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STING is at the center of the cGAS-STING signaling and acts as the hub of the innate immune system. Hyper-activation of STING has been observed in various severe autoimmune diseases, such as AGS, SLE, and many other diseases including neurological and metabolic disorders. Therefore, STING has been considered as a promising target. In recent years, several STING inhibitors have been claimed in patents.Small-molecule STING inhibitors reported in patents (disclosed before May 2022 through the public database at https://worldwide.espacenet.com) were summarized in this review and the available structure-activity relationships (SARs) and molecular mechanisms of action were presented.Compared with STING agonists, the development of STING inhibitors is still in its infancy and no candidates have entered clinical investigation stage. Fortunately, patent applications are appearing at an increasing rate and a few of them have been validated

The raising of container seedlings with light substrates has become an important method of seedling raising, without delaying the seedling period. In order to reduce reliance on non-renewable peat and to promote the reuse of organic waste, this study compared the growth of sour jujube seedlings in different substrate formulations (i.e., different proportions of vermicompost instead of peat), using a semi-subterranean placement of root control bags, and explored the application of vermicompost in the raising of sour jujube seedlings. The results showed that there were significant differences in the growth and the physiological and photosynthetic characteristics of sour jujube seedlings treated with different substrates, among which substrates A2 (peat: vermicompost: vermiculite: garden soil = 0.5:0.5:1:1) and A3 (peat: vermiculite: garden soil = 1:2:1) were suitable for sour jujube seedling raising. The seedling height, the seedling ground diameter, the number of secondary branches, the length of the longest secondary branch, the total fresh weight, the aboveground fresh weight, the total root length, the root projection area, and the root surface area were all significantly greater than those of jujube seedlings grown on other substrates. Especially in A3, vermicompost can replace peat as the nursery substrate for sour jujube seedlings, removing dependence on non-renewable peat resources, reducing costs, and providing more prospects for application. The suitable substrate conditions for sour jujube seedlings were as follows: soil porosity 44.0–54.0%, electric conductivity (EC) value 0.2 mS/cm, organic matter 40.39~54.05 g·kg−1, total nitrogen and total phosphorus of 1.67~1.91 g·kg−1 and 0.95~1.20 g·kg−1, respectively, alkali-hydrolyzed nitrogen 139.75~154.69 mg·kg−1, and available phosphorus 137~224 mg·kg−1.

Due to the complicated influences of the car door system, the closing comfort is difficult to evaluate in the design of the car door system. In order to solve the problem and increase the development efficiency, based on the work of the whole process and the law of energy conservation, this paper models the power and resistance work under the closing conditions of the door system, and focuses on the construction of the work by door gravity, door limiter, sealing force of the seal, air resistance inside the seal and air resistance inside the vehicle in particular, and designs a computational model of the door closing comfort. The use of the model will effectively guide the development of door system parameterization.

Nonhuman primates are ideal animal models for studying intervertebral disc degeneration. Radiomics technology could be used to accurately evaluate intervertebral disc degeneration, which is the basis for disc-related studies. In the study of nonhuman primates, the number of precious animals is limited, which cannot meet the sample size requirements of radiomics for study subjects, while these radiomics models could be obtained more easily in humans. Therefore, it is possible to construct radiomics models based on human intervertebral disc data, and then apply the models to nonhuman primates. However, cross-species application of the radiomics models has not previously been well established in the literature. Here we show that a total of 12.30% (438/3562) of radiomics features are reproducible between humans and cynomolgus monkeys. Furthermore, the human dataset is used as the training set to construct radiomics models, and the cynomolgus monkey’s dataset is used as the testing set to verify the inter species universality of the radiomics models. We found that the radiomics models constructed using human datasets as training sets still has good performance in cynomolgus monkeys. This study provides a theoretical basis for the cross-species application of radiomics model.

Image style transfer has become a key technique in modern photo-editing applications. Although significant progress has been made to blend content from one image with style from another image, the synthesized image may have a hallucinatory effect when the texture from the style image is rich when processing high-resolution image style transfer tasks. In this paper, we propose a novel attention mechanism, named compositional attention, to design a compositional transformer-based autoencoder (CTA) to solve this above-mentioned issue. With the support from this module, our model is capable of generating high-quality images when transferring from texture-riched style images to content images with semantics. Additionally, we embed region-based consistency terms in our loss function for ensuring internal structure semantic preservation in our synthesized image. Moreover, information theory-based CTA is discussed and Kullback–Leibler divergence loss is introduced to preserve more brightness information for photo-realistic style transfer. Extensive experimental results based on three benchmark datasets, namely Churches, Flickr Landscapes, and Flickr Faces HQ, confirmed excellent performance when compared to several state-of-the-art methods. Based on a user study assessment, the majority number of users, ranging from 61% to 66%, gave high scores on the transfer effects of our method compared to 9% users who supported the second best method. Further, for the questions of realism and style transfer quality, we achieved the best score, i.e., an average of 4.5 out of 5 compared to other style transfer methods.

Crop nutrition measurement is of great significance in agricultural practice, especially in variable rate fertilization. The chlorophyll content, an important indicator of nitrogen nutrition in crops, largely depends on crop growth and development, photosynthesis, and crop yield, and plays an important role in the monitoring of crop growth. This paper tries to detect the chlorophyll content of wheat quickly, using the digital image processing technology. Specifically, a feature selection method was developed based on wrapper and light gradient boosting machine (LGBM), and combined with logistic regression (LR) to predict the chlorophyll content of wheat. The results show that: the optimal model is the combination between the 17 image evaluation indices screened by LGBM and the LR prediction model; the optimal results were coefficient of determination (R2) of 0.728, and root mean square error (RMSE) of 4.979. The optimal model can predict the chlorophyll content of wheat accurately based on digital images in field prototype.

Gene-edited pigs for agricultural and biomedical applications are typically generated using somatic cell nuclear transfer (SCNT). However, SCNT requires the use of monoclonal cells as donors, and the time-consuming and laborious monoclonal selection process limits the production of large populations of gene-edited animals. Here, we developed a rapid and efficient method named RE-DSRNP (reporter RNA enriched dual-sgRNA/CRISPR-Cas9 ribonucleoproteins) for generating gene-edited donor cells. RE-DSRNP takes advantage of the precise and efficient editing features of dual-sgRNA and the high editing efficiency, low off-target effects, transgene-free nature, and low cytotoxic characteristics of reporter RNA enriched RNPs (CRISPR-Cas9 ribonucleoproteins), thus eliminating the need for the selection of monoclonal cells and thereby greatly reducing the generation time of donor cells from 3–4 weeks to 1 week, while also reducing the extent of apoptosis and chromosomal aneuploidy of donor cells. We applied RE-DSRNP to produce cloned pigs bearing a deletion edit of the wild-type p53-induced phosphatase 1 (WIP1) gene: among 32 weaned cloned pigs, 31 (97%) carried WIP1 edits, and 15 (47%) were homozygous for the designed fragment deletion, and no off-target event was detected. The WIP1 knockout (KO) pigs exhibited male reproductive disorders, illustrating the utility of RE-DSRNP for rapidly generating precisely edited animals for functional genomics and disease research. RE-DSRNP’s strong editing performance in a large animal and its marked reduction in the required time for producing SCNT donor cells support its application prospects for rapidly generating populations of transgene-free cloned animals. Electronic Supplementary Material Supplementary material is available in the online version of this article at 10.1007/s11427-021-2058-2.

A simpler and user-friendly nucleic acid sensing platform with 10 aM sensitivity, named USPCRP (Combines the ultrashort PCR with Pyrococcus furiosus Argonaute cleavage for nuleic acids detection), among which the product of ultrashort PCR could be used as DNA guide directly to mediate PfAgo cleaving molecular beacons.

With the development of high-performance chips, the heat flux of Internet datacenter (IDC) is on the rise, and heat dissipation becomes a major bottleneck of IDC development. The cooling needs of the IDC room can hardly be met by the traditional method of air cooling. In recent years, immersion liquid cooling has attracted a growing attention, due to its excellent performance. This paper designs and optimizes an immersion liquid cooling system for IDC. Multiple numerical simulations were carried out to analyze the influence of the system parameters on heat dissipation, and improve the system efficiency using a dielectric coolant. Specifically, 20 graphics processing units (GPUs) and 2 central processing units (CPUs) were set up in each machine of the liquid cooling server. Then, the GPU and CPU temperature was examined under different opening positions on the server top plate, inlet coolant temperatures, and coolant flow speeds. The results show that a 30mm-wide, 430mm-long opening should be set at the upper part of the GPU array, 20mm away from the top plate. The cooling effect can be optimized at the inlet temperature of 30℃, and the coolant flow speed of 3m3/h.

It is widely considered that lithium metal is the most ideal anode for the next-generation rechargeable batteries with high energy and power density. The growth of lithium dendrite and low coulombic efficiency, however, result in a sluggish pace for the real application of lithium metal anode. Here, the lithiophilic coating, like the metal oxide-based composite membrane, can be readily reacted with lithium ions to form multi-phase interface, leading to a uniform fast pathway for lithium ion transport. Through the metal oxide-based composite membrane, the Li dendrite can be suppressed effectively and the excellent cycling stability of the Li anode can be achieved. The life of Li–Li symmetric cells can be improved significantly from less than 240 h to more than 3200 h (0.5 mA cm−2, 1 mAh cm−2), and the Li-Cu cells can maintain a coulombic efficiency of 98.7% after 250 cycles. The composite membrane can also improve the electrochemical performance of the Li/NCM cells. Finally, the mechanism of dendrite suppression by the composite membrane is also discussed in detail.

The X-ray irradiation of gold salt aqueous solutions in the synthesis of gold nanoparticles (AuNPs) in the absence of any reducing agent or stabilizer is presented. The size, dispersion, number of particles, yield and morphology evolution during the radiolytic formation of AuNPs were followed simultaneously using in situ small-angle X-ray scattering. This study provides an insight into the overall kinetics and formation mechanisms at the initial stage of AuNP synthesis without reductants and stabilizers. The pH-dependent speciation of aqueous HAuCl4 and its influence on the synthesis, structure and properties of AuNPs were observed. The result sheds light on the key parameters required to obtain stable monomodal particles and the influence of the surface charge and reactivity of the chemical solution on the final particle size and shape.

Background SEPALLATA3 (SEP3), which is conserved across various plant species, plays essential and various roles in flower and fruit development. However, the regulatory network of the role of SEP3 in flowering time at the molecular level remained unclear. Results Here, we investigated that SEP3 in Ziziphus jujuba Mill. (ZjSEP3) was expressed in four floral organs and exhibited strong transcriptional activation activity. ZjSEP3 transgenic Arabidopsis showed an early-flowering phenotype and altered the expression of some genes related to flowering. Among them, the expression of LATE ELONGATED HYPOCOTYL (AtLHY), the key gene of circadian rhythms, was significantly suppressed. Yeast one-hybrid (Y1H) and electrophoretic mobility shift assays (EMSAs) further verified that ZjSEP3 inhibited the transcription of AtLHY by binding to the CArG-boxes in its promoter. Moreover, ZjSEP3 also could bind to the ZjLHY promoter and the conserved binding regions of ZjSEP3 were found in the LHY promoter of various plant species. The ectopic regulatory pathway of ZjSEP3-AtLHY was further supported by the ability of 35S::AtLHY to rescue the early-flowering phenotype in ZjSEP3 transgenic plants. In ZjSEP3 transgenic plants, total chlorophyll content and the expression of genes involved in chlorophyll synthesis increased during vegetative stages, which should contribute to its early flowering and relate to the regulatory of AtLHY. Conclusion Overall, ZjSEP3-AtLHY pathway represents a novel regulatory mechanism that is involved in the regulation of flowering time.

In order to study the bearing performance of the new prefabricated airport pavement panel (PAPP) structure, a three-dimensional finite element model (3D-FEM) of “square PAPP – stratum” was established based on ABAQUS finite element analysis platform, and then the mechanical and deformation performance analysis under single wheel various limit load positions was carried out. The research showed that the influence radius was less than the side length R of the panel, The maximum opening or minimum compression of the joint under single wheel conditions was very small, and the maximum principal stress value of the precast concrete panel was an important key control factor for the ultimate load-bearing capacity. Under the action of vertical load, the tenon and groove joint connects multiple independent prefabricated panels to form a whole through mutual occlusal action. The research work provided a useful reference for the design and construction of PAPP.

Background Inonotus obliquus, a famous dark brown white-rot fungus on birch trees, has remarkable anti-cancer activity due to its special triterpenpoid components. The aims of this study were to develop an efficient and integrated strategy for preparative separation of triterpenoids from Inonotus obliquus and to provide ideas for the preparation of bioactive ingredients in other complex materials. Methods In the present study, an integrated technology of negative pressure cavitation extraction (NPCE) and high-speed counter-current chromatography (HSCCC) separation of four main triterpenoids in Inonotus obliquus was developed for the first time. Response surface methodology was used to optimize the negative pressure cavitation extraction parameters of triterpenoids from Inonotus obliquus. For the rapid and effective preparative separation of triterpenoids, the HSCCC method with Hex-ACN (1:1; v/v) system was established. Significant Findings The extraction yield of total triterpenoids reached 17.41 mg/g under the optimal NPCE extraction conditions. The specific four triterpenoids including 3β-hydroxy-lanosta-8, 24-diene-21-al (0.84 mg/g), Inoterpene F (1.09 mg/g), Inotodiol (2.93 mg/g), Lanosterol (1.42 mg/g) were obtained by one step separation with the purities of more than 95%. This is the first report on the preparative separation of triterpenoids from Inonotus obliquus by NPCE-HSCCC.

In the present study, surveys of case numbers, constituent ratios, conventional biotyping, and multilocus sequence typing (MLST) were applied to characterize the incidence rate and epidemiological characteristics of human brucellosis in Shaanxi Province, China. A total of 12,215 human brucellosis cases were reported during 2008–2020, for an annual average incidence rate of 2.48/100,000. The most significant change was that the county numbers of reported cases increased from 36 in 2008 to 84 in 2020, with a geographic expansion trend from northern Shaanxi to Guanzhong, and southern Shaanxi regions; the incidence rate declined in previous epidemic northern Shaanxi regions while increasing each year in Guanzhong and southern Shaanxi regions such as Hancheng and Xianyang. The increased incidence was closely related to the development of large-scale small ruminants (goats and sheep) farms in Guanzhong and some southern Shaanxi regions. Another significant feature was that student cases (n = 261) were ranked second among all occupations, accounting for 2.14% of the total number of cases, with the majority due to drinking unsterilized goat milk. Three Brucella species were detected (B. melitensis (bv. 1, 2, 3 and variant), B. abortus bv. 3/6, and B. suis bv. 1) and were mainly distributed in the northern Shaanxi and Guanzhong regions. Three known STs (ST8, ST2, and ST14) were identified based on MLST analysis. The characteristics that had not changed were that B. melitensis strains belonging to the ST8 population were the dominant species and were observed in all nine regions during the examined periods. Strengthened human and animal brucellosis surveillance and restriction of the transfer of infected sheep (goats) as well as students avoiding drinking raw milk are suggested as optimal control strategies.

COL1A1 encodes the type I collagen α1 chain, which shows the highest abundance among members of the collagen family and is widely expressed in different mammalian cells and tissues. However, its molecular characteristics are not completely elucidated. In this study, the molecular profiles of COL1A1 and characteristics of the COL1A1 protein were investigated using a promoter activity assay and multiple bioinformatics tools. The results showed that the 5′ flanking region of porcine COL1A1 contained two CpG islands, five core promoter sequences, and twenty-six transcription factor-binding sites. In the luciferase assay, the upstream 294 bp region of the initiation codon of COL1A1 showed the highest activity, confirming that this section is the core region of the porcine COL1A1 promoter. Bioinformatic analysis revealed that COL1A1 is a negatively charged, hydrophilic secreted protein. It does not contain a transmembrane domain and is highly conserved in humans, mice, sheep, and pigs. Protein interaction analysis demonstrated that the interaction coefficient of COL1A1 with COL1A2, COL3A1, ITGB1, and ITGA2 was greater than 0.9, suggesting that this protein plays a crucial role in collagen structure formation and cell adhesion. These results provide a theoretical basis for further investigation of the functions of porcine COL1A1.

A glancing incident X-ray fluorescence (GIXRF) spectrometry using a single-bounce parabolic capillary (SBPC) was proposed for the analysis of layered samples. The divergence of the X‐ray beam was 0.33 mrad. In this paper, we used this instrumental setup to analyze Si single crystal and a 50 nm HfO2 single layer film deposited on a Si substrate.

High quality quasi-parallel x-ray microbeams have an appreciable application value in the x-ray diffraction analysis technique, which is currently one of the most significant non-destructive analysis techniques. A simulation of a parabolic single capillary is carried out based on the Monte Carlo simulation toolkit Geant4. The simulation results show that it is feasible to obtain high quality quasi-parallel x-ray microbeams based on a parabolic capillary and a traditional laboratorial x-ray source. We manufacture a parabolic capillary based on the simulation results. The physical parameters of the obtained x-ray beams are characterized by building an x-ray imaging system. The experimental results show that the x-ray beam with submicrometer size and almost zero divergence can be obtained from the traditional laboratorial x-ray source by utilizing a parabolic single capillary as a collimator.