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1.
J Genet Genomics ; 2024 May 07.
Article En | MEDLINE | ID: mdl-38723744

Drought is a natural disaster that has a profound impact on global agricultural production, significantly reduces crop yields and thereby poses a severe threat to worldwide food security. Addressing the challenge of effectively improving crop drought resistance (DR) to mitigate yield loss under drought conditions is a global issue. An optimal root system architecture (RSA) plays a pivotal role in enhancing crops' capacity to efficiently uptake water and nutrients, which consequently strengthens their resilience against environmental stresses. In this review, we discuss the compositions and roles of crop RSA and summarize the most recent developments in augmenting drought tolerance in crops by manipulating RSA-related genes. Based on current research, we propose the potential optimal RSA configuration that could be helpful in enhancing crop DR. Lastly, we discussed the existing challenges and future directions for breeding crops with enhanced DR capabilities through genetic improvements targeting RSA.

2.
Environ Manage ; 2024 May 07.
Article En | MEDLINE | ID: mdl-38713413

Scientific assessment of urban ecological security (ES) is an important prerequisite to realize regional sustainable development. Previous studies lack the consideration of quality and poor systematic correlation, which could not reflect the internal dynamic relationship. On the basis of considering the time lag, this study divided the research process into the natural operation stage and the management feedback stage based on the driving forces, pressures, state, impacts, responses, management (DPSIRM) framework model and DEA theory, so as to effectively overcome the above shortcomings. Finally, we analyzed the spatio-temporal characteristics and influencing factors of the ES level of 108 cities in the Yangtze River Economic Belt (YREB) during 2005-2019. The results showed that: (a) both two stages showed a slow and fluctuating upward trend in time series, and the level of urban ES in the management feedback stage was significantly higher than that in the natural operation stage; (b) with the passage of time, the spatial distribution of ES in the natural operation stage gradually developed towards the middle and downstream of the YREB, while the management feedback stage mainly evolved from the midstream to the edge area; (c) the level of urban ES presented a different degree of spatial agglomeration phenomenon, and showed an increasing trend over time; and (d) the key influencing factors gradually changed from pressure to response during 2005-2019. This research aims to provide an innovative perspective for the measurement of urban ES, and provide scientific reference for improving urban ecological sustainable development.

3.
BMC Cancer ; 24(1): 573, 2024 May 09.
Article En | MEDLINE | ID: mdl-38724951

BACKGROUND: Microsatellite instability-high (MSI-H) has emerged as a significant biological characteristic of colorectal cancer (CRC). Studies reported that MSI-H CRC generally had a better prognosis than microsatellite stable (MSS)/microsatellite instability-low (MSI-L) CRC, but some MSI-H CRC patients exhibited distinctive molecular characteristics and experienced a less favorable prognosis. In this study, our objective was to explore the metabolic transcript-related subtypes of MSI-H CRC and identify a biomarker for predicting survival outcomes. METHODS: Single-cell RNA sequencing (scRNA-seq) data of MSI-H CRC patients were obtained from the Gene Expression Omnibus (GEO) database. By utilizing the copy number variation (CNV) score, a malignant cell subpopulation was identified at the single-cell level. The metabolic landscape of various cell types was examined using metabolic pathway gene sets. Subsequently, functional experiments were conducted to investigate the biological significance of the hub gene in MSI-H CRC. Finally, the predictive potential of the hub gene was assessed using a nomogram. RESULTS: This study revealed a malignant tumor cell subpopulation from the single-cell RNA sequencing (scRNA-seq) data. MSI-H CRC was clustered into two subtypes based on the expression profiles of metabolism-related genes, and ENO2 was identified as a hub gene. Functional experiments with ENO2 knockdown and overexpression demonstrated its role in promoting CRC cell migration, invasion, glycolysis, and epithelial-mesenchymal transition (EMT) in vitro. High expression of ENO2 in MSI-H CRC patients was associated with worse clinical outcomes, including increased tumor invasion depth (p = 0.007) and greater likelihood of perineural invasion (p = 0.015). Furthermore, the nomogram and calibration curves based on ENO2 showed potential prognosis predictive performance. CONCLUSION: Our findings suggest that ENO2 serves as a novel prognostic biomarker and is associated with the progression of MSI-H CRC.


Biomarkers, Tumor , Colorectal Neoplasms , Disease Progression , Microsatellite Instability , Phosphopyruvate Hydratase , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/mortality , Colorectal Neoplasms/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Phosphopyruvate Hydratase/genetics , Phosphopyruvate Hydratase/metabolism , Prognosis , Female , Male , Gene Expression Regulation, Neoplastic , Epithelial-Mesenchymal Transition/genetics , Middle Aged , Nomograms , Single-Cell Analysis , DNA Copy Number Variations
4.
Vaccine ; 2024 May 06.
Article En | MEDLINE | ID: mdl-38714449

To assess the levels of and neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its mutants in serum samples from patients with breakthrough infection. Sixty-four patients with breakthrough infections were recruited for this cross-sectional study. All samples were used to neutralizing antibodies (nAbs) against SARS-CoV-2 and its mutants using a focused reduction neutralization assay. A total of 512 serum samples were obtained from unvaccinated patients who received one dose of vaccine (n = 12), received two doses of vaccine (n = 15), and received three doses of vaccine (n = 37). The geometric mean titer (GMT) of neutralizing antibodies against the Omicron subvariant was significantly lower (GMT 66.8 and 56.1) compared to the original strain, regardless of whether two or three doses of vaccine were administered. This result highlights that sera from breakthrough infections induce broad neutralization, but Omicron XBB.1.16 exhibits high immune evasion potential.

6.
J Ethnopharmacol ; 331: 118337, 2024 Sep 15.
Article En | MEDLINE | ID: mdl-38740110

ETHNOPHARMACOLOGICAL RELEVANCE: Microthrombosis is commonly seen in sepsis and COVID-19. Zixue Powder (ZXP) is a traditional Chinese herbal formula with the potential to treat microvascular and infectious diseases. However, the role and mechanism of ZXP in sepsis-associated thrombosis remain unclear. AIM OF THE STUDY: Investigating the therapeutic effectiveness and underlying mechanisms of ZXP in septic thrombosis. MATERIALS AND METHODS: ZXP's compositions were examined with UPLC-QTOF-MS. The efficacy of ZXP on sepsis-induced thrombosis was assessed through various methods: liver tissue pathology was examined using hematoxylin-eosin staining, platelet count was determined by a blood cell analyzer, and an enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum tissue factor (TF), thromboxane B2 (TXB2), D-Dimer, and plasminogen activator inhibitor-1 (PAI-1). Neutrophil extracellular traps (NETs) were localized and expressed in liver tissues by immunofluorescence, and the number of NETs in peripheral blood was evaluated by ELISA, which measured the quantity of cf-DNA and MPO-DNA in serum. Platelet P-selectin expression and platelet-neutrophil aggregation were measured by flow cytometry, and plasma P-selectin expression was measured by ELISA. Furthermore, the mechanism of the stimulator of interferon genes (STING) signaling pathway in ZXP's anti-sepsis thrombosis effect was investigated using the STING agonist, Western blot experiments, and immunoprecipitation experiments. RESULTS: UPLC-QTOF-MS identified 40 chemical compositions of ZXP. Administration of ZXP resulted in significant improvements in liver thrombosis, platelet counts, and levels of TXB2, TF, PAI-1, and D-Dimer in septic rats. Moreover, ZXP inhibited NETs formation in both liver tissue and peripheral blood. Additionally, ZXP decreased the levels of P-selectin in both platelets and plasma, as well as the formation of platelet-neutrophil aggregates, thereby suppressing P-selectin-mediated NETs release. Immunoprecipitation and immunofluorescence staining experiments revealed that ZXP attenuated P-selectin secretion by inhibiting STING-mediated assembly of platelet soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) complex, ultimately preventing inhibition of NETs formation. CONCLUSION: Our study showed that ZXP effectively mitigates platelet granule secretion primarily through modulation of the STING pathway, consequently impeding NET-associated thrombosis in sepsis. These findings offer valuable insights for future research on the development and application of ZXP.


Drugs, Chinese Herbal , Extracellular Traps , Membrane Proteins , Sepsis , Thrombosis , Animals , Extracellular Traps/drug effects , Extracellular Traps/metabolism , Drugs, Chinese Herbal/pharmacology , Male , Sepsis/drug therapy , Thrombosis/drug therapy , Membrane Proteins/metabolism , Blood Platelets/drug effects , Blood Platelets/metabolism , Rats , Neutrophils/drug effects , Neutrophils/metabolism , Liver/drug effects , Liver/metabolism , Liver/pathology , Rats, Sprague-Dawley , Mice
7.
Int J Biol Macromol ; 271(Pt 2): 132593, 2024 May 22.
Article En | MEDLINE | ID: mdl-38788865

This study delves into the effects of curdlan integration and thermal sterilization on the rheological properties, structure, and quality attributes of concentrated rice starch gel. Acting as a heat-set polysaccharide, curdlan established a dual-network gel structure with rice starch gel, displaying strong interactions with rice starch, as confirmed by confocal laser scanning microscopy and Fourier-transform infrared spectroscopy. The addition of curdlan expedited the gel formation of rice starch, yielding a denser gel structure. Consequently, this enhanced G', solid-like behavior, textural properties, and cooking quality while reducing frequency-dependence. Given the cooling-induced gelation behavior of pure rice starch, thermal treatment disrupted inter-chain hydrogen bonding, compromising the structural integrity of the gel. This disruption manifested in a softer texture and diminished mechanical properties and cooking quality. Notably, this decline in mechanical properties and cooking quality of rice starch gel was markedly ameliorated with the incorporation of curdlan, particularly at a content of ≥1.0 %. Compared with pure RS, 1.0 % CD inclusion showed a reduction in cooking breakage rate by 30.69 % and an increase in hardness by 38.04 %. This work provides valuable insights for the advancement of fresh starch gel-based foods that exhibit exceptional quality and an extended shelf life.

8.
Sci Rep ; 14(1): 10339, 2024 May 06.
Article En | MEDLINE | ID: mdl-38710719

Reservoir temperature estimation is crucial for geothermal studies, but traditional methods are complex and uncertain. To address this, we collected 83 sets of water chemistry and reservoir temperature data and applied four machine learning algorithms. These models considered various input factors and underwent data preprocessing steps like null value imputation, normalization, and Pearson coefficient calculation. Cross-validation addressed data volume issues, and performance metrics were used for model evaluation. The results revealed that our machine learning models outperformed traditional fluid geothermometers. All machine learning models surpassed traditional methods. The XGBoost model, based on the F-3 combination, demonstrated the best prediction accuracy with an R2 of 0.9732, while the Bayesian ridge regression model using the F-4 combination had the lowest performance with an R2 of 0.8302. This study highlights the potential of machine learning for accurate reservoir temperature prediction, offering geothermal professionals a reliable tool for model selection and advancing our understanding of geothermal resources.

9.
Thromb Haemost ; 2024 May 10.
Article En | MEDLINE | ID: mdl-38729191

OBJECTIVE: The association between tea consumption and venous thromboembolism (VTE) remains unknown. We aimed to evaluate the association between tea consumption with different additives (milk and/or sweeteners) and incident VTE, and the modifying effects of genetic variation in caffeine metabolism on the association. METHODS: A total of 190,189 participants with complete dietary information and free of VTE at baseline in the UK Biobank were included. The primary outcome was incident VTE, including incident deep vein thrombosis and pulmonary embolism. RESULTS: During a median follow-up of 12.1 years, 4,485 (2.4%) participants developed incident VTE. Compared with non-tea drinkers, tea drinkers who added neither milk nor sweeteners (hazard ratio [HR]: 0.85; 95% confidence interval [95% CI]: 0.76-0.94), only milk (HR: 0.86; 95% CI: 0.80-0.93), and both milk and sweeteners to their tea (HR: 0.90; 95% CI: 0.81-0.99) had a lower risk of VTE, while those who added only sweeteners to their tea did not (HR: 0.94; 95% CI: 0.75-1.17). Moreover, there was an L-shaped relationship between tea consumption and incident VTE among tea drinkers who added neither milk nor sweeteners, only milk, and both milk and sweeteners to their tea, respectively. However, a nonsignificant association was found among tea drinkers who added only sweeteners to their tea. Genetic variation in caffeine metabolism did not significantly modify the association (p-interaction = 0.659). CONCLUSION: Drinking unsweetened tea, with or without added milk, was associated with a lower risk of VTE. However, there was no significant association between drinking tea with sweeteners and incident VTE.

10.
Sci Bull (Beijing) ; 2024 Apr 03.
Article En | MEDLINE | ID: mdl-38644130

Colorectal cancer (CRC), a widespread malignancy, is closely associated with tumor microenvironmental hydrogen peroxide (H2O2) levels. Some clinical trials targeting H2O2 for cancer treatment have revealed its paradoxical role as a promoter of cancer progression. Investigating the dynamics of cancer cell H2O2 eustress at the single-cell level is crucial. In this study, non-contact hopping probe mode scanning ion conductance microscopy (HPICM) with high-sensitive Pt-functionalized nanoelectrodes was employed to measure dynamic extracellular to intracellular H2O2 gradients in individual colorectal cancer Caco-2 cells. We explored the relationship between cellular mechanical properties and H2O2 gradients. Exposure to 0.1 or 1 mmol/L H2O2 eustress increased the extracellular to intracellular H2O2 gradient from 0.3 to 1.91 or 3.04, respectively. Notably, cellular F-actin-dependent stiffness increased at 0.1 mmol/L but decreased at 1 mmol/L H2O2 eustress. This H2O2-induced stiffness modulated AKT activation positively and glutathione peroxidase 2 (GPX2) expression negatively. Our findings unveil the failure of some H2O2-targeted therapies due to their ineffectiveness in generating H2O2, which instead acts eustress to promote cancer cell survival. This research also reveals the complex interplay between physical properties and biochemical signaling in cancer cells' antioxidant defense, illuminating the exploitation of H2O2 eustress for survival at the single-cell level. Inhibiting GPX and/or catalase (CAT) enhances the cytotoxic activity of H2O2 eustress against CRC cells, which holds significant promise for developing innovative therapies targeting cancer and other H2O2-related inflammatory diseases.

13.
Anim Biosci ; 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38575127

Objective: As a charismatic species, cashmere goats have rich genetic resources. In the Inner Mongolia Autonomous Region, there are three cashmere goat varieties named and approved by the state. These goats are renowned for their high cashmere production and superior cashmere quality. Therefore, it is vitally important to protect their genetic resources as they will serve as breeding material for developing new varieties in the future. Methods: Three breeds including Inner Mongolia cashmere goats (IMCG), Hanshan White cashmere goats (HS), and Ujimqin white cashmere goats (WZMQ) were studied. IMCG were of three types: Aerbas (ARBS), Erlangshan (ELS) and Alashan (ALS). Nine DNA samples were collected for each population, and they were genomically re-sequenced to obtain high-depth data. The genetic diversity parameters of each population were estimated to determine selection intensity. Principal component analysis, phylogenetic tree construction and genetic differentiation parameter estimation were performed to determine genetic relationships among populations. Results: Samples from the 45 individuals from the five goat populations were sequenced, and 30,601,671 raw SNPs obtained. Then, variant calling was conducted using the reference genome, and 17,214,526 SNPs were retained after quality control. Individual sequencing depth of individuals ranged from 21.13X to 46.18X, with an average of 28.5X. In the ARBS, locus polymorphism (79.28) and expected heterozygosity (0.2554) proportions were the lowest, and the homologous consistency ratio (0.1021) and average inbreeding coefficient (0.1348) were the highest, indicating that this population had strong selection intensity. Conversely, ALS and WZMQ selection intensity was relatively low. Genetic distance between HS and the other four populations was relatively high, and genetic exchange existed among the other four populations. Conclusion: s: The Inner Mongolia cashmere goat (ARBS type) population has a relatively high selection intensity and a low genetic diversity. The IMCG (ALS type) and WZMQ populations had relatively low selection intensity and high genetic diversity. The genetic distance between HS and the other four populations was relatively high, with a moderate degree of differentiation. Overall, these genetic variations provide a solid foundation for resource identification of Inner Mongolia Autonomous Region cashmere goats in the future.

14.
Front Neurosci ; 18: 1329884, 2024.
Article En | MEDLINE | ID: mdl-38591067

Person re-identification(Re-ID) aims to retrieve pedestrians under different cameras. Compared with image-based Re-ID, video-based Re-ID extracts features from video sequences that contain both spatial features and temporal features. Existing methods usually focus on the most attractive image parts, and this will lead to redundant spatial description and insufficient temporal description. Other methods that take temporal clues into consideration usually ignore misalignment between frames and only focus on a fixed length of one given sequence. In this study, we proposed a Reciprocal Global Temporal Convolution Network with Adaptive Alignment(AA-RGTCN). The structure could address the drawback of misalignment between frames and model discriminative temporal representation. Specifically, the Adaptive Alignment block is designed to shift each frame adaptively to its best position for temporal modeling. Then, we proposed the Reciprocal Global Temporal Convolution Network to model robust temporal features across different time intervals along both normal and inverted time order. The experimental results show that our AA-RGTCN can achieve 85.9% mAP and 91.0% Rank-1 on MARS, 90.6% Rank-1 on iLIDS-VID, and 96.6% Rank-1 on PRID-2011, indicating we could gain better performance than other state-of-the-art approaches.

15.
Foods ; 13(7)2024 Apr 05.
Article En | MEDLINE | ID: mdl-38611417

Natural macromolecular substances are prevalent in the organs of plants and animals, such as polysaccharides, resins, proteins, etc [...].

16.
Plant Dis ; 2024 Apr 28.
Article En | MEDLINE | ID: mdl-38679598

Aucuba japonica var. variegata Dombrain is a common evergreen cultivated ornamental in China (Li et al. 2016). In December 2022, severe leaf blight on A. japonica was observed next to the Meishiyuan of Zhejiang Normal University (29°8'4″N, 119°37'54″E) in Jinhua City, Zhejiang Province, China. There were seven plants in the surveyed area, and over 50% of leaves were affected. The early symptoms were small gray spot parts with brown borders on the tip of the leaves. Then the grey parts gradually expanded and became brownish black. In severe cases, the whole leaves became black and blighted. To identify the pathogen, 5 symptomatic leaves were randomly collected from 5 plants and cut into small pieces (5 mm × 5 mm), surface disinfected in 1% sodium hypochlorite solution for 3 min, followed by 75% alcohol for 30 s, then rinsed in sterile distilled water thrice. Tissues were cultured on potato dextrose agar (PDA) and incubated at 28°C for 7 days. Pure cultures were obtained by the single-spore method. Thirteen strains were isolates from the tissues, and nine of them showed similar morphological characteristics. Colonies were white initially, then became gray. The undersides of the colonies became black gradually. Hyaline, fusiform conidia (n = 30) were 17.1 to 24.76 µm (average 20.39 ± 1.906 µm) in length and 5.4 to 6.61 µm (average 6.19 ± 0.434 µm) in width. The DNA of nine isolates were extracted by Ezup Column Bacteria Genomic DNA Purification Kit, and their sequences were identical, so they were named QM1. The internal transcribed spacer (ITS) region, translation elongation factor 1-α (TEF1), and ß-tubulin (TUB2) genes were amplified with primer pairs ITS1/ITS4, TEF1-728F/TEF1-986R and ßt2a/ßt2b (Slippers et al. 2004), respectively. The BLAST analysis indicated that ITS (OR215464), TEF1 (OR243689), and TUB2 (OR243688) of the isolate QM1 were 99 to 100% identical to those of Botryosphaeria dothidea (GenBank accession nos. MH329646 for ITS sequences; OL891702 for TEF1 sequences; MK511445 for TUB2 sequences). In addition, the phylogenetic tree based on sequences from ITS, TEF1 and TUB2 was constructed with MEGA 11 by use of the maximum likelihood method with 1,000 bootstrapping iterations. Based on the multi-locus phylogeny and morphological features, the isolate QM1 was identified as B. dothidea. To test the Koch's postulates, ten leaves from three healthy two- to three-year-old A. japonica plants were surface disinfested with 75% ethanol for 30 s, rinsed with ddH2O three times. The leaves were wounded with a sterile needle and inoculated with 2ml drop of the isolate QM1 conidial suspension (106 spores/mL), with sterile distilled water as a control. All plants were placed in a greenhouse at 28°C, >70% relative humidity and 12 h light/day. The experiment was repeated three times. After 7 days, leaves of the inoculated group showed symptoms similar to those observed on the naturally infected leaves, while leaves of the control group remained asymptomatic. The pathogen was reisolated from inoculated leaves and was confirmed as B. dothidea based on morphological and molecular analyses. It has been reported B. dothidea cause leaf disease in a wide range of hosts in China, such as Camellia oleifera (Hao et al. 2023), Kadsura coccinea (Su et al. 2021). To our knowledge, this is the first report of Botryosphaeria dothidea causing leaf blight on Aucuba japonica in Zhejiang Province of China. B. dothidea are usually secondary invaders and are known to cause diseases in stressed plants. The results further expand the host-range of B. dothidea, and would help to establish control strategy against the disease.

17.
Virol Sin ; 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38677713

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, encodes several accessory proteins that have been shown to play crucial roles in regulating the innate immune response. However, their expressions in infected cells and immunogenicity in infected humans and mice are still not fully understood. In this study, we detected accessory protein-specific antibodies in COVID-19 patients' sera using various techniques, including Luciferase Immunoprecipitation System (LIPS), Immunofluorescence assay (IFA), and Western blot (WB). Proteins 3a, 3b, 7b, 8 and 9c specific antibodies can be detected by LIPS, but only protein 3a antibody was detected by IFA or WB. And antibodies against protein 3a and 7b only detected in ICU patients, which may serve as a marker for predicting the disease progression. Further, we investigated the expression of accessory proteins in SARS-CoV-2-infected cells and identified the expressions of proteins 3a, 6, 7a, 8, and 9b. We also analyzed their ability to induce antibodies in immunized mice and found that only proteins 3a, 6, 7a, 8, 9b and 9c were able to induce measurable antibody productions, but these antibodies lacked neutralizing activities and did not protect mice from SARS-CoV-2 infection. Our findings validate the expression of SARS-CoV-2 accessory proteins and elucidate their humoral immune response, providing a basis for the protein detection assays and their role in pathogenesis.

18.
Animals (Basel) ; 14(8)2024 Apr 22.
Article En | MEDLINE | ID: mdl-38672394

Cashmere goats are valuable genetic resources which are famous worldwide for their high-quality fiber. Runs of homozygosity (ROHs) have been identified as an efficient tool to assess inbreeding level and identify related genes under selection. However, there is limited research on ROHs in cashmere goats. Therefore, we investigated the ROH pattern, assessed genomic inbreeding levels and examined the candidate genes associated with the cashmere trait using whole-genome resequencing data from 123 goats. Herein, the Inner Mongolia cashmere goat presented the lowest inbreeding coefficient of 0.0263. In total, we identified 57,224 ROHs. Seventy-four ROH islands containing 50 genes were detected. Certain identified genes were related to meat, fiber and milk production (FGF1, PTPRM, RERE, GRID2, RARA); fertility (BIRC6, ECE2, CDH23, PAK1); disease or cold resistance and adaptability (PDCD1LG2, SVIL, PRDM16, RFX4, SH3BP2); and body size and growth (TMEM63C, SYN3, SDC1, STRBP, SMG6). 135 consensus ROHs were identified, and we found candidate genes (FGF5, DVL3, NRAS, KIT) were associated with fiber length or color. These findings enhance our comprehension of inbreeding levels in cashmere goats and the genetic foundations of traits influenced by selective breeding. This research contributes significantly to the future breeding, reservation and use of cashmere goats and other goat breeds.

19.
World J Gastroenterol ; 30(14): 2018-2037, 2024 Apr 14.
Article En | MEDLINE | ID: mdl-38681125

BACKGROUND: Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally. Recent reports suggest that Fusobacterium nucleatum (F. nucleatum) contributes to the initiation, progression, and prognosis of CRC. Butyrate, a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber, is known to inhibit various cancers. This study is designed to explore whether F. nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid. AIM: To investigate the mechanism by which F. nucleatum affects CRC occurrence and development. METHODS: Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F. nucleatum. Additionally, DLD-1 and HCT116 cell lines were exposed to sodium butyrate (NaB) and F. nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function. RESULTS: Our research indicates that the prevalence of F. nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts, while the prevalence of butyrate-producing bacteria is notably lower. In mice colonized with F. nucleatum, the population of butyrate-producing bacteria decreased, resulting in altered levels of butyric acid, a key intestinal metabolite of butyrate. Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells. Consequently, this leads to modulated production of adenosine triphosphate and reactive oxygen species, thereby inhibiting cancer cell proliferation. Additionally, NaB triggers the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, blocks the cell cycle in HCT116 and DLD-1 cells, and curtails the proliferation of CRC cells. The combined presence of F. nucleatum and NaB attenuated the effects of the latter. By employing small interfering RNA to suppress AMPK, it was demonstrated that AMPK is essential for NaB's inhibition of CRC cell proliferation. CONCLUSION: F. nucleatum can promote cancer progression through its inhibitory effect on butyric acid, via the AMPK signaling pathway.


Butyric Acid , Cell Proliferation , Colorectal Neoplasms , Feces , Fusobacterium nucleatum , Gastrointestinal Microbiome , Mice, Inbred BALB C , Animals , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Gastrointestinal Microbiome/drug effects , Butyric Acid/pharmacology , Butyric Acid/metabolism , Humans , Mice , Feces/microbiology , Cell Proliferation/drug effects , HCT116 Cells , Male , Mitochondria/metabolism , Mitochondria/drug effects , Fusobacterium Infections/microbiology , Disease Models, Animal , Cell Line, Tumor , Female , Disease Progression , Dysbiosis , Membrane Potential, Mitochondrial/drug effects
20.
New Phytol ; 242(6): 2524-2540, 2024 Jun.
Article En | MEDLINE | ID: mdl-38641854

Leaf senescence is a complex process strictly regulated by various external and endogenous factors. However, the key signaling pathway mediating leaf senescence remains unknown. Here, we show that Arabidopsis SPX1/2 negatively regulate leaf senescence genetically downstream of the strigolactone (SL) pathway. We demonstrate that the SL receptor AtD14 and MAX2 mediate the age-dependent degradation of SPX1/2. Intriguingly, we uncover an age-dependent accumulation of SLs in leaves via transcriptional activation of SL biosynthetic genes by the transcription factors (TFs) SPL9/15. Furthermore, we reveal that SPX1/2 interact with the WRKY75 subclade TFs to inhibit their DNA-binding ability and thus repress transcriptional activation of salicylic acid (SA) biosynthetic gene SA Induction-Deficient 2, gating the age-dependent SA accumulation in leaves at the leaf senescence onset stage. Collectively, our new findings reveal a signaling pathway mediating sequential activation of SL and salicylate biosynthesis for the onset of leaf senescence in Arabidopsis.


Arabidopsis Proteins , Arabidopsis , Gene Expression Regulation, Plant , Lactones , Plant Leaves , Plant Senescence , Transcription Factors , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis/drug effects , Plant Leaves/metabolism , Plant Leaves/drug effects , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Gene Expression Regulation, Plant/drug effects , Lactones/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Salicylic Acid/metabolism , Salicylates/metabolism , Signal Transduction , Protein Binding/drug effects , Proteolysis/drug effects , Biosynthetic Pathways/drug effects , Biosynthetic Pathways/genetics
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