Estimation of forest canopy closure in northwest Yunnan based on multi-source remote sensing data colla-boration.

Forest canopy closure (FCC) is an important parameter to evaluate forest resources and biodiversity. Using multi-source remote sensing collaborative means to achieve regional forest canopy closure inversion with low cost and high-precision is a research hotspot. Taking ICESat-2/ATLAS data as the main information source and combined with data of 54 measured plots, we estimated FCC value by the Bayesian optimization (BO) algorithm improved random forest (RF), K-nearest neighbor (KNN), and gradient boosting regression tree (GBRT) model at footprint-scale. Combined with multi-source remote sensing image Sentinel-1/2 and terrain factors, we estimated the regional-scale FCC value of Shangri-La in the northwest Yunnan based on deep neural network (DNN) optimized by BO algorithm. The results showed that six characteristic parameters (percentage of tree canopy, standard deviation of relative height of photons at the top of the canopy, minimum canopy height, difference between 98% canopy height and median canopy height in the segment, number of top canopy photons, apparent surface reflectance) out of the 50 parameters that were extracted from ATLAS lidar footprint had higher contribution rate after RF characteristic variable optimization, which could be used as model variable for footprint-scale remote sensing estimation. Among BO-RF, BO-KNN, and BO-GBRT models, the FCC results estimated by the BO-GBRT model were the best at footprint-scale. The coefficient of determination (R2) was 0.65, the root mean square error (RMSE) was 0.10, the mean absolute residual (RS) was 0.079, and the prediction accuracy (P) was 0.792 for leave-one-out cross validation. It could be used as the FCC estimation model of 74808 ATLAS footprints for forest in the study area. We used the ATLAS footprint-scale FCC value of forest as the large sample data of the regional-scale BO-DNN model and combined with multi-source remote sensing factors to estimate FCC in the study area, the accuracy of the 10-fold cross-validation BO-DNN model was R2=0.47, RMSE=0.22, P=0.558. The mean values of FCC in the study area estimated by BO-DNN model and ordinary Kriging (OK) interpolation were 0.46 and 0.52, respectively, and the values mainly distributed in 0.3-0.6, accounting for 77.8% and 81.4%, respectively. The FCC efficiency obtained directly by the OK interpolation method was higher (R2=0.26), but the prediction accuracy was significantly lower than the BO-DNN model (R2=0.49). The FCC high value was distributed from northwest to southeast in the study area, and the northern and southeastern regions were the main distribution areas of high and low FCC values, respectively. It had certain advantages to estimate mountain area FCC based on ICESat-2/ATLAS high-density footprint, and the estimation results of small sample data at footprint-scale could be used as large sample data of deep learning model at region-scale, which would provide a reference for the low-cost and high-precision to FCC estimation on the footprint-scale up to the extrapolated regional-scale.

Programmable Thermo-Responsive Actuation of Hydrogels via Light-Guided Surface Growth of Active Layers on Shape Memory Substrates.

Hydrogel shape memory and actuating functionalities are heavily pursued and have found great potential in various application fields. However, their combination for more flexible and complicated morphing behaviors is still challenging. Herein, it is reported that by controlling the light-initiated polymerization of active hydrogel layers on shape memory hydrogel substrates, advanced morphing behaviors based on programmable hydrogel shapes and actuating trajectories are realized. The formation and photo-reduction-induced dissociation of Fe3+ -carboxylate coordination endow the hydrogel substrates with the shape memory functionality. The photo-reduced Fe2+ ions can diffuse from the substrates into the monomer solutions to initiate the polymerization of the thermally responsive active layers, whose actuating temperatures and amplitudes can be facially tuned by controlling their thicknesses and compositions. One potential application, a shape-programmable 3D hook that can lift an object with a specific shape, is also unveiled. The demonstrated strategy is extendable to other hydrogel systems to realize more versatile and complicated actuating behaviors.

Laser-treated wood for high-efficiency solar thermal steam generation.

Solar-driven water vaporization is considered one of the most sustainable ways to solve water scarcity. The design of highly efficient solar absorber systems has received extensive attention. Here, we report a novel light absorption material for water evaporation using laser-treated wood. The obtained laser-treated wood possesses interconnected 3D porous networks formed by the random construction of carbon arrays and a hydrophilic surface due to the oxygen implantation by laser treatment. When under 1 sun solar-simulated light irradiation (1 kW m-2), the surface temperatures of dry and water-saturated wood reach 59.5 °C and 40.4 °C, respectively, indicating good heat localization. As a result, the laser-treated wood under 1 sun illumination shows high solar to vapor efficiencies of 93.1% and 92.6% for pure water and seawater, respectively, which are higher than that of most wood-based reported photo-thermal conversion materials. Therefore, the fabricated laser-treated wood may pave the way for harvesting solar energy to produce clean water at low cost.

Factors Related to Psychological Distress in Multiparous Women in the First Trimester: A Cross-Sectional Study.

BACKGROUND: The birth rate in Taiwan has declined rapidly; thus, encouraging women to give birth is an important issue in the country. Pregnant women may experience psychological distress, which may negatively impact the health of children and mothers. Prenatal psychological distress is more common in multiparous women than in primiparous women. In addition, compared with that in the second and third trimesters, psychological distress in the first trimester is relatively high. Understanding psychological distress and the associated factors for multiparous women in the first trimester is important to providing early interventions and preventing subsequent maternal and child health problems. PURPOSE: This study was designed to examine the important predictive factors related to depression, anxiety, and stress among Taiwanese multiparous women in the first trimester. METHODS: A cross-sectional design was used. In all, 216 multiparous women at 16 weeks of pregnancy were recruited from three hospitals in Taiwan. Self-reported questionnaires were used to gather data on demographic characteristics, the parenting stress of motherhood, spousal support, and psychological distress. A multiple logistic regression analysis was conducted to examine the factors associated with psychological distress. RESULTS: The prevalence of depression, anxiety, and stress in multiparous women was found to be 31.9%, 42.6%, and 11.1%, respectively. The multiple logistic regression analysis indicated that the stress related to parent-child interaction was a significant predictor of depression and anxiety, the stress related to child-rearing was a significant predictor of anxiety, and low spousal instrumental support was a significant predictor of stress. The model respectively explained 30%, 27%, and 23% of the variance in depression, anxiety, and stress. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Reducing the stress related to parent-child interaction and child-rearing and encouraging spousal instrumental support should be considered during prenatal care when designing interventions to reduce the psychological distress of multiparous women in their first trimester.

Filling the gap between topological insulator nanomaterials and triboelectric nanogenerators.

Reliable energy modules and higher-sensitivity, higher-density, lower-powered sensing systems are constantly required to develop wearable electronics and the Internet of Things technology. As an emerging technology, triboelectric nanogenerators have been potentially guiding the landscape of sustainable power units and energy-efficient sensors. However, the existing triboelectric series is primarily populated by polymers and rubbers, limiting triboelectric sensing plasticity to some extent owing to their stiff surface electronic structures. To enrich the current triboelectric group, we explore the triboelectric properties of the topological insulator nanofilm by Kelvin probe force microscopy and reveal its relatively positive electrification charging performance. Both the larger surface potential difference and the conductive surface states of the nanofilms synergistically improve the charge transfer behavior between the selected triboelectric media, endowing the topological insulator-based triboelectric nanogenerator with considerable output performance. Besides serving as a wearable power source, the ultra-compact device array demonstrates innovative system-level sensing capabilities, including precise monitoring of dynamic objects and real-time signal control at the human-machine interface. This work fills the blank between topological quantum matters and triboelectric nanogenerators and, more importantly, exploits the significant potential of topological insulator nanofilms for self-powered flexible/wearable electronics and scalable sensing technologies.

Ultrathin and High-Modulus LiBO2 Layer Highly Elevates the Interfacial Dynamics and Stability of Lithium Anode under Wide Temperature Range.

Lithium (Li) metal batteries (LMBs) face huge challenges to achieve long cycling life at wide temperature range owing to the severe dendrite growth at subambient temperature and the intense side reactions with electrolyte at high temperature. Herein, an ultrathin LiBO2 layer with an extremely high Young's modulus of 8.0 GPa is constructed on Li anode via an in situ reaction between Li metal and 4,4,5,5-tetramethyl-1,3,2-dioxa-borolane (TDB) to form LiBO2 @Li anode, which presents two times higher exchange current density than pristine Li anode. The LiBO2 layer presents a strong absorption to Li ions and greatly improves the interfacial dynamics of Li-ion migration, which induces homogenous lithium nucleation and deposition to form a dense lithium layer. Consequently, the Li dendrite growth during cycling at subambient temperature and the side reactions with electrolyte at high temperature are simultaneously suppressed. The LiBO2 @Li/LiNi0.8 Co0.1 Mn0.1 O2 (NCM811) full batteries with limited Li capacity and high cathode mass loading of 9.9 mg cm-2 can steadily cycle for 300 cycles with a capacity retention of 86.6%. The LiBO2 @Li/NCM811 full batteries and LiBO2 @Li/LiBO2 @Li symmetric batteries also present excellent cycling performance at both -20 and 60 °C. This work develops a strategy to achieve outstanding performance of LMBs at wide working temperature-range.

Circular RNAs in liver diseases: Mechanisms and therapeutic targets.

Circular RNAs (circRNAs) are formed from the genome through diverse back splicing and feature the closed loop. circRNAs are widely available in a variety of cells and characterized by conservation, structural stability, high abundance and tissue-specific or developmental-specific expression. Recent studies have shown that circRNAs are closely related to liver diseases, such as metabolic-associated fatty liver disease, hepatitis, liver cirrhosis and hepatocellular carcinoma. circRNAs play an important role in the progression of liver diseases, are potential diagnostic and prognostic markers, and have translational value in therapy. This article reviews the research on circRNAs in liver diseases, with a view to providing a theoretical basis and new ideas for future research and treatment of liver diseases.

Comparisons of Papanicolaou Utilization and Cervical Cancer Detection between Rural and Urban Women in Taiwan.

Using the claims data of one million insured residents in Taiwan from 1996-2013, this study identified 12,126 women in an urban city (Taichung) and 7229 women in a rural county (Yunlin), aged 20 and above. We compared Papanicolaou (Pap) test uses and cervical cancer detection rates between urban and rural women. Results showed that the Pap screening rate was slightly higher in rural women than in urban women (86.1 vs. 81.3 percent). The cervical cancer incidence was much greater for women without Pap test than women with the test (35.8 vs. 9.00 per 1000 in rural women and 20.3 vs. 7.00 per 1000 in urban women). Nested case-control analysis showed that Pap test receivers had an adjusted odds ratio (OR) of 0.35 (95% CI = 0.25-0.51) to be diagnosed with cervical cancer as compared to those who did not receive the test. The rural women had an adjusted OR of 1.46 (95% CI = 1.03-2.06) to be diagnosed with cervical cancer as compared to urban women. In conclusion, women in rural area are at higher cancer risk than city women. Women who do not undergo Pap tests deserve timely intervention of Pap test to prevent the onset of cancer, particularly in rural women with low income.

Demonstration of Dissipative Quasihelical Edge Transport in Quantum Anomalous Hall Insulators.

Doping a topological insulator (TI) film with transition metal ions can break its time-reversal symmetry and lead to the realization of the quantum anomalous Hall (QAH) effect. Prior studies have shown that the longitudinal resistance of the QAH samples usually does not vanish when the Hall resistance shows a good quantization. This has been interpreted as a result of the presence of possible dissipative conducting channels in magnetic TI samples. By studying the temperature- and magnetic-field-dependence of the magnetoresistance of a magnetic TI sandwich heterostructure device, we demonstrate that the predominant dissipation mechanism in thick QAH insulators can switch between nonchiral edge states and residual bulk states in different magnetic-field regimes. The interactions between bulk states, chiral edge states, and nonchiral edge states are also investigated. Our Letter provides a way to distinguish between the dissipation arising from the residual bulk states and nonchiral edge states, which is crucial for achieving true dissipationless transport in QAH insulators and for providing deeper insights into QAH-related phenomena.

Imaging Bulk and Edge Transport near the Dirac Point in Graphene Moiré Superlattices.

Van der Waals structures formed by aligning monolayer graphene with insulating layers of hexagonal boron nitride exhibit a moiré superlattice that is expected to break sublattice symmetry. Despite an energy gap of several tens of millielectronvolts opening in the Dirac spectrum, electrical resistivity remains lower than expected at low temperature and varies between devices. While subgap states are likely to play a role in this behavior, their precise nature is unclear. We present a scanning gate microscopy study of moiré superlattice devices with comparable activation energy but with different charge disorder levels. In the device with higher charge impurity (∼1010 cm-2) and lower resistivity (∼10 kΩ) at the Dirac point we observe current flow along the graphene edges. Combined with simulations, our measurements suggest that enhanced edge doping is responsible for this effect. In addition, a device with low charge impurity (∼109 cm-2) and higher resistivity (∼100 kΩ) shows subgap states in the bulk, consistent with the absence of shunting by edge currents.

Expedite random structure searching using objects from Wyckoff positions.

Random structure searching has been proved to be a powerful approach to search and find the global minimum and the metastable structures. A true random sampling is in principle needed yet it would be highly time-consuming and/or practically impossible to find the global minimum for the complicated systems in their high-dimensional configuration space. Thus the implementations of reasonable constraints, such as adopting system symmetries to reduce the independent dimension in structural space and/or imposing chemical information to reach and relax into low-energy regions, are the most essential issues in the approach. In this paper, we propose the concept of "object" which is either an atom or composed of a set of atoms (such as molecules or carbonates) carrying a symmetry defined by one of the Wyckoff positions of space group and through this process it allows the searching of global minimum for a complicated system to be confined in a greatly reduced structural space and becomes accessible in practice. We examined several representative materials, including Cd3As2 crystal, solid methanol, high-pressure carbonates (FeCO3), and Si(111)-7 × 7 reconstructed surface, to demonstrate the power and the advantages of using "object" concept in random structure searching.

FTY720-induced enhancement of autophagy protects cells from FTY720 cytotoxicity in colorectal cancer.

FTY720, also known as fingolimod, is a widely used immunomodulator in multiple sclerosis and multiple organ transplantation. It is also an important protein phosphatase 2A (PP2A) activator. Based on this, a number of studies have recently demonstrated the cytotoxic effect of FTY720 in various cancers. Yet in colorectal cancer (CRC), the underlying mechanisms of FTY720 cytotoxicity remain less clear, especially the relationship between a drug and autophagy. We demonstrate here for the first time that FTY720 promotes the appearance of autophagic hallmarks such as autophagosome formation and light chain 3 (LC3)-II accumulation, indicating the participation of autophagy in FTY720 cytotoxicity on CRC. Moreover, inhibition of autophagy using 3-methyladenine (3-MA), a specific inhibitor of autophagy, enhanced FTY720 cytotoxicity, indicating the protective role of autophagy against the drug's own cytotoxic effect. The protective autophagy was likely affected by cancerous inhibitor of PP2A (CIP2A), an endogenous PP2A inhibitor that is closely related with poor prognosis and drug resistance. Consequently, our data not only demonstrate a new mechanism underlying the cytotoxic effect of FTY720 in CRC, but also a new strategy for CRC treatment, especially in cases resistant to conventional chemotherapies because of high CIP2A levels.

MUC20 promotes aggressive phenotypes of epithelial ovarian cancer cells via activation of the integrin ß1 pathway.

OBJECTIVE: Mucin (MUC) 20 has recently been implicated to play a role in human carcinogenesis. However, the role of MUC20 in epithelial ovarian cancer (EOC) remains to be elucidated. METHODS: MUC20 expression was assessed in tissue microarray and tumor specimens of EOC patients by immunohistochemistry. Effects of MUC20 on cell viability, adhesion, migration, and invasion were analyzed in MUC20 overexpressing or knockdown EOC cells. Western blotting was performed to analyze signaling pathways modulated by MUC20. RESULTS: MUC20 was overexpressed in EOC samples compared with benign tissues. High MUC20 expression was significantly associated with poor overall survival in patients with advanced-stage disease. MUC20 overexpression significantly enhanced EOC cell migration and invasion, but not viability. Mechanistic investigations showed that MUC20 increased cell adhesion to extracellular matrix (ECM) proteins and enhanced activation of integrin ß1 and phosphorylation of focal adhesion kinase (FAK). The enhancement of cell motility and the integrin ß1 signaling by MUC20 was significantly suppressed by integrin ß1 blocking antibody. Furthermore, these effects of MUC20 on EOC cells were also demonstrated in MUC20 knockdown cells. CONCLUSIONS: Our results suggest that MUC20 enhances aggressive behaviors of EOC cells by activating integrin ß1 signaling and provide novel insights into the role of MUC20 in ovarian cancer metastasis.

Proximal aortic repair versus extensive aortic repair in the treatment of acute type A aortic dissection: a meta-analysis.

OBJECTIVES: The optimal surgical strategy for acute type A aortic dissection (ATAAD) is still controversial because of the inconsistent or even conflicting results of proximal aortic repair (PR) versus extensive aortic repair (ER) on early and late prognostic outcomes. This meta-analysis pooled data from all available studies of PR versus ER to get a summarized conclusion. METHODS: Studies were identified by searching the Medline, EMBASE and Cochrane databases. Early and late prognostic outcomes of interest were evaluated with meta-analysis. Fixed- or random-effect models were used according to the significance of heterogeneity. Robustness of pooled estimates and the source of heterogeneity were assessed via sensitivity analyses and meta-regression, respectively. Publication bias was evaluated by the funnel plot and Egger's test. RESULTS: Nine studies with a total of 1872 patients were included for the meta-analysis. Pooled results indicated that, when compared with the ER procedure, PR was associated with lower early mortality [risk ratio (RR) = 0.69, 95% confidence interval (CI) 0.54-0.90, P = 0.005] but higher incidence of postoperative aortic events including reoperation of the distal aorta (RR = 3.14, 95% CI 1.74-5.67, P < 0.001). PR and ER demonstrated analogous prognosis on long-term mortality (HR = 1.02, 95% CI 0.51-2.06, P = 0.96) and the incidences of early postoperative renal failure (RR = 0.75, 95% CI 0.49-1.14, P = 0.17) and stroke (RR = 0.73, 95% CI 0.30-1.78, P = 0.50). All the pooled results were robust to sensitivity analysis. Heterogeneity was insignificant except for the meta-analysis of late mortality. CONCLUSIONS: Performing a less aggressive initial surgical procedure of PR in ATAAD patients would have lower early mortality but elevated incidence rates of late aortic reintervention, when compared with ER. Other prognostic results of the two surgical strategies including long-term mortality were similar for both.

TWIST-1 promotes cell growth, drug resistance and progenitor clonogenic capacities in myeloid leukemia and is a novel poor prognostic factor in acute myeloid leukemia.

Alterations of TWIST-1 expression are often seen in solid tumors and contribute to tumorigenesis and cancer progression. However, studies concerning its pathogenic role in leukemia are scarce. Our study shows that TWIST-1 is overexpressed in bone marrow mononuclear cells of patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Gain-of-function and loss-of-function analyses demonstrate that TWIST-1 promotes cell growth, colony formation and drug resistance of AML and CML cell lines. Furthermore, TWIST-1 is aberrantly highly expressed in CD34+CD38- leukemia stem cell candidates and its expression declines with differentiation. Down-modulation of TWIST-1 in myeloid leukemia CD34+ cells impairs their colony-forming capacity. Mechanistically, c-MPL, which is highly expressed in myeloid leukemia cells and associated with poor prognosis, is identified as a TWIST-1 coexpressed gene in myeloid leukemia patients and partially contributes to TWIST-1-mediated leukemogenic effects. Moreover, patients with higher TWIST-1 expression have shorter overall and event-free survival (OS and EFS) in AML. Multivariate analysis further demonstrates that TWIST-1 overexpression is a novel independent unfavourable predictor for both OS and EFS in AML. These data highlight TWIST-1 as a new candidate gene contributing to leukemogenesis of myeloid leukemia, and propose possible new avenues for improving risk and treatment stratification in AML.

MiR-125a-3p regulates glioma apoptosis and invasion by regulating Nrg1.

The current study was designed to examine the functional role and mechanism of miR-125a-3p in glioma development. Quantitative RT-PCR was used to evaluate miR-125a-3p expression in 60 glioma cases of different malignant grades. Then, the clinic pathologic significance of miR-125a-3p expression was determined in combination with the prognosis of the patients. In addition, the effects and mechanisms of miR-125a-3p on the proliferation, apoptosis and invasion of glioma cells were further investigated. The results showed that the expression of miR-125a-3p was decreased significantly in most malignant glioma samples relative to normal brain tissues and glioma tissues of low-malignant degree. Further kaplan-meier survival analysis showed that the lower expression of miR-125a-3p was associated with a poor prognosis of GBM patients. Functional analysis showed that the reintroduction of miR-125a-3p into glioblastoma cell lines induces markedly the apoptosis and suppresses the proliferation and migration of glioblastoma cells in vitro and in vivo. Luciferase assay and Western blot analysis revealed that Nrg1 is a direct target of miR-125a-3p. Furthermore, an increased expression of Nrg1 could reverse the effects of overexpression of miR-125a-3p on the proliferation, apoptosis and migration of glioblastoma cells. These findings suggest that miR-125a-3p performed an important role in glioma development mediated by directly regulating the expression of Nrg1. This study also provides a potential target for diagnosis and treatment of malignant glioma.

AZD1480, a JAK inhibitor, inhibits cell growth and survival of colorectal cancer via modulating the JAK2/STAT3 signaling pathway.

Interleukin (IL)-6 and the downstream Janus kinase (JAK)/signal activator of transcription (STAT) pathway have been found to be important in the development of colorectal cancer (CRC). To develop novel therapies for CRC, we have explored the effects of a novel small-molecule JAK inhibitor (AZD1480) on IL-6/JAK/STAT3 pathway and its potential antitumor activity on the human CRC cell lines (HCT116, HT29 and SW480). The results showed that, AZD1480 effectively prevents constitutive and IL-6-induced JAK2 and STAT-3 phosphorylation and exerted antitumor functional effects by a decrease in proliferation and an increase in apoptosis in CRC cells. The inhibition of tumorigenesis was consistent with the decreased phosphorylated JAK2 and phosphorylated STAT3, and the decreased expression of STAT3­targeted genes c-Myc, cyclin D2 and IL-6. Thus, AZD1480 is a potential new clinical therapeutic agent for patients with CRC.

Genome organisation of the Acinetobacter lytic phage ZZ1 and comparison with other T4-like Acinetobacter phages.

BACKGROUND: Phage ZZ1, which efficiently infects pathogenic Acinetobacter baumannii strains, is the fifth completely sequenced T4-like Acinetobacter phage to date. To gain a better understanding of the genetic characteristics of ZZ1, bioinformatics and comparative genomic analyses of the T4 phages were performed. RESULTS: The 166,687-bp double-stranded DNA genome of ZZ1 has the lowest GC content (34.4%) of the sequenced T4-like Acinetobacter phages. A total of 256 protein-coding genes and 8 tRNA genes were predicted. Forty-three percent of the predicted ZZ1 proteins share up to 73% amino acid identity with T4 proteins, and the homologous genes generally retained the same order and transcriptional direction. Beyond the conserved structural and DNA replication modules, T4 and ZZ1 have diverged substantially by the acquisition and deletion of large blocks of unrelated genes, especially in the first halves of their genomes. In addition, ZZ1 and the four other T4-like Acinetobacter phage genomes (Acj9, Acj61, 133, and Ac42) share a well-organised and highly conserved core genome, particularly in the regions encoding DNA replication and virion structural proteins. Of the ZZ1 proteins, 70, 64, 61, and 56% share up to 86, 85, 81, and 83% amino acid identity with Acj9, Acj61, 133, and Ac42 proteins, respectively. ZZ1 has a different number and types of tRNAs than the other 4 Acinetobacter phages, although some of the ZZ1-encoded tRNAs share high sequence similarity with the tRNAs from these phages. Over half of ZZ1-encoded tRNAs (5 out of 8) are related to optimal codon usage for ZZ1 proteins. However, this correlation was not present in any of the other 4 Acinetobacter phages. CONCLUSIONS: The comparative genomic analysis of these phages provided some new insights into the evolution and diversity of Acinetobacter phages, which might elucidate the evolutionary origin and host-specific adaptation of these phages.

Twist-related protein 1 negatively regulated osteoblastic transdifferentiation of human aortic valve interstitial cells by directly inhibiting runt-related transcription factor 2.

OBJECTIVE: Valve calcification involves transdifferentiation of valve interstitial cells (VICs) into osteoblasts. Twist-related protein 1 (TWIST1) has been established as a negative regulator of osteoblast differentiation in both mouse and human mesenchymal stem cells, but its function in human aortic VICs is unknown. In our study, we determined the mechanism of TWIST1 action in regulating osteoblastic transdifferentiation of human aortic VICs. METHODS: Human calcified and noncalcified aortic valves were examined for TWIST1 expression. Human aortic VICs were isolated and cultured. RESULTS: The data showed that calcified aortic valves express lower levels of TWIST1. In vitro experiments showed that TWIST1 overexpression inhibited the transdifferentiation of VICs into osteoblasts by decreasing the expression of runt-related transcription factor 2 (RUNX2) and its downstream osteoblastic markers. Through chromatin immunoprecipitation and dual luciferase assays, we found that TWIST1 repressed the expression of RUNX2 by directly binding to an E-box located at -820 bp of the RUNX2 P2 promoter region and inhibiting its activity. CONCLUSIONS: Our study results suggest that TWIST1 could play an important role in preventing human aortic valve calcification by negatively regulating osteoblastic transdifferentiation of human aortic VICs through direct inhibition of RUNX2.