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Deepwater oil and gas exploitation has become an important field in the petroleum industry development. However, there are still no mature methods for hydrate prevention in the deepwater wells clea...

Resistance to intense electron beam bombardment of TiC/Graphite was investigated numerically and experimentally. The results indicate that the decreasing of initial electron energy and the increasing of TiC coating thickness could both enhance the electron energy deposition inside the surface layer of the TiC/Graphite, and finally cause the increasement of the temperature differences at the interface between TiC coating and graphite substrate. The graphite substrate is well coated with TiC in all the TiC/graphite targets, and the morphology of the TiC coatings could be controlled by adjusting its thickness. Under electron beam with accelerating voltage of 850 keV, current of 11 kA, pulsewidth of 40 ns and pulse number of 30 times, TiC/Graphite target with TiC coating thickness of 1 μm shows more excellent electron beam bombardment resistance, agreeing with the results of the numerical modeling.

Emotion-cause pair extraction (ECPE), which aims to extract emotions and the corresponding causes in documents, has a wide range of applications in network public opinion analysis. Current two-stage methods first extract emotion and cause clauses, and then pair them. However, there are two problems in these methods: 1) the unidirectional enhancement between emotion and cause extraction fails to make full use of the correlation between them; 2) the errors from the first stage directly degrade the performance of the second stage. To address these problems, we firstly propose a mutually auxiliary multitask model to promote the extraction of emotion and cause clauses by adding two auxiliary tasks which are identical to the original tasks. The proposed model uses the predicted results generated by the two auxiliary tasks as extra features of each other’s main tasks, so as to establish the bidirectional correlation between emotion and cause extraction. Secondly, to reduce the influence of error propagation on the second stage, we design a self-distillation method for pairwise tasks to train the proposed model, which further improve the accuracy of emotion and cause extraction. Experimental results on the ECPE benchmark dataset show that the proposed model has achieved good performance on emotion-cause pair extraction, outperforming the baseline models by 1.92% in F1 score.

Short half-life is one of the main causes of drug attrition in clinical development, which also leads to the failure of many leading compounds and hits to become drug candidates. Nowadays, nanomaterials have been applied to drug development to address this problem. In fact, the clinical application of nanoparticles (NPs) is severely limited due to their rapid elimination by the reticuloendothelial system (RES) in vivo. In this paper, we aim to summarize representative strategies on prolonging the circulation time for bridging the gap between excellent pharmaceutics and proper half-life and encourage clinical translation.

Purpose The purpose of this paper is to establish a strain prediction model of mining overburden deformation, to predict the strain in the subsequent mining stage. In this way, the mining area can be divided into zones with different degrees of risk, and the prevention measures can be taken for the areas predicted to have large deformation. Design/methodology/approach A similar-material model was built by geological and mining conditions of Zhangzhuang Coal Mine. The evolution characteristics of overburden strain were studied by using the distributed optical fiber sensing (DOFS) technology and the predictive model about overburden deformation was established by applying machine learning. The modeling method of the predictive model based on the similar-material model test was summarized. Finally, this method was applied to engineering. Findings The strain value predicted by the proposed model was compared with the actual measured value and the accuracy is as high as 97%, which proves that it is feasible to combine DOFS technology with machine learning and introduce it into overburden deformation prediction. When this method was applied to engineering, it also showed good performance. Originality/value This paper helps to promote the application of machine learning in the geosciences and mining engineering. It provides a new way to solve similar problems.

This article proposes a novel parallel gradient-based electromagnetic (EM) optimization approach to microwave components using adjoint-sensitivity-based neuro-transfer function (neuro-TF) surrogate. In the proposed technique, the surrogate model is trained using not only the input-output behavior but also the adjoint sensitivity information generated from the EM simulation simultaneously. By exploiting adjoint EM sensitivity for surrogate modeling, the proposed technique can obtain accurate surrogate models with larger valid range using the same amount of fine model evaluations compared with the existing gradient-based surrogate optimization without adjoint sensitivity. Furthermore, because the surrogate model is developed using adjoint EM sensitivity, the gradients calculated using the developed surrogate model in the proposed technique are much more accurate. The accurate gradients lead to further speedup of the surrogate optimization and improved quality of surrogate optimal solution in each surrogate optimization iteration. Since the surrogate model is valid in a large neighborhood and the gradients are sufficiently accurate, the proposed technique can achieve the optimal EM solution faster than the existing gradient-based surrogate optimization without adjoint sensitivity. Three examples of EM optimizations of microwave components are used to demonstrate the proposed technique.

Consumer Internet-of-Things platforms, especially in smart home, have received widespread attention. A large number of end-to-end and edge-to-end wireless communication links are subject to significant security and privacy risks. Key generation using radio link side-channel information is a burgeoning technology to solve this problem. This article designs a symmetric key generation method without environmental constraints, namely, MobiKey. The basic idea is taking the human mobility in home or the swing of the antenna to generate symmetric keys based on channel reciprocity. We leverage the practical phase information as the channel feature to generate symmetric keys between two communicating parties. To overcome the effects of noise on both communication sides and get a better performance, MobiKey harnesses the adaptive quantization method to make the bit generation rate and bit matching rate higher. MobiKey also uses the adaptive inconsecutive samples to increase the confusion of the adversary. Moreover, we propose the D-Gray code to enhance the randomness of quantization. MobiKey is implemented on different commercial devices, and the results show that it has comparative advantages in key generation consistency, randomness, and security. In addition, the performance in preventing predictable channel attacks and eavesdropping attack is discussed.

Shopping behavior information acquisition and mining are of great importance for marketing and merchandizing strategies developing. With a single tag on each commodity, the previous pattern-based works only can be considered as behavior recognition solutions with behavior streams as output for each tag. In this article, we introduce a completely new mode of dual tags and propose a fine-grained shopping behavior acquisition solution called as fine-grained shopping behavior information acquisition (FGSA). FGSA enables shopping behaviors recognition by taking advantage of the phase calibrated Doppler shift of dual tags and extracts fine-grained behavior information for each behavior from the fusion Doppler spectrums with only one antenna. We implement a prototype of FGSA with COTS radio-frequency identification (RFID) devices and conduct extensive experiments to evaluate its performance. The experimental results demonstrate that FGSA achieves excellent performance in terms of both behavior recognition and information extraction.

Suspended sediment concentration detection is a critical task for many practical applications. Traditional schemes suffer from complex operation, poor real-time performance and high cost. This paper explores the possibility of detecting sediment concentration in water with low-cost passive RFID tags. We propose a simple yet effective signal model, in which the received signal is separated into static and dynamic components. We establish the relationship between measured signal changes and sediment concentration via polynomial fitting in offline step. Therefore, the sediment concentration can be accurately detected with a simple mapping operation in the following online step. We implement a prototype system with COTS RFID devices, and extensive experiments are conducted to validate our design. The experimental results demonstrate that our scheme is able to achieve more than 95% accuracy for sediment concentration detection in water.

To discover novel BChE inhibitors, a hierarchical virtual screening protocol followed by biochemical evaluation was applied. The most potent compound 8012-9656 (eqBChE IC50 = 0.18 ± 0.03 μM, hBChE IC50 = 0.32 ± 0.07 μM) was purchased and synthesized. It inhibited BChE in a noncompetitive manner and could occupy the binding pocket forming diverse interactions with the target. 8012-9656 was proven to be safe in vivo and in vitro and showed comparable performance in ameliorating the scopolamine-induced cognition impairment to tacrine. Additionally, treatment with 8012-9656 could almost entirely recover the Aβ1-42 (icv)-impaired cognitive function to the normal level and showed better behavioral performance than donepezil. The evaluation of the Aβ1-42 total amount confirmed its anti-amyloidogenic profile. Moreover, 8012-9656 possessed blood-brain barrier (BBB) penetrating ability, a long T1/2, and low intrinsic clearance. Hence, the novel potential BChE inhibitor 8012-9656 can be considered as a promising lead compound for further investigation of anti-AD agents.

We study the interaction effect of financial intermediaries and family ties on labor participation and employment type in China. Although existing studies examine these effects separately, we investigate the effects of both factors in one model. We give empirical evidence to support earlier arguments that family ties negatively affect labor force participation and positively affect self‐/family‐employment behavior and that financial development positively affects labor force participation. Departing from the extant literature, our results overall indicate a compensating effect of financial intermediaries for family ties in labor participation and employment type. We further argue that there are gender, urban/rural, and age differences in the role of financial intermediaries. The effect of financial intermediaries on the strength of family ties is more relevant for female, rural, and younger people compared to male, urban, and older people.

Human aldo-keto reductase family 1 member C3 (AKR1C3) is known as a hormone activity regulator and prostaglandin F (PGF) synthase that regulates the occupancy of hormone receptors and cell proliferation. Because of the overexpression in metabolic diseases and various hormone-dependent and -independent carcinomas, as well as the emergence of clinical drug resistance, an increasing number of studies have investigated AKR1C3 inhibitors. Here, we briefly review the physiological and pathological function of AKR1C3 and then summarize the recent development of selective AKR1C3 inhibitors. We propose our viewpoints on the current problems associated with AKR1C3 inhibitors with the aim of providing a reference for future drug discovery and potential therapeutic perspectives on novel, potent, selective AKR1C3 inhibitors.

Tetragonal-to-monoclinic Bi4Ti3O12 (BIT) exhibits complicated domain patterns thanks to its two independently switchable spontaneous polarizations that lie in the ac plane of the monoclinic unit cell. Utilizing the nonlinear theory of ferroelectric phase transformation based on the deformation gradient tensor and spontaneous polarization, we systematically analyzed domain patterns in BIT, classifying its domain walls (DWs) into five different classes. Three-dimensional piezoresponse force microscopy (3D PFM) was then adopted to characterize the ceramic BIT, revealing intriguing domain patterns in planar, lateral, as well as tilted grains. Guided by the nonlinear theoretical analysis, 3D polarization distributions were successfully reconstructed, wherein 9°-, 90°-, 91°-, and 180°-DWs were observed along with 171°-charged DWs. The nonlinear analysis is thus confirmed by 3D PFM characterizations, and the combined theoretical analysis and experimental investigation contribute to our understanding on the 3D tetragonal-to-monoclinic ferroelectric domain patterns.

This article proposes a multifeature-assisted neuro-transfer function (neuro-TF) surrogate-based electromagnetic (EM) optimization technique exploiting trust-region algorithms for microwave filter design. The proposed optimization technique addresses the situation where the response of the starting point is far away from the design specifications. We propose to utilize multiple feature parameters to help move the passband of the filter response into the range of design specifications. The pole–zero-based neuro-TF is introduced in this article to help extract the multiple feature parameters when the feature parameters of filter responses are not explicitly identified. Furthermore, we propose to derive new optimization objective functions to involve the multiple feature parameters. A new trust-region updating formulation for the modified optimization objective functions is derived to guarantee the optimization convergence. With the assistance of multiple feature parameters, the proposed surrogate-based EM optimization has a better capability of avoiding local minima and can reach the optimal EM solution faster than the surrogate-based EM optimizations without feature assistance. Three examples of EM optimizations of microwave filters are used to demonstrate the proposed technique.

The prevention and control of natural gas hydrate (hereinafter, “hydrate” for short) blockage during deepwater gas well production tests is very important in ensuring the test safety. In this paper, the distribution of wellbore temperature and pressure field under different test conditions was analyzed, and the changes of hydrate deposition and blockage degree in the pipe string in the whole process of test under different test systems were evaluated using the hydrate generation–deposition–decomposition calculation method. On this basis, a deepwater gas well production test method based on hydrate prevention and control was proposed. And the following research results were obtained. First, in the process of deepwater gas well tests, the vapor–liquid phase of annular-mist flow pattern with the greatest risk of hydrate blockage is often formed in the wellbore. Therefore, it is more reasonable to take measures to prevent hydrate blockage in the process of tests than to prevent the formation of hydrate. Second, when the conventional four-point test method is used, it is required to set low gas production measurement points with lower flowing temperature. In the wellbore with high temperature and low temperature, however, hydrate tends to form and deposit easily, and a long period of test will increase the risk of test string blockage. Third, the mixed-sequence test system suitable for deepwater gas well tests can change wellbore temperature by adjusting the sequence of measuring points without changing the production rate and duration, so as to decompose hydrate sediment layers and reduce the maximum blockage degree of test string in the process of tests. Fourth, a three-point or two-point test method is recommended for deepwater gas wells without sand production, stress sensitivity, retrograde condensation and water production. Superior to the conventional four-point test method, three-point and two-point test methods can effectively reduce the risk of hydrate deposition and blockage in the test string, and it can shorten the testing time and reduce the test cost on the premise of ensuring the accuracy of the productivity equation. In conclusion, the research results are of help to the field test construction of deepwater gas wells. Keywords: Deepwater gas well, Production test, Natural gas hydrate, Prevention and control method, Mixed-sequence test, Pipe blockage degree, Flow assurance

Butyrylcholinesterase (BChE) is recently regarded as a biomarker in progressed Alzheimer's disease (AD), the development of selective BChE inhibitors has attracted a great deal of interest and may be a viable therapeutic strategy for AD. Previously, an aromatic tertiary amine derivative (S17-1001) was screened and validated as a selective BChE inhibitor. Structured-based molecular modification guided the synthesis of 43 analogs. Biological test of cholinesterase inhibition, in vitro blood brain barrier permeation assay, neurotoxicity assay and neuroprotective effects assay indicated two optimal compounds 17c and 19c. Both compounds showed selective BChE inhibitory (hBChE20 nM, eeAChE10 μM), good BBB permeation and primary cell safety. Besides, 17c can dose-response protect cell from Aβ

As a crucial target which is overexpressed in a variety of cancers, aldo-keto reductase 1C3 (AKR1C3) confers chemotherapeutic resistance to many clinical agents. However, a limited number of AKR1C3-selective inhibitors are applied clinically, which indicates the importance of identifying active compounds. Herein, we report the discovery, synthesis, and evaluation of novel and potent AKR1C3 inhibitors with structural diversity. Molecular dynamics simulations of these active compounds provide reasonable clarification of the interpreted biological data. Moreover, we demonstrate that AKR1C3 inhibitors have the potential to be superior therapeutic agents for re-sensitizing drug-resistant cell lines to chemotherapy, especially the pan-AKR1C inhibitor

Yaling Hu,1,2 Shuang Liu,3 Wenyuan Liu,2 Ziyuan Zhang,2 Yuxiang Liu,1 Sufen Li,2 Dalin Sun,2 Guang Zhang,2 Jingai Fang2 1Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China; 2Department of Nephrology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China; 3Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of ChinaCorrespondence: Jingai Fang, Department of Nephrology, First Hospital of Shanxi Medical University, 85 Jiefangnan Road, Taiyuan, Shanxi, 030001, People’s Republic of China, Email jingaifang2017003@126.comPurpose: Using network pharmacology and molecular docking to explore the mechanism of Yishen Capsule in the treatment of diabetic nephropathy.Materials and Methods: Active components of Yishen Capsule were obtained using database such as TCMSP and TCMID. UniProt protein database was used to screen and standardize the human-derived targets of the active chemical components. Diabetic nephropathy (DN) targets were obtained from databases such as GeneCards, OMIM, TTD, DisGeNET and DrugBank. A network of “Yishen Capsule Components-diabetic nephropathy Targets-Pathways” was constructed by analyzing data above to screening out core targets for molecular docking verification. DN is induced by streptozocin in rats after left nephrectomy. Renal tubular epithelial cells (RTECs) was isolated and cultured under high glucose conditions. Based on these experimental models, key pathway target genes screened by network pharmacology were verified both in vitro and in vivo.Results: The main active components of Yishen Capsule in the treatment of DN include quercetin, kaempferol, gallic acid, astragaloside IV, etc. Some key targets (such as AR, AKT1, TP53, ESR1, JUN) and important signal pathways (such as AGE-RAGE, HIF-1 and JAK-STAT signal pathway) were included in the treatment of DN with Yishen Capsule. Molecular docking assay showed that most of the targets have good binding activity with the components of Yishen Capsule. Based on the results of network pharmacology, key target proteins in HIF-1α and JAK2/STAT3 signaling pathways were selected for experimental verification. Results presented that HIF-1α, JAK2, STAT3, TGF-β and MCP-1 were increased under high glucose environment. With the treatment of Yishen Capsule, the expression of HIF-1α further increased, while the expression of JAK2, STAT3, MCP-1 and TGF-β was decreased.Conclusion: This study revealed the mechanism of Yishen Capsule in the treatment of DN, which possesses the characteristics of multi-component, multi-target, and multi-pathway. Further experiments confirmed that Yishen Capsule interfered with HIF-1α and JAK/STAT signaling pathways to reduce inflammation and fibrosis damage in the kidney tissue of rats with diabetic nephropathy.Keywords: diabetic nephropathy, network pharmacology, molecular docking, HIF-1α, JAK/STAT

Abstract: The leukocyte immunoglobulin (Ig)-like receptors (LILRs) are constituted by five inhibitory subpopulations (LILRB1-5) and six stimulatory subpopulations (LILRA1-6). The LILR populations substantially reside in immune cells, especially myeloid cells, functioning as a regulator in immunosuppressive and immunostimulatory responses, during which the nonclassical major histocompatibility complex (MHC) class I molecules are widely involved. In addition, LILRs are also distributed in certain tumor cells, implicated in the malignancy progression. Collectively, the suppressive Ig-like LILRB2 is relatively well-studied to date. Herein, we summarized the whole family of LILRs and their biologic function in various diseases upon ligation to the critical ligands, therefore providing more information on their potential roles in these pathological processes and giving the clinical significance of strategies targeting LILRs.

Qifu decoction (QFD) is a famous traditional Chinese medicine (TCM) composed of Astragali Radix (HuangQi) and Aconiti Lateralis Radix Praeparaia (Fuzi), which can alleviate doxorubicin (DOX)-induced cardiotoxicity (DIC). However, its protective mechanism remains obscured.The present study aimed to uncover the cardioprotective mechanism and the synergistic effect of QFD against DIC in mice.The cardioprotective activity of QFD against DIC was assessed by electrocardiogram, serum biochemical assays and histopathology. Mass spectrometry-based metabolomic approach was conducted to elucidate the preventive mechanisms of QFD, HuangQi decoction (HQD), and Fuzi decoction (FZD) against DIC. QFD, HQD, FZD-targeted metabolic pathways were identified and compared to investigate the synergistic mechanism of QFD by computational systems analysis. Quantitative real-time PCR (qRT-PCR) was further employed to validate the key metabolic pathways at the level of the gene.The electrocardiogram combined with the biochemical analysis and histopathology showed that the protection effects were sorted as QFD HQD ≈ FZD. A total of 41 metabolites contributing to DIC were identified in the mice serum, among which 32, 12 and 10 metabolites were significantly reverted by QFD, HQD and FZD, respectively. Metabolic pathway analysis revealed that DOX perturbed 12 metabolic pathways, and QFD, HQD, and FZD-treated groups could significantly reverse 12, 7 and 6 metabolic pathways of these 12 metabolic pathways. Metabolic pathway and qRT-PCR revealed that QFD could protect DIC mainly by regulating energy metabolism, amino acids metabolism, arachidonic acid metabolism and glycerophospholipid metabolism, and HQD and FZD mutually reinforced each other.These evidences revealed that QFD was a promising drug candidate for DIC by maintaining metabolic homeostasis. Meanwhile, this work provided a useful approach for evaluating the efficacy and the synergistic effects of TCMs against cardiomyopathy.

Radix Astragali is widely used in the traditional Chinese medicine with the effect of antiaging. The purpose of this study is to explore the main active ingredients and targets of Radix Astragali against renal aging by network pharmacology and further to verify the mechanism of the main active ingredients in vitro. TCMSP, ETCM, and TCMID databases were used to screen active ingredients of Radix Astragali. Targets of active ingredients were predicted using BATMAN-TCM and cross validated using kidney aging-related genes obtained from GeneCards and NCBI database. Pathways enrichment and protein-protein interaction (PPI) analysis were performed on core targets. Additionally, a pharmacological network was constructed based on the active ingredients-targets-pathways. HK-2 cell was treated with D-galactose to generate a cell model of senescence. CCK-8 and β-galactosidase were used to detect the effect of Radix Astragali active components on cell proliferation and aging. ELISA was used to detect the expression of senescence-associated secreted protein (TGF-β and IL-6) in the cell culture supernatant. Western blot was used to detect the expression of key proteins in the SIRT1/ p 53 pathway. Five active ingredients (Astragaloside I, II, III, IV and choline) were identified from Radix Astragali, and all these active ingredients target a total of 128 genes. Enrichment analysis showed these genes were implicated in 153 KEGG pathways, including the p 53 , FoxO, and AMPK pathway. 117 proteins and 572 interactions were found in PPI network. TP53 and SIRT1 were two hub genes in PPI network, which interacted with each other. The pharmacological network showed that the five main active ingredients target on some coincident genes, including TP53 and SIRT1. These targeted genes were involved in the p53, FoxO, and AMPK pathway. Proliferation of HK-2 cells was increased by Astragaloside IV treatment compared with that of the D-Gal treatment group. However, the proliferation of the SA-β-gal positive cells were inhibited. The expression of TGF-β and IL-6 in the D-Gal group was higher than that in the normal group, and the treatment of Astragaloside IV could significantly reduce the expression of TGF-β and IL-6. The expression of SIRT1 in the Astragaloside IV group was higher than that in the D-Gal group. However, the expression of p 53 and p 21 was less in the Astragaloside IV group than that in the D-Gal group. This study suggested that Astragaloside IV is an important active ingredient of Radix Astragali in the treatment of kidney aging via the SITR1- p 53 pathway.

We designed and demonstrated experimentally a silicon photonics integrated dynamic polarization controller. The overall size of the dynamic polarization controller on chip is 2.830 mm × 0.210 mm × 1 mm. The modulation bandwidth is 30 kHz. By using a variable step simulated annealing approach, we achieve a dynamic polarization extinction ratio greater than 25 dB. A numerical simulation method was used to optimize the relevant parameters of the dynamic polarization controller. It is expected that the dynamic polarization controller can be utilized in fiber communication systems or silicon photonics integrated quantum communication systems to minimize the size and decrease the cost further. This work was supported by the Aeronautical Science Foundation of China (No. 20200020115001), National Natural Science Foundation of China (No. 62175138), Key Research and Development Program of Guangdong Province (No. 2020B0303040002), Shanxi 1331KSC, and Open Project of the State Key Laboratory of Quantum Optics and Quantum Optics Devices of Shanxi University (No. KF202006).

Percolation theory has been widely used to study phase transitions in network systems. It has also successfully explained various macroscopic spreading phenomena across different fields. Yet, the theoretical frameworks have been focusing on direct interactions among nodes, while recent empirical observations have shown that indirect interactions are common in many network systems like social and ecological networks, among others. By investigating the detailed mechanism of both direct and indirect influence on scientific collaboration networks, here we show that indirect influence can play the dominant role in behavioral influence. To address the lack of theoretical understanding of such indirect influence on the macroscopic behavior of the system, we propose a percolation mechanism of indirect interactions called induced percolation. Surprisingly, our model exhibits a unique anisotropy property. Specifically, directed networks show first-order abrupt transitions as opposed to the second-order continuous transition in the same network structure but with undirected links. A mix of directed and undirected links leads to rich hybrid phase transitions. Furthermore, a unique feature of the nonmonotonic pattern is observed in network connectivities near the critical point. We also present an analytical framework to characterize the proposed induced percolation, paving the way to further understanding network dynamics with indirect interactions. Published version This work is supported by the Guangdong High-Level Personnel of Special Support Program, Young TopNotch Talents in Technological Innovation (grant no. 2019TQ05X138), Natural Science Foundation of Guangdong for Distinguished Youth Scholar, Guangdong Provincial Department of Science and Technology (grant no. 2020B1515020052), the National Natural Science Foundation of China (grant nos. 61903385 and 62003156), Guangdong Major Project of Basic and Applied Basic Research (grant no. 2020B0301030008), and the Chinese Academy of Sciences (grant no. QYZDJSSW-SYS018).

Behavioural and emotional problems (e.g., disruptive behaviours, hyperactivity, and anxiety, Chandler et al., 2016) are highly co-occurring in children with autism spectrum disorder (ASD, American Psychiatric Association, 2013). It has persistent effects on both individual (e.g., the occurrence of psychiatric disorders, Lai et al., 2019) and family functioning (e.g., maladjustment in parents, Zaidman-Zait et al., 2014). However, less is known about the trajectories of behavioural and emotional problems in this population. Although an overall improvement in behavioural and emotional problems has been reported in most studies (e.g., Stringer et al., 2020), a stable and increasing trend was also observed in a few studies (e.g., Mandy et al., 2022). The inconsistent finding may be attributed to differences in methodology across studies, such as sampling strategies (Vaillancourt et al., 2017), age ranges of participants, intervals between assessment points (Stringer et al., 2020), and even analysis methods (e.g., linear or curvilinear growth is estimated). Sample characteristics such as diagnosis time (Mandy et al., 2022), comorbid diagnoses (e.g., intellectual disability [ID], Gray et al., 2012; attention-deficit/hyperactivity disorder [ADHD], Flouri et al., 2015), and family deprivation (Flouri et al., 2015) can also lead to differences in findings. Population-based studies with longer periods of data may be able to provide further clarification. Data do suggest that behavioural and emotional problems occur more frequently in children with ASD compared with other children ( Woodman et al., 2016). However, evidence on whether and how trajectories of behavioural and emotional problems differ between children with and without ASD is sparse (Bos et al., 2018; Orm et al., 2021). There is a particular lack of studies that examine differences in trajectories of behavioural and emotional problems between children with and without ASD from early childhood forward. There is limited evidence reporting gender differences in trajectories of behavioural and emotional problems. From childhood to adolescence, Gotham et al. (2015) reported that the observed increase in emotional problems is more prominent in girls. However, gender differences have not always been found. For example, behavioural and emotional problems in boys and girls were reported to change similarly across childhood to adolescence (from 3 to 14 years) in both earlier-diagnosed (7 years or younger) and later-diagnosed (between 8 and 14 years) children (Mandy et al., 2022). This study aims to use population-based data to examine whether and how behavioural and emotional problems of children with and without ASD change from early childhood to late adolescence. A secondary focus is whether and how trajectories of problems differ between boys and girls.

CuO nanorods bearing Au nanoparticles (Au/CuO nanocomposites) were prepared by a solution-phase synthesis and exhibited efficient hydroquinone (HQ)-oxidase activity with good specificity. The Au/CuO nanocomposites effectively catalyzed the oxidation of colorless HQ to brown benzoquinone with an absorbance maximum at 376 nm but did not catalyze the conversions of catechol or resorcinol. Kinetic studies indicated that the Au/CuO nanocomposites exhibited a strong affinity for HQ, with a Michaelis-Menten constant of K

Efficient antibacterial therapy holds great promise for human health. However, it is often limited by the insufficient activity of antibacterial agents. Herein, we demonstrate that the localized surface plasmon resonance (LSPR) excitation of gold nanostars (AuNSs) can dramatically improve the antibacterial activity of a Zn-metal–organic frameworks (Zn-MOFs) nanosheet, which exhibits higher ability to generate reactive oxygen species (ROS) (∼2.5-fold) for bacterial inactivation under light irradiation. Mechanistic investigations demonstrate that the enhancement is closely related to a plasmon-induced “dual excited synergistic effect”. On the one hand, the Zn-MOFs nanosheets as photosensitive agents can be excited to generate ROS with bacterial toxicity. More importantly, abundant plasmonic hot electrons are generated on the surface of AuNSs upon LSPR excitation, which are then transferred from AuNSs into the Zn-MOFs due to the energy matching. As a result, the Zn-MOFs nanosheet presents an electron-rich condition, which activates the adsorbed O2 molecule into a transition state followed by its decomposition into ROS for bacterial inactivation. This study highlights the superiority of LSPR excitation on improving the antibacterial activity of MOFs and provides a novel strategy for effective antibacterial therapy.

Background : Using network pharmacology and molecular docking technology to explore the mechanism of Yishen capsules in the treatment of diabetic nephropathy. Methods: Active components of Yishen Capsules were obtained using database such as TCMSP and TCMID, and diabetic nephropathy targets were obtained from databases such as Gencards, OMIM, DisGeNET. A network of "Yishen Capsule Components-Diabetic Nephropathy Targets-Pathways" was constructed by analyzing data above to screening out core targets for molecular docking verification. Finally, a rat model of diabetic nephropathy was generated, and renal tubular epithelial cells were extracted and cultured under high glucose conditions. Based on these experimental models, the key signal pathway target protein genes screened by network pharmacology were verified both in vitro and in vivo. Results: The main active components of Yishen Capsule in the treatment of diabetic nephropathy include quercetin, kaempferol, gallic acid, astragaloside IV and so on. Some key targets (such as AR, AKT1, TP53, ESR1, JUN) and important signal pathways (such as AGE-RAGE signal pathway, HIF-1 signal pathway and JAK-STAT signal pathway) were included in the treatment of diabetic nephropathy of Yishen Capsule. Molecular docking assay showed that most of the targets have good binding activity with the components of Yishen Capsules. Based on the results of network pharmacology, key target proteins in HIF-1α and JAK2/STAT3 signaling pathways were selected for experimental verification. Results presented that HIF-1α, JAK2, STAT3, TGF-β and MCP were increased under high glucose environment. With the treatment of Yishen Capsule, the expression of HIF-1α further increased, while the expression of JAK2, STAT3, MCP-1 and TGF-β were decreased. Conclusions : This study revealed the mechanism of Yishen Capsules in the treatment of diabetic nephropathy, which possesses the characteristics of multi-component, multi-target, and multi-pathway. Further experiments confirmed that Yishen Capsules interfered with HIF-1α and JAK/STAT signaling pathways to reduce inflammation and fibrosis damage in the kidney tissue of rats with diabetic nephropathy. Key Words: Diabetic Nephropathy(DN); Network pharmacology; Molecular docking;HIF-1α; JAK/STAT

Gallium nitride (GaN) HEMT has board application prospect for 5G wireless communication systems. This paper reviews the recent advance in space mapping technique for GaN HEMT modeling technique. A novel decomposed-based space mapping technique is discussed. This method is a systematic modeling approach with fast developing speed. A 2×350 µm GaN HEMT device are used as an example.

Surrogate based optimization techniques are widely used for electromagnetic design optimization of microwave filters. This paper review the recent advanced works in surrogate optimization using feature parameter. Feature frequency and feature height are further utilized to speedup optimization process. A microwave filter example is applied to illustrate this advanced techniques.

Epithelial-mesenchymal transition (EMT) is implicated in the pathological processes of cancer metastasis and drug resistance. Anti-cancer drugs may also potentially lead to EMT, resulting in their reduced therapeutic effect. Therefore, the combination of these anti-cancer drugs with anti-EMT agents has been promoted in clinic. Screening anti-EMT drugs and evaluation of EMT process are highly dependent on EMT biomarkers on cell membrane. At present, the detection of EMT biomarker is mainly by Western blot method, which is time-consuming and complicated. In this work, for effectively screening anti-EMT drugs by evaluation of the EMT process, a type of aptamer probe based on aggregation-induced emission (AIE) was designed. The aptamer SYL3C was employed to target the EMT biomarker EpCAM on cell membrane. Two fluorophores, FAM and tetraphenylethene (TPE, an AIE dye), were modified at the two ends of SYL3C, respectively. This aptamer probe (TPE-SYL3C-FAM) can monitor the EpCAM expression, which can be recovered by anti-EMT drugs. By observation of the change in TPE emission intensity, the anti-EMT effect of drugs can be evaluated. The FAM emission was used as internal reference to reduce environmental interferences. This probe can be potentially used to screen anti-EMT agents as anti-cancer adjuvant drugs with high throughput.

Cholinesterase inhibitor plays an important role in the treatment of patients with Alzheimer’s disease (AD). Herein, we report the medicinal chemistry efforts leading to a new series of 1,3-dimethylbenzimidazolinone derivatives. Among the synthesised compounds, 15b and 15j showed submicromolar IC50 values (15b, eeAChE IC50 = 0.39 ± 0.11 µM; 15j, eqBChE IC50 = 0.16 ± 0.04 µM) towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Kinetic and molecular modelling studies revealed that 15b and 15j act in a competitive manner. 15b and 15j showed neuroprotective effect against H2O2-induced oxidative damage on PC12 cells. This effect was further supported by their antioxidant activity determined in a DPPH assay in vitro. Morris water maze test confirmed the memory amelioration effect of the two compounds in a scopolamine-induced mouse model. Moreover, the hepatotoxicity of 15b and 15j was lower than tacrine. In summary, these data suggest 15b and 15j are promising multifunctional agents against AD.

Shale reservoirs are promising geological sites for CO2 storage due to their high total organic content (TOC) and the large-scale hydraulic fracturing operations. In order to critically evaluate a potential storage reservoir, fast, robust tools are needed to assess the CO2 storage capacity. Based on our previous work, an efficient method based on semi-analytical solution for calculating the maximum CO2 storage capacity in shale formations is derived, based on the injection wellbore pressure. The new methodology fully reflects the flow, diffusion, and adsorption processes of CO2 in shales. It also simulates natural fractures, hydraulic fractures, and the stimulated reservoir volume (SRV). The semi-analytical solution utilizing a Laplace transform and Stehfest numerical inversion is developed to evaluate the wellbore pressure and storage capacity in shale formations, which is verified using numerical simulations. A case study of the derived method on the Bakken Shale shows that the CO2 storage capacity is strongly controlled by the CO2 injection rate, adsorption index, and storage ratio. It is also found that the effective diffusion coefficient and mobility ratio affect the CO2 storage capacity during different periods of the CO2 storage process.

With the development and progress of carbon dioxide (CO2) capture and storage technology, the study of the flow assurance of CO2 in transmission pipelines needs to be further deepened. In this study, aiming at the gas‐phase transportation mode of CO2, first, a new prediction model of temperature, pressure as well as hydrate formation risk in buried CO2 transmission pipelines is established. Second, the model solving methods of differential discretization and piecewise iteration are introduced in detail. Third, model validation and sensitivity analysis of typical transmission parameters are performed. The results show that: (a) there is good agreement between the model prediction results and software simulation results. (b) The subcooling and the length of the hydrate formation region increase with the increase in the transmission rate. Appropriate increase in the CO2 transmission rate can reduce the risk of hydrate formation in CO2 transmission pipelines. (c) The subcooling and the length of the hydrate formation region decrease as the transmission temperature increases. In order to prevent hydrate risk in the CO2 transmission process, low transmission temperatures should be avoided. (d) The subcooling and the length of the hydrate‐formation area increase first and then decrease as the transmission pressure increases. Appropriate increase in CO2 transmission pressure is conducive to avoiding hydrate formation risk. This study provides basic theoretical guidance for optimizing transmission parameters and risk assessment of hydrate formation in CO2 transmission pipelines. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.

An induction voltage adder (IVA) has been developed to drive rod-pinch diodes (RPDs), to produce X-rays for flash radiography. The IVA facility consists of four-stage induction cavities stacked in series, each of which is single-point driven by a 6- $\Omega $ pulseline. The prime pulsed-power source comprises two Marx generators and four de-ionized water pulselines. Each Marx generator fast charges two pulselines to about 2.2 MV in less than 370 ns. Four electrically triggered, SF6-insulated gas switches serve as energy-transfer switches from pulse-forming lines to output transmission lines, and thus without an additional intermediate energy storage. A stepped inner stalk is utilized to make the vacuum impedance of the secondary transmission line increase from $30~\Omega $ at the first cavity to $120~\Omega $ at the last cavity, to prevent the electron emission from cathode surfaces. The RPD is chosen to create bremsstrahlung X-rays, which are believed to be optimal at voltage levels of about 4 MV. In this article, the design details and experimental results concerning the main components, such as the Marx/PFLs, IVA, and RPD, are demonstrated. The electrical performances of the facility are characterized. Presently, the IVA provides voltages of up to 4.3 MV and currents of up to 85 kA. The X-ray dose is up to 15.5 Rad [lithium fluoride (LiF)] at 1 m with a spot size of 1.4 mm and a FWHM time of 55 ns.

Herein, an operationally simple and mild strategy to construct sulfenation of oxindoles with a series of thiols in the absence of transition metals was developed. This methodology provides an effic...

Ferroptosis is an iron-dependent cell death caused by accumulation of lipid peroxidation (LPO), which is a new strategy for cancer treatment. Th current ferroptosis therapy nanodevices have low efficiency and side effects generally. Hence, we developed a Black Hole Quencher (BHQ)-based fluorescence "off-on" nanophotosensitizer complex assembly (CSO-BHQ-IR780-Hex/MIONPs/Sor). CSO-connected BHQ-IR780-Hex and -loaded magnetic iron oxide nanoparticles (MIONPs) and sorafenib (Sor) formed a very concise functionalized delivery system. CSO-BHQ-IR780-Hex disassembled by GSH attack and released IR780-Hex, MIONPs, and sorafenib. IR780-Hex anchored to the mitochondrial membrane, which would contribute to amplifying the efficiency of the photosensitizer. When NIR irradiation was given to CSO-BHQ-IR780-Hex/MIONPs/Sor-treated cells, iron supply increased, the xCT/GSH/GPX-4 system was triggered, and a lot of LPO burst. A malondialdehyde test showed that LPO in complex assembly-treated cells was explosive and increased about 18-fold compared to the control. The accumulation process of particles was monitored by an IR780-Hex photosensitizer, which showed an excellent tumor target ability by magnetic of nanodevice in vivo. Interestingly, the half-life of sorafenib in a nanodevice was increased about 26-fold compared to the control group. Importantly, the complex assembly effectively inhibits tumor growth in the breast tumor mouse model. This work would provide ideas in designing nanomedicines for the ferroptosis treatment of cancer.

Hydraulic fracturing is an important process to increase the productivity of wells. In shallow reservoirs, tectonically active reservoirs, and abnormally high-pressure reservoirs, fractures caused by hydraulic stimulation are likely to be in the horizontal direction. To date, the study of transient pressure behavior arising from horizontal fractures has been limited to that of a single horizontal fracture, without consideration of the interference from multiple fractures. In this work, we develop an analytical method to model, and analyze the transient pressure behaviors from multiple horizontal fractures. The results show that the flow regimes of multiple horizontal fractures can be divided into linear flow, transition flow, first pseudo radial flow, bi-radial flow, and second pseudo radial flow. Compared to the case of a single horizontal fracture, the first pseudo radial flow and bi-radial flow represent new flow regimes inherent in the multiple horizontal fracture system. Sensitivity analysis indicates that changes in horizontal fracture length affect the linear flow, transition flow, and first pseudo radial flow. In addition, the first pseudo radial flow and bi-radial flow are closely related to the fracture spacing and fracture number. The transition flow is dominated by the fracture's vertical position and formation thickness.