ABSTRACT
Plants evolved sophisticated machineries to monitor levels of external nitrogen supply, respond to nitrogen demand from different tissues and integrate this information for coordinating its assimilation. Although roles of inorganic nitrogen in orchestrating developments have been studied in model plants and crops, systematic understanding of the origin and evolution of its assimilation and signaling machineries remains largely unknown. We expanded taxon samplings of algae and early-diverging land plants, covering all main lineages of Archaeplastida, and reconstructed the evolutionary history of core components involved in inorganic nitrogen assimilation and signaling. Most components associated with inorganic nitrogen assimilation were derived from the ancestral Archaeplastida. Improvements of assimilation machineries by gene duplications and horizontal gene transfers were evident during plant terrestrialization. Clusterization of genes encoding nitrate assimilation proteins might be an adaptive strategy for algae to cope with changeable nitrate availability in different habitats. Green plants evolved complex nitrate signaling machinery that was stepwise improved by domains shuffling and regulation co-option. Our study highlights innovations in inorganic nitrogen assimilation and signaling machineries, ranging from molecular modifications of proteins to genomic rearrangements, which shaped developmental and metabolic adaptations of plants to changeable nutrient availability in environments.
Subject(s)
Nitrates , Nitrogen , Nitrates/metabolism , Nitrogen/metabolism , Signal Transduction , Crops, Agricultural/metabolismABSTRACT
CuIn(SxSe1-x)2 nanocrystals as an emerging class of functional materials present huge potential for industrial applications; however, the synthesis of CuIn(SxSe1-x)2 nanocrystals remains a formidable challenge in achieving both tunable band gap and phase. Here, we reported a facile hot-injection method for synthesizing a family of wurtzite CuIn(SxSe1-x)2 nanocrystals, enabling manipulation of the S and Se contents across the entire compositional range (0 ≤ x ≤ 1). The obtained nanocrystals exhibit band gaps ranging from 1.21 to 1.58 eV, which vary depending on the S/Se ratios in the products. This approach can be readily extended to other scenarios involving chalcogenide nanomaterials, thereby facilitating the advancement of next-generation functional materials and applications.
ABSTRACT
The subfamilies Salassinae and Agliinae are two monogeneric groups of the family Saturniidae. They were regarded as the non-cocooning saturniids in Asia. Since very little information on their life history and mitogenome has been reported, their origin and evolution are still poorly understood. In this study, nature-imitated rearing is used to record the life history of two Aglia and five Salassa species. In addition, four complete mitogenomes are presented, which are the first ones of these two subfamilies. The results show that both Salassinae and Agliinae have lost their cocooning. Moreover, the phylogenetic analysis demonstrates that the subfamily Saturniinae is not monophyletic due to the inclusion of Agliinae and Salassinae.
Subject(s)
Genome, Mitochondrial , Lepidoptera , Animals , Lepidoptera/genetics , Phylogeny , Insecta , AsiaABSTRACT
Thermal mechanical responses under high temperature and high pressure are basic information to understand the performance of energetic materials. In this work, the pressure effects on the thermal decay of 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) are explored. Up to the initial pressure of 4.6 GPa, the pressure dependent decomposition boundary is built and no phase transition occurs until the decomposition of the LLM-105 crystal. The decomposition temperature is significantly lifted via a weak loading pressure. The experimental measurement confirms the decomposition products, including NO2, CO2 and NH3, which are predicted by the density functional tight-binding molecular dynamics method. The calculation described the details of thermal decay in the initial stages under high pressure. The sudden drop in the shifts of the Raman modes associated with hydrogen bonds under high pressure indicates the strengthening of the intermolecular hydrogen bonds and the occurrence of intermolecular hydrogen transfer prior to crystal decomposition. The simulation supported the existence of intermolecular hydrogen transfer and provided the transfer path and decomposition mechanism. All of these jobs not only contribute significantly to the understanding of thermal decomposition of energetic materials as a function of pressure, but also contribute to the understanding of sensitivity mechanisms and safety issues.
ABSTRACT
Van der Waals (vdW) chemistry in simple molecular systems may be important for understanding the structure and properties of the interiors of the outer planets and their satellites, where pressures are high and such components may be abundant. In the current study, Raman spectra and visual observation are employed to investigate the phase separation and composition determination for helium-nitrogen mixtures with helium concentrations from 20 to 95% along the 295 K isothermal compression. Fluid-fluid-solid triple-phase equilibrium and several equilibria of two phases including fluid-fluid and fluid-solid have been observed in different helium-nitrogen mixtures upon loading or unloading pressure. The homogeneous fluid in helium-nitrogen mixtures separates into a helium-rich fluid (F1) and a nitrogen-rich fluid (F2) with increasing pressure. The triple-phase point occurs at 295 K and 8.8 GPa for a solid-phase (N2)11He vdW compound, fluid F1 with around 50% helium, and fluid F2 with 95% helium. Helium concentrations of F1 coexisted with the (N2)11He vdW compound or δ-N2 in helium-nitrogen mixtures with different helium concentrations between 40 and 50% and between 20 and 40%, respectively. In addition, the helium concentration of F2 is the same in helium-nitrogen mixtures with different helium concentrations and decreases upon loading pressure. Pressure-induced nitrogen molecule ordering at 32.6 GPa and a structural phase transition at 110 GPa are observed in (N2)11He. In addition, at 187 GPa, a pressure-induced transition to an amorphous state is identified.
ABSTRACT
CONTEXT: Sevoflurane (Sev) is a commonly used surgical anaesthetic; it has neurotoxic effects on the brain. Echinatin (Ech) is reported to have anti-inflammatory and antioxidant activity. OBJECTIVE: This research confirms the effect of Ech on Sev-induced neurotoxicity and cognitive deficits. MATERIALS AND METHODS: Primary rat hippocampal neurons were treated with 4.1% Sev for 6 h in the presence of Ech (5, 10, and 20 µM) or vehicle, followed by a further 42 h of culture. Male Sprague-Dawley aged rats were divided into 6 groups (n = 6): control, Sev, Sev + Ech (20 mg/kg;), Sev + Ech (40 mg/kg), and Sev + Ech (80 mg/kg). Rats were intraperitoneally injected with Ech or vehicle 1 h before Sev exposure (2% Sev for 5 h). RESULTS: We found that Ech (5, 10, and 20 µM) elevated cell viability (1.29-, 1.51-, 1.68-fold) but mitigated apoptosis (23.87% vs. 16.48%, 12.72%, 9.02%), oxidative stress, and ferroptosis in hippocampal neurons with Sev treatment. Ech activated the Nrf2 expression in Sev-induced in vitro and in vivo models of anaesthetic neurotoxicity. Ech also weakened neurotoxicity in hippocampal neurons with Sev treatment by increasing Nrf2 expression level. Moreover, Ech alleviated hippocampus neurons apoptosis (19.38% vs. 16.05%, 11.71%, 8.88%), oxidative stress, and ferroptosis in rats with Sev treatment. Ech improved Sev-induced cognitive deficits in rats. CONCLUSIONS: Ech alleviates Sev-induced neurotoxicity and cognitive deficits by mitigation of ferroptosis and oxidative stress. Ech may be developed as a new promising therapeutic drug for treatment of cerebral nerve injury caused by surgical anaesthesia.
Subject(s)
Iron Overload , Neurotoxicity Syndromes , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Apoptosis , Chalcones , Cognition , Hippocampus , Iron Overload/metabolism , Male , NF-E2-Related Factor 2/metabolism , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/metabolism , Neurotoxicity Syndromes/prevention & control , Oxidative Stress , Rats , Rats, Sprague-Dawley , Sevoflurane/metabolism , Sevoflurane/toxicityABSTRACT
Diabetic ED (DMED) is a sexual dysfunction disease accompanied by poor blood sugar control, which is a most common organic ED clinically, with the lesions of the nervous system as the most important pathological mechanism in the process of its occurrence. Ferroptosis is a new form of autophagy-dependent cell death involved in the development and progression of a variety of diseases and closely related to the death of nerve cells. The ferroptosis pathway has been conformed to be involved in the mechanism of neuromodulation of DMED, which can be used as an important basis for the treatment of the disease. Studies have shown that some herbal extracts can inhibit the ferroptosis pathway of nerve cells. This review summarizes the neuroprotective mechanism of traditional Chinese medicine extracts in the treatment of DMED by inhibiting the ferroptosis pathway of nerve cells, and provides a theoretical foundation for future clinical treatment of the disease.
Subject(s)
Diabetes Mellitus , Erectile Dysfunction , Ferroptosis , Male , Humans , Erectile Dysfunction/drug therapy , Medicine, Chinese TraditionalABSTRACT
Background: Dual-energy computed tomography (CT) can provide a range of image information beyond conventional CT through virtual monoenergetic images (VMIs). The purpose of this study was to investigate the impact of material decomposition in detector-based spectral CT on radiomics features and effectiveness of using deep learning-based image synthesis to improve the reproducibility of radiomics features. Methods: In this paper, spectral CT image data from 45 esophageal cancer patients were collected for investigation retrospectively. First, we computed the correlation coefficient of radiomics features between conventional kilovoltage peak (kVp) CT images and VMI. Then, a wavelet loss-enhanced CycleGAN (WLL-CycleGAN) with paired loss terms was developed to synthesize virtual monoenergetic CT images from the corresponding conventional single-energy CT (SECT) images for improving radiomics reproducibility. Finally, the radiomic features in 6 different categories, including gray-level co-occurrence matrix (GLCM), gray-level difference matrix (GLDM), gray-level run-length matrix (GLRLM), gray-level size-zone matrix (GLSZM), neighborhood gray-tone difference matrix (NGTDM), and wavelet, were extracted from the gross tumor volumes from conventional single energy CT, synthetic virtual monoenergetic CT images, and virtual monoenergetic CT images. Comparison between errors in the VMI and synthetic VMI (sVMI) suggested that the performance of our proposed deep learning method improved the radiomic feature accuracy. Results: Material decomposition of dual-layer dual-energy CT (DECT) can substantially influence the reproducibility of the radiomic features, and the degree of impact is feature dependent. The average reduction of radiomics errors for 15 patients in testing sets was 96.9% for first-order, 12.1% for GLCM, 12.9% for GLDM, 15.7% for GLRLM, 50.3% for GLSZM, 53.4% for NGTDM, and 6% for wavelet features. Conclusions: The work revealed that material decomposition has a significant effect on the radiomic feature values. The deep learning-based method reduced the influence of material decomposition in VMIs and might improve the robustness and reproducibility of radiomic features in esophageal cancer. Quantitative results demonstrated that our proposed wavelet loss-enhanced paired CycleGAN outperforms the original CycleGAN.
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Amylopectin and amylose components are natural polymers within rice starch granules, intertwined in specific conditions to form gel polymerized with pore crosslink network, has potential printing properties. In this study, a rice starch gel preparation scheme is proposed for stable properties, and starch granule phase transition mechanism is analyzed based on RVA test during preparation, it can be divided into four-stage, swelling, reacting, homogenizing and self-assembling stages. Gel surface tension and contact angle tested with starch concentration effect, a correlation is developed, reflecting a competition result to gel droplet macro-morphology between the intermolecular cohesion and crosslink network. SEM is used to reveal typical crosslink structures of different starch molecular component proportions, providing objective support for starch gel rheologic property change. Results indicate gel interior crosslink network formed under concentration 12 %, the gel with amylose 4.475 % presents better printing accuracy. Gel shear modulus positively correlated with amylose proportion. Japonica gel under 20 % is of higher viscosity and rapid reassembly ability after interior crosslink network is broken. Max dynamic viscosity is positively correlated with starch concentration. The study aims to provide theoretical and practical support for in-depth analysis of rice starch material application in direct-write 3D printing.
ABSTRACT
Brown rice over-milling causes high economic and nutrient loss. The rice degree of milling (DOM) detection and prediction remain a challenge for moderate processing. In this study, a self-established grain image acquisition platform was built. Degree of bran layer remaining (DOR) datasets is established with image capturing and processing (grain color, texture, and shape features extraction). The mapping relationship between DOR and the DOM is in-depth analyzed. Rice grain DOR typical machine learning and deep learning prediction models are established. The results indicate that the optimized Catboost model can be established with cross-validation and grid search method, with the best accuracy improving from 84.28% to 91.24%, achieving precision 91.31%, recall 90.89%, and F1-score 91.07%. Shapley additive explanations analysis indicates that color, texture, and shape feature affect Catboost prediction accuracy, the feature importance: color > texture > shape. The YCbCr-Cb_ske and GLCM-Contrast features make the most significant contribution to rice milling quality prediction. The feature importance provides theoretical and practical guidance for grain DOM prediction model. PRACTICAL APPLICATION: Rice milling degree prediction and detection are valuable for rice milling process in practical application. In this paper, image processing and machine learning methods provide an automated, nondestructive, and cost-effective way to predict the quality of rice. The study may serve as a valuable reference for improving rice milling methods, retaining rice nutrition, and reducing broken rice yield.
Subject(s)
Food Handling , Machine Learning , Oryza , China , Color , Edible Grain/chemistry , Food Handling/methods , Image Processing, Computer-Assisted/methods , Oryza/chemistryABSTRACT
As an oncogenic phosphatase, SHP2 acts as a converging node in the RTK-RAS-MAPK signaling pathway in cancer cells and suppresses antitumor immunity by passing signals downstream of PD-1. Here, we utilized the extra druggable pocket outside the previously identified SHP2 allosteric tunnel site by the (6,5 fused), 6 spirocyclic system. The optimized compound, JAB-3312, exhibited a SHP2 binding Kd of 0.37 nM, SHP2 enzymatic IC50 of 1.9 nM, KYSE-520 antiproliferative IC50 of 7.4 nM and p-ERK inhibitory IC50 of 0.23 nM. For JAB-3312, an oral dose of 1.0 mg/kg QD was sufficient to achieve 95% TGI in KYSE-520 xenograft model of mouse. JAB-3312 was well-tolerated in animal models, and a close correlation was observed between the plasma concentration of JAB-3312 and the p-ERK inhibition in tumors. Currently, JAB-3312 is undergoing clinical trials as a potential anticancer agent.
Subject(s)
Antineoplastic Agents , Protein Tyrosine Phosphatase, Non-Receptor Type 11 , Humans , Animals , Protein Tyrosine Phosphatase, Non-Receptor Type 11/antagonists & inhibitors , Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/chemical synthesis , Mice , Allosteric Regulation/drug effects , Cell Line, Tumor , Structure-Activity Relationship , Xenograft Model Antitumor Assays , Cell Proliferation/drug effects , Drug Discovery , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/therapeutic use , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacokinetics , Mice, Nude , Female , Neoplasms/drug therapyABSTRACT
Castor oil has been widely used in various fields due to its properties, leading to large attention for its extraction mechanism. To research the castor oil extraction mechanism during pressing, a self-developed uniaxial compression device combined with an in situ observation is established. The effects of pressure, loading speed, and creep time are investigated, and a finite element model coupling with multi-physics is established for castor oil pressing extraction, verified by the seed cake experimental compression strain matching with numerical simulation under the same condition. Simulation results indicated that the pressing oil extraction process can be divided into two stages, Darcy's speed shows the first sharp decreasing stage and the second gradual increasing stage during porosity and pressure interaction. In the first stage, porosity is dominant on Darcy's speed. With porosity decreasing, the pressure effect on Darcy's speed exceeds porosity in the second stage. With seed thickness increasing, Darcy's speed first increases and then decreases. With loading speed increasing, Darcy's speed increases. Darcy's speed decreases constantly with creep time increasing. This study can provide basic theoretical and practical guidance for oil extraction.
Subject(s)
Castor Oil , Pressure , Castor Oil/chemistry , Porosity , Food Handling/methods , Seeds/chemistry , Computer SimulationABSTRACT
PD-1 is a co-inhibitory receptor expressed by CD8+ T cells which limits their cytotoxicity. PD-L1 expression on cancer cells contributes to immune evasion by cancers, thus, understanding the mechanisms that regulate PD-L1 protein levels in cancers is important. Here we identify tumor-cell-expressed otubain-2 (OTUB2) as a negative regulator of antitumor immunity, acting through the PD-1/PD-L1 axis in various human cancers. Mechanistically, OTUB2 directly interacts with PD-L1 to disrupt the ubiquitination and degradation of PD-L1 in the endoplasmic reticulum. Genetic deletion of OTUB2 markedly decreases the expression of PD-L1 proteins on the tumor cell surface, resulting in increased tumor cell sensitivity to CD8+ T-cell-mediated cytotoxicity. To underscore relevance in human patients, we observe a significant correlation between OTUB2 expression and PD-L1 abundance in human non-small cell lung cancer. An inhibitor of OTUB2, interfering with its deubiquitinase activity without disrupting the OTUB2-PD-L1 interaction, successfully reduces PD-L1 expression in tumor cells and suppressed tumor growth. Together, these results reveal the roles of OTUB2 in PD-L1 regulation and tumor evasion and lays down the proof of principle for OTUB2 targeting as therapeutic strategy for cancer treatment.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , T-Lymphocytes, Cytotoxic/metabolism , CD8-Positive T-Lymphocytes , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , B7-H1 Antigen/metabolism , Cell Line, Tumor , Programmed Cell Death 1 Receptor/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Pharmaceutical Preparations/metabolism , Thiolester Hydrolases/metabolismABSTRACT
Background and aims: There are few population studies on the associations of serum alkaline phosphatase (AlkP) with all-cause and cardiovascular mortality. We aimed to investigate the relevancy of serum AlkP with all-cause and cardiovascular mortality in the general population. Methods and results: Our research included 34,147 adults in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014. Cox proportional hazards regression models were used to assess the associations of serum AlkP with all-cause and cardiovascular mortality. Mediation analysis was used to analyze mechanisms that might link serum AlkP to all-cause and cardiovascular mortality. After 139.7 ± 57.8 months of follow-up, 5413 participants experienced all-cause death and 1820 participants experienced cardiovascular death. Mortality rates per 1000 person-years from various diseases increased with increasing serum concentrations of AlkP, especially all-cause death, cerebrovascular disease and cardiovascular death. High serum AlkP level significantly increased all-cause and cardiovascular mortality. After multivariate adjustment, the highest AlkP group had the highest risk to experience all-cause (hazard ratio [HR] = 1.30, P < 0.001) and cardiovascular mortality (HR = 1.39, P < 0.001) than the lowest AlkP group. γ-glutamyl transpeptidase (GGT) (13.33% and 15.79%), followed by Vitamin D (8.33% and 7.14%) and C-reactive protein (CRP) (7.69% and 10.35%) were identified as possible major mediators. Conclusion: Higher AlkP concentrations were associated with higher all-cause and cardiovascular mortality, largely related to mediated factors such as GGT, Vitamin D, and CRP. These findings suggest that lower serum AlkP level may reduce all-cause and cardiovascular mortality in general population.
Subject(s)
Alkaline Phosphatase , Cardiovascular Diseases , Adult , Humans , Nutrition Surveys , Cardiovascular Diseases/epidemiology , Risk Factors , Vitamin DABSTRACT
As a valuable Chinese traditional medicinal species, Chaenomeles speciosa (Sweet) Nakai (C. speciosa) is a natural resource with significant economic and ornamental value. However, its genetic information is not well understood. In this study, the complete mitochondrial genome of C. speciosa was assembled and characterized to explore the repeat sequences, recombination events, rearrangements, and IGT, to predict RNA editing sites, and to clarify the phylogenetic and evolutionary relationship. The C. speciosa mitochondrial genome was found to have two circular chromosomes as its major conformation, with a total length of 436,464 bp and 45.2% GC content. The mitochondrial genome contained 54 genes, including 33 unique protein-coding genes, 18 tRNAs, and 3 rRNA genes. Seven pairs of repeat sequences involving recombination events were analyzed. Both the repeat pairs, R1 and R2, played significant roles in mediating the major and minor conformations. In total, 18 MTPTs were identified, 6 of which were complete tRNA genes. There were 454 RNA editing sites in the 33 protein-coding sequences predicted by the PREPACT3 program. A phylogenetic analysis based on 22 species of mitochondrial genomes was constructed and indicated highly conserved PCG sequences. Synteny analyses showed extensive genomic rearrangements in the mitochondrial genome of C. speciosa and closely related species. This work is the first to report the C. speciosa mitochondrial genome, which is of great significance for conducting additional genetic studies on this organism.
Subject(s)
Genome, Mitochondrial , Rosaceae , Phylogeny , Biological Evolution , Genomics , Rosaceae/geneticsABSTRACT
The recent surge in plant genomic and transcriptomic data has laid a foundation for reconstructing evolutionary scenarios and inferring potential functions of key genes related to plants' development and stress responses. The classical scheme for identifying homologous genes is sequence similarity-based searching, under the crucial assumption that homologous sequences are more similar to each other than they are to any other non-homologous sequences. Advances in plant phylogenomics and computational algorithms have enabled us to systemically identify homologs/orthologs and reconstruct their evolutionary histories among distantly related lineages. Here, we present a comprehensive pipeline for homologous sequences identification, phylogenetic relationship inference, and potential functional profiling of genes in plants. Key features ⢠Identification of orthologs using large-scale genomic and transcriptomic data. ⢠This protocol is generalized for analyzing the evolution of plant genes.
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Vegetables are essential for maintaining health and preventing diseases due to their nutrients and functional components. However, vegetables specifically designed for blood sugar control are limited. The mulberry tree (Morus) offers potential as a source of functional vegetables with blood-sugar-lowering properties, mainly attributed to 1-Deoxynojirimycin (DNJ). This study compared the nutritional composition and DNJ content in various edible parts of twelve mulberry tree varieties. Sensory evaluations were also conducted to assess sensory attributes. Interestingly, DNJ was found to show a positive correlation with sensory evaluations. Furthermore, the sugar content, particularly sucrose, was significantly higher in tender shoots than leaves, indicating tender shoots as a preferable choice for development as a functional food for blood sugar control. Finally, VM 19 and VM 22 are considered as good candidates for the mulberry vegetable using varieties after sensory evaluation and combining with the DNJ content. These findings provide valuable insights for future research into vegetable selections for blood sugar management and support the potential commercialization of mulberry leaf vegetables as functional food options.
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The exploration of the microstructural evolution and reaction kinetics of energetic materials with high-temperature and high-pressure water contributes to the understanding of their microscopic physicochemical origin, which can provide critical experimental data for the use of energetic materials. As a promising high-energy and insensitive energetic material, LLM-105 has been investigated under extreme conditions such as high pressure and high temperature. However, little information is available about the effect of water on LLM-105 under high pressure and high temperature. In this work, the interaction between LLM-105 and water under HP-HT was investigated in detail. As a result, the dissolving behavior of LLM-105 in water under high pressure and high temperature is related to the initial pressure. When the initial pressure is less than 1 GPa, LLM-105 crystals are dissolved in high-temperature water; when the initial pressure is above 1 GPa, LLM-105 particles are only decomposed in high-temperature water. When the solution is saturated at a high temperature, recrystallization of the LLM-105 sample appears in the solution. High pressure hindered the dissolution process of the sample in HP-HT water because the interaction between the solute and the solvent was weakened by high pressure. The initial pressure is one of the significant parameters that determines whether LLM-105 crystals can be dissolved in high-temperature water. More importantly, water under high pressure and high temperature can not only act as a solvent when dissolving the samples but also act as a catalyst to accelerate the decomposition process. In addition, the HP-HT water reduced the decomposition temperature of the LLM-105 crystal to a large extent. The research in this paper not only provides insights into the interaction between LLM-105 and water but also contributes to the performance of energetic materials under extreme conditions and their practical applications in complex conditions.
ABSTRACT
OBJECTIVES: Intestinal inflammation and intestinal barrier dysfunction are two important pathological changes in Crohn's disease (CD). Sotetsuflavone (SF) is a natural monomeric herbal compound with anti-inflammatory and cytoprotective effects that is mostly nontoxic. The effect of SF on CD-like spontaneous colitis was investigated in this study. METHODS: Il-10-/- mice were used as a CD model and were administered different doses of SF. Lipopolysaccharide (LPS) plus IFN-γ-induced macrophages (RAW264.7) and a coculture system (RAW264.7 and organoids) were used in vitro. The protective effects of SF against CD-like colitis and macrophage differentiation and the mechanisms were evaluated. RESULTS: SF treatment markedly improved spontaneous colitis in the CD model, as shown by the following evidence: reductions in the DAI, macroscopic scores (3.63 ± 1.30), colonic tissue inflammatory scores (2 ± 0.76) and proinflammatory factor levels and the attenuation of colon shortening (8 ± 0.93 cm) and weight loss (1.75 ± 1.83 g). Decreased intestinal permeability and intestinal bacterial translocation rates provided evidence of the protective effect of SF on intestinal barrier function. We also found that SF suppressed M1 macrophage-induced inflammatory responses. In the coculture system of mouse colonic organoids and RAW264.7 cells, SF significantly ameliorated M1 macrophage-induced intestinal epithelial damage. In addition, SF inhibited JNK and MAPK (p38) signalling in both Il-10-/- mice and LPS plus IFN-γ-induced macrophages (RAW264.7). CONCLUSIONS: The protective effects of SF against CD-like colitis may be achieved partially by inhibiting M1 macrophage-induced intestinal barrier damage via JNK and p38 signalling. SF may have therapeutic potential for treating CD, especially considering its safety.
Subject(s)
Colitis , Crohn Disease , MAP Kinase Signaling System , Animals , Mice , Colitis/chemically induced , Colitis/drug therapy , Colitis/pathology , Colon/pathology , Crohn Disease/drug therapy , Cytokines/pharmacology , Dextran Sulfate/adverse effects , Interleukin-10 , Lipopolysaccharides/adverse effects , Macrophages , Mice, Inbred C57BLABSTRACT
In this study, we discovered a new virus named Quanzhou mulberry virus (QMV), which was identified from the leaves of an ancient mulberry tree. This tree is over 1300 years old and is located at Fujian Kaiyuan Temple, a renowned cultural heritage site in China. We obtained the complete genome sequence of QMV using RNA sequencing followed by rapid amplification of complementary DNA ends (RACE). The QMV genome is 9256 nucleotides (nt) long and encodes five open reading frames (ORFs). Its virion was made of icosahedral particles. Phylogenetic analysis suggests that it belongs to the unclassified Riboviria. An infectious clone for QMV was generated and agroinfiltrated into Nicotiana benthamiana and mulberry, resulting in no visible disease symptoms. However, systemic movement of the virus was only observed in mulberry seedlings, suggesting that it has a host-specific pattern of movement. Our findings provide a valuable reference for further studies on QMV and related viruses, contributing to the understanding of viral evolution and biodiversity in mulberry.