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Endomorphins (EMs) are potent pharmaceuticals for the treatment of pain. Herein, we investigated several novel EM analogues with multiple modifications and oligoarginine conjugation. Our results showed that analogues 1-6 behaved as potent μ-opioid agonists and enhanced stability and lipophilicity. Analogues 5 and 6 administered centrally and peripherally induced significant and prolonged antinociceptive effects in acute pain. Both analogues also produced long-acting antiallodynic effects against neuropathic and inflammatory pain. Furthermore, they showed a reduced acute antinociceptive tolerance. Analogue 6 decreased the extent of chronic antinociceptive tolerance, and analogue 5 exhibited no tolerance at the supraspinal level. Particularly, they displayed nontolerance-forming antinociception at the peripheral level. In addition, analogues 5 and 6 exhibited reduced or no opioid-like side effects on gastrointestinal transit, conditioned place preference (CPP), and motor impairment. The present investigation established that multiple modifications and oligoarginine-vector conjugation of EMs would be helpful in developing novel analgesics with fewer side effects.

Background With the increasing fragmentation of landscape induced by rapid urbanization, the construction of ecological networks is of great significance to alleviate the degradation of urban habitats and protect natural environments. However, there is considerable uncertainty when constructing ecological networks, especially the different approaches to selecting ecological sources. We used the southern Chinese city of Shenzhen as a study area to construct and optimize ecological networks using a coupling approach. Ecological source areas were extracted using morphological spatial pattern analysis (MSPA) and the landscape index method. Ecological networks were constructed using the minimal cumulative resistance (MCR) model and the gravity model. Stepping stones and ecological fault points were added in corridors to optimize the ecological network. Results Ten core areas with maximum importance patch values were extracted by the landscape index method as ecological source areas according to MSPA, after which corridors between ecological sources were constructed based on the MCR model. The constructed ecological networks were optimized using 35 stepping stones and 17 ecological fault points. The optimized ecological networks included 11 important corridors, 34 general corridors, and seven potential corridors. The results of corridor landscape-type analysis showed that a suitable ecological corridor is 60 to 200 m wide. Conclusions Overall, our results imply that ecological source areas can be identified virtually, and that ecological networks can be significantly optimized by combining MSPA and MCR models. These results provide a methodological reference for constructing ecological networks, and they will be useful for urban planning and biodiversity protection in Shenzhen and other similar regions around the world.

Two-dimensional flow of the pulsed co-flow jet (CFJ) and the influence of the pulsed parameters on the lift and power consumption are investigated numerically. Firstly, the jet channel of traditional CFJ airfoil is improved. The stall margin is increased by 3° compared with the corresponding traditional CFJ airfoil, and the lift is increased, while the drag is reduced significantly. Then, the influence of the pulsed parameters, such as the pulse waveform, including sinusoidal and rectangular waves, the duty cycle, and the pulse frequency on the lift and power consumption are presented and analyzed in detail. It is concluded that, compared with the steady CFJ, the pulsed CFJ possesses much better ability in suppressing separation and can improve the lift characteristics significantly with limited cost of power consumption. For example, at an angle of attack of 20° flow separation occurs severely, when the steady CFJ is adopted; however, the airflow becomes fully attached on the upper airfoil, when the rectangular pulsed CFJ is employed. As a result, the lift corresponding to the rectangular wave is higher than that of the sinusoidal wave. The results also indicate that the lower duty cycle and pulse frequency can lead to the higher lift but with more power consumption.

During different periods of rock fracture engineering, the surrounding rock is subject to intermittent and periodic vibration disturbances of different degrees. This disturbance has a great influence on the permeability characteristics of bedrock fissures. The permeability characteristics of bedrock fissure permeability are the most important hydrogeological element of underground water-containing medium, and determining the stratum permeability is an important link to evaluate the hydrogeological conditions of the mining area. Therefore, this paper studies the permeability characteristics of bedrock fissures based on the disturbance of neural network. First, use the basic structure of the neural network to understand the method applied to the study of permeability characteristics of bedrock cracks; secondly, put forward the rock permeability model driven by coal mining to help the subsequent experimental design of various relevant factors after the bedrock cracks Finally, the stress intensity factor method at the tip of the fracture is used to calculate the permeability of the bedrock fracture. The experimental data shows that the infiltration rate tested in the first minute of the experiment is 5.5 * 10−4 cm/s, which is equivalent to 12 times the stable infiltration rate. At 50 min after the start of the test, the infiltration rate dropped to 4.6 * 10−4 cm/s, which was close to the stable infiltration rate. The experimental results show that under the disturbance condition of neural network, the infiltration rate of bedrock fissures is accelerated and the permeability is increased.

Two dimensional (2D) materials have generated enormous interest in various research fields in recent years due to their fascinating properties, such as atomic thickness, distinct structures and superior characteristics. In particular, electronic and optoelectronic devices based on 2D materials have been widely investigated, which is promising for the innovation of future nanoelectronics technology. Recently, the technique of laser processing 2D materials with the advantages of facile operation, versatility and low cost has been reported to enable the fabrication of diverse 2D material electronic and optoelectronic devices, such as field-effect transistors (FETs), p–n junction diodes, bipolar junction transistors (BJTs), inverters, memory devices, photodetectors, photovoltaic devices and light-emitting devices. Here, various interactions between lasers and 2D materials are introduced, such as direct writing processing, reduction, doping, phase transition engineering, thinning, oxidation and creating defects. The current advances in laser processing-assisted 2D material electronic and optoelectronic devices are reviewed. A comprehensive outlook on the future development of 2D material nanoelectronics/optoelectronics via laser processing is also presented.

Highly stable nanopores with precise size and film thickness are essential for ultrasensitive molecular biosensors and efficient ion filters. However, the stability of both solid-state nanopores and biological nanopores is of a few hours. Even for two-dimensional (2D) materials with excellent properties, it is very difficult to prepare nanopores with stability for more than 1 day. Here, in mechanically exfoliated 2D materials with excellent quality, highly stable nanopores have been fabricated. Through the manual control of defect density and laser spot irradiation, the breakdown process is more controllable. The nanopore diameter can be precisely adjusted from 1 to 10 nm. The 2 nm thick graphene nanopore (with a diameter of 2 nm) maintains good consistency in conductivity during the 1-month immersion in KCl (1 M) solution. The pore size changes less than 0.7% per day. We found that 2D material nanopores can produce a strong rectification ratio (∼50) due to the morphology undulation. In addition, our devices can recognize modified 5 nm Au nanoparticles, showing great potential for single-molecule detection. This work can guide the development of high-quality ion rectifier devices and biosensors based on 2D material nanopores.

The security of quantum key distribution (QKD) usually relies on that the users' devices are well characterized according to the security models made in the security proofs. In contrast, device-independent QKD-an entanglement-based protocol-permits the security even without any knowledge of the underlying quantum devices. Despite its beauty in theory, device-independent QKD is elusive to realize with current technologies. Especially in photonic implementations, the requirements for detection efficiency are far beyond the performance of any reported device-independent experiments. In this Letter, we report a proof-of-principle experiment of device-independent QKD based on a photonic setup in the asymptotic limit. On the theoretical side, we enhance the loss tolerance for real device imperfections by combining different approaches, namely, random postselection, noisy preprocessing, and developed numerical methods to estimate the key rate via the von Neumann entropy. On the experimental side, we develop a high-quality polarization-entangled photon source achieving a state-of-the-art (heralded) detection efficiency about 87.5%. Although our experiment does not include random basis switching, the achieved efficiency outperforms previous photonic experiments involving loophole-free Bell tests. Together, we show that the measured quantum correlations are strong enough to ensure a positive key rate under the fiber length up to 220 m. Our photonic platform can generate entangled photons at a high rate and in the telecom wavelength, which is desirable for high-speed generation over long distances. The results present an important step toward a full demonstration of photonic device-independent QKD.

The security of quantum key distribution (QKD) usually relies on that the users’s devices are well characterized according to the security models made in the security proofs. In contrast,device-independent QKD an entanglement-based protocol permits the security even without any knowledge of the underlying devices. Despite its beauty in theory, device-independent QKD is elusive to realize with current technology. This is because a faithful realization requires ahigh-quality violation of Bell inequality without the fair-sampling assumption. Particularly, in a photonic realization, a rather high detection efficiency is needed where the threshold values depend on the security proofs; this efficiency is far beyond the current reach. Here, both theoretical and experimental innovations yield the realization of device-independent QKD based on a photonic setup. On the theory side, to relax the threshold efficiency for practical deviceindependent QKD, we exploit the random post-selection combined with adding noise for preprocessing, and compute the entropy with complete nonlocal correlations. On the experiment side, we develop a high-quality polarization-entangled photonic source and achieve state-of-theart (heralded) detection efficiency of 87.49%, which outperforms previous experiments and satisfies the threshold efficiency for the first time. Together, we demonstrate device-independent QKD at a secret key rate of 466 bits/s over 20 m standard fiber in the asymptotic limit against collective attacks. Besides, we show the feasibility of generating secret keys at a fiber length of 220 meters. Importantly, our photonic implementation can generate entangled photons at a high rate and in the telecom wavelength, which is desirable for high-speed key generation over long distances. The results not only prove the feasibility of device-independent QKD with realistic devices, but also push the security of communication to an unprecedented level.

Device-independent quantum key distribution (QKD) can permit the superior security even with unknown devices. In practice, however, the realization of device-independent QKD is technically challenging because of its low noise tolerance. In photonic setup, due to the limited detection efficiency, a large amount of the data generates from no-detection events which contain little correlations but contribute high errors. Here we propose the device-independent QKD protocol with random post selection, where the secret keys are extracted only from the post-selected subset of outcomes. This could not open the detection loophole as long as the entropy of the post-selected subset is evaluated from the information of the entire set of data, including both detection and no-detection events. This post selection has the advantage to significantly reduce the error events, thus relaxing the threshold of required detection efficiency. In the model of collective attacks, our protocol can tolerate detector efficiency as low as 68.5%, which goes beyond standard security proofs. The results make a concrete step for the implementation of device-independent QKD in practice., An experimental demonstration of the protocol can be seen in arXiv:2110.01480

In this paper, we employ theoretical and experimental efforts and realize a proof-of-principle verification of device-independent QKD based on the photonic setup. On the theoretical side, we enhance the loss tolerance for real device imperfections by combining different approaches, namely, random post-selection, noisy preprocessing, and developed numerical methods to estimate the key rate via the von Neumann entropy. On the experimental side, we develop a high-quality polarization-entangled photon source achieving a state-of-the-art (heralded) detection efficiency about 87.5%. This efficiency outperforms previous photonic experiments involving loophole-free Bell tests. Together, we show that the measured quantum correlations are strong enough to ensure a positive key rate under the fiber length up to 220 m. Our photonic platform can generate entangled photons at a high rate and in the telecom wavelength, which is desirable for high-speed generation over long distances. The results present an important step towards a full demonstration of photonic device-independent QKD., 17 pages, 6 figures

We have realized optical excitation, trapping, and detection of the radioisotope $^{81}\mathrm{Kr}$ with an isotopic abundance of 0.9 ppt. The 124 nm light needed for the production of metastable atoms is generated by a resonant discharge lamp. Photon transport through the optically thick krypton gas inside the lamp is simulated and optimized to enhance both brightness and resonance. We achieve a state-of-the-art $^{81}\mathrm{Kr}$ loading rate of $1800\text{ }\text{ }\mathrm{atoms}/\mathrm{h}$, which can be further scaled up by adding more lamps. The all-optical approach overcomes the limitations on precision and sample size of radiokrypton dating, enabling new applications in the earth sciences, particularly for dating of polar ice cores.

The rapid development of urbanization has caused many ecological issues and greatly threatened the sustainable development of human society. The construction of ecological security patterns (ESPs) offers an effective way to balance ecological conservation and urbanization. This study aimed to take the highly urbanized city of Shenzhen, China, as a study area to construct an urban ESP and put forward suggestions for the urban development of ecological security. Ecological sources were identified through the Habitat Quality module in the InVEST model, and ecological corridors, strategic ecological nodes, and stepping-stone patches were extracted based on the minimum cumulative resistance (MCR) model. These elements together constituted the ESP. In particular, with the results of the continuous decline in the overall habitat quality, this study identified ten ecological sources with superior habitat quality, mainly distributed in rural woodlands, in urban green land, and in forest park patches. An optimized pattern for Shenzhen City with one axis, three belts, and four zones is proposed, with the study area divided into an ecological preservation zone, a limited development zone, an optimized development zone, and a key development zone. Moreover, forty-five ecological corridors were extracted and graded into three levels, presenting a spatial pattern of one axis and three belts. The appropriate widths of these ecological corridors were suggested to be between 30 and 60 m in Shenzhen City. In addition, we identified twenty-five ecological nodes, sixteen ecological fracture points, and sixteen stepping stones to improve the maintenance and construction of the ecological corridor network. More generally, this study demonstrates a scientific approach to identifying ESPs based on habitat quality, and can serve as a reference for the planning of urban ecological function regionalization.

Human beings have entered the stage of big data in the information age. How to use big data to serve all walks of life is a very worthy of discussion. This article thought that the mine well under - ground real-time monitoring data and mining production, living and ecological water demands as the research object, from the large data set up, management, analysis, and maintain the four aspects, combining the reality of mine work, using the large system decomposition-coordination principle and fuzzy hierarchy comprehensive evaluation method, the multi-objective dynamic programming model for nonlinear iterative simulation optimization, determine coal water - coordinate the development of new pattern and the underground water source water coal mining technology, mine Wells under - ground multi-objective efficient mixing technology, realizing the accurate, intelligent mine water utilization. Research method, this paper USES “Knowledgediscovery from GIS” and “Simonett rubik’s cube” concept, cyber GIS method is applied to build the mine Wells under - ground real-time monitoring to the big data is discussed, at the same time points out the characteristics of the coal mining situation of real-time, and possible problems are derived, which provide reference for other mines to establish large data.

Coal is China’s main energy, and this situation in the future in a long period of time is unlikely to have fundamental changes. As an underground activity, coal mining inevitably causes local damage and pollution to underground water cut system due to improper application of coal mining technology. And a large number of mine drainage, not only need to spend a lot of drainage costs, increase the cost of coal production, but also waste very valuable water resources. In this paper, based on the water - coal, on the basis of coordination development, through big data analysis methods, proposes the establishment process of coal mining and mine water quality, and the whole life cycle of the coal - water coordination development precision control technology system, through a series of research on the laws of the evolution of time and space and nonlinear multiobjective model building and simulation development plan, research and development of the evaluation method of mine water resource utilization efficiency and benefit, help to realize the coordinated development of the coal - water control in whole life cycle of technology. So as to realize the exploitation and utilization of mine drainage and turn waste into treasure, it can not only relieve the tight situation of water supply in coal mines, but also reduce the environmental pollution caused by coal mining to the mining areas and surrounding cities, and realize the unity of economic and environmental benefits.

The details of experimental setup and more experimental results.

For clinical use, it is essential to develop potent endomorphin (EM) analogs with reduced antinociceptive tolerance. In the present study, the antinociceptive activities and tolerance development of four potent EM-1 analogs with C-terminal oligoarginine-conjugation was evaluated and compared in the radiant heat paw withdrawal test. Following intracerebroventricular (i.c.v.) administration, all analogs 1-4 produced potent and prolonged antinociceptive effects. Notably, analogs 2 and 4 with the introduction of D-Ala in position 2 exhibited relatively higher analgesic potencies than those of analogs 1 and 3 with β-Pro substitution, consistent with their μ-opioid binding characteristic. In addition, at a dose of 50 μmol/kg, endomorphin-1 (EM-1) failed to produce any significant antinociceptive activity after peripheral administration, whereas analogs 1-4 induced potent antinociceptive effects with an increased duration of action. Herein, our results indicated the development of antinociceptive tolerance to EM-1 and morphine at the supraspinal level on day 7. By contrast, analogs 1-4 decreased the antinociceptive tolerance. Furthermore, subcutaneous (s.c.) administration of morphine at 50 μmol/kg also developed the antinociceptive tolerance, whereas the extent of tolerance developed to analogs 1-4 was largely reduced. Especially, analog 4 exhibited non-tolerance-forming antinociception after peripheral administration. The present investigation gave the evidence that C-terminal conjugation of EM-1 with oligoarginine vector will facilitate the development of novel opioid analgesics with reduced opioid tolerance.

Quantum resetting protocols allow a quantum system to be sent to a state in the past by making it interact with quantum probes when neither the free evolution of the system nor the interaction is controlled. We experimentally verify the simplest non-trivial case of a quantum resetting protocol, known as the $\mathcal{W}_4$ protocol, with five superconducting qubits, testing it with different types of free evolutions and target-probe interactions. After projection, we obtained a reset state fidelity as high as $0.951$, and the process fidelity was found to be $0.792$. We also implemented 100 randomly-chosen interactions and demonstrated an average success probability of $0.323$ for $|1\rangle$ and $0.292$ for $|-\rangle$, experimentally confirmed the nonzero probability of success for unknown interactions; the numerical simulated values are about $0.3$. Our experiment shows that the simplest quantum resetting protocol can be implemented with current technologies, making such protocols a valuable tool in the eternal fight against unwanted evolution in quantum systems., 9 pages, 6 figures, 1 table + Supplementary Materials

Contrary to the usual assumption of at least partial control of quantum dynamics, a surprising recent result proved that an arbitrary quantum state can be probabilistically reset to a state in the past by having it interact with probing systems in a consistent, but $uncontrolled$ way. We present a photonic implementation to achieve this resetting process, experimentally verifying that a state can be probabilistically reset to its past with a fidelity of $0.870\pm0.012$. We further demonstrate the preservation of an entangled state, which still violates a Bell inequality, after half of the entangled pair was reset. The ability to reset uncontrolled quantum states has implications in the foundations of quantum physics and applications in areas of quantum technology., 8 pages, 9 figures

Quantum computing has seen tremendous progress in the past years. Due to the implementation complexity and cost, the future path of quantum computation is strongly believed to delegate computational tasks to powerful quantum servers on cloud. Universal blind quantum computing (UBQC) provides the protocol for the secure delegation of arbitrary quantum computations, and it has received significant attention. However, a great challenge in UBQC is how to transmit quantum state over long distance securely and reliably. Here, we solve this challenge by proposing and demonstrating a resource-efficient remote blind qubit preparation (RBQP) protocol with weak coherent pulses for the client to produce, using a compact and low-cost laser. We demonstrate the protocol in field, experimentally verifying the protocol over 100-km fiber. Our experiment uses a quantum teleportation setup in telecom wavelength and generates $1000$ secure qubits with an average fidelity of $(86.9\pm1.5)\%$, which exceeds the quantum no-cloning fidelity of equatorial qubit states. The results prove the feasibility of UBQC over long distances, and thus serving as a key milestone towards secure cloud quantum computing., 11 pages, 9 figures

The present study was undertaken to further investigate the spinal anti-allodynic effects of endomorphins (EMs) and their C-terminal hydrazide modified analogs EM-1-NHNH2 and EM-2-NHNH2 in the spared nerve injury (SNI) model of neuropathic pain in mice. Our results demonstrated that intrathecal (i.t.) administration of endomorphin-1 (EM-1), endomorphin-2 (EM-2), EM-1-NHNH2 and EM-2-NHNH2 produced potent anti-allodynic effects ipsilaterally in neuropathic pain model. Judging from the area under the curve (AUC) values, these two analogs exhibited higher antinociception than their parent peptides. Moreover, they also displayed significant antinociceptive effects in the contralateral paw administered intrathecally. Interestingly, EM-1 and its analog EM-1-NHNH2 displayed their antinociception probably by μ2-opioid receptor subtype since the μ1-opioid receptor antagonist naloxonazine didn't significantly block the anti-allodynia of EM-1 and EM-1-NHNH2, which implied a same opioid mechanism. However, the anti-allodynia induced by EM-2, but not EM-2-NHNH2 was significantly reduced by both μ1-opioid antagonist, naloxonazine and κ-antagonist, nor-binaltorphamine (nor-BNI), indicating multiple opioid receptors were involved in the anti-allodynic effects of EM-2. Most importantly, EM-1-NHNH2 decreased the antinociceptive tolerance, and EM-2-NHNH2 displayed non-tolerance-forming antinociception. Therefore, C-terminal amide to hydrazide conversion changed the spinal antinociceptive profiles of EMs in neuropathic pain. The present investigation is of great value in the development of novel opioid therapeutics against neuropathic pain.

To effectively protect shallow groundwater and to evaluate the environmental impact of groundwater, we set up a monitoring network of 30 monitoring wells and collected 11 water samples from the wells during the rainy and dry seasons. Hydrochemical characteristics of the shallow groundwater were identified with the Piper and Gibbs diagrams. Groundwater quality was assessed with the single standard index method and the entropy-weighted water quality index. Finally, we used a numerical simulation of the impact of the power plant operation on the groundwater environment. The average abundance of the major ions in groundwater from the dry to the wet season occurred in the following orders: Ca2+ > Na+ > Mg2+ > K+ for cations and HCO3− > SO42− > Cl− for anions. The shallow groundwater usually has elevated hardness and alkalinity values comparison with the standard values. The dominant hydrochemical facies of the groundwater is the HCO3–Ca type. Rock weathering is likely to be the dominant process that controls the groundwater chemical composition. Groundwater in the study area is suitable for drinking under ordinary conditions, according to the single standard index method and the entropy-weighted water quality index. However, the groundwater quality has been influenced by anthropogenic activities (including near the west Ash Yard and Huangji Sunaba). Numerical modeling shows that leakage during abnormal operating conditions is of limited extent within the boundary of the simulated area and does not enter into the Yangtze River. Overall, it is necessary to carry out effective anti-seepage and pollution control measures to ensure that shallow groundwater is not contaminated.

In the title compound, C15H17NO8, the nitro group is essentially coplanar with the aromatic ring [dihedral angle = 6.4 (3) Å]. The five-membered ring has a twist conformation. In the crystal, C—H...O interactions link the molecules into a helical chain propagating along [010].

The equilibrium and dynamic adsorption data of H(2) and D(2) on different micro- and mesoporous adsorbents with orderly structure including 3A, 4A, 5A, Y, and 10X zeolites; carbon CMK-3; silica SBA-15; and so forth were collected. Critical effect of the nanodimension of adsorbents on the adsorption behavior of hydrogen and its isotopes is shown. The highest adsorption capacity was observed at pore size 0.7 nm, but equal or even larger isotope difference in the equilibrium adsorption was observed at larger pore sizes, whereas the largest isotope difference in the dynamic adsorption was observed at 0.5 nm. The adsorption rate of D(2) is larger than that of H(2) in microporous adsorbents, but the sequence could be switched over in mesoporous materials. Linear relationship was observed between the adsorption capacity for hydrogen and the specific surface area of adsorbents although the adsorbents are made of different material, which provides a convincing proof of the monolayer mechanism of hydrogen adsorption. The linear plot for microporous adsorbents has a larger slope than that for mesoporous adsorbents, which is attributed to the stronger adsorption potential in micropores.

In the title compound, C12H14N2O5, the five-membered 1,3-dioxolane ring has a twisted conformation. In the crystal, N—H...O and C—H...O hydrogen bonds link the molecules into a two-dimensional network lying parallel to the ab plane. There are also C—H...π interactions present in the crystal structure.