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University of Western Australia’s Oceans Graduate School to transform the design methods used to analyse the on-bottom stability of subsea power cables. These cables form the vital connection enabling renewable energy to be reliably and cost-effectively transported from the source to the consumer — whether the collection device at the end of the line is wave, tidal, fixed or floating wind. These novel design methods are equally applicable to umbilicals and other small diameter pipelines. Existing oil and gas pipeline codes overlook much of the physics that is relevant to small diameter pipes and cables. The new research has unlocked significant improvements through new laboratory, numerical and field observational analysis and modelling. The results of this research are presently being incorporated into new design guidance, including the draft British Standards Institute BS 10009 being developed under PEL 114 technical committee guidance. This paper provides a summary of the research together with observations and lessons learnt in the application of these new design methods to over 7.4 GW of new offshore wind and other renewable energy cables. Given that as at 2020 the global grid-connected total offshore wind capacity was 35 GW, this contribution demonstrates strong evidence of field validation of these research outcomes, as well as their relative importance and transformative potential to contribute to global decarbonisation.

Osmotic energy from the ocean, also called blue energy, serves as a clean, renewable, and vast energy source for the energy demands of the world. Reverse electrodialysis-based blue energy harvestin...

Both high ionic conductivity and selectivity of a membrane are required for efficient salinity gradient energy conversion. An efficient method to improve energy conversion is to align ionic transport along the membrane thickness to address low ionic conductivity in traditional membranes used for energy harvesting. Here, we fabricate a free-standing covalent organic frameworks membrane (TpPa-SO 3 H) with excellent stability and mechanical properties. This membrane with one-dimensional nanochannels and high charge density demonstrates high ionic conductivity and selectivity. Its power density can reach up to 5.9 W/m 2 by mixing artificial seawater and river water. Based on our results, we propose that the high energy conversion is attributed to the high ion conductivity through aligned one-dimensional nanochannels and high ion selectivity via the size of the nanochannel at ~1 nm in the membrane. This study paves the way for designing covalent organic framework membranes for high salinity gradient energy conversion.

Employing chemical-potential with reverse electrodialysis is a sustainable way to generate electricity. Based on this observation, efforts have been made to utilize this energy, such as the development of nanomaterials and the introduction of external fields. However, the reported systems mainly focus on a single type of physical field on the enhancement of energy conversion but ignore the synergy between cross-factor types. Here, we report a light and acid–base reaction enhanced energy conversion system based on 1D/2D composite nanofluidics. The contributions of light (physical) and acid–base reaction (chemical) in a chemical-potential-driven ionic generation system are studied separately and jointly. With the synergistic effect of the joint system, the output power density increases to 87.23 W m−2, exceeding the output power density of the state-of-the-art membrane-based systems. Both experimental and theoretical results indicate that the physical–chemical synergistic effect can significantly improve the magnitude of ionic migration. Hence, our work demonstrates the vast potential of a physical–chemical synergistic assistant factor in the enhancement of chemical-potential-driven energy conversion.

Biological ion channels, as fundamental units participating in various daily behaviors with incredible mass transportation and signal transmission, triggered booming researches on manufacturing their artificial prototypes. Biomimetic ion channel with the nanometer scale for smart responding functions has been successfully realized in sorts of materials by employing state-of-art nanotechnology. Ion track-etching technology, as crucial branches of fabricating solid-state nanochannels, exhibits outstanding advantages, such as easy fabrication, low cost, and high customization. To endow the nanochannel with smart responsibility, various modification methods are developed, including chemical grafting, non-covalent adsorption, and electrochemical deposition, enriching the reservoir of accessible stimuli-responses combinations, whereas were limited by their relatively lengthy and complex procedure. Here, based on the electric field induced self-assembly of polyelectrolytes, a universal customizable modifying strategy has been proposed, which exhibits superiorities in their functionalization with convenience and compatibility. By using this protocol, the channels’ ionic transport behaviors could be easily tuned, and even the specific ionic or molecular responding could be realized with superior performance. This strategy surely accelerates the nanochannels functionalization into fast preparing, high efficiency, and large-scale application scenarios.

Biological ion channel-based mass transport and signal transduction play a crucial role in physiological activities, and biomimetic nanochannels in aqueous solutions for ion transport regulation have been extensively studied. Few studies on non-aqueous systems, gel-based nanochannels, mainly focus on the charged gel network or embedded electrolytes. However, the basic issue of how a nanoscale gel network affects the ion transport in nanochannels has been neglected. Here, we demonstrate a non-aqueous biomimetic nanochannel system by employing the agarose hydrogel in conical nanochannels. To tune the hydrogel network by adjusting the gel concentration, the ion transport behavior in gel-based nanochannels is systemically investigated. The experimental results show that the ion transport behaviors in gel-nanochannels with 2% gel present similar ion selectivity and rectification performance to the aqueous system, indicating fast investigation of gel-based systems with the knowledge of the extensively studied aqueous systems. Furthermore, a gel-based solid-state diode and logic circuits were fabricated.

We have previously developed several kinds of rapamycin-encapsulated nanoparticles to achieve sustained release of rapamycin to treat hemangioma. However, lack of intrinsic targeting and easy clearance by the immune system are major hurdles that artificial fabricated nanoparticles must overcome. We constructed rapamycin-encapsulated macrophage-derived exosomes mimic nanoparticles-in-microspheres (RNM), to achieve the goal of continuous targeted therapy of hemangiomas. The rapamycin-encapsulated exosome mimic nanoparticles (RN) were firstly prepared by the extrusion-based method from the U937 cells (the human macrophage cell line). After then, RN was encapsulated with PLGA (poly(lactic-co-glycolic acid)) microspheres to obtain RNM. The release profile, targeting activity, and biological activity of RN and RNM were investigated on hemangioma stem cells (HemSCs). RN has a size of 100 nm in diameter, with a rapamycin encapsulation efficacy (EE) of 83%. The prepared microspheres RNM have a particle size of ~30 µm), and the drug EE of RNM is 34%. The sustained release of RNM can remarkably be achieved for 40 days. As expected, RN and RNM showed effective inhibition of cellular proliferation, significant cellular apoptosis, and remarkable repressed expression of angiogenesis factors in HemSCs. Our results showed that RNM is an effective approach for prolonged and effective delivery of rapamycin to hemangiomas.

As an approach to harvesting sustainable energy from ambient conditions, the osmotic energy between river water and seawater contributes to solving global issues such as the energy shortage and environmental pollution. Current attempts based on a reverse electrodialysis technique are limited mainly due to the economically unviable power density and inadequate mass transportation of membrane materials. Here, we demonstrate a benign strategy for designing a multilayer graphene oxide-silk nanofiber-graphene oxide biomimetic nacre-like sandwich as an osmotic power generator. Enhanced interfacial bonding endows the composite membranes with long-term stability in saline, and meanwhile, the two-dimensional nanofluidic channel configuration also reduces the ion transport resistance and provides large storage spaces for ions. Thus, the output power density of the proposed membrane-based generator achieves a value of up to 5.07 W m-2 by mixing seawater and river water. Furthermore, we experimentally and theoretically demonstrate that the thermal-field drives the increased output power density due to the advances in ionic movement range and activity of electrode reaction, showing the promise of strengthened thermo-osmotic energy conversion.

Significance Mammalian nervous systems, as natural ionic circuitries, have interested researchers with their powerful abilities in environmental perceptions and information transmission, which triggered booming development in artificial prototypes such as biomimetic ionic nanochannels. Most studied artificial ionic systems are more focused on their functions of perception, whereas the ionic information transmission system is rarely reported. Here, two-dimensional laminar nanofluidics are fabricated from MXene nanosheets and the noncontact external electrostatic potential applied patterns to generate and transmit alternating signals, from basic sine to frequency-modulated binary information. This work demonstrates the potentiality of bioinspired nervous signal transmission to simulate the neural ion-carried information system, which might lead to the avenue of alternating current ionics., Mammalian nervous systems, as natural ionic circuitries, stand out in environmental perception and sophisticated information transmission, relying on protein ionic channels and additional necessary structures. Prosperously emerged ionic regulated biomimetic nanochannels exhibit great potentialities in various application scenarios, especially signal transduction. Most reported direct current systems possess deficiencies in informational density and variability, which are superiorities of alternating current (AC) systems and necessities in bioinspired nervous signal transmission. Here, inspired by myelinated saltatory conduction, alternating electrostatic potential controlled nanofluidics are constructed with a noncontact application pattern and MXene nanosheets. Under time-variant external stimuli, ions confined in the interlaminar space obtain the capability of carriers for the AC ionic circuit. The transmitted information is accessible from typical sine to a frequency-modulated binary signal. This work demonstrates the potentiality of the bioinspired nervous signal transmission between electronics and ionic nanofluidics, which might push one step forward to the avenue of AC ionics.

In the present paper, a new defect function is proposed to predict the first harmonic motion in turbulent wave boundary layer (WBL) flows, based on the existing and newly acquired experimental evidences over a universal range of the governing flow parameters (A/ks & Re), taking the advantage of the existing defect function models. The defect function, denoted as D(z), having a complex form, describes the spatio-temporal velocity deficit in the WBL as the only function of z. For the new defect function, two sets of model parameters (p1 & λ1, p2 & λ2) are introduced to formulate the amplitude and phase defects, namely − ln | D | = ( z / λ 1 ) p 1 and arg ( D ) = ( z / λ 2 ) p 2 . Correlation relationships between model parameters (p1 & λ1, p2 & λ2) and governing flow parameters (A/ks & Re) were established. Through (i) matching the logarithmic and the defect laws of velocity distribution and (ii) the ‘one particle analysis’ of turbulent diffusion process, we demonstrated that the model parameters λ1 and λ2 represent the characteristic length scales, and the model parameters p1 and p2 reflect the nonlinearities of amplitude defect and phase defect respectively. The new defect function not only leads to better predictions of the flow in the phase space than the existing models but also extends the applicable parameter ranges of the existing models.

Experimental results, based on two-dimensional (2-D) laboratory tests, for impulse waves generated by subaerial landslides of combined solid block and granular materials are presented in this study. The results are compared with those of individual models of pure solid block and granular landslides. By considering an identical slide mass and release height, the effect of the mass ratio m* on wave generation was investigated. The mass ratio is defined as m* = MB/M, where MB is the mass of the solid block, M = MB + MG is the total mass and MG is the mass of the granular portion. The experimental results show that the combined landslides with m* = 0.6 and 0.8 in this study generally produce much larger impulse waves in the impact zone compared with those triggered by pure solid block landslides (m* = 1) and pure granular landslides (m* = 0). This suggests that the primary wave amplitudes of impulse waves might have been underestimated in previous laboratory tests with solely solid or granular assemblies when using the same slide mass and release height. The larger primary wave amplitudes of the combined landslides compared with those of the pure solid block landslides are mainly attributed to the relatively large thickness of the combined landslides and the continuous motion of the granular portion, as the inside solid block stops at the hill slope toe. Compared with pure granular landslides, combined landslides generally have a larger Froude number and slide thickness, which account for the larger primary wave amplitudes. The latter plays a quantifiably more important role – nearly two times that of the former. The effects of the hill slope angle α, and the grain size of the granular materials D, were also studied in this work. Four different hill slope angles (α = 22.5°, 30°, 37.5° and 45°) and four different mean grain diameters (D = 5 mm, 10 mm, 20 mm and 30 mm) were tested. By comparing the measured maxima of the wavelet spectra obtained via a wavelet transform method with those reconstructed by means of the phase celerity of the solitary wave cs and the group celerity of linear wave cg(f), it is found that the measured maxima travel at either cs or cg(f), depending on the landslide type and the hill slope angle α. However, the celerity of the measured maxima for the high frequency is lower than cg(f) and cs for the impulse waves generated by combined landslides when α ≤ 37.5° in this study. Further investigations show that the wave amplitude decreases rapidly during wave propagation, following an exponential function. The decrease in the wave amplitude during propagation is mainly attributed to dispersion.

Numerical simulations were carried out to investigate hydrodynamic forces on submarine pipelines in oscillatory flows, with a focus on the conditions under which the pipeline diameter D is of a similar order of magnitude to the boundary-layer thickness δ, i.e., δ/D ∼ O(1). Two-dimensional Reynolds-Averaged Navier-Stokes (RANS) equations with shear stress transport (SST) k-ω turbulence closure were solved using a Petrov–Galerkin finite element method (PG-FEM). The effects of the seabed roughness ks/D and the Keulegan-Carpenter number KC = UmT/D on the hydrodynamic force coefficients were investigated, where ks is the Nikuradse's equivalent roughness, T is the period of oscillatory flow and Um is the amplitude of the oscillatory velocity. The diameter of the submarine pipeline is fixed at D = 0.1 m. The Reynolds number, defined as Re = UmD/υ (where ν is the kinetic fluid viscosity), ranges from 1 × 104 to 4.5 × 104. The numerical results show that the boundary-layer thickness increases with ks. Hydrodynamic force coefficients are significantly affected by δ/D in the range of δ/D ∼ O(1), while δ/D depends on ks/D and KC number. The negligence of velocity reductions in the wave boundary layer leads to overestimations of the submerged weight required for achieving on-bottom stability.

With the aim of developing a new sort of highly effective and eco-friendly catalyst for NOx abatement, 40 wt.% 12-tungstophosphoric acid (TPA)-decorated Fe 2 O 3 nanorings were synthesized via a microwave-assisted hydrothermal method followed by simple mechanical-chemistry grinding. Analyses of SEM,TEM and XRD demonstrated the successful synthesis of Fe 2 O 3 nanorings. HRTEM image manifested that 3 layers of TPA polyanions were coated on the external surface of Fe 2 O 3 nanorings. FTIR and NH 3 -TPD were also employed to characterize the loading of TPA on Fe 2 O 3 and the distribution of acid sites of the composite material. The results indicated the existence of interaction between the terminal oxygen of TPA and Fe 3+ of Fe 2 O 3 nanorings. H 2 -TPR and SCR experiment showed that TPA played a significant promotion role in the SCR reaction of NOx, while Fe 2 O 3 served not only as the active ingredient but also as the support of TPA. TPA/Fe 2 O 3 achieved a satisfactory SCR performance, with the NOx conversion higher than 92% maintained in a wide temperature range between 230 and 500 °C. Additionally, the catalyst exhibited an excellent SO 2 -resistance capacity.

Although infantile hemangiomas is benign, its rapid growth may induce serious complications. However, only one drug Hemangeol™ has been approved by US Food and Drug Administration (FDA) to treat infantile hemangiomas. Thus it is necessary to develop novel alternative drugs to treat infantile hemangiomas. Rapamycin is a well-know potent antiangiogenic agent, whereas the daily oral administration of rapamycin exerts undesired metabolic effects due to its inhibition of mechanistic target of rapamycin (mTOR) which is critical in cell metabolism. We hereby developed rapamycin-loaded polymer-lipid hybrid nanoparticles (Rapamycin-PLNPs) as a local controlled release system to realize local and sustained release of rapamycin, aiming to reduce the side effects and frequency of administration of rapamycin. Rapamycin-PLNPs are of a small size (129.1nm), desired drug encapsulation efficiency (63.7%), and sustained drug release for 5 days. Rapamycin-PLNPs were shown to be able to effectively bind to hemangioma endothelia cells (HemECs), induce significant proliferation inhibition and reduce expression of angiogenesis factors in HemECs. The therapeutic effect of Rapamycin-PLNPs against infantile hemangioma in vivo was superior to rapamycin, as reflected by reduced hemangioma volume, weight and microvessel density. Taken together, Rapamycin-PLNPs represent a very promising local approach in the treatment of infantile hemangiomas.

Experimental investigations on the hydrodynamic forces on an intermittently spanning pipeline exposed to steady currents were carried out. The effect of intermittent local spanning sections on the global hydrodynamic behavior was studied by changing the ratio between the non-spanning length (B) and the total length (L), namely the blocking ratio B / L. A range of gap height (G) to diameter (D) ratios, i.e. gap ratio G / D, and 4 different Reynolds numbers (Re) in the subcritical region were tested in the experiments. The results show: i) for a certain gap ratio, the mean drag increases gently with the decreasing blocking ratio at Re = 5.5 × 104, whereas the mean lift decreases significantly with the decreasing blocking ratio at all values of Re tested; and ii) for a certain blocking ratio, increasing the gap ratio leads to an increase in mean drag and decrease in mean lift. Further, simple approaches are proposed based on the present dataset for estimating the global effects on hydrodynamic drag and lift forces due to local spanning geometry.

The on-bottom stability design of subsea pipelines and cables is important to ensure safety and reliability but can be challenging to achieve, particularly for renewable energy projects which are preferentially located in high energy metocean environments. Often these conditions lead to the seabed being stripped of all loose sediment, leaving the cables to rest on exposed bedrock where roughness features can be similar in size to the cables. As offshore renewable energy projects progress from concept demonstration to commercial-scale developments, new approaches are needed to capture the relevant physics for small diameter cables on rocky seabeds to reduce the costs and risks of export power transmission and increase operational reliability. These same considerations also apply to the cables and small diameter pipes — such as umbilicals — required by oil and gas projects located on rocky seabeds. Recent experimental testing using the University of Western Australia’s unique Large O-tube has enabled the experimental measurement of hydrodynamic forces on small diameter cables and pipes in proximity to smooth and rough beds. The tested conditions extend well beyond the existing published parameter range including much higher KC conditions together with seabed roughness which is comparable in size to the diameter. The results provide design data of great relevance to the ongoing development of marine renewable and conventional oil and gas projects, especially on rocky seabeds. This paper presents a summary of the existing knowledge on the subject as a preface to preliminary test results and gives tentative conclusions on the likely outcomes from this work.

The early diagnosis of recurrence and metastasis is critically important for decreasing the morbidity and mortality associated with oral cancers. Although liquid biopsy methods hold great promise that provide a successive "time-slice" profile of primary and metastatic oral cancer, the development of non-invasive, rapid, simple, and cost-effective liquid biopsy techniques remains challenging. In this study, an ultrasensitive and selective electrochemical liquid biopsy is developed for oral cancer screening based on tracking trace amounts of cancer biomarker by functionalized asymmetric nano-channels. Detection via antigen-antibody reactions is assayed by evaluating changes in ionic current. Upon the recognition of cancer biomarker antigens in bio-fluids, the inner wall of nano-channel immobilized with the corresponding antibodies undergoes molecular conformation transformation and surface physicochemical changes, which significantly regulate the ion transport through the nano-channel and help achieve sensitivity with a detection limit of 10

Correction for ‘Synergy of light and acid–base reaction in energy conversion based on cellulose nanofiber intercalated titanium carbide composite nanofluidics’ by Pei Liu et al., Energy Environ. Sci., 2021, 14, 4400–4409, DOI: 10.1039/D1EE90054D.

The boundary layer flow induced by surface waves has been extensively investigated due to its significance in engineering applications such as sediment transport and hydrodynamic forces on subsea structures. Several forms of defect functions (referred to as DF hereafter) were developed in the past decades, e.g. Sleath (1970, 1982), Nielsen (1985, 2016) and etc., due to their good efficiency in the description of the velocity distribution in one dimensional wave boundary layer (WBL). In this work, two forms of DFs are proposed: (i) DF-I describes the velocity distributions and bottom shear stresses in phase space with 4 model parameters; (ii) DF-II describes the maximum WBL profile with 3 model parameters. A number of datasets to support the validation of the DFs were obtained through experimental and numerical tests. Two sets of experiments were conducted individually in a free-surface-wave flume located in Dalian University of Technology and an oscillating-flow flume located in the University of Western Australia. For the free surface wave tests, the velocity was measured.Recorded Presentation from the vICCE (YouTube Link): https://youtu.be/RK-z0Q8rTjk

Many studies have indicated that metabolic disorders are positively correlated with idiopathic venous thromboembolism (VTE), whereas the risk factor serum uric acid (SUA) for idiopathic VTE has yet to be investigated. In this retrospective case-control study, 276 idiopathic VTE patients and 536 gender- and age-matched control subjects were included. The subjects in the case and control groups exhibiting common known VTE risk factors and the patients with a first VTE onset in one month were excluded. For the control group, primary and secondary VTE patients were excluded. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, total cholesterol, fasting blood glucose, and current smoking were significantly associated with idiopathic VTE in the univariate analysis. Hyperuricemia was detected in 56/276 (20.29%) idiopathic patients compared with 71/536 (13.25%) in the control group. HDL-C was considered the most prominent interactive factor for SUA in idiopathic VTE by the interaction analysis. After testing for the interaction terms, SUA was closely associated with idiopathic VTE in the high HDL-C population (P=0.0026 for interaction), while there was no such correlation in the low HDL-C group. The results indicated no obvious correlation between triglyceride and hypertension to idiopathic VTE. In conclusion, SUA is closely associated with an increased risk of idiopathic VTE in the high HDL-C population. The abnormality of SUA may act as an important linkage between atherosclerosis and idiopathic VTE through HDL-C.

Correction for ‘Bioinspired hydrogel-based nanofluidic ionic diodes: nano-confined network tuning and ion transport regulation’ by Congcong Zhu et al., Chem. Commun., 2020, 56, 8123–8126, DOI: 10.1039/D0CC01313G.

The most common tumors in children are infantile hemangiomas which could cause morbidity and severe complications. The development of novel alternative drugs to treat infantile hemangiomas is necessary, since Hemangeol is the only US Food and Drug Administration-approved drug for infantile hemangiomas. However, Hemangeol has several disadvantages, including a high frequency of administration and adverse effects. Rapamycin is a well‑established antiangiogenic drug, and we have previously developed rapamycin lipid polymer nanoparticles (R‑PLNPs) as a local sustained‑release drug delivery system to achieve controlled rapamycin release and to decrease the frequency of administration and side effects of rapamycin. To improve the targeting of R‑PLNPs to infantile hemangiomas in the present study, R‑PLNPs were modified to include an antibody against vascular endothelial growth factor receptor (VEGF). The characteristics, and the anti‑hemangioma activity of the resulting R‑PLNPs coupled with the anti‑VEGFR2 antibody (named R‑PLNPs‑V) were examined in vitro and in vivo. R‑PLNPs‑V possessed a small size (115 nm) and sustained drug release for 6 days. The anti‑VEGFR2 antibody promoted the targeting and cytotoxic effect of R‑PLNPs‑V to human hemangioma endothelial cells and human umbilical vein endothelial cells. Using a subcutaneous infantile hemangioma xenograft in mice, the in vivo therapeutic effect (evaluated with hemangioma weight, volume, and microvessel density) of R‑PLNPs‑V was demonstrated to be superior compared with rapamycin alone and other non‑targeted nanoparticles, without any total body weight loss. In summary, R‑PLNPs‑V could facilitate targeted delivery and sustained release of rapamycin to infantile hemangiomas, and thus may represent a promising candidate treatment for infantile hemangiomas.

Background Rap1 is involved in a multitude of cellular signal transduction pathways, which has extensively been linked to cell proliferation and migration. It has been shown to be important in the regulation of physiological and pathological processes. The present study aims to elucidate its detailed mechanistic in proliferation and migration. Material/methods Vascular smooth muscle cells (VSMCs) were transfected with pcDNA3.1(empty vector), pcDNA3.1 containing Myc-Tagged-Rap1V12 (Rap1V12) or pcDNA3.1 containing Flag-Tagged-Rap1GAP (Rap1GAP).The cells were presence or absence with 8CPT-2′OMe-cAMP or SDF-1 before transfection. The proliferation and migration were examined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and transwell analysis, respectively. Afterwards, western blot was performed to detect the expression of ERK, phosphorylated-ERK, Rap1, Rap1GAP and Rap1GTP. Results The results showed that proliferation, migration and the expression of Rap1, Rap1GAP, p-EKR were boosted in treatment of Rap1V12-transfection. However, Rap1GAP presented the opposite effects. Subsequently, VSMCs were pretreatment with stimulators Rap1 guanine exchange factor (Rap1GEF), 8CPT-2′OMe-cAMP and stromal cell-derived factor 1 (SDF-1), then transfected with different vectors and the expression of Rap1, Rap1GAP and p-EKR were obviously decreased. Conclusions Taken together, these findings indicated for the first time that Rap1 was essential for the VSMCs in proliferation and migration by ERK signaling pathway.

Extracellular ATP (eATP), released as a “danger signal” by injured or stressed cells, plays an important role in the regulation of immune responses, but the relationship between ATP release and innate immune responses is still uncertain. In this study, we demonstrated that ATP was released through Toll-like receptor (TLR)-associated signaling in both Escherichia coli -infected mice and lipopolysaccharide (LPS)- or Pam3CSK4-treated macrophages. This ATP release could be blocked completely only by N -ethylmaleimide (NEM), not by carbenoxolone (CBX), flufenamic acid (FFA), or probenecid, suggesting the key role of exocytosis in this process. Furthermore, LPS-induced ATP release could also be reduced dramatically through suppressing calcium mobilization by use of U73122, caffeine, and thapsigargin (TG). In addition, the secretion of interleukin-1β (IL-1β) and CCL-2 was enhanced significantly by ATP, in a time- and dose-dependent manner. Meanwhile, macrophage-mediated phagocytosis of bacteria was also promoted significantly by ATP stimulation. Furthermore, extracellular ATP reduced the number of invading bacteria and protected mice from peritonitis by activating purinergic receptors. Mechanistically, phosphorylation of AKT and ERK was overtly increased by ATP in antibacterial immune responses. Accordingly, if we blocked the P2X- and P2Y-associated signaling pathway by using suramin and pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid), tetrasodium salt (PPADS), the ATP-enhanced immune response was restrained significantly. Taken together, our findings reveal an internal relationship between danger signals and TLR signaling in innate immune responses, which suggests a potential therapeutic significance of calcium mobilization-mediated ATP release in infectious diseases.

Nanopores in two-dimensional (2D) membranes hold immense potential in single-molecule sensing, osmotic power generation, and information storage. Recent advances in 2D nanopores, especially on single-layer MoS2, focus on the scalable growth and manufacturing of nanopore devices. However, there still remains a bottleneck in controlling the nanopore stability in atomically thin membranes. Here, we evaluate the major factors responsible for the instability of the monolayer MoS2 nanopores. We identify chemical oxidation and delamination of monolayers from their underlying substrates as the major reasons for the instability of MoS2 nanopores. Surface modification of the substrate and reducing the oxygen from the measurement solution improves nanopore stability and dramatically increases their shelf-life. Understanding nanopore growth and stability can provide insights into controlling the pore size, shape and can enable long-term measurements with a high signal-to-noise ratio and engineering durable nanopore devices.