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Emerging technology in the new era of sensors to detect and quantify neurological reaction-based research has demanded the development of sensors for the neurotransmitter dopamine (DA). In recent decades, electrochemical sensors have offered rapid and sensitive detection of DA, but the presence of interfering compounds, such as uric acid (UA) and ascorbic acid (AA), poses a great threat to the development of DA sensors. Additionally, reusing traditional methods leads to challenges like prolonged preparation and expensive instruments. This research work offers a nanohybrid two-dimensional (2D) paper-like graphene oxide (GO) and three-dimensional (3D) cerium oxide nanosphere (CeONS) heterostructure composite (G-CeONS) created via stoichiometric synthesis for the non-enzymatic detection of DA oxidation in the presence of other complex biological compounds. The constructed G-CeONS nanohybrid composite enables enhanced selectivity and sensitivity towards DA detection through its interfacial engineering. The heterostructure formation of a 2D nanosheet draped over 3D nanospheres exhibits a wide linear concentration range of 100-30 800 nM with a low detection limit of 20.98 nM. Further investigation of the real-time performance on human saliva and DA injections afforded prominent results. In addition, the synergetic effect of G-CeONS improves DA detection accuracy and reliability towards enabling transformational neurochemical and medicinal applications.
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BACKGROUND: Lipid droplet (LD) is a metabolically active organelle, which changes dynamically with the metabolic state and energy requirements of cells. Proteins that either insert into the LD phospholipid monolayer or are present in the cytoplasm, playing a crucial role in lipid homeostasis and signaling regulation, are known as LD-associated proteins. METHODS: The keywords "lipid droplets" and "metabolic diseases" were used to obtain literature on LD metabolism and pathological mechanism. After searching databases including Scopus, OVID, Web of Science, and PubMed from 2013 to 2024 using terms like "lipid droplets", "lipid droplet-associated proteins", "fatty liver disease", "diabetes", "diabetic kidney disease", "obesity", "atherosclerosis", "hyperlipidemia", "natural drug monomers" and "natural compounds", the most common natural compounds were identified in about 954 articles. Eventually, a total of 91 studies of 10 natural compounds reporting in vitro or in vivo studies were refined and summarized. RESULTS: The most frequently used natural compounds include Berberine, Mangostin, Capsaicin, Caffeine, Genistein, Epigallocatechin-3-gallate, Chlorogenic acid, Betaine, Ginsenoside, Resveratrol. These natural compounds interact with LD-associated proteins and help ameliorate abnormal LDs in various metabolic diseases. CONCLUSION: Natural compounds involved in the regulation of LDs and LD-associated proteins hold promise for treating metabolic diseases. Further research into these interactions may lead to new therapeutic applications.
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Carbendazim (CBZ) insecticides have been widely employed, raising serious concerns about their impacts on human health and the environment. A facile hydrothermal technique was used to prepare a zinc ferrite (ZnFe2O4) combined with porous graphene oxide (PGO) as a nanocomposite for selective CBZ detection. The ZnFe2O4/PGO nanocomposite was then used to modify a glassy carbon electrode (GCE), an affordable platform for CBZ detection. Various spectroscopic techniques were employed to confirm the nanomaterial. The electrochemical properties were further investigated using cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). The ZnFe2O4/PGO nanocomposite modified the glassy carbon electrode surface for CBZ detection. A broad linear response range of 0.0039 to 200 µM, high sensitivity (2.184 µAµM-1 cm-2), a low detection limit of 0.0013 µM, outstanding stability, repeatability, and practical applicability are the intriguing qualities of the ZnFe2O4/PGO-modified electrode for CBZ detection.
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BACKGROUND: Cognitive impairment (CI) is now well-accepted as a complication and comorbidity of diabetes mellitus (DM), becoming a serious medical and social problem. Jiao-tai-wan (JTW), one of noted traditional Chinese medicine (TCM), showed dual therapeutic effects on DM and CI. Nevertheless, the potential mechanism is unclear. PURPOSE: This study sought to investigate the mechanism how JTW protected against DM and CI and screen the active component in JTW. METHODS: Db/db mice were used as mouse models. Mice were treated by gavage with 0.9 % saline (0.1 mL/10g/d), low dose of JTW (2.4 g/kg/d) or high dose of JTW (4.8 g/kg/d) for 8 weeks separately. To access the effects of JTW, the levels of OGTT, HOMA-IR, blood lipids, inflammatory cytokines in serum and hippocampus were measured, behavioral tests were conducted, and histopathological changes were observed. The mechanism exploration was performed via network pharmacology, RT-qPCR, western blot, and immunofluorescence staining (IF). The impact and mechanism of coptisine in vitro were investigated using BV2 cells induced by LPS as cellular models. In vitro experiments were conducted in two parts. The first part comprised four groups: Control group, LPS group, LPS+LCOP group and LPS+HCOP group. The second part consisted of four groups: Control group, LPS group, LPS+HCOP group, and LPS+ Fed group. The western blot and RT-qPCR methods were used to examine the changes in biomarkers of the JAK2/STAT3 signaling pathways in BV2 cells. RESULTS: The results demonstrated that JTW could improve OGTT and HOMA-IR, reduce the serum levels of LDL-C, HDL-C, TG, and TC, restore neuronal dysfunction and synaptic plasticity, and decrease the deposition of Aß in the hippocampus. The findings from ELISA, IF, and RT-qPCR revealed that JTW could alleviate microglial activation and inflammatory status in vivo and coptisine could play the same role in vitro. Moreover, the changes of the JAK2/STAT3 signaling pathway in LPS-induced BV2 cells or hippocampus of db/db mice were distinctly reversed by coptisine or JTW, respectively. CONCLUSION: Our study suggested that JTW and its effective component coptisine could alleviate diabetes mellitus-related cognitive impairment, closely linked to the JAK2/STAT3 signaling pathway.
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Hexavalent chromium (Cr(VI)) exposure has been linked with gastrointestinal toxicity, whereas the molecular pathways and key targets remain elusive. Computational toxicology analysis predicted the correlation between protein phosphatase 2A (PP2A) and genes regarding Cr(VI)-induced intestinal injury. Here, we generated a mouse model with intestinal epithelium-specific knock out of Ppp2r1a (encoding PP2A Aα subunit) to investigate the mechanisms underlying Cr(VI)-induced small intestinal toxicity. Heterozygous (HE) mice and matched WT littermates were administrated with Cr(VI) at 0, 5, 20, and 80 mg/l for 28 successive days. Cr(VI) treatment led to crypt hyperplasia, epithelial cell apoptosis, and intestinal barrier dysfunction, accompanied by the decline of goblet cell counts and Occludin expression in WT mice. Notably, these effects were aggravated in HE mice, indicating that PP2A Aα deficiency conferred mice with susceptibility to Cr(VI)-induced intestinal injury. The combination of data analysis and biological experiments revealed Cr(VI) exposure could decrease YAP1 phosphorylation at Ser127 but increase protein expression and activity, together with elevated transcriptional coactivator with PDZ-binding motif protein driving epithelial crypt cells proliferation following damage, suggesting the involvement of Hippo/YAP1 signaling pathway in Cr(VI)-induced intestinal toxicity. Nevertheless, the enhanced phosphorylation of YAP1 in HE mice resulted in proliferation/repair defects in intestinal epithelium, thereby exacerbating Cr(VI)-induced gut barrier dysfunction. Notably, by molecular docking and further studies, we identified urolithin A, a microbial metabolite, attenuated Cr(VI)-induced disruption of intestinal barrier function, partly by modulating YAP1 expression and activity. Our findings reveal the novel molecular pathways participated in Cr(VI)-caused small intestinal injury and urolithin A could potentially protect against environmental hazards-induced intestinal diseases.
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PM2.5 pollution has been associated with the incidence of lung cancer, but the underlying mechanism is still unclear. PIWI-interacting RNAs (piRNAs), initially identified in germline cells, have emerged as a novel class of small non-coding RNAs (26 - 32 nucleotides) with diverse functions in various diseases, including cancer. However, the role and mechanism of piRNAs in the development of PM2.5-induced lung cancer remain to be clarified. In the presented study, we used a PM2.5-induced malignant transformation cell model to analyze the change of piRNA profiles. Among the disturbed piRNAs, piR-27222 was identified as an oncogene that inhibited cell death in a m6A-dependent manner. Mechanistically, we found that piR-27222 could deubiquitinate and stabilize eIF4B by directly binding to eIF4B and reducing its interaction with PARK2. The enhanced expression of eIF4B, in turn, promoted the expression of WTAP, leading to increased m6A modification in the Casp8 transcript. Consequently, the stability of Casp8 transcripts was reduced, rendering lung cancer cells resistant to PANoptosis. Collectively, our findings reveal that PM2.5 exposure up-regulated piR-27222 expression, which could affect EIF4B/WTAP/m6A axis, thereby inhibiting PANoptosis of cells and promoting lung cancer. Our study provides new insights into understanding the epigenetic mechanisms underlining PM2.5-induced lung cancer.
Subject(s)
Lung Neoplasms , Particulate Matter , RNA, Small Interfering , Lung Neoplasms/genetics , Lung Neoplasms/chemically induced , Lung Neoplasms/pathology , Particulate Matter/toxicity , Humans , Air Pollutants/toxicityABSTRACT
PURPOSE: To investigate the effect of Scutellaria baicalensis Georgi gargle on oral health and changes in oral bacteria among orthodontic patients. METHODS: About 110 cases of oral fixed orthodontic patients were screened from January 2020 to June 2022 at Taizhou Hospital in Zhejiang Province. They were randomly divided into the experimental group (receiving compound S. baicalensis Georgi gargle once a day) and the control group (receiving 0.9% NS gargle once a day), with 55 cases in each group. Gingival samples were collected from both groups before and 3 months after the orthodontic surgery for bacterial culture, and the differences between the 2 groups of patients in Plaque Index (PLI), gingival bleeding index (sBl), and periodontal depth (PD) before and after the operation were compared. Results: The detection levels of PLI, PD, and sBI in the experimental group were lower than those in the control group (Pâ <â .05) 3 months after orthodontic surgery (Pâ <â .05); after orthodontic correction for 3 months, there was a significant difference in coccus, bacillus, Campylobacter, Clostridium, Helicobacter, and filamentous bacteria between the experimental group and the control group (Pâ <â .05); and Porphyromonas gingivalis, Fusobacterium nucleatum, Bacteroides forsythus (B.f), and Agglomerata actinomycetes in the 2 groups were statistically significant after 3 months of orthodontic treatment (Pâ <â .05). CONCLUSION SUBSECTIONS: In fixed orthodontic treatment, S. baicalensis Georgi gargle can effectively inhibit oral pathogens and maintain periodontal health.
Subject(s)
Oral Health , Scutellaria baicalensis , Humans , Female , Male , Adolescent , Periodontal Index , Plant Extracts/pharmacology , Young Adult , Dental Plaque Index , Bacteria/isolation & purification , Bacteria/classification , Gingiva/microbiologyABSTRACT
Heavy metals are crucial carcinogenic agents threatening the environment and living habituates. Among them, arsenic (As) is an important metalloid that is categorized as a group I toxic carcinogen. Roxarsone (RX) is an organoarsenic antibiotic compound primarily used as a veterinarian drug and growth promoter for poultry animals. The extensive usage of RX increased the accumulation of As in living beings and the ecosystem. Therefore, we have prepared an electrochemical sensor based on 3D bismuth oxybromide with 2D selenium-doped graphitic carbon nitride (BOB/SCN) electrocatalyst for the rapid detection of RX. The elemental and structural details were thoroughly investigated with several spectroscopic techniques. The electrochemical properties were measured by impedance and voltammetric measurements. The electrocatalytic behavior toward the RX was estimated with different voltammetric methods. Therefore, our BOB/SCN-based electrochemical sensor demonstrated a low detection limit (2.3 nM), low quantification value (7.7 nM), optimal sensitivity (0.675 µA µM-1 cm-2), and good linear ranges (0.01-77 and 77-857 µM). Additionally, this sensor showed good electrochemical performance and was applied to monitor the RX in various real samples with remarkable recoveries. Based on these results, our BOB/SCN sensor is a promising electrochemical platform for determining RX.
Subject(s)
Bismuth , Electrochemical Techniques , Graphite , Roxarsone , Selenium , Graphite/chemistry , Electrochemical Techniques/methods , Catalysis , Selenium/chemistry , Bismuth/chemistry , Roxarsone/analysis , Roxarsone/chemistry , Animals , Nitrogen Compounds/chemistry , Limit of Detection , Nitriles/chemistryABSTRACT
Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), two prominent per- and polyfluoroalkyl substances (PFASs), are potentially harmful to many human organs. However, there only exist limited methods to mitigate their health hazards. The aim of this study is to combine a bioinformatics analysis with in vitro experiments to discover small molecules that can alleviate liver damage caused by PFOA/PFOS. We identified 192 and 82 key genes related to hepatocytes exposed to PFOA and PFOS, respectively. The functional enrichment analysis of key genes suggested cellular senescence may be important in PFOA/PFOS-induced hepatotoxicity. The in vitro models revealed that PFOA/PFOS led to hepatocyte senescence by increasing the activity of SA-ß-gal, inducing mitochondrial dysfunction, impacting cell cycle arrest, and elevating the expressions of p21, p53, IL-1ß, and SASP-related cytokines. The drug-target gene set enrichment analysis method was employed to compare the transcriptome data from the Gene Expression Omnibus database (GEO), Comparative Toxicogenomics Database (CTD), and the high-throughput experiment- and reference-guided database (HERB), and 21 traditional Chinese medicines (TCMs) were identified that may alleviate PFOA/PFOS-induced liver aging. The experimental results of co-exposure to PFOA/PFOS and TCMs showed that sanguinarine has particular promise in alleviating cellular senescence caused by PFOA/PFOS. Further investigations revealed that the mTOR-p53 signaling pathway was involved in PFOA/PFOS-mediated hepatic senescence and can be blocked using sanguinarine.
Subject(s)
Alkanesulfonic Acids , Caprylates , Cellular Senescence , Fluorocarbons , Hepatocytes , Isoquinolines , Fluorocarbons/toxicity , Hepatocytes/drug effects , Hepatocytes/metabolism , Cellular Senescence/drug effects , Caprylates/toxicity , Humans , Alkanesulfonic Acids/toxicity , Isoquinolines/pharmacology , Benzophenanthridines/pharmacology , Computational Biology , Animals , Hep G2 Cells , Signal Transduction/drug effectsABSTRACT
Zeolitic Imidazolate (metal organic) Frameworks (ZIFs) and Prussian Blue Analogues (PBAs) are promising materials in electrochemical sensing due to their unique properties. In this study, a composite material comprising NiFe-PBA and ZIF-67 was synthesized and made to form a uniform layer onto a glassy carbon electrode (GCE) to enhance electrochemical performance for furazolidone (FZD) detection. The synthesized NiFe-PBA/ZIF-67 composite exhibited excellent sensitivity, selectivity, and stability towards FZD detection, with a low limit of detection (LOD). The electrochemical behaviour of FZD on the NiFe-PBA/ZIF-67/GCE electrode was investigated, revealing a diffusion-controlled process. Differential pulse voltammetry (DPV) analysis demonstrated the synergetic effect of the PBA/MOF core-shell structure in enhancing FZD electro-reduction. The sensor exhibited exceptional LOD of 0.007 µM. Selectivity studies confirmed the sensor's ability to distinguish FZD from potential interferents. Extensive evaluations demonstrated the sensor's reproducibility, repeatability, and long-term stability, affirming its practical utility. Real sample analysis further validated the sensor's excellent analytical capabilities in diverse matrices.
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Micro/nanostructured metal surfaces fabricated by laser direct writing (LDW) have been widely used in wettability-related fields. Previous studies focused on the effects of surface structural patterns or chemical composition on wettability, while the coupling mechanism and respective contributions of the two are not distinct. This paper reveals the coupling effect of micro/nanoscale characteristics on the wettability of LDW aluminum surfaces and elucidates the transition mechanism between wetting states on the surfaces with linear laser energy density. Through the contact angle experiments, a wetting state transition of the LDW surface is found from a more hydrophilic than pristine rose petal effect to lotus effect. Based on the bionic analysis method of the superhydrophobicity factors of lotus leaves, the contributions to the wettability of LDW surfaces are divided into the micro/nanoscale characteristics. The theoretical model for identifying the wetting state of a rough surface is proposed. Based on this model, the average Young's contact angle, Î¸Ì Y, is calculated, which indicates the contribution of the nanoscale characteristics. During the transition process from rose petal effect to lotus effect, Î¸Ì Y > 90° is a necessary condition for detachment from the rose petal effect, which is contributed by the high specific surface organic adsorption at the nanoscale. What is more, the wetting state determined by the microscale characteristics further enhances its hydrophobicity, leading to the lotus effect. Based on the wetting state identification model and the Cassie-Baxter equation, the change of micro/nanoscale characteristics on aluminum surfaces after LDW treatment is presented, and the influence of micro/nanoscale characteristics on the wetting state is decoupled and quantified. This research helps to coordinate the effects of surface structure and chemical composition on wettability in the design of specific wettability functional surfaces and can also be applied to other high heat density surface processing fields.
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BACKGROUND: Oncomelania hupensis is the exclusive intermediate host of Schistosoma japonicum in China. Snail control is an essential component of schistosomiasis elimination programme. With 70 years of continuous efforts, the range of O. hupensis had reduced significantly, but slowed down in last decades. A large number of levees against flooding were constructed along Yangtze River and its affiliated lakes in the middle and lower reaches, which influenced the hydrology and ecology in the alluvial plains. The purpose of this study was to assess the impact of levees on the distribution of O. hupensis in the middle and lower reaches of the Yangtze River. METHODS: The snail habitats were digitalised by hand-held GPS system. The years for discovery and elimination of snail habitats were extracted from historical records. The accumulated snail-infested range for each habitat was calculated on the basis of annual reports. The current distribution of O. hupensis was determined by systematic and environmental sampling. The geographical distribution of levees was obtained from satellite imagery. To assess the impact of levees, the data pertaining to O. hupensis were divided into two parts: inside and outside the Yangtze River. Joinpoint regression was utilised to divide the study time span and further characterise the regression in each period. The 5-year-period moving averages of eliminated area infested by snails were calculated for the habitats inside and outside Yangtze River. The moving routes of corresponding geographical median centres were simulated in ArcGIS. Hotspot analysis was used to determine the areas with statistical significance clustering of O. hupensis density. RESULTS: Three periods were identified according to Joinpoint regression both inside and outside Yangtze River. The area infested by O. hupensis increased in the first two periods. It decreased rapidly outside Yangtze River year over year after 1970, while that inside the Yangtze River did not change significantly. Furthermore, the latter was significantly higher than the former. It was observed that the present density of O. hupensis inside Yangtze River was lower than outside the Yangtze River. The median centre for eliminated ranges inside Yangtze River wavered between the east (lower reach) and the west (middle reach). In contrast, the median centre for eliminated ranges continuously moved from the east to the west. CONCLUSIONS: Our findings indicated that the levees had a considerable negative impact on the distribution of O. hupensis outside Yangtze River. Some hotspots observed in the irrigation areas need a sluice system at the inlet of branch for snail control. The major distribution of O. hupensis located in Hubei might be caused by severe waterlogging. The intensive surveillance should be implemented there. The biggest two freshwater lakes, the major endemic regions historically, were identified as cold spots. The long-term impact of Three Gorges Dam on the distribution of O. hupensis in the lakes should be monitored and evaluated.
Subject(s)
Ecosystem , Rivers , Schistosoma japonicum , Snails , Animals , Snails/parasitology , Rivers/parasitology , China , Schistosoma japonicum/physiology , Schistosomiasis japonica/transmission , Schistosomiasis japonica/epidemiology , Schistosomiasis japonica/parasitologyABSTRACT
5-hydroxymethyl-2-furfural (5-HMF) is a by-product of Maillard reaction and widely exists in food and environment, which may lead to lung cancer. However, the relevant mechanism is unknown. This study aims to predict the key targets of 5-HMF-induced lung cancer through network toxicology, analyze the relationship between the key targets and lung cancer through network informatics, and further validate them through in vitro experiments. By using ChEMBL, STITCH, GeneCards, and OMIM databases, 51 toxic targets were identified. GO and KEGG enrichment analyses indicated a strong correlation between toxic targets and lung cancer. Through protein-protein interaction (PPI) analysis, MAPK3, MAPK1, and SRC were identified as key targets implicated in 5-HMF-induced lung cancer. The HPA database showed high expression of these three key targets in lung cancer tissues. Kaplan-Meier database demonstrated that the higher expression of these key targets in lung cancer patients was associated with a poorer prognosis. The TIMER database revealed that the high expression of these key targets had a significant impact on the level of immune cell infiltration in lung cancer, particularly impacting CD4+ T cells and macrophages. Finaly, in In vitro experiments demonstrated that prolonged exposure to 5-HMF induced malignant transformation of BEAS-2B cells and the upregulation of key targets. The findings suggest that 5-HMF is a contributing factor in the development of lung cancer, with MAPK3, MAPK1, and SRC potentially playing crucial roles in this process.
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Previously, researchers have employed Lipid nanoparticles (LNPs) to directly encapsulate medicines. In the realm of gene therapy, researchers have begun to employ lipid nanoparticles to encapsulate nucleic acids such as messenger RNA, small interfering RNA, and plasmid DNA, which are known as nucleic acid lipid nanoparticles. Recent breakthroughs in LNP-based medicine have provided significant prospects for the treatment of ocular disorders, such as corneal, choroidal, and retinal diseases. The use of LNP as a delivery mechanism for medicines and therapeutic genes can increase their effectiveness while avoiding undesired immune reactions. However, LNP-based medicines may pose ocular concerns. In this review, we discuss the general framework of LNP. Additionally, we review adjustable approaches and evaluate their possible risks. In addition, we examine newly described ocular illnesses in which LNP was utilized as a delivery mechanism. Finally, we provide perspectives for solving these potential issues.
Subject(s)
Eye Diseases , Lipids , Nanoparticles , Humans , Nanoparticles/chemistry , Lipids/chemistry , Animals , Eye Diseases/drug therapy , Genetic Therapy/methods , Drug Delivery Systems/methods , Administration, Ophthalmic , Gene Transfer Techniques , LiposomesABSTRACT
Daqu is used as the fermentation starter of Baijiu and contributes diversified functional microbes for saccharifying grains and converting sugars into ethanol and aroma components in Baijiu products. Daqu is mainly classified into three types, namely low (LTD), medium (MTD) and high (HTD) temperature Daqu, according to the highest temperatures reached in their fermentation processes. In this study, we used the PacBio small-molecule real-time (SMRT) sequencing technology to determine the full-length 16 S rRNA gene sequences from the metagenomes of 296 samples of different types of Daqu collected from ten provinces in China, and revealed the bacterial diversity at the species level in the Daqu samples. We totally identified 310 bacteria species, including 78 highly abundant species (with a relative abundance >0.1% each) which accounted for 91.90% of the reads from all the Daqu samples. We also recognized the differentially enriched bacterial species in different types of Daqu, and in the Daqu samples with the same type but from different provinces. Specifically, Lactobacillales, Enterobacterales and Bacillaceae were significantly enriched in the LTD, MTD and HTD groups, respectively. The potential co-existence and exclusion relationships among the bacteria species involved in all the Daqu samples and in the LTD, MTD and HTD samples from a specific region were also identified. These results provide a better understanding of the bacterial diversity in different types of Daqu at the species level.
Subject(s)
Bacteria , Fermentation , RNA, Ribosomal, 16S , RNA, Ribosomal, 16S/genetics , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification , Bacteria/metabolism , China , Microbiota , Phylogeny , DNA, Bacterial/genetics , Biodiversity , Alcoholic Beverages/microbiology , Alcoholic Beverages/analysis , Food Microbiology , Metagenome , Fermented Foods/microbiologyABSTRACT
Magnaporthe oryzae, one of the most destructive rice pathogens, causes significant losses during the rice harvest every year. Bacillus amyloliquefaciens has been explored in many crops as a potential biocontrol agent. However, the mechanisms of B. amyloliquefaciens controled rice blast are not fully understood. Here, a biocontrol strain LM-1, isolated from a contaminated medium, was identified as B. amyloliquefaciens using morphological observation, physiological and biochemical tests, and 16S rDNA sequencing. LM-1 inhibited the growth and pathogenicity of M. oryzae and Bipolaris oryzae (Breda de Haan) Shoem. The mycelia of M. oryzae co-cultured with LM-1 were enlarged and broken by fluorescence microscopy using calcofluor white. LM-1 inhibited the mycelia of M. oryzae from producing conidia. Genes itu, srf, and fenB were detected in LM-1. Furthermore, the supernatant of LM-1 interfered with the appressorium formation of M. oryzae, blocked conidial cell death, and reduced autophagy degradation but did not affect the normal germination of rice seeds and seeding growth. Additionally, we observed hypersensitivity reactions, reactive oxygen species, and iron accumulation reduction in rice cells inoculated with supernatant. Our study reveals that LM-1 has a control effect on rice blast and affects cell wall integrity, sporulation, appressorium formation, cell death, and autophagy.
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Rice, a critical staple on a global scale, faces escalating challenges in yield preservation due to the rising prevalence of abiotic and biotic stressors, exacerbated by frequent climatic fluctuations in recent years. Moreover, the scorching climate prevalent in the rice-growing regions of South China poses obstacles to the cultivation of good-quality, heavy-grain varieties. Addressing this dilemma requires the development of resilient varieties capable of withstanding multiple stress factors. To achieve this objective, our study employed the broad-spectrum blast-resistant line Digu, the brown planthopper (BPH)-resistant line ASD7, and the heavy-grain backbone restorer lines Fuhui838 (FH838) and Shuhui527 (SH527) as parental materials for hybridization and multiple crossings. The incorporation of molecular markers facilitated the rapid pyramiding of six target genes (Pi5, Pita, Pid2, Pid3, Bph2, and Wxb ). Through a comprehensive evaluation encompassing blast resistance, BPH resistance, cold tolerance, grain appearance, and quality, alongside agronomic trait selection, a promising restorer line, Guihui5501 (GH5501), was successfully developed. It demonstrated broad-spectrum resistance to blast, exhibiting a resistance frequency of 77.33% against 75 artificially inoculated isolates, moderate resistance to BPH (3.78 grade), strong cold tolerance during the seedling stage (1.80 grade), and characteristics of heavy grains (1,000-grain weight reaching 35.64 g) with good grain quality. The primary rice quality parameters for GH5501, with the exception of alkali spreading value, either met or exceeded the second-grade national standard for premium edible rice varieties, signifying a significant advancement in the production of good-quality heavy-grain varieties in the southern rice-growing regions. Utilizing GH5501, a hybrid combination named Nayou5501, characterized by high yield, good quality, and resistance to multiple stresses, was bred and received approval as a rice variety in Guangxi in 2021. Furthermore, genomic analysis with gene chips revealed that GH5501 possessed an additional 20 exceptional alleles, such as NRT1.1B for efficient nitrogen utilization, SKC1 for salt tolerance, and STV11 for resistance to rice stripe virus. Consequently, the restorer line GH5501 could serve as a valuable resource for the subsequent breeding of high-yielding, good-quality, and stress-tolerant hybrid rice varieties.
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Background: Gowing number of studies have demonstrated the association between gut microbiome and T2DM microvascular complications, however the causal relationship remains unclear. Therefore, we using the Mendelian randomization (MR) approach to investigate this causal relation. Methods: Using gut microbiome data from the International MiBioGen Consortium genome-wide association study (GWAS) and T2DM microvascular complications data from the FinnGen Consortium GWAS to perform MR analyses. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs), the inverse variance weighting (IVW) method was used as the primary analysis method, and the results were tested for heterogeneity and horizontal pleiotropy. Results: Our research identified that there are 5 known microbial species and 2 unknown microbial species in the gut microbiome that were causally related to T2DM retinopathy. Besides, three and seven known microbial species causal relationships between the gut microbiome and T2DM neuropathy and T2DM nephropathy, respectively. Conclusions: Using MR methods, we demonstrated the causal relationship between gut microbiome and microvascular complications in T2DM, providing a new strategy for the prevention and treatment of it.
Subject(s)
Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Genome-Wide Association Study , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Humans , Gastrointestinal Microbiome/genetics , Diabetes Mellitus, Type 2/microbiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Microvessels/microbiologyABSTRACT
Globally, breast cancer (BC) is the predominant malignancy with a significant death rate due to metastasis. The epithelial-mesenchymal transition (EMT) is a fundamental initiator for metastatic progression. Through advanced computational strategies, TCF19 was identified as a critical EMT-associated gene with diagnostic and prognostic significance in BC, based on a novel EMT score. Molecular details and the pro-EMT impact of the TCF19/miR-199a-5p/SP1/LOXL2 axis were explored in BC cell lines through in vitro validations, and the oncogenic and metastatic potential of TCF19 and LOXL2 were investigated using subcutaneous and tail-vein models. Additionally, BC-specific enrichment of TCF19 and LOXL2 was measured using a distribution landscape driven by diverse genomic analysis techniques. Molecular pathways revealed that TCF19-induced LOXL2 amplification facilitated migratory, invasive, and EMT activities of BC cells in vitro, and promoted the growth and metastatic establishment of xenografts in vivo. TCF19 decreases the expression of miR-199a-5p and alters the nuclear dynamics of SP1, modulating SP1's affinity for the LOXL2 promoter, leading to increased LOXL2 expression and more malignant characteristics in BC cells. These findings unveil a novel EMT-inducing pathway, the TCF19/miR-199a-5P/SP1/LOXL2 axis, highlighting the pivotal role of TCF19 and suggesting potential for novel therapeutic approaches for more focused BC interventions.
Subject(s)
Amino Acid Oxidoreductases , Breast Neoplasms , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , MicroRNAs , Sp1 Transcription Factor , Humans , Epithelial-Mesenchymal Transition/genetics , Female , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Sp1 Transcription Factor/metabolism , Sp1 Transcription Factor/genetics , Animals , Amino Acid Oxidoreductases/genetics , Amino Acid Oxidoreductases/metabolism , Mice , Cell Line, Tumor , Cell Movement , Neoplasm Metastasis , Signal Transduction , Mice, NudeABSTRACT
Bayesian inference has recently gained momentum in explaining music perception and aging. A fundamental mechanism underlying Bayesian inference is the notion of prediction. This framework could explain how predictions pertaining to musical (melodic, rhythmic, harmonic) structures engender action, emotion, and learning, expanding related concepts of music research, such as musical expectancies, groove, pleasure, and tension. Moreover, a Bayesian perspective of music perception may shed new insights on the beneficial effects of music in aging. Aging could be framed as an optimization process of Bayesian inference. As predictive inferences refine over time, the reliance on consolidated priors increases, while the updating of prior models through Bayesian inference attenuates. This may affect the ability of older adults to estimate uncertainties in their environment, limiting their cognitive and behavioral repertoire. With Bayesian inference as an overarching framework, this review synthesizes the literature on predictive inferences in music and aging, and details how music could be a promising tool in preventive and rehabilitative interventions for older adults through the lens of Bayesian inference.