data volume. Compared with the state-of-the-art geometry-based point cloud compression (G-PCC) schemes, our approach obtains more than 70-90% BD-Rate gain on an object point cloud dataset and achieves a better point cloud reconstruction quality. Additionally, compared to the state-of-the-art PCGCv2, we achieve an average gain of about 10% in BD-Rate.

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Adnexal masses are common in pregnancy, with 2-10% of pregnancies presenting with an ovarian mass and approximately 1-6% of these masses being malignant. For suspected malignancy or masses with symptoms, surgery must be performed as early as possible. We retrospectively investigated the effect of two-port laparoscopic surgery on the outcomes of patients with concurrent adnexal masses between 2012 and 2019 (including large mucinous tumor, large teratoma, serous borderline tumor, and heterotopic pregnancy). Laparoscopic right partial oophorectomy was performed for a 27 cm ovarian mucinous tumor at a gestational age (GA) of 21 weeks, laparoscopic right oophorocystectomy for an 18 cm teratoma at a GA of 10 weeks, and laparoscopic left salpingo-oophorectomy for a 7 cm serous borderline tumor at a GA of 7 weeks after ultrasonographic confirmation of an intrauterine gestational sac with a fetal heartbeat. Laparoscopic excision of a tubal pregnancy was performed in a heterotopic pregnancy at a GA of 12 weeks with massive internal bleeding. Laparoscopic surgery is easier and safe to perform during early pregnancy because a smaller uterus allows for superior visualization. All of these patients had optimal postoperative recovery and normal spontaneous delivery at term. We discussed several aspects of treatment and delivery, namely treatment option (expectant management or surgery), surgery timing (early or advanced pregnancy), surgery type (laparoscopy or laparotomy), and delivery route (normal spontaneous delivery or cesarean section), in patients with concurrent adnexal tumors and their effects on pregnancy outcomes.

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Aims: Studies have observed changes in autophagic flux in the adipose tissue of type 2 diabetes patients with obesity. However, the role of autophagy in obesity-induced insulin resistance is unclear. We propose to confirm the effect of a high-fat diet (HFD) on autophagy and insulin signaling transduction from adipose tissue to clarify whether altered autophagy-mediated HFD induces insulin resistance, and to elucidate the possible mechanisms in autophagy-regulated adipose insulin sensitivity. Methods: Eight-week-old male C57BL/6 mice were fed with HFD to confirm the effect of HFD on autophagy and insulin signaling transduction from adipose tissue. Differentiated 3T3-L1 adipocytes were treated with 1.2 mM fatty acids (FAs) and 50 nM Bafilomycin A1 to determine the autophagic flux. 2.5 mg/kg body weight dose of Chloroquine (CQ) in PBS was locally injected into mouse epididymal adipose (10 and 24 h) and 40 µM of CQ to 3T3-L1 adipocytes for 24 h to evaluate the role of autophagy in insulin signaling transduction. Results: The HFD treatment resulted in a significant increase in SQSTM1/p62, Rubicon expression, and C/EBP homologous protein (CHOP) expression, yet the insulin capability to induce Akt (Ser473) and GSK3ß (Ser9) phosphorylation were reduced. PHLPP1 and PTEN remain unchanged after CQ injection. In differentiated 3T3-L1 adipocytes treated with CQ, although the amount of phospho-Akt stimulated by insulin in the CQ-treated group was significantly lower, CHOP expressions and cleaved caspase-3 were increased and bafilomycin A1 induced less accumulation of LC3-II protein. Conclusion: Long-term high-fat diet promotes insulin resistance, late-stage autophagy inhibition, ER stress, and apoptosis in adipose tissue. Autophagy suppression may not affect insulin signaling transduction via phosphatase expression but indirectly causes insulin resistance through ER stress or apoptosis.

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Maternal and passionate love are both crucial for reproduction and involve attachment behaviors with high rewards. Neurobiological studies of attachment in animal and human neuroimaging studies have suggested that the coordination of oxytocinergic and vasopressinergic pathways, coupled with the dopaminergic reward system, contribute to the formation and maintenance of maternal and passionate love. In the present study, we carried out a quantitative meta-analysis of human neuroimaging to identify common and dissociable neural substrates associated with maternal and passionate love, using the activation likelihood estimation (ALE) approach. The ALE results showed significant activation of the brain regions in the left ventral tegmental area (VTA), right thalamus, left substantia nigra, and the left putamen for maternal love, but in the bilateral VTA for passionate love. The meta-analytic neuroimaging evidence suggests the greater involvement of cognitive-affective regulation in maternal attachment and the greater desire to combine liking and wanting in romantic love behaviors. The conjunction analysis highlights the functional convergence of the VTA across the two types of human love, indicating a shared neurobiological mechanism of maternal and passionate love with evolutionary roots. Our findings suggest that the processing of both maternal and passionate love involve the affective and motivational regulation associated with dopaminergic systems; our neuroimaging evidence supports the notion that maternal and passionate love share a common evolutionary origin and neurobiological basis in the human brain.

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Top-k dominating (TKD) query is one of the methods to find the interesting objects by returning the k objects that dominate other objects in a given dataset. Incomplete datasets have missing values in uncertain dimensions, so it is difficult to obtain useful information with traditional data mining methods on complete data. BitMap Index Guided Algorithm (BIG) is a good choice for solving this problem. However, it is even harder to find top-k dominance objects on incomplete big data. When the dataset is too large, the requirements for the feasibility and performance of the algorithm will become very high. In this paper, we proposed an algorithm to apply MapReduce on the whole process with a pruning strategy, called Efficient Hadoop BitMap Index Guided Algorithm (EHBIG). This algorithm can realize TKD query on incomplete datasets through BitMap Index and use MapReduce architecture to make TKD query possible on large datasets. By using the pruning strategy, the runtime and memory usage are greatly reduced. What's more, we also proposed an improved version of EHBIG (denoted as IEHBIG) which optimizes the whole algorithm flow. Our in-depth work in this article culminates with some experimental results that clearly show that our proposed algorithm can perform well on TKD query in an incomplete large dataset and shows great performance in a Hadoop computing cluster.

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BACKGROUND: The biting midge, Forcipomyia taiwana, is one of the most annoying blood-sucking pests in Taiwan. Current chemical control methods only target the adult, not the immature stages (egg to pupa), of F. taiwana. Discovering new or alternative tactics to enhance or replace existing methods are urgently needed to improve the effectiveness of F. taiwana control. The egg is the least understood life stage in this pest species but may offer a novel point of control as addition of NaCl to the egg environment inhibits development. Thus, the objective of this study was to use RNA profiling to better understand the developmental differences between wild-type melanized (black) and NaCl-induced un-melanized (pink), infertile F. taiwana eggs. RESULTS: After de novo assembly with Trinity, 87,415 non-redundant transcripts (Ft-nr) with an N50 of 1099 were obtained. Of these, 26,247 (30%) transcripts were predicted to have long open reading frames (ORFs, defined here as ≥300 nt) and 15,270 (17.5%) transcripts have at least one predicted functional domain. A comparison between two biological replicates each of black and pink egg samples, although limited in sample size, revealed 5898 differentially expressed genes (DEGs; 40.9% of the transcripts with long ORFs) with ≥2-fold difference. Of these, 2030 were annotated to a Gene Ontology biological process and along with gene expression patterns can be separated into 5 clusters. KEGG pathway analysis revealed that 1589 transcripts could be assigned to 18 significantly enriched pathways in 2 main categories (metabolism and environmental information processing). As expected, most (88.32%) of these DEGs were down-regulated in the pink eggs. Surprisingly, the majority of genes associated with the pigmentation GO term were up-regulated in the pink egg samples. However, the two key terminal genes of the melanin synthesis pathway, laccase2 and DCE/yellow, were significantly down-regulated, and further verified by qRT-PCR. CONCLUSION: We have assembled and annotated the first egg transcriptome for F. taiwana, a biting midge. Our results suggest that down-regulation of the laccase2 and DCE/yellow genes might be the mechanism responsible for the NaCl-induced inhibition of melanization of F. taiwana eggs.

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Background: Calcific aortic valve disease is common in the aging population and is characterized by the histological changes of the aortic valves including extracellular matrix remodeling, osteochondrogenic differentiation, and calcification. Combined, these changes lead to aortic sclerosis, aortic stenosis (AS), and eventually to heart failure. Runt-related transcription factor 2 (Runx2) is a transcription factor highly expressed in the calcified aortic valves. However, its definitive role in the progression of calcific aortic valve disease (CAVD) has not been determined. In this study, we utilized constitutive and transient conditional knockout mouse models to assess the molecular, histological, and functional changes in the aortic valve due to Runx2 depletion. Methods: Lineage tracing studies were performed to determine the provenance of the cells giving rise to Runx2+ osteochondrogenic cells in the aortic valves of LDLr-/- mice. Hyperlipidemic mice with a constitutive or temporal depletion of Runx2 in the activated valvular interstitial cells (aVICs) and sinus wall cells were further investigated. Following feeding with a diabetogenic diet, the mice were examined for changes in gene expression, blood flow dynamics, calcification, and histology. Results: The aVICs and sinus wall cells gave rise to Runx2+ osteochondrogenic cells in diseased mouse aortic valves. The conditional depletion of Runx2 in the SM22α+ aVICs and sinus wall cells led to the decreased osteochondrogenic gene expression in diabetic LDLr-/- mice. The transient conditional depletion of Runx2 in the aVICs and sinus wall cells of LDLr-/-ApoB100 CAVD mice early in disease led to a significant reduction in the aortic peak velocity, mean velocity, and mean gradient, suggesting the causal role of Runx2 on the progression of AS. Finally, the leaflet hinge and sinus wall calcification were significantly decreased in the aortic valve following the conditional and temporal Runx2 depletion, but no significant effect on the valve cusp calcification or thickness was observed. Conclusions: In the aortic valve disease, Runx2 was expressed early and was required for the osteochondrogenic differentiation of the aVICs and sinus wall cells. The transient depletion of Runx2 in the aVICs and sinus wall cells in a mouse model of CAVD with a high prevalence of hemodynamic valve dysfunction led to an improved aortic valve function. Our studies also suggest that leaflet hinge and sinus wall calcification, even in the absence of significant leaflet cusp calcification, may be sufficient to cause significant valve dysfunctions in mice.