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Soybean represents a vital source of premium plant-based proteins for human nutrition. Importantly, the level of water-soluble protein (WSP) is crucial for determining the overall quality and nutritional value of such crops. Enhancing WSP levels in soybean plants is a high-priority goal in crop improvement. This study aimed to elucidate the genetic basis of WSP content in soybean seeds by identifying quantitative trait loci (QTLs) and set the foundation for subsequent gene cloning and functional analysis. Using 180 F10 recombinant inbred lines generated by crossing the high-protein soybean cultivar JiDou 12 with the wild variety Ye 9, our researcher team mapped the QTLs influencing protein levels, integrating Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene expression profiling to identify candidate genes. During the 2020 and 2022 growing seasons, a standard bell-shaped distribution of protein content trait data was observed in these soybean lines. Eight QTLs affecting protein content were found across eight chromosomes, with LOD scores ranging from 2.59 to 7.30, explaining 4.15-11.74% of the phenotypic variance. Notably, two QTLs were newly discovered, one with a elite allele at qWSPC-15 from Ye 9. The major QTL, qWSPC-19, on chromosome 19 was stable across conditions and contained genes involved in nitrogen metabolism, amino acid biosynthesis, and signaling. Two genes from this QTL, Glyma.19G185700 and Glyma.19G186000, exhibited distinct expression patterns at maturity, highlighting the influence of these genes on protein content. This research revealed eight QTLs for WSP content in soybean seeds and proposed a gene for the key QTL qWSPC-19, laying groundwork for gene isolation and enhanced soybean breeding through the use of molecular markers. These insights are instrumental for developing protein-rich soybean cultivars.
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Mapeo Cromosómico , Glycine max , Sitios de Carácter Cuantitativo , Semillas , Glycine max/genética , Glycine max/metabolismo , Semillas/genética , Semillas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Agua/metabolismo , Solubilidad , FenotipoRESUMEN
OBJECTIVE: To investigate changes of myeloid differentiation factor 2 (MD2) in inflammation-induced pain and acupuncture-mediated analgesia. METHODS: Mice were randomly divided into three groups by a random number table method: saline group (n=16), complete Freund's adjuvant (CFA) group (n=24) and CFA+electroacupuncture (EA) group (n=26). Inflammation-induced pain was modelled by injecting CFA to the plantar surface of the hind paw of mice and EA was applied to bilateral Zusanli (ST 36) to alleviate pain. Only mice in the CFA+EA group received EA treatment (30 min/d for 2 weeks) 24 h after modelling. Mice in the saline and CFA groups received sham EA. von-Frey test and Hargreaves test were used to assess the pain threshold. Brain and spinal tissues were collected for immunofluorescence staining or Western blotting to quantify changes of MD2 expression. RESULTS: CFA successfully induced plantar pain and EA significantly alleviated pain 3 days after modelling (P<0.01). Compared with the CFA group, the number of MD2+/c-fos+ neurons was significantly increased in the dorsal horn of the spinal cord 7 and 14 days after EA, especially in laminae I - IIo (P<0.01). The proportion of double positive cells to the number of c-fos positive cells and the mean fluorescence intensity of MD2 neurons were also significantly increased in laminae I - IIo (P<0.01). Western blotting showed that the level of MD2 was significantly decreased by EA only in the hippocampus on day 7 and 14 (both P<0.01) and no significant changes were observed in the cortex, thalamus, cerebellum, or the brainstem (P<0.05). Fluorescence staining showed significant decrease in the level of MD2 in periagueductal gray (PAG) and locus coeruleus (LC) after CFA injection on day 7 (P<0.01 for PAG, P<0.05 for LC) and EA significantly reversed this decrease (P<0.01 for PAG, P<0.05 for LC). CONCLUSION: The unique changes of MD2 suggest that EA may exert the analgesic effect through modulating neuronal activities of the superficial laminae of the spinal cord and certain regions of the brain.
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BACKGROUND: Pork quality is affected by the type of muscle fibers, which is closely related to meat color, tenderness and juiciness. Exosomes are tiny vesicles with a diameter of approximately 30-150 nm that are secreted by cells and taken up by recipient cells to mediate communication. Exosome-mediated muscle-fat tissue crosstalk is a newly discovered mechanism that may have an important effect on intramuscular fat deposition and with that on meat quality. Various of adipose tissue-derived exosomes have been discovered and identified, but the identification and function of muscle exosomes, especially porcine fast/slow myotube exosomes, remain unclear. Here, we first isolated and identified exosomes secreted from porcine extensor digitorum longus (EDL) and soleus (SOL), which represent fast and slow muscle, respectively, and further explored their effects on lipid accumulation in longissimus dorsi adipocytes. RESULTS: Porcine SOL-derived exosomes (SOL-EXO) and EDL-derived exosomes (EDL-EXO) were first identified and their average particle sizes were approximately 84 nm with double-membrane disc- shapes as observed via transmission electron microscopy and scanning electron microscopy. Moreover, the intramuscular fat content of the SOL was greater than that of the EDL at 180 days of age, because SOL intramuscular adipocytes had a stronger lipid-accumulating capacity than those of the EDL. Raman spectral analysis revealed that SOL-EXO protein content was much greater than that of EDL-EXO. Proteomic sequencing identified 72 proteins that were significantly differentially expressed between SOL-EXO and EDL-EXO, 31 of which were downregulated and 41 of which were upregulated in SOL-EXO. CONCLUSIONS: Our findings suggest that muscle-fat tissue interactions occur partly via SOL-EXO promoting adipogenic activity of intramuscular adipocytes.
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In China, Camellia plants are widely used to reduce atopic dermatitis and inflammation-related diseases, but their protective mechanisms remain unclear. This study investigated the anti-allergic dermatitis, anti-oxidation and anti-inflammation effect and underlying mechanism of five Camellia species, including Camellia ptilophylla Chang, Camellia assamica Chang var. Kucha Chang, Camellia parvisepala Chang, Camellia arborescens Chang, and C. assamica M. Chang. A total of about 110 chemical compositions were detected from five Camellia teas extracts. The level of mast cell infiltration in the model mice skin was determined by HE (Hematoxylin and eosin) staining and toluidine blue staining, and the level of interleukin-1ß (IL-1ß) and nerve growth factor was detected by immunohistochemistry. The five Camellia tea leaf extracts have histamine-induced allergic dermatitis. Lipopolysaccharide (Lipopolysaccharide)-induced murine macrophage RAW264.7 inflammation model was found to secrete NF-κB factor, as shown by immunofluorescence, and reactive oxygen species secretion and related cytokine levels were detected. The results suggested that Camellia's five tea extracts had the ability to resist cellular oxidative stress. In addition, the results of cell inflammatory cytokines including fibronectin (FN) and interleukin-6 (IL-6) suggested that the five tea extracts of Camellia had anti-inflammatory effects. Therefore, it is suggested that five Camellia teas may possess inhibitory properties against allergic reactions, oxidative stress, and inflammation, and may prove beneficial in the treatment of allergies.
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2-Ethylhexyl diphenyl phosphate (EHDPP) is a representative organophosphorus flame retardant (OPFR) that has garnered attention due to its widespread use and potential adverse effects. EHDPP exhibits cytotoxicity, genotoxicity, developmental toxicity, and endocrine disruption. However, the toxicity of EHDPP in mammalian oocytes and the underlying mechanisms remain poorly understood. Melatonin is a natural free radical scavenger that has demonstrated cytoprotective properties. In this study, we investigated the effect of EHDPP on mouse oocytes in vitro culture system and evaluated the rescue effect of melatonin on oocytes exposed to EHDPP. Our results indicated that EHDPP disrupted oocyte maturation, resulting in the majority of oocytes arrested at the metaphase I (MI) stage, accompanied by cytoskeletal damage and elevated levels of reactive oxygen species (ROS). Nevertheless, melatonin supplementation partially rescued EHDPP-induced mouse oocyte maturation impairment. Results of single-cell RNA sequencing (scRNA-seq) analysis elucidated potential mechanisms underlying these protective effects. According to the results of scRNA-seq, we conducted further tests and found that EHDPP primarily disrupts mitochondrial distribution and function, kinetochore-microtubule (K-MT) attachment, DNA damage, apoptosis, and histone modification, which were rescued upon the supplementation of melatonin. This study reveals the mechanisms of EHDPP on female reproduction and indicates the efficacy of melatonin as a therapeutic intervention for EHDPP-induced defects in mouse oocytes.
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Retardadores de Llama , Melatonina , Mitocondrias , Oocitos , Animales , Melatonina/farmacología , Ratones , Oocitos/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Femenino , Retardadores de Llama/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Organofosfatos/toxicidad , Daño del ADN/efectos de los fármacos , Apoptosis/efectos de los fármacos , Compuestos Organofosforados/toxicidadRESUMEN
Intramuscular fat (IMF) contributed positively to pork quality, whereas subcutaneous fat (SCF) was often considered to be a detrimental factor impacting growth and carcass traits. Reducing SCF while maintaining optimal IMF levels requires a thorough understanding of the adipogenic differences between these two adipose depots. Our study explored the differences in adipogenesis between porcine IMF and SCF, and the results showed that subcutaneous adipocytes (SCAs) demonstrate a greater potential for adipogenic differentiation, both in vivo and in vitro. Lipidomic and transcriptomic analyses suggested that intramuscular adipocytes (IMAs) are more inclined to biosynthesize unsaturated fatty acids. Furthermore, single-cell RNA sequencing (scRNA-seq) was employed to dissect the intrinsic and microenvironmental discrepancies in adipogenesis between porcine IMF and SCF. Comparative analysis indicated that SCF was enriched with preadipocytes, exhibiting an enhanced adipogenic potential, while IMF was characterized by a higher abundance of stem cells. Furthermore, coculture analyses of porcine intramuscular adipogenic cells and myogenetic cells indicated that the niche of IMAs inhibited its adipogenic differentiation. Cell communication analysis identified 160 ligand-receptor pairs and channels between adipogenic and myogenetic cells in IMF. Collectively, our study elucidated two intrinsic and microenvironmental novel mechanisms underpinning the divergence in adipogenesis between porcine SCF and IMF.
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Endometrial cancer (EC) is a common malignancy among women worldwide, and its recurrence makes it a common cause of cancer-related death. Surgery and external radiation, chemotherapy, or a combination of strategies are the cornerstone of therapy for EC patients. However, adjuvant treatment strategies face certain drawbacks, such as resistance to chemotherapeutic drugs; therefore, it is imperative to explore innovative therapeutic strategies to improve the prognosis of EC. With the development of pathology and pathophysiology, several biological targets associated with EC have been identified, including PI3K/Akt/mTOR, PARP, GSK-3ß, STAT-3, and VEGF. In this review, we summarize the progress of small molecule targeted therapies in terms of both basic research and clinical trials and provide cases of small molecules combined with fluorescence properties in the clinical applications of integrated diagnosis and treatment. We hope that this review will facilitate the further understanding of the regulatory mechanism governing the dysregulation of oncogenic signaling in EC and provide insights into the possible future directions of targeted therapeutic regimens for EC treatment by developing new agents with fluorescence properties for the clinical applications of integrated diagnosis and treatment.
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INTRODUCTION: This study aims to evaluate the effectiveness of aprepitant in preventing postoperative nausea and vomiting (PONV) following metabolic bariatric surgery (MBS). METHODS: Clinical trials meeting the inclusion criteria were identified through searches of PubMed, Embase, and the Cochrane Library databases, as well as clinical trials registered at clinicaltrials. gov. These trials compared aprepitant with the control or placebo groups among patients who underwent MBS. Meta-analysis was performed using StataSE 17.0 software to calculate the pooled risk ratio (RR) and its 95% confidence interval (CI) to assess the effectiveness of aprepitant in preventing PONV following MBS. RESULTS: A total of five articles comprising six studies including 929 patients undergoing MBS were included. Meta-analysis revealed a significant reduction in the incidence of PONV among patients receiving aprepitant (pooled RR = 0.51, 95% CI: 0.38-0.68, P < 0.05). Subgroup analysis indicated that aprepitant effectively reduced PONV incidence at 0, 6, and 12 h postoperatively in patients with MBS, but did not decrease PONV occurrence at 24 and 48 h postoperatively. CONCLUSION: Aprepitant demonstrated significant clinical efficacy in preventing PONV following MBS, effectively reducing patient discomfort, and improving postoperative recovery. Therefore, aprepitant should be considered a preventive measure in patients undergoing MBS to enhance patient satisfaction and recovery rates. Additionally, to maintain an effective drug concentration, aprepitant should be administered within the first 24 h postoperatively. PROSPERO REGISTRATION: CRD 42024528154.
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Antieméticos , Aprepitant , Cirugía Bariátrica , Morfolinas , Náusea y Vómito Posoperatorios , Humanos , Náusea y Vómito Posoperatorios/prevención & control , Aprepitant/uso terapéutico , Antieméticos/uso terapéutico , Cirugía Bariátrica/efectos adversos , Morfolinas/uso terapéutico , Resultado del Tratamiento , Obesidad Mórbida/cirugía , Femenino , Masculino , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The issue of soil acidification in tea plantations has become a critical concern due to its potential impact on tea quality and plant health. Understanding the factors contributing to soil acidification is essential for implementing effective soil management strategies in tea-growing regions. In this study, a field study was conducted to investigate the effects of tea plantations on soil acidification and the associated acid-base buffering capacity (pHBC). We assessed acidification, pHBC, nutrient concentrations, and cation contents in the top 0-20 cm layer of soil across forty tea gardens of varying stand ages (0-5, 5-10, 10-20, and 20-40 years old) in Anji County, Zhejiang Province, China. The results revealed evident soil acidification due to tea plantation activities, with the lowest soil pH observed in tea gardens aged 10-20 and 20-40 years. Higher levels of soil organic matter (SOM), total nitrogen (TN), Olsen phosphorus (Olsen-P), available iron (Fe), and exchangeable hydrogen (H+) were notably recorded in 10-20 and 20-40 years old tea garden soils, suggesting an increased risk of soil acidification with prolonged tea cultivation. Furthermore, prolonged tea cultivation correlated with increased pHBC, which amplified with tea stand ages. The investigation of the relationship between soil pHBC and various parameters highlighted significant influences from soil pH, SOM, cation exchange capacity, TN, available potassium, Olsen-P, exchangeable acids (including H+ and aluminum), available Fe, and available zinc. Consequently, these findings underscore a substantial risk of soil acidification in tea gardens within the monitored region, with SOM and TN content being key driving factors influencing pHBC.
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Camellia sinensis , Monitoreo del Ambiente , Nitrógeno , Suelo , Suelo/química , Camellia sinensis/química , Nitrógeno/análisis , China , Concentración de Iones de Hidrógeno , Ecosistema , Fósforo/análisis , Té/química , AgriculturaRESUMEN
Postnatal immune activation (PIA) induces persistent glial activation in the brain and causes various neuropathologies in adults. Exercise training improves stress-related mood disorders; however, the role of exercise in psychiatric disorders induced by early-life immune activation and the association between exercise training and glial activation remain unclear. We compared the effects of different exercise intensities on the PIA model, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Both HIIT and MICT in adolescent mice inhibited neuroinflammation, remodeled synaptic plasticity, and improved PIA-induced mood disorders in adulthood. Importantly, HIIT was superior to MICT in terms of reducing inflammation and increasing body weight. RNA-seq of prefrontal cortex (PFC) tissues revealed a gene expression pattern, confirming that HIIT was more effective than MICT in improving brain glial cell activation through epigenetic modifications of KDM6B. We investigated the role of KDM6B, a specific histone lysine demethylation enzyme - histone 3 lysine 27 demethylase, in inhibiting glial activation against PIA-induced depression and anxiety by regulating the expression of IL-4 and brain-derived neurotrophic factor (BDNF). Overall, our data support the idea that HIIT improves PIA-induced mood disorders by regulating KDM6B-mediated epigenetic mechanisms and indicate that HIIT might be superior to MICT in improving mood disorders with PIA in mice. Our findings provide new insights into the treatment of anxiety and depression disorders.
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Entrenamiento de Intervalos de Alta Intensidad , Histona Demetilasas con Dominio de Jumonji , Trastornos del Humor , Neuroglía , Condicionamiento Físico Animal , Animales , Ratones , Histona Demetilasas con Dominio de Jumonji/metabolismo , Neuroglía/metabolismo , Neuroglía/inmunología , Entrenamiento de Intervalos de Alta Intensidad/métodos , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Trastornos del Humor/metabolismo , Masculino , Corteza Prefrontal/metabolismo , Ratones Endogámicos C57BL , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Plasticidad Neuronal/fisiología , Encéfalo/metabolismo , Encéfalo/inmunología , Epigénesis Genética , Modelos Animales de Enfermedad , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/metabolismo , Inflamación/metabolismo , Inflamación/inmunología , FemeninoRESUMEN
Modifications at different positions on the aloperine molecule were performed to improve its anticancer activity and develop anticancer drugs. The in vitro anticancer activities of 44 synthesized compounds were evaluated. The effect of modification positions on anticancer activity was discussed and a structure-activity relationship analysis was established. A novel series of compounds with modifications at the N12 position showed much higher cytotoxicity than aloperine. Among them, compound 22 displayed promising in vitro anticancer activity against PC9 cells with a median inhibitory concentration (IC50) of 1.43 µM. The mechanism studies indicated that compound 22 induced cell apoptosis and cell cycle arrest in PC9 cells. These results demonstrate the potential of aloperine thiourea derivatives in anticancer activity.
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Antineoplásicos , Apoptosis , Ensayos de Selección de Medicamentos Antitumorales , Piperidinas , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Humanos , Relación Estructura-Actividad , Estructura Molecular , Apoptosis/efectos de los fármacos , Piperidinas/farmacología , Piperidinas/química , Piperidinas/síntesis química , Diseño de Fármacos , Quinolizidinas/farmacología , Quinolizidinas/química , Quinolizidinas/síntesis química , Línea Celular Tumoral , Puntos de Control del Ciclo Celular/efectos de los fármacosRESUMEN
Limited information is available on the cardiovascular health (CVH) index and risk of high-normal blood pressure (HNBP) in elderly people. Randomized cluster sampling, multivariate logistic regression, and mediating effects analysis were used in this study analyze the relationship between CVH index and HNBP in the elderly. 1089 non-hypertensive residents aged 65 years or older completed the study. The positive rate of HNBP was 75.85% (male vs. female: 76.13% vs. 75.64%, P = 0.852); The ideal rate of CVH (ideal CVH index ≥ 5 items) was 14.51% (male vs. female: 15.91% vs. 13.46%, P = 0.256). Compared with people with 0-2 ideal CVH index, the risk of HNBP in people with 4 ideal indexes and ≥ 5 ideal indexes decreased by 50% and 63%, respectively, and their OR (95% CI) were 0.50 (0.31, 0.81) and 0.37 (0.21, 0.66), respectively. The results of the trend test showed that the risk of HNBP decreased by 32% for every increase in the ideal CVH index (trend P < 0.001) and TyG index does not play a mediating role in this relationship. That is, increasing the number of ideal CVH index may effectively reduce the risk of HNBP in elderly by one-third.
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Presión Sanguínea , Humanos , Anciano , Femenino , Masculino , Presión Sanguínea/fisiología , Anciano de 80 o más Años , Hipertensión/fisiopatología , Hipertensión/epidemiología , Enfermedades Cardiovasculares/epidemiología , Factores de RiesgoRESUMEN
Maillard reaction (MR) plays a pivotal role in the food flavor industry, including a cascade of reactions starting with the reaction between amino compounds and reducing sugars, and thus provides various colors and flavors. A new group of volatile compounds called pyrazinones found in MR are now getting more attention. In this study, eight volatile pyrazinones were found in the asparagine MR systems, in which 3,5-dimethyl- and 3,6-dimethyl-2(1H)-pyrazinones were reported for the first time. The major formation pathways were the reactions between asparagine and α-dicarbonyls, with decarboxylation as a critical step. Besides, novel alternative pathways involving alanine amidation and successive reactions with α-dicarbonyls were explored and successfully formed eight pyrazinones. The major differences between alanine-amidated pathways and decarboxylation pathways are the amidation step and absence of the decarboxylation step. For the alanine-amidated pathways, the higher the temperature, the better the amidation effect. The optimal amidation temperature was 200 °C in this study. The reaction between the alanine amide and α-dicarbonyls after amidation can happen at low temperatures, such as 35 and 50 °C, proposing the possibility of pyrazinone formation in real food systems. Further investigations should be conducted to investigate volatile pyrazinones in various food systems as well as the biological effects and kinetic formation differences of the volatile pyrazinones.
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Alanina , Asparagina , Reacción de Maillard , Pirazinas , Compuestos Orgánicos Volátiles , Pirazinas/química , Alanina/química , Asparagina/química , Compuestos Orgánicos Volátiles/química , Aromatizantes/químicaRESUMEN
Abiotic stresses can increase the total fatty acid (TFA) and astaxanthin accumulation in microalgae. However, it remains unknown whether a unified signal transduction mechanism exists under different stresses. This study explored the link between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) and the accumulation of fatty acids and astaxanthin in Chromochloris zofingiensis under three abiotic stresses. Results showed significant increases in fatty acid, astaxanthin, and ROS levels under nitrogen deficiency, phosphorus deficiency, and high-salinity stress. The introduction of the NADPH oxidase inhibitor diphenyleneiodonium (DPI) decreased the content of these components. This underscores the pivotal role of NADPH oxidase-derived ROS in the accumulation of fatty acid and astaxanthin under abiotic stress. Analysis of transcriptomes across three conditions following DPI addition revealed 1,445 shared differentially expressed genes (DEGs). Enrichment analysis revealed that biotin, betalain, thiamine, and glucosinolate may be important in stress responses. The heatmap demonstrated that DPI notably suppressed gene expression in the fatty acid and carotenoid biosynthesis pathways. Our findings underscore the pivotal role of NADPH oxidase-derived ROS in the accumulation of fatty acid and astaxanthin under abiotic stresses.
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BACKGROUND: Autophagy is a crucial process of cellular self-destruction and component reutilization that can affect the accumulation of total fatty acids (TFAs) and carotenoids in microalgae. The regulatory effects of autophagy process in a docosahexaenoic acid (DHA) and carotenoids simultaneously producing microalga, Crypthecodinium sp. SUN, has not been studied. Thus, the autophagy inhibitor (3-methyladenine (MA)) and activator (rapamycin) were used to regulate autophagy in Crypthecodinium sp. SUN. RESULTS: The inhibition of autophagy by 3-MA was verified by transmission electron microscopy, with fewer autophagy vacuoles observed. Besides, 3-MA reduced the glucose absorption and intracellular acetyl-CoA level, which resulting in the decrease of TFA and DHA levels by 15.83 and 26.73% respectively; Surprisingly, 3-MA increased intracellular reactive oxygen species level but decreased the carotenoids level. Comparative transcriptome analysis showed that the downregulation of the glycolysis, pentose phosphate pathway and tricarboxylic acid cycle may underlie the decrease of acetyl-CoA, NADPH and ATP supply for fatty acid biosynthesis; the downregulation of PSY and HMGCR may underlie the decreased carotenoids level. In addition, the class I PI3K-AKT signaling pathway may be crucial for the regulation of carbon and energy metabolism. At last, rapamycin was used to activate autophagy, which significantly enhanced the cell growth and TFA level and eventually resulted in 1.70-fold increase in DHA content. CONCLUSIONS: Our findings indicate the mechanisms of autophagy in Crypthecodinium sp. SUN and highlight a way to manipulate cell metabolism by regulating autophagy. Overall, this study provides valuable insights to guide further research on autophagy-regulated TFA and carotenoids accumulation in Crypthecodinium sp. SUN.
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Triocresyl phosphate (TOCP) was commonly used as flame retardant, plasticizer, lubricant, and jet fuel additive. Studies have shown adverse effects of TOCP on the reproductive system. However, the potential harm brought by TOCP, especially to mammalian female reproductive cells, remains a mystery. In this study, we employed an in vitro model for the first time to investigate the effects of TOCP on the maturation process of mouse oocytes. TOCP exposure hampered the meiotic division process, as evidenced by a reduction in the extrusion of the first polar body from oocytes. Subsequent research revealed the disruption of the oocyte cell cytoskeleton induced by TOCP, resulting in abnormalities in spindle organization, chromosome alignment, and actin filament distribution. This disturbance further extended to the rearrangement of organelles within oocytes, particularly affecting the mitochondria. Importantly, after TOCP treatment, mitochondrial function in oocytes was impaired, leading to oxidative stress, DNA damage, cell apoptosis, and subsequent changes of epigenetic modifications. Supplementation with nicotinamide mononucleotide (NMN) alleviated the harmful effects of TOCP. NMN exerted its mitigating effects through two fundamental mechanisms. On one hand, NMN conferred stability to the cell cytoskeleton, thereby supporting nuclear maturation. On the other hand, NMN enhanced mitochondrial function within oocytes, reducing the excess reactive oxygen species (ROS), restoring meiotic division abnormalities caused by TOCP, preventing oocyte DNA damage, and suppressing epigenetic changes. These findings not only enhance our understanding of the molecular basis of TOCP induced oocyte damage but also offer a promising avenue for the potential application of NMN in optimizing reproductive treatment strategies.
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Mononucleótido de Nicotinamida , Fosfatos , Tritolilfosfatos , Femenino , Ratones , Animales , Mononucleótido de Nicotinamida/metabolismo , Mononucleótido de Nicotinamida/farmacología , Fosfatos/metabolismo , Oocitos , Citoesqueleto , Mitocondrias , Especies Reactivas de Oxígeno/metabolismo , MamíferosRESUMEN
Macrophages are the main component of the tumor microenvironment, which are differentiated from monocytes in the blood and play an important role in cancer development. Tumor-associated macrophages (TAMs) can promote tumor growth, invasion, metastasis, and resistance to anti-programmed death receptor 1 therapy by regulating programmed cell death ligand 1 expression and interacting with other immune cells in the tumor microenvironment. However, when activated properly, macrophages can also play an anti-tumor role by enhancing the phagocytosis and cytotoxicity of tumor cells. TAM is associated with poor prognosis and drug resistance in patients treated with immunotherapy, indicating that macrophages are attractive targets for combined therapy in cancer treatment. Combination of targeting TAMs and immunotherapy overcomes the drug resistance and achieved excellent results in some cancers, which may be a promising strategy for cancer treatment in the future. Herein, we review the recent findings on the role of macrophages in tumor development, metastasis, and immunotherapy. We focus mainly on macrophage≥centered therapy, including strategies to deplete and reprogram TAMs, which represent the potential targets for improving tumor immunotherapy efficacy.
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Macrófagos , Neoplasias , Humanos , Inmunoterapia , Fagocitosis , Microambiente TumoralRESUMEN
The inactivated whole-virion vaccine, CoronaVac, is one of the most widely used coronavirus disease 2019 (COVID-19) vaccines worldwide. There is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron infection. In this prospective cohort study, 41 recipients of triple-dose CoronaVac and 14 unvaccinated individuals were recruited. We comprehensively profiled adaptive immune parameters in both groups, including spike-specific immunoglobulin (Ig) G and IgA titers, neutralizing activity, B cells, circulating follicular helper T (cTfh) cells, CD4+ and CD8+ T cells, and their memory subpopulations at 12 months after the third booster dose and at 4 and 20 weeks after Omicron BA.5 infection. Twelve months after the third CoronaVac vaccination, spike-specific antibodies and cellular responses were detectable in most vaccinated individuals. BA.5 infection significantly augmented the magnitude, cross-reactivity, and durability of serum neutralization activities, Fc-mediated phagocytosis, nasal spike-specific IgA responses, memory B cells, activated cTfh cells, memory CD4+ T cells, and memory CD8+ T cells for both the ancestral strain and Omicron subvariants, compared to unvaccinated individuals. Notably, the increase in BA.5-specific immunity after breakthrough infection was consistently comparable to or higher than that of the ancestral strain, suggesting no evidence of immune imprinting. Immune landscape analyses showed that vaccinated individuals have better synchronization of multiple immune components than unvaccinated individuals upon heterologous infection. Our data provide detailed insight into the protective role of the inactivated COVID-19 vaccine in shaping humoral and cellular immunity to Omicron infection. IMPORTANCE: There is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron breakthrough infection. In this prospective cohort study, the anti-severe acute respiratory syndrome coronavirus 2 adaptive responses were analyzed before and after the Omicron BA.5 infection. Our data provide detailed insight into the protective role of the inactivated COVID-19 vaccine in shaping humoral and cellular immune responses to heterologous Omicron infection. CLINICAL TRIAL: This study is registered with ClinicalTrials.gov as NCT05680896.
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COVID-19 , Inmunidad Mucosa , Vacunas de Productos Inactivados , Humanos , Vacunas contra la COVID-19 , SARS-CoV-2 , Infección Irruptiva , Linfocitos T CD8-positivos , Estudios Prospectivos , Inmunoglobulina G , Inmunoglobulina A , Anticuerpos Antivirales , Anticuerpos NeutralizantesRESUMEN
Psoriasis is a common chronic inflammatory disease, but most of its current treatments come with a high risk of side effects. As one of the world's top three beverages, tea has a traditional history of being used as a treatment for skin conditions due to its high safety profile, anti-inflammatory and other properties. In this study, we investigated the anti-psoriasis effects of ethanol extracts of black tea, green tea and white tea from southeastern China. The compositions of the tea extracts (TEs) were first determined by UPLC-Q-Exactive-Orbitrap MS and then genetic analysis, antibacterial, anti-inflammatory, and immunocompetence assays were performed. Imiquimod was used to establish a mouse model of psoriasis-like dermatitis and treating with the extracts to examine their efficacy. A total of 88 chemical components, mainly phenols and organic acids, were identified from the TEs. These TEs ameliorated skin damage and they all reduced the expression of cytokines IL-17 and TNF-α. By analyzing the genes, TEs may affect the inflammatory signaling pathway by regulating the metabolic changes. In addition, TEs can significantly scavenge ROS, NO, and inhibit cellular inflammation. In conclusion, this study examined the inhibitory effects of three TEs on psoriasis and their potential as nutritional supplements for the treatment of skin inflammation.
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Psoriasis , Animales , Ratones , Psoriasis/tratamiento farmacológico , Psoriasis/inducido químicamente , Imiquimod/efectos adversos , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Té , Modelos Animales de Enfermedad , PielRESUMEN
BACKGROUND: This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome (AS) following coronavirus disease 2019 (COVID-19) in a 33-year-old man diagnosed with Klinefelter syndrome (KS). CASE SUMMARY: A 33-year-old man with a diagnosis of KS was admitted to the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of COVID-19. Computed tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs, accompanied by signs of partial bronchial inflation. Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen. A biopsy specimen revealed organizing pneumonia with alveolar septal thickening. Additionally, extensive auto-antibody tests showed strong positivity for anti-SSA, anti-SSB, anti-Jo-1, and anti-Ro-52. Following multidisciplinary discussions, the patient received a final diagnosis of AS, leading to rapidly progressing respiratory failure. CONCLUSION: This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.