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Climate change and anthropogenic activities have significantly contributed to the degradation of wet meadows on the Qinghai-Tibet Plateau (QTP). Soil nitrogen (N) availability is a crucial determinant of the productivity of wet meadow vegetation. Furthermore, soil microbial nitrogen functional genes (NFGs) are critical in the transformation of soil N. Nevertheless, the dynamics of NFGs in response to vegetation degradation, as well as the underlying drivers, remain poorly understood. In this study, wet meadows at varying levels of vegetation degradation on the QTP, categorized as non-degraded (ND), slightly degraded (SD), moderately degraded (MD), and heavily degraded (HD), were examined. Soil samples from depths of 0 to 10 cm and 10 to 20 cm were collected during different growth cycles (June 2020, August 2020, and May 2021). The analysis focused on NFGs involved in organic nitrogen fixation (nifH), archaeal and bacterial ammonia oxidation (amoA-AOA and amoA-AOB, respectively), and nitrite reduction (nirK), utilizing real-time fluorescence quantitative PCR. Our findings indicate a significant decline in the abundance of NFGs with intensified vegetation degradation, exhibiting notable spatial and temporal fluctuations. Specifically, the relative NFGs followed the pattern: nirK > amoA-AOA > amoA-AOB > nifH. Redundancy analysis revealed that vegetation cover was the primary regulator of NFGs abundance, accounting for 56.1%-57% of the variation. Additionally, soil total nitrogen, pH, and total phosphorus content were responsible for 38.5%, 28.2%, and 7% of the variability in NFGs, respectively. The (amoA-AOA + amoA-AOB + nirK) ratios associated with effective N transformation indicated that the vegetation degradation process moderately increased the nitrification potential. IMPORTANCE: Our research investigates how the degradation of meadows affects the tiny organisms in soil that help plants use nitrogen, which is essential for their growth. In the Qinghai-Tibet Plateau, a region known for its unique ecosystems, we found that as meadows deteriorate-due to climate change and human activities-the number of these beneficial organisms significantly decreases. This decline could reduce soil fertility, impacting plant life and the overall health of the ecosystem. Understanding these changes helps us grasp how environmental pressures influence soil and plant health. Such knowledge is crucial for developing strategies to preserve these vulnerable ecosystems and ensure they continue to sustain biodiversity and provide resources for local communities.
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Maedi-visna virus (MVV) and caprine arthritis encephalitis virus (CAEV) are members of a group of genetically highly homologous lentiviruses collectively referred to as small ruminant lentiviruses (SRLVs). SRLVs can infect sheep, goats and other small ruminants, causing multisystemic disease with progressive and persistent inflammatory changes, severely reducing animal productivity and impeding animal trade. The capsid protein of SRLVs, p28, is highly conserved among strains and is a commonly used marker for the detection of SRLVs. In this study, two monoclonal antibodies (mAbs), designated G8F7 and A10C12, against p28 were generated using a recombinant p28 protein expressed in Escherichia coli as an immunogen. Functional analysis showed that these two monoclonal antibodies could be used in iELISA, immunofluorescence assays (IFA) and western blot assays to detect p28 or Gag precursor proteins of SRLVs. Two linear epitopes, 61GNRAQKELIQGKLNEEA77 (E61-77) and 187CQKQMDRVLGTRVQQATVEEKMQACR212 (E187-212), which are recognized by G8F7 and A10C12, respectively, were identified through truncation of the GST-fused p28. Amino acid sequence alignment showed that the epitope E61-77 is conserved among SRLVs, with a dominant mutation site (K72R) that does not disrupt recognition by G8F7. E187-212 was found to exhibit variability among SRLVs, but the majority of mutant epitopes are recognized by A10C12, with the exception of a mutant epitope from an isolate with undefined subtypes from Ovis aries, which was not recognized. These findings may facilitate future study of SRLVs and promote the development of methods for the detection of these viruses.
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BACKGROUND: The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear. RESULTS: Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomics. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P < 0.05). Subsequent in vitro experiments using eEF2K siRNA and in vivo experiments with eEF2K-knockout mice demonstrated significant improvements in abnormal indicators related to ACR-induced learning and memory deficits (P < 0.05). Proteomic analysis of the hippocampus revealed Lpcat1 as a crucial downstream protein regulated by eEF2K. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that eEF2K may play a role in the process of ACR-induced learning and memory impairment by affecting ether lipid metabolism. CONCLUSIONS: In summary, eEF2K as a pivotal treatment target in the mechanisms underlying ACR-induced learning and memory impairment, and studies have shown that it provides robust evidence for potential clinical interventions targeting ACR-induced impairments.
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Colorectal cancer (CRC) is the third-largest cancer worldwide. Lactobacillus can regulate the intestinal barrier and gut microbiota. However, the mechanisms of Lactobacillus that alleviate CRC remained unknown. This study aimed to explore the regulatory effect of Lactobacillus plantarum on CRC and its potential mechanism. CCFM8661 treatment significantly ameliorated CRC compared with phosphate-buffered solution (PBS) treatment in ApcMin/+ mice. In addition, conjugated linoleic acid (CLA) was proved to be the key metabolite for CCFM8661 in ameliorating CRC by molecular biology techniques. Peroxisome proliferator-activated receptor γ (PPAR-γ) was proved to be the key receptor in ameliorating CRC by inhibitor intervention experiments. Moreover, supplementation with CCFM8661 ameliorated CRC by producing CLA to inhibit NF-κB pathway and pro-inflammatory cytokines, up-regulate ZO-1, Claudin-1, and MUC2, and promote tumor cell apoptosis in a PPAR-γ-dependent manner. Metagenomic analysis showed that CCFM8661 treatment significantly increased Odoribacter splanchnicus, which could ameliorate CRC by repairing the intestinal barrier. Clinical results showed that intestinal CLA, butyric acid, PPAR-γ, and Lactobacillus were significantly decreased in CRC patients, and these indicators were significantly negatively correlated with CRC. CCFM8661 alleviated CRC by ameliorating the intestinal barrier through the CLA-PPAR-γ axis. These results will promote the development of dietary probiotic supplements for CRC.
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Neoplasias Colorrectales , Microbioma Gastrointestinal , Mucosa Intestinal , Lactobacillus plantarum , Ácidos Linoleicos Conjugados , Ratones Endogámicos C57BL , PPAR gamma , Probióticos , Lactobacillus plantarum/metabolismo , PPAR gamma/metabolismo , PPAR gamma/genética , Animales , Ratones , Neoplasias Colorrectales/metabolismo , Humanos , Probióticos/administración & dosificación , Probióticos/farmacología , Masculino , Ácidos Linoleicos Conjugados/farmacología , Ácidos Linoleicos Conjugados/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Femenino , FN-kappa B/metabolismo , FN-kappa B/genética , Apoptosis/efectos de los fármacos , Claudina-1/metabolismo , Claudina-1/genética , Proteína de la Zonula Occludens-1/metabolismo , Proteína de la Zonula Occludens-1/genéticaRESUMEN
Excess phosphorus (P) in wastewater has potential risk of causing harmful algal bloom and eutrophication in receiving wastewater. In this study, alginate-like extracellular polymers (ALE) derived from conventional activated sludge were modified with ionic cross-linking agents (Fe3+, Ca2+, and Mg2+) to develop Fe-ALE and FeCaMg-ALE for the adsorption of phosphate from wastewater. The adsorption process of phosphate by Fe-ALE and FeCaMg-ALE can be well described by pseudo-second-order kinetics and Freundlich isotherm model with a high level of accuracy, indicating that the adsorption processes were chemical, multi-layer adsorption process. The maximum adsorption capacity of dry Fe-ALE and FeCaMg-ALE concerning phosphate were 15.06 and 20.10 mg/g, respectively at 298 K. The adsorption capacity remained relatively consistent across a pH range of 2.0-11.0. FT-IR, XRD, SEM coupled with XPS analysis demonstrated the ALE had been successfully compounded with Fe3+ or Fe3+/Ca2+/Mg2+. Based on the experimental results and characteristic analysis, the main mechanism of phosphate by Fe-ALE and FeCaMg-ALE are physical filling, electrostatic attraction, ligand exchange and precipitation reaction. This work provides a new perspective for preparing ALE-based adsorbent using conventional activated sludge as raw material, realizing the treatment of waste with waste and effectively recovering phosphate from wastewater.
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In the immunoassay process, for fulfilling the need to identify multiple analytes in a small amount of complex sample matrix, it is desirable to develop highly efficient and specific multiplex suspension array technology. Raman coding strategy offers an attractive solution to code the suspension arrays by simply combing narrow spectral bands with stable signal intensities through solid-phase synthesis on the resin beads. Based on this strategy, we report the bead-based spontaneous Raman codes for multiplex immunoassay. The study resulted in superior selectivity of the Raman-encoded beads for binding with single and multiple analytes, respectively. With the use of mixed types of Raman-encoded immunoassay beads, multiple targets in small amounts of samples were identified rapidly and accurately. By confirming the feasibility of bead-based spontaneous Raman codes for multiplex immunoassay, we anticipate this novel technology to be widely applied in the near future.
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Espectrometría Raman , Espectrometría Raman/métodos , Inmunoensayo/métodos , HumanosRESUMEN
This investigation was to study the effects of different formula components on the brain growth of rats. Fifty male SD rats were randomly divided into five groups: a basic diet group; a 20% ordinary milk powder group; a 20% special milk powder group; a 30% ordinary milk powder group; and a 30% special milk powder group by weight. LC-MS was used to detect brain lipidomics. After 28 days of feeding, compared with the basic diet group, the brain/body weights of rats in the 30% ordinary milk powder group were increased. The serum levels of 5-HIAA in the 30% ordinary milk powder group were lower than in the 20% ordinary milk powder group. Compared with the basic diet group, the expressions of DLCL, MePC, PI, and GM1 were higher in the groups with added special milk powder, while the expressions of LPE, LdMePE, SM, and MGTG were higher in the groups with added ordinary milk powder. The expression of MBP was significantly higher in the 20% ordinary group. This study found that different formula components of infant milk powder could affect brain growth in SD rats. The addition of special formula infant milk powder may have beneficial effects on rat brains by regulating brain lipid expression.
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Encéfalo , Fórmulas Infantiles , Ratas Sprague-Dawley , Animales , Encéfalo/metabolismo , Encéfalo/crecimiento & desarrollo , Encéfalo/efectos de los fármacos , Masculino , Ratas , Leche/química , Suplementos Dietéticos , Lipidómica , Polvos , Metabolismo de los Lípidos/efectos de los fármacos , Dieta/métodosRESUMEN
Spider mite infestation has a severe impact on tea growth and quality. In this study, we conducted a deep exploration of the functions and regulations of the CsPIP5K gene family using chromosomal localization and collinearity analysis. Additionally, we carefully examined the cis elements within these genes. To fully understand the metabolic response of CsPIP5K under spider mite infection, we integrated previously published metabolomic and transcriptomic data. Our analysis revealed that multiple CsPIP5K genes are associated with phospholipid metabolism, with CsPIP5K06 showing the strongest correlation. Therefore, we employed qPCR and subcellular localization techniques to determine the expression pattern of this gene and its functional location within the cell. Overall, this study not only comprehensively elucidated the characteristics, structure, and evolution of the CsPIP5K gene family but also identified several candidate CsPIP5K genes related to phospholipid biosynthesis and associated with spider mites based on previously published data. This research makes a significant contribution to enhancing the resistance of tea to spider mite and maintaining optimal tea quality.
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Camellia sinensis , Familia de Multigenes , Proteínas de Plantas , Camellia sinensis/genética , Camellia sinensis/parasitología , Animales , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Filogenia , Tetranychidae/genética , Fosfolípidos/metabolismoRESUMEN
SUMMARY: Utilizing the Mendelian randomization technique, this research clarifies the putative causal relationship between body mass index (BMI) andbone mineral density (BMD), and the mediating role of low-density lipoprotein (LDL). The implications of these findings present promising opportunities for enhancing our understanding of complex bone-related characteristics and disorders, offering potential directions for treatment and intervention. OBJECTIVE: The objective of this study is to examine the correlation between BMI and BMD, while exploring the intermediary role of LDL in mediating the causal impact of BMI on BMD outcomes via Mendelian randomization. METHODS: In this study, we employed genome-wide association study (GWAS) data on BMI, LDL, and BMD to conduct a comparative analysis using both univariate and multivariate Mendelian randomization. RESULTS: Our study employed a two-sample Mendelian randomization design. Considering BMI as the exposure and BMD as the outcome, our results suggest that BMI may function as a potential protective factor for BMD (ß = 0.05, 95% CI 1.01 to 1.09, P = 0.01). However, when treating LDL as the exposure and BMD as the outcome, our findings indicate LDL as a risk factor for BMD (ß = -0.04, 95% CI 0.92 to 0.99, P = 0.04). In our multivariate Mendelian randomization (MVMR) model, the combined influence of BMI and LDL was used as the exposure for BMD outcomes. The analysis pointed towards a substantial protective effect of LDL on BMD (ß = 0.08, 95% CI 0.85 to 0.97, P = 0.006). In the analysis of mediation effects, LDL was found to mediate the relationship between BMI and BMD, and the effect was calculated at (ß = 0.05, 95% CI 1.052 to 1.048, P = 0.04). CONCLUSION: Our findings suggest that BMI may be considered a protective factor for BMD, while LDL may act as a risk factor. Moreover, LDL appears to play a mediatory role in the causal influence of BMI on BMD.
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Índice de Masa Corporal , Densidad Ósea , Estudio de Asociación del Genoma Completo , Lipoproteínas LDL , Análisis de la Aleatorización Mendeliana , Humanos , Densidad Ósea/genética , Lipoproteínas LDL/sangre , Polimorfismo de Nucleótido Simple , FemeninoRESUMEN
Leukemic stem cells (LSCs) in chronic myeloid leukemia (CML) contribute to treatment resistance and disease recurrence. Metabolism regulates LSCs, but the mechanisms remain elusive. Here, we show that hypoxia-inducible factor 2α (HIF-2α) is highly expressed in LSCs in mouse and human CML and increases after tyrosine kinase inhibitor (TKI) treatment. Deletion of HIF-2α suppresses disease progression, reduces LSC numbers, and enhances the efficacy of TKI treatment in BCL-ABL-induced CML mice. Mechanistically, HIF-2α deletion reshapes the metabolic profile of LSCs, leading to increased production of reactive oxygen species (ROS) and apoptosis in CML. Moreover, HIF-2α deletion decreases vascular endothelial growth factor (VEGF) expression, thereby suppressing neovascularization in the bone marrow of CML mice. Furthermore, pharmaceutical inhibition of HIF-2α by PT2399 attenuates disease progression and improves the efficacy of TKI treatment in both mouse and human CML. Overall, our findings highlight the role of HIF-2α in controlling the metabolic state and vascular niche remodeling in CML, suggesting it is a potential therapeutic target to enhance TKI therapy.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Leucemia Mielógena Crónica BCR-ABL Positiva , Células Madre Neoplásicas , Inhibidores de Proteínas Quinasas , Microambiente Tumoral , Animales , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/antagonistas & inhibidores , Ratones , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Microambiente Tumoral/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Apoptosis/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Combining hydromorphone with ropivacaine in ultrasound-guided erector spinae plane blocks enhances postoperative analgesia and reduces interleukin-6 expression in breast surgery patients. METHODS: In this study, breast cancer patients undergoing modified radical mastectomy were randomized into 3 groups for anesthesia (30 patients in each group): standard general (group C), Erector Spinae Plane Block (ESPB) with ropivacaine (group R), and ESPB with ropivacaine plus hydromorphone (group HR). Diagnosis: Breast cancer patients. Postsurgery, pain levels, IL-6, anesthetic doses, additional analgesia needs, and recovery milestones were compared to evaluate the efficacy of the ESPB enhancements. RESULTS: The 3 groups were not significantly different in baseline characteristics, operation time, number of cases with postoperative nausea, and serum IL-6 concentrations at T1 (the time of being returned to the ward after surgery). At T2 (at 6:00 in the next morning after surgery), the serum IL-6 concentration in group HR was significantly lower than that in groups R and C (Pâ <â .05); the intraoperative doses of remifentanil, sufentanil, and propofol were significantly lower in groups HR and R than those in group C (Pâ <â .05); Groups HR and R had significantly lower visual analog scale scores at T3 (4 hours postoperatively), T4 (12 hours postoperatively), and T5 (24 hours postoperatively) than those in group C (Pâ <â .05); the proportions of patients receiving postoperative remedial analgesia were significantly lower in groups HR and R than in group C (Pâ <â .05); groups HR and R had significantly lower proportions of patients with postoperative nausea than group C (Pâ <â .05); the time to the first anal exhaust and the time to the first ambulation after surgery were significantly shorter in groups HR and R than those in group C (Pâ <â .05). CONCLUSION: Hydromorphone combined with ropivacaine for ESPB achieved a greater postoperative analgesic effect for patients receiving MRM under general anesthesia. The combined analgesia caused fewer adverse reactions and inhibited the expression level of the inflammatory factor IL-6 more effectively, thereby facilitating postoperative recovery. ESPB using hydromorphone with ropivacaine improved pain control post-MRM, reduced adverse effects, and more effectively suppressed IL-6, enhancing recovery.
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Analgésicos Opioides , Anestésicos Locales , Neoplasias de la Mama , Hidromorfona , Mastectomía Radical Modificada , Bloqueo Nervioso , Dolor Postoperatorio , Ropivacaína , Humanos , Ropivacaína/administración & dosificación , Ropivacaína/uso terapéutico , Femenino , Hidromorfona/administración & dosificación , Persona de Mediana Edad , Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/tratamiento farmacológico , Estudios Prospectivos , Anestésicos Locales/administración & dosificación , Anestésicos Locales/uso terapéutico , Neoplasias de la Mama/cirugía , Mastectomía Radical Modificada/métodos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Adulto , Interleucina-6/sangre , Músculos Paraespinales/efectos de los fármacos , Ultrasonografía Intervencional/métodos , Quimioterapia Combinada , Dimensión del DolorRESUMEN
Dissolved organic matter (DOM) exists widely in natural water, which inevitably influences microplastic (MP) photoaging. Nevertheless, the impacts of DOM fractions with diverse molecular structures on MP photoaging remain to be elucidated. This study explored the photoaging mechanisms of polylactic acid (PLA)-MPs and polystyrene (PS)-MPs in the presence of DOM and its subfractions (hydrophobic acid (HPOA), hydrophobic neutral (HPON), and hydrophilic (HPI)). Across DOM fractions, HPI exhibited the highest electron accepting capacity (23 µmol e- (mg C)-1) due to its abundant tannin-like species (36.8%) with carboxylic groups, which facilitated more reactive oxygen species generation (particularly hydroxyl radical), leading to the strongest photoaging rate of two MPs by HPI. However, the sequences of bond cleavage during photoaging of each MPs were not clearly shifted as revealed by two-dimensional infrared correlation spectra. Inconspicuous effects on the extent of PS- and PLA-MPs photoaging were observed for HPOA and HPON, respectively. This was mainly ascribed to the occurrence of inhibitory mechanisms (e.g., light-shielding and quenching effect) counteracting the reactive oxygen species-promoting effects. The findings identified the HPI fraction of DOM for promoting PS- and PLA-MPs photoaging rate and first constructed a link among DOM molecular structures, redox properties, and effects on MP photoaging.
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Interacciones Hidrofóbicas e Hidrofílicas , Microplásticos , Oxidación-Reducción , Especies Reactivas de Oxígeno , Especies Reactivas de Oxígeno/metabolismo , Poliestirenos/química , Poliésteres/química , Contaminantes Químicos del Agua/químicaRESUMEN
Human health and the ecological balance are both gravely threatened by heavy metal pollution brought on by global industrialization. Probiotics are thought to represent a novel class of medicinal products for reducing heavy metal toxicity. Though simultaneous poisoning of numerous heavy metals is more prevalent, the majority of current studies on probiotics in the treatment of heavy metal poisoning concentrate on a single heavy metal. Thus, a mouse damage model was created in this investigation using five heavy metals (Pb, Cd, Hg, Cr, and As), and Lactiplantibacillus plantarum CCFM8661 was utilized as an intervention therapy. The oxidative stress markers, including superoxide dismutase (SOD), catalase (CAT), antioxidant capacity (T-AOC), and malondialdehyde (MDA), were evaluated in the blood, liver, and kidney tissues of mice throughout the experiment by tracking changes in body weight. Additionally, the amounts of five heavy metals were measured in the liver and kidney tissues. The alleviation of tissue damage and the detoxifying activity of L. plantarum CCFM8661 in mice with combined heavy metal intoxication were assessed by histopathological examination of liver and kidney tissues. Results revealed that during the test period, L. plantarum CCFM8661 significantly reduced the content of MDA and the contents of Pb, Cd, Hg, Cr, and As in liver and kidney tissues, while also significantly increasing weight gain and the activities of SOD, CAT, and T-AOC in mouse blood, liver, and kidney tissues compared to the model group. Mouse liver and kidney tissue damage from combined heavy metal exposure was considerably lessened by L. plantarum CCFM8661 when compared to the model group, according to H&E staining. This study demonstrates that L. plantarum CCFM8661 may be utilized as a useful intervention for the treatment of combined heavy metal poisoning by efficiently reducing the harm that heavy metals do to the body and maintaining bodily health.
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Riñón , Hígado , Metales Pesados , Probióticos , Animales , Ratones , Probióticos/farmacología , Probióticos/uso terapéutico , Hígado/efectos de los fármacos , Hígado/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Lactobacillus plantarum , Superóxido Dismutasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas , Malondialdehído/metabolismo , Catalasa/metabolismoRESUMEN
Paclitaxel (PTX) remains an essential drug in the treatment of breast cancer. To improve metabolic stability and real-time monitoring of drug location, we develop a visualized nano-prodrug. Novel hyaluronic acid (HA)-coated glutathione (GSH)-sensitive chitosan (CS)-based nano-prodrug (HA/TPE-CS-SS-PTX NPs) with aggregation-induced emission effects (AIE) were accomplished. The prodrug NPs (drug loading 29.32%, particle size 105 nm, regular sphericity) exhibit excellent fluorescence stability. The prodrug NPs could target tumor cells with high expression of CD44 and decompose in the presence of high concentrations of glutathione. In vitro evaluations revealed that the prodrug NPs have significant cytotoxicity on 4T1 cells, and due to their excellent AIE characteristics, their position in cells can be tracked. Moreover, the prodrug NPs also shown superior anti-tumor effects in vivo experimental. Overall, the HA/TPE-CS-SS-PTX NPs we constructed have excellent bio-imaging capabilities and can be served as a potential nanomedicine for PTX delivery against breast cancer.
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Background and Objective: Cognitive dysfunction is highly prevalent in obese people, and food is a key factor in obesity, and dietary inflammatory index (DII) can reflect whether diet has anti-inflammatory or pro-inflammatory potential. In addition, dietary fatty acid consumption is linked to inflammation, obesity, and cognitive impairment. Erythrocyte membrane fatty acids can reflect dietary fatty acid intake. Our hypothesis was that erythrocyte membrane fatty acids might have a significant impact on the relationship between DII and cognition in obese individuals, and we designed experiments to test the hypothesis. Methods: In three villages in Beijing, we collected 579 respondents from individuals 45 to 75 years old and categorized them by body mass index. The Montreal Cognitive Assessment (MoCA) score and DII score was calculated and gas chromatography was used to measure the proportion of erythrocyte membrane fatty acids. The relationship between the DII score and cognition was examined using multiple linear regression and binary logistic regression. Mediation analysis can help to understand the causal chain between variables, deeply explore the internal relationship and mechanism of action between variables. So a multiple chain mediation model was developed to investigate the mediating factors between the DII score and cognitive association. Results: According to adjusted linear regression, higher DII scores were linked to lower MoCA scores in the obese group. The negative correlation between DII score and cognitive function score remains in binary linear regression. We discovered through mediation analysis that erythrocyte membrane fatty acids mediate the detrimental link between DII and cognitive function in obese individuals. Conclusion: We propose that higher DII scores in obese people are associated with a decline in cognitive function. In addition, this effect might be mediated via the fatty acids in the erythrocyte membrane.
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Prostate cancer (PCa) is an extensive heterogeneous disease with a complex cellular ecosystem in the tumor microenvironment (TME). However, the manner in which heterogeneity is shaped by tumors and stromal cells, or vice versa, remains poorly understood. In this study, single-cell RNA sequencing, spatial transcriptomics, and bulk ATAC-sequence are integrated from a series of patients with PCa and healthy controls. A stemness subset of club cells marked with SOX9highARlow expression is identified, which is markedly enriched after neoadjuvant androgen-deprivation therapy (ADT). Furthermore, a subset of CD8+CXCR6+ T cells that function as effector T cells is markedly reduced in patients with malignant PCa. For spatial transcriptome analysis, machine learning and computational intelligence are comprehensively utilized to identify the cellular diversity of prostate cancer cells and cell-cell communication in situ. Macrophage and neutrophil state transitions along the trajectory of cancer progression are also examined. Finally, the immunosuppressive microenvironment in advanced PCa is found to be associated with the infiltration of regulatory T cells (Tregs), potentially induced by an FAP+ fibroblast subset. In summary, the cellular heterogeneity is delineated in the stage-specific PCa microenvironment at single-cell resolution, uncovering their reciprocal crosstalk with disease progression, which can be helpful in promoting PCa diagnosis and therapy.
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Neoplasias de la Próstata , Análisis de la Célula Individual , Microambiente Tumoral , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Análisis de la Célula Individual/métodos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Perfilación de la Expresión Génica/métodos , MultiómicaRESUMEN
Functional constipation (FC) can seriously affect the physical and mental health of children. The goal of this study is to assess the efficacy and safety of Bifidobacterium animalis subsp. lactis XLTG11 in treating FC in children through a randomized, double-blinded, placebo-controlled approach. Eligible children were randomized into either the intervention group (IG, n = 65, receiving conventional treatment with probiotics) or the control group (CG, n = 66, receiving conventional treatment without probiotics). The primary outcome measure was fecal frequency. Fecal gut microbiota analysis and PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) were used to predict gene family abundances based on 16S information. Over the course of treatment, the weekly frequency of feces within each group increased significantly (F = 41.97, p < 0.001). The frequency of feces (times/week (t/w)) in the IG was significantly higher than that in the CG (3.69 ± 2.62 t/w vs.3.18 ± 1.43 t/w, 4.03 ± 2.54 t/w vs. 2.89 ± 1.39 t/w and 3.74 ± 2.36 t/w vs. 2.94 ± 1.18 t/w and 3.45 ± 1.98 vs. 3.17 ± 1.41 t/w for the 1st, 2nd, 3rd, and 4th week after intervention, respectively) (F = 7.60, p = 0.0067). After the intervention, dominate species shifted to Bifidobacterium longum, Bifidobacterium breve, and Escherichia coli in the IG. Additionally, genes related to short-chain fatty acid (SCF) metabolism were upregulated, while methane metabolism was downregulated. Administration of XLTG11 at a dose of 1 × 1010 CFU/day to children increased fecal frequency, induced beneficial changes in gut microbiota, and regulated SCFs and methane metabolism-related genes.
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Bifidobacterium animalis , Estreñimiento , Heces , Microbioma Gastrointestinal , Probióticos , Estreñimiento/microbiología , Estreñimiento/terapia , Estreñimiento/fisiopatología , Humanos , Probióticos/administración & dosificación , Bifidobacterium animalis/genética , Bifidobacterium animalis/fisiología , Heces/microbiología , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Niño , Femenino , Método Doble Ciego , Preescolar , Resultado del Tratamiento , Filogenia , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/efectos de los fármacosRESUMEN
BACKGROUND: Tuberculosis (TB) is not only related to infection but also involves immune factors. This study explores the changes in T-lymphocyte subsets in children with TB who are human immunodeficiency virus (HIV)-negative and examines their relationship using chest computed tomography (CT) scans. Additionally, the study identifies risk factors for severe TB (STB) in children and establishes relevant risk prediction models. METHODS: We recruited 235 participants between 2018 and 2022, comprising 176 paediatric patients with TB who were HIV-negative and 59 age-matched children with bacterial community-acquired pneumonia (CAP). We quantitatively analysed and compared T-lymphocyte subsets between the two groups and among different types of TB infection. Both univariate and multivariate analyses of clinical and laboratory characteristics were conducted to identify independent risk factors for STB in children and to establish a risk prediction model. RESULTS: The absolute counts of CD3, CD4 and CD8 T-cells in children with TB infection decreased significantly compared with bacterial CAP. The percentage of CD8 T-cells increased, whereas the percentage of CD4 T-cells did not change significantly. The absolute count of CD3, CD4 and CD8 T-cells in extrapulmonary TB (EPTB) was significantly higher than in extra-respiratory TB, with unchanged subset percentages. According to chest CT lesion classification, CD4 T-cell counts decreased significantly in S3 compared with S1 or S2, with no significant change in CD3 and CD8 T-cell counts and percentages. No significant differences were observed in lymphocyte subset counts and percentages between S1 and S2. Univariate analyses indicated that factors such as age, symptom duration, white blood cell count, platelet count, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate, prealbumin level, albumin level, globulin level, albumin/globulin (A/G) ratio, high-sensitivity C-reactive protein (Hs-CRP) level and CD4 and CD8 T-cell counts are associated with STB. Multivariate logistic regression analysis revealed that age, Hs-CRP level, NLR, symptom duration and A/G ratio are independent risk factors for STB in children. Increased age, Hs-CRP levels and NLR, along with decreased A/G, correlate with increased susceptibility to STB. A nomogram model, based on these independent risk factors, demonstrated an area under the receiver operating characteristics curve of 0.867 (95% CI: 0.813-0.921). Internal verification confirmed the model's accuracy, with the calibration curve approaching the ideal and the Hosmer-Lemeshow goodness-of-fit test showing consistent results (χ2 = 12.212, p = 0.142). CONCLUSION: In paediatric patients with TB, the absolute counts of all lymphocyte subsets were considerably reduced compared with those in patients with bacterial CAP. Clinicians should consider the possibility of EPTB infection in addition to respiratory infections in children with TB who have higher CD3, CD4 and CD8 T-cell counts than the ERTB group. Furthermore, CD4 T-cell counts correlated closely with the severity of chest CT lesions. Age, symptom duration, A/G ratio, Hs-CRP level and NLR were established as independent risk factors for STB. The nomogram model, based on these factors, offers effective discrimination and calibration in predicting STB in children.
Asunto(s)
Globulinas , Infecciones por VIH , Tuberculosis Latente , Mycobacterium tuberculosis , Tuberculosis , Humanos , Niño , Proteína C-Reactiva , Subgrupos de Linfocitos T , Tuberculosis/diagnóstico , Factores de Riesgo , Subgrupos Linfocitarios , Recuento de LinfocitosRESUMEN
BACKGROUND: Osteoarthritis (OA), a prevalent musculoskeletal disorder, has been suggested to have a potential association with metabolic syndrome, particularly lipid metabolism. Studies exploring the effects of lipid-lowering drugs on OA have yielded conflicting results. OBJECTIVE: This study employed a drug-targeted Mendelian randomization approach to investigate the association between genetically predicted lipid-modulating effects of commonly targeted lipid-lowering agents and the risk of OA, with the aim of providing a theoretical foundation for the use of lipid-lowering drugs in OA treatment. METHODS: Employing Mendelian randomization (MR) analysis, we examined the potential causal relationship between lipid-lowering drugs and OA. Genetic variants associated with LDL cholesterol levels were selected from the GWAS summary data, and a series of statistical analyses, including inverse-variance weighted (IVW), weighted median (WM), and MR-Egger, were performed to estimate causal effects. RESULTS: We observed significant associations between genetically proxied lipid-lowering drug targets and OA risk. Notably, HMGCR-mediated LDL cholesterol showed an association with overall OA of the hip or knee (OR = 0.865, 95%CI: 0.762 to 0.983, p = 0.026, q = 0.07) and knee osteoarthritis specifically (OR = 0.746, 95%CI: 0.639 to 0.871, p = 2.180×10-4, q = 0.004). PCSK9-mediated LDL cholesterol also demonstrated an association with OA of the hip or knee (OR = 0.915, 95%CI: 0.847 to 0.988, p = 0.023, q = 0.07) and knee osteoarthritis (OR = 0.901, 95%CI: 0.821 to 0.990, p = 0.03, q = 0.07). NPC1L1-mediated LDL cholesterol showed a positive association with OA of the hip or knee (OR = 1.460, 95%CI: 1.127 to 1.890, p = 0.004, q = 0.033). Furthermore, LDLR-mediated LDL cholesterol demonstrated an association with OA of the hip or knee (OR = 0.882, 95%CI: 0.788 to 0.988, p = 0.03, q = 0.07) and hip osteoarthritis (OR = 0.867, 95%CI: 0.769 to 0.978, p = 0.02, q = 0.07). CONCLUSIONS: These findings provide preliminary evidence for the potential therapeutic use of lipid-lowering drugs in OA treatment. Further investigation is needed to validate these findings and explore the precise mechanisms underlying the observed associations.
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Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/tratamiento farmacológico , Osteoartritis de la Rodilla/genética , Proproteína Convertasa 9 , LDL-Colesterol , Análisis de la Aleatorización Mendeliana , Hipolipemiantes/efectos adversos , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido SimpleRESUMEN
Leukaemia stem cells (LSCs) in acute myeloid leukaemia present a considerable treatment challenge due to their resistance to chemotherapy and immunosurveillance. The connection between these properties in LSCs remains poorly understood. Here we demonstrate that inhibition of tyrosine phosphatase SHP-1 in LSCs increases their glycolysis and oxidative phosphorylation, enhancing their sensitivity to chemotherapy and vulnerability to immunosurveillance. Mechanistically, SHP-1 inhibition leads to the upregulation of phosphofructokinase platelet (PFKP) through the AKT-ß-catenin pathway. The increase in PFKP elevates energy metabolic activities and, as a consequence, enhances the sensitivity of LSCs to chemotherapeutic agents. Moreover, the upregulation of PFKP promotes MYC degradation and, consequently, reduces the immune evasion abilities of LSCs. Overall, our study demonstrates that targeting SHP-1 disrupts the metabolic balance in LSCs, thereby increasing their vulnerability to chemotherapy and immunosurveillance. This approach offers a promising strategy to overcome LSC resistance in acute myeloid leukaemia.