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Abstract Background Huashi Baidu Formula (HBF) is a clinical formula known for its efficacy against coronavirus disease 2019 (COVID-19). HBF may reduce the number of patients with abnormal serum creatinine while improving respiratory symptoms, suggesting that this formula may have potential for treating acute kidney injury (AKI). However, the protective effect of HBF on AKI has not been definitively confirmed, and the mechanism remains unclear. Therefore, the present study explored the renoprotective effects and molecular mechanisms of HBF and screened for its active ingredients to identify new potential applications of renoprotection by HBF. Methods The present study first assessed the protective effects of HBF on AKI in a DOX-induced mouse model. Then, RNA-seq and bioinformatics analyses were used to explore the related pathological processes and potential molecular mechanisms, which were subsequently validated using qRT-PCR and Western blotting. Furthermore, candidate compounds with potential binding affinity to two pivotal targets, sphingosine kinase 1 (SphK1) and plasminogen activator inhibitor-1 (PAI-1), were screened from the 29 constituents present in the blood using Microscale Thermophoresis (MST). Finally, to identify the active ingredients, the candidate components were re-screened using the SphK1 kinase activity detection system or the uPA/PAI-1 substrate colorimetric assay system. Results In the DOX-induced AKI mouse model, therapeutic administration of HBF significantly reduced the levels of CRE, BUN, TNF-α, IL-1β, IL-6, and UA in plasma and the levels of MDA, T-CHO, and TG in kidney tissue. Additionally, the levels of TP and Alb in plasma and SOD and CAT in the kidney tissue were significantly increased. Histopathological assessment revealed that HBF reduced tubular vacuolation, renal interstitial inflammatory cell infiltration, tubular atrophy, and positive staining of renal interstitial collagen. RNA-seq and bioinformatics analyses showed that oxidative stress, the immune-inflammatory response, and extracellular matrix (ECM) formation could be the pathological processes that HBF targets to exerts its renoprotective effects. Furthermore, HBF regulated the APJ/SPHK1/NF-κB and APJ/PAI-1/TGFβ signaling axes and reduced the phosphorylation levels of NF-κB p65 and SMAD2 and the expression of cytokines and the ECM downstream of the axis. Finally, six SphK1 inhibitors (paeoniflorin, astragalin, emodin, glycyrrhisoflavone, quercetin, and liquiritigenin) and three PAI-1 inhibitors (glycyrrhisoflavone, licochalcone B, and isoliquiritigenin) were identified as potentially active ingredients in HBF. Conclusion In brief, our investigation underscores the renoprotective effect of HBF in a DOX-induced AKI model mice, elucidating its mechanisms through distinct pathological processes and identifying key bioactive compounds. These findings offer new insights for broadening the clinical applications of HBF and unravelling its molecular mode of action.

Abstract Purpose Respiratory movement, as one of the main challenges in proton therapy for pancreatic cancer patients, could not only lead to harm to normal tissues but also lead to failure of the tumor control, resulting in irreversible consequences. Including respiratory movements into the plan optimization, i.e. 4D robust optimization, may mitigate the interplay effect. However, 4D robust optimization considering images of all breathing phases is time-consuming and less efficient. This work aims to investigate the effect of the breathing phase number on the 4D robust optimization for pancreatic cancer intensity modulated proton therapy (IMPT) by examining plan quality and computational efficiency. Methods A total of 15 pancreatic cancer patients were retrospectively analyzed. In this study, both anterior-fields and posterior-fields plans were created for each patient. For each plan, six four-dimensional (4D) robust treatment planning strategies with different numbers of respiratory phases and one three-dimensional (3D) treatment plan were created. Optimization of the plans were performed on all ten phases (10phase plan), two extreme phases (2phase plan), two extreme phases plus an intermediate state (3phase plan), two extreme phases plus the 3D CT (3Aphase plan), six phases during the exhalation stage (6Exphase plan), six phases during the inhalation stage (6Inphase plan) and 3D Computed Tomography (CT) scan image (3D plan), respectively. 4D dynamic dose (4DDD) was then calculated to access the interplay effect by considering respiratory motion and dynamic beam delivery. Plan quality and dosimetric parameters for the target and organs at risk (OARs) were then analyzed. Results Compared to the 4D plans, 3D plan performed terribly in terms of target coverage and organs at risk. Target dose in anterior-fields plan varied slightly among all six 4D treatment planning strategies. Both the 6Exphase and 6Inphase plans demonstrated performance that was comparable to the 10phase plan in target coverage, outperforming the other five plans for anterior-fields plan. It’s basically the same for the posterior-fields plan. The six strategies showed similar OARs sparing effect for both anterior-fields and posterior-fields plan. Compared with the 10phase plan, the average decline rates of the optimization time of the six plans of 2phase, 3phase, 3Aphase, 6Exphase, 6Inphase, and 3D were 73.26 ± 6.54% vs. 74.48 ± 6.63%, 65.80 ± 7.89% vs. 65.81 ± 9.58%, 54.67 ± 11.52% vs. 65.75 ± 9.58%, 42.14 ± 13.57% vs. 39.63 ± 16.93%, 37.72 ± 11.70% vs. 40.79 ± 13.62% and 75.52 ± 8.21% vs. 80.67 ± 5.62%, respectively (anterior vs. posterior). With the decrease of the number of phases selected for optimization, the decline rates increased, while the other dosimetry parameters generally showed a deterioration trend. Conclusion In this study, a comprehensive evaluation of six 4D robust treatment planning strategies and one 3D treatment planning strategy for pancreatic cancer patients receiving IMPT was performed. The results showed that six 4D robust optimization strategies were comparable in common posterior field therapy. 2phase and 3phase (including 3Aphase) treatment planning strategies could replace the 10phase treatment planning strategy. It should be noted that patients with large motion amplitudes should receive special attention. The dosimetric performance of the 6Exphase and 6Inphase plans closely aligned with that of the 10phase plan in anterior fields. These plans offered a feasible alternative to 10phase treatment planning strategy by reducing optimization time while maintaining dose coverage of the target and protection of OARs. This research provides guidelines to reduce optimization time and improve clinical efficiency for pancreatic cancer IMPT.

Abstract Background Cotton is an important economic crop and a host of Liriomyza sativae. Pectin methylesterase (PME)-mediated pectin metabolism plays an indispensable role in multiple biological processes in planta. However, the pleiotropic functions of PME often lead to unpredictable effects on crop resistance to pests. Additionally, whether and how PME affects susceptibility to Liriomyza sativae remain unclear. Results Here, we isolated GhPME36, which is located in the cell wall, from upland cotton (Gossypium hirsutum L.). Interestingly, the overexpression of GhPME36 in cotton caused severe susceptibility to Liriomyza sativae but increased leaf biomass in Arabidopsis. Cytological observations revealed that the cell wall was thinner with more demethylesterified pectins in GhPME36-OE cotton leaves than in WT leaves, whereas the soluble sugar content of GhPME36-OE cotton leaf cell walls was accordingly higher; both factors attracted Liriomyza sativae to feed on GhPME36-OE cotton leaves. Metabolomic analysis demonstrated that glucose was significantly differentially accumulated. Transcriptomic analysis further revealed DEGs enriched in glucose metabolic pathways when GhPME36 was overexpressed, suggesting that GhPME36 aggravates susceptibility to Liriomyza sativae by affecting both the structure and components of cell wall biosynthesis. Moreover, GhPME36 interacts with another pectin-modifying enzyme, GhC/VIF1, to maintain the dynamic stability of pectin methyl esterification. Conclusions Taken together, our results reveal the cytological and molecular mechanisms by which GhPME36 aggravates susceptibility to Liriomyza sativae. This study broadens the knowledge of PME function and provides new insights into plant resistance to pests and the safety of genetically modified plants.

Abstract Background Acute gouty arthritis (AGA) is classified as ‘arthritis’ in traditional Chinese medicine (TCM) theory. Shirebi granules (SGs), derived from the classic prescription SiMiaoWan, exerts satisfying therapeutic efficacy in ameliorating AGA clinically. However, the underlying mechanisms of SGs against AGA remain unclarified. Methods AGA-related biological processes, signal pathways and biomarker genes were mined from the GEO database through bioinformatics. SGs components were systematically recognized using the UPLC-Q-TOF–MS/MS. A correlation network was established based on the biomarker genes and the chemical components, from which the signal pathway used for further study was selected. Finally, we established an AGA model using SD rats injected with monosodium urate (MSU) in the ankle joint for experimental validation. A combination of behavioral tests, H&E, safranin O- fast green, western blotting, and immunofluorescence were employed to reveal the mechanism of action of SGs on AGA. Results The deterioration of AGA was significantly related to the imbalance between immunity and inflammation, neutrophil chemotaxis and inflammatory factor activation. HDAC5, PRKCB, NFκB1, MPO, PRKCA, PIK3CA were identified to be the candidate targets of SGs against AGA, associated with neutrophil extracellular traps (NETs) signal pathway. Animal experiments demonstrated that SGs effectively repaired cartilage damage, blocked TLR4 activation, and inhibited the expression of NETs indicators and inflammatory factors. In addition, SGs prominently alleviated joint redness and swelling, improved joint dysfunction, inhibited inflammatory infiltration of AGA rats. Conclusion Our data reveal that SGs may effectively alleviate the disease severity of AGA by suppressing NETs-promoted imbalance between immunity and inflammation.

Abstract Background Histone ubiquitination modification is emerging as a critical epigenetic mechanism involved in a range of biological processes. In vitro reconstitution of ubiquitinated nucleosomes is pivotal for elucidating the influence of histone ubiquitination on chromatin dynamics. Results In this study, we introduce a Non-Denatured Histone Octamer Ubiquitylation (NDHOU) approach for generating ubiquitin or ubiquitin-like modified histone octamers. The method entails the co-expression and purification of histone octamers, followed by their chemical cross-linking to ubiquitin using 1,3-dibromoacetone. We demonstrate that nucleosomes reconstituted with these octamers display a high degree of homogeneity, rendering them highly compatible with in vitro biochemical assays. These ubiquitinated nucleosomes mimic physiological substrates in function and structure. Additionally, we have extended this method to cross-linking various histone octamers and three types of ubiquitin-like proteins. Conclusions Overall, our findings offer an efficient strategy for producing ubiquitinated nucleosomes, advancing biochemical and biophysical studies in the field of chromatin biology.

Exploring the relationships between habitat fragmentation on ecosystem services (ESs) is important for ecological conservation and spatial pattern optimisation. However, analyzing the influence of different habitat fragmentation processes on ESs and their trade-offs from a multiple perspective is still relatively lacking. Therefore, taking Southwest (SW) China as an example, this paper evaluated the dynamics and trade-off relationship of four main types of ESs (i.e., carbon storage (CS), grain production (GP), water retention (WR), soil retention (SR)) during 2000–2020, and analyzed the effects of four habitat fragmentation processes (i.e., decreasing habitat area, increasing habitat density, increasing habitat shape complexity and decreasing habitat cohesion) on ESs and their trade-offs by using geographically and temporally weighted regression model. The results showed that ESs showed a deterioration trend during 2000–2020, with GP, WR, CS, SR, and total ecosystem services (TES) declined by 66.45 %, 54.33 %, 41.68 %, 76.25 % and 65.83 %, respectively. The GP-SR, GP-CS and GP-WR pairs exhibited trade-offs, while other ES types pairs exhibited synergies with each other. Increasing habitat density and increasing in habitat shape complexity were the two strongest fragmentation processes influencing ESs and their trade-offs. The effects of various habitat fragmentation processes on ESs and their trade-offs have obvious spatial heterogeneity. With changes in terrain relief, proportion of karst area, habitat quality, and urbanization level, the association of habitat fragmentation-ESs and habitat fragmentation-ESs trade-offs existed different sensitivities. The results can provide effective guidance for landscape planning and ecosystem management in the SW.

The yield strength of metallic materials is commonly estimated using linear superposition methods, but this method has limited adaptability to new materials. The mapping relationship between input and output in machine learning methods is difficult to quantify. This study employs a rapid screening method to identify the key strengthening mechanisms that influence the yield strength of typical homogeneous and heterogeneous metallic materials. A non-linear physical neural information network model is developed to describe the yield strength of heterogeneous structures, capturing the main parameters contributing to yield strength from selected physical quantity data. By considering the non-linear strengthening mechanisms arising from interactions among multiple strengthening mechanisms in heterogeneous metal structures, the microstructure and mechanical properties of eutectic high-entropy alloys are optimized through warm rolling and short-time annealing. By inducing microstructural spheroidization and introducing nanoscale precipitates, significant coupling effects of multiple strengthening mechanisms are achieved for eutectic high-entropy alloys. As a result, the yield strength increases by approximately 2.5 times, while plasticity remains nearly unchanged. Transmission electron microscopy, scanning electron microscopy, and electron backscatter diffraction observations provide evidence for the sources of these coupling effects. This study offers guidance for accelerating material design and exploring the physical relationship between microstructure and mechanical properties.

Abstract The existing physical layer security schemes, which are based on the key generation model and the wire-tap channel model, achieve security by utilizing channel reciprocity entropy and noise entropy, respectively. In contrast, we propose a novel secure transmission framework that combines noise entropy with reciprocity entropy, achieved by inserting reciprocity entropy into the frozen bits of polar codes. Note that in real-world scenarios, when eavesdroppers employ polynomial-time attacks, the bit error rate (BER) increases due to the introduction of computational entropy. To achieve indistinguishability security, we convert the practical physical layer security metric, BER, into the average min-entropy, a widely accepted concept in cryptography. The simulation results demonstrate that the eavesdropper’s BER can be significantly increased without compromising the communication performance of the legitimate receiver. Under concrete parameters we selected, when compared to the joint scheme of physical layer key generation and one time pad, the modular semantically-secure scheme based on the wire-tap channel model, and the simple channel entropy combination scheme, our scheme achieves a message rate approximately 1.2 times, 3.8 times, and 1.4 times better, respectively. Experimental testing validates the feasibility of our scheme.

Abstract Background Intestinal barrier is a dynamic interface between the body and the ingested food components, however, dietary components or xenobiotics could compromise intestinal integrity, causing health risks to the host. Gossypol, a toxic component in cottonseed meal (CSM), caused intestinal injury in fish or other monogastric animals. It has been demonstrated that probiotics administration benefits the intestinal barrier integrity, but the efficacy of probiotics in maintaining intestinal health when the host is exposed to gossypol remains unclear. Here, a strain (YC) affiliated to Pediococcus pentosaceus was isolated from the gut of Nile tilapia (Oreochromis niloticus) and its potential to repair gossypol-induced intestinal damage was evaluated. Results A total of 270 Nile tilapia (2.20 ± 0.02 g) were allotted in 3 groups with 3 tanks each and fed with 3 diets including CON (control diet), GOS (control diet containing 300 mg/kg gossypol) and GP (control diet containing 300 mg/kg gossypol and 108 colony-forming unit (CFU)/g P. pentosaceus YC), respectively. After 10 weeks, addition of P. pentosaceus YC restored growth retardation and intestinal injury induced by gossypol in Nile tilapia. Transcriptome analysis and siRNA interference experiments demonstrated that NOD-like receptors (NLR) family caspase recruitment domain (CARD) domain containing 3 (Nlrc3) inhibition might promote intestinal stem cell (ISC) proliferation, as well as maintaining gut barrier integrity. 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) revealed that addition of P. pentosaceus YC altered the composition of gut microbiota and increased the content of propionate in fish gut. In vitro studies on propionate’s function demonstrated that it suppressed nlrc3 expression and promoted wound healing in Caco-2 cell model. Conclusions The present study reveals that P. pentosaceus YC has the capacity to ameliorate intestinal barrier injury by modulating gut microbiota composition and elevating propionate level. This finding offers a promising strategy for the feed industry to incorporate cottonseed meal into fish feed formulations. Graphical Abstract

Lightweight lattice structures can have their mechanical properties and failure modes predicted through computer simulation. This approach has great potential for use in aerospace, the automotive industry, and defense equipment. However, due to the limitations of the LPBF process, fabricated lattice structures contain internal defects that affect the compression response, which leads to high-level errors in finite element method (FEM) predictions and experimental results. Thus, in this paper, a finite element model considering the effect of pore defects was built by using finite element simulation in connection with the Gurson-Tvergaard-Needleman (GTN) damage model to investigate the compressive behavior and mechanical response of the body-centered cubic lattice structure of AlSi10Mg alloys prepared by the LPBF process. A three-dimensional reconstruction of the molded BCC lattice structure was performed by computed tomography (CT) to obtain the structure's distribution and shape of micropores. Using a combination of simulation (FEM-GTN) and experimentation, the effects of process parameters on the compressive properties and mechanical behavior of the BCC lattice structure during quasi-static compression were investigated. The results show that the FEM simulation results corrected by the GTN damage model are in better accordance with the experimental results (the error rate is reduced by more than 10 %) compared to the FEM simulation results without considering the influence of the pore defects, which proves the higher accuracy of the FEM-GTN simulation model. This work provides a reference for the property prediction and fabrication of high-performance, lightweight lattice structures.

Southwest China is one of the most concentrated regions of wild kiwifruit germplasm. With the increased instances of extreme weather and the impact of human activities, the wild kiwifruit population is being destroyed. However, there is little research on the wild kiwifruit resources. Therefore, strengthening research on wild resources of kiwifruit and determining the genetic diversity of kiwifruit are essential. In this study, 110 wild kiwifruit germplasms were collected as test materials. We selected 13 primers out of 256 pairs to analyze the genetic diversity. A total of 178 loci were amplified, including 175 polymorphic loci, accounting for 98.31%. The genetic similarity coefficient ranged from 0.551 to 0.905, with an average of 0.721. The effective allele number (Ne), Nei’s gene diversity index (H) and Shannon’s information index (I) were 1.452, 0.245 and 0.439, respectively. Very low genetic differentiation (Gst: 0.051) and very high gene flow (Nm: 11.899) were observed. When the genetic similarity coefficient was 0.652, the kiwifruit germplasms were divided into four categories, and the geographical distribution of samples in different categories was inconsistent. The result of principal coordinate analysis (PCoA) and structure analysis showed that the population of wild kiwifruit was divided into two subgroups. Our research contributed to identifying the genetic background of wild kiwifruits in Guizhou Province, China, and can be an important reference for the protection of wild kiwifruit and the breeding of new kiwifruit varieties.

Land-use changes dominated by high-intensity human activities have seriously threatened regional ecosystem health (EH) and will continue to increase in the future, especially in mountainous cities. Therefore, there is a need to systematically assess the contribution and spatial effects of future land use conversion on EH from a multi-scenario simulation perspective, which is essential for ecological conservation and management. For this purpose, taking Chongqing as an example, this study assessed the static distribution and dynamic evolution of EH over historical periods (2000–2020) and future multi-scenarios in 2030 using the vigor-organization-resilience-ecosystem services balance (VORSB) framework and patch-level land use simulation (PLUS) model, then analyzed the influence of land use conversion on EH and identified sensitive areas under multiple scenarios based on the contribution index and ecological sensitivity index. The results showed that Chongqing ecosystems were generally at a moderate healthy level during 2000–2020, with an increasing trend in EH level, with high-EH located in the eastern mountainous areas, while low-EH clustered in the western urban core and its peripheral areas. From 2020 to 2030, the EH level was improved by about 0.21% under the ecological protection scenario due to the transformation from farmland to forestland, which has the largest positive contribution of 0.111. In contrast, the EH level under the natural development and economic development scenarios declined by 1.95% and 3.07%, especially in the metropolitan developed circle, which was significantly related to the occupation of farmland resources by urban land, with negative contribution of −0.103 and −0.189, respectively. In the future, these regions should strictly control the urban expansion scale and strengthen high-quality farmland protection to achieve the balance of ecological protection and economic development. The findings will provide scientific guidance for the regional ecosystem conservation, land use planning, and urban sustainable development of mountainous cities.

Environmental managers have sought to optimize landscape structure to maintain regional ecosystem health (EH). However, we still lack a full understanding of the effects of changing landscape structure on EH, especially in terms of shorter time scales (e.g., monthly or seasonal scales) and spatial heterogeneity. To address this gap, this study used the vigor-organization-resilience-services (VORS) model to assess the annual and seasonal variation of EH in the Loess Plateau (LP) during 2000–2015, and then applied the geographically weighted regression (GWR) model to investigate the spatial effects of different aspects (i.e., landscape composition and configuration) of the landscape structure change on EH over time. Our results showed that the EH level in the LP from 2000 to 2015 displayed temporal non-stationarity at annual and seasonal scales, and a spatial pattern of decreasing from southeast to northwest. The effects of landscape structure on EH had obvious spatial and temporal heterogeneity, depending on the local landscape composition and configuration. In general, landscape configuration exerted a greater impact on EH than landscape composition apart from Shannon’s diversity index and percentage of forestland area, but the intensity and direction of the impact displayed higher temporally instability and therefore should receive more attention. Furthermore, regulation of the dominant patch size, landscape connectivity and forest spatial spacing is the optimal choice for regional ecosystem management. The results suggest that EH responses to changes in landscape structure in the LP vary by time and place, and that the integrating temporal variation and spatial characteristics can help decision-makers make precise spatial arrangements and temporal adjustments to keep the negative ecological impacts within reasonable limits.

Building a human-like dialogue system is a challenging task that requires effective use of context, common sense and personal information. In a conversation, the responder usually analyzes the emotion, intention, and common sense involved in the speaker’s sentence. Based on this analysis, the responder considers both the above-mentioned content and their personal information to formulate a response. Previous work in this area has only focused on one or some aspects, such as emotion, intention, common sense or persona, rather than considering all of them together. To address this issue, we propose a response generation framework called EFCP, which is based on empathy factors, common sense, and persona. This framework simulates a rich dialogue generation process that is rarely seen in previous work. In predicting the type of empathy factors a responder should adopt, we consider both the responder’s personal information and the conversation history. Our experiments show that this method effectively improves the accuracy of prediction. EFCP outperforms the baseline on a variety of automatic metrics and manual metrics, showing its potential for building more effective and human-like dialogue systems.

In recent years, hate speech spread on the Internet has seriously affected society’s harmony, stability, and development. A way to quickly identify hate speech from the vast amount of data on the Internet is urgent. In this paper, different from previous traditional methods, we explore a novel scenario of constructing a syntax dependency graph for each instance based on the syntactical information retrieved from an external tool. We propose a model called the Dependency Graph Convolutional and Sentiment Knowledge Transfer (DGCSKT) network. DGCSKT utilizes syntactic dependency graphs and dependency graph convolutional operations to enhance the model’s ability to perceive contextual information. Additionally, we introduce sentiment resources that are data-homogeneous as an auxiliary task at the bottom level of the model to share effective sentiment features and improve recognition performance. Then, we propose the Dynamic Normalized Weighting (DNW) method to weight the training information of different tasks and thus improve the model’s generalization ability. Compared to the current state-of-the-art methods, our proposed approach improves the Macro-F1 by 3.88% and 0.54% in OLID and HateEval respectively.

Abstract Background Exercise is postulated to be a promising non-pharmacological intervention for the improvement of neurodegenerative disease pathology. However, the mechanism of beneficial effects of exercise on the brain remains to be further explored. In this study, we investigated the effect of an exercise-induced metabolite, lactate, on the microglia phenotype and its association with learning and memory. Results Microglia were hyperactivated in the brains of AlCl3/D-gal-treated mice, which was associated with cognitive decline. Running exercise ameliorated the hyperactivation and increased the anti-inflammatory/reparative phenotype of microglia and improved cognition. Mice were injected intraperitoneally with sodium lactate (NaLA) had similar beneficial effects as that of exercise training. Exogenous NaLA addition to cultured BV2 cells promoted their transition from a pro-inflammatory to a reparative phenotype. Conclusion The elevated lactate acted as an “accelerator” of the endogenous “lactate timer” in microglia promoting this transition of microglia polarization balance through lactylation. These findings demonstrate that exercise-induced lactate accelerates the phenotypic transition of microglia, which plays a key role in reducing neuroinflammation and improving cognitive function.

The seismic response detection and operational safety assessment of high-speed railway (HSR) bridges play a crucial role in ensuring HSR systems’ operational safety and reliability. Smartphones have introduced intelligent inspection tools for structural health detection, becoming a new tool for intelligent structural inspection. Combining the public and smartphones is the key to public participation in structural health detection. This study utilizes smartphone-based structural seismic response inspection technology to investigate the framework of public participation in earthquake response inspection and assessment. This system comprises the Smart Bridge Brain (SBB), which integrates data from multiple sources and systems, an assigning mechanism for public participation inspection tasks, and smartphone-based HSR bridge structural seismic response inspection technology. At the same time, the Unreal Engine 5.0 software is used to create a mixed-reality virtual simulation experimental environment to validate the feasibility of this framework. The results indicate that the intelligent optimization of task allocation by the SBB successfully assigns detection tasks to each public participant. Public participants can promptly reach predefined damage structure detection targets and rapidly inspect bridge structural seismic response indicators using smartphones. In addition, this paper also conducts a comprehensive evaluation and analysis of the detection of the work efficiency index (WEI) within the system. Furthermore, optimization strategies for the efficient execution of detection tasks are proposed based on WEI variations influenced by different factors. The system framework is expected to enhance cluster-based HSR bridges’ intelligent disaster prevention and mitigation capabilities.

In order to investigate the relationship between the invasion of the exotic plant Solidago canadensis and diversity of native plants in Nanjing, the species composition and diversity of its community were studied by using the tracking and quadrat methods. The results were as follows: (1) A total of 200 vascular plant species, including varieties and subspecies classification, were found in the invaded communities, belong to 156 genera and 62 families, including 195 angiosperms, one gymnosperm, and four ferns. The species-richest families were Asteraceae and Poaceae, with 25 and 24 species respectively. In terms of their life forms, herbaceous plants accounted for the majority, with 133 species (66.50%). In addition, there were 29 other alien plant species in these communities. The most dominant species in the community was Solidago canadensis, with a high ecological important value of 40.00%, followed by Vicia sativa (7.00%). (2) There were four floristic types of flora families in uninvaded communities, and only three types in invaded communities. Pantropic type, cosmopolitan type and north temperate type existed in both communities, while East Asia and North America disjunct type only in uninvaded communities. In the uninvaded communities, the floristic types were mainly cosmopolitan, with 13 families, accounting for 39.39% of all families. Pantropic was the dominant species in the invaded communities, with 16 families, accounting for 45.71% of the total. There were 10 floristic types of flora genera in uninvaded habitats and 12 in invaded habitats, with similar floristic composition, but the old-world temperate type and tropical Asia to tropical Australasia type only appeared in invaded communities. The north temperate and cosmopolitan type were the most important components of both invaded and uninvaded communities. The R/T values of invaded and uninvaded communities of genera were 0.58 and 0.38, and the species differentiation were 3.29 and 3.11, respectively. (3) The Margalef index (E) of heavily invaded communities was significantly lower than that of uninvaded and lightly invaded communities. In addition, the Simpson index (D), Shannon Weiner index (H′), and Pielou index(J) of heavily invaded communities were significantly reduced compared to uninvaded, lightly invaded, and moderately invaded communities. (4) There were no significant differences in E, D, H′, and J in different habitats. This study can provide basic data for the management, prevention and control, and ecological restoration of the invaded areas of S. canadensis in Nanjing, as well as further scientific research.

New complex-shaped and thin-walled carbon/carbon (C/C) composites have become the main hot structural material for new hypersonic vehicles because of their superior properties. In the preparation of complex-shaped and thin-walled C/C composites by chemical vapor infiltration (CVI) method, problems such as slow density growth and inhomogeneity of density distribution have been hindering the development of C/C hot structure, in order to solve which, this paper proposes a design method for domain-limited CVI reactors for complex-shaped and thin-walled C/C structure, as well as conducts CVI experiments with the designed domain-limited reactor for a L-shaped and thin-walled C/C structure. A coupled multi-physical field model considering flow, diffusion, and chemical reactions was established, which was verified by comparison with experiments. The effects of diameter of hole, distance of neighboring holes, depth of hole and length of reactor on deposition quality were analyzed by simulation. The results showed that larger diameter of hole and smaller distance of neighboring holes would be more favorable for the accumulation of density of structure and depth of hole has little effect on deposition. The best solution is diameter of hole with 18 mm and distance of neighboring holes with 20 mm. Homogeneity of density can be improved by adjusting the specific length of the reactor. For the fabric sizes given in the study, when the specific length of the preform is 3.4, the deposition rate and homogeneity can reach a good level at the same time. This study is a guideline for optimization the quality of C/C structure during processing.

The high-resolution spacecraft poses an urgent need for opto-mechanical structure with ultra-high stability and light-weight. Owing to the advantages of both carbon fiber-reinforced carbon-based composites (C/C composites) and honeycomb sandwich structure, a novel C/C honeycomb sandwich structure strategy is proposed in this study. It was fabricated by using weaving fabrics and Chemical Vapor Infiltration (CVI) process, then was tested under out-of-plane compression. Taking the weave structure of honeycomb wall, anisotropy characteristics and damage mechanism of C/C composites, as well as the parameters of core size, a multi-scale damage model is established and validated to investigate mechanical behavior of the novel structure. The effects of influence factors (side length, thickness and height of core) on mechanical properties and damage mode of the novel sandwich structure are investigated. The results demonstrate that the optimal honeycomb core sizes for improving the light-weight and high load-bearing integration performance are l = 5 mm–7.5 mm and t = 0.3 mm–0.4 mm. The matrix damage occurs in the middle region of core, while fiber damage occurs at the end of core when its height reaches 15 mm. This study is helpful for design and optimization for opto-mechanical structure of high-resolution spacecraft.

Objective To analyze differences of eplets between the patient who generated HLA allele-specific antibodies after platelet transfusion with donors. Methods The HLA genotypes of the patient and donors were detected by PCR-SBT, and the Luminex single antigen beads coating was used to screen HLA-Ⅰ antibodies in the patient’s serum. HLA Matchmaker was utilized to analyze different amino acids and eplets. Results The patient carried HLA-A*02∶03 allele, and HLA-A2 antibodies were found in his serum after platelet transfusion (A*02∶01, A*02∶06, and A*02∶07). Sequence alignment showed that the patient′s A*02∶03 has a difference in position 149, which resulted in a different eplet between A*02∶03 and A*02∶01, A*02∶06, A*02∶07 and then induced the production of antibodies. Conclusion HLA antibodies are specific for HLA epitopes that have structural differences due to amino acid differences between HLA alleles, suggesting that high-resolution typing of HLA-A, -B need to be conducted in patients and donors, and the acceptable mismatch of HLA should be determined based on epitopes rather than antigens, so as to reduce alloimmune response and improve platelet count after transfusion.

In order to overcome the poor dispersion of traditional inorganic zinc-rich coating, addressing the sedimentation and the agglomeration caused by high zinc powder content and improve the anti-corrosion performance of coatings. In this paper, the molybdate intercalated hydrotalcite flake zinc layer double hydroxide (ZnAl–NO3-/LDH) was synthesized by hydrothermal synthesis method at first, and the KH560 modified the Mo/LDH flake zinc powder was further obtained by ion exchange method. The results show that the samples have a layered structure of hydrotalcite with good crystal structure through X-ray diffraction (XRD) and Fourier transform infrared (FT-IR), and the molybdate corrosion inhibiting ions inserted successfully into the interlayer structure of hydrotalcite. Meanwhile, different contents of pigments and fillers were added into the inorganic zinc-rich coatings. It was found that the Nyquist radius of curvature and modulus value of the coating were the largest with a pigment and filler content of 40 %, the maximum corrosion potential was −0.017V, and the minimum corrosion current density was 3.377 × 10−7 A-cm−2. The result indicates that the coating has the best corrosion resistance with 40 % pigment content, which has good application prospects in the fields of cross-sea bridges, natural gas and oil pipelines et al.

Abstract Background Cold-dampness Syndrome (RA-Cold) and Hot-dampness Syndrome (RA-Hot) are two distinct groups of rheumatoid arthritis (RA) patients with different clinical symptoms based on traditional Chinese medicine (TCM) theories and clinical empirical knowledge. However, the biological basis of the two syndromes has not been fully elucidated, which may restrict the development of personalized medicine and drug discovery for RA diagnosis and therapy. Methods An integrative strategy combining clinical transcriptomics, phenomics, and metabolomics data based on clinical cohorts and adjuvant-induced arthritis rat models was performed to identify novel candidate biomarkers and to investigate the biological basis of RA-Cold and RA-Hot. Results The main clinical symptoms of RA-Cold patients are joint swelling, pain, and contracture, which may be associated with the dysregulation of T cell-mediated immunity, osteoblast differentiation, and subsequent disorders of steroid biosynthesis and phenylalanine metabolism. In contrast, the main clinical symptoms of RA-Hot patients are fever, irritability, and vertigo, which may be associated with various signals regulating angiogenesis, adrenocorticotropic hormone release, and NLRP3 inflammasome activation, leading to disorders of steroid biosynthesis, nicotinamide, and sphingolipid metabolism. IL17F, 5-HT, and IL4I1 were identified as candidate biomarkers of RA-Cold, while S1P and GLNS were identified as candidate biomarkers of RA-Hot. Conclusions The current study presents the most comprehensive metabonomic and transcriptomic profiling of serum, urine, synovial fluid, and synovial tissue samples obtained from RA-Cold and RA-Hot patients and experimental animal models to date. Through the integration of multi-omics data and clinical independent validation, a list of novel candidate biomarkers of RA-Cold and RA-Hot syndromes were identified, that may be useful in improving RA diagnosis and therapy.

[Objective] The spatiotemporal interactive coupling characteristics between mountainous urbanization and ecosystem health, and the complex relationship between ecosystem health and urbanization were studied to provide a scientific basis for the scientific management and sustainable development of urban areas in the region. [Methods] The spatial and temporal evolution characteristics of urbanization and ecosystem health subsystems were analyzed for Chongqing City (a mountainous city) from 2000 to 2020 using the entropy value method and the vigor-organizational-resilience-service (V-O-R-S) model to determine the mechanism of the interactive coupling relationship between urbanization and ecosystem health subsystems. [Results] ① The comprehensive urbanization level in Chongqing City from 2000 to 2020 increased year by year. However, there was still a problem of uneven spatial development, and both the core zone and the low-value area were significantly affected by topographic relief. ② The ecosystem health index from 2000 to 2020 was moderate. The ecosystem health of the regions with rapid urbanization deteriorated significantly, while the ecosystem health of Southeast Chongqing and Northeast Chongqing with higher vegetation cover was good. [Conclusion] The interactive coupling between urbanization and ecosystem health subsystems was on the rise, but has not yet reached a highly coordinated stage, and contradictions still exist. To achieve high-quality and sustainable development in Chongqing City, it will still be necessary to take the green development path and solve the problem of spatial and temporal inequality.

Five-generation communication, foldable cell phone, and wearable devices promote the development of Cu foils by applying multi-layer printed circuit board (MLPCB) and flexible printed circuit board (FPCB). However, few research focused on the combined influence of processing, defects (dislocation, stacking faults, and grain boundaries), and textures modification and its effects on applied performance evolution in the electronic circuit board of ultra-thin Cu foil. In this paper, 12 μm Cu foils were fabricated by the rolling process at reduction deformations of 93.3% and 95.2%. The low-temperature annealing process was utilized to simulate the application of printed circuit boards. The results show that the dislocation density is significantly decreased after annealing, but the influence of reduction deformation has no changes and the dislocation density of the samples with large deformation increased by 40%. In addition to defects, grain orientation has a significant influence on copper foil properties. With the increase of brass and S textures, the tensile strength increased 28.5%. Moreover, the high index of grain plane of S, R, and {025} improves the corrosion resistance by about 130.7%. This work has great significance for preparing high-performance Cu foil applied in PCB.

In today’s fast-paced and ever-changing environment, the need for algorithms with enhanced global optimization capability has become increasingly crucial due to the emergence of a wide range of optimization problems. To tackle this issue, we present a new algorithm called Random Particle Swarm Optimization (RPSO) based on cosine similarity. RPSO is evaluated using both the IEEE Congress on Evolutionary Computation (CEC) 2022 test dataset and Convolutional Neural Network (CNN) classification experiments. The RPSO algorithm builds upon the traditional PSO algorithm by incorporating several key enhancements. Firstly, the parameter selection is adapted and a mechanism called Random Contrastive Interaction (RCI) is introduced. This mechanism fosters information exchange among particles, thereby improving the ability of the algorithm to explore the search space more effectively. Secondly, quadratic interpolation (QI) is incorporated to boost the local search efficiency of the algorithm. RPSO utilizes cosine similarity for the selection of both QI and RCI, dynamically updating population information to steer the algorithm towards optimal solutions. In the evaluation using the CEC 2022 test dataset, RPSO is compared with recent variations of Particle Swarm Optimization (PSO) and top algorithms in the CEC community. The results highlight the strong competitiveness and advantages of RPSO, validating its effectiveness in tackling global optimization tasks. Additionally, in the classification experiments with optimizing CNNs for medical images, RPSO demonstrated stability and accuracy comparable to other algorithms and variants. This further confirms the value and utility of RPSO in improving the performance of CNN classification tasks.

Summary: Tianhe Zhuifeng Gao (TZG) shows a satisfying therapeutic efficacy in treating arthromyodynia, which shares similar etiology to myofascial pain syndrome (MPS). We herein aim to explore whether TZG could be a potential prescription for MPS therapy. An MPS rat model was successfully established presenting with reduced pain thresholds, abnormal local switch responses, etc., which was effectively reversed by TZG treatment externally. A transcriptome sequencing based on the active MTrPs samples of rats, combined with network analysis revealed that TZG might ameliorate the progression of MPS by impairing neutrophil extracellular traps (NETs) release through inhibiting PI3K-RAC2 signaling to reduce NADPH oxidase-originated ROS. Experimentally, the expression levels of inducers, biomarkers of NETs formation and vessel injury, and p-PI3K, p-P47, and RAC2 proteins were all significantly up-regulated in affected tissues, which were markedly reversed by TZG. Our results not only shed light into broadening the clinical indications of TZG, but benefit MPS therapy.

Abstract Compound Danshen Dripping Pills (CDDPs) have been used in clinical treatment to protect the heart from ischemia/reperfusion (IR) injury for many years. However, the underlying mechanism implicated in the protective effects remains to be explored. Here, we determined the effects of CDDPs in Sprague-Dawley rats with the IR model. Cardiac function in vivo was assessed by echocardiography. Transmission electron microscopy, histological and immunohistochemical techniques, Western blotting and recombinant adeno-associated virus 9 transfection were used to illustrate the effects of CDDPs on IR and autophagy. Our results showed that pretreatment with CDDPs decreased the level of serum myocardial enzymes and infarct size in rats after IR. Apoptosis evaluation showed that CDDPs significantly ameliorated the cardiac apoptosis level after IR. Meanwhile, CDDPs pretreatment increased myocardial autophagic flux, with upregulation of LC3B, downregulation of p62, and increased autophagosomes and autolysosomes. Moreover, the autophagic flux inhibitor chloroquine could increase IR injury, while CDDPs could partially reverse the effects. Furthermore, our results showed that the activation of AMPK/mTOR was involved in the cardioprotective effect exerted by CDDPs. Herein, we suggest that CDDPs partially protect the heart from IR injury by enhancing autophagic flux through the activation of AMPK/mTOR.

Vehicle recognition is a fundamentale problem in synthetic aperture radar (SAR) image interpretation. However, robustly recognizing vehicle targets is a challenging task in SAR due to the large intraclass variations and small interclass variations. In addition, the lack of large datasets further complicates the task. Inspired by the analysis of target signature variations and deep learning explainability, this article proposes a novel domain alignment framework, named the hierarchical disentanglement-alignment network (HDANet), to achieve robustness under various operating conditions. Concisely, HDANet integrates feature disentanglement and alignment into a unified framework with three modules: domain data generation; multitask-assisted mask disentanglement; and the domain alignment of target features. The first module generates diverse data for alignment, and three simple but effective data augmentation methods are designed to simulate target signature variations. The second module disentangles the target features from background clutter using the multitask-assisted mask to prevent clutter from interfering with subsequent alignment. The third module employs a contrastive loss for domain alignment to extract robust target features from generated diverse data and disentangled features. Finally, the proposed method demonstrates impressive robustness across nine operating conditions in the MSTAR dataset, and extensive qualitative and quantitative analyses validate the effectiveness of our framework.

Abstract Background Baihu-Guizhi decoction (BHGZD) is a well-documented traditional Chinese Medicine (TCM) prescription that has been extensively applied to treating rheumatoid arthritis. Despite of its beneficial outcomes, the chemical constituents of BHGZD have not been fully portrayed and the in vivo absorption, distribution, metabolism, and excretion (ADME) patterns of absorbed components have never been described. Methods Characterization of absorbed components and in vivo biotransformation profiling of these feature compounds were based on the ultra-fast liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS). Furthermore, the ultra-high-performance liquid chromatography tandem ion trap quadrupole mass spectrometry (UHPLC-Q-TRAP-MS/MS) system were performed to investigate the pharmacokinetics of active ingredients from BHGZD. Results In this study, we have identified and tentatively characterized 18 feature absorbed prototype and 15 metabolites of BHGZD in rat serum and the in vivo transformation pathways of these absorbed constituents were proposed. Besides, we have established novel quantitative methodology of five crucial components of BHGZD and have monitored the pharmacokinetic behaviors of these constituents spontaneously in rat serum after BHGZD gavage. After rats received two ways of BHGZD gavage, the pharmacokinetic behaviors of each compound exhibited relatively similar behaviors, as evidenced by similar curve track as well as relatively close time to reach maximum concentration (Tmax) and half washout time (T1/2). Whereas the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) values of five analytes with multiple dosage were a bit higher than single dosage. Conclusion This study added knowledge into the material basis and bio-transformation patterns of BHGZD in vivo, which would be of great value for exploring pharmacological effects and mechanism of BHGZD.

As a polycrystalline polymer, isotactic polybutene-1 (iPB-1) will form different crystalline structures when it crystallizes under different conditions. In this work, we found a simple method to manipulate the cell structure of iPB-1 foams by controlling the annealing time of crystalline form II at room temperature and employing supercritical CO2 foaming. As the content of crystalline form II increases, the storage modulus (G′) and complex viscosity (|η * |) increase, and the solubility of CO2 in iPB-1 increases. Crystalline form II has a wider foaming temperature window compared to crystalline form I and exhibits a more uniform cell structure at temperatures between 95 °C and 125 °C. The average cell diameters of crystalline form II and I are 33.9 µm and 11.2 µm at 115 °C and 15 MPa CO2, respectively. A small amount of crystalline form I acts as a heterogeneous nucleation agent during the foaming process, resulting in the formation of a “petal-like” cell structure. During the foaming saturation process, the melted portion of iPB-1 with unstable crystalline form II transforms into crystalline form I′ under high-pressure CO2, while the unmelted portion transforms into crystalline form I. As the pressure increases, the cell structure of iPB-1 undergoes a transition from “petal-like” to bimodal cell structure, ultimately achieving a more uniform structure. Moreover, increasing foaming pressure can also change the cell structure of the foamed material from closed-cell to open-cell. The occurrence of bimodal melting peaks in the foamed samples is beneficial for the adhesion of beads during the molding process.

Abstract Objective Kawasaki disease (KD) can lead to permanent damage to coronary structures, the pathogenesis of which remains unknown. This experiment was designed to investigate whether miR‐223‐3p secreted in the serum of KD patients affects the proliferation and apoptosis of HCAECs in KD by regulating FOXP3. Methods Blood samples were collected in acute febrile phase of KD, after IVIG treatment, and from healthy controls. Transfected into HCAECs cells by synthetic FOXP3 siRNA/NC. A co‐culture system was established between HCAECs cells transfected with FOXP3 siRNA/NC and THP1 cells added with three sera. Results Compared with the control group, the expressions of miR‐223‐3p, RORγt, and Th17 in serum of KD patients were significantly upregulated, and the expressions of TGF‐β1, FOXP3 and Treg were significantly downregulated. At the same time, the levels of IL‐6, IL‐17, and IL‐23 were significantly increased, and the levels of IL‐10 and FOXP3 were significantly decreased. After IVIG treatment, the patient's above results were reversed. The serum of KD patients increased the expression of miR‐223‐3p and inhibited the expression of FOXP3 in HCAECs cells. IVIG serum is the opposite. Overexpression of miR‐223‐3p also promoted the apoptosis of HCAECs. In addition, serum from KD patients promoted apoptosis, whereas serum after IVIG treatment inhibited apoptosis. KD patient serum downregulated the expression of FOXP3, Bcl2, TGF‐β1 and IL‐10 in cells, and upregulated the expression of caspase3, Bax, IL‐17, IL‐6, and IL‐23. The opposite results were obtained with IVIG‐treated sera. Conclusion miR‐223‐3p secreted in serum of KD patients can regulate the expression of FOXP3 and affect the proliferation, apoptosis, and inflammation of cells.

The occurrence and propagation of resistance genes due to exposure to heavy metals (HMs) in rivers is an emerging environmental issue. Little is known about resistance genes in microbial communities in river sediments with low HM concentrations. The profiles and spatial distributions of HMs, the microbial community, and metal resistance genes (MRGs) were analyzed in sediment samples from the Zhilong River basin in Yangjiang city, near the Pearl River Delta. Concentrations of copper (Cu), cadmium (Cd), lead (Pb), chromium (Cr), and nickel (Ni) were relatively low compared with those in other urban river sediments in China. HM chemical composition and fractions and the structure of the microbial community varied along the main channel, but the composition and abundance of MRGs were relatively homogeneous. Variations in HMs and microbial communities in mid- to upstream areas were related to the presence of tributaries, whose inputs were one of the major factors affecting HM chemical fractions and genera structure in mainstream sediments. There were no significant correlations (p < 0.05) between HM concentrations, bacterial communities, and the MRG profiles; thus, HM concentrations were not the main factor affecting MRGs in sediments. These results contribute to understanding the propagation of MRGs in urban rivers in developing cities.

Comprehending invasive alien species’ potential habitat area and spread trend are of great importance for effective prevention and control strategy and prevention of spread. However, previous studies have mainly been based on large regional scales (national or global level). Research on the smaller regional scale of ecologically fragile karst makes the prevention and control measures more feasible and targeted, it is of great significance to protect mountainous region species diversity and maintain national nature reserves. In this study, based on the distribution point data of Solidago canadensis in Guizhou Province and environmental factors, Pearson correlation analysis and contribution rate analysis of environmental factors were carried out by SPSS and knife cutting method, and current and future potential distribution vector maps were obtained by MaxEnt model, and then imported into ArcGIS for reclassification and visualization. The results show that, (1) the main drivers of S canadensis distribution were precipitation changes and human activities, the total contribution rate more than 70%; (2) S canadensis occurrence probability initially increased, and then decreased with increased precipitation variables, and increased rapidly initially, then gradually with increasing human footprint; (3) under current climate conditions, S canadensis suitable area is 8.13 × 10 ^4 km ^2 , with the highly suitable area concentrated in Guiyang, east of Bijie, Zunyi, Anshun and Qiannan. Under climate conditions of the 2050s, the suitable area drops slightly to 8.00 × 10 ^4 km ^2 , mainly in the west and north of Zunyi, Anshun and other areas reduced. Under climate conditions of the 2070s, the suitable area expands to 8.31 × 10 ^4 km ^2 , it expands in the adjacent areas of Anshun, Qiannan and Qianxinan and the junction of Zunyi, Tongren, Qiannan and Qiandongnan. And move toward the south within the study area; (4) finally, using the spatial optimization software ZONATION, according to the landscape loss proportion curve, the key monitoring area of 79,857 km ^2 was obtained, including a primary monitoring area mainly distributed in Guiyang, east of Bijie, northeast of Anshun and northwest of Qiannan, a secondary monitoring area mainly outside the primary monitoring area, and a third-level monitoring area widely distributed in Zunyi, Tongren, Qiannan, west of Qiandongnan and Anshun and east of Bijie. Linking our results with this specie’s invasive power, we thus recommended to increase the prevention and control sites in the first-level monitoring area, and continue to pay attention to the risk of the southward spread of this species.

Abstract Chemokine receptors are a family of G-protein-coupled receptors with key roles in leukocyte migration and inflammatory responses. Here, we present cryo-electron microscopy structures of two human CC chemokine receptor–G-protein complexes: CCR2 bound to its endogenous ligand CCL2, and CCR3 in the apo state. The structure of the CCL2–CCR2–G-protein complex reveals that CCL2 inserts deeply into the extracellular half of the transmembrane domain, and forms substantial interactions with the receptor through the most N-terminal glutamine. Extensive hydrophobic and polar interactions are present between both two chemokine receptors and the Gα-protein, contributing to the constitutive activity of these receptors. Notably, complemented with functional experiments, the interactions around intracellular loop 2 of the receptors are found to be conserved and play a more critical role in G-protein activation than those around intracellular loop 3. Together, our findings provide structural insights into chemokine recognition and receptor activation, shedding lights on drug design targeting chemokine receptors.

The integration of photothermal therapy (PTT) with gene therapy (GT) in a single nanoscale platform demonstrates great potential in cancer therapy. Porous iron oxide nanoagents (PIONs) are widely used as magnetic nanoagents in the drug delivery field and also serve as a photothermal nanoagent for photothermal therapy. However, the therapeutic efficacy of PIONs-mediated GT has not been studied. The long noncoding RNA (lncRNA) CRYBG3 (LNC CRYBG3), a lncRNA induced by heavy ion irradiation in lung cancer cells, has been reported to directly bind to globular actin (G-actin) and cause degradation of cytoskeleton and blocking of cytokinesis, thus indicating its potential for use in GT by simulating the effect of heavy ion irradiation and functioning as an antitumor drug. In the present study, we investigated the possibility of combining PIONs-mediated PTT and LNC CRYBG3-mediated GT to destroy non-small cell lung cancer (NSCLC) cells both in vitro and in vivo. The combination therapy showed a high cancer cell killing efficacy, and the cure rate was better than that achieved using PTT or GT alone. Moreover, as a type of magnetic nanoagent, PIONs can be used for magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) both in vitro and in vivo. These findings indicate that the new combination therapy has high potential for cancer treatment.

Aerospace vehicle connection constructions are in urgent need of joint structures with excellent aerodynamic profiles and environmental adaptability. To address issues such as poor aerodynamic profile, material thermal expansion coefficient mismatch, and limited joint structure evaluation indexes, a multi-bolt, countersunk C/SiC composite joint structure is presented in this study. The development of a 3D Hashin progressive damage model and its dedicated solver code is presented. The validity of the model is confirmed by comparing simulation results with experimental data. Three evaluation indexes are proposed, peak load, weight increment efficiency, and bolt load distribution, to thoroughly evaluate the mechanical performance of multi-bolt, countersunk C/SiC composite joint structures. Using the proposed model and evaluation indices, we evaluate sixteen different designs of multi-bolt, countersunk C/SiC composite joint structures and analyze how design parameters affect their mechanical properties and damage patterns. The results show that the best mechanical properties of the joint structure are achieved when the ratio of bolt pitch to through hole diameter is 3, the ratio of bolt spacing between columns to through hole diameter is 4, the ratio of the distance between the free edge of the substrate to through hole diameter is 1.5, the ratio of through hole diameter to specimen thickness is 1.7, and the ratio of the distance between the edge of the substrate to through hole diameter is 1.5.

Strain measurements have a significant role in evaluating the condition of various structural types and have become an essential component in the area of structural health monitoring. However, there are some limitations in the current means of strain measurement, and this study aims to improve these methods. We have designed a novel strain measurement method based on template matching algorithms and microscopic vision techniques, developed a new sliding strain sensor, and paired it with a new microscope to realize strain measurement. The method has the function of remote wireless acquisition with a cell phone, which is more widely applicable. In the laboratory performance testing, the zero drift of the sensor is mainly concentrated in the fluctuation range of ±2 με, and the effective range reaches nearly 40,000 με. In the comparison experiments with the linear variable differential transformer, the maximum error of the static loading is only 5 με, and the maximum error rate of the dynamic loading is less than 1%, which proves that it has a relatively high accuracy. Finally, the short-term real-time monitoring of the local structure of the footbridge was accomplished, and the strain changes on the surface of the structure were captured instantly, stably, and efficiently in the actual measurements. The proposed strain measurement system has the advantages of high accuracy, a low cost, convenient measurement, and wide applicability, and it provides a novel alternative means for strain measurement in the field of structural health monitoring.

This study proposes a detuned resonant capacitor selection strategy to eliminate the influence of the changed coupling coefficient on the transferred power and efficiency of a wireless power transfer (WPT) system using the LCC-S resonant topology. The output characteristics of the conventional tuned LCC-S system and the novel detuned system are analyzed and compared in detail, the different effects of the detuned parameters on the system output performance are expounded by simulations, and an optimal detuned parameter design process is presented. By adjusting the compensated capacitors on the transmitting side, the output voltage can be constant under varying coupling conditions without changing the switching frequency. Experiments with a 1.5kW power scale were conducted to verify the proposed theoretical analysis. The results show that the fluctuation of the output voltage is restricted to 8.2% in the optimized system when the coupling coefficient changes from 0.18 to 0.38. Under the rated coupling conditions, the experimental results demonstrate that compared with ZPA (88.29%) and ZVS (90.66%), ZCS (91.52%) operating conditions are more suitable for a WPT system equipped with IGBTs to improve the overall efficiency.

Human induced pluripotent stem cells (hiPSCs) possess tremendous potential for tissue regeneration and banking hiPSCs by cryopreservation for their ready availability is crucial to their widespread use. However, contemporary methods for hiPSC cryopreservation are associated with both limited cell survival and high concentration of toxic cryoprotectants and/or serum. The latter may cause spontaneous differentiation and/or introduce xenogeneic factors, which may compromise the quality of hiPSCs. Here, sand from nature is discovered to be capable of seeding ice above −10 °C, which enables cryopreservation of hiPSCs with no serum, much-reduced cryoprotectant, and high cell survival. Furthermore, the cryopreserved hiPSCs retain high pluripotency and functions judged by their pluripotency marker expression, cell cycle analysis, and capability of differentiation into the three germ layers. This unique sand-mediated cryopreservation method may greatly facilitate the convenient and ready availability of high-quality hiPSCs and probably many other types of cells/tissues for the emerging cell-based translational medicine.

Abstract Background The high misdiagnosis rate of asymptomatic neurosyphilis (ANS) has long challenged infectious disease clinicians. We aim to develop a model for diagnosing ANS in asymptomatic syphilis (AS) patients without CSF indicators. Results 277 AS patients with HIV-negative and underwent lumbar puncture were enrolled in this horizontal study.The area under the curve for predicting ANS by CSF leukocytes and protein was 0.643 and 0.675 [95% CI, 0.583–0.699VS.0.616–0.729]. Through LRM, the AUC increased to 0.806 [95% CI, 0.732–0.832], and the Youden's index was 0.430. If the score is ≤ 0.159, ANS can be excluded with a predictive value of 92.9%; we can identify ANS while the score is over 0.819, with a predictive value of 91.7% and a specificity of 99.25%. This study showed that the LRM can diagnose ANS in AS patients effectively. Conclusion Given a large number of misdiagnosis ANS patients and CSF results' insufficiency, the model is more practical. Our research will help clinicians track suspected syphilis, especially those who cannot accept the CSF test.

The flourishing of the Internet of Things (IoT) in recent years creates a huge demand for various humidity sensors, since the humidity is closely related to our daily life. Transparent humidity sensors have great application prospects in the fields such as smart furniture and human-machine interface. However, it is difficult for devices made from traditional moisture sensitive materials to have both high optical transparency and sensitive humidity response. Herein, we developed a novel humidity sensor based on 2D MoO3-x nanosheets, in which the nanosheets were liquid-phase exfoliated from α-MoO3 powder. With the assistance of ethyl cellulose, a high concentration dispersion of oxygen-deficient MoO3-x nanosheets can be easily prepared by probe sonicating. The as-prepared humidity sensor shows a transmittance as high as 86% in visible range. Under a constant bias, the current of the sensor increases monotonically over a broad RH range from 11% to 95%. Moreover, the fast response and recovery speed in the subsecond timescale (0.12 s and 0.53 s) enables the transparent humidity sensor to work as a real-time device in the expiration monitoring system. This work demonstrates a promising application of 2D MoO3-x nanosheets and opens up a new avenue for designing transparent humidity sensors.

The oral mucosal vaccine has great potential in preventing a series of diseases caused by porcine circovirus type 2 (PCV2) infection. This study constructed a recombinant Bacillus subtilis RB with PCV2 Capsid protein (Cap) on its spore surface and cotB as a fusion partner. The immune properties of the recombinant strain were evaluated in a mouse model. IgA in intestinal contents and IgG in serum were detected by enzyme-linked immunosorbent assay (ELISA). The results demonstrated that recombinant spores could activate strong specific mucosal and humoral immune responses. In addition, spores showed good mucosal immune adjuvant function, promoting the proliferation of CD3+, CD4+ and CD8+ T cells and other immune cells. We also found that the relative expression of inflammatory cytokines such as IL-1β, IL-6, IL-10, TNF-α and IFN in the small intestinal mucosa was significantly up-regulated under the stimulation of recombinant bacteriophage. These effects are important for the balance of Th1/Th2-like responses. In summary, our results suggest that recombinant B. subtilis RB as a feed additive provides a new strategy for the development of novel and safe PCV2 mucosal subunit vaccines.

Existing pavement defect detection models face challenges in balancing detection accuracy and speed while being constrained by large parameter sizes, hindering deployment on edge terminal devices with limited computing resources. To address these issues, this paper proposes a lightweight pavement defect detection model based on an improved YOLOv7 architecture. The model introduces four key enhancements: first, the incorporation of the SPPCSPC_Group grouped space pyramid pooling module to reduce the parameter load and computational complexity; second, the utilization of the K-means clustering algorithm for generating anchors, accelerating model convergence; third, the integration of the Ghost Conv module, enhancing feature extraction while minimizing the parameters and calculations; fourth, introduction of the CBAM convolution module to enrich the semantic information in the last layer of the backbone network. The experimental results demonstrate that the improved model achieved an average accuracy of 91%, and the accuracy in detecting broken plates and repaired models increased by 9% and 8%, respectively, compared to the original model. Moreover, the improved model exhibited reductions of 14.4% and 29.3% in the calculations and parameters, respectively, and a 29.1% decrease in the model size, resulting in an impressive 80 FPS (frames per second). The enhanced YOLOv7 successfully balances parameter reduction and computation while maintaining high accuracy, making it a more suitable choice for pavement defect detection compared with other algorithms.

Abstract Crohn’s disease (CD) is an intestinal immune-dysfunctional disease. Extracellular vesicles (EVs) are membrane-enclosed particles full of functional molecules, e.g., nuclear acids. Recently, EVs have been shown to participate in the development of CD by realizing intercellular communication among intestinal cells. However, the role of EVs carrying double-strand DNA (dsDNA) shed from sites of intestinal inflammation in CD has not been investigated. Here we isolated EVs from the plasma or colon lavage of murine colitis and CD patients. The level of exosomal dsDNA, including mtDNA and nDNA, significantly increased in murine colitis and active human CD, and was positively correlated with the disease activity. Moreover, the activation of the STING pathway was verified in CD. EVs from the plasma of active human CD triggered STING activation in macrophages in vitro. EVs from LPS-damaged colon epithelial cells were also shown to raise inflammation in macrophages via activating the STING pathway, but the effect disappeared after the removal of exosomal dsDNA. These findings were further confirmed in STING-deficient mice and macrophages. STING deficiency significantly ameliorated colitis. Besides, potential therapeutic effects of GW4869, an inhibitor of EVs release were assessed. The application of GW4869 successfully ameliorated murine colitis by inhibiting STING activation. In conclusion, exosomal dsDNA was found to promote intestinal inflammation via activating the STING pathway in macrophages and act as a potential mechanistic biomarker and therapeutic target of CD.

BackgroundAlthough studies have shown that cell pyroptosis is involved in the progression of asthma, a systematic analysis of the clinical significance of pyroptosis-related genes (PRGs) cooperating with immune cells in asthma patients is still lacking.MethodsTranscriptome sequencing datasets from patients with different disease courses were used to screen pyroptosis-related differentially expressed genes and perform biological function analysis. Clustering based on K-means unsupervised clustering method is performed to identify pyroptosis-related subtypes in asthma and explore biological functional characteristics of poorly controlled subtypes. Diagnostic markers between subtypes were screened and validated using an asthma mouse model. The infiltration of immune cells in airway epithelium was evaluated based on CIBERSORT, and the correlation between diagnostic markers and immune cells was analyzed. Finally, a risk prediction model was established and experimentally verified using differentially expressed genes between pyroptosis subtypes in combination with asthma control. The cMAP database and molecular docking were utilized to predict potential therapeutic drugs.ResultsNineteen differentially expressed PRGs and two subtypes were identified between patients with mild-to-moderate and severe asthma conditions. Significant differences were observed in asthma control and FEV1 reversibility between the two subtypes. Poor control subtypes were closely related to glucocorticoid resistance and airway remodeling. BNIP3 was identified as a diagnostic marker and associated with immune cell infiltration such as, M2 macrophages. The risk prediction model containing four genes has accurate classification efficiency and prediction value. Small molecules obtained from the cMAP database that may have therapeutic effects on asthma are mainly DPP4 inhibitors.ConclusionPyroptosis and its mediated immune phenotype are crucial in the occurrence, development, and prognosis of asthma. The predictive models and drugs developed on the basis of PRGs may provide new solutions for the management of asthma.

Background: Immune targeted therapy has become an attractive therapeutic approach for patients with dilated cardiomyopathy (DCM) recently. Genetic predisposition and gender play a critical role in immune-related responses of DCM. This study aimed to perform a bioinformatics analysis of molecular differences between male and female samples and identify immune-related ceRNA network in DCM.Methods: The gene expression microarray and clinical features dataset of GSE19303 was downloaded from the GEO. The raw data were preprocessed, followed by identification of differentially expressed genes (DEGs) between male and female DCM samples. Crucial functions and pathway enrichment analysis of DEGs were investigated through GO analysis and KEGG pathway analysis, respectively. A lncRNA–miRNA–mRNA network was constructed and a central module was extracted from the ceRNA network.Results: Compared with the female group, the male group benefits more from IA/IgG immunotherapy. Male patients of DCM had a significant positive correlation with the abundance of inflammatory cells (B cells, memory B cells, CD8+ Tem cells, and NK cells). Sex difference DEGs had a widespread impact on the signaling transduction, transcriptional regulation, and metabolism in DCM. Subsequently, we constructed an immune-related ceRNA network based on sex differences in DCM, including five lncRNAs, six miRNAs, and 29 mRNAs. Furthermore, we extracted a central module from the ceRNA network, including two lncRNAs (XIST and LINC00632), three miRNAs (miR-1-3p, miR-17-5p, and miR-22-3p), and six mRNAs (CBL, CXCL12, ESR1, IGF1R, IL6ST, and STC1). Among these DEGs, CBL, CXCL12, and IL6ST expression was considered to be associated with inflammatory cell infiltration in DCM.Conclusions: The identified ceRNA network and their enriched pathways may provide genetic insights into the phenotypic diversity of female and male patients with DCM and may provide a basis for development of sex-related individualization of immunotherapy.