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Abstract Systemic lupus erythematosus (SLE) is an autoimmune disorder that commonly affects the skin, kidneys, joints, and various other systemic tissues, with its development intricately linked to the process of immunosenescence. Quercetin (QC), a phytochemical that occurs naturally, demonstrates many different biological capabilities, such as antibacterial, antioxidant, and anti-inflammatory activities. Our investigation found that QC effectively reduced kidney damage and relieved mesenteric lymph nodes (mLNs) swelling in MRL/lpr lupus mice. Moreover, QC has been found to decrease the number of senescent follicular helper T (Tfh) cells, a pivotal kind of T cells that contribute to the progression of SLE. In vitro, QC exhibited the capacity to modulate mRNA expression levels, with the downregulation of IL-6, IL21-AS1, IL-27, BCL6, and BCL2L12, and the upregulation of FOXP1 and BIM. This modulation resulted in the suppression of Tfh cells differentiation and the enhancement of apoptosis in senescent CD4+ T cells. In addition, the HuProtTM Human Proteome Microarray revealed that QC can directly bind to BCL-2 protein and therefore promote the apoptosis of senescent CD4+ T cell. As a result, our investigative elucidate the potent inhibitory action of QC on the ontogeny of Tfh cells, along with its capacity to abrogate the immunosenescent phenotype. This positions QC as a promising therapeutic strategy for treating SLE.

Analyzing rock mass seepage using the discrete fracture network (DFN) flow model poses challenges when dealing with complex fracture networks. This paper presents a novel DFN flow model that incorporates the actual connections of large-scale fractures. Notably, this model efficiently manages over 20,000 fractures without necessitating adjustments to the DFN geometry. All geometric analyses, such as identifying connected fractures, dividing the two-dimensional domain into closed loops, triangulating arbitrary loops, and refining triangular elements, are fully automated. The analysis processes are comprehensively introduced, and core algorithms, along with their pseudo-codes, are outlined and explained to assist readers in their programming endeavors. The accuracy of geometric analyses is validated through topological graphs representing the connection relationships between fractures. In practical application, the proposed model is employed to assess the water-sealing effectiveness of an underground storage cavern project. The analysis results indicate that the existing design scheme can effectively prevent the stored oil from leaking in the presence of both dense and sparse fractures. Furthermore, following extensive modification and optimization, the scale and precision of model computation suggest that the proposed model and developed codes can meet the requirements of engineering applications.

Abstract The accumulation of secondary metabolites in Panax ginseng Meyer (P. ginseng) exhibits significant geographical variation, normally due to environmental factors. The current study aimed at elucidating the key environmental factors modulating the accumulation of secondary metabolites in P. ginseng. Plant and the associated soil samples were collected from ten geographical locations within the latitudinalrange of 27.09°N − 42.39°N and longitudinal range of 99.28°E − 128.19°E. 12 secondary metabolites in P. ginseng toots were measured. And the correlation between secondary metabolites with a series of soil properties and 7 climatic factors were investigated through Pearson’s correlation, mantel test, random forest and pathway analysis. The results revealed that climatic factors were stronger drivers of ginseng secondary metabolite profile than soil nutrients. Specifically, temperature seasonality (TS) and soil available phosphorus (AP) were the most effective environments to have significantly and positively influence on the secondary metabolites of ginseng. This findings contribute to identifying optimal cultivation areas for P. ginseng, and hopefully establishing methods for interfering/shaping microclimate for cultivating high-quality P. ginseng.

Intelligent control of the hole-seeking process of a rock drilling rig boom is crucial for enhancing the accuracy and efficiency of rock drilling operations. The inverse kinematics solution (IKS) is the core of achieving precise and rapid hole-seeking control of the boom. However, existing analytical and numerical techniques are inadequate in fulfilling the accuracy and time efficiency requirements for IKS in complex drilling boom scenarios. Conventional neural network (NN) approaches heavily depend on labeled data comprising target borehole sets derived from the activities of each joint and forward kinematics. The distribution of drill endpoints generated by this data cannot cover the entire workspace, resulting in the low reliability of the solution. To overcome these challenges, this study introduces an unsupervised learning-based NN method for IKS emphasizing safety constraints. This innovative method differs from traditional approaches in that it does not depend on labeled data. Instead, it utilizes the desired end position of the drilling boom as the network input. The network generates an eight-dimensional joint vector, and the actual drill end pose is derived through forward kinematics calculations on this vector. Then, the difference between the actual and desired drill end poses is used as the optimization objective, driving the network updates through gradient descent. The advantage of this method lies in eliminating the need for complex joint label data required in supervised learning IKS and using the differences in drill end poses directly as optimization objectives, which helps improve the accuracy of IKS. Meanwhile, a critical innovation of this study is integrating a safety collision penalty into the objective function of the solution, ensuring that the network’s output for joint positions adheres to specific environmental limitations. If the actual distance falls below the safety threshold, penalty terms are incorporated into the objective function, allowing for the adjustment of weights to maintain a balance between the precision demands of hole drilling and the design requirements of the safety constraints. This method improves the accuracy of IKS and significantly reduces its collision rate. Experimental results reveal that the mean hole-seeking error obtained using this unsupervised learning-based method achieves a mean hole-seeking error of 5–7 mm in IKS, a significant improvement of approximately 70.72% over supervised learning methods. Moreover, introducing safety constraints has successfully reduced the collision rate in IKS solutions by 90.28% without sacrificing the accuracy of the solutions.

Abstract Improving thermal insulation is vital for addressing thermal protection and energy efficiency challenges. Though silica aerogel has a record-low thermal conductivity at ambient pressure, its high production cost, due to its nanoscale porous structure, has hindered its widespread use. In this study, we introduce a cost-effective and mild method that enhances insulation by incorporating phase change materials (PCMs) into a micron-porous framework. With a thermal conductivity at 0.041 W m−1K−1 on par with conventional insulation materials, this PCMs aerogel presents additional advantages for thermal protection from transient high-temperature loads by effectively delaying heat propagation through heat absorption. Moreover, the PCMs aerogel remains stable under cyclic deformation and heating up to 300 °C and is self-extinguishing in the presence of fire. Our approach offers a promising alternative for affordable insulation materials with potential wide applications in thermal protection and energy conservation areas.

Abstract Traditional optical anti-counterfeiting (AC) is achieved by static printed images, which makes them susceptible to lower levels of security and easier replication. Therefore, it is essential to develop AC device with dynamic modulation for higher security. Electrophoretic display (EPD) has the advantages of low power consumption, high ambient contrast ratio, and capability of showing dynamic images which is suitable for dynamic AC applications. Herein, we prepared a dynamical AC device based on a fluorescent EPD, and achieving the image switch between black, white, and green fluorescence states under the dual-mode driving (electronic field and UV light). We loaded perovskite quantum dots (CsPbBr3) onto the TiO2 particles and further prepared fluorescent electrophoretic particles TiO2/CsPbBr3-3-PLMA (TiO/CPB-3) by grafting and polymerizing method. In addition, we fabricated the AC devices based on the fluorescent EPD, which exhibits the multifunctional AC, where the fluorescent EPD has a fast response time of 350 ms, a high contrast ratio of 17, and bright green fluorescence. This prototype demonstrates a new way for future dynamic AC and identification.

Drug discovery is a sophisticated process that incorporates scientific innovations and cutting-edge technologies. Compared to traditional bioactivity-based screening methods, encoding and display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments to promising tools for pharmaceutical hit discovery due to their high screening efficiency, throughput, and resource minimization. This review systematically summarizes the development history, typology, and prospective applications of encoding and displayed technologies, including phage display, ribosomal display, mRNA display, yeast cell display, one-bead one-compound, DNA-encoded, peptide nucleic acid-encoded, and new peptide-encoded technologies, and examples of preclinical and clinical translation. We discuss the progress of novel targeted therapeutic agents, covering a spectrum from small-molecule inhibitors and nonpeptidic macrocycles to linear, monocyclic, and bicyclic peptides, in addition to antibodies. We also address the pending challenges and future prospects of drug discovery, including the size of screening libraries, advantages and disadvantages of the technology, clinical translational potential, and market space. This review is intended to establish a comprehensive high-throughput drug discovery strategy for scientific researchers and clinical drug developers.

High-entropy alloys (HEAs) with a face-centered cubic (FCC) lattice exhibit remarkable work-hardenability and high fracture toughness at cryogenic temperatures. However, in some non-equiatomic FCC HEAs, grain boundary melting defects may form during the homogenization process, which may lead to embrittlement of the grain boundaries. To address this issue, in this study, we propose the use of friction stir processing (FSP) to tailor the microstructure of a typical non-equiatomic Fe40Mn27Ni26Co5Cr2 HEA. After FSP, the mechanical properties of the non-equiatomic Fe40Mn27Ni26Co5Cr2 HEA were substantially improved. The study revealed that the improved mechanical properties could be attributed to the intense thermal-shear effect of FSP, which simultaneously eliminated grain boundary segregation and induced discontinuous dynamic recrystallization to refine grain size. Our findings not only shed light on understanding the embrittlement mechanism of homogenization treatment in non-equiatomic FCC HEAs, but also provide a useful route to improve the mechanical properties of FCC HEAs.

To better understand the failure behaviours and strength of bolt-reinforced blocky rocks, large scale extensive laboratory experiments are carried out on blocky rock-like specimens with and without rockbolt reinforcement. The results show that both shear failure and tensile failure along joint surfaces are observed but the shear failure is a main controlling factor for the peak strength of the rock mass with and without rockbolts. The rockbolts are necked and shear deformation simultaneously happens in bolt‑reinforced rock specimens. As the joint dip angle increases, the joint shear failure becomes more dominant. The number of rockbolts has a significant impact on the peak strain and uniaxial compressive strength (UCS), but little influence on the deformation modulus of the rock mass. Using the Winkler beam model to represent the rockbolt behaviours, an analytical model for the prediction of the strength of bolt-reinforced blocky rocks is proposed. Good agreement between the UCS values predicted by proposed model and obtained from experiments suggest an encouraging performance of the proposed model. In addition, the performance of the proposed model is further assessed using published results in the literature, indicating the proposed model can be used effectively in the prediction of UCS of bolt-reinforced blocky rocks.

Abstract With the rapid development of digital technologies such as intelligent control and information communication, digitization has gradually become an inevitable trend to promote technology innovation and industrial upgrading for the power grid. As the basis of digital technology, digital sensing technology will gradually penetrate all aspects of the power system for comprehensive perception and high operational reliability. First, this article introduces the application status and technical requirements of power intelligent sensor technology in various aspects of the power system, including the generation, transmission, transformation, distribution, and consumption of electricity. Next, domestic and foreign scholars' latest research achievements in power sensing technology are described from three major aspects, that is, optical fiber sensing technology, MEMS sensing technology, and sensor self‐powered technology. Finally, future challenges for the electric power intelligent sensors are discussed and an outlook of future widespread application in the clean, safe, and efficient digital power grid is provided.

Segmentation of mitral valve is not only important for clinical diagnosis, but also has far-reaching impact on prevention and prognosis of the disease by experts and doctors. In this paper, the multi-channel cross fusion transformer based U-Net network model (MCCT-UNet) is proposed according to the classical U-Net architecture. First, the jump connection part of MCCT-UNet is designed by using a multi-channel cross-fusion based attention mechanism module (MCCT) instead of the original jump connection, and this module fuses the feature maps from different scales in different stages of the encoder. Second, the optimization of the feature fusion method is proposed in the decoding stage by designing the cross-compression excitation sub-module (C-SENet) to replace the simple feature splicing, and the C-SENet is used to bridge the inconsistency of the semantic hierarchy by effectively combining the deeper information in the encoding stage with the shallower information. This two modules can establish a close connection between the encoder and decoder by exploring multi-scale global contextual information to solve the semantic divide problem, thus it significantly improves the segmentation performance of the network. The experimental results show that the improvement is effective, and the MCCT-UNet model outperforms the other 9 network models. Specifically, the MCCT-UNet achieved a Dice coefficient of 0.8734, an IoU of 0.7854, and an accuracy of 0.9977, demonstrating significant improvements over the compared models.

BackgroundDue to the scarcity and high cost of MRI in resource-constrained regions, prompt diagnosis and treatment of rotator cuff tears remain problematic in these areas. Therefore, extensive research has been conducted to predict rotator cuff tears using simple and affordable anteroposterior radiographs. It remains unclear whether non-standard anteroposterior radiographs would have a notable impact on the preciseness of the diagnosis.MethodWe analyzed patients treated for shoulder pain at hospitals. These patients underwent shoulder joint MRI and standard anteroposterior radiographs, were categorized into those with rotator cuff tears and a control group. We assessed whether the radiographs were standard anteroposterior radiographs using classification criteria from previous studies. Three assessors independently measured the acromiohumeral interval, upwards migration index, acromion index, critical shoulder angle, and double-circle radius ratio in radiographic images. The intraclass correlation coefficient and receiver operating characteristic curves were used to assess measurement reliability and predictive capabilities of each predictive method for rotator cuff tears.ResultsThis study included 102 non-standard radiographs that met the research criteria for the measurement and analysis. The intragroup correlation coefficients for the acromiohumeral interval, upwards migration index, and double-circle radius ratio were above 0.7 (0.77, 0.71, 0.76), while those for the acromion index and critical shoulder angle exceeded 0.8 (0.86 and 0.87). In non-standard radiographs, the double-circle radius ratio reliably predicted rotator cuff tears (p 0.05). The areas under the receiver operating characteristic curves of the double-circle radius ratio, estimated by the three researchers for rotator cuff tears.ConclusionThis study found that non-standard radiographs significantly impaired the diagnostic performance of the acromiohumeral interval, upwards migration index, acromion index, and critical shoulder angle. Only the double-circle radius ratio maintained its predictive power (although this diminished capability may fall short of clinical relevance) and demonstrated high applicability. These findings indicate the need for researchers to prioritize the quality of radiographs and focus on reducing the sensitivity of the prediction method in relation to radiograph quality. The capability exhibited by the double-circle radius ratio warrants further investigation, to facilitate a simplified diagnosis of rotator cuff tears.

BackgroundThe brain and kidneys share similar low-resistance microvascular structures, receiving blood at consistently high flow rates and thus, are vulnerable to blood pressure fluctuations. This study investigates the causative factors of cerebral microbleeds (CMBs), aiming to quantify the contribution of each risk factor by constructing a multivariate model via stepwise regression.MethodsA total of 164 hospitalized patients were enrolled from January 2022 to March 2023 in this study, employing magnetic susceptibility-weighted imaging (SWI) to assess the presence of CMBs. The presence of CMBs in patients was determined by SWI, and history, renal function related to CMBs were analyzed.ResultsOut of 164 participants in the safety analysis, 36 (21.96%) exhibited CMBs and 128 (78.04%) did not exhibit CMBs, and the median age of the patients was 66 years (range: 49–86 years). Multivariate logistic regression identified hypertension (OR = 13.95%, 95% CI: 4.52, 50.07%), blood urea nitrogen (BUN) (OR = 1.57, 95% CI: 1.06–2.40), cystatin C (CyC) (OR = 4.90, 95% CI: 1.20–22.16), and urinary β-2 microglobulin, (OR = 2.11, 95% CI: 1.45–3.49) as significant risk factors for CMBs. The marginal R-square (RM2) was 0.25. Among all determinants, hypertension (47.81%) had the highest weight, followed by UN (11.42%). Quasi-curves plotted using the bootstrap method (999 times) showed good agreement between the predictive model and actual observations.ConclusionHypertension, BUN, urinary β-2 microglobulin, CyC were risk factors for CMBs morbidity, and controlling the above indicators within a reasonable range will help to reduce the incidence of CMBs.

Abstract Modern microprocessor performance is limited by local hot spots induced at high frequency by busy integrated circuit elements such as the clock generator. Locally embedded thermoelectric devices (TEDs) are proposed to perform active cooling whereby thermoelectric effects enhance passive cooling by the Fourier law in removing heat from the hot spot to colder regions. To mitigate transient heating events and improve temperature stability, we propose a novel analytical solution that describes the temperature response of a periodically heated hot spot that is actively cooled by a TED driven electrically at the same frequency. The analytical solution that we present is validated by experimental data from frequency domain thermal reflectance (FDTR) measurements made directly on an actively cooled Si thermoelectric device where the pump laser replicates the transient hot spot. We herein demonstrate a practical method to actively cancel the transient temperature variations on circuit elements with TEDs. This result opens a new path to optimize the design of cooling systems for transient localized hot spots in integrated circuits.

Abstract Diphthamide is a modified histidine residue unique for eukaryotic translation elongation factor 2 (eEF2), a key ribosomal protein. Loss of this evolutionarily conserved modification causes developmental defects through unknown mechanisms. In a patient with compound heterozygous mutations in Diphthamide Biosynthesis 1 (DPH1) and impaired eEF2 diphthamide modification, we observe multiple defects in neural crest (NC)-derived tissues. Knockin mice harboring the patient’s mutations and Xenopus embryos with Dph1 depleted also display NC defects, which can be attributed to reduced proliferation in the neuroepithelium. DPH1 depletion facilitates dissociation of eEF2 from ribosomes and association with p53 to promote transcription of the cell cycle inhibitor p21, resulting in inhibited proliferation. Knockout of one p21 allele rescues the NC phenotypes in the knockin mice carrying the patient’s mutations. These findings uncover an unexpected role for eEF2 as a transcriptional coactivator for p53 to induce p21 expression and NC defects, which is regulated by diphthamide modification.

Abstract Electroencephalography (EEG) microstate analysis is a neuroimaging analytical method that has received considerable attention in recent years and is widely used for analysing EEG signals. EEG is easily influenced by internal and external factors, which can affect the repeatability and stability of EEG microstate analysis. However, there have been few reports and publicly available datasets on the repeatability of EEG microstate analysis. In the current study, a 39-year-old healthy male underwent a total of 60 simultaneous electroencephalography and electrocardiogram measurements over a period of three months. After the EEG recording was completed, magnetic resonance imaging (MRI) was also conducted. To date, this EEG dataset has the highest number of repeated measurements for one individual. The dataset can be used to assess the stability and repeatability of EEG microstates and other analytical methods, to decode resting EEG states among subjects with open eyes, and to explore the stability and repeatability of cortical spatiotemporal dynamics through source analysis with individual MRI.

In this paper, by using critical point theory, we study the infinitely many solutions of partial discrete Kirchhoff type problems. Moreover, we acquire some sufficient conditions for the existence of positive solutions to the boundary value problems by using the strong maximum principle. As far as we know, this is the research of partial discrete Kirchhoff type problems for the first time. Finally, our major results are explained with four examples.

Prioritizing multiple potentially unstable slopes based on varying levels of criticality is an essential approach when resources are limited. This study presents a framework for planning the prioritization of unstable rock slope remediation. The prioritization of mitigation measures for these slopes is determined using deformation values derived from indirect information, such as rock classification systems. To demonstrate the application of this framework, a case study involving unstable rock slopes in southwestern China is presented. Initially, the most appropriate estimation model was chosen from among six candidates for estimating the deformation modulus of the unstable rock mass in the slope, utilizing indirect information. Subsequently, the deformation modulus, updated through Bayesian analysis, was employed to generate the corresponding deformation distributions for the rock slopes. Compared to traditional quantitative methods, the proposed framework is adaptable to various working conditions and yields more definitive results. The indirect data used in this framework are cost-effective, enabling the assessment of all unstable slopes. Moreover, the effect of the amount of indirect data and prior information on slope remediation prioritization is discussed. The proposed framework offers a valuable tool for decision-makers in planning and prioritizing mitigation measures.

Underground liquified natural gas (LNG) storage is essential in guaranteeing national energy strategic reserves, and its construction is being accelerated. The stability of surrounding rock of underground LNG storage caverns under stress-low temperature coupling effect is the key factor determining the feasibility of LNG storage. First, a mathematical model used for controlling the stress-low temperature coupling and the processes of rock damage evolution is given, followed by a 2-D numerical execution process of the mathematical model mentioned above described based on Comsol Multiphysics and Matlab code. Finally, a series of 2-D simulations are performed to study the influence of LNG storage cavern layout, burial depth, temperature and internal pressure on the stability of surrounding rocks of these underground storage caverns. The results indicate that all the factors mentioned above affect the evolution of deformation and plastic zone of surrounding rocks. The research results contribute to the engineering design of underground LNG storage caverns.

Nonalcoholic steatohepatitis (NASH) represents a severe disease subtype of nonalcoholic fatty liver disease (NAFLD) that is thought to be highly associated with systemic metabolic abnormalities. It is characterized by a series of substantial liver damage, including hepatocellular steatosis, inflammation, and fibrosis. The end stage of NASH, in some cases, may result in cirrhosis and hepatocellular carcinoma (HCC). Nowadays a large number of investigations are actively under way to test various therapeutic strategies, including emerging oligonucleotide drugs (e.g., antisense oligonucleotide, small interfering RNA, microRNA, mimic/inhibitor RNA, and small activating RNA) that have shown high potential in treating this fatal liver disease. This article systematically reviews the pathogenesis of NASH/NAFLD, the promising druggable targets proven by current studies in chemical compounds or biological drug development, and the feasibility and limitations of oligonucleotide-based therapeutic approaches under clinical or pre-clinical studies.

Interstitial fluid, owing to its similarity to blood components and higher sensitivity and specificity, finds widespread application in disease diagnosis and tumor marker detection. However, collecting interstitial fluid, particularly from the deep subcutaneous connective tissue, remains challenging. • This study aimed to compare three different collection methods - push-pull perfusion, multi-filament nylon thread implantation, and tissue centrifugation - for collecting interstitial fluid from the subcutaneous connective tissue layer of mini-pigs. High-performance ion chromatography was employed to analyze the conventional cation components in the samples and compare ion composition analysis between the different methods. • Results indicated that while the distribution of conventional cations in the interstitial fluid collected by the three methods was generally consistent, there were slight variations in the detection rates and concentrations of different ions. Hence, suitable collection methods should be selected based on the ions or collection sites of interest.

With an extension of the geological entropy concept in porous media, the approach called directional entrogram is applied to link hydraulic behavior to the anisotropy of the 3D fracture networks. A metric called directional entropic scale is used to measure the anisotropy of spatial order in different directions. Compared with the traditional connectivity indexes based on the statistics of fracture geometry, the directional entropic scale is capable to quantify the anisotropy of connectivity and hydraulic conductivity in heterogeneous 3D fracture networks. According to the numerical analysis of directional entrogram and fluid flow in a number of the 3D fracture networks, the hydraulic conductivities and entropic scales in different directions both increase with spatial order (i.e., trace length decreasing and spacing increasing) and are independent of the dip angle. As a result, the nonlinear correlation between the hydraulic conductivities and entropic scales from different directions can be unified as quadratic polynomial function, which can shed light on the anisotropic effect of spatial order and global entropy on the heterogeneous hydraulic behaviors.

This study examines the frequency attenuation characteristics of elastic waves in marble, granite, and red sandstone through laboratory tests and numerical simulations based on ABAQUS software on eight rock samples. The correlation between the distance of the decay of the peak frequency and the petrophysical and mechanical parameters is also analyzed. The results show that elastic waves undergo stepwise attenuation of their peak frequency during laboratory attenuation tests. This finding was confirmed by numerical simulations. As elastic waves propagate through a rock medium, the amplitude of the high-frequency peak area near the excitation frequency decreases rapidly, while the proportion of low-frequency signals increases. As the propagation continues, the signal spectrum is dominated by low-frequency components, resulting in a stepwise attenuation of the peak frequency. It has been observed that the step decay distance of the peak frequency of elastic waves varies with the degree of particle bonding, which can be used to characterize the attenuation properties of elastic waves in a medium.

Anisodus tanguticus (Maxim.) Pascher, which is an important species used in traditional Tibetan medicine, is grown on the Qinghai–Tibet Plateau. A quantitative analysis of 18 elements in A. tanguticus and the soil was conducted using an inductively coupled plasma optical emission spectrometer. The elemental contents of A. tanguticus underwent principal component analysis, linear discriminant analysis, and orthogonal partial least-squares discriminant analysis. Furthermore, elemental accumulation and elemental transfer coefficients were calculated, and the correlation between environmental factors and elemental content was further explored. The multivariate statistical results indicated that A. tanguticus plants can be distinguished by their geographical origin. Elemental accumulation and transfer patterns differed significantly among the analysed elements. Some positive or negative correlation relationships were found between environmental factors and contents in root parts of A. tanguticus. The present study provides an efficient and practical method to discriminate the geographical origin of A. tanguticus from different regions.

The nuclear receptor, farnesoid X receptor (FXR/NR1H4), is increasingly recognized as a promising drug target for metabolic diseases, including nonalcoholic steatohepatitis (NASH). Protein-coding genes regulated by FXR are well known, but whether FXR also acts through regulation of long non-coding RNAs (lncRNAs), which vastly outnumber protein-coding genes, remains unknown. Utilizing RNA-seq and global run-on sequencing (GRO-seq) analyses in mouse liver, we found that FXR activation affects the expression of many RNA transcripts from chromatin regions bearing enhancer features. Among these we discovered a previously unannotated liver-enriched enhancer-derived lncRNA (eRNA), termed FXR-induced non-coding RNA (Fincor). We show that Fincor is specifically induced by the hammerhead-type FXR agonists, including GW4064 and tropifexor. CRISPR/Cas9-mediated liver-specific knockdown of Fincor in dietary NASH mice reduced the beneficial effects of tropifexor, an FXR agonist currently in clinical trials for NASH and primary biliary cholangitis (PBC), indicating that amelioration of liver fibrosis and inflammation in NASH treatment by tropifexor is mediated in part by Fincor. Overall, our findings highlight that pharmacological activation of FXR by hammerhead-type agonists induces a novel eRNA, Fincor, contributing to the amelioration of NASH in mice. Fincor may represent a new drug target for addressing metabolic disorders, including NASH.

In order to improve the interior sound quality of electric vehicles (EVs) under acceleration and uniform speed conditions, to balance the comfort and dynamics of the interior sound, and to improve the accuracy and performance of the active sound generation system (ASGS), this article carries out the research related to the parameter design, sound calibration, evaluation methodology, and control system of the EV ASGS. Propose an in-vehicle sound design method focusing on three dimensions, including engine order composition, spectral energy distribution, and sound amplitude enhancement in the typical speed range, and determine the in-vehicle sound design scheme and the total sound value target. Focus on the sound parameter design, calibration and evaluation methods of EV ASGS considering the frequency response characteristics of the loudspeaker, sound amplitude control accuracy, sound quality, and psychoacoustic parameters, clarify the active sound parameter settings of EVs, complete the analysis of sound extraction methods, complete the engine order sound fitting, and design the ASGS of the EV interior by combining the subjective and objective evaluations. Develop the control software and hardware of the ASGS, complete the construction and accuracy verification of the ASGS based on the in-vehicle sound system, and realize the sound calibration of the ASGS under the static conditions of the real vehicle and the verification of the target achievement. The real-vehicle test shows that the ASGS reduces the sharpness of 1.0 acum and 0.52 acum under acceleration and constant speed conditions, respectively, and improves the comfort and dynamics of in-vehicle sound. The objective and subjective evaluation results show that the parameter design, selection and accuracy of the sound calibration and evaluation methods of the ASGS in the EV determines the accuracy and effect of the ASGS.

BackgroundA novel non-contact system for remote parameter testing and reprogramming offers an alternative method for assessing device parameters during cardiac implantable electronic devices (CIEDs) implantation without the need for physical contact with the manufacturer's clinical service technician. The safety and feasibility of using this system in CIEDs implantation procedures remains to be determined.ObjectiveEvaluate the safety and feasibility of remote parameter testing in CIEDs implantation procedures.MethodsA single center, randomized, open-label, non-inferiority trial (ChiCTR2200057587) was conducted to compare the two approaches for interrogating CIEDs during implantation procedures: routine interrogation performed by on-site technicians or remote interrogation performed by technicians using the 5G-Cloud Technology Platform. Patients aged ≥18 years and elected to receive CIEDs were eligible for inclusion. The primary endpoint was the completion rate of the parameter test. Safety and efficiency were evaluated in all randomly assigned participants.ResultsA total of 480 patients were finally enrolled and were randomly assigned to routine group (n = 240) or remote group (n = 240). The primary endpoint was achieved by 100% in both groups (P = 0.0060 for noninferiority). The parameters of sensing, threshold, and impedance regarding the right atrium, right ventricle, and left ventricle had no statistical significance between the two groups (P > 0.05). Procedure time, parameter testing time, and both duration and dose of x-ray irradiation were not significantly different between the two groups (P > 0.05). Shut-open door frequency was significantly higher in the routine group than the remote group [6.00 (4.00, 8.00) vs. 0, P

Carbon fiber reinforced plastic (CFRP) thin-walled structures have been widely acknowledged as superior energy absorbers due to comprehensive advantages on crashworthiness and light weight. However, few studies have been reported concerning CFRP thin-walled structures with nonlinearly variable sectional dimensions along the longitudinal direction. Hence, in the present study, a novel CFRP functionally-graded conical square thin-walled structure with variable circumscribed diameter (functionally-graded conical square tube, FGCST) is proposed and comprehensively investigated. Specifically, finite element (FE) models of FGCST under multi-angle crushing loading are first built and validated. Second, a comprehensive crashworthiness comparison among the FGCST, the conventional CFRP conical square tube (CST) and the CFRP straight square tube (SST) under multi-angle crushing loading is executed to explore the relative merits of FGCST over others. Third, a parameter study is implemented on FGCST to explore the action laws of its structural parameters on its overall crashworthiness under multi-angle crushing loading. Finally, the FGCST is multi-objective crashworthiness optimized for maximizing overall specific energy absorption (SEA θ ) and minimizing overall peak crushing force (PCF 0 ) simultaneously through Taguchi method coupled with grey relational analysis (GRA). The optimized FGCST obtains 6.06% higher of SEA θ and meanwhile 40.58% lower of PCF 0 compared with the baseline design, thus demonstrating good potential as a superior candidate for vehicle collision energy absorbers.

Abstract Background Long term care (LTC) services for functionally impaired senior citizens are crucial for addressing the challenges of aging. However, research on eligibility criteria and coverage of LTC in China is lacking. Our objective is to assess the current status of LTC and explore eligibility criteria and coverage for the elderly. Methods This is a cross-sectional study conducted in two first-tier cities in China. Residents aged 65 or over were recruited from a nursing home and four primary hospitals. Participants were divided into three groups (bedridden, domestic, and community), then six grades (grade one to six) according to the Longshi Scale, and their functional ability was assessed using the Modified Barthel Index. Information such as diseases, complications, and daily care needs were collected. Nursing staff were invited to indicate patients’ needs for care. A one-way ANOVA test, Kruskal Wallis H test and Mann–Whitney U test were used to explore the differences of variables in three Longshi groups or Longshi grades. Results Among all 1157 participants, with an average age of 80.54, 69.3% were in the bedridden group. The most common diagnosis was stroke (71.4%), with the most prevalent complication being pulmonary infection (25.2%). In the nursing assessment, basic health care, disease care, activity care, complication prevention care and psychosocial care were summarized as the five main aspects of LTC for the elderly. Feeding, bathing, drinking, bowel management and bladder management were identified as the basic care which fulfills participants’ basic physical needs in each Longshi group. Mouth care, artificial airway management, and body reposition, which can prevent immobility complications, were highly demanded by bedridden elderly. Conclusions The elderly in grade one to three are the ones in need of LTC most. The content of LTC for elderly should include basic care which fulfills their basic physical needs and complication care which can prevent immobility complications. The evidence of this research may contribute to the design of LTC in China. Trial registration The study design was registered in the Chinese Clinical Trial Registry (ChiCTR-2000034067, Registered 22 Jun 2020, http://www.chictr.org.cn/showproj.aspx?proj=54770 ).

Underground coal gasification (UCG) is an efficient method for the conversion of deep coal resources into energy. The scope of this work is to model the subsidence of four gasification cavities with a size of 30 m × 30 m × 15 m, separated by 15 m wide pillars. Two scenarios of gasification sequence are modelled, one with the gasification of cavities 1 and 2 followed by 3 and 4, and the other one with the sequence of cavities 1 and 3, followed by 2 and 4. The results show that the final surface subsidence after gasification of four cavities is 9.8 mm and the gasification sequence has an impact only on the subsidence at the intermediate stage but has no impact on the final subsidence after all four cavities are formed, when only the elasticity regime is considered. Additionally, the maximum surface subsidence for the studied cavities of different sizes ranges from 0.016 mm to 7.14 mm, and the relationship between the subsidence and the cavity volume is approximately linear. Finally, a prediction model of surface subsidence deformation is built up using the elastic plate theory, and the formula of surface deformation at a random point is given. The maximum difference between measured and calculated deformation is 4.6%, demonstrating that the proposed method can be used to predict the ground subsidence induced by UCG.

Image super-resolution (SR) technology can improve the resolution of images and provide clearer and more reliable remote sensing images of high quality to better serve the subsequent applications. However, when reconstructing high-frequency feature areas of remote sensing images, existing SR reconstruction methods are prone to artifacts that affect visual effects and make it difficult to generate real texture details. In order to address this issue, a texture-detail-enhanced dense generative adversarial network (TDEGAN) for remote sensing image SR is presented. The generator uses multi-level dense connections, residual connections, and Shuffle attention (SA) to improve the feature extraction ability. A PatchGAN-style discrimination network is designed to effectively perform local discrimination and helps the network generate rich, detailed features. To reduce the impact of artifacts, we introduce an artifact loss function, which is combined with the exponential moving average (EMA) technique to distinguish the artifacts generated from the actual texture details through local statistics, which can help the network reduce artifacts and generate more realistic texture details. Experiments show that TDEGAN can better restore the texture details of remote sensing images and achieves certain advantages in terms of evaluation indicators and visualization.

Background : The biophysical properties of the meridian system, an important concept of traditional Chinese medicine, include low impedance, resounding voice, and high acoustic conductance, all of which are helpful for elucidating the essence of meridians. Objectives: To visualize the human pericardium meridian (PC) based on the resounding voice property of meridians. Methods : Visualization of the PC was performed by injection of fluorescein sodium at the PC6 acupoint (Neiguan) on the PC. Before injection, percussion active points (PAPs) were identified by the virtue of their resounding voice properties. After injection, the trajectories of fluorescein migration throughout the body surface were recorded and analyzed. The distribution of fluorescein in the tissue was further studied using cross-sections of hind limbs of mini-pigs, in which fluorescein was injected into low impedance points. Results : The identified PAP lines were colocalized with PC. Following intradermal fluorescein injection, 1-3 fluorescent lines, which were unrelated to the arm veins, were observed in 7 of 10 participants; 85.4% of fluorescent signals were coincident with PAPs and their intensity had a negative correlation with the body mass index (r = -0.56, p = 0.045). Cross-sections showed a Y-shaped fluorescence pattern where the two migration lines on the surface were the two vertices of the “Y.” Conclusion : The trajectories of fluorescein in the body are suggestive of the anatomical structure of meridians. The PC is related to the deep horizontal interstitial channels that connect to the body surface through vertical interstitial spaces. These biophysical properties and techniques for meridian visualization are valuable for revealing the anatomical structure of meridians.

This paper reports the fabrication of silicon PN diode by using DNA nanostructure as the etching template for SiO2 and also as the n-dopant of Si. DNA nanotubes were deposited onto p-type silicon wafer that has a thermal SiO2 layer. The DNA nanotubes catalyze the etching of SiO2 by HF vapor to expose the underlying Si. The phosphate groups in the DNA nanotube were used as the doping source to locally n-dope the Si wafer to form vertical P-N junctions. Prototype PN diodes were fabricated and exhibited expected blockage behavior with a knee voltage of ca. 0.7 V. Our work highlights the potential of DNA nanotechnology in future fabrication of nanoelectronics.

Conclusion: Patients who are bedridden after stroke face a higher potential risk of cardiac hemodynamic impairment following SARS-CoV-2 infection, emphasizing the need for meticulous hemodynamic monitoring during treatment and rehabilitation of these patients to prevent any potential cardiovascular complications.

In the construction of the civil engineering infrastructure, the noise and vibration are affected by the geological conditions, adopting specific construction techniques based on the geological conditions is of great significance in suppressing the noise and vibration caused by the construction. To classify and evaluate the rock mass quality, the rock quality designation (RQD) is adopted widely in the geological and mining engineering. Traditionally, to obtain RQD, lengths of drilling core pieces are measured and RQD is calculated manually, which is labor-expensive and time-consuming. With the development of the computational power, the image treatment driven by the computer vision creates a potential approach to obtain RQD automatically. In the present work, the image treatment process with the aid of the object detection and the image segmentation is adopted to obtain RQD automatically, based on the similarity of features such as color and texture, the segment anything model is adopted to detect the rock cores in the image, then, the YOLOv8 algorithm is adopted to train the model, and the gap features of the rock chip segments are extracted for segmentation of different rock core segments. To test the performance of the proposed approach, 10 boreholes from Shapingba Railway Comprehensive Reconstruction Project are adopted to conduct the case study. Compared to the traditional manual approach, RQD obtained by the proposed approach is relatively accurate and obviously efficient, namely, the average error is less than 5% and the time consumed is less than 70%.

The dysregulation of the m6A epitranscriptomic networks have been reported to contribute to the development of gliomas. Here, the authors utilize induced pluripotent stem cell-derived astrocytes with a p53 mutation and demonstrate that mutant p53 upregulates the m6A reader YTHDF2, resulting in the initiation of gliomas.

Immunotherapy has shown promising clinical results in clear cell renal cell carcinoma (ccRCC), but low clinical target response rates due to dysfunction of the major histocompatibility complex (MHC) and an inhibitory tumor immune microenvironment (TIME) have largely limited the associated clinical benefits. In the present study, we explored the feasibility of enhancing tumor-specific-MHC-II-HLA-DRA expression, counteracting the TIME’s suppressive effects, thereby improving the sensitivity of immune checkpoint inhibitor (ICI) therapy from the standpoint of cuproptosis. Immunohistochemical staining and in vitro experiments validated the expression of HLA-DRA in ccRCC and its positive impact on ICI therapy. Subsequently, we observed that cuproptosis upregulated HLA-DRA expression in a dose-dependent manner, further confirming the link between cuproptosis and HLA-DRA. In vivo experiments showed that cuproptosis increased the sensitivity to ICI treatment, and implementing cuproptosis alongside anti-PD-1 treatment curtailed tumor growth. Mechanistically, cuproptosis upregulates HLA-DRA expression at the transcriptional level in a dose-dependent manner by inducing the production of reactive oxygen species; high levels of HLA-DRA promote the expression of chemokines CCL5, CXCL9, and CXCL10 in the TIME, inhibiting the development of a pro-tumor microenvironment by promoting the infiltration of CD4+T and CD8+T cells, thereby synergizing ICI therapy and exerting anti-tumor effects. Taken together, this work highlights the role of cuproptosis in mediating TIME remodeling and synergistic immunotherapy, providing new evidence that cuproptosis can evoke effective anti-tumor immune responses.

Aims: Changes in myocardial mitochondrial morphology and function in premature ventricular contractions (PVCs)-induced cardiomyopathy (PVCCM) remain poorly studied. Here, we investigated the effects of PVCs with different coupling intervals (CIs) on myocardial mitochondrial remodelling in a canine model of PVCCM. Methods and Results: Twenty-one beagles underwent pacemaker implantation and were randomised into the sham (n = 7), short-coupled PVCs (SCP, n = 7), and long-coupled PVCs (LCP, n = 7) groups. Right ventricular (RV) apical bigeminy was produced for 12-week to induce PVCCM in the SCP (CI, 250 ms) and LCP (CI, 350 ms) groups. Echocardiography was performed at baseline and biweekly thereafter to evaluate cardiac function. Masson’s trichrome staining measured ventricular interstitial fibrosis. The ultrastructural morphology of the myocardial mitochondria was analysed using transmission electron microscopy. Mitochondrial Ca2+ concentration, reactive oxygen species (ROS) levels, adenosine triphosphate (ATP) content, membrane potential, and electron transport chain (ETC) complex activity were measured to assess myocardial mitochondrial function. Twelve-week-PVCs led to left ventricular (LV) enlargement with systolic dysfunction, disrupted mitochondrial morphology, increased mitochondrial Ca2+ concentration and ROS levels, decreased mitochondrial ATP content and membrane potential, and impaired ETC complex activity in both the SCP and LCP groups (all p < 0.01 vs the sham group). Ventricular fibrosis was observed only in canines with LCP. Worse cardiac function and more pronounced abnormalities in mitochondrial morphology and function were observed in the LCP group than to the SCP group (all p < 0.05). Conclusion: We demonstrated myocardial mitochondrial abnormalities in dogs with PVCCM, characterised by abnormal mitochondrial morphology, mitochondrial Ca2+ overload, oxidative stress, and impaired mitochondrial energy metabolism. Compared to SCP, long-term LCP exposure resulted in more severe mitochondrial remodelling and cardiac dysfunction in dogs.

The identification of stay cable icing is crucial for robot deicing to improve efficiency and prevent damage to stay cables. Therefore, it is significant to identify the areas and degree of icing in the images of stay cables. This study proposed a two-stage model that combines U-Net and ResNet50. In the first stage, this model used U-Net to segment the surface ice and icicles from the stay cable. The image of icing obtained after segmentation was used as the input for the second stage. In the second stage, ResNet50 was used to classify the degree of icing. The experimental results show that the proposed model can successfully segment the icicles and surface ice from the stay cable icing image to complete the classification of the icing degree. The mean pixel accuracy and intersection over the union of icing were 96.65% and 82.10%, respectively. The average accuracy of the icing degree classification was 95.71%. The method proposed in this study meets the requirements of robustness, segmentation accuracy, and classification accuracy for stay cable icing recognition, which provides a research basis for the precise icing recognition of cable-deicing robots.

Abstract The development of self‐healing conductive hydrogels is critical in electroactive nerve tissue engineering. Typical conductive materials such as polypyrrole (PPy) are commonly used to fabricate artificial nerve conduits. Moreover, the field of tissue engineering has advanced toward the use of products such as hyaluronic acid (HA) hydrogels. Although HA‐modified PPy films are prepared for various biological applications, the cell–matrix interaction mechanisms remain poorly understood; furthermore, there are no reports on HA‐modified PPy‐injectable self‐healing hydrogels for peripheral nerve repair. Therefore, in this study, a self‐healing electroconductive hydrogel (HASPy) from HA, cystamine (Cys), and pyrrole‐1‐propionic acid (Py‐COOH), with injectability, biodegradability, biocompatibility, and nerve‐regenerative capacity is constructed. The hydrogel directly targets interleukin 17 receptor A (IL‐17RA) and promotes the expression of genes and proteins relevant to Schwann cell myelination mainly by activating the interleukin 17 (IL‐17) signaling pathway. The hydrogel is injected directly into the rat sciatic nerve‐crush injury sites to investigate its capacity for nerve regeneration in vivo and is found to promote functional recovery and remyelination. This study may help in understanding the mechanism of cell–matrix interactions and provide new insights into the potential use of HASPy hydrogel as an advanced scaffold for neural regeneration.

In this paper, a novel thin-walled double-hexagonal crash box is first proposed and then multi-objective robust optimized for better overall crashworthiness under multi-angle impact loading, using a proposed hybrid method combining aluminum foam-filling and Taguchi-grey relational analysis (GRA). Specifically, the finite element (FE) models of the regularly-shaped double-hexagonal column (DHC) extracted from original irregularly-shaped crash box under multi-angle impact loading, including hollow (H-DHC) and foam-filled (F-DHC), are first built and validated by experiments. On this basis, a comprehensive crashworthiness comparison is conducted to explore relative merits of F-DHC over original H-DHC under multi-angle impact loading. After that, the F-DHC is multi-objective robust optimized for maximizing overall specific energy absorption (SEA θ ) and minimizing overall initial peak crushing force (IPCF 0 ) simultaneously under multi-angle impact loading, using a hybrid method of Taguchi-GRA. At last, a bumper-crash box integrated crashworthiness analysis under multi-angle impact loading is executed to further verify the optimization. The optimal F-DHC and the optimized crash box within the optimal F-DHC demonstrate evident improvement of crashworthiness compared to their respective initial designs, indicating aluminum foam-filling combined with Taguchi-GRA could be an effective approach for multi-objective robust optimization of the novel crash box and other similar vehicle structures.

Abstract Background Addison’s disease which is due to dysfunction of the adrenal gland, with abnormal secretion of glucocorticoids and mineralocorticoids, is rare. By inducing inflammation and disorders of water and electrolyte metabolism, Addison’s disease may accelerate progression of co-existed cardiovascular diseases. Addison’s disease combined with cardiovascular disease is infrequent, only 10 cases in the literature. Case presentation We reported a 51-year-old male patient with unstable angina pectoris and hypotension. Changes on coronary angiography within 2 years suggested rapid progression of coronary artery disease in a patient with low cardiovascular risk. An additional clue of skin hyperpigmentation, fatigue and further examination confirmed the diagnosis of Addison’s disease caused by adrenal tuberculosis. After hormone replacement treatment, the frequency and severity of the angina pectoris were alleviated significantly, as were hypotension, hyperpigmentation and fatigue. Conclusions The combination of Addison’s disease and coronary artery disease in one patient is rare. Addison’s disease can induce inflammation and disorders of water and electrolyte metabolism, which may further accelerate the course of coronary artery disease. Meanwhile, the hypotension in Addison’s disease may affect the coronary blood flow, which may result in an increased susceptibility to unstable angina in the presence of coronary stenosis. So, we should analyze comprehensively if the coronary artery disease progress rapidly.

Abstract Atractylodes lancea rhizome (AR) has high medicinal and economic value. A previous study has reported that the accumulation of sesquiterpenoids in AR has obvious advantages under bamboo canopy. A concrete shade value to promote the cultivation of high-quality AR has not been established. In this study, 80% shading was screened at six different light intensities (100%, 80%, 60%, 40%, 20%, 7%), and the mechanism was explored in terms of photosynthetic efficiency and phytohormones levels. The results indicated that the total sesquiterpenoid content of 80% mild shading increased by 58%, 52%, and 35%, respectively, compared to 100% strong light in seedling, expansion, and harvest stages and increased by 144%, 178%, and 94%, respectively, compared with 7% low light. The sesquiterpenoids hinesol and β-eudesmol contributed approximately 70% to the differential contribution ratio between mild shading and strong light (100%) or between mild shading and low light (7%). Furthermore, HMGR, DXR, and FPPS genes, which regulate sesquiterpenoid synthesis, were significantly upregulated in 80% mild shading. Transpiration rate; the intercellular CO2 concentration; net photosynthetic rate; and levels of jasmonic acid, abscisic acid, and gibberellin were strongly correlated (r > 0.85) with sesquiterpenoid accumulation. Cis-acting elements responding to light and phytohormones were present within the promoter regions of HMGR, DXR, and FPPS. Therefore, 80% shading promotes the synthesis and accumulation of sesquiterpenoids in AR by regulating photosynthetic efficiency and phytohormone production, thereby promoting transcriptional expression.

Minimizing toxicity of herpes simplex virus 1 (HSV) based tools for anterograde tracing is important for functional studies. Here the authors generate an anterograde monosynaptic tracer system based on HSV amplicon, which shows fast tracing, bright labeling, low toxicity, input-defined postsynaptic neurons’ anterograde monosynaptic tracing feature, and has potential for functional mapping.

Abstract Background Long non-coding RNA (lncRNA) LINC00460 is an onco-lncRNA in a variety of cancers, including pancreatic cancer (PC). This study is aimed to investigate the regulatory mechanisms of LINC00460 in PC. Methods The tumor and adjacent normal tissues were collected from 73 PC patients. The expression of LINC00460, miR-503-5p, and ANLN was detected using qRT-PCR. We then analyzed the proliferation, migration, invasion, and apoptosis/cell cycle of PC cells by performing the MTT/EdU, transwell, and flow cytometry assays, respectively. The xenograft tumor model were utilized to confirm the effect of LINC00460 knockdown on PC through anti-PD-1 therapy in vivo, and the sensitivity of PANC-1 cells to the cytotoxicity of CD8+ T cells in vitro. Western blotting was used to determine the protein levels. A co-culture model was utilized to explore the effects of exosomes on macrophages. Results LINC00460 was up-regulated in PC tissues and cells. LINC00460 knockdown suppressed cell proliferation, migration, and invasion, facilitated cell apoptosis and G0/G1 phase arrest, and inhibited the tumor growth through anti-PD-1 therapy. Both miR-503-5p down-regulation and ANLN up-regulation reversed the effects of LINC00460 knockdown on inhibiting the proliferation, migration and invasion, and on promoting the apoptosis, G0/G1 phase arrest, and the sensitivity of PC cells to the cytotoxicity of CD8+ T cells. Exosomes were uptaken by the ambient PC cells. PANC-1 cells-derived exosomal LINC00460-induced M2 macrophage polarization accelerates the cell migration and invasion. Conclusions LINC00460 silencing attenuates the development of PC by regulating the miR-503-5p/ANLN axis and exosomal LINC00460-induced M2 macrophage polarization accelerates the migration and invasion of PANC-1 cells, thus LINC00460 may act as a possible therapeutic target for treating PC.

Abstract Background Regulation of gene expression plays an essential role in controlling the phenotypes of plants. Brassica napus (B. napus) is an important source for the vegetable oil in the world, and the seed oil content is an important trait of B. napus. Results We perform a comprehensive analysis of the transcriptional variability in the seeds of B. napus at two developmental stages, 20 and 40 days after flowering (DAF). We detect 53,759 and 53,550 independent expression quantitative trait loci (eQTLs) for 79,605 and 76,713 expressed genes at 20 and 40 DAF, respectively. Among them, the local eQTLs are mapped to the adjacent genes more frequently. The adjacent gene pairs are regulated by local eQTLs with the same open chromatin state and show a stronger mode of expression piggybacking. Inter-subgenomic analysis indicates that there is a feedback regulation for the homoeologous gene pairs to maintain partial expression dosage. We also identify 141 eQTL hotspots and find that hotspot87-88 co-localizes with a QTL for the seed oil content. To further resolve the regulatory network of this eQTL hotspot, we construct the XGBoost model using 856 RNA-seq datasets and the Basenji model using 59 ATAC-seq datasets. Using these two models, we predict the mechanisms affecting the seed oil content regulated by hotspot87-88 and experimentally validate that the transcription factors, NAC13 and SCL31, positively regulate the seed oil content. Conclusions We comprehensively characterize the gene regulatory features in the seeds of B. napus and reveal the gene networks regulating the seed oil content of B. napus.

Abstract Background Curcuminoids (CURs) are the principal ingredients of Curcuma longa L. [Zingiberaceae] (CL)—an herbal plant used in east Asia to alleviate pain and inflammation. Thus far, the therapeutic effects of CURs for knee osteoarthritis (OA) uncovered by multiple reviews remained uncertain due to broadly involving trials with different agents-combined or CURs-free interventions. Therefore, we formed stringent selection criteria and assessment methods to summarize current evidence on the efficacy and safety of CURs alone in the treatment of knee OA. Methods A series of databases were searched for randomized controlled trials (RCTs) evaluating the efficacy and safety of CURs for knee OA. Clinical outcomes were evaluated using meta-analysis and the minimum clinically important difference (MCID) for both statistical and clinical significance. Results Fifteen studies with 1670 patients were included. CURs were significantly more effective than placebo in the improvements of VAS for pain ( WMD: − 1.77, 95% CI: − 2.44 to − 1.09), WOMAC total score ( WMD: − 7.06, 95% CI: − 12.27 to − 1.84), WOMAC pain score ( WMD: − 1.42, 95% CI: − 2.41 to − 0.43), WOMAC function score ( WMD: − 5.04, 95% CI: − 7.65 to − 2.43), and WOMAC stiffness score ( WMD: − 0.54, 95% CI: − 1.03 to − 0.05). Meanwhile, CURs were not inferior to NSAIDs in the improvements of pain- and function-related outcomes. Additionally, CURs did not significantly increase the incidence of adverse events (AEs) compared with placebo ( RR: 1.03, 95% CI: 0.69 to 1.53, P = 0.899, I2 = 23.7%) and NSAIDs (RR: 0.71 0.65, 95% CI: 0.57 0.41 to 0.90 1.03). Conclusions CURs alone can be expected to achieve considerable analgesic and functional promotion effects for patients with symptomatic knee OA in short term, without inducing an increase of adverse events. However, considering the low quality and substantial heterogeneity of present studies, a cautious and conservative recommendation for broader clinical use of CURs should still be made. Further high-quality studies are necessary to investigate the impact of different dosages, optimization techniques and administration approaches on long-term safety and efficacy of CURs, so as to strengthen clinical decision making for patients with symptomatic knee OA.

In this paper, the different dumping process (0, 3, 7, 15, 30 d) of Zhenjiang vinegar was studied in order to better control the quality. The contents of total acid, reducing sugar, nonvolatile acid, amino acid nitrogen, organic acid, amino acid and volatile substances in different dumping processes were analyzed. The results showed that the contents of total acid, nonvolatile acid and lactic acid in vinegar were significantly (P