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The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood1,2. Here we generate a cross-species proteomic map of synapse development in the human, macaque and mouse neocortex. By tracking the changes of more than 1,000 postsynaptic density (PSD) proteins from midgestation to young adulthood, we find that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons reveal that human PSDs mature about two to three times slower than those of other species and contain higher levels of Rho guanine nucleotide exchange factors (RhoGEFs) in the perinatal period. Enhancement of RhoGEF signalling in human neurons delays morphological maturation of dendritic spines and functional maturation of synapses, potentially contributing to the neotenic traits of human brain development. In addition, PSD proteins can be divided into four modules that exert stage- and cell-type-specific functions, possibly explaining their differential associations with cognitive functions and diseases. Our proteomic map of synapse development provides a blueprint for studying the molecular basis and evolutionary changes of synapse maturation.
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Proteómica , Sinapsis , Adolescente , Animales , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Ratones , Adulto Joven , Cognición/fisiología , Espinas Dendríticas , Edad Gestacional , Macaca , Neuronas/metabolismo , Densidad Postsináptica/metabolismo , Factores de Intercambio de Guanina Nucleótido Rho/metabolismo , Transducción de Señal , Especificidad de la Especie , Sinapsis/metabolismo , Sinapsis/fisiologíaRESUMEN
Self-assembled protein cages are attractive scaffolds for organizing various proteins of interest (POIs) toward applications in synthetic biology and medical science. However, specifically attaching multiple POIs to a single protein cage remains challenging, resulting in diversity among the functionalized particles. Here, we present the engineering of a self-assembled protein cage, DTMi3ST, capable of independently recruiting two different POIs using SpyCatcher (SC)/SpyTag (ST) and DogCatcher (DC)/DogTag (DT) chemistries, thereby reducing variability between assemblies. Using fluorescent proteins as models, we demonstrate controlled targeting of two different POIs onto DTMi3ST protein cages both in vitro and inside living cells. Furthermore, dual functionalization of the DTMi3ST protein cage with a membrane-targeting peptide and ß-galactosidase resulted in the construction of membrane-bound enzyme assemblies in Escherichia coli, leading to a 69.6% enhancement in substrate utilization across the membrane. This versatile protein cage platform provides dual functional nanotools for biological and biomedical applications.
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Escherichia coli , Ingeniería de Proteínas , Escherichia coli/genética , Péptidos/química , beta-Galactosidasa/química , beta-Galactosidasa/metabolismo , HumanosRESUMEN
Naturally evolved metabolons have the ability to assemble and disassemble in response to environmental stimuli, allowing for the rapid reorganization of chemical reactions in living cells to meet changing cellular needs. However, replicating such capability in synthetic metabolons remains a challenge due to our limited understanding of the mechanisms by which the assembly and disassembly of such naturally occurring multienzyme complexes are controlled. Here, we report the synthesis of chemical- and light-responsive protein cages for assembling synthetic metabolons, enabling the dynamic regulation of enzymatic reactions in living cells. Particularly, a chemically responsive domain was fused to a self-assembled protein cage subunit, generating engineered protein cages capable of displaying proteins containing cognate interaction domains on their surfaces in response to small molecular cues. Chemical-induced colocalization of sequential enzymes on protein cages enhances the specificity of the branched deoxyviolacein biosynthetic reactions by 2.6-fold. Further, by replacing the chemical-inducible domain with a light-inducible dimerization domain, we created an optogenetic protein cage capable of reversibly recruiting and releasing targeted proteins onto and from the exterior of the protein cages in tens of seconds by on-off of blue light. Tethering the optogenetic protein cages to membranes enables the formation of light-switchable, membrane-bound metabolons, which can repeatably recruit-release enzymes, leading to the manipulation of substrate utilization across membranes on demand. Our work demonstrates a powerful and versatile strategy for constructing dynamic metabolons in engineered living cells for efficient and controllable biocatalysis.
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Complejos Multienzimáticos , Proteínas , Proteínas/química , Complejos Multienzimáticos/químicaRESUMEN
Autoimmune uveitis is a leading cause of severe vision loss, and animal models provide unique opportunities for studying its pathogenesis and therapeutic strategies. Here we employ scRNA-seq, RNA-seq and various molecular and cellular approaches to characterize mouse models of classical experimental autoimmune uveitis (EAU), revealing that EAU causes broad retinal neuron degeneration and marker downregulation, and that Müller glia may act as antigen-presenting cells. Moreover, EAU immune response is primarily driven by Th1 cells, and results in dramatic upregulation of CC chemokines, especially CCL5, in the EAU retina. Accordingly, overexpression of CCR5, a CCL5 receptor, in mesenchymal stem cells (MSCs) enhances their homing capacity and improves their immunomodulatory outcomes in preventing EAU, by reducing infiltrating T cells and activated microglia and suppressing Nlrp3 inflammasome activation. Taken together, our data not only provide valuable insights into the molecular characteristics of EAU but also open an avenue for innovative MSC-based therapy.
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Células Madre Mesenquimatosas , Ratones Endogámicos C57BL , Receptores CCR5 , Análisis de la Célula Individual , Uveítis , Animales , Ratones , Células Madre Mesenquimatosas/metabolismo , Uveítis/inmunología , Receptores CCR5/metabolismo , Receptores CCR5/genética , Enfermedades Autoinmunes/terapia , Perfilación de la Expresión Génica , Modelos Animales de Enfermedad , Femenino , Análisis de Expresión Génica de una Sola CélulaRESUMEN
Severe pneumonia caused by respiratory viruses has become a major threat to humans, especially with the SARS-CoV-2 outbreak and epidemic. The aim of this study was to investigate the universal molecular mechanism of severe pneumonia induced by multiple respiratory viruses and to search for therapeutic strategies targeting this universal molecular mechanism. The common differential genes of four respiratory viruses, including respiratory syncytial virus (RSV), rhinovirus, influenza, and SARS-CoV-2, were screened by GEO database, and the hub gene was obtained by Sytohubba in Cytoscape. Then, the effect of hub genes on inflammasome and pyrodeath was investigated in the model of RSV infection in vitro and in vivo. Finally, through virtual screening, drugs targeting the hub gene were obtained, which could alleviate severe viral pneumonia in vitro and in vivo. The results showed that CMPK2 is one of the hub genes after infection by four respiratory viruses. CMPK2 activates the inflammasome by activating NLRP3, and promotes the releases of inflammatory factors interleukin (IL)-1ß and IL-18 to induce severe viral pneumonia. Z25 and Z08 can reduce the expression level of CMPK2 mRNA and protein, thereby inhibiting NLRP3 and alleviating the development of severe viral pneumonia. In conclusion, the inflammatory response mediated by CMPK2 is the common molecular mechanism of severe pneumonia induced by viral infection, and Z25 and Z08 can effectively alleviate viral infection and severe pneumonia through this mechanism.
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Inflamasomas , Piroptosis , Piroptosis/efectos de los fármacos , Humanos , Animales , Inflamasomas/metabolismo , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , Interleucina-18/metabolismo , Interleucina-18/genética , SARS-CoV-2 , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/virologíaRESUMEN
Mitochondria are vital organelles that provide energy for the metabolic processes of cells. These include regulating cellular metabolism, autophagy, apoptosis, calcium ions, and signaling processes. Despite their varying functions, mitochondria are considered semi-independent organelles that possess their own genome, known as mtDNA, which encodes 13 proteins crucial for oxidative phosphorylation. However, their diversity reflects an organism's adaptation to physiological conditions and plays a complex function in cellular metabolism. Mitochondrial heterogeneity exists at the single-cell and tissue levels, impacting cell shape, size, membrane potential, and function. This heterogeneity can contribute to the progression of diseases such as neurodegenerative diseases, metabolic diseases, and cancer. Mitochondrial dynamics enhance the stability of cells and sufficient energy requirement, but these activities are not universal and can lead to uneven mitochondria, resulting in heterogeneity. Factors such as genetics, environmental compounds, and signaling pathways are found to affect these cellular processes and heterogeneity. Additionally, the varying roles of metabolites such as NADH and ATP affect glycolysis's speed and efficiency. An imbalance in metabolites can impair ATP production and redox potential in the mitochondria. Therefore, this review will explore the influence of metabolites in shaping mitochondrial morphology, how these changes contribute to age-related diseases and the therapeutic targets for regulating mitochondrial heterogeneity.
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Mitocondrias , Humanos , Mitocondrias/metabolismo , Animales , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/tratamiento farmacológicoRESUMEN
Cerebrospinal fluid rhinorrhea (CSFR) is a condition in which the cerebrospinal fluid flows out of the nasal cavity due to rupture of the arachnoid, dura, and nasal membranes because of bone defects in the skull base. The authors report a rare case of CSFR in a 2-year-old girl who experienced trauma in the nasal cavity by a bamboo stick. She underwent endoscopic repair for the CSFR. During surgery, a bulged vesicle was observed at the left cribriform plate with a small amount of cerebrospinal fluid draining from the surrounding area. Postoperative recovery was good. Endoscopic CSFR repair in pediatric patients is minimally invasive, effective, and safe as demonstrated in this case. Prevention of CSFR in children is important. Parents and caretakers of children need to be more aware, and potentially dangerous objects should not be kept within reach of children.
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Rinorrea de Líquido Cefalorraquídeo , Femenino , Humanos , Niño , Preescolar , Rinorrea de Líquido Cefalorraquídeo/diagnóstico por imagen , Rinorrea de Líquido Cefalorraquídeo/etiología , Rinorrea de Líquido Cefalorraquídeo/cirugía , Endoscopía/efectos adversos , Base del Cráneo/cirugía , Cavidad Nasal , Duramadre , Estudios RetrospectivosRESUMEN
BACKGROUND: Remdesivir is approved for treatment of coronavirus disease 2019 (COVID-19) in nonhospitalized and hospitalized adult and pediatric patients. Here we present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resistance analyses from the phase 3 ACTT-1 randomized placebo-controlled trial conducted in adult participants hospitalized with COVID-19. METHODS: Swab samples were collected at baseline and longitudinally through day 29. SARS-CoV-2 genomes were sequenced using next-generation sequencing. Phenotypic analysis was conducted directly on participant virus isolates and/or using SARS-CoV-2 subgenomic replicons expressing mutations identified in the Nsp12 target gene. RESULTS: Among participants with both baseline and postbaseline sequencing data, emergent Nsp12 substitutions were observed in 12 of 31 (38.7%) and 12 of 30 (40.0%) participants in the remdesivir and placebo arms, respectively. No emergent Nsp12 substitutions in the remdesivir arm were observed in more than 1 participant. Phenotyping showed low to no change in susceptibility to remdesivir relative to wild-type Nsp12 reference for the substitutions tested: A16V (0.8-fold change in EC50), P323L + V792I (2.2-fold), C799F (2.5-fold), K59N (1.0-fold), and K59N + V792I (3.4-fold). CONCLUSIONS: The similar rate of emerging Nsp12 substitutions in the remdesivir and placebo arms and the minimal change in remdesivir susceptibility among tested substitutions support a high barrier to remdesivir resistance development in COVID-19 patients. Clinical Trials Registration. NCT04280705.
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COVID-19 , Adulto , Humanos , Niño , SARS-CoV-2/genética , Tratamiento Farmacológico de COVID-19 , Adenosina Monofosfato/uso terapéutico , Alanina/uso terapéutico , Antivirales/uso terapéuticoRESUMEN
This paper aims to study the therapeutic effect and safety of Bushen Culuan Formula in the treatment of patients with infertility caused by hyperprolactinemia. Sixty patients with infertility caused by hyperprolactinemia of kidney deficiency and blood stasis were divided into the treatment group(Bushen Culuan Formula + Bromocriptine Mesylate Tablets placebo) and the control group(Bromocriptine Mesylate Tablets + Bushen Culuan Formula placebo), and ovulation rate, pregnancy rate, serum sex hormones, basal body temperature(BBT), and traditional Chinese medicine(TCM) symptom scores were observed. The results showed the clinical effective rate was 90.00% in the treatment group and 80.00% in the control group. The treatment group was able to significantly reduce the PRL level and increase the pregnancy rate, and it was superior to the control group in increasing the BBT biphasic ratio, improving the TCM symptom scores, and enhancing the ovulation rate. The results show that Bushen Culuan Formula is safe and reliable in treating ovulatory disorder infertility caused by hyperprolactinemia, with remarkable effects.
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Medicamentos Herbarios Chinos , Hiperprolactinemia , Infertilidad Femenina , Ovulación , Hiperprolactinemia/tratamiento farmacológico , Hiperprolactinemia/complicaciones , Humanos , Femenino , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/uso terapéutico , Adulto , Ovulación/efectos de los fármacos , Infertilidad Femenina/tratamiento farmacológico , Infertilidad Femenina/etiología , Embarazo , Adulto JovenRESUMEN
Transcriptomics was used to investigate the mechanism of action of Bushen Culuan Formula in the treatment of infertility caused by hyperprolactinemia(HPRL), and animal experiments were carried out to verify the results. After establishing an animal model of HPRL-induced infertility, the mice were divided into normal group, model group, Bushen Culuan Formula groups with high-, medium-, and low-doses, and bromocriptine group, and they were observed in terms of the estrous cycle, gonadal index, serum sex hormones, morphology of ovary and mammary gland, follicle count, and fertility. The results showed that the Bushen Culuan Formula could effectively restore the estrous cycle, down-regulate the levels of prolactin(PRL), follicle-stimulating hormone(FSH), and luteinizing hormone(LH), up-regulate the level of estradiol(E_2), increase the number of primordial follicles and sinus follicles, and improve the ovulation rate and fertility of mice. Through RNA sequencing combined with biosignature analysis, Bushen Culuan Formula may regulate the metabolism of lipids, antioxidant enzymes, and other substances in the cells of the ovary and pituitary gland through the signaling pathways of cAMP-PKA, Kiss-1/GPR54, and Hippo and exert therapeutic effects. The results of animal experiments showed that Bushen Culuan Formula could up-regulate serum dopamine(DA) level and pituitary DRD2 expression, down-regulate hypothalamus and ovary cAMP levels, as well as protein expressions of the pituitary gland and ovary PKA, CREB, and p-CREB, and treat HPRL-induced infertility by regulating the cAMP-PKA signaling pathway.
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Medicamentos Herbarios Chinos , Hormonas Esteroides Gonadales , Hiperprolactinemia , Ovulación , Animales , Femenino , Ratones , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Hiperprolactinemia/tratamiento farmacológico , Ovulación/efectos de los fármacos , Humanos , Hormona Folículo Estimulante/sangre , Hormona Luteinizante/sangre , Ovario/efectos de los fármacos , Ovario/metabolismo , Ciclo Estral/efectos de los fármacos , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/genéticaRESUMEN
This study aims to observe the efficacy and safety of Bushen Culuan Formula in the treatment of infertility caused by polycystic ovary syndrome(PCOS) and to explore the mechanism using metabolomics. Ninety-four patients with infertility caused by PCOS with the syndrome of kidney deficiency and blood stasis were selected and assigned into treatment and control groups(n=47). The basal body temperature(BBT) was measured, and B-ultrasonography was employed to monitor follicles, ovarian volume, endometrium, ovulation, and pregnancy. The serum levels of sex hormones including follicle-stimulating hormone(FSH), luteinizing hormone(LH), prolactin(PRL), estradiol(E_2), progestin(P), testosterone(T), free testosterone(FT), androstenedione(A2), inhibin B(INHB), and anti-Müllerian hormone(AMH) were measured. The coagulation function, traditional Chinese medicine(TCM) symptom scores, blood and urine routine, liver and kidney functions and other safety indicators were determined. Metabolomics was employed to comparatively analyze the serum metabolites of 26 patients(13 patients in each group) in the clinical study. The results showed that the total response rate and pregnancy rate of the treatment group were higher than those of the control group(P<0.001), suggesting that Bushen Culuan Formula regulated the sex hormones and ovarian function. Specifically, it reduced the levels of LH, T, FT, A2, and INHB(P<0.05 or P<0.01) and the LH/FSH ratio(P<0.05), elevated the level of P(P<0.05), promoted ovulation, increased endothelial thickness, and lowered TCM symptom scores without causing adverse reactions. A total of 24 differential metabolites were screened by metabolomics, and there were correlations between sex hormones and differential metabolites in the PCOS-induced infertility patients with kidney deficiency and blood stasis. In conclusion, Bushen Culuan Formula may regulate hormone levels through lipid and amino acid metabolism.
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Medicamentos Herbarios Chinos , Infertilidad Femenina , Síndrome del Ovario Poliquístico , Humanos , Femenino , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/fisiopatología , Síndrome del Ovario Poliquístico/complicaciones , Medicamentos Herbarios Chinos/administración & dosificación , Adulto , Infertilidad Femenina/tratamiento farmacológico , Infertilidad Femenina/etiología , Infertilidad Femenina/fisiopatología , Adulto Joven , Embarazo , Hormona Luteinizante/sangreRESUMEN
Uterine fibroids are a prevalent factor that impacts fertility in women of reproductive age. This study discusses the theoretical foundation and formula principles of Professor MA Kun's clinical treatment for infertility caused by uterine fibroids. The kidney stores essence and is responsible for reproduction, while blood serves as a vital material basis for women's physiological functions. Kidney deficiency is the fundamental pathogenesis of infertility, and imbalances in kidney Qi and essence or deficiencies in kidney Yin and Yang can result in blood stasis. Blood stasis plays a significant role throughout this condition by impeding the flow of blood, which is crucial for nourishing Qi. Therefore, both kidney deficiency and blood stasis are key factors contributing to infertility caused by uterine fibroids. Professor MA Kun treats infertility caused by uterine fibroids using an approach that involves tonifying the kidneys and activating blood circulation based on changes in Qi and blood during the menstrual cycle as well as follicular growth processes. By identifying stage-specific evidence, appropriate treatments can be applied accordingly. During menstruation when the uterus opens and menstrual blood flows out, promoting follicular development through nourishing kidney Yin and activating blood circulation becomes essential. In later stages of menstruation, additional measures are taken to remove blood stasis, alleviate symptoms, disperse knots, attack pathogens while simultaneously replenishing vital energy. During intermenstrual periods when Yin holds greater importance than Yang, tonifying the kidneys and activating blood circulation helps facilitate smooth discharge of eggs by promoting transformation between Yin and Yang energies. Premenstrual period to warm kidney Yang to promote pregnant egg implantation, and at the same time to dredge the liver and regulate Qi, Qi elimination stagnation, complementary in the line, with the symptoms of additional subtractions. Clinical effect is remarkable, for the reference of colleagues.
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Medicamentos Herbarios Chinos , Infertilidad Femenina , Riñón , Leiomioma , Humanos , Femenino , Riñón/fisiopatología , Infertilidad Femenina/etiología , Infertilidad Femenina/terapia , Infertilidad Femenina/fisiopatología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Two-dimensional low-melting-point (LMP) metal nanocrystals are attracting increasing attention with broad and irreplaceable applications due to their unique surface and topological structures. However, the chemical synthesis, especially the fine control over the nucleation (reduction) and growth (crystallization), of such LMP metal nanocrystals remains elusive as limited by the challenges of low standard redox potential, low melting point, poor crystalline symmetry, etc. Here, a controllable reduction-melting-crystallization (RMC) protocol to synthesize free-standing and surfactant-free bismuth nanocrystals with tunable dimensions, morphologies, and surface structures is presented. Especially, ultrathin bismuth nanosheets with flat or jagged surfaces/edges can be prepared with high selectivity. The jagged bismuth nanosheets, with abundant surface steps and defects, exhibit boosted electrocatalytic CO2 reduction performances in acidic, neutral, and alkaline aqueous solutions, achieving the maximum selectivity of near unity at the current density of 210 mA cm-2 for formate evolution under ambient conditions. This work creates the RMC pathway for the synthesis of free-standing two-dimensional LMP metal nanomaterials and may find broader applicability in more interdisciplinary applications.
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MAIN CONCLUSION: Enhanced secretion of Na+ and Cl- in leaf glands and leaf vacuolar sequestration of Na+ or root retention of Cl-, combined with K+ retention, contribute to the improved salt tolerance of tetraploid recretohalophyte P. auriculata. Salt stress is one of the major abiotic factors threatening plant growth and development, and polyploids generally exhibit higher salt stress resistance than diploids. In recretohalophytes, which secrete ions from the salt gland in leaf epidermal cells, the effects of polyploidization on ion homeostasis and secretion remain unknown. In this study, we compared the morphology, physiology, and ion homeostasis regulation of diploid and autotetraploid accessions of the recretohalophyte Plumbago auriculata Lam. after treatment with 300 mM NaCl for 0, 2, 4, 6, and 8 days. The results showed that salt stress altered the morphology, photosynthetic efficiency, and chloroplast structure of diploid P. auriculata to a greater extent than those of its tetraploid counterpart. Moreover, the contents of organic osmoregulatory substances (proline and soluble sugars) were significantly higher in the tetraploid than in the diploid, while those of H2O2 and malondialdehyde (MDA) were significantly lower. Analysis of ion homeostasis revealed that the tetraploid cytotype accumulated more Na+ in stems and leaves and more Cl- in roots but less K+ loss in roots compared with diploid P. auriculata. Additionally, the rate of Na+ and Cl- secretion from the leaf surface was higher, while that of K+, Mg2+, and Ca2+ secretion was lower in tetraploid plants. X-ray microanalysis of mesophyll cells revealed that Na+ mainly accumulated in different cellular compartments in the tetraploid (vacuole) and diploid (cytoplasm) plants. Our results suggest that polyploid recretohalophytes require the ability to sequester Na+ and Cl-(via accumulation in leaf cell vacuoles or unloading by roots) and selectively secrete these ions (through salt glands) together with the ability to prevent K+ loss (by roots). This mechanism required to maintain K+/Na+ homeostasis in polyploid recretohalophytes under high salinity provides new insights in the improved maintenance of ion homeostasis in polyploids under salt stress.
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Plumbaginaceae , Tetraploidía , Plumbaginaceae/genética , Tolerancia a la Sal , Peróxido de Hidrógeno , Sodio , Poliploidía , Hojas de la Planta/genéticaRESUMEN
The chromosomal structure derived from UVB-stimulated HaCaT cells was detected by atomic force microscopy (AFM) to evaluate the effect of UVB irradiation. The results showed that the higher the UVB irradiation dose, the more the cells that had chromosome aberration. At the same time, different representative types of chromosome structural aberrations were investigated. We also revealed damage to both DNA and cells under the corresponding irradiation doses. It was found that the degree of DNA damage was directly proportional to the irradiation dose. The mechanical properties of cells were also changed after UVB irradiation, suggesting that cells experienced a series of chain reactions from inside to outside after irradiation. The high-resolution imaging of chromosome structures by AFM after UVB irradiation enables us to relate the damage between chromosomes, DNA, and cells caused by UVB irradiation and provides specific information on genetic effects.
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Daño del ADN , Rayos Ultravioleta , Microscopía de Fuerza Atómica , Rayos Ultravioleta/efectos adversos , CromosomasRESUMEN
A facile and efficient synthetic method for 3-aminoquinolines has been reported. The straightforward process starts from easily available triazoles and 2-aminobenzaldehydes. Low catalyst loading and good functional group compatibility are the other two merits of this transformation. Easy decoration of the 3-aminoquinoline motifs enabled the convenient synthesis of bioactive molecules, demonstrating the potential of this protocol in organic synthesis.
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BACKGROUND The role of nutritional parameter prealbumin in predicting the incidence of hepatic encephalopathy (HE) remains unclear. This study was designed to assess the diagnostic performance of prealbumin in predicting the incidence of HE in hepatitis B virus (HBV)-related decompensated liver cirrhosis patients. MATERIAL AND METHODS A retrospective cohort of 262 patients with HBV-related decompensated liver cirrhosis was involved in this study. Prealbumin, albumin, and other indicators were collected at admission, and independent factors were identified by logistic regression analysis. The Mann-Whitney U test and receiver operating characteristic (ROC) curves were used to compare the groups and indicators. RESULTS A total of 262 patients were enrolled in the study, including 197 men and 65 women. In patients with HBV-related decompensated liver cirrhosis accompanied by HE, the model for end-stage liver disease (MELD) scores, and prothrombin time (PT) and international normalized ratio (INR) values were significantly increased, while prealbumin and albumin levels were significantly decreased. Multivariate analysis showed that only serum prealbumin level (P=0.014) was independently related to the incidence of HE. Moreover, prealbumin level was negatively correlated with MELD (r=-0.63, P<0.001) and Child-Turcotte-Pugh (r=-0.35, P<0.001) scores. ROC curves were performed, and prealbumin showed the highest area under the ROC curve (0.781) compared with MELD and Child-Turcotte-Pugh scores. CONCLUSIONS Low prealbumin levels were associated with increased frequency of hepatic encephalopathy in HBV-related decompensated cirrhosis, which showed better performance than traditional models.
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Enfermedad Hepática en Estado Terminal , Encefalopatía Hepática , Masculino , Humanos , Femenino , Virus de la Hepatitis B , Prealbúmina , Encefalopatía Hepática/complicaciones , Estudios Retrospectivos , Enfermedad Hepática en Estado Terminal/complicaciones , Cirrosis Hepática , Índice de Severidad de la Enfermedad , Albúminas , Curva ROC , PronósticoRESUMEN
Repetitive transcranial magnetic stimulation (rTMS) play a important role for rehabilitation in stroke. But therapeutic schedule of rTMS in dysphagia after acute stroke is still controversial. The purpose of this study was to investigate the therapeutic effect of rTMS with different frequencies on dysphagia after acute stroke. From August 2019 to December 2020, 45 patients with post-stroke dysphagia were selected as research subjects, and randomly divided into 3 groups: the high frequency stimulation on bilateral hemisphere group (High group), bilateral high frequency stimulation on the affected hemisphere and low frequency stimulation on the unaffected hemisphere group (High-low group), and sham stimulation group (Sham group). On the basis of routine swallowing training (30 min) for all patients, the high group received 5 Hz rTMS in both hemispheres, the high- low group received 5 Hz rTMS in the unaffected hemisphere, 1 Hz rTMS in the affected hemisphere, and the sham stimulation group received sham stimulation in bilateral hemisphere. All participants were assessed with dysphagia handicap index (DHI), functional oral intake scale (FOIS) and videofluoroscopic swallowing study (VFSS) before the intervention (T1), immediately after intervention (T2) and 1 month after the intervention (T3). Meanwhile, according to the results of VFSS, Rosenbek penetration aspiration scale (PAS), the moving distance of hyoid bone towards the superior side (H), and pharyngeal response time (T) were analyzed and evaluated. After intervention, all three groups showed significant improvement in post-treatment scores from baseline (P = 0.000). The results of DHI, PAS and H showed that the improvement in high group and high-low group was significantly greater than sham group (P = 0.000). The results of FOIS and T showed that the improvement of bilateral high-frequency group was significantly greater than that of high-low group and sham group (P = 0.000), and the difference lasted until 1 month after the end of treatment. Therefore, bilateral pharyngeal cortex high frequency rTMS and affected side high frequency/unaffected side low frequency rTMS can effectively improve swallowing disorder after acute stroke. However, the effect of bilateral high frequency rTMS is significantly higher than high-low in improving oral feeding function and pharyngeal response time.
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Trastornos de Deglución , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Deglución/fisiología , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Estimulación Magnética Transcraneal/métodos , Resultado del TratamientoRESUMEN
How to efficiently activate peroxymonosulfate (PMS) in a complex water matrix to degrade organic pollutants still needs greater efforts, and cobalt-based bimetallic nanomaterials are desirable catalysts. In this paper, sea urchin-like NiCo2O4 nanomaterials were successfully prepared and comprehensively characterized for their structural, morphological and chemical properties via techniques, such as X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), among others. The sea urchin-like NiCo2O4 nanomaterials exhibited remarkable catalytic performance in activating PMS to degrade phenol. Within the NiCo2O4/PMS system, the removal rate of phenol (50 mg L-1, 250 mL) reached 100% after 45 min, with a reaction rate constant k of 0.091 min-1, which was 1.4-times higher than that of the monometallic compound Co3O4/PMS system. The outstanding catalytic activity of sea urchin-like NiCo2O4 primarily arises from the synergistic effect between Ni and Co ions. Additionally, a comprehensive analysis of key parameters influencing the catalytic activity of the sea urchin-like NiCo2O4/PMS system, including reaction temperature, initial pH of solution, initial concentration, catalyst and PMS dosages and coexisting anions (HCO3-, Cl-, NO3- and humic acid), was conducted. Cycling experiments show that the material has good chemical stability. Electron paramagnetic resonance (EPR) and quenching experiments verified that both radical activation (SO4â¢-, â¢OH, O2â¢-) and nonradical activation (1O2) are present in the NiCo2O4/PMS system. Finally, the possible degradation pathways in the NiCo2O4/PMS system were proposed based on gas chromatography-mass spectrometry (GC-MS). Favorably, sea urchin-like NiCo2O4-activated PMS is a promising technology for environmental treatment and the remediation of phenol-induced water pollution problems.
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Hypoxia inducible factor-1α (HIF-1α), as a hypoxia inducible factor, affects women's reproductive function by regulating the development and excretion of follicles. HIF-1α induces glycolysis and autophagy in the granule cells by promoting oocyte development, regulating the secretion of related angiogenic factors, and improving follicle maturity. In addition, HIF-1α promotes the process of luteinization of follicular vesicles, maintains luteal function, and finally completes physiological luteal atrophy through cumulative oxidative stress. Dysfunction of HIF-1α will cause a series of pathological consequences, such as angiogenesis defect, energy metabolism abnormality, excessive oxidative stress and dysregulated autophagy and apoptosis, resulting in ovulation problem and infertility. This article summarizes the previous studies on the regulation of follicle development and excretion and maintenance of luteal function and structural atrophy by HIF-1α. We also describe the effective intervention mechanism of related drugs or bioactive ingredients on follicular dysplasia and ovulation disorders through HIF-1α, in order to provide a systematic and in-depth insights for solving ovulation disorder infertility.