摘要：
Cancer immunotherapy, particularly with immune checkpoint inhibitors, has revolutionized the paradigm of cancer treatment. Nevertheless, the efficacy of cancer immunotherapy remains limited in most clinical settings due to the lack of a preexisting antitumor T-cell response in tumors. Therefore, the clinical outcomes of cancer immunotherapy must be improved crucially. With increased awareness of the importance of the innate immune response in the recruitment of T cells, as well as the onset and maintenance of the T cell response, great interest has been shown in activating the cGAS-STING signaling pathway to awaken the innate immune response, thereby orchestrating both innate and adaptive immune responses to induce tumor clearance. However, tumor cells have evolved to overexpress ectonucleotide pyrophosphate phosphodiesterase 1 (ENPP1), which degrades the immunotransmitter 2',3'-cGAMP and promotes the production of immune-suppressing adenosine, resulting in inhibition of the anticancer immune response in the tumor microenvironment. Clinically, ENPP1 overexpression is closely associated with poor prognosis in patients with cancer. Conversely, depleting or inhibiting ENPP1 has been verified to elevate extracellular 2',3'-cGAMP levels and inhibit the generation of adenosine, thereby reinvigorating the anticancer immune response for tumor elimination. A variety of ENPP1 inhibitors have recently been developed and have demonstrated significant promise for cancer immunotherapy. In this review, we provide an overview of ENPP1, dissect its immunosuppressive mechanisms, and discuss the development of ENPP1 inhibitors with the potential to further improve the efficacy of cancer immunotherapy.
摘要：
In this study, the speciation, leachability, phytoaccessibility, and environmental risks of heavy metals (Cd, Zn, and Cu) during liquefaction of contaminated peanut straw in ethanol at different temperatures (220, 260, 300, 340, and 380 degrees C) were comprehensively investigated. The results showed that elevated temperatures facilitated heavy metal accumulation in the biochar. The acid-soluble/exchangeable and reducible fraction percentages of heavy metals were substantially reduced in the biochar after liquefaction as the temperature increased, and the oxidizable fraction became the dominant heavy metal fraction, accounting for 44.14-78.67%. Furthermore, although an excessively high liquefaction temperature (380 degrees C) increased the residual fraction percentages of Zn and Cu, it was detrimental to Cd immobilization. The acid-soluble/exchangeable Cd in the contaminated peanut straw readily migrates to the bio-oil during liquefaction, with the highest concentration of 1.60 mg/kg at 260 degrees C liquefaction temperature, whereas Zn and Cu are predominantly bound to the unexchangeable fraction in the bio-oil. Liquefaction inhibited heavy metal leachability and phytoaccessibility in biochar, the lowest extraction rates of Cd, Zn, and Cu were 0.71%, 1.66% and 0.95% by diethylenetriamine pentaacetic acid, respectively. However, the leaching and extraction concentrations increased when the temperature was raised to 380 degrees C. Additionally, heavy metal risk was reduced from medium and high risk to no and low risk. In summary, liquefaction reduces heavy metal toxicity and the risks associated with contaminated peanut straw, and a temperature range of 300-340 degrees C for ethanol liquefaction can be considered optimal for stabilizing heavy metals.
摘要：
The color of the seed coat has great diversity and is regarded as a biomarker of metabolic variations. Here we isolated a soybean variant (BLK) from a population of recombinant inbred lines with a black seed coat, while its sibling plants have yellow seed coats (YL). The BLK and YL plants showed no obvious differences in vegetative growth and seed weight. However, the BLK seeds had higher anthocyanins and flavonoids level and showed tolerance to various abiotic stresses including herbicide, oxidation, salt, and alkalinity during germination. Integrated metabolomic and transcriptomic analyses revealed that the upregulation of biosynthetic genes probably contributed to the overaccumulation of flavonoids in BLK seeds. The transient expression of those biosynthetic genes in soybean root hairs increased the levels of total flavonoids or anthocyanins. Our study revealed the molecular basis of flavonoid accumulation in soybean seeds, leveraging genetic engineering for both nutritious and stress-tolerant soybean germplasm.
作者机构：
[Liu, Gang; Liu, Naiyuan; Liu, Zhuangzhuang; Zhao, Jinfeng; Fang, Jun; Wang, Keyu] Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha 410128, Hunan, Peoples R China.;[Liu, Gang; Liu, Naiyuan; Liu, Zhuangzhuang; Zhao, Jinfeng; Fang, Jun; Wang, Keyu] Hunan Engn Lab Pollut Control & Waste Utilizat Swi, Changsha 410128, Peoples R China.;[Yao, Hao] Changsha IMADEK Intelligent Technol Co Ltd, Changsha, Peoples R China.;[Pan, Junting] Chinese Acad Agr Sci, Inst Agr Resources & Reg Planning, State Key Lab Efficient Utilizat Arid & Semiarid A, Beijing 100081, Peoples R China.
通讯机构：
[Fang, J ] H;Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha 410128, Hunan, Peoples R China.;Hunan Engn Lab Pollut Control & Waste Utilizat Swi, Changsha 410128, Peoples R China.
关键词：
Meta genomic analysis;Network analysis;Rice straw-mushroom compost;Sawdust-rice husk compost
摘要：
This study aimed to assess the impact of microbial agent and different compost material, on physicochemical parameters dynamic change, nitrogen-transfer gene/bacterial community interaction network during the pig manure composting. Incorporating a microbial agent into rice straw-mushroom compost reduced the NH(3) and total ammonia emissions by 25.52% and 14.41%, respectively. Notably, rice straw-mushroom with a microbial agent reduced the total ammonia emissions by 37.67%. NH(4)(+)-N and pH emerged as primary factors of phylum-level and genus-level microorganisms. Microbial agent increased the expression of narG, nirK, and nosZ genes. Rice straw-mushroom elevated the content of amoA, nirK, nirS, and nosZ genes. Alcanivorax, Luteimonas, Pusillimonas, Lactobacillus, Aequorivita, Clostridium, Moheibacter and Truepera were identified as eight core microbial genera during the nitrogen conversion process. This study provides a strategy for reducing ammonia emissions and analyzes the potential mechanisms underlying compost processes.
期刊：
FRONTIERS IN IMMUNOLOGY,2024年14:1289795 ISSN：1664-3224
通讯作者：
Zhu, Ying;Liu, S
作者机构：
[Zhu, Ying; Liu, Shi; Xu, Ke; Zhou, Li; Yu, Chen; Yan, Huan; Liu, S; Ma, Caijiao; Luo, Chuanjin; Zhu, Y; Nie, Longyu; Zhu, Qingmei] Wuhan Univ, Coll Life Sci, State Key Lab Virol Modern Virol Res Ctr, State Key Lab Virol,Modern Virol Res Ctr, Wuhan, Peoples R China.;[Liu, Shi; Lu, Zhibing; Liu, S; Cai, Huanhuan] Wuhan Univ, Inst Myocardial Injury & Repair, Wuhan, Peoples R China.;[Lu, Zhibing; Cai, Huanhuan] Wuhan Univ, Zhongnan Hosp, Wuhan, Peoples R China.;[Liu, Shi; Wang, Qiming; Liu, S] Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha, Hunan, Peoples R China.;[Liu, Shi; Wang, Fubing; Liu, S] Chinese Acad Med Sci, Wuhan Res Ctr Infect Dis & Canc, Wuhan, Peoples R China.
通讯机构：
[Liu, S ; Zhu, Y] W;Wuhan Univ, Coll Life Sci, State Key Lab Virol Modern Virol Res Ctr, State Key Lab Virol,Modern Virol Res Ctr, Wuhan, Peoples R China.;Wuhan Univ, Inst Myocardial Injury & Repair, Wuhan, Peoples R China.;Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha, Hunan, Peoples R China.;Chinese Acad Med Sci, Wuhan Res Ctr Infect Dis & Canc, Wuhan, Peoples R China.
关键词：
HCC;MVP;STAT6;TAMs;TME;polarization
摘要：
Tumor-associated macrophages (TAMs) are critical in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). Major vault protein (MVP) mediates multidrug resistance, cell growth and development, and viral immunity. However, the relationship between MVP and TAMs polarization has not been clarified in HCC. We found that MVP significantly increased M2-TAMs infiltration levels in tumor tissues of HCC patients. MVP promoted HCC proliferation, metastasis, and invasion by regulating M2 polarization in vivo and in vitro. Mechanistically, MVP associated with signal transducer and activator of transcription 6 (STAT6) and enhanced STAT6 phosphorylation. STAT6 translocated from the cytosol to the nucleus and regulated M2 macrophage-associated gene transcription. These findings suggest that MVP modulates the macrophage M2 transcriptional program, revealing its potential role in the TAMs of TME.
摘要：
Soil salinity seriously hinders the sustainable development of green agriculture. The emergence of engineered nanomaterials has revolutionized agricultural research, providing a new means to overcome the limitations associated with current abiotic stress management and achieve highly productive agriculture. Herein, we synthesized a brand-new engineered nanomaterial (Cs-Se NMs) through the Schiff base reaction of oxidized chitosan with selenocystamine hydrochloride to alleviate salt stress in plants. After the addition of 300 mg/L Cs-Se NMs, the activity of superoxide dismutase, catalase, and peroxidase in rice shoots increased to 3.19, 1.79, and 1.85 times those observed in the NaCl group, respectively. Meanwhile, the MDA levels decreased by 63.9%. Notably, Cs-Se NMs also raised the transcription of genes correlated with the oxidative stress response and MAPK signaling in the transcriptomic analysis. In addition, Cs-Se NMs augmented the abundance and variety of rhizobacteria and remodeled the microbial community structure. These results provide insights into applying engineered nanomaterials in sustainable agriculture.
摘要：
Understanding how phytoplankton interacts with local and regional drivers as well as their feedbacks is a great challenge, and quantitative analyses of the regulating role of human activities and climate changes on these feedback loops are also limited. By using monthly monitoring dataset (2000-2017) from Lake Taihu and empirical dynamic modelling to construct causal networks, we quantified the strengths of causal feedbacks among phytoplankton, local environments, zooplankton, meteorology as well as global climate oscillation. Prevalent bidirectional causal linkages between phytoplankton biomass (chlorophyll a) and the tested drivers were found, providing holistic and quantitative evidence of the ubiquitous feedback loops. Phytoplankton biomass exhibited the highest feedbacks with total inorganic nitrogen and ammonia and the lowest with nitrate. The feedbacks between phytoplankton biomass and environmental factors from 2000 to 2017 could be classified into two groups: the local environments (e.g., nutrients, pH, transparency, zooplankton biomass)-driven enhancement loops promoting the response of the phytoplankton biomass, and the climate (e.g., wind speed)-driven regulatory loops suppressing it. The two counterbalanced groups modified the emergent macroecological patterns. Our findings revealed that the causal feedback networks loosened significantly after 2007 following nutrient loading reduction and unsuccessful biomanipulation restoration attempts by stocking carp. The strength of enhancement loops underwent marked decreases leading to reduced phytoplankton responses to the tested drivers, while the climate (decreasing wind speed, warming winter)-driven regulatory loops increased- like a tug-of-war. To counteract the self-amplifying feedback loops, the present eutrophication mitigation efforts, especially nutrient reduction, should be continued, and introduction of alternative measures to indirectly regulate the critical components (e.g., pH, Secchi depth, zooplankton biomass) of the loops would be beneficial.
作者机构：
[Xiong, Xiaoran; Pan, Weisong; Kong, Zhicheng] College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, Hunan, China;[Xiong, Xiaoran; Pan, Weisong; Kong, Zhicheng] Hunan Engineering Research Center for Cell Mechanics and Functional Analysis, Changsha 410128, Hunan, China;[Wu, Chuan] Hunan Novomore Biotechnology Co., Ltd., Changsha 410000, Hunan, China
关键词：
molecular farming;plant bioreactor;protein purification;recombinant protein
摘要：
Plant bioreactor is a new production platform for expression of recombinant protein, which is one of the cores of molecular farming. In this study, the anti DYKDDDDK (FLAG) antibody was recombinantly expressed in tobacco (Nicotiana benthamiana) and purified. FLAG antibody with high affinity was obtained after immunizing mice for several times and its sequence was determined. Based on this, virus vectors expressing heavy chain (HC) and light chain (LC) inoculated into Nicotiana benthamiana leaves by using Agrobacterium-mediated delivery. Accumulation of the HC and LC was analyzed by SDS/PAGE followed by Western blotting probed with specific antibodies from 2 to 9 days postinfiltration (dpi). Accumulation of the FLAG antibody displayed at 3 dpi, and reached a maximum at 5 dpi. It was estimated that 66 mg of antibody per kilogram of fresh leaves could be obtained. After separation and purification, the antibody was concentrated to 1 mg/mL. The 1:10 000 diluted antibody can probe with 1 ng/mL FLAG fused antigen well, indicating the high affinity of the FLAG antibody produced in plants. In conclusion, the plant bioreactor is able to produce high affinity FLAG antibodies, with the characteristics of simplicity, low cost and highly added value, which contains enormous potential for the rapid and abundant biosynthesis of antibodies.
期刊：
Current Microbiology,2024年81(1):1-8 ISSN：0343-8651
通讯作者：
Pan, H;Pan, Hu;Tian, Y
作者机构：
[Dai, Yan-na; Pan, H; Zhang, Yi-fan; Pan, Hu; Pu, Ji-feng] Tibet Acad Agr & Anim Husb Sci, Inst Agr Qual Stand & Testing, Lhasa 850032, Peoples R China.;[Tian, Yun; Liu, Hu-hu; Tian, Y; Pan, Hu; Pan, H] Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha 410128, Peoples R China.;[Dai, Yan-na; Pan, H; Zhang, Yi-fan; Pan, Hu; Pu, Ji-feng] Agr & Livestock Prod Engn Technol Res Ctr Tibet Au, Lhasa 850032, Peoples R China.;[Yang, Xiao-feng] Sichuan Acad Agr Sci, Inst Agr Qual Stand & Testing Technol, Chengdu 610066, Peoples R China.
通讯机构：
[Pan, H ] T;[Tian, Y ; Pan, H] H;Tibet Acad Agr & Anim Husb Sci, Inst Agr Qual Stand & Testing, Lhasa 850032, Peoples R China.;Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha 410128, Peoples R China.;Agr & Livestock Prod Engn Technol Res Ctr Tibet Au, Lhasa 850032, Peoples R China.
摘要：
A novel Gram-stain-negative, aerobic, rod-shaped bacterium named T808(T) was isolated from an alpine soil in Qamdo, Tibet, PR China. Strain T808(T) grew at 5-30degree celsius, pH 5.0-9.0 (optimum, 25degree celsius and pH 7.0-8.0) with 0-2% (w/v) NaCl (optimum, 0%). The 16S rRNA gene sequences of strain T808(T) showed the highest similarity with Pararhizobium herbae CCBAU83011(T) (98.8%), followed by Pararhizobium polonicum F5.1(T) (98.7%), Pararhizobium giardinii H152(T) (98.5%), Rhizobium gei ZFJT-2( T) (98.4%), and Pararhizobium antarcticum NAQVI59(T) (97.5%). The highest digital DNA-DNA hybridization (dDDH), core-proteome average amino acid identity (cpAAI) and average nucleotide identity (ANI) values between strain T808(T) and related strains were estimated as 28.0%, 92.1% and 84.4%, respectively. Phylogenetic analysis based on 16S rRNA, core-proteome and whole-genome indicated that strain T808(T) belonged to the genus Pararhizobium. The genome size was 6.24 Mbp with genomic DNA G + C content of 60.1%. The major cellular fatty acids were Summed feature 8 (C-18:1 omega 7c or C-18:1 omega 6c), C-16:0 and C-19:0 cyclo omega 8c. The polar lipids were diphosphatidyl glycerol, phosphatidyl glycerol, phosphatidyl ethanolamine, phosphatidyl choline and unidentified aminophospholipid. The isoprenoid quinone were ubiquinone-10 and ubiquinone-9. Based on phenotypic, phylogenetic, and genotypic data, strain T808(T) is considered to represent a novel species of the genus Pararhizobium, for which the name Pararhizobium qamdonense sp. nov. is proposed. The type strain is T808(T) (= JCM 36247( T) = CICC 25216( T)). According to phylogenetic coherence based on 16S rRNA, core-proteome and whole-genome, it is also proposed that the type strain Rhizobium gei Shi et al. 2016 should be reclassified as Pararhizobium gei comb. nov., the type strain is ZFJT-2( T) (= CCTCC AB 2013015( T) = KCTC 32301( T) = LMG 27603( T)).
作者机构：
[Zhang, Ya; Zhou, Leyin; Zeng, Hao] College of Plant Protection, Hunan Agricultural University, Changsha 410128, China;[Wang, Chong] College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China;[Yang, Xiao] Key Laboratory of Land Surface Pattern and Simulation, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing 100101, China;[Liu, Shuangqing] College of Plant Protection, Hunan Agricultural University, Changsha 410128, China. Electronic address: liushuangqing@hunau.edu.cn
通讯机构：
[Shuangqing Liu] C;College of Plant Protection, Hunan Agricultural University, Changsha 410128, China
摘要：
Phenazine-1-carboxylic acid (PCA) is a new type of agrochemical used to prevent plant diseases, but its effects on aquatic organisms are unclear. To comprehensively assess the impacts of PCA for aquatic organisms and its associated environmental risks, this study investigated, taking zebrafish as the research object, the toxicological mechanism of PCA by means of optical microscopy, hematoxylin and eosin (HE) staining, ultrastructural observation, physiological and biochemical testing, transcriptome sequencing, metabolome analysis, fluorescence quantitative PCR and molecular simulation. The results indicated that PCA was detrimental to zebrafish embryos, larvae and adults, with LC(50) values at 96h of 3.9093mg/L, 8.5075mg/L, and 13.6388mg/L, respectively. PCA caused abnormal spontaneous movement, slowed the heart rate, delayed hatching, shortened the body length, slowed growth, and caused malformations. PCA mainly affected the brain, liver, heart, and ovaries. PCA distorted cell morphology, damaged mitochondrial membranes, disintegrated mitochondrial ridges, and dissociated nuclear membranes. PCA inhibited the enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX), decreased the malondialdehyde (MDA) content and disrupted antioxidant effects. The results of omics studies confirmed that PCA interfered with the transcriptional and metabolic network of zebrafish, downregulating most genes and metabolites. PCA mainly affected functions related to mitochondrial steroids, lipids, sterols, oxidoreductase activity and pathways involving cofactors, steroids, porphyrin, cytochromes, which specifically bound to targets such as panx3, agmat, and ace2. PCA was moderately toxic to zebrafish, and its usage should be strictly controlled to reduce toxic effects on aquatic organisms. The results of this study provide a new insights for ecotoxicology research.
摘要：
Recycling livestock manure in agroecosystems can maintain crop production, improve soil fertility, and reduce environmental losses. However, there has been no comprehensive assessment of synergies and trade-offs in the food-energy-soil-environment nexus under manure application. Here, we evaluate the sustainability of maize production under four fertilization regimes (mineral, mineral and manure mixed, manure, and no fertilization) from the aspect of food security, energy output, soil quality, and environmental impact based on a five-year field experiment. Manure and mineral mixed fertilization maintained grain and straw quantity and quality compared with mineral fertilization. Manure and mineral mixed fertilization increased stem/leaf ratio and field residue index by 9.1-28.9% and 4.5-17.9%, respectively. Manure also maintained the theoretical ethanol yield but reduced the straw biomass quality index by increasing ash. Further, manure application increased the soil quality index by 40.5% and reduced N(2)O emissions by 55.0% compared with mineral fertilization. Manure application showed the highest sustainability performance index of 19, followed by mineral (15), mixed (13), and without fertilization (8). In conclusion, manure application maintains food production and energy output, enhances soil quality, and reduces environmental impact, thereby improving the sustainability of maize production.
摘要：
In traditional Chinese medicine, Angelica dahurica is a valuable herb with numerous therapeutic applications for a range of ailments. There have not yet been any articles on the methodical assessment and choice of the best reference genes for A. dahurica gene expression studies. Real-time quantitative PCR (RT-qPCR) is widely employed as the predominant method for investigating gene expression. In order to ensure the precise determination of target gene expression outcomes in RT-qPCR analysis, it is imperative to employ stable reference genes. In this study, a total of 11 candidate reference genes including SAND family protein (SAND), polypyrimidine tract-binding protein (PTBP), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), TIP41-like protein (TIP41), cyclophilin 2 (CYP2), elongation factor 1 α (EF1α), ubiquitin-protein ligase 9 (UBC9), tubulin β-6 (TUB6), thioredoxin-like protein YLS8 (YLS8), and tubulin-α (TUBA) were selected from the transcriptome of A. dahurica. Subsequently, three statistical algorithms (geNorm, NormFinder, and BestKeeper) were employed to assess the stability of their expression patterns across seven distinct stimulus treatments. The outcomes obtained from these analyses were subsequently amalgamated into a comprehensive ranking using RefFinder. Additionally, one target gene, phenylalanine ammonia-lyase (PAL), was used to confirm the effectiveness of the selected reference genes. According to the findings of this study, the two most stable reference genes for normalizing the expression of genes in A. dahurica are TIP41 and UBC9. Overall, our research has determined the appropriate reference genes for RT-qPCR in A. dahurica and provides a crucial foundation for gene screening and identifying genes associated with the biosynthesis of active ingredients in A. dahurica.
作者机构：
[Zhang, Hongming; Ding, Yunyun; Jiang, Shuai; Chen, Fenglin; You, Changqiao; Zou, Xiaoxiao; Li, Zeqi] College of Biology, Hunan University, Changsha, 410082, China;[Ye, Shunxing] College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, 410128, China;[Li, Yongliang] College of Biology, Hunan University, Changsha, 410082, China. Electronic address: lyl13618481357@hnu.edu.cn;[Ge, Xingyi] College of Biology, Hunan University, Changsha, 410082, China. Electronic address: xyge@hnu.edu.cn;[Guo, Xinhong] College of Biology, Hunan University, Changsha, 410082, China. Electronic address: gxh@hnu.edu.cn
通讯机构：
[Yongliang Li; Xingyi Ge; Xinhong Guo] C;College of Biology, Hunan University, Changsha, 410082, China
关键词：
Complete genome sequences;Genetic tests;HCoVs;RNA barcode segments;SARS-CoV-2 variants and related lineages
摘要：
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for coronavirus disease 2019 (COVID-19), continues to evolve, giving rise to more variants and global reinfections. Previous research has demonstrated that barcode segments can effectively and cost-efficiently identify specific species within closely related populations. In this study, we designed and tested RNA barcode segments based on genetic evolutionary relationships to facilitate the efficient and accurate identification of SARS-CoV-2 from extensive virus samples, including human coronaviruses (HCoVs) and SARSr-CoV-2 lineages. Nucleotide sequences sourced from NCBI and GISAID were meticulously selected and curated to construct training sets, encompassing 1733 complete genome sequences of HCoVs and SARSr-CoV-2 lineages. Through genetic-level species testing, we validated the accuracy and reliability of the barcode segments for identifying SARS-CoV-2. Subsequently, 75 main and subordinate species-specific barcode segments for SARS-CoV-2, located in ORF1ab, S, E, ORF7a, and N coding sequences, were intercepted and screened based on single-nucleotide polymorphism sites and weighted scores. Post-testing, these segments exhibited high recall rates (nearly 100%), specificity (almost 30% at the nucleotide level), and precision (100%) performance on identification. They were eventually visualized using one and two-dimensional combined barcodes and deposited in an online database (http://virusbarcodedatabase.top/). The successful integration of barcoding technology in SARS-CoV-2 identification provides valuable insights for future studies involving complete genome sequence polymorphism analysis. Moreover, this cost-effective and efficient identification approach also provides valuable reference for future research endeavors related to virus surveillance.
关键词：
Clostridium butyricum;mycelium of Phellinus igniarius;colitis;intestinal flora;serum metabolome
摘要：
Clostridium butyricum (CB) and Phellinus igniarius (PI) have anti-inflammatory, immune regulation, anti-tumor, and other functions. This study aimed to explore the therapeutic effect of CB and mycelium of PI (MPI) alone and in combination on colitis mice induced by dextran sodium sulfate (DSS). Mice were randomly assigned to five groups: (1) control (CTRL), (2) DSS, (3) CB, (4) MPI, and (5) CB + MPI (CON). The weight of the mice was recorded daily during the experiment, and the length of the colon was measured on the last day of the experiment. The colons were collected for hematoxylin and eosin staining, colon contents were collected for intestinal flora analysis, and serum was collected for metabolite analysis. The results showed that compared with the DSS group, CB, MPI, and CON treatments inhibited the weight loss and colon length shortening caused by DSS, significantly increased the concentrations of interleukin (IL)-4, IL-10, and superoxide dismutase, and significantly decreased the concentrations of IL-6, tumor necrosis factor-α, and myeloperoxidase. Gene sequence analysis of 16S rRNA showed that CB, MPI, and CON treatments changed the composition and structure of intestinal microorganisms. Metabolome results showed that CB, MPI, and CON treatments changed serum metabolites in DSS-treated mice, including dodecenoylcarnitine, L-urobilinogen, and citric acid. In conclusion, CB, MPI, and CON treatments alleviated DSS-induced colitis in mice by regulating intestinal flora and metabolites, with the CON group having the best effect.
通讯机构：
[Hu, SW ] W;[Liu, G ] H;Wenzhou Med Univ, Peoples Hosp Wenling 1, Wenling Hosp, Orthopaed Ctr, Wenzhou, Zhejiang, Peoples R China.;Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha, Hunan, Peoples R China.
关键词：
L. plantarum;dexamethasone;differential metabolites;food active ingredients;glucocorticoids;gut microbes;osteoporosis;probiotics
摘要：
INTRODUCTION: Osteoporosis, one of the most common non-communicable human diseases worldwide, is one of the most prevalent disease of the adult skeleton. Glucocorticoid-induced osteoporosis(GIOP) is the foremost form of secondary osteoporosis, extensively researched due to its prevalence.Probiotics constitute a primary bioactive component within numerous foods, offering promise as a potential biological intervention for preventing and treating osteoporosis. This study aimed to evaluate the beneficial effects of the probiotic Lactobacillus plantarum on bone health and its underlying mechanisms in a rat model of glucocorticoid dexamethasone-induced osteoporosis, using the osteoporosis treatment drug alendronate as a reference. METHODS: We examined the bone microstructure (Micro-CT and HE staining) and analyzed the gut microbiome and serum metabolome in rats. RESULTS AND DISCUSSION: The results revealed that L. plantarum treatment significantly restored parameters of bone microstructure, with elevated bone density, increased number and thickness of trabeculae, and decreased Tb.Sp. Gut microbiota sequencing results showed that probiotic treatment increased gut microbial diversity and the ratio of Firmicutes to Bacteroidota decreased. Beneficial bacteria abundance was significantly increased (Lachnospiraceae_NK4A136_group, Ruminococcus, UCG_005, Romboutsia, and Christensenellaceae_R_7_group), and harmful bacteria abundance was significantly decreased (Desulfovibrionaceae). According to the results of serum metabolomics, significant changes in serum metabolites occurred in different groups. These differential metabolites were predominantly enriched within the pathways of Pentose and Glucuronate Interconversions, as well as Propanoate Metabolism. Furthermore, treatment of L. plantarum significantly increased serum levels of Pyrazine and gamma-Glutamylcysteine, which were associated with inhibition of osteoclast formation and promoting osteoblast formation. Lactobacillus plantarum can protect rats from DEX-induced GIOP by mediating the "gut microbial-bone axis" promoting the production of beneficial bacteria and metabolites. Therefore L. plantarum is a potential candidate for the treatment of GIOP.
摘要：
The chemical structure of sinoacutine is formed by a phenanthrene nucleus and an ethylamine bridge. Because it has a similar parent structure to morphine, it is subdivided into morphinane. At present, all reports have pointed out that the basic skeleton of morphine alkaloids is salutaridine (the isomer of sinoacutine), which is generated by the phenol coupling reaction of (R)-reticuline. This study shows that the biosynthetic precursors of sinoacutine and salutaridine are different. In this paper, the sinoacutine synthetase (SinSyn) gene was cloned from Sinomenium acutum and expressed SinSyn protein. Sinoacutine was produced by SinSyn catalyzed (S)-reticuline, according to the results of enzyme-catalyzed experiments. The optical activity, nuclear magnetic resonance, and mass spectrum of sinoacutine and salutaridine were analyzed. The classification and pharmacological action of isoquinoline alkaloids were discussed. It was suggested that sinoacutine should be separated from morphinane and classified as sinomenine alkaloids.
期刊：
Drug Design, Development and Therapy,2024年18:699-717 ISSN：1177-8881
通讯作者：
Chun Guo
作者机构：
[Yang, Yi; Lei, Shihui] Experiment Center of Medical Innovation, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China;The First Clinical College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China;[Li, Jiaqi; He, Ying; Yang, Hua] College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, 410128, People’s Republic of China;[Zhang, Mengxue; Zhou, Desheng] Department of Neurology, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China;[Zhou, Xuqing; Wang, Xu; Guo, Chun] Experiment Center of Medical Innovation, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China<&wdkj&>The First Clinical College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China
通讯机构：
[Chun Guo] E;Experiment Center of Medical Innovation, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China<&wdkj&>The First Clinical College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China
摘要：
BACKGROUND: Annao Pingchong decoction (ANPCD) is a traditional Chinese decoction which has definite effects on treating intracerebral hemorrhage (ICH) validated through clinical and experimental studies. However, the impact of ANPCD on oxidative stress (OS) after ICH remains unclear and is worth further investigating. AIM: To investigate whether the therapeutic effects of ANPCD on ICH are related to alleviating OS damage and seek potential targets for its antioxidant effects. MATERIALS AND METHODS: The therapeutic candidate genes of ANPCD on ICH were identified through a comparison of the target genes of ANPCD, target genes of ICH and differentially expressed genes (DEGs). Protein-protein interaction (PPI) network analysis and functional enrichment analysis were combined with targets-related literature to select suitable antioxidant targets. The affinity between ANPCD and the selected target was verified using macromolecular docking. Subsequently, the effects of ANPCD on OS and the selected target were further investigated through in vivo experiments. RESULTS: Forty-eight candidate genes were screened, in which silent information regulator sirtuin 1 (SIRT1) is one of the core genes that has antioxidant effects and ICH significantly affected its expression. The good affinity between 6 compounds of ANPCD and SIRT1 was also demonstrated by macromolecular docking. The results of in vivo experiments demonstrated that ANPCD significantly decreased modified neurological severity scoring (mNSS) scores and serum MDA and 8-OHdG content in ICH rats, while significantly increasing serum SOD and CAT activity, complicated with the up-regulation of ANPCD on SIRT1, FOXO1, PGC-1α and Nrf2. Furthermore, ANPCD significantly decreased the apoptosis rate and the expression of apoptosis-related proteins (P53, cytochrome c and caspase-3). CONCLUSION: ANPCD alleviates OS damage and apoptosis after ICH in rats. As a potential therapeutic target, SIRT1 can be effectively regulated by ANPCD, as are its downstream proteins.
摘要：
Ulcerative colitis (UC) is a chronic, non-specific inflammatory sickness of the intestinal tract, chiefly implicating the rectum and colon, which is characterized by chronic or subacute diarrhea, mucopurulent stools, and abdominal pain. The pathogeny of UC is still uncertain, and it is thought that multiple factors interact to cause the disease, such as environment, genetics, gut microbes, and immunity. Injuring the intestinal barrier is one of the most significant features of UC and includes mechanical, chemical, immune, and biological barriers. Plenty of research has shown that probiotics, as profitable bacteria in the gut, can play a prominent role in the treatment of UC by improving gut barrier function and modulating gut immunity. Lactobacillus plantarum (L. plantarum), a common probiotic, has made outstanding contributions to food and medicine, and many studies in recent years have shown that L. plantarum has great preventive and therapeutic effects on ulcerative colitis and restores the intestinal barrier. This paper reviews the mechanisms of L. plantarum for improving the intestinal barrier function of UC organisms, mainly including regulating the immune response, inhibiting oxidative stress, raising the expression of tight junction (TJ) proteins, promoting the formation of mucin, improving the composition of gut flora, and raising the levels of short-chain fatty acids (SCFAs), which offers some help for the clinical therapy of UC.
摘要：
Squalene is an important triterpene with a wide range of applications. Given the growing market demand for squalene, the development of microbial cell factories capable of squalene production is considered a sustainable method. This study aimed to investigate the squalene production potential of Yarrowia lipolytica. First, HMG-CoA reductase from Saccharomyces cerevisiae and squalene synthase from Y. lipolytica was co-overexpressed in Y. lipolytica. Second, by enhancing the supply of NADPH in the squalene synthesis pathway, the production of squalene in Y. lipolytica was effectively increased. Furthermore, by constructing an isoprenol utilization pathway and overexpressing YlDGA1, the strain YLSQ9, capable of producing 868.1 mg/L squalene, was obtained. Finally, by optimizing the fermentation conditions, the highest squalene concentration of 1628.2 mg/L (81.0 mg/g DCW) in Y. lipolytica to date was achieved. This study demonstrated the potential for achieving high squalene production using Y. lipolytica.
