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When online retailers allow third-party sellers to place certain products on their platforms, these sellers become not only collaborators but also competitors. The purpose of this study is to compare the differences in price discounts between Third-Party Marketplace (3PM) sellers and Fulfilled by Walmart (FBW) sellers on Walmart.com over time. The results, based on data collected in the form of the daily prices of 54,162 products offered by Walmart during the holiday season, show that the average discount for 3PM sellers is significantly lower than that for FBW sellers. In addition, across product categories, FBW sellers had significantly higher average discounts than 3PM sellers in the electronics, housewares, and toys categories. Furthermore, the level of discount began to increase in early November and peaked around Christmas. Our findings may help retailers manage their dealings with these third-party sellers while also helping consumers to optimize their purchasing decisions.

Background: Extracorporeal membrane oxygenation (ECMO) is rapidly becoming a mainstream technology for lung or heart/lung support especially during the COVID-19 pandemic. “Awake ECMO”is frequently used to indicate an alternative approach of using ECMO without invasive mechanical ventilation, and it has the unique advantages of application. In this study, we explored the feasibility and stability of the establishment method and management strategy of long-term awake ECMO model in healthy sheep. As the sheep are healthy, according to the histopathological analysis , we explored the effect of ECMO circuit itself on organs and tissues. As a preclinical study in large animals, our study aims to provide clues for further research on application expansion, management strategy optimization, pathophysiology exploration, equipment development and subsequent establishment of the disease animal model.Methods: Ten healthy sheep were treated with awake veno-arterial (V-A) or veno-venous (V-V) ECMO for 7 days. They were transferred into the monitoring cages after operation and were ambulatory after anesthesia recovery. ECMO configurations, hemodynamic and hematologic parameters were measured every day. Necropsy was conducted at the endpoint of the experiment to visualize the cannula position in vivo and to examine cannulation related injury and thrombus formation in blood vessels and major organs. Main organs and blood vessels were harvested for pathological investigation.Results: All sheep survived to the end of the experiment (the 7th day). In the whole process of the experiment, the vital signs of which were stable, and no serious bleeding and coagulation events occurred. Hemoglobin concentration and platelet count were in normal reference range, plasma free hemoglobin concentration was maintained at a low level. ECMO flow was stable, and oxygenation performance of oxygenator was satisfied. There was no major adverse pathological injury occurred.Conclusions: Long term awake extracorporeal membrane oxygenation model in large animal is feasible and stable. Perioperative management is the key to the success of this model. As a basic research, it can also provide an alternative strategy for mechanical circulatory support in patients with awake ECMO indications.

We demonstrate a new type of haptic actuator, which we call MagnetIO, that is comprised of two parts: one battery-powered voice-coil worn on the user's fingernail and any number of interactive soft patches that can be attached onto any surface (everyday objects, user's body, appliances, etc.). When the user's finger wearing our voice-coil contacts any of the interactive patches it detects its magnetic signature via magnetometer and vibrates the patch, adding haptic feedback to otherwise input-only interactions. To allow these passive patches to vibrate, we make them from silicone with regions doped with polarized neodymium powder, resulting in soft and stretchable magnets. This stretchable form-factor allows them to be wrapped to the user's body or everyday objects of various shapes. We demonstrate how these add haptic output to many situations, such as adding haptic buttons to the walls of one's home.

We demonstrate two trigeminal-based interfaces. The first provides a temperature illusion that uses low-powered electronics and enables the miniaturization of simple warm and cool sensations. Our illusion relies on the properties of certain scents, such as the coolness of mint or hotness of peppers. These odors trigger not only the olfactory bulb, but also the nose's trigeminal nerve, which has receptors that respond to both temperature and chemicals. The second is a novel type of olfactory device that creates a stereo-smell experience, i.e., directional information about the location of an odor, by rendering the readings of external odor sensors as trigeminal sensations using electrical stimulation of the user's nasal septum. We propose that electrically stimulating the trigeminal nerve is an ideal candidate for stereo-smell rendering. We demonstrate these interfaces by allowing an audience to stimulate an author and receive an explanation of the sensations.

Current head-mounted displays enable users to explore virtual worlds by simply walking through them (i.e., real-walking VR). This led researchers to create haptic displays that can also simulate different types of elevation shapes. However, existing shape-changing floors are limited by their tabletop scale or the coarse resolution of the terrains they can display due to the limited number of actuators and low vertical resolution. To tackle this challenge, we introduce Elevate, a dynamic and walkable pin-array floor on which users can experience not only large variations in shapes but also the details of the underlying terrain. Our system achieves this by packing 1200 pins arranged on a 1.80 × 0.60m platform, in which each pin can be actuated to one of ten height levels (resolution: 15mm/level). To demonstrate its applicability, we present our haptic floor combined with four walkable applications and a user study that reported increased realism and enjoyment.

We propose a nail-mounted foldable haptic device that provides tactile feedback to mixed reality (MR) environments by pressing against the user's fingerpad when a user touches a virtual object. What is novel in our device is that it quickly tucks away when the user interacts with real-world objects. Its design allows it to fold back on top of the user's nail when not in use, keeping the user's fingerpad free to, for instance, manipulate handheld tools and other objects while in MR. To achieve this, we engineered a wireless and self-contained haptic device, which measures 24×24×41 mm and weighs 9.5 g. Furthermore, our foldable end-effector also features a linear resonant actuator, allowing it to render not only touch contacts (i.e., pressure) but also textures (i.e., vibrations). We demonstrate how our device renders contacts with MR surfaces, buttons, low- and high-frequency textures. In our first user study, we found that participants perceived our device to be more realistic than a previous haptic device that also leaves the fingerpad free (i.e., fingernail vibration). In our second user study, we investigated the participants’ experience while using our device in a real-world task that involved physical objects. We found that our device allowed participants to use the same finger to manipulate handheld tools, small objects, and even feel textures and liquids, without much hindrance to their dexterity, while feeling haptic feedback when touching MR interfaces.

We propose a new type of haptic actuator, which we call MagnetIO, that is comprised of two parts: one battery-powered voice-coil worn on the user's fingernail and any number of interactive soft patches that can be attached onto any surface (everyday objects, user's body, appliances, etc.). When the user's finger wearing our voice-coil contacts any of the interactive patches it detects its magnetic signature via magnetometer and vibrates the patch, adding haptic feedback to otherwise input-only interactions. To allow these passive patches to vibrate, we make them from silicone with regions doped with polarized neodymium powder, resulting in soft and stretchable magnets. This stretchable form-factor allows them to be wrapped to the user's body or everyday objects of various shapes. We demonstrate how these add haptic output to many situations, such as adding haptic buttons to the walls of one's home. In our technical evaluation, we demonstrate that our interactive patches can be excited across a wide range of frequencies (0-500 Hz) and can be tuned to resonate at specific frequencies based on the patch's geometry. Furthermore, we demonstrate that MagnetIO's vibration intensity is as powerful as a typical linear resonant actuator (LRA); yet, unlike these rigid actuators, our passive patches operate as springs with multiple modes of vibration, which enables a wider band around its resonant frequency than an equivalent LRA.

Zinc oxide (ZnO) possesses superior chemical and physical properties so that it can occupy an essential position in the application of nanostructures. In this paper, ZnO nano-rod arrays were synthesized by a simple one-step hydrothermal approach with the assistance of cetyl trimethyl ammonium bromide (CTAB). Exposure of the {0001} facets could be controlled by adjusting the amount of CTAB and the maximum exposure of the {0001} facets of ZnO nanorods is obtained at 1.2 g of CTAB. The photocurrent, EIS, and PL measurements support the facile charge transfer with minimum recombination of the photogenerated excitons of the ZnO nano-rod arrays obtained at 1.2 g of CTAB. Consequently, the obtained ZnO nano-rod arrays at the optimal CTAB of 1.2 g exhibit an excellent photocatalytic degradation rate of 99.7% for rhodamine B (RhB), while the degradation rate of RhB by the ZnO obtained without CTAB is only 35%.

A novel archetype of nonlinear energy sink (NES) enhanced by an inerter is proposed for vibration reduction of vibrating systems. The proposed NES-inerter suppressed vibration more effectively than a convenient NES measured by both energy dissipation and amplitude frequency responses. Complexification-averaging technique is applied to analyze a coupled system to find steady-state periodic solutions, and the analytical results are confirmed by numerical simulations. The analytical solutions are used to bifurcation analysis, and the results show that the saddle node and the Hopf bifurcations occur under a series of parameters in the steady-state responses. The effects of parameters, such as inertance, cubic stiffness, viscous damping, and amplitude of the external excitation, on the performance of the proposed NES are examined based on the analytical solutions. The investigation reveals that the optimal value of the inerter exists in a certain range.

In this study, high quality monodispersed nanocrystalline cupric oxide (CuO) nanopowder was prepared through novel sol-gel green synthesis method, assisted by sodium alginate (Na-ALG) as the green ionic exchange material. The morphology and structural properties of CuO nanopowders synthesized with and without the incorporation of extrusion dripping, at different Na-ALG solution concentrations and calcination temperatures, were studied using thermalgravimetric analysis (TGA), field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX) and Raman spectroscopy. Optimum synthesis conditions were identified, resulting in high-purity, monodispersed nanocrystalline CuO powder in the range of 9.92 – 12.4 nm, which could have a promising future in various applications.

This study proposes a new measure of systemic risk named CSRISK, which identifies a financial institution's capital shortfall under the worst scenario conditional on a substantial market decline. The CSRISK index requires only public financial data, including accounting and market trading information, which is time and cost effective. The empirical sample consists of 238 US banks over the time period 2003–2013. Overall, we find that it is increasing from 2004 to 2009 and then starts to slightly decrease. This systemic risk measure has the potential to be widely applied in the practical aspects of risk management and macroprudential policy making.

Motivated by the recent literature on cryptocurrency volatility dynamics, this paper adopts the ARJI, GARCH, EGARCH, and CGARCH models to explore their capabilities to make out-of-sample volatility...

Because of physically separated sensing region from field-effect region, the extended-gate ion-sensitive field-effect transistor (EG-ISFET) has many advantages over the ISFET including light insensitivity, easy fabrication, and flexibility of sensor array arrangement [1-2]. However, in the EG-ISFET configuration, there is an additional capacitance derived from the passivation layer on the top of extended gate. As a consequence, part of sensing voltages drop across the derived capacitance and the transconductance of EG-ISFET is attenuated. It should be noted that a small transconductance would result in a less current variation and lead to a poor performance in sensitivity. Increasing the capacitance by increasing the two-dimensional area of the top metal layer of the extended gate can ameliorate this issue [3]. However, it will arise other issues such as increasing the fabrication cost at the expense of larger wafer area and decreasing the pixel-resolution of sensor array because of enlargement of each sensing pixel. To address this issue, in this study we propose a lifted three-dimensional (3D) metal architecture as the extended gate for an EG-ISFET. Compared with the conventional EG-ISFET with a planar electrode surface (Fig. 1A), the proposed lifted EG-ISFET, namely the LEG-ISFET, has two metal layers lifted beyond the planar surface (Fig. 1B). Obviously, the LEG-ISFET has larger liquid/solid interface surface area than the conventional EG-ISFET does. In other words, the LEG-ISFET should have a better transconductance than the conventional EG-ISFET does. At the same time, the LEG-ISFET keeps the same wafer area as the conventional EG-ISFET. To fabricate the proposed LEG-ISFET, conventional EG-ISFETs and LEG-ISFETs with different size of top metal layer are implemented on the same chip by a standard CMOS 0.35 μm process. Then the fabricated chip undergoes wet etching to remove passivation-free metal/via layers including the oxides surrounded by them to realize the lifted 3D metal structure as shown in Fig. 2. In experiments, the ID-VG curve of each FET device is measured using Ag/AgCl reference electrode in a pH7 buffer solution. Based on the slope of the measured curves, the transconductance can be extracted. To facilitate the comparison, Table 1 shows different symbols representing different device designs. Based on the experiment, it shows that the transconductance attenuates seriously in the conventional EG-ISFET with the smallest top metal area (Fig. 3A). Compared with the MOSFET with exactly the same structure, the transconductance measured from conventional EG-ISFET is about 3 times lower than that of the MOSFET with the same structure. As the top metal area increased, the transconductance of the conventional EG-ISFET is gradually increased. On the other hand, the transconductance of each proposed LEG-ISFET is at the same level as the intrinsic MOSFET (Fig. 3B). It should be noted that the smallest LEG-ISFET has a 3D electrode surface area estimated about 3 times to the 2D top-electrode area of the smallest EG-ISFET. However, the transconductance improvement of the smallest LEG-ISFET is roughly the same as the largest EG-ISFET, which has about 600 times the top-electrode area of the smallest EG-ISFET. This finding suggests that factors other than surface area should also account for the transconductance enhancement. It is interesting to investigate the underlying mechanism to further improve the performance of ISFET. In conclusion, a high-transconductance configuration of LEG-ISFET is proposed and verified. This development has potentials for realization of sensor array with high pixel-resolution and high sensitivity. [1] Kaisti, Matti. "Detection principles of biological and chemical FET sensors." Biosensors and Bioelectronics 98 (2017): 437-448. [2] Chi, Li-Lun, et al. "Study on extended gate field effect transistor with tin oxide sensing membrane." Materials Chemistry and Physics 63.1 (2000): 19-23. [3] Sohbati, Mohammadreza, and Christofer Toumazou. "Dimension and shape effects on the ISFET performance." IEEE Sensors Journal 15.3 (2015): 1670-1679. Figure 1

Surface mounted microelectronic (SMT) consist of components and packages mounted on printed circuit board (PCB) via solder joints. The SMT assemblies are subjected to elevated temperature during processing as well as during usage cycles. The processes result in thermal-mechanical strain to the SMT package which can reduce the lifespan of the product. In this work, the thermomechanical behaviour of a surface mounted microelectronic package-a solid state drive (SSD) is studied by finite element analysis (FEA). The results show that bared PCB warped when it is heated while PCB with packages resists the warpage thus generating stress at the solder joints. The results show that the stress level at the top of the solder joint (between the package and solder ball) is higher than the stress generated at the bottom of the solder joint (between the solder ball and PCB). FEA simulation also shows when a package is reduced in size by 50%, the thermomechanical induced stress at the solder joints decreased to a value well below the stress limit of the solder joint materials.

A phytochemical study on the aerial parts of Hypericum elatoides led to the isolation of a previously undescribed polycyclic polyprenylated acylphloroglucinol derivative, hyperelatone A, seven previously undescribed phenolic metabolites, hyperelatones B–H, along with ten known analogues. The structures of hyperelatones A–H were elucidated by 1D and 2D NMR spectroscopy, HRESIMS experiment, single-crystal X-ray diffraction and comparison of experimental and calculated ECD spectra, as well as chemical derivatization. All compounds were evaluated for their neuroprotective activity against hydrogen peroxide (H2O2)-induced cell injury in rat pheochromocytoma PC-12 cells and inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglial cells. Hyperelatones B–D and H, cinchonain Ib, and tenuiside A showed noticeable neuroprotection at concentrations of 1.0–100.0 μM. Hyperelatones D, G, and H, (−)-epicatechin, tenuiside A, and (Z)-3-hexenyl-β-D-glucopyranoside exhibited significant anti-neuroinflammatory activity with IC50 values ranging from 0.75 ± 0.02 to 5.83 ± 0.23 μM.

High-quality graphene grown on metal-free substrates represents a vital milestone that provides an atomic clean interface and a complementary metal-oxide-semiconductor-compatible manufacturing process for electronic applications. We report a scalable approach to fabricate radio frequency field-effect transistors with a graphene channel grown directly on the sapphire substrate using the technique of remote-catalyzed chemical vapor deposition (CVD). A mushroom-shaped AlO

Drought stress led to a decrease in PSII photochemical activity in tobacco leaves and the blockage of electron transfer, especially from QA to QB on PSII acceptor side. In addition, drought stress caused a dramatic increase in H2O2 and MDA contents. However, the overexpression of 2-Cys Prx significantly reduced the H2O2 accumulation in tobacco seedlings and alleviated the degree of oxidative damage under drought stress. It also improved stomatal limitation and net photosynthetic rate of tobacco seedlings and reduced its PSII photoinhibition under drought stress which promoted the ability of PSII electron transfer.

Measuring the perceived quality of professors’ teaching effectiveness is a critical issue in higher education. This study involves a large-scale data exploration with a sample of 16,802 professors, in which each professor had received at least 20 ratings from the RateMyProfessors website. We find that perceived difficulty (from the students’ perspective) has a significantly negative effect on perceived quality. However, when professors teach more difficult courses at top colleges, the decline in perceived quality is relatively small when compared to other colleges. In other words, whether professors come from top colleges has a moderating effect on the relationship between perceived quality and perceived difficulty. Furthermore, through a consideration of the characteristic differences among disciplines in terms of the relationship between perceived quality and perceived difficulty, we obtain three specific groups of disciplines. These findings facilitate a better understanding of quality for prof...

As the Chinese RMB internationalization process accelerates, Chinese institutions and investors are increasingly seeking to invest in overseas financial markets. Accordingly, Chinese investors have more opportunities to hold foreign assets in US dollars and face currency risk in their portfolios. In this paper, we investigate the difference between fully hedged and unhedged portfolios consisting of 10 different risky asset datasets from 2006 to 2014 from the perspective of Chinese investors. The empirical results show that the fully hedged portfolios have significantly higher Sharpe ratios than the unhedged ones. In terms of economic benefit, a risk-averse investor would be willing to pay more per year to construct the fully hedged portfolio. For instance, using the equal-weighted portfolio strategy, investors are willing to pay more than 7.2% and 3.3% annually to eliminate the RMB currency risk in terms of CNY and CNH, respectively. Moreover, according to the outcomes in subperiods and time-varying rolling estimations, we conclude that currency hedging in portfolio management will become increasingly important during RMB internationalization.

Producing good economic value in trading strategies for investors based on technical analysis is an issue of major interest in the academe and in practice. This study considers 9,555 trading rules and examines the usability of technical analysis. The double‐or‐out (DO) and the optimal‐portfolio (OP) strategies are used to investigate how investors construct their ass et allocation. The sample for empirical study is comprised of 20 major stock indexes from global markets as risky assets from 1998 to 2013. The DO strategy on average produces higher terminal wealth rather than does the buy‐and‐hold (BH) strategy, but the average utility (AU) of the former is worse than the latter. Nevertheless, using the OP strategy not only increases the terminal wealth of investors but also generates higher utility. Given a starting investment of one dollar and considering the best 100 trading rules, the DO and OP strategies result in average terminal wealth of 17.6 dollars and 5.9 dollars, respectively. In addition, in terms of AU, both of them are better than the BH strategy. These pieces of evidence demonstrate that investors who use an appropriate strategy of technical analysis in ass et allocation can produce good economic value, a finding that supports the continued use of technical analysis in practice.

Background Online health care services are a possible solution to alleviate the lack of medical resources in rural areas, and further understanding of the related medical service pricing system would contribute to improvement of the online health care community (OHC). Although many studies have investigated the OHC, the impact of physicians’ reputations and wage levels on consulting prices in the OHC has rarely been discussed in the literature. Objective This study was designed to explore the determinants of consulting prices in the OHC. We addressed the following questions: (1) Are the prices of online health consultation services affected by wage levels at the doctor’s location? (2) How does a physician’s online and offline reputation affect their consulting prices? Methods Employing a large-scale sample of 16,008 doctors in China, we first used descriptive statistics to investigate the determinants of consulting prices in their entirety. Hierarchical linear modeling was then used to investigate the determinants of consulting prices in the OHC. Results The empirical results led to the conclusion that if doctors have more elevated clinic titles, work in higher-level hospitals, have better online reputations, and/or have made more past sales, their consulting prices will be higher. Additionally, the wage level in the city in which the doctor is working determines their opportunity cost and therefore also affects consulting prices. Conclusions The findings indicate that the characteristics of the doctor, the doctor’s online reputation, and past sales affect the consulting price. In particular, the wage level in the city affects the price of the consultation. These findings highlight that the OHC is important because it can indeed break through geographical restrictions and give rural residents the opportunity to obtain medical service from doctors in big cities. However, doctors from cities often charge higher fees because of their higher opportunity cost. The results reveal that one of the most important functions of the OHC is to reduce the medical disparity between urban and rural areas; however, planners appear to ignore the possibility that rural residents with lower incomes may not be able to afford such high medical consultation costs. Therefore, the government should consider providing incentives to encourage urban doctors to provide discounts to rural residents or directly offer appropriate subsidies.

BACKGROUND Online health care services are a possible solution to alleviate the lack of medical resources in rural areas, and further understanding of the related medical service pricing system would contribute to improvement of the online health care community (OHC). Although many studies have investigated the OHC, the impact of physicians’ reputations and wage levels on consulting prices in the OHC has rarely been discussed in the literature. OBJECTIVE This study was designed to explore the determinants of consulting prices in the OHC. We addressed the following questions: (1) Are the prices of online health consultation services affected by wage levels at the doctor’s location? (2) How does a physician’s online and offline reputation affect their consulting prices? METHODS Employing a large-scale sample of 16,008 doctors in China, we first used descriptive statistics to investigate the determinants of consulting prices in their entirety. Hierarchical linear modeling was then used to investigate the determinants of consulting prices in the OHC. RESULTS The empirical results led to the conclusion that if doctors have more elevated clinic titles, work in higher-level hospitals, have better online reputations, and/or have made more past sales, their consulting prices will be higher. Additionally, the wage level in the city in which the doctor is working determines their opportunity cost and therefore also affects consulting prices. CONCLUSIONS The findings indicate that the characteristics of the doctor, the doctor’s online reputation, and past sales affect the consulting price. In particular, the wage level in the city affects the price of the consultation. These findings highlight that the OHC is important because it can indeed break through geographical restrictions and give rural residents the opportunity to obtain medical service from doctors in big cities. However, doctors from cities often charge higher fees because of their higher opportunity cost. The results reveal that one of the most important functions of the OHC is to reduce the medical disparity between urban and rural areas; however, planners appear to ignore the possibility that rural residents with lower incomes may not be able to afford such high medical consultation costs. Therefore, the government should consider providing incentives to encourage urban doctors to provide discounts to rural residents or directly offer appropriate subsidies.

This paper uses compensation peer groups to measure peer effects in corporate innovation. This approach provides a true peer group and better leader-follower link and thus can mitigate the reflection problem suggested by Manski (1993). We find that the average innovation activity of the compensation peers is a significant and first-order predictor for corporate innovation. Further analyses show that (1) the peer effect is stronger when peer companies experience higher innovation competition and are closer to the median peer company in the peer group, (2) the results are not likely to be attributed to the knowledge spillover mechanism but rather are more consistent with the peer pressure mechanism, and (3) the SEC’s 2006 executive compensation disclosure rules can generate the peer effects. Overall, the results suggest that corporate innovation decisions are responses to innovation activities and, to a lesser extent, the characteristics of the compensation peer groups.

Pif1 is an SF1B helicase that is evolutionarily conserved from bacteria to humans and plays multiple roles in maintaining genome stability in both nucleus and mitochondria. Though highly conserved, Pif1 family harbors a large mechanistic diversity. Here, we report crystal structures of Thermus oshimai Pif1 (ToPif1) alone and complexed with partial duplex or single-stranded DNA. In the apo state and in complex with a partial duplex DNA, ToPif1 is monomeric with its domain 2B/loop3 adopting a closed and an open conformation, respectively. When complexed with a single-stranded DNA, ToPif1 forms a stable dimer with domain 2B/loop3 shifting to a more open conformation. Single-molecule and biochemical assays show that domain 2B/loop3 switches repetitively between the closed and open conformations when a ToPif1 monomer unwinds DNA and, in contrast with other typical dimeric SF1A helicases, dimerization has an inhibitory effect on its helicase activity. This mechanism is not general for all Pif1 helicases but illustrates the diversity of regulation mechanisms among different helicases. It also raises the possibility that although dimerization results in activation for SF1A helicases, it may lead to inhibition for some of the other uncharacterized SF1B helicases, an interesting subject warranting further studies.

Chronic high-dose alcohol consumption impairs bone remodeling, reduces bone mass, and increases the risk of osteoporosis and bone fracture. However, the mechanisms underlying alcohol-induced osteoporosis are yet to be elucidated. In this study, we showed that excess intake of ethyl alcohol (EtOH) resulted in osteopenia and osteoblast necroptosis in mice that led to necrotic lesions and reduced osteogenic differentiation in bone marrow mesenchymal stem cells (BMMSCs). We found that EtOH treatment led to the activation of the RIPK1/RIPK3/MLKL signaling, resulting in increased osteoblast necroptosis and decreased osteogenic differentiation and bone formation both in vivo and in vitro. We further discovered that excessive EtOH treatment-induced osteoblast necroptosis might partly depend on reactive oxygen species (ROS) generation; concomitantly, ROS contributed to necroptosis of osteoblasts through a positive feedback loop involving RIPK1/RIPK3. In addition, blocking of the RIPK1/RIPK3/MLKL signaling by necrostatin-1 (Nec-1), a key inhibitor of RIPK1 kinase in the necroptosis pathway, or antioxidant N-acetylcysteine (NAC), an inhibitor of ROS, could decrease the activation of osteoblast necroptosis and ameliorate alcohol-induced osteopenia both in vivo and in vitro. Collectively, we demonstrated that chronic high-dose alcohol consumption induced osteopenia via osteoblast necroptosis and revealed that RIPK1 kinase may be a therapeutic target for alcohol-induced osteopenia.

RecQ family helicases are highly conserved from bacteria to humans and have essential roles in maintaining genome stability. Mutations in three human RecQ helicases cause severe diseases with the main features of premature aging and cancer predisposition. Most RecQ helicases shared a conserved domain arrangement which comprises a helicase core, an RecQ C-terminal domain, and an auxiliary element helicase and RNaseD C-terminal (HRDC) domain, the functions of which are poorly understood. In this study, we systematically characterized the roles of the HRDC domain in E. coli RecQ in various DNA transactions by single-molecule FRET. We found that RecQ repetitively unwinds the 3′-partial duplex and fork DNA with a moderate processivity and periodically patrols on the ssDNA in the 5′-partial duplex by translocation. The HRDC domain significantly suppresses RecQ activities in the above transactions. In sharp contrast, the HRDC domain is essential for the deep and long-time unfolding of the G4 DNA structure by RecQ. Based on the observations that the HRDC domain dynamically switches between RecA core- and ssDNA-binding modes after RecQ association with DNA, we proposed a model to explain the modulation mechanism of the HRDC domain. Our findings not only provide new insights into the activities of RecQ on different substrates but also highlight the novel functions of the HRDC domain in DNA metabolisms.