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ABSTRACT E3 ubiquitin ligase (E3) plays a vital role in regulating inflammatory responses by mediating ubiquitination. Previous studies have shown that ankyrin repeat and SOCS box-containing protein 3 (ASB3) is involved in immunomodulatory functions associated with cancer. However, the impact of ASB3 on the dynamic interplay of microbiota and inflammatory responses in inflammatory bowel disease (IBD) is unclear. Here, we systematically identify the E3 ligase ASB3 as a facilitative regulator in the development and progression of IBD. We observed that ASB3 exhibited significant upregulation in the lesions of patients with IBD. ASB3−/− mice are resistant to dextran sodium sulfate-induced colitis. IκBα phosphorylation levels and production of proinflammatory factors IL-1β, IL-6, and TNF-α were reduced in the colonic tissues of ASB3−/− mice compared to WT mice. This colitis-resistant phenotype was suppressed after coprophagic microbial transfer and reversed after combined antibiotics removed the gut commensal microbiome. Mechanistically, ASB3 specifically catalyzes K48-linked polyubiquitination of TRAF6 in intestinal epithelial cells. In contrast, in ASB3-deficient organoids, the integrity of the TRAF6 protein is shielded, consequently decelerating the onset of intestinal inflammation. ASB3 is associated with dysregulation of the colitis microbiota and promotes proinflammatory factors’ production by disrupting TRAF6 stability. Strategies to limit the protein level of ASB3 in intestinal epithelial cells may help in the treatment of colitis.IMPORTANCEUbiquitination is a key process that controls protein stability. We determined the ubiquitination of TRAF6 by ASB3 in intestinal epithelial cells during colonic inflammation. Inflammatory bowel disease patients exhibit upregulated ASB3 expression at focal sites, supporting the involvement of degradation of TRAF6, which promotes TLR-Myd88/TRIF-independent NF-κB aberrant activation and intestinal microbiota imbalance. Sustained inflammatory signaling in intestinal epithelial cells and dysregulated protective probiotic immune responses mediated by ASB3 collectively contribute to the exacerbation of inflammatory bowel disease. These findings provide insights into the pathogenesis of inflammatory bowel disease and suggest a novel mechanism by which ASB3 increases the risk of colitis. Our results suggest that future inhibition of ASB3 in intestinal epithelial cells may be a novel clinical strategy.

Previous research indicates that post-fault grid-forming (GFM) converters only work in current limiting control (CLC) mode. However, converters integrating the current saturation algorithm (CSA) can operate in both constant voltage control (CVC) and CLC modes. This paper firstly derives the angle-switched model of the grid-connected system governed by CSA and virtual synchronous generator (VSG). Then, combining the fault and three types of post-fault trajectories, critical clearing angle is analytically formulated through the Segmental Equal Area Criterion (SEAC). Finally, a range of values for the saturated current angle is proposed to ensure that the system is stabilized in CVC mode. Notably, the optimal saturated current angle, which is the minimum value within the range, provides the maximum critical clearing angle.

Abstract Here, the stability region of grid‐connected VSC with phase locked loop (PLL) is estimated. First, the conservative stability region is derived via the classical Lyapunov method. Then an energy function is constructed as the general stable condition for the VSC system. Based on the constructed energy function, two estimation methods of the system stability region by approximation of phase trajectory are proposed. The stability regions by the proposed methods are less conservative than that by the classical Lyapunov method. A stability evaluation function for the initial states of the VSC system is further proposed based on the estimated stability region. Time‐domain simulations verify the correctness of the proposed methods and the effectiveness of the stability evaluation function.

Abstract African swine fever virus (ASFV) is an important pathogen causing acute infectious disease in domestic pigs and wild boars that seriously endangers the global swine industry. As ASFV is structurally complex and encodes a large number of functional proteins, no effective vaccine has been developed to date. Thus, dissecting the mechanisms of immune escape induced by ASFV proteins is crucial. A previous study showed that the ASFV-encoded protein is an important factor in host immunity. In this study, we identified a negative regulator, MGF505-3R, that significantly downregulated cGAS/STING- and poly (dG:dC)-mediated IFN-β and interferon stimulation response element (ISRE) reporter activity and suppressed IFNB1 and IFIT2 mRNA levels. In addition, TBK1, IRF3 and IκBα phosphorylation levels were also inhibited. Mechanistically, MGF505-3R interacted with cGAS/TBK1/IRF3 and targeted TBK1 for degradation, thereby disrupting the cGAS-STING-mediated IFN-β signaling pathway, which appears to be highly correlated with autophagy. Knockdown MGF505-3R expression enhanced IFN-β and IL-1β production. Taken together, our study revealed a negative regulatory mechanism involving the MGF505-3R-cGAS-STING axis and provided insights into an evasion strategy employed by ASFV that involves autophagy and innate signaling pathways.

Zbtb1 (zinc finger and BTB domain containing 1) is a member of mammalian zbtb gene family. A series of bioinformatics analysis was carried out for the EL4 cell and the Zbtb1-deficient EL4 cell by Hi-C, ATAC-seq and RNA-seq techniques. Finally, Hi-C results showed that the intensity of chromatin interaction in the deletion group decreased with distance, the degree of chromosome interaction decreased significantly, the AB division region changed significantly, and the compactness of TAD structure decreased; The results of ATAC-seq showed that the open area and degree of chromatin in the deletion group decreased; 7778 differentially expressed mRNAs were found by RNA-seq. Our experimental results for the first time expounded the significance of Zbtb1 gene for T cell development, lymphocyte production and apoptosis from the aspects of chromosome spatial structure and chromatin opening degree, and provided relevant theoretical basis and data support for the in-depth study of related Zbtb1 genes in the future.

In previous experiments, we identified the effect of deletion of the Zbtb1 gene on circRNAs and microRNAs. In this study, we examined the expression profiles of lncRNAs and mRNAs using the RNA-seq method for Zbtb1-deficient EL4 cells and performed a clustering analysis of differentially expressed lncRNAs and mRNAs. GO term histograms and KEGG scatter plots were drawn. For the experimental results, a joint analysis was performed, which predicted the regulatory relationships among lncRNAs, mRNAs, microRNAs and circRNAs. For the regulatory relationship between lncRNAs and target genes, the chromatin structure and the degree of openness were verified for the possible target gene locations regulated by lncRNA using experimental methods such as Hi-C and ATAC-seq. Ultimately, the possible differential regulation of the Brcal and Dennd5d genes by lncRNAs and the differential changes in transcription factor binding sites in the promoter region were identified. For neRNA-regulated target genes with significantly differentially expressed mRNAs, a combined screen was performed, and the final obtained candidate target genes were subjected to GO and KEGG term enrichment analyses. Our results illustrate that the Zbtb1 gene can not only function as a regulatory factor but also regulate EL4 cells from multiple perspectives based on ceRNA theory.

Due to its distinct capability to improve the efficiency of shale gas production, supercritical carbon dioxide (SC-CO2) fracturing has attracted increased attention in recent years. Heat transfer occurs in the transportation and fracture processes. To better predict and understand the heat transfer of SC-CO2 near the critical region, numerical simulations focusing on a vertical flow pipe were performed. Various turbulence models and turbulent Prandtl numbers (Prt) were evaluated to capture the heat transfer deterioration (HTD). The simulations show that the turbulent Prandtl number model (TWL model) combined with the Shear Stress Transport (SST) k-ω turbulence model accurately predicts the HTD in the critical region. It was found that Prt has a strong effect on the heat transfer prediction. The HTD occurred under larger heat flux density conditions, and an acceleration process was observed. Gravity also affects the HTD through the linkage of buoyancy, and HTD did not occur under zero-gravity conditions.

Green mining and the formation of an effective and efficient development model have become key issues that aggregates enterprises around the world need to solve urgently. On the basis of analyzing the development status of aggregates industry in Xiluodu area, the paper studied the main problems faced in the construction of green aggregates mines at present, and proposed a "three-in-one" ecological, intelligent and efficient green mine construction model for "ecological development", "green logistics" and "solid waste recycling" of aggregates. The study has certain theoretical value and practical significance for the construction of green aggregates mine in Xiluodu area. [ABSTRACT FROM AUTHOR]

The non-uniform usage of synonymous codons occurs in genomes of all organisms, including DNA and RNA viruses. The preferential selection of a codon at the expense of other synonymous codons within the same group is known as Codon Usage Bias. The understanding of this bias assists in unveiling the factors driving molecular evolution, as defined by the selection-mutationdrift theory. According to this model, molecular evolution is predominantly driven by mutation, natural selection, and genetic drift. Nevertheless, elements like nucleotide composition, gene length, and protein secondary structure also contribute to this process. Comprehensive genomic analyses that highlight the codon usage preference of the African Swine Fever Virus (ASFV) are infrequent. ASFV, a hemorrhagic and highly contagious viral disease, almost invariably results in 100% fatality among infected pigs and wild boars. This study, therefore, embarked on a thorough examination of codon usage patterns in ASFV's complete genomic sequences, an endeavor of great relevance to molecular evolution studies, complex transmission models, and vaccine research. For an exhaustive evaluation of ASFV's whole-genome codon usage, we used parameters like ENC, RSCU, and CAI. A Principal Component Analysis was carried out to reaffirm the interconnected RSCU lineages based on the continent, and their evolutionary relationships were later elucidated through phylogenetic tree construction. ASFV emerged as a low-biased codon user (ENC = 52.8) that is moderately adapted to its host. Its genome has a high AT composition (64.05%), suggesting the impact of mutational pressure on genomic evolution. However, neutrality plot analysis revealed natural selection's slight supremacy over mutational pressure. The low codon bias (>45) implies ASFV's diverse usage of synonymous codons within a given codon family, allowing for effective translation and subsequent successful viral replication cycles. Its moderate. [ABSTRACT FROM AUTHOR]

Abstract Introduction Conditioned pain modulation (CPM) is a quantitative estimation of the capacity for endogenous pain modulation. Reduced CPM enables chronic painful event development or exacerbates pre-existing pain symptoms. Emerging reports indicate that patients with trigeminal neuralgia (TN) have dysregulated endogenous pain modulation. Transauricular vagus nerve stimulation (taVNS) is known to alleviate both acute and chronic pain symptoms. Its role in modulation or management of TN remains unknown. Here, we evaluated the taVNS efficacy in modulating CPM among TN patients. Conclusions from this investigation may facilitate establishment of novel non-invasive adjunctive approaches to treating TN patients. Methods All research work was conducted at the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital). In all, we recruited 62 study participants, 31 TN patients and 31 healthy volunteers, for a 2-day experimental test. At the beginning of the experiment (Day 1), all subjects received 30 min of active taVNS. On Day 2, they received sham taVNS with the same duration and intensity. Meanwhile, technicians documented participant pressure pain thresholds (PPT) and CPM values at baseline, and at 15 and 30 min post-active or sham taVNS. Results A 30-min active taVNS exposure substantially elevated the PPT and CPM effect (P

Since Coppersmith proposed the use of the LLL algorithm to solve univariate modular polynomial equations at EUROCRYPT’96, it has sparked a fervent research interest in lattice analysis among cryptographers. Despite its polynomial-time nature, the LLL algorithm exhibits a high-order polynomial upper bound in terms of theoretical complexity, particularly with longer computation times when applied to high-dimensional lattices. In addressing this issue, we propose an improved algorithm based on block preprocessing, building on the original Coppersmith algorithm and thus providing proof of correctness for this algorithm. This approach effectively reduces the solution time of the algorithm, offering a maximum improvement of 8.1% compared to the original Coppersmith algorithm. Additionally, we demonstrate the compatibility of our algorithm with the rounding algorithm proposed at PKC 2014. The combined utilization of these approaches further enhances the efficiency of our algorithm. The experimental results show that the combined algorithm achieves a maximum improvement of 22.4% in solution time compared to the original Coppersmith algorithm. It also outperforms the standalone rounding algorithm with a maximum improvement of 12.1%. When compared to the improved Coppersmith algorithm based on row common factor extraction, our proposed algorithm demonstrates comparable or even superior performance in certain dimensions. The block preprocessing algorithm in our approach enables independent execution without data exchange, making it suitable for leveraging multi-processing advantages in scenarios involving higher degrees of modular polynomial equations. This offers a new perspective for achieving the parallel computation of the Coppersmith algorithm, facilitating parallel execution and providing valuable insights.

Abstract Background Bletilla striata is the main medicine of many skin whitening classic formulas in traditional Chinese medicine (TCM) and is widely used in cosmetic industry recently. However, its active ingredients are still unclear and its fibrous roots are not used effectively. The aim of the present study is to discover and identify its potential anti-melanogenic active constituents by zebrafish model and molecular docking. Methods The antioxidant activities were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, 2,2′-azino-bis-(3-ethylbenthiazoline-6-sulphonic acid) (ABTS) radical scavenging activity and ferric reducing antioxidant power (FRAP) assay. The anti-melanogenic activity was assessed by tyrosinase inhibitory activity in vitro and melanin inhibitory in zebrafish. The chemical profiles were performed by ultra-high-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Meanwhile, the potential anti-melanogenic active constituents were temporary identified by molecular docking. Results The 95% ethanol extract of B. striata fibrous roots (EFB) possessed the strongest DPPH, ABTS, FRAP and tyrosinase inhibitory activities, with IC50 5.94 mg/L, 11.69 mg/L, 6.92 mmol FeSO4/g, and 58.92 mg/L, respectively. In addition, EFB and 95% ethanol extract of B. striata tuber (ETB) significantly reduced the melanin synthesis of zebrafish embryos in a dose-dependent manner. 39 chemical compositions, including 24 stilbenoids were tentatively identified from EFB and ETB. Molecular docking indicated that there were 83 (including 60 stilbenoids) and 85 (including 70 stilbenoids) compounds exhibited stronger binding affinities toward tyrosinase and adenylate cyclase. Conclusion The present findings supported the rationale for the use of EFB and ETB as natural skin-whitening agents in pharmaceutical and cosmetic industries.

Vehicular ad hoc networks (VANETs) are the communication foundation for future intelligent transportation systems and guarantee safe driving of intelligent networked vehicles. Moreover, VANETs face a series of security challenges related to the protection of vehicle privacy, authenticity of transmitted information, and bandwidth limitations. To resolve these contradictions, many certificateless aggregate signature (CLAS) schemes have been proposed. However, the majority of them can neither resist malicious-but-passive key generation center attacks, replay attacks, and link attacks, nor track the actual identities of malicious vehicles. Meanwhile, the security of previous CLAS schemes in VANETs is only formally provided in the random oracle model (ROM), which might be insecure in actual implementation. In addition, most CLAS schemes still have problems of large verification delays and high communication overhead. To address the above-mentioned problems, a new conditional privacy-preserving CLAS scheme in VANETs is proposed, which adopts full aggregation technology to reduce computation and bandwidth resources. According to the formal security proofs under the computational Diffie-Hellman problem (CDHP) given in the standard model (SM), the security level of this scheme is higher than that of other CLAS schemes under ROM in practical applications. Additionally, the use of pseudonym mechanism realizes conditional privacy protection in VANETs. The performance analysis shows that this scheme has a higher efficiency in terms of computation and communication overhead compared with several previous CLAS schemes.

Asthma is a common chronic disease that is characterized by respiratory symptoms including cough, wheeze, shortness of breath, and chest tightness. The underlying mechanisms of this disease are not fully elucidated, so more research is needed to identify better therapeutic compounds and biomarkers to improve disease outcomes. In this present study, we used bioinformatics to analyze the gene expression of adult asthma in publicly available microarray datasets to identify putative therapeutic molecules for this disease. We first compared gene expression in healthy volunteers and adult asthma patients to obtain differentially expressed genes (DEGs) for further analysis. A final gene expression signature of 49 genes, including 34 upregulated and 15 downregulated genes, was obtained. Protein–protein interaction and hub analyses showed that 10 genes, including POSTN, CPA3, CCL26, SERPINB2, CLCA1, TPSAB1, TPSB2, MUC5B, BPIFA1, and CST1, may be hub genes. Then, the L1000CDS2 search engine was used for drug repurposing studies. The top approved drug candidate predicted to reverse the asthma gene signature was lovastatin. Clustergram results showed that lovastatin may perturb MUC5B expression. Moreover, molecular docking, molecular dynamics simulation, and computational alanine scanning results supported the notion that lovastatin may interact with MUC5B via key residues such as Thr80, Thr91, Leu93, and Gln105. In summary, by analyzing gene expression signatures, hub genes, and therapeutic perturbation, we show that lovastatin is an approved drug candidate that may have potential for treating adult asthma.

Due to its distinct capability to improve the efficiency of shale gas production, supercritical carbon dioxide (SC-CO2) fracturing has attracted increased attention in recent years. Heat transfer occurs in the transportation and fracture processes. To better predict and understand the heat transfer of SC-CO2 near the critical region, numerical simulations focusing on a vertical flow pipe were performed. Various turbulence models and turbulent Prandtl numbers (Prt) were evaluated to capture the heat transfer deterioration (HTD). The simulations show that the turbulent Prandtl number model (TWL model) combined with the Shear Stress Transport (SST) k-w turbulence model accurately predicts the HTD in the critical region. It was found that Prt has a strong effect on the heat transfer prediction. The HTD occurred under larger heat flux density conditions, and an acceleration process was observed. Gravity also affects the HTD through the linkage of buoyancy, and HTD did not occur under zero-gravity conditions. [ABSTRACT FROM AUTHOR]

The issue of how to improve the usability of data publishing under differential privacy has become one of the top questions in the field of machine learning privacy protection, and the key to solving this problem is to allocate a reasonable privacy protection budget. To solve this problem, we design a privacy budget allocation algorithm based on out-of-bag estimation in random forest. The algorithm firstly calculates the decision tree weights and feature weights by the out-of-bag data under differential privacy protection. Secondly, statistical methods are introduced to classify features into best feature set, pruned feature set, and removable feature set. Then, pruning is performed using the pruned feature set to avoid decision trees over-fitting when constructing an ϵ-differential privacy random forest. Finally, the privacy budget is allocated proportionally based on the decision tree weights and feature weights in the random forest. We conducted experimental comparisons with real data sets from Adult and Mushroom to demonstrate that this algorithm not only protects data security and privacy, but also improves model classification accuracy and data availability.

When analyzing a block cipher, the first step is to search for some valid distinguishers, for example, the differential trails in the differential cryptanalysis and the linear trails in the linear cryptanalysis. A distinguisher is advantageous if it can be utilized to attack more rounds and the amount of the involved key bits during the key-recovery process is small, as this leads to a long attack with a low complexity. In this article, we propose a two-step strategy to search for such advantageous distinguishers. This strategy is inspired by the intuition that if a differential is advantageous only when some properties are satisfied, then we can predefine some constraints describing these properties and search for the differentials in the small set. As applications, our strategy is used to analyze GIFT-128, which was proposed in CHES 2017. Based on some 20-round differentials, we give the first 27-round differential attack on GIFT-128, which covers one more round than the best previous result. Also, based on two 17-round linear trails, we give the first linear hull attack on GIFT-128, which covers 22 rounds. In addition, we also give some results on two GIFT-128 based AEADs GIFT-COFB and SUNDAE-GIFT.

Introduction: Lindera aggregata is a main Chinese herb of ancient prescriptions Suoquan pill applied for treating the chronic kidney disease (CKD). A large number of application histories of Lindera aggregata in the treatment of CKD have been recorded in Chinese traditional medical literature. The previous reports revealed that Lindera aggregata can treat CKD. Methods: Rats were randomly divided into control, model, Huangkui,Lindera aggregata ethanol extract (LEE) and Lindera aggregata water extract (LWE) groups. hematoxylin-eosin (HE) staining was used to detect the pathology of kidney. The levels of serum creatinine (Scr), serum Neutrophil gelatinase-associated lipocalin (NGAL), blood urea nitrogen (BUN), urine protein (UP), kidney index(KI) were evaluated. The UPLC − QTOF/MS were applied to probe the metabolic profile. Furthermore, Indoxyl sulfate-induced human renal tubular epithelial (HK-2) cell model was built to determine the expression levels of pathogenesis-related proteins. Results: The results demonstrated that LEE and LWE significantly inhibited the rebound in Scr, BUN, NGAL, UP and KI in models, except for the effect of LWE at low dose (LWE-L) and LEE at low dose (LEE-L) on KI and the effect of LWE-H at high dose (LWE-H) and LEE-L on BUN and NGAL. Moreover,Lindera aggregata extracts alleviated renal tubular dilatation, interstitial fibrosis and interstitial inflammation. By analysis, twenty-eight metabolites were related to CKD. After intervention of Lindera aggregata extracts, some metabolites approach to a normal-like level, such as Indoxyl sulfate. These metabolites are mainly involved in tryptophan, fatty acid, glycerophospholipid, tyrosine and arachidonic acid metabolic pathways. Furthermore, Lindera aggregata extracts mediate the expression of smad2, smad3, smad7 and TGF-β in Indoxyl sulfate-induced HK-2 cell. Conclusions: Lindera aggregata extracts can mitigate adenine-induced CKD by modulating the metabolic profile and TGF-β/Smad signaling pathway, providing important supports for developing protective agent of Lindera aggregata for CKD.

In maintaining organismal homeostasis, gut immunity plays a crucial role. The coordination between the microbiota and the immune system through bidirectional interactions regulates the impact of microorganisms on the host. Our research focused on understanding the relationships between substantial changes in jejunal intestinal flora and metabolites and intestinal immunity during porcine epidemic diarrhea virus (PEDV) infection in piglets. We discovered that Lactobacillus rhamnosus GG (LGG) could effectively prevent PEDV infection in piglets. Further investigation revealed that LGG metabolites interact with type 3 innate lymphoid cells (ILC3s) in the jejunum of piglets through the aryl hydrocarbon receptor (AhR). This interaction promotes the activation of ILC3s and the production of interleukin-22 (IL-22). Subsequently, IL-22 facilitates the proliferation of IPEC-J2 cells and activates the STAT3 signaling pathway, thereby preventing PEDV infection. Moreover, the AhR receptor influences various cell types within organoids, including intestinal stem cells (ISCs), Paneth cells, and enterocytes, to promote their growth and development, suggesting that AhR has a broad impact on intestinal health. In conclusion, our study demonstrated the ability of LGG to modulate intestinal immunity and effectively prevent PEDV infection in piglets. These findings highlight the potential application of LGG as a preventive measure against viral infections in livestock. IMPORTANCE We observed high expression of the AhR receptor on pig and human ILC3s, although its expression was negligible in mouse ILC3s. ILC3s are closely related to the gut microbiota, particularly the secretion of IL-22 stimulated by microbial signals, which plays a crucial regulatory role in intestinal immunity. In our study, we found that metabolites produced by beneficial gut bacteria interact with ILC3s through AhR, thereby maintaining intestinal immune homeostasis in pigs. Moreover, LGG feeding can enhance the activation of ILC3s and promote IL-22 secretion in the intestines of piglets, ultimately preventing PEDV infection. [ABSTRACT FROM AUTHOR]

A suitable mutual authentication protocol for an RFID system should provide mutual authentication along with user privacy. In addition, such protocol must be resistant to active and passive attacks, e.g. man-in-the-middle attack, replay attack, reader-/tag-impersonation attack, denial of service attack and traceability attack. Among them, tag-impersonation attack refers to a forgery attack in which the adversary fools the legitimate reader to authenticate it as a valid tag. In this paper we exam the security of three RFID mutual authentication protocols which have been recently proposed by Luo et al., Shen et al. and Habibi and Gardeshi, under tag impersonation attack. We found that these three protocols share a same vulnerability – in each session, the tag and the reader generate a random value respectively and they use the exclusive-or (XOR) of those random values in the authentication process. We exploit this vulnerability to present effective and efficient tag impersonation attacks against these protocols, e.g., the success probabilities of our attacks are “1” and the complexity is at most two runs of each protocol. In addition, we exhibit the improved version of these protocols, which are immune from tag impersonation attacks.

Pseudostellariae Radix (PR) is an important traditional Chinese medicine (TCM), which is consumed commonly for its positive health effects. However, the chemical differences of PR from different cultivated fields and germplasms are still unknown. In order to comprehensively compare the chemical compositions of PR from different cultivated fields, in this study, 1H-NMR-based metabolomics coupled with high performance liquid chromatography (HPLC) were used to investigate the different metabolites in PR from five germplasms (jr, zs1, zs2, sb, and xc) cultivated in traditional fields (Jurong, Jiangsu, JSJR) and cultivated fields (Zherong, Fujian, FJZR). A total of 34 metabolites were identified based on 1H-NMR data, and fourteen of them were found to be different in PR from JSJR and FJZR. The relative contents of alanine, lactate, lysine, taurine, sucrose, tyrosine, linolenic acid, γ-aminobutyrate, and hyperoside in PR from JSJR were higher than that in PR from FJZR, while PR from FJZR contained higher levels of glutamine, raffinose, xylose, unsaturated fatty acid, and formic acid. The contents of Heterophyllin A and Heterophyllin B were higher in PR from FJZR. This study will provide the basic information for exploring the influence law of ecological environment and germplasm genetic variation on metabolite biosynthesis of PR and its quality formation mechanism.

Scrophulariae Radix is one of the most popular traditional Chinese medicines (TCMs), which needs to be processed by ‘sweating’ methods. Primary processing of Scrophulariae Radix is an important link which closely relates to the quality of products in this TCM. To facilitate selection of the suitable ‘sweating’ processing method for Scrophulariae Radix, in this study the quality of Scrophulariae Radix processed by different ‘sweating’ methods was evaluated based on simultaneous determination of multiple bioactive constituents combined with grey relational analysis. The contents of iridoid glycosides, phenylpropanoid glycosides, and organic acids in Scrophulariae Radix processed by different ‘sweating’ methods were simultaneously determined using ultra high performance liquid chromatography coupled with triple quadrupole-linear ion trap mass spectrometry (UPLC-QTRAP-MS/MS). Furthermore, grey relational analysis (GRA) was performed to evaluate the ‘sweating’ processed samples according to the contents of twelve constituents. All of the results demonstrated that the quality of Scrophulariae Radix processed by oven drying at 35 °C and ‘sweating’ for three days was better. The developed method was useful for the overall assessment on quality of Scrophulariae Radix, and this study may provide the foundation and support for ‘sweating’ processing of Scrophulariae Radix in normalization and standardization.

African swine fever (ASF) is a devastating infectious disease of pigs caused by the African swine fever virus (ASFV), which poses a great danger to the global pig industry. Many viral proteins can suppress with interferon signaling to evade the host's innate immune responses. Therefore, the development of an effective vaccine against ASFV has been dampened. Recent studies have suggested that the L83L gene may be integrated into the host genome, weakening the host immune system, but the underlying mechanism is unknown. Our study found that L83L negatively regulates the cGAS-STINGmediated type I interferon (IFN-I) signaling pathway. Overexpression of L83L inhibited IFNb promoter and ISRE activity, and knockdown of L83L induced higher transcriptional levels of interferon-stimulated genes (ISGs) and phosphorylation levels of IRF3 in primary porcine alveolar macrophages. Mechanistically, L83L interacted with cGAS and STING to promote autophagy-lysosomal degradation of STING by recruiting Tollip, thereby blocking the phosphorylation of the downstream signaling molecules TBK1, IRF3, and Ik Ba and reducing IFN-I production. Altogether, our study reveals a negative regulatory mechanism involving the L83L-cGAS-STING-IFN-I axis and provides insights into an evasion strategy involving autophagy and innate signaling pathways employed by ASFV. IMPORTANCE African swine fever virus (ASFV) is a large double-stranded DNA virus that primarily infects porcine macrophages. The ASFV genome encodes a large number of immunosuppressive proteins. Current options for the prevention and control of this pathogen remain pretty limited. Our study showed that overexpression of L83L inhibited the cGASSTING-mediated type I interferon (IFN-I) signaling pathway. In contrast, the knockdown of L83L during ASFV infection enhanced IFN-I production in porcine alveolar macrophages. Additional analysis revealed that L83L protein downregulated IFN-I signaling by recruiting Tollip to promote STING autophagic degradation. Although L83L deletion has been reported to have little effect on viral replication, its immune evade mechanism has not been elucidated. The present study extends our understanding of the functions of ASFVencoded pL83L and its immune evasion strategy, which may provide a new basis for developing a live attenuated vaccine for ASF. [ABSTRACT FROM AUTHOR]