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In this paper, we mainly study the p-Kirchhoff type equations with logarithmic nonlinear terms and critical growth: −M∫Ω∇updxΔpu=up∗−2u+λup−2u−up−2ulnu2 x∈Ω, u=0 x∈∂Ω, where Ω⊂ℝN is a bounded domain with a smooth boundary, 2

With the rise of the Internet of Things (IoT), maintaining data confidentiality and protecting user privacy have become increasingly challenging. End devices in the IoT are often deployed in unattended environments and connected to open networks, making them vulnerable to physical tampering and other security attacks. Different authentication key agreement (AKA) schemes have been used in practice; several of them do not cover the necessary security features or are incompatible with resource-constrained end devices. Their security proofs have been performed under the Random-Oracle model. We present an AKA protocol for end devices and servers. The proposal leverages the ECC-based key exchange mechanism and one-way hash function-based message authentication method to achieve mutual authentication, user anonymity, and forward security. A formal security proof of the proposed scheme is performed under the standard model and the eCK model with the elliptic curve encryption computational assumptions, and formal verification is performed with ProVerif. According to the performance comparison, it is revealed that the proposed scheme offers user anonymity, perfect forward security, and mutual authentication, and resists typical attacks such as ephemeral secret leakage attacks, impersonation attacks, man-in-the-middle attacks, and key compromise impersonation attacks. Moreover, the proposed scheme has the lowest computational and communication overhead compared to existing schemes.

Understanding the adoption patterns of clean energy is crucial for designing government subsidies that promote the use of these technologies. Existing work has examined a variety of adoption models to explain and predict how economic factors and other technology and demographic attributes influence adoption, helping to understand the cost-effectiveness of government policies. This study explores the impact of adoption modeling choices on optimal subsidy design within a single techno–economic framework for residential solar PV technology. We applied identical datasets to multiple adoption models and evaluated which model forms appear feasible and how using different choices affects policy decisions. We consider three existing functional forms for rooftop solar adoption: an error function, a mixed log-linear regression, and a logit demand function. The explanatory variables used are a combination of net present value (NPV), socio-demographic, and prior adoption. We compare how the choice of model form and explanatory variables affect optimal subsidy choices. Among the feasible model forms, there exist justified subsidies for residential solar, though the detailed schedule varies. Optimal subsidy schedules are highly dependent on the social cost of carbon and the learning rate. A learning rate of 10% and a social carbon cost of USD 50/ton suggest an optimal subsidy starting at USD 46/kW, while the initial subsidy is 10× higher (USD 540/kW) with a learning rate of 15% and social carbon cost of USD 70/ton. This work illustrates the importance of understanding the true drivers of adoption when developing clean energy policies.

β-Ga2O3, with excellent bandgap, breakdown field, and thermal stability properties, is considered to be one of the most promising candidates for power devices including field-effect transistors (FETs) and for other applications such as Schottky barrier diodes (SBDs) and solar-blind ultraviolet photodetectors. Ohmic contact is one of the key steps in the β-Ga2O3 device fabrication process for power applications. Ohmic contact techniques have been developed in recent years, and they are summarized in this review. First, the basic theory of metal–semiconductor contact is introduced. After that, the representative literature related to Ohmic contact with β-Ga2O3 is summarized and analyzed, including the electrical properties, interface microstructure, Ohmic contact formation mechanism, and contact reliability. In addition, the promising alternative schemes, including novel annealing techniques and Au-free contact materials, which are compatible with the CMOS process, are discussed. This review will help our theoretical understanding of Ohmic contact in β-Ga2O3 devices as well as the development trends of Ohmic contact schemes.

The plant Artemisia annua L. is famous for producing “artemisinin”, which is an essential component in the treatment of malaria. The glandular secretory trichomes (GSTs) on the leaves of A. annua secrete and store artemisinin. Previous research has demonstrated that raising GST density can effectively raise artemisinin content. However, the molecular mechanism of GST initiation is not fully understood yet. In this study, we identified an MYB transcription factor, the AaMYB108-like, which is co-induced by light and jasmonic acid, and positively regulates glandular secretory trichome initiation in A. annua. Overexpression of the AaMYB108-like gene in A. annua increased GST density and enhanced the artemisinin content, whereas anti-sense of the AaMYB108-like gene resulted in the reduction in GST density and artemisinin content. Further experiments demonstrated that the AaMYB108-like gene could form a complex with AaHD8 to promote the expression of downstream AaHD1, resulting in the initiation of GST. Taken together, the AaMYB108-like gene is a positive regulator induced by light and jasmonic acid for GST initiation in A. annua.

Recently, Heptafluoroisobutyronitrile (C4F7N) has received widespread attention in replacing one of the most greenhouse-insulating gas, SF6. However, gas leakage is incredibly harmful to the health of operational personnel and the security of industry production, and developing C4F7N detection technology is of great necessity. In this work, the adsorption properties, as well as the sensing performance of C4F7N on 3d VIII atom-decorated γ-graphyne (γ-GY), were theoretically discussed. The adsorption structures, adsorption energies, electron transfer, adsorption distance, electron distribution, and electronic properties were compared. The results show that the introduction of Fe and Co atom enhance the chemisorption of C4F7N, and the adsorption of C4F7N brings the maximum electron redistribution of Fe/γ-GY among three TM/γ-GY. Only the adsorption on Fe/γ-GY leads to the vanishing of the magnetic moment and creates a band gap. For three different modifications of γ-GY, the chemical interactions are highly related to the overlapping of transition metal 3d and N 2p orbitals in the density of states. The adsorption on Co/γ-GY causes the maximum change in work function from 5.06 eV to 5.26 eV. In addition, based on the band structure, work function, and desorption properties, the sensing properties of 3d VIII atom-decorated γ-GY were evaluated in order to promote the experimental exploration and development of high-performance C4F7N gas sensors.

Multiple functional-material-filled nitrile butadiene rubber/chloroprene rubber (NBR/CR) acoustic composites were extensively studied and prepared. According to the orthogonal test table L25 (56), 25 groups of samples were prepared by using a low-temperature one-time rubber mixing process. With tensile strength, average transmission loss, and damping peak as indexes, the influence degree of different factors and levels on the properties of acoustic composites was quantitatively discussed and analyzed. The matrix weight analysis was employed to optimize the material formula of rubber composites, and the corresponding influence weight was given. Results showed that the acoustic composite with blending ratio of 70/30 for NBR/CR matrix had preferable mechanical and acoustic properties; adding mica powder (MP) and montmorillonite (MMT) in matrix contributed to improve all above three indexes owing to their specific lamellar structures; hollow glass beads (HGB) had a positive influence on improving acoustic property due to its hollow microcavities, however, it had a negative impact on damping property because of the smooth spherical surfaces. Accordingly, the optimal formulation was found to be NBR/CR blending ratio of 70/30, MP of 10 phr (per hundred rubber), HGB of 4 phr, and MMT of 10 phr.

Background: Although hundreds of studies have been conducted, our understanding of the pathogenesis, indications for surgical intervention, and disease markers of Takayasu arteritis (TAK) are still limited. Collection of biological specimens, clinical data and imaging data will facilitate translational research and clinical studies. In this study, we aim to introduce the design and protocol for the Beijing Hospital Takayasu Arteritis (BeTA) Biobank. Methods: Based in the Department of Vascular Surgery of Beijing Hospital and Beijing Hospital Clinical Biological Sample Management Center, the BeTA Biobank is composed of clinical data and sample data from patients with TAK requiring surgical treatment. All clinical data of participants are collected, including demographic characteristics, laboratory tests, imaging results, operation information, perioperative complications, follow-up data, etc. Both blood samples including plasma, serum and cells, and vascular tissues or perivascular adipose tissue are collected and stored. These samples will promote the establishment of a multiomic database for TAK and help to identify disease markers and to explore potential targets for specific future drugs for TAK.

Gradient structures have been created in single crystal nickel-based superalloys (SX alloys) via surface mechanical creep-feed grinding treatment (SMCGT). It has been found that these gradient structures are mainly composed of nano-sized grains, sub-micron-sized grains, dislocation structures, and the matrix material of single crystals along the depth from the treated surface. In addition, the evolution of such structures is found to be dominated by the dislocation movements which run through both γ channels and γ’ precipitates, subdividing the two types of microstructures into various dislocation structures, and eventually introducing the refined grains into the surface layer. Furthermore, the evolution process of gradient structures primarily originates from the mechanical effect between abrasive grits and workpiece material, owing to the large grinding force (up to 529 N) and low grinding temperature (less than 150 °C) during the unique creep-feed grinding treatment in the present investigation. Due to the typical grain refinement, the hardness of the nanostructures exhibits the largest value of around 10 GPa in the surface layer, approximately 26% higher than that of the matrix material. This study further enhances the understanding of the microstructure–property relationship of SX alloys subjected to creep-feed grinding treatment and contributes to achievement of high-performance components.

Data-driven deep neural networks have demonstrated their superiority in high-resolution remote-sensing image (HRSI) classification based on superpixel-based objects. Currently, most HRSI classification methods that combine deep learning and superpixel object segmentation use multiple scales of stacking to satisfy the contextual semantic-information extraction of one analyzed object. However, this approach does not consider the long-distance dependencies between objects, which not only weakens the representation of feature information but also increases computational redundancy. To solve this problem, a superpixel-based long-range dependent network is proposed for HRSI classification. First, a superpixel segmentation algorithm is used to segment HRSI into homogeneous analysis objects as input. Secondly, a multi-channel deep convolutional neural network is proposed for the feature mapping of the analysis objects. Finally, we design a long-range dependent framework based on a long short-term memory (LSTM) network for obtaining contextual relationships and outputting classes of analysis objects. Additionally, we define the semantic range and investigate how it affects classification accuracy. A test is conducted by using two HRSI with overall accuracy (0.79, 0.76) and kappa coefficients (κ) (0.92, 0.89). Both qualitative and quantitative comparisons are adopted to test the proposed method’s efficacy. Findings concluded that the proposed method is competitive and consistently superior to the benchmark comparison method.

AZ31 magnesium alloy sheets with 2 mm thickness were successfully fabricated by multi-pass lowered-temperature rolling. The evolution of the microstructure, texture, and mechanical properties during the rolling process was investigated. Based on the effect of multiple dynamic recrystallization, multi-pass lowered-temperature rolling not only refined the grain size obviously but also markedly improved the microstructure homogeneity. The resulting sheets had the optimal microstructure morphology with an average grain size of 4.38 μm. For the texture evolution, the stress state of the rolling process made the (0002) basal plane gradually rotate toward the rolling plane. However, the activation of non-basal slips due to the higher rolling temperature slightly rotated the (0002) basal plane point to the rolling direction (RD). As a result, the grain refinement strengthening and the texture strengthening together increased the yield stress to 202 MPa in the transverse direction (TD) and 189.8 MPa in the RD. Importantly, the resulting sheet concurrently exhibited excellent fracture elongation, about 38% in the TD and 39.2% in the RD. This was mainly ascribed to the finer grain size, giving rise to a significant effect of grain boundary sliding and the activation amount of non-basal slips.

In recent years, van der Waals heterostructures (vdWHs) of two-dimensional (2D) materials have attracted extensive research interest. By stacking various 2D materials together to form vdWHs, it is interesting to see that new and fascinating properties are formed beyond single 2D materials; thus, 2D heterostructures-based nanodevices, especially for potential optoelectronic applications, were successfully constructed in the past few decades. With the dramatically increased demand for well-controlled heterostructures for nanodevices with desired performance in recent years, various interfacial modulation methods have been carried out to regulate the interfacial coupling of such heterostructures. Here, the research progress in the study of interfacial coupling of vdWHs (investigated by Photoluminescence, Raman, and Pump–probe spectroscopies as well as other techniques), the modulation of interfacial coupling by applying various external fields (including electrical, optical, mechanical fields), as well as the related applications for future electrics and optoelectronics, have been briefly reviewed. By summarizing the recent progress, discussing the recent advances, and looking forward to future trends and existing challenges, this review is aimed at providing an overall picture of the importance of interfacial modulation in vdWHs for possible strategies to optimize the device’s performance.

AlGaN/GaN high electron mobility transistors (HEMTs) are regarded as promising candidates for a 5G communication system, which demands higher frequency and power. Source/drain ohmic contact is one of the key fabrication processes crucial to the device performance. Firstly, Au-contained metal stacks combined with RTA high-temperature ohmic contact schemes were presented and analyzed, including process conditions and contact formation mechanisms. Considering the issues with the Au-contained technique, the overview of a sequence of Au-free schemes is given and comprehensively discussed. In addition, in order to solve various problems caused by high-temperature conditions, novel annealing techniques including microwave annealing (MWA) and laser annealing (LA) were proposed to form Au-free low-temperature ohmic contact to AlGaN/GaN HEMT. The effects of the annealing method on surface morphology, gate leakage, dynamic on-resistance (RON), and other device characteristics are investigated and presented in this paper. By using a low-temperature annealing atmosphere or selective annealing method, gate-first Si-CMOS compatible AlGaN/GaN HEMT technology can be realized for high frequency and power application.

Aiming at the problem of fault diagnosis in continuous time systems, a kind of fault diagnosis algorithm based on adaptive nonlinear proportional integral (PI) observer, which can realize the effective fault identification, is studied in this paper. Firstly, the stability and stability conditions of fault diagnosis method based on the PI observer are analyzed, and the upper bound of the fault estimation error is given. Secondly, the fault diagnosis algorithm based on adjustable nonlinear PI observer is designed and constructed, it is analyzed and we proved that the upper bound of fault estimation under this algorithm is better than that of the traditional method. Finally, the L-1011 unmanned aerial vehicle (UAV) is taken as the experimental object for numerical simulation, and the fault diagnosis method based on adaptive observer factor achieves faster response speed and more accurate fault identification results.

Cucumber monoculture could cause soil salinization and acidification, soilborne diseases, and eventually yield loss. However, after a 25-year monoculture in Wafangdian county, Liaoning province, China, cucumber yields have remained satisfactory. In the present study, we investigated how the soil abiotic and biotic properties, in addition to soil rhizosphere microbial community structure in the greenhouses, could still sustain plant growth after such long-term monoculture production. Soil organic carbon, total nitrogen, and available nitrogen were accumulated significantly after monoculture. Such increasing soil fertility was accompanied by increased soil microbial abundance, which reshaped soil microbial community structure. Both bacterial and fungal diversity, including observed and estimated richness, Heip evenness, and Shannon diversity, decreased significantly, while the monoculture period had a greater influence on fungal diversity than on bacterial diversity. Although the high accumulation of soil nutrients increased soil salinity and acidity, the abundance of potential plant pathogenic fungi did not show an obvious increase. These results indicated that maintaining soil abiotic and biotic properties using organic fertilizers and balanced chemical fertilizers, especially improving potassium fertilizer application, could be useful measurements for the sustainable development of greenhouse vegetable production. In addition, appropriate management strategies should be considered to reduce the potential risk of soil salinization.

Psocids are a new risk for global food security and safety because they are significant worldwide pests of stored products. Among these psocids, Liposcelis bostrychophila has developed high levels of resistance or tolerance to heat treatment in grain storage systems, and thus has led to investigation of molecular mechanisms underlying heat tolerance in this pest. In this study, the time-related effects of thermal stress treatments at relatively high temperatures on the activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidases (POD), glutathione-S-transferases (GST) and malondialdehyde (MDA), of L. bostrychophila were determined. Thermal stress resulted that L. bostrychophila had a significantly higher MDA concentration at 42.5 °C, which indicated that the heat stress increased lipid peroxidation (LPO) contents and oxidative stress in this psocid pest. Heat stress also resulted in significant elevation of SOD, CAT and GST activities but decreased POD activity. Our data indicates that different antioxidant enzymes contribute to defense mechanisms, counteracting oxidative damage in varying levels. POD play minor roles in scavenging deleterious LPO, while enhanced SOD, CAT and GST activities in response to thermal stress likely play a more important role against oxidative damage. Here, we firstly identified five LbHsps (four LbHsp70s and one LbHsp110) from psocids, and most of these LbHsps (except LbHsp70-1) are highly expressed at fourth instar nymph and adults, and LbHsp70-1 likely presents as a cognate form of HSP due to its non-significant changes of expression. Most LbHsp70s (except LbHsp70-4) are significantly induced at moderate high temperatures (LbHsp110-1 can be significantly induced at all high temperatures. Results of this study suggest that the LbHsp70s and LbHsp110 genes are involved in tolerance to thermal stress in L. bostrychophila, and antioxidant enzymes and heat shock proteins may be coordinately involved in the tolerance to thermal stress in psocids.

Fraxinellone (1) is a naturally occurring degraded limonoid isolated from Meliaceae and Rutaceae plants. As a potential natural-product-based insecticidal agent, fraxinellone has been structurally modified to improve its activity. Furan ring of fraxinellone is critical in exhibiting its insecticidal activity, but with few modifications. Herein, C-ring-modified cyclopropyl analogues were semi-synthesized by Rh(II)-catalyzed cyclopropanation. The structures of the target compounds were well characterized by NMR and HRMS. The precise three-dimensional structural information of 3a was established by X-ray crystallography. Their insecticidal activity was evaluated against Mythimna separata Walker by a leaf-dipping method. Compound 3c exhibited stronger insecticidal activity than 1 and toosendanin against M. separata with teratogenic symptoms during the different periods, implying that cyclopropanation of the furan ring could strengthen the insecticidal activity of fraxinellone.

Bone mesenchymal stem cells (BMSCs) have multiple potentials to differentiate into osteoblasts and adipocytes, and methods to enhance their osteogenic differentiation are gaining increasing attention. MicroRNAs are critical regulation factors during the process of the osteogenic induction in BMSCs, and mir-205 has been substantiated to be involved in the osteogenic process, but the underlying mechanisms remain unclear. The purpose of this article is to investigate the role of mir-205 in the osteogenic differentiation of BMSCs. We found that mir-205 expression was down-regulated in a time-dependent manner during BMSC osteo-induction. Inhibition of mir-205 enhanced osteogenic abilities by up-regulating bone sialoprotein (BSP) and osteopontin (OPN) protein levels and increasing alkaline phosphatase (ALP) activity and osteocalcin secretion. Furthermore, we found that mir-205 could regulate protein expression of special AT-rich sequence-binding protein 2 (SATB2) and runt-related transcription factor 2 (Runx2), and over-expression of SATB2 activated Runx2 and reversed the negative effects of mir-205 on osteoblastic differentiation. Furthermore, we examined the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) pathways during osteogenic induction and our data indicates that mir-205 might exert negative functions on the osteogenic differentiation in BMSCs at least partly via altering phosphorylation of ERK and p38 MAPK. These results shed new light on the molecular mechanisms of microRNAs in governing differentiation of BMSCs.

This paper analyzes the nonlocal elliptic system involving the p(x)-biharmonic operator. We give the corresponding variational structure of the problem, and then by means of Ricceri’s Variational theorem and the definition of general Lebesgue-Sobolev space, we obtain sufficient conditions for the infinite solutions to this problem.

The development of a multifunctional nanoprobe capable of non-invasive multimodal imaging is crucial for precise tumour diagnosis. Herein, we report a facile polymer-assisted method to produce Au-Fe3O4 nanocomposites (NCPs) for the dual-modal magnetic resonance (MR) and X-ray computed tomography (CT) imaging of tumours. In this approach, amino-functionalized Au nanospheres were first obtained by surface modification of the bifunctional polymer SH-PEG-NH2. Hydrophilic and carboxyl-functionalized Fe3O4 nanoparticles were produced by phase transfer of reverse micelle oxidation in our previous work. The Au nanoparticles were conjugated with hydrophilic Fe3O4 nanoparticles through an amide reaction. The obtained Au-Fe3O4 nanocomposites display a high r2 relativity (157.92 mM−1 s−1) and a Hounsfield units (HU) value (270 HU) at Au concentration of 8 mg/mL and could be applied as nanoprobes for the dual-modal MR/CT imaging of a xenografted tumour model. Our work provides a facile method to prepare Au-Fe3O4 nanocomposites for dual-modal MR/CT imaging, and this method can be extended to prepare other multifunctional nanoparticles for multimodal bioimaging.

In this work, the influence of various rolling temperatures and thickness reductions on the dynamic recrystallization (DRX) behavior of AZ31 magnesium alloy sheets was investigated. Meanwhile, the texture variation controlled by DRX behavior was analyzed. Results suggested that, with the help of DRX behavior, reasonable matching of rolling temperature and thickness reduction could effectively refine the grain size and improve the microstructure homogeneity. Using the grain refinement and microstructure homogeneity as the reference, the critical rolling process parameters were 400 °C—30%, 300 °C—30%, and 250 °C—40% in the present work. In terms of basal texture variation, the occurrence of twins produced the largest maximum texture intensity. However, for the sheets with DRX behavior, the maximum texture intensity decreased sharply, but would steadily increase with the growth of DRXed grain. Additionally, for DRXed grains, the //RD (RD: rolling direction) grains would gradually annex the //RD grains with the growth of DRXed grains, which finally made their texture component become the dominant texture state. However, when the deformation continued, the in DRXed grains would rotate toward the RD again. Weighted by the fracture elongation of AZ31 magnesium alloy sheet, the critical thickness reductions were 30–40% under the rolling temperature of 400 °C.

The traditional Chinese medicine bufalin, extracted from toad’s skin, has been demonstrated to exert anticancer activities in various kinds of human cancers. The mechanisms of action lie in its capacity to induce apoptosis, or termed type I programmed cell death (PCD). However, type II PCD, or autophagy, participates in cancer proliferation, progression, and relapse, as well. Recent studies on autophagy seem to be controversial because of the dual roles of autophagy in cancer survival and death. In good agreement with previous studies, we found that 100 nM bufalin induced extensive HepG2 cell apoptosis. However, we also noticed bufalin triggered autophagy and enhanced Beclin-1 expression, LC3-I to LC3-II conversion, as well as decreased p62 expression and mTOR signaling activation in HepG2 cells. Blockage of autophagy by selective inhibitor 3-MA decreased apoptotic ratio in bufalin-treated HepG2 cells, suggesting a proapoptotic role of bufalin-induced autophagy. Furthermore, we investigated the underlying mechanisms of bufalin-induced autophagy. Bufalin treatment dose-dependently promoted AMPK phosphorylation while AMPK inhibition by compound C significantly attenuated bufalin-induced autophagy. Taken together, we report for the first time that bufalin induces HepG2 cells PCD, especially for autophagy, and the mechanism of action is, at least in part, AMPK-mTOR dependent.

Hypoxic pulmonary hypertension is a life-threatening emergency if untreated. Consistent pulmonary hypertension also leads to arteries and ventricular remodeling. The clinical therapeutic strategy for pulmonary hypertension and the corresponding remodeling mainly interacts with NO, angiotensin II (Ang II) and elevated endothelin (ET) targets. In the present study, we evaluated the effects of polydatin on hypoxia-induced pulmonary hypertension. It was observed that polydatin attenuated hypoxic pulmonary hypertension, reversed remodeling, and regulated NO, Ang II, ET contents in the serum and lung samples. However, forced activation of PKC signaling by its selective activator thymeleatoxin (THX) could abate the effects of polydatain. These results suggest that polydatin might be a promising candidate for hypoxic pulmonary treatment through interaction with PKC mechanisms.

Genistein, a major phytoestrogen of soy, is considered a potential drug for the prevention and treatment of post-menopausal osteoporosis. Mounting evidence suggested a positive correlation between genistein consumption and bone health both in vivo and in vitro. Earlier studies have revealed that genistein acted as a natural estrogen analogue which activated estrogen receptor and exerted anti-osteoporotic effect. However, it remains unclear whether PTH, the most crucial hormone that regulates mineral homeostasis, participates in the process of genistein-mediated bone protection. In the present study, we compared the therapeutic effects between genistein and nilestriol and investigated whether PTH and its specific receptor PTHR1 altered in response to genistein-containing diet in the animal model of ovariectomy. Our results showed that genistein administration significantly improved femoral mechanical properties and alleviates femoral turnover. Genistein at all doses (4.5 mg/kg, 9.0 mg/kg and 18.0 mg/kg per day, respectively) exerted improved bending strength and b-ALP limiting effects than nilestriol in the present study. However, genistein administration did not exert superior effects on bone protection than nilestriol. We also observed circulating PTH restoration in ovariectomized rats receiving genistein at the dose of 18 mg/kg per day. Meanwhile, PTHR1 abnormalities were attenuated in the presence of genistein as confirmed by RT-PCR, Western blot and immunohistochemistry. These findings strongly support the idea that besides serving as an estrogen, genistein could interact with PTH/PTHR1, causing a superior mineral restoring effect than nilestriol on certain circumstance. In conclusion, our study reported for the first time that the anti-osteoporotic effect of genistein is partly PTH/PTHR1-dependent. Genistein might be a potential option in the prevention and treatment of post-menopausal osteoporosis with good tolerance, more clinical benefits and few undesirable side effects.

Tryptanthrin, a kind of indole quinazoline alkaloid, has been shown to exhibit anti-microbial, anti-inflammation and anti-tumor effects both in vivo and in vitro. However, its biological activity on human chronic myeloid leukemia cell line K562 is not fully understood. In the present study, we investigated the proliferation-attenuating and apoptosis-inducing effects of tryptanthrin on leukemia K562 cells in vitro and explored the underlying mechanisms. The results showed that tryptanthrin could significantly inhibit K562 cells proliferation in a time- and dose-dependent manner as evidenced by MTT assay and flow cytometry analysis. We also observed pyknosis, chromatin margination and the formation of apoptotic bodies in the presence of tryptanthrin under the electron microscope. Nuclei fragmentation and condensation by Hoechst 33258 staining were detected as well. The amount of apoptotic cells significantly increased whereas the mitochondrial membrane potential decreased dramatically after tryptanthrin exposure. K562 cells in the tryptanthrin treated group exhibited an increase in cytosol cyt-c, Bax and activated caspase-3 expression while a decrease in Bcl-2, mito cyt-c and pro-caspase-3 contents. However, the changes of pro-caspase-3 and activated caspase-3 could be abolished by a pan-caspase inhibitor ZVAD-FMK. These results suggest that tryptanthrin has proliferation-attenuating and apoptosis-inducing effects on K562 cells. The underlying mechanism is probably attributed to the reduction in mitochondria membrane potential, the release of mito cyt-c and pro-caspase-3 activation.