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Background: Schisanlactone E, also known as XueTongSu (XTS), is an active compound extracted from the traditional Tujia medicine Kadsura heteroclita ("XueTong"). Recent studies highlight its anti-inflammatory and antioxidant properties, yet the mechanisms of XTS's therapeutic effects on Alzheimer's disease (AD) are unclear. This study aims to elucidate the therapeutic efficacy and mechanisms of XTS in AD. Methods: Ten C57BL/6 mice were assigned to the control group (NC), and twenty APP/PS1 transgenic mice were randomly divided into the model group (M) (10 mice) and the XTS treatment group (Tre) (10 mice). After an acclimatization period of 7 days, intraperitoneal injections were administered over a 60-day treatment period. The NC and M groups received saline, while the Tre group received XTS at 2 mg/kg. Learning and memory abilities were assessed using the Morris Water Maze (MWM) test. Histopathological changes were evaluated using hematoxylin and eosin (HE) and Nissl staining, and immunofluorescence was used to assess pathological products and glial cell activation. Cytokine levels (IL-1ß, IL-6, TNF-α) in the hippocampus were quantified by qPCR. 16S rDNA sequencing analyzed gut microbiota metabolic alterations, and metabolomic analysis was performed on cortical samples. The KEGG database was used to analyze the regulatory mechanisms of XTS in AD treatment. Results: XTS significantly improved learning and spatial memory in APP/PS1 mice and ameliorated histopathological changes, reducing Aß plaque aggregation and glial cell activation. XTS decreased the expression of inflammatory cytokines IL-1ß, IL-6, and TNF-α. It also enhanced gut microbiota diversity, notably increasing Akkermansia species, and modulated levels of metabolites such as isosakuranetin, 5-KETE, 4-methylcatechol, and sphinganine. Pathway analysis indicated that XTS regulated carbohydrate metabolism, neuroactive ligand-receptor interactions, and alanine, aspartate, and glutamate metabolism, mitigating gut microbiota dysbiosis and metabolic disturbances. Conclusion: XTS ameliorates cognitive deficits, pathological changes, and inflammatory responses in APP/PS1 mice. It significantly modulates the gut microbiota, particularly increasing Akkermansia abundance, and influences levels of key metabolites in both the gut and brain. These findings suggest that XTS exerts anti-AD effects through the microbial-gut-brain axis (MGBA).
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The extraction of typical features of underwater target signals and excellent recognition algorithms are the keys to achieving underwater acoustic target recognition of divers. This paper proposes a feature extraction method for diver signals: frequency-domain multi-sub-band energy (FMSE), aiming to achieve accurate recognition of diver underwater acoustic targets by passive sonar. The impact of the presence or absence of targets, different numbers of targets, different signal-to-noise ratios, and different detection distances on this method was studied based on experimental data under different conditions, such as water pools and lakes. It was found that the FMSE method has the best robustness and performance compared with two other signal feature extraction methods: mel frequency cepstral coefficient filtering and gammatone frequency cepstral coefficient filtering. Combined with the commonly used recognition algorithm of support vector machines, the FMSE method can achieve a comprehensive recognition accuracy of over 94% for frogman underwater acoustic targets. This indicates that the FMSE method is suitable for underwater acoustic recognition of diver targets.
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As a Japanese graphic symbol widely used in the world, Emoji plays an important role in computer mediated communication. Despite its prevalent use, the interaction dynamics between emoji and textual sentences remain inadequately explored. Based on the emotional function of emoji, this study uses the indirect priming method to explore the emotional impact of emoji on subsequent text in computer mediated communication through two progressive behavioral experiments. The results show that: (1) Emoji positioned at the onset of a sentence induce an emotional priming effect; (2) The processing speed is slowest when emoji and text are emotionally conflicting, while in non-conflicting condition, the type of emoji moderates the processing of combined sentences; (3) The emotional influence of emoji plays an auxiliary role, and the valence of textual sentence plays a decisive role in emotional perception.
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Globally, nonsmall cell lung cancer (NSCLC) is a significant threat to human health, and constitutes >80% of lung cancer cases. Cisplatin (CDDP), a commonly used drug in clinical treatment, has been the focus of research aiming to mitigate its potent toxicity through encapsulation within liposomes. However, challenges, such as a reduced drug loading efficiency and nonspecific release, have emerged as obstacles. The present study aimed to improve the encapsulation efficiency of CDDP within liposomes by prepreparation of CDDP and modifying the liposome surface through the incorporation of peanut agglutinin (PNA) as a ligand [CDDPloaded PNAmodified liposomes (CDDPPNALip)]. This strategy was designed to enhance the delivery of CDDP to tumour tissues, thereby reducing associated side effects. The effect of CDDPPNALip on the proliferation and migration of NSCLC cell lines with high MUC1 expression was elucidated through in vitro studies. Additionally, the capacity of PNA modification to augment the targeted antitumour efficacy of liposomes was assessed through xenograft tumour experiments. The results indicated that in an in vitro uptake assay Rhodamine B (RhB)loaded PNAmodified liposomes were taken up by cells with ~50% higher efficiency compared with free RhB. In addition, CDDPPNALip resulted in a 2.65fold enhancement of tumour suppression in vivo compared with free CDDP. These findings suggested that the encapsulation of CDDP within ligandmodified liposomes may significantly improve its tumourtargeting capabilities, providing valuable insights for clinical drug development.
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Carcinoma de Pulmón de Células no Pequeñas , Cisplatino , Liposomas , Neoplasias Pulmonares , Aglutinina de Mani , Cisplatino/farmacología , Cisplatino/administración & dosificación , Liposomas/química , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Animales , Aglutinina de Mani/química , Línea Celular Tumoral , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto , Proliferación Celular/efectos de los fármacos , Ratones Desnudos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Ratones Endogámicos BALB C , Movimiento Celular/efectos de los fármacos , Femenino , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Bolt's Farm is the name given to a series of non-hominin bearing fossil sites that have often been suggested to be some of the oldest Pliocene sites in the Cradle of Humankind, South Africa. This article reports the results of the first combined Uranium-Series and Electron Spin Resonance (US-ESR) dating of bovid teeth at Milo's Cave and Aves Cave at Bolt's Farm. Both tooth enamel fragments and tooth enamel powder ages were presented for comparison. US-ESR, EU and LU models are calculated. Overall, the powder ages are consistent with previous uranium-lead and palaeomagnetic age estimates for the Aves Cave deposit, which suggest an age between ~3.15 and 2.61 Ma and provide the first ages for Milo's Cave dates to between ~3.1 and 2.7 Ma. The final ages were not overly dependent on the models used (US-ESR, LU or EU), which all overlap within error. These ages are all consistent with the biochronological age estimate (<3.4->2.6 Ma) based on the occurrence of Stage I Metridiochoerus andrewsi. Preliminary palaeomagnetic analysis from Milo's Cave indicates a reversal takes place at the site with predominantly intermediate directions, suggesting the deposit may date to the period between ~3.03 and 3.11 Ma within error of the ESR ages. This further suggests that there are no definitive examples of palaeocave deposits at Bolt's Farm older than 3.2 Ma. This research indicates that US-ESR dating has the potential to date fossil sites in the Cradle of Humankind to over 3 Ma. However, bulk sample analysis for US-ESR dating is recommended for sites over 3 Ma.
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Fósiles , Datación Radiométrica , Uranio , Sudáfrica , Espectroscopía de Resonancia por Spin del Electrón/métodos , Uranio/análisis , Animales , Cuevas/química , Diente/química , Diente/anatomía & histología , Esmalte Dental/químicaRESUMEN
Electroreduction of nitrate (NO3RR) to ammonia in membraneless electrolyzers is of great significance for reducing the cost and saving energy consumption. However, severe chemical crossover with side reactions makes it challenging to achieve ideal electrolysis. Herein, we propose a general strategy for efficient membraneless ammonia synthesis by screening NO3RR catalysts with inferior oxygen reduction activity and matching the counter electrode (CE) with good oxygen evolution activity while blocking anodic ammonia oxidation. Consequently, screening the available Co-Co system, the membraneless NO3--to-NH3 conversion performance was significantly higher than H-type cells using costly proton-exchange membranes. At 200 mA cm-2, the full-cell voltage of the membraneless system (â¼2.5 V) is 4 V lower than that of the membrane system (â¼6.5 V), and the savings are 61.4 kW h (or 56.9%) per 1 kg NH3 produced. A well-designed pulse process, inducing reversible surface reconstruction that in situ generates and restores the active Co(III) species at the working electrode and forms favorable Co3O4/CoOOH at the CE, further significantly improves NO3--to-NH3 conversion and blocks side reactions. A maximum NH3 yield rate of 1500.9 µmol cm-2 h-1 was achieved at -0.9 V (Faraday efficiency 92.6%). This pulse-coupled membraneless strategy provides new insights into design complex electrochemical synthesis.
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Amoníaco , Nitratos , Amoníaco/química , Electrodos , Oxidación-Reducción , Técnicas Electroquímicas , Electrólisis , CatálisisRESUMEN
Considerable work has investigated similarities between the processing of music and language, but it remains unclear whether typical, genuine music can influence speech processing via cross-domain priming. To investigate this, we measured ERPs to musical phrases and to syntactically ambiguous Chinese phrases that could be disambiguated by early or late prosodic boundaries. Musical primes also had either early or late prosodic boundaries and we asked participants to judge whether the prime and target have the same structure. Within musical phrases, prosodic boundaries elicited reduced N1 and enhanced P2 components (relative to the no-boundary condition) and musical phrases with late boundaries exhibited a closure positive shift (CPS) component. More importantly, primed target phrases elicited a smaller CPS compared to non-primed phrases, regardless of the type of ambiguous phrase. These results suggest that prosodic priming can occur across domains, supporting the existence of common neural processes in music and language processing.
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Electroencefalografía , Potenciales Evocados , Música , Percepción del Habla , Humanos , Masculino , Femenino , Adulto Joven , Percepción del Habla/fisiología , Adulto , Potenciales Evocados/fisiología , Habla/fisiología , Encéfalo/fisiología , Estimulación Acústica , Lenguaje , Potenciales Evocados Auditivos/fisiologíaRESUMEN
Skin macrophages are critical to maintain and restore skin homeostasis. They serve as major producers of cytokines and chemokines in the skin, participating in diverse biological processes such as wound healing and psoriasis. The heterogeneity and functional diversity of macrophage subpopulations endow them with multifaceted roles in psoriasis development. A distinct subpopulation of skin macrophages, characterized by high expression of CD169, has been reported to exist in both mouse and human skin. However, its role in psoriasis remains unknown. Here, we report that CD169+ macrophages exhibit increased abundance in imiquimod (IMQ) induced psoriasis-like skin lesions. Specific depletion of CD169+ macrophages in CD169-ditheria toxin receptor (CD169-DTR) mice inhibits IMQ-induced psoriasis, resulting in milder symptoms, diminished proinflammatory cytokine levels and reduced proportion of Th17 cells within the skin lesions. Furthermore, transcriptomic analysis uncovers enhanced activity in CD169+ macrophages when compared with CD169- macrophages, characterized by upregulated genes that are associated with cell activation and cell metabolism. Mechanistically, CD169+ macrophages isolated from IMQ-induced skin lesions produce more proinflammatory cytokines and exhibit enhanced ability to promote Th17 cell differentiation in vitro. Collectively, our findings highlight the crucial involvement of CD169+ macrophages in psoriasis development and offer novel insights into the heterogeneity of skin macrophages in the context of psoriasis.
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Imiquimod , Macrófagos , Psoriasis , Lectina 1 Similar a Ig de Unión al Ácido Siálico , Piel , Animales , Psoriasis/inmunología , Psoriasis/metabolismo , Psoriasis/patología , Psoriasis/inducido químicamente , Psoriasis/genética , Macrófagos/metabolismo , Macrófagos/inmunología , Ratones , Piel/metabolismo , Piel/patología , Piel/inmunología , Lectina 1 Similar a Ig de Unión al Ácido Siálico/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Células Th17/inmunología , Células Th17/metabolismo , Diferenciación Celular , Ratones Endogámicos C57BLRESUMEN
Microglia are natural immune cells in the central nervous system, and the activation of microglia is accompanied by a reprogramming of glucose metabolism. In our study, we investigated the role of long non-coding RNA taurine-upregulated gene 1 (TUG1) in regulating microglial glucose metabolism reprogramming and activation. BV2 cells were treated with Lipopolysaccharides (LPS)/Interferon-γ (IFN-γ) to establish a microglial activation model. The glycolysis inhibitor 2-Deoxy-D-glucose (2-DG) was used as a control. The expression levels of TUG1 mRNA and proinflammatory cytokines such as Interleukin-1ß (IL-1ß), Interleukin -6, and Tumor Necrosis Factor-α mRNA and anti-inflammatory cytokines such as IL-4, Arginase 1(Arg1), CD206, and Ym1 were detected by RT-qPCR. TUG1 was silenced using TUG1 siRNA and knocked out using CRISPR/Cas9. The mRNA and protein expression levels of key enzymes involved in glucose metabolism, such as Hexokinase2, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Lactate dehydrogenase, Glucose 6 phosphate dehydrogenase, and Pyruvate dehydrogenase (PDH), were determined by RT-qPCR and Western blotting. The glycolytic rate of microglial cells was measured using Seahorse. Differential metabolites were determined by metabolomics, and pathway enrichment was performed using these differential metabolites. Our findings revealed that the expression of TUG1 was elevated in proinflammatory-activated microglia and positively correlated with the levels of inflammatory factors. The expression of anti-inflammatory cytokines such as IL-4, Arg1, CD206, and Ym1 were decreased when induced with LPS/IFN-γ. However, this decrease was reversed by the treatment with 2-DG. Silencing of GAPDH led to an increase in the expression of TUG1 and inflammatory factors. TUG1 knockout (TUG1KO) inhibited the expression of glycolytic key enzymes and promoted the expression of oxidative phosphorylation key enzymes, shifting the metabolic profile of activated microglia from glycolysis to oxidative phosphorylation. Additionally, TUG1KO reduced the accumulation of metabolites, facilitating the restoration of the tricarboxylic acid cycle and enhancing oxidative phosphorylation in microglia. Furthermore, the downregulation of TUG1 was found to reduce the expression of both proinflammatory and anti-inflammatory cytokines under normal conditions. Interestingly, when induced with LPS/IFN-γ, TUG1 downregulation showed a potentially beneficial effect on microglia in terms of inflammation. Downregulation of TUG1 expression inhibits glycolysis and facilitates the shift of microglial glucose metabolism from glycolysis to oxidative phosphorylation, promoting their transformation towards an anti-inflammatory phenotype and exerting anti-inflammatory effects in BV2.
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Glucosa , Glucólisis , Lipopolisacáridos , Microglía , ARN Largo no Codificante , Microglía/metabolismo , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Glucosa/metabolismo , Ratones , Lipopolisacáridos/farmacología , Citocinas/metabolismo , Inflamación/metabolismo , Inflamación/genética , Interferón gamma/metabolismo , beta-N-Acetilhexosaminidasas/metabolismo , beta-N-Acetilhexosaminidasas/genética , Línea Celular , Receptor de Manosa , Lectinas de Unión a Manosa/metabolismo , Lectinas de Unión a Manosa/genética , Desoxiglucosa/farmacología , Interleucina-4/metabolismo , Interleucina-1beta/metabolismo , Reprogramación Metabólica , Arginasa , Hexoquinasa , LectinasRESUMEN
In order to explore the risk factors of relapse and potential optimized therapeutic regimen of low-risk acute promyelocytic leukaemia (APL), here we retrospectively analysed 282 patients who were diagnosed between February 2014 and September 2021. The median follow-up was 59 (9-102) months. The 5-year overall survival and cumulative relapse incidence were 97.9% and 5.9%, respectively. In terms of different cytoreductive therapies, 86 patients were administered with hydroxycarbamide (30.5%), 113 with anthracyclines or cytarabine (40.1%), 31 with etoposide (11.0%) and 52 with no cytoreductive therapy (18.4%) during the induction therapy. The hydroxycarbamide treatment group did not decrease the relapse rate compared to the no cytoreduction group (11.4% vs. 5.9%, p = 0.289). Compared with the hydroxycarbamide group, the anthracyclines/cytarabine treatment group showed improved 5-year RFS (88.145% vs. 98.113%, p = 0.008). Multivariate Cox regression analysis revealed that myeloblasts in bone marrow at diagnosis, and PML-RARA transcript level of 6.5% or more after induction therapy were associated with a subsequent risk of relapse. The only factor positively reducing the relapse rate was anthracyclines/cytarabine cytoreductive treatment. In conclusion, cytoreductive chemotherapy in induction therapy plays a potential key role in the prognosis of low-risk APL.
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Quimioterapia de Inducción , Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/mortalidad , Leucemia Promielocítica Aguda/genética , Femenino , Masculino , Adulto , Persona de Mediana Edad , Pronóstico , Adulto Joven , Adolescente , Estudios Retrospectivos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factores de Riesgo , RecurrenciaRESUMEN
To generate a new murine model for virus, DC-SIGN gene in murine was humanized. In this study, we successfully generated a humanized C57BL/6N mouse model expressing human DC-SIGN (hDC-SIGN) using CRISPR/Cas9 technology, and evaluated its characters and susceptibility to virus. The humanized mice could survival as usual, and with normal physiological index just like the wild-type mice. Whereas, we found significant differences in the intestinal flora and metabolic profiles between wild-type mice and humanized mice. Following intranasal infection with SARS-CoV-2, hDC-SIGN mice exhibited significantly increased viral loads in the lungs and nasal turbinates, along with more severe lung damage. This phenomenon may be associated with differential lipid metabolism and Fcγ receptor-mediated phagocytosis in two mouse models. This study provides a useful tool for investigating the mechanisms of coronavirus infection and potential drug therapies against novel coronavirus.
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COVID-19 , Moléculas de Adhesión Celular , Modelos Animales de Enfermedad , Lectinas Tipo C , Ratones Endogámicos C57BL , Receptores de Superficie Celular , SARS-CoV-2 , Animales , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/genética , COVID-19/virología , Humanos , Ratones , Receptores de Superficie Celular/metabolismo , Receptores de Superficie Celular/genética , Lectinas Tipo C/metabolismo , Lectinas Tipo C/genética , Susceptibilidad a Enfermedades , Pulmón/virología , Carga Viral , Microbioma Gastrointestinal , Fagocitosis , Ratones Transgénicos , Receptores de IgG/genética , Receptores de IgG/metabolismo , Metabolismo de los LípidosRESUMEN
Molecular imprinting polymers (MIPs) are synthetic receptors as biomimetic materials for various applications ranging from sensing to separation and catalysis. However, currently existing MIPs are stuck to some of the issues including the longer preparation steps and poor performance. In this report, a facile and one-pot strategy by integrating the in-situ growth of magnetic nanoparticles and reversed phase microemulsion oriented molecularly imprinting strategy to develop magnetic molecular imprinted nanocomposites was proposed. Through self-assembling of the template, it brought up highly ordered and uniform arrangement of the imprinting structure, which offered faster adsorption kinetic as adsorption equilibrium was achived within 15 min, higher adsorption capacity (Qmax = 48.78 ± 1.54 µmol/g) and high affinity (Kd = 127.63 ± 9.66 µM) toward paradigm molecule-adenosine monophosphate (AMP) compared to the conventional bulk imprinting. The developed MIPs offered better affinity and superior specificity which allowed the specific enrichment toward targeted phosphorylated peptides from complex samples containing 100-fold more abundant interfering peptides. Interestingly, different types of MIPs can be developed which could targetly enrich the specific phosphorylated peptides for mass spectrometry analysis by simply switching the templates, and this strategy also successfully achieved imprinting of macromolecular peptides. Collectively, the approach showed broad applicability to target specific enrichment from metabolites to phosphorylated peptides and providing an alternative choice for selective recognition and analysis from complex biological systems.
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Impresión Molecular , Polímeros , Polímeros/química , Péptidos , Sustancias Macromoleculares , Adsorción , Impresión Molecular/métodosRESUMEN
Staphylococcus aureus (S. aureus) poses a serious threat to global public health, necessitating the establishment of rapid and simple tools for its accurate identification. Herein, we developed a terahertz (THz) metamaterial biosensor based on aptamer-functionalized Fe3O4@Au nanocomposites for quantitative S. aureus assays in different clinical samples. Fe3O4@Au@Cys@Apt has the dual advantages of magnetism and a high refractive index in the THz range and was used to rapidly separate and enrich target bacteria in a complex environmental solution. Furthermore, conjugation to the nanocomposites significantly increased the resonance frequency shift of the THz metamaterial after target loading. Our results showed that the shifts in the metamaterial resonance frequency were linearly related to S. aureus concentrations ranging from 1.0 × 103 to 1.0 × 107 CFU/mL, with a detection limit of 4.78 × 102 CFU/mL. The biosensor was further applied to S. aureus detection in spiked human urine and blood with satisfactory recoveries (82.4-109.6%). Our approach also demonstrated strong concordance with traditional plate counting (R2 = 0.99306) while significantly lowering the analysis time from 24 h to <1 h. In conclusion, the proposed biosensor can not only perform culture-free and extraction-free detection of target bacteria but can also be easily extended to the determination of other pathogenic bacteria, rendering it suitable for various bacteria-related disease diagnoses.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Nanocompuestos , Infecciones Estafilocócicas , Humanos , Staphylococcus aureus , Técnicas Biosensibles/métodos , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/microbiología , Bacterias , OroRESUMEN
Improved survival of preterm low birthweight (LBW) infants due to advances in neonatal care has brought issues such as postnatal development trajectories to the foreground. This study pools evidence from three cluster-randomized experiments evaluating community-based psychosocial stimulation programs conducted from 2014 to 2017 that included 3571 rural Chinese children aged 6-24 months (51.1% male, 96.2% Han Chinese). The risk of severe cognitive delay was found to be 26.5 percentage points higher for preterm LBW children than for their peers at age 2.5, with a prevalence rate of 48.3%. Results show that psychosocial stimulation interventions can improve child cognitive development at scale, with beneficial impacts on child cognition disproportionately larger for preterm LBW children, helping them to catch up developmentally.
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Desarrollo Infantil , Recién Nacido de Bajo Peso , Recien Nacido Prematuro , Intervención Psicosocial , Población Rural , Humanos , China , Masculino , Femenino , Lactante , Intervención Psicosocial/métodos , Desarrollo Infantil/fisiología , Preescolar , Disfunción Cognitiva , Recién NacidoRESUMEN
Inflammation is a common and important pathological process occurring in any part of the body and relating to a variety of diseases. Effective tissue repair is critical for the survival of impaired organisms. Considering the side effects of the currently used anti-inflammatory medications, new therapeutic agents are urgently needed for the improvement of regenerative capacities of inflammatory-impaired tissues. Mesenchymal stromal stem/progenitor cells (MSCs) are characterized by the capabilities of self-renewal and multipotent differentiation and exhibit immunomodulatory capacity. Due to the ability to modulate inflammatory phenotypes and immune responses, MSCs have been considered as a potential alternative therapy for autoimmune and inflammatory diseases. Natural compounds (NCs) are complex small multiple-target molecules mostly derived from plants and microorganisms, exhibiting therapeutic effects in many disorders, such as osteoporosis, diabetes, cancer, and inflammatory/autoimmune diseases. Recently, increasing studies focused on the prominent effects of NCs on MSCs, including the regulation of cell survival and inflammatory response, as well as osteogenic/adipogenic differentiation capacities, which indicate the roles of NCs on MSC-based cytotherapy in several inflammatory diseases. Their therapeutic effects and fewer side effects in numerous physiological processes, compared to chemosynthetic drugs, made them to be a new therapeutic avenue combined with MSCs for impaired tissue regeneration. Here we summarize the current understanding of the influence of NCs on MSCs and related downstream signaling pathways, specifically in pathological inflammatory conditions. In addition, the emerging concepts through the combination of NCs and MSCs to expand the therapeutic perspectives are highlighted. A promising MSC source from oral/dental tissues is also discussed, with a remarkable potential for MSC-based therapy in future clinical applications.
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Enfermedades Autoinmunes , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Humanos , Células Madre Mesenquimatosas/metabolismo , Inflamación/metabolismo , Diferenciación Celular , Adipogénesis , InmunomodulaciónRESUMEN
Electroreduction of waste nitrate to valuable ammonia offers a green solution for environmental restoration and energy storage. However, the electrochemical self-reconstruction of catalysts remains a huge challenge in terms of maintaining their stability, achieving the desired active sites, and managing metal leaching. Herein, we present an electrical pulse-driven Co surface reconstruction-coupled Coδ+ shuttle strategy for the precise in situ regulation of the Co(II)/Co(III) redox cycle on the Co-based working electrode and guiding the dissolution and redeposition of Co-based particles on the counter electrode. As result, the ammonia synthesis performance and stability are significantly promoted while cathodic hydrogen evolution and anodic ammonia oxidation in a membrane-free configuration are effectively blocked. A high rate of ammonia production of 1.4 ± 0.03 mmol cm-2 h-1 is achieved at -0.8 V in a pulsed system, and the corresponding nitrate-to-ammonia Faraday efficiency is 91.7 ± 1.0%. This work holds promise for the regulation of catalyst reactivity and selectivity by engineering in situ controllable structural and chemical transformations.
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Prostate cancer (PCa) is witnessing a concerning rise in incidence annually, with the androgen receptor (AR) emerging as a pivotal contributor to its growth and progression. Mounting evidence underscores the AR's ability to recruit cofactors, influencing downstream gene transcription and thereby fueling the proliferation and metastasis of PCa cells. Although, clinical strategies involving AR antagonists provide some relief, managing castration resistant prostate cancer (CRPC) remains a formidable challenge. Thus, the need of the hour lies in unearthing new drugs or therapeutic targets to effectively combat PCa. This review encapsulates the pivotal roles played by coactivators and corepressors of AR, notably androgen receptor-associated protein (ARA) and steroid receptor Coactivators (SRC) in PCa. Our data unveils how these cofactors intricately modulate histone modifications, cell cycling, SUMOylation, and apoptosis through their interactions with AR. Among the array of cofactors scrutinised, such as ARA70ß, ARA24, ARA160, ARA55, ARA54, PIAS1, PIAS3, SRC1, SRC2, SRC3, PCAF, p300/CBP, MED1, and CARM1, several exhibit upregulation in PCa. Conversely, other cofactors like ARA70α, PIASy, and NCoR/SMRT demonstrate downregulation. This duality underscores the complexity of AR cofactor dynamics in PCa. Based on our findings, we propose that manipulating cofactor regulation to modulate AR function holds promise as a novel therapeutic avenue against advanced PCa. This paradigm shift offers renewed hope in the quest for effective treatments in the face of CRPC's formidable challenges.
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Neoplasias de la Próstata Resistentes a la Castración , Neoplasias de la Próstata , Masculino , Humanos , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata/genética , Línea Celular Tumoral , Chaperonas Moleculares/metabolismo , Proteínas Inhibidoras de STAT Activados/metabolismo , Proteínas Inhibidoras de STAT Activados/uso terapéuticoRESUMEN
Ginseng is a perennial herb of the genus Panax in the family Araliaceae as one of the most important traditional medicine. Genomic studies of ginseng assist in the systematic discovery of genes related to bioactive ginsenosides biosynthesis and resistance to stress, which are of great significance in the conservation of genetic resources and variety improvement. The transcriptome reflects the difference and consistency of gene expression, and transcriptomics studies of ginseng assist in screening ginseng differentially expressed genes to further explore the powerful gene source of ginseng. Protein is the ultimate bearer of ginseng life activities, and proteomic studies of ginseng assist in exploring the biosynthesis and regulation of secondary metabolites like ginsenosides and the molecular mechanism of ginseng adversity adaptation at the overall level. In this review, we summarize the current status of ginseng research in genomics, transcriptomics and proteomics, respectively. We also discuss and look forward to the development of ginseng genome allele mapping, ginseng spatiotemporal, single-cell transcriptome, as well as ginseng post-translational modification proteome. We hope that this review will contribute to the in-depth study of ginseng and provide a reference for future analysis of ginseng from a systems biology perspective.
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Ginsenósidos , Panax , Panax/genética , Proteómica , Perfilación de la Expresión Génica , Genoma de Planta , Raíces de Plantas/metabolismoRESUMEN
Inter-channel nonlinearity compensation plays a crucial role in wavelength division multiplexing (WDM) systems for improving transmission capacity and distance. In this work, we propose a novel, to the best of our knowledge, inter-channel nonlinearity compensation method called generalized Rayleigh quotient optimization (GRQO) method with two different working modes. In an 8 × 64 GBaud 16-ary quadrature amplitude modulation (16-QAM) experimental system over 1600 km standard single-mode fiber (SSMF), the proposed method shows a 0.40 dB Q2 factor improvement over nonlinear polarization cross talk canceller (NPCC) with a moderately low computational complexity of about 2000 real multiplications per bit (RMb).