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Abstract Polymyxin resistance is conferred by MCR‐1 (mobile colistin resistance 1)‐induced lipopolysaccharide (LPS) modification of G− bacteria. However, the peptide MSI‐1 exerts potent antimicrobial activity against mcr‐1‐carrying bacteria. To further investigate the potential role of MCR‐1 in improving bacterial virulence and facilitating immune evasion, and the immunomodulatory effect of peptide MSI‐1, we first explored outer membrane vesicle (OMV) alterations of mcr‐1‐carrying bacteria in the presence and absence of sub‐MIC MSI‐1, and host immune activation during bacterial infection and OMV stimulation. Our results demonstrated that LPS remodelling induced by MCR‐1 negatively affected OMV formation and protein cargo by E. coli. In addition, MCR‐1 diminished LPS‐stimulated pyroptosis but facilitated mitochondrial dysfunction, further aggravating apoptosis in macrophages induced by OMVs of E. coli. Similarly, TLR4‐mediated NF‐κB activation was markedly alleviated once LPS was modified by MCR‐1. However, peptide MSI‐1 at the sub‐MIC level inhibited the expression of MCR‐1, further partly rescuing OMV alteration and attenuation of immune responses in the presence of MCR‐1 during both infection and OMV stimulation, which can be exploited for anti‐infective therapy.

With the development of electronic warfare technology, the intelligent jammer dramatically reduces the performance of traditional radar anti-jamming methods. A key issue is how to actively adapt radar to complex electromagnetic environments and design anti-jamming strategies to deal with intelligent jammers. The space of the electromagnetic environment is dynamically changing, and the transmitting power of the jammer and frequency diversity array (FDA) radar in each frequency band is continuously adjustable. Both can learn the optimal strategy by interacting with the electromagnetic environment. Considering that the competition between the FDA radar and the jammer is a confrontation process of two agents, we find the optimal power allocation strategy for both sides by using the multi-agent deep deterministic policy gradient (MADDPG) algorithm based on multi-agent reinforcement learning (MARL). Finally, the simulation results show that the power allocation strategy of the FDA radar and the jammer can converge and effectively improve the performance of the FDA radar and the jammer in the intelligent countermeasure environment.

Abstract Atomically precise metal nanoclusters (MNCs), as a potential type of photoacoustic (PA) contrast agent, are limited in application due to their low PA conversion efficiency (PACE). Here, with hydrophilic Au25SR18 (SR = thiolate) as model NCs, we present a result that weakly polar solvent induces aggregation, which effectively enhances PA intensity and PACE. The PA intensity and PACE are highly dependent on the degree of aggregation, while the aggregation‐enhanced PA intensity (AEPA) positively correlates to the protected ligands. Such an AEPA phenomenon indicates that aggregation actually accelerates the intramolecular motion of Au NCs, and enlarges the proportion of excited state energy dissipated through vibrational relaxation. This result conflicts with the restriction of intramolecular motion mechanism of aggregation‐induced emission. Further experiments show that the increased energy of AEPA originates from the aggregation inhibiting the intermolecular energy transfer from excited Au NCs to their surrounding medium molecules, including solvent molecule and dissolved oxygen, rather than restricting radiative relaxations. This study develops a new strategy for enhancing the PA intensity of Au NCs, and contributes to a deeper understanding of the origin of the PA signal and the excited state energy dissipation processes for MNCs.

ABSTRACT Streptococcus pneumoniae is a notorious human opportunistic pathogen which undergoes a spontaneous and reversible phenotypic change in response to the host environment. We demonstrated that the regulatory gene hsdSA of DNA methylation in the type I restriction modification system altered colony transparency and substantially contributed to S. pneumoniae virulence. Most importantly, hsdSA regulated the production of extracellular vesicles (EVs) which package cytosolic, surface, and secreted proteins, including pneumolysin (PLY). Interestingly, we confirmed that EV-associated PLY utilized internalization into macrophages to prolong the survival of intracellular bacteria as a major immune evasion strategy; that is, EV-associated PLY produced by the D39 strain (EVs-D39) could induce the formation of LC3-associated monolayer vacuoles [LC3-associated phagocytosis (LAP)] and co-localize with the NADPH oxidase 2 (NOX2) complex but not ULK1 when macrophages were infected with the D39Δply strain. In addition, EV-associated PLY derived from the EVs-D39 promoted macrophages to release more reactive oxygen species (ROS) and expression of p-p70s6k than EV-associated PLY derived from the D39ΔhsdSA strain (EVs-D39ΔhsdSA ), whereas the expression of p-ULK1 was reversed, indicating that EVs-D39ΔhsdSA was more likely to induce conventional xenophagy. Furthermore, we identified the β1 integrin receptor as a crucial inducer of ROS to mediate LAP activation. Bacterial evasion of host clearance is closely related to insufficient acidification after the fusion of autophagosomes or LAPosomes with lysosomes. Of note, we found EV-associated PLY damaged the integrity of the lysosome membrane and changed the pH gradient, resulting in lysosomes being unable to remove intracellular bacteria and ultimately prolonging the survival of S. pneumoniae in macrophages. Finally, the extracted mouse alveolar macrophages and mouse intranasal infection models were employed to further verify the above findings. IMPORTANCE S. pneumoniae is a major human pathogen that undergoes a spontaneous and reversible phase variation that allows it to survive in different host environments. Interestingly, we found hsdSA , a gene that manipulated the phase variation, promoted the survival and replication of S. pneumoniae in macrophages by regulating EV production and EV-associated PLY. More importantly, here we provided the first evidence that higher EV-associated PLY (produced by D39) could form LAPosomes that were single membrane compartments containing S. pneumoniae, which are induced by integrin β1/NOX2/ROS pathway. At the same time, EV-associated PLY increased the permeability of lysosome membrane and induced an insufficient acidification to escape the host killing, and ultimately prolonged the survival of S. pneumoniae in macrophages. In contrast, lower EV-associated PLY (produced by D39ΔhsdSA ) activated ULK1 recruitment to form double-layered autophagosomes to eliminate bacteria.

Abstract Frequency diversity array (FDA) radar provides more degrees of freedom and can generate range‐angle‐time‐dependent beampattern. Furthermore, based on the receiver's multi‐input multi‐output (MIMO) scheme, the frequency diversity array‐multi‐input multi‐output (FDA‐MIMO) radar can develop a range‐dependent but time‐independent beampattern. Taking advantage of this feature, this article improves the signal‐to‐interference‐plus‐noise ratio and the effective suppression of interference by jointly optimising the transmit beamspace and the receive filter. Since the optimisation problem is a non‐convex problem with constant energy constraints, we transform it into two convex subproblems with restrictions. The whole algorithm follows the alternate optimisation over receive filter and transmit beamspace. By simulating challenging scenarios, we confirmed the effectiveness and superiority of the method.

The interactions between active pharmaceutical ingredients (APIs) and excipients may lead to API degradation, thereby affecting the safety and efficacy of drug products. Cbf-14 is a synthetic peptide derived from Cathelicidin-BF, showing potential for bacterial and fungal infections. In order to assess impurities in Cbf-14 gel, we developed a two-dimensional liquid chromatography coupled with quadrupole/time-of-flight mass spectrometric method. A total of eleven peptide degradation impurities were identified and characterized. Furthermore, the compatibility tests were conducted to evaluate the interactions of Cbf-14 with glycerol and methylcellulose, respectively. The results revealed that the impurities originated from condensation reactions between Cbf-14 and aldehydes caused by glycerol degradation. Several aldehydes were employed to validate this hypothesis. The formation mechanisms were elucidated as Maillard reactions between primary amino groups of Cbf-14 and aldehydes derived from glycerol degradation. Additionally, the compatibility of Cbf-14 with glycerol from different sources and with varying storage times was investigated. Notably, the interaction products in the gel increased with extended storage time, even when fresh glycerol for injection was added. This study offers unique insights into the compatibility study of peptides and glycerol, contributing to the ongoing quality study of Cbf-14 gel. It also serves as a reference for the design of other peptide preparations and excipients selections.

Abstract The frequency diverse array (FDA) can provide degrees of freedom in both the range and angle domains by controlling the frequency offset across adjacent elements. Nevertheless, the time‐variant problem affects the analysis and application of FDA, and there is a notable lack of research on the receivers of multicarrier FDA. In this paper, a novel perspective to understand the factor of time parameter is proposed. Furthermore, combined with the multiple input and multiple output scheme, two multicarrier FDA radar receivers are proposed to obtain the time‐invariant and dot‐shaped beampattern. Numerical simulations demonstrate the validity of theoretical results.

The transmitted beam of frequency diversity array (FDA) has the range–angle–time coupling property, which has essential applicative potential in angle deception and active anti-jamming. In this paper, the concept of time index within pulse is introduced. Firstly, the phase characteristics of FDA-transmitted signals based on the time index within pulse concept are studied. Then, the deceptive angle performance of FDA-transmitted signals is discussed. The theoretical analysis and simulation results show that the phase characteristics of the FDA signal are not related to the range, but to the time index within pulse. With the phase center as the reference point, the phase is equal as long as the time index within the pulse is the same. Angle deception and active anti-jamming can be achieved using the optimized frequency increment of each FDA.

This paper deals with the problem of robust beamforming and target power estimation in the presence of main-lobe interference with frequency division array multiple-input multiple-output (FDA-MIMO) radar by adopting a weighting matrix at the receiving end. Based on the semi-definite programming (SDP) to solve the covariance matrix of the weighting matrix, we propose two beamforming methods and two methods for estimating the target power when the interference has a position error. Then, we propose obtaining the weighting matrix by performing singular value decomposition on the covariance matrix. We confirm the effectiveness of the developed method by comparing beam pattern and target signal estimation performance.

The carbonate gas reservoir of the fourth Member of Upper Sinian Dengying Formation (hereinafter referred as “Deng 4 Member”) is characterized by deep burial, high temperature, low porosity, low permeability and strong heterogeneity in the Gaoshiti-Moxi area of the central Sichuan Basin. In order to effectively enhance the well productivity and gas reservoir development benefits, this paper defines the reservoir stimulation factor by comprehensively considering the drilling, logging and well type characteristic parameters, to carry out quantitative reservoir evaluation. Then, the refined segmentation method was developed by fully considering the reservoir stimulation factor, in-situ stress and borehole condition. In addition, the differential acid fracturing technology was prepared for different types of reservoirs. On this basis, the specified staged acid fracturing technology of horizontal well for strong-heterogeneity carbonate reservoirs was developed and then applied in the field. And the following research results were obtained. First, the reservoir stimulation factor (y) can be used to accurately evaluate the reservoir characteristics. The high quality reservoir has y ≥ 1.0, the moderate reservoir has 0.5 ≤ y

In order to solve the difficulties in the volume fracturing stimulation of Middle Jurassic Shaximiao Formation tight sandstone reservoirs in the Qiulin Block of Central Sichuan Basin and explore the adaptability of high-intensity volume fracturing technology, we selected the outcrop samples of Shaximiao Formation tight sandstone in the Qiulin Block to carry out the physical simulation experiment of true triaxial hydraulic fracturing. On this basis, horizontal well cluster perforation was optimally designed by using the production prediction model of staged multi-cluster fracturing horizontal wells. Then, based on the liquid control and proppant increase mode, three rounds of pilot tests were carried out on the tight sandstone reservoirs in this area. And the following research results were obtained. First, natural fractures in the Shaximiao Formation tight sandstone reservoir of the Qiulin Block are undeveloped, and hydraulic fractures are morphologically dominated by symmetric double-wing fractures, so complex fracture networks can be hardly formed. In addition, the reservoir is of medium to strong water sensitivity, so conventional volume fracturing is not adaptive to the reservoir stimulation in this block. Second, the connotation of high-intensity volume fracturing technology is to carry out multi-cluster perforation in each section to form multiple independent double-wing fractures and to implement the proppant injection mode of liquid control and proppant increase to reduce the inflow fluid while ensuring the high-intensity proppant injection, so as to reduce the damage of inflow fluid to the formation. Third, there are 10 fracturing sections in Well Qiulin 207-5-H2, with 7–12 clusters in each section, and the displacement is in the range of 16–18 m3/min. According to the fluid control and proppant increase mode, 12146 m3 slick water and 4170 t proppant are injected in total. The tested production rate and absolute open flow of natural gas after the fracturing are up to 83.88 × 104 m3/d and 214.05 × 104 m3/d, respectively. Fourth, with the decrease of cluster spacing, the cumulative gas production increases gradually, but when the cluster spacing is less than 15 m, the increase amplitude of cumulative gas production decreases. Fifth, when the proppant injection intensity is lower than 6 t/m, the tested gas production per kilometer of stimulated section in a horizontal well overall presents an increasing trend with the increase of proppant injection intensity. When the proppant injection intensity is higher than 6 t/m, however, the tested gas production per kilometer of stimulated section does not increase significantly with the increase of proppant injection intensity. Sixth, as the included angle between the borehole trajectory and the direction of maximum horizontal principal stress increases, the tested gas production per kilometer of stimulated section overall presents an increasing trend. When the hydraulic fracture is nearly perpendicular to the borehole, the effective drainage area is the largest and the tested gas production per kilometer of stimulated section is also the highest. In conclusion, the fracturing mode of high production well has a borehole trajectory of large included angle, perforation cluster spacing of 10 m or so, proppant injection intensity of 5 t/m and large-displacement slick water + continuous injection of combined particle size proppant.

Abstract A multiple‐input multiple‐output (MIMO) radar with frequency diverse array (FDA) produces a range‐angle‐dependent steering vector, which can suppress the deceptive jamming in joint range‐angle domain. This in turn complicates the task of radar jamming. With the emergence and development of digital radio frequency memory (DRFM), radar electronic jamming technique has entered the age of coherent jamming. Based on the analysis of the superiority of the FDA‐MIMO radar in cancelling the deceptive jammers, a novel range gate pull‐off method via DRFM against FDA‐MIMO radar is proposed. Compared with the traditional deceptive jamming methods, the proposed method cannot be suppressed due to the mismatch in range. In particular, even the anti‐jamming methods based on power domain cease to be effective. The effectiveness of the proposed scheme in jamming the tracking performance of the FDA‐MIMO radar is demonstrated via computer simulations.

During radar detection, the adaptive beamforming technique needs to create nulls to resist the interference. When the interference appears within the mainlobe, the main detection beam will become distorted. To solve this problem, a new method for the covariance matrix reconstruction is proposed for the mainlobe maintenance problem, and a worst-case performance optimization (WCPO) algorithm with enhanced waveform robustness is obtained. Its integration is performed over a known region without the target information to obtain the improved covariance matrix, which is then brought into the convex optimization equation to solve for the weight vector. Simulation results show that the output signal-to-noise ratio of this algorithm is higher than that of the conventional WCPO algorithm with a robust beam for the same signal-to-noise ratio. It can also effectively eliminate the primary lobe offset and secondary lobe elevation problems.

Hepatitis B virus (HBV) infection remains a major global threat to human health worldwide. Recently, the Chinese medicines with antiviral properties and low toxicity have been a concern. In our previous study, Eupolyphaga sinensis Walker polysaccharide (ESPS) has been isolated and characterized, while its antiviral effect on HBV remained unclear. The anti-HBV activity of ESPS and its regulatory pathway were investigated in vitro and in vivo. The results showed that ESPS significantly inhibited the production of HBsAg, HBeAg, and HBV DNA in the supernatants of HepG2.2.15 in a dose-dependent manner; HBV RNA and core protein expression were also decreased by ESPS. The in vivo studies using HBV transgenic mice further revealed that ESPS (20 and 40 mg/kg/2 days) significantly reduced the levels HBsAg, HBeAg, and HBV DNA in the serum, as well as HBV DNA and HBV RNA in mice liver. In addition, ESPS activated the Toll-like receptor 4 (TLR4) pathway; elevated levels of IFN-β, TNF-α, and IL-6 in the serum were observed, indicating that the anti-HBV effect of ESPS was achieved by potentiating innate immunity function. In conclusion, our study shows that ESPS is a potential anti-HBV ingredient and is of great value in the development of new anti-HBV drugs.

Antibiotics resistance is one of the most significant public health threats globally. Strategies that strengthen host defenses to control pathogen infection has become a hot research field. Macrophages are part of early host defense mechanisms, and are activated via host pattern recognition receptors (PRRs), such as Toll-like receptor 4 (TLR4), which then facilitates phagocytosis and elimination of invading pathogens. However, few activators of PRRs have been approved for clinical use because of their toxic effects. This study aimed to investigate whether Strongylocentrotus nudus eggs polysaccharide (SEP), a non-toxic extract from seafood, contributes to host defense against bacterial infection. Results showed that SEP promoted bacterial clearance by enhancing phagocytosis by macrophages during E. coli infection in vitro, but was inhibited by TLR4 specific inhibitor TAK-242, STAT3 inhibitor Stattic or blockade of CD64. In addition, SEP protected mice from E. coli induced mortality, reduced pulmonary inflammation and inhibited dissemination of bacteria to organs, while TAK-242 retarded the protection of SEP. Overall, SEP strengthened innate host defense and improved the outcome in bacterial infection, suggesting that SEP could be used as a potential immunomodulator in host-directed therapies.

Abstract Understanding spontaneous imbibition helps to determine the fracturing fluid volume and optimize the flowback design. At present, many studies have mainly focused on shale, but few on igneous rocks. As such, in this study, imbibition experiments were conducted on igneous rocks. The effects of KCl concentration, confining pressure, and imbibition direction on the spontaneous imbibition were systematically investigated. This study then introduces a new imbibition capacity index. The results show that KCl concentration has certain inhibitory effects on igneous rock imbibition, which reduce the absorption of clay minerals to liquid. Different imbibition directions result in distinct imbibition volumes. The co-current imbibition process is similar to fluid leak-off, but this rule is not satisfied in countercurrent imbibition, the n of which is fitted as 0.1.0.3. Increasing the confining pressure will slightly decrease the imbibition capacity of igneous rock. Rock imbibition causes a decrease in the surface hardness and physical properties of igneous rock, and increasing the KCl concentration in the fluid will effectively hinder clay swelling.

Thioredoxin (Trx) is a hydrogen acceptor of ribonucleotide reductase and a regulator of some enzymes and receptors. It has been previously shown that significantly elevated levels of Trx expression are associated with the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), but it is not clear how Trx regulates the effects of hydrogen peroxide (H2O2) on myogenic differentiation of BMSCs. Here, we report that rat BMSCs treated with a high dose (150 µm) of H2O2 exhibited a significant reduction in viability, cell cycling, and superoxide dismutase and glutathione peroxidase levels, and an increase in reactive oxygen species and malondialdehyde levels, which was accompanied by reductions in protein kinase B activation and forkhead Box O1, myogenic differentiation 1 and myogenin expression during myogenic differentiation. Furthermore, treatment with recombinant human Trx significantly mitigated the effects of H2O2 on the myogenic differentiation of BMSCs, and this was abrogated by cotreatment with wortmannin [a specific phosphatidylinositol 3‐kinase inhibitor]. In summary, our results suggest that treatment with recombinant human Trx mitigates H2O2‐induced oxidative stress and may promote myogenic differentiation of rat BMSCs by enhancing phosphatidylinositol 3‐kinase/protein kinase B/forkhead Box O1 signaling.

The hybrid of the frequency diversity array (FDA) radar and multiple-input multiple-output (MIMO) radar, namely, FDA–MIMO radar, provides more degrees of freedom and improves the overall performance of the system. The essence of FDA–MIMO radar transmitting subaperture design is to divide the transmit array into multiple subapertures to improve the interference suppression capability of the radar. Among them, orthogonal waveforms are transmitted between each subaperture, and each element inside the subaperture transmits the same waveform. Aiming at the problem of how the subaperture design of the FDA–MIMO radar affects its interference suppression performance, we analyzed the two aspects of the normalized beampattern and (non-)adaptive beamforming. We conclude that when interference is dominant, setting the number of subapertures to half of the number of transmit array elements can effectively reduce the sidelobe level and increase the output signal-to-interference-plus-noise ratio. A large number of simulation results verify the effectiveness and superiority of this method.

Aimed at the current problem of insufficient analysis of the influence of the diversified formation of dual aircraft on monopulse radar position tracking, the dual aircraft echo equivalent two point source jamming model is built. We designed the dual aircraft formation penetration movement scenario and three different formation spacings of 150, 250, and 350 m and extracted the dynamic radar cross section sequences of dual aircraft under different formation spacings. We established the dual aircraft formation equivalent scenario and calculated the dynamic signal-to-noise ratio and distance measurement accuracy of the radar received echo signals with different formation spacings. We fully considered the randomness characteristics of the phase difference of the actual dual aircraft echo and built the random angle error model of dual aircraft echo equivalent jamming. The distribution and random numerical characteristics of the random angular error are simulated and analyzed, and we combined the radar measurement conversion target position tracking algorithm to analyze the influence of different formation spacings on the monopulse radar tracking target position and position tracking accuracy. The simulation results show that a formation spacing of 350 m produces a greater randomness of angular error for dual targets, resulting in a greater dispersion of radar measurement traces, and the final average position mean square error is 132.8 m, which improves the position error by 15.6% compared with 150 m spacing.

For the purpose of improving the accuracy and effectiveness of acid fracturing design for carbonate reservoirs with developed natural fractures, an acidizing fluid flow and reaction model taking the multiple leak-off effect of natural fracture, wormhole and matrix into account was established according to the liquid phase reaction equilibrium principle and the local reaction equilibrium principle after the dynamic change of fracture geometry in the process of fracture created by prepad fluid was simulated in the classical pseudo-three dimensional mathematical model of fracture propagation. Then, the acid fracturing stimulation of a case well on site was taken as an example. The newly developed model was used to simulate the filtration process of acidizing fluid in fractures and the dynamic etching morphology of acidic rocks during the acidizing fluid injection of prepad acid fracturing. The effective length of etched fractures was determined by analyzing the concentration change of acidizing fluid along the direction of hydraulic fracture length and the threshold concentration of residual acidizing fluid comprehensively, and then it was compared with the interpretation result of pressure buildup test. And the following research results were obtained. First, in the process of acid fracturing in fractured–porous reservoirs, the acidizing fluid filtration velocity along the direction of fracture length is not constant and the filtration velocity curve fluctuates in a serrated shape. And the acidizing fluid filtration velocity where etched wormholes meet natural fractures is commonly higher than that in matrix. Second, acidizing fluid is lost seriously and the effective distance of acidizing fluid gets short significantly during the acid fracturing of fractured–porous reservoirs. Third, acid fracturing in the verification well is remarkable in blockage removing and stimulation, and its well test interpretation results are consistent with the simulation interpretation results provided by the newly developed mathematical model. It is indicated that this newly developed model is reliable. In conclusion, the mathematical model of prepad acid fracturing which considers multiple leak-off effect is more suitable for acid fracturing simulation of fractured–porous reservoirs. Keywords: Carbonate rock, Reservoir, Natural facture, Wormhole, Prepad acid fracturing, Acidizing fluid filtration, Effective fracture length, Fractured–porous, Acid fracturing simulation

In this paper, a series of novel form-stable phase change materials (PCMs) containing phosphorus and silica were prepared by transesterification of diethyl phosphite with 1-tetradecanol, 1-hexadecanol and 1-octadecanol, followed by ring-opening reaction and hydrolytic condensation of 2,3-epoxypropoxy propyltrimethoxysilane (silane coupler KH-560). The leakage of pure higher alcohols in molten state was effectively solved due to the support of cross-linked silicon network structure. The co-incorporated phosphorus and silicon would accelerate the formation of chars and improve the thermal stability and fire resistance. The chemical structure and crystalline structure of form-stable PCMs were determined by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Differential scanning calorimeter (DSC) results indicate the melting points are in the range of 29 °C to 55 °C with the latent heat between 81.5 J/g to 116.9 J/g. Thermogravimetric (TG) analyses exhibit improved thermal stability of prepared PCMs compared to pure higher alcohols. The results of scanning electronic microscope (SEM), energy dispersive spectroscope (EDS) and FT-IR confirm the formation of phosphorus-rich and silicon-rich compact chars after thermal treatments. Keywords: Form-stable phase change materials, Higher alcohols, Diethyl phosphite, Silane coupler KH-560, Fire resistance

Steering acid fracturing is a technique that improves the conductivity of carbonate reservoir. It is widely used in a carbonate reservoir. However, due to the lack of comparative experiments, the application of steering acid to improve the fracturing results is still unknown. Therefore, a series of true triaxial acid fracturing experiments were conducted to study steering acid fracturing in carbonate reservoir. The carbonate specimens used in the experiment were from the Qixia group and Dengsi Member in Sichuan, China. In this study, slick water, cross-linked gel, and self-generating acid were used as ahead fluid to cooperate with steering acid. Experimental results show that (1) the low-viscosity ahead fluid with steering acid can result in more complex fractures; (2) the complexity of fractures is influenced by natural fracture and the viscosity of the ahead fluid; and (3) based on the 3D scanning results of the fracture surface, different ahead fluids will lead to different corrosion results. This study provides useful suggestions on steering acid fracturing design and physical simulation experiments.

Acid fracturing is the most important stimulation method in the carbonate reservoir. Due to the high cost and high risk of acid fracturing, it is necessary to predict the reservoir productivity before acid fracturing, which can provide support to optimize the parameters of acid fracturing. However, the productivity of a single well is affected by various construction parameters and geological conditions. Overfitting can occur when performing productivity prediction tasks on the high-dimension, small-sized reservoir, and acid fracturing dataset. Therefore, this study developed a stacking heterogeneous ensemble model with a hybrid wrapper-based feature selection strategy to forecast reservoir productivity, resolve the overfitting problem, and improve productivity prediction. Compared to other baseline models, the proposed model was found to have the best predictive performances on the test set and effectively deal with the overfitting. The results proved that the hybrid wrapper-based feature selection strategy introduced in this study reduced data acquisition costs and improved model comprehensibility without reducing model performance.

Since the beampattern has the characteristics of range-angle dependence, frequency diverse array multiple-input multiple-output (FDA-MIMO) radar has a good application prospect. There have been many studies to improve the performance of the beampattern by optimizing the frequency offset. However, on the basis of fully understanding the time parameters, the relationship between the array element frequency offset and the beampattern performance still needs to be clarified. Based on a new FDA-MIMO radar framework, this paper presents an analytical solution of the beampattern, which removes the influence of the time parameter. Taking the minimum main lobe as the objective function, an analytical method for solving a better frequency offset is given. Then, a method of using the window function was proposed to reduce the high side lobes of the range dimension. Comparing with the existing FDA radar beampattern design methods, it can achieve a more focusing beampattern. The simulation results verify the correctness of the theory.

In order to study the dynamic mechanical properties of recycled concrete with ferronickel slag, dynamic experiments on cylindrical specimens (φ 73 mm × 36.5 mm) were performed using a split Hopkinson pressure bar (SHPB) system. The effects of loading rate and recycled aggregate replacement rate on the compressive strength, toughness index, peak strain, and failure pattern of the concrete were investigated, and four different loading rates and aggregate replacement rates were selected. In addition, cohesive elements were embedded between C3D8R elements in the numerical model using Python language to simulate the failure process of the recycled concrete, and the reliability of the simulation was validated by the obtained experimental results. It was found that the peak strain of the recycled concrete was significantly higher than that of the ordinary concrete; however, its peak stress was lower than that of the ordinary concrete. In comparison to the recycled concretes containing 70% and 100% recycled coarse aggregates (RCAs), the toughness index amplification of the recycled concrete containing 30% RCAs was the most obvious. The failure pattern and mechanical properties of the numerical model were consistent with those of the test specimens, thus validating the reliability of the numerical simulation.

ABSTRACT: Background: The antibiotic resistance and biofilm formation of pathogenic microbes exacerbate the difficulties of anti-infection therapy in the clinic. The structural modification of antimicrobial peptides (AMP) is an effective strategy to develop novel anti-infective agents. Method: Seventeen amino acids (AA) in the longer chain of EeCentrocin 1 (from the edible sea-urchin Echinus esculentus) were truncated and underwent further modification. To produce lead peptides with low toxicity and high efficacy, the antimicrobial activity or cytotoxicity of peptides was evaluated against various multidrug-resistant bacteria/fungi or mammalian cells in vivo/ in vitro. In addition, the stability and modes of action of the lead peptide were investigated. Findings: EC1-17KV displayed potent activity and an expanded antimicrobial spectrum, especially against drug-resistant gram-negative bacteria and fungi, attributable to its enhanced amphiphilicity and net charge. In addition, it exhibits bactericidal/fungicidal activity and effectively increased the animal survival rate and mitigated the histopathological damage induced by multidrug-resistant P. aeruginosa or C. albicans in infected mice or G. mellonella. Moreover, EC1-17KV had a poor ability to induce resistance in bacteria and fungi and exhibited desirable high-salt/high-temperature tolerance properties. In bacteria, EC1-17KV promoted divalent cation release to damage bacterial membrane integrity. In fungi, it changed C. albicans membrane fluidity to increase membrane permeabilization or reduced hyphal formation to suppress biofilm formation. Interpretation: EC1-17KV is a promising lead peptide for the development of antimicrobial agents against antibiotic resistant bacteria and fungi. Funding: This work was funded by the National Natural Science Foundation of China (No. 81673483, 81803591); National Science and Technology Major Project Foundation of China (2019ZX09721001-004-005); National Key Research and Development Program of China (2018YFA0902000); ''Double First-Class'' University project (CPU2018GF/GY16); Natural Science Foundation of Jiangsu Province of China (No. BK20180563); and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Triple-negative breast cancer (TNBC) is an aggressive disease with worst prognosis than other subtypes of breast cancer. Owing to the lack of hormone receptors and HER2 expression on TNBC cells, patients do not have targeted therapy options available with other breast cancer subtypes. Extensive efforts have been made to identify novel therapeutics against TNBC. Interestingly, recent studies had shown that plant-derived natural products could modulate the autophagy and induce the breast cancer cells death. Seed of Brucea javanica has been used as an important traditional Chinese medicine against cancers. In the present study, the anti-breast cancer potential of ethanol crude extracts from B. javanica seed (BJE) was explored. Data demonstrated that BJE could inhibit the TNBC cell line MDA-MB-231 proliferation and induced apoptosis. In the cells exposed to BJE, protein expressions of UNC-51-like kinase-1 (ULK1) and Beclin-1 and the ratio of light chain 3 II/I (LC3 II/I) were reduced, while the expression of p62 was increased, indicating an inhibition on autophagy. Moreover, BJE promoted the phosphorylation of mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and Akt in MDA-MB-231. BJE also suppressed the MDA-MB-231 tumor growth in vivo. Coincide with the results in vitro, autophagy in the tumor tissue was weakened as indicated by decreased ratio of LC 3 II/I and Beclin-1 accompanied by enhanced phosphorylation of mTOR, which confirmed that autophagy restraint via the PI3K/Akt/mTOR signaling pathway contributes to the suppression by BJE. Notably, no noticeable toxicity in non-targeted organs was found, including small intestine, liver, and kidney. Taken together, this study revealed anti-breast cancer activity of BJE based on autophagy restraint, highlighting its clinical importance as a novel natural agent against TNBC.

Defects such as voids, pores, and joints will transform into big scale cracks in the rock of tunnel surrounding under dynamic load like blasting and earthquake. In this paper, three kinds of symmetrical cracks were chosen as an example, and experiments and numerical simulations were conducted to study the effect of symmetric cracks on a blast-induced crack. The relationship of main crack propagation characteristic and distribution of symmetrical cracks was investigated. Some circular specimens using two kinds of material, PMMA and sandstone, including a center hole charged with a detonator and pre-existing cracks were used in the experiments. The test system consisted of an oscilloscope and an ultradynamic strain amplifier and crack propagation gauges (CPGs) were employed in monitoring propagation velocity. AUTODYN code was applied in numerical simulation to investigate the propagation behavior of main crack between symmetrical cracks. Linear equation of state and a modified major principal stress failure criterion was utilized to describe the status of rock material. Based on experimental and numerical results, it can be concluded that (1) the pre-existing symmetrical cracks have arrest effect on main crack propagation, (2) compressive stress in y-direction plays very important roles in crack arrest, and (3) the spacing of parallel cracks has a great influence on crack propagation length and velocity.

The Lower Cambrian Longwangmiao dolomite gas reservoirs in the Sichuan Basin are characterized by well-developed natural micro-fractures and dissolved pores and cavities. Due to the strong heterogeneity of reservoirs and the serious damage of drilling and completion fluids, acid placement is difficult, and especially the acidizing stimulation of long-interval highly deviated wells or horizontal wells is more difficult. In this paper, the diverting mechanism and rheological behavior of viscoelastic surfactant (VES) based diverting acid was firstly investigated, and the diverting acid with good diversion performance and low secondary damage was selected as the main acid. Then, based on the experimental results of its rheological behaviors, an empirical model of effective viscosity was fitted and a two-scale wormhole propagation model was coupled. And accordingly, a mathematical model for the acidizing of self-diverting acid was established to simulate the pH value, Ca2+ concentration, effective viscosity and wormhole shape under the effect of diverting acid in long-interval highly deviated wells that are non-uniformly damaged. Finally, gelled acid and 5% VES diverting acid were compared in terms of their etched wormhole shapes, flow rate distribution and acid imbibition profiles. It is shown that the diverting acid can obviously improve the acid imbibition profile of strong-heterogeneity reservoirs to intensify low-permeability reservoir stimulation. In view of the strong heterogeneity of Longwangmiao dolomite reservoirs and the complexities of drilling and completion fluid damage in the Sichuan Basin, a placement technology was developed for variable VES concentration diverting acid in horizontal wells and long-interval highly deviated wells completed with slotted liners. This acid placement technology has been practically applied in 8 wells and their cumulative gas production rate tested at the wellhead is 1233.46 × 104 m3/d. The average production stimulation ratio per well is up to 1.95. It provides a support for the efficient development of the Longwangmiao giant gas reservoir. Keywords: Sichuan Basin, Early Cambrian, Longwangmiao Fm gas reservoir, Dolomite, Diverting acid, Rheological behavior, Matrix acidizing, Numerical simulation, Field application, Highly-efficient development

BACKGROUND:Preclinical studies of the therapeutic role of stem cell based therapy in animal models of osteoporosis have largely yielded inconsistent results. We performed a meta-analysis to provide an overview of the currently available evidence. METHODS:Pubmed, Embase and Cochrane Library databases were systematically searched for relevant controlled studies. A random-effect model was used for pooled analysis of the effect of stem cell based therapy on bone mineral density (BMD). Stratified analyses were performed to explore the effect of study characteristics on the outcomes. RESULTS:Pooled results from 12 preclinical studies (110 animals in stem cell treatment groups, and 106 animals in control groups) indicated that stem cell based treatment was associated with significantly improved BMD (standardized mean difference [SMD] = 1.29, 95% Confidence Interval [CI]: 0.84-1.74, P < 0.001) with moderate heterogeneity (Cochrane's Q test: P = 0.02, I2 = 45%) among the constituent studies. Implantation of bone marrow cells, bone marrow mesenchymal stem cells, adipose-derived stem cells, and human umbilical cord blood-derived CD34+ cells, were all associated with improved BMD as compared to that in the controls (P < 0.05 for all); the only exception being the use of embryonic stem cell transplantation (P > 0.05). Egger's test detected potential publication bias (P = 0.055); however, 'trim and fill' analysis yielded similar results after statistically incorporating the hypothetical studies in the analysis (SMD = 1.24, 95% CI: 0.32-2.16, P < 0.001). CONCLUSIONS:Stem cell transplantation may improve BMD in animal models of osteoporosis. Our meta-analysis indicates a potential therapeutic role of stem cell based therapy for osteoporosis, and serves to augment the rationale for clinical studies.

Mesenchymal stem cells (MSCs) are an attractive source for the clinical cell therapy of liver injury. Although the use of adult serum, platelet lysate, or cord blood serum solves some of the problems caused by fetal bovine serum (FBS), the allogeneic immune response, contamination, and donor-to-donor and donor-to-receptor differences still obstruct the application of MSCs. In this study, the influences of autoserum from liver-injured rats (LIRs) and allogeneic serum from healthy rats on the isolation and culture of bone marrow MSCs (BMSCs) were examined and compared to FBS. The results showed that BMSCs cultured with autoserum or allogeneic serum exhibited better MSC-specific morphology, lower rate of cell senescent, and higher proliferation kinetics than those with FBS. In addition, autoserum promoted the osteogenic differentiation potential of BMSCs as allogeneic serum did. Although there were no significant differences in proliferation activity, immunophenotypic characterization, and differentiation potential between BMSCs cultured with autoserum and those with allogeneic serum, the potential adverse immunological reactions in patients with allogeneic material transplantation must be considered. We therefore believe that the autoserum from liver-injured patients may be a better choice for MSC expansion to meet the needs of liver injury therapy.