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BACKGROUND: Isolated methylmalonic acidemia, an autosomal recessive disorder of propionate metabolism, is usually caused by mutations in the methylmalonyl-CoA mutase gene (mut-type). Because no universal consensus was made on whether mut-type methylmalonic acidemia should be included in newborn screening (NBS), we aimed to compare the outcome of this disorder detected by NBS with that detected clinically and investigate the influence of NBS on the disease course. DESIGN & METHODS: In this study, 168 patients with mut-type methylmalonic acidemia diagnosed by NBS were compared to 210 patients diagnosed after disease onset while NBS was not performed. Clinical data of these patients from 7 metabolic centers in China were analyzed retrospectively, including initial manifestations, biochemical metabolites, the responsiveness of vitamin B12 therapy, and gene variation, to explore different factors on the long-term outcome. RESULTS: By comparison of the clinically-diagnosed patients, NBS-detected patients showed younger age at diagnosis, less incidence of disease onset, better responsiveness of vitamin B12, younger age at start of treatment, lower levels of biochemical features before and after treatment, and better long-term prognosis (P < 0.01). Onset of disease, blood C3/C2 ratio and unresponsiveness of vitamin B12 were more positively associated with poor outcomes of patients whether identified by NBS. Moreover, the factors above as well as older age at start of treatment were positively associated with mortality. CONCLUSIONS: This research highly demonstrated NBS could prevent major disease-related events and allow an earlier treatment initiation. As a key prognostic factor, NBS is beneficial for improving the overall survival of infants with mut-type methylmalonic acidemia.
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Errores Innatos del Metabolismo de los Aminoácidos , Metilmalonil-CoA Mutasa , Tamizaje Neonatal , Vitamina B 12 , Humanos , Errores Innatos del Metabolismo de los Aminoácidos/genética , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/patología , Errores Innatos del Metabolismo de los Aminoácidos/sangre , Recién Nacido , Metilmalonil-CoA Mutasa/genética , China/epidemiología , Masculino , Femenino , Vitamina B 12/sangre , Vitamina B 12/genética , Lactante , Estudios Retrospectivos , Mutación/genética , Pronóstico , Resultado del Tratamiento , PreescolarRESUMEN
To date, NH3 synthesis under mild conditions is largely confined to precious Ru catalysts, while nonprecious metal (NPM) catalysts are confronted with the challenge of low catalytic activity due to the inverse relationship between the N2 dissociation barrier and NHx (x = 1-3) desorption energy. Herein, we demonstrate NPM (Co, Ni, and Re)-mediated Mo2CTx MXene (where Tx denotes the OH group) to achieve efficient NH3 synthesis under mild conditions. In particular, the NH3 synthesis rate over Re/Mo2CTx and Ni/Mo2CTx can reach 22.4 and 21.5 mmol g-1 h-1 at 400 °C and 1 MPa, respectively, higher than that of NPM-based catalysts and Cs-Ru/MgO ever reported. Experimental and theoretical studies reveal that Mo4+ over Mo2CTx has a strong ability for N2 activation; thus, the rate-determining step is shifted from conventional N2 dissociation to NH2* formation. NPM is mainly responsible for H2 activation, and the high reactivity of spillover hydrogen and electron transfer from NPM to the N-rich Mo2CTx surface can efficiently facilitate nitrogen hydrogenation and the subsequent desorption of NH3. With the synergistic effect of the dual active sites bridged by H-spillover, the NPM-mediated Mo2CTx catalysts circumvent the major obstacle, making NH3 synthesis under mild conditions efficient.
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BACKGROUND: Inborn errors of metabolism (IEMs) frequently result in progressive and irreversible clinical consequences if not be diagnosed or treated timely. The tandem mass spectrometry (MS/MS)-based newborn screening (NBS) facilitates early diagnosis and treatment of IEMs. The aim of this study was to determine the characteristics of IEMs and the successful deployment and application of MS/MS screening over a 19-year time period in Shanghai, China, to inform national NBS policy. METHODS: The amino acids and acylcarnitines in dried blood spots from 1,176,073 newborns were assessed for IEMs by MS/MS. The diagnosis of IEMs was made through a comprehensive consideration of clinical features, biochemical performance and genetic testing results. The levels of MS/MS testing parameters were compared between various IEM subtypes and genotypes. RESULTS: A total of 392 newborns were diagnosed with IEMs from January 2003 to June 2022. There were 196 newborns with amino acid disorders (50.00%, 1: 5910), 115 newborns with organic acid disorders (29.59%, 1: 10,139), and 81 newborns with fatty acid oxidation disorders (20.41%; 1:14,701). Phenylalanine hydroxylase deficiency, methylmalonic acidemia and primary carnitine deficiency were the three most common disorders. Some hotspot variations in eight IEM genes (PAH, SLC22A5, MMACHC, MMUT, MAT1A, MCCC2, ACADM, ACAD8), 35 novel variants and some genotype-biochemical phenotype associations were identified. CONCLUSIONS: A total of 28 types of IEMs were identified, with an overall incidence of 1: 3000 in Shanghai, China. Our study offered clinical guidance for the implementation of MS/MS-based NBS and genetic counseling for IEMs in this city.
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Errores Innatos del Metabolismo de los Aminoácidos , Errores Innatos del Metabolismo , Humanos , Recién Nacido , Espectrometría de Masas en Tándem/métodos , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/epidemiología , Errores Innatos del Metabolismo/genética , China/epidemiología , Tamizaje Neonatal/métodos , Miembro 5 de la Familia 22 de Transportadores de Solutos , Oxidorreductasas/metabolismoRESUMEN
Corneal neovascularization (CNV) is a vision-threatening disease that is becoming a growing public health concern. While Yes-associated protein (YAP) plays a critical role in neovascular disease and allow for the sprouting angiogenesis. Verteporfin (VP) is a classical inhibitor of the YAP-TEAD complex, which is used for clinical treatment of neovascular macular degeneration through photodynamic therapy. The purpose of this study is to explore the effect of verteporfin (VP) on the inhibition of CNV and its potential mechanism. Rat CNV model were established by suturing in the central cornea and randomly divided into three groups (control, CNV and VP group). Neovascularization was observed by slit lamp to extend along the corneal limbus to the suture line. RNA-sequencing was used to reveal the related pathways on the CNV and the results revealed the vasculature development process and genes related with angiogenesis in CNV. In CNV group, we detected the nuclear translocation of YAP and the expression of CD31 in corneal neovascular endothelial cells through immunofluorescence. After the application of VP, the proliferation, migration and the tube formation of HUVECs were significantly inhibited. Furthermore, VP showed the CNV inhibition by tail vein injection without photoactivation. Then we found that the expression of phosphorylated YAP significantly decreased, and its downstream target protein connective tissue growth factor (CTGF) increased in the CNV group, while the expression was just opposite in other groups. Besides, both the expression of vascular endothelial growth factor receptor 2 (VEGFR2) and cofilin significantly increased in CNV group, and decreased after VP treatment. Therefore, we conclude that Verteporfin could significantly inhibited the CNV without photoactivation by regulating the activation of YAP.
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Neovascularización Coroidal , Neovascularización de la Córnea , Verteporfina , Animales , Ratas , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/metabolismo , Neovascularización de la Córnea/tratamiento farmacológico , Células Endoteliales/metabolismo , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Verteporfina/farmacología , Verteporfina/uso terapéuticoRESUMEN
BACKGROUND: Obesity is associated with a wide variety of metabolic disorders that impose significant burdens on patients and society. The "browning" phenomenon in white adipose tissue (WAT) has emerged as a promising therapeutic strategy to combat metabolic disturbances. However, though the anti-diabetic drug dapagliflozin (DAPA) is thought to promote "browning," the specific mechanism of this was previously unclear. METHODS: In this study, C57BL/6 J male mice were used to establish an obesity model by high-fat diet feeding, and 3T3-L1 cells were used to induce mature adipocytes and to explore the role and mechanism of DAPA in "browning" through a combination of in vitro and in vivo experiments. RESULTS: The results show that DAPA promotes WAT "browning" and improves metabolic disorders. Furthermore, we discovered that DAPA activated "browning" through the fibroblast growth factor receptors 1-liver kinase B1-adenosine monophosphate-activated protein kinase signaling pathway. CONCLUSION: These findings provide a rational basis for the use of DAPA in treating obesity by promoting the browning of white adipose tissue.
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Tejido Adiposo Blanco , Compuestos de Bencidrilo , Glucósidos , Proteínas Serina-Treonina Quinasas , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos , Transducción de Señal , Animales , Masculino , Ratones , Células 3T3-L1 , Adipocitos/metabolismo , Adipocitos/efectos de los fármacos , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Compuestos de Bencidrilo/farmacología , Dieta Alta en Grasa , Glucósidos/farmacología , Ratones Endogámicos C57BL , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Proteínas Serina-Treonina Quinasas/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Transducción de Señal/efectos de los fármacosRESUMEN
Two acylhydrazone based zinc(II) complexes [Zn(HL)2Cl2(CH3OH)2] (Zn1) and [ZnL(AC)]2 (Zn2) were synthesized from 3-(1-(salicyloylhydrazono)ethyl) pyridine (HL). Single crystal X-ray structure analyses showed that complexes Zn1 and Zn2 have a zero-dimensional monomer or dimer structure. Antiproliferative activity studies revealed that Zn1 and Zn2 are both more effective against A549 cells than cisplatin. The results of the reactive oxygen species (ROS) generation assay on A549 cells showed that both Zn1 and Zn2 induced apoptosis through ROS accumulation. The apoptosis-inducing and cell cycle arrest effects of Zn1 and Zn2 on A549 cells indicated that the antitumor effect was achieved through apoptosis induction and inhibition of DNA synthesis by blocking the G0/G1 phase of the cell cycle. What's more, the results of wound-healing assay showed that Zn1 and Zn2 could inhibit the migration of A549 cells. Western blot analysis further demonstrated that Zn1 and Zn2 induced cell apoptosis through the mitochondrial pathway, in which process, the expression level of cytochrome C, cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 9 proteins increased while pro-caspase 3 and pro-caspase 9 expression decreased. In vivo anticancer evaluation demonstrated that both Zn1 and Zn2 complexes effectively inhibited tumor growth without causing significant toxicity in systemic organs.
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Antineoplásicos , Apoptosis , Proliferación Celular , Complejos de Coordinación , Ensayos de Selección de Medicamentos Antitumorales , Hidrazonas , Neoplasias Pulmonares , Zinc , Animales , Ratones , Células A549 , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Relación Dosis-Respuesta a Droga , Hidrazonas/química , Hidrazonas/farmacología , Hidrazonas/síntesis química , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Ratones Endogámicos BALB C , Ratones Desnudos , Estructura Molecular , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Neoplasias Experimentales/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad , Zinc/química , Zinc/farmacologíaRESUMEN
BACKGROUND: Primary adrenal insufficiency (PAI) is a rare but life-threatening condition. Differential diagnosis of numerous causes of PAI requires a thorough understanding of the condition. METHODS: To describe the genetic composition and presentations of PAI. The following data were collected retrospectively from 111 patients with non-21OHD with defined genetic diagnoses: demographic information, onset age, clinical manifestations, laboratory findings and genetic results. Patients were divided into four groups based on the underlying pathogenesis: (1) impaired steroidogenesis, (2) adrenal hypoplasia, (3) resistance to adrenocorticotropic hormone (ACTH) and (4) adrenal destruction. The age of onset was compared within the groups. RESULTS: Mutations in the following genes were identified: NR0B1 (n=39), STAR (n=33), CYP11B1 (n=12), ABCD1 (n=8), CYP17A1 (n=5), HSD3B2 (n=4), POR (n=4), MRAP (n=2), MC2R (n=1), CYP11A1 (n=1), LIPA (n=1) and SAMD9 (n=1). Frequent clinical manifestations included hyperpigmentation (73.0%), dehydration (49.5%), vomiting (37.8%) and abnormal external genitalia (23.4%). Patients with adrenal hypoplasia typically presented manifestations earlier than those with adrenal destruction but later than those with impaired steroidogenesis (both p<0.01). The elevated ACTH (92.6%) and decreased cortisol (73.5%) were the most common laboratory findings. We generated a differential diagnosis flowchart for PAI using the following clinical features: 17-hydroxyprogesterone, very-long-chain fatty acid, external genitalia, hypertension and skeletal malformation. This flowchart identified 84.8% of patients with PAI before next-generation DNA sequencing. CONCLUSIONS: STAR and NR0B1 were the most frequently mutated genes in patients with non-21OHD PAI. Age of onset and clinical characteristics were dependent on aetiology. Combining clinical features and molecular tests facilitates accurate diagnosis.
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Enfermedad de Addison , Insuficiencia Suprarrenal , Humanos , Enfermedad de Addison/genética , Estudios Retrospectivos , Hormona Adrenocorticotrópica , China , Insuficiencia Suprarrenal/diagnóstico , Insuficiencia Suprarrenal/genética , Péptidos y Proteínas de Señalización IntracelularRESUMEN
BACKGROUND: Methylmalonic acidemia (MMA), which results from defects in methylmalonyl-CoA mutase (mut type) or its cofactor, is the most common inherited organic acid metabolic disease in China. This study aimed to investigate the phenotype and genotype of mut-type MMA in Chinese patients. METHODS: We recruited 365 patients with mut-type MMA; investigated their disease onset, newborn screening (NBS) status, biochemical metabolite levels, gene variations and prognosis; and explored the relationship between phenotype and genotype. RESULTS: There were 152 patients diagnosed by tandem mass spectrometry (MS/MS) expanded NBS, 209 patients diagnosed because of disease onset without NBS and 4 cases diagnosed because of sibling diagnosis. The median age of onset was 15 days old, with a variety of symptoms without specificity. Urinary levels of methylmalonic acid and methylcitric acid (MCA) decreased after treatment. Regarding the prognosis, among the 152 patients with NBS, 50.6% were healthy, 30.3% had neurocognitive impairment and/or movement disorders and 13.8% died. Among the 209 patients without NBS, 15.3% were healthy, 45.9% had neurocognitive impairment and/or movement disorders and 33.0% died. In total, 179 variants were detected in the MMUT gene, including 52 novel variations. c.729_730insTT, c.1106G>A, c.323G>A, c.914T>C and c.1663G>A were the five most frequent variations. The c.1663G>A variation led to a milder phenotype and better prognosis. CONCLUSION: There is a wide spectrum of variations in the MMUT gene with several common variations. Although the overall prognosis of mut-type MMA was poor, participation in MS/MS expanded NBS, vitamin B12 responsive and late onset are favourable factors for the prognosis.
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Trastornos del Movimiento , Espectrometría de Masas en Tándem , Recién Nacido , Humanos , Mutación , Genotipo , China/epidemiologíaRESUMEN
Strip steel plays a crucial role in modern industrial production, where enhancing the accuracy and real-time capabilities of surface defect classification is essential. However, acquiring and annotating defect samples for training deep learning models are challenging, further complicated by the presence of redundant information in these samples. These issues hinder the classification of strip steel surface defects. To address these challenges, this paper introduces a high real-time network, ODNet (Orthogonal Decomposition Network), designed for few-shot strip steel surface defect classification. ODNet utilizes ResNet as its backbone and incorporates orthogonal decomposition technology to reduce the feature redundancies. Furthermore, it integrates skip connection to preserve essential correlation information in the samples, preventing excessive elimination. The model optimizes the parameter efficiency by employing Euclidean distance as the classifier. The orthogonal decomposition not only helps reduce redundant image information but also ensures compatibility with the Euclidean distance requirement for orthogonal input. Extensive experiments conducted on the FSC-20 benchmark demonstrate that ODNet achieves superior real-time performance, accuracy, and generalization compared to alternative methods, effectively addressing the challenges of few-shot strip steel surface defect classification.
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Small-molecule positive allosteric modulator 1 (SPAM1), which targets pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R), has been found to have a neuroprotective effect, and the underlying mechanism was explored in this study. First, using a D-galactose (D-gal)-induced aging mouse model, we confirmed that SPAM1 improves the structure of the hippocampal dentate gyrus and restores the number of neurons. Compared with D-gal model mice, SPAM1-treated mice showed up-regulated expression of Sirtuin 6 (SIRT6) and Lamin B1 and down-regulated expression of YinYang 1 (YY1) and p16. A similar tendency was observed in senescent RGC-5 cells induced by long-term culture, indicating that SPAM1 exhibits significant in vitro and in vivo anti-senescence activity in neurons. Then, using whole-transcriptome sequencing and proteomic analysis, we further explored the mechanism behind SPAM1's neuroprotective effects and found that SPAM is involved in the longevity-regulating pathway. Finally, the up-regulation of neurofilament light and medium polypeptides indicated by the proteomics results was further confirmed by Western blotting. These results help to lay a pharmacological network foundation for the use of SPAM1 as a potent anti-aging therapeutic drug to combat neurodegeneration with anti-senescence, neuroprotective, and nerve regeneration activity.
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Proteómica , Transcriptoma , Animales , Ratones , Perfilación de la Expresión Génica , Envejecimiento/genética , Longevidad , Galactosa/farmacologíaRESUMEN
Oridonin (Ori) is a naturally existing diterpenoid substance that mainly exists in the Chinese medicinal plant Rabdosia rubescens. It was previously found to possess intriguing biological properties; however, the quick clearance from plasma and limited solubility in water restricts its use as a drug. Several metal-organic frameworks (MOFs), having big surfaces and large pores, have recently been considered promising drug transporters. The zeolitic imidazolate framework-8 (ZIF-8), a form of MOF consisting of 2-methylimidazole with zinc ions, is structurally stable under physiologically neutral conditions, while it can degrade at low pH values such as in tumor cells. Herein, a nanosized drug delivery system, Ori@ZIF-8, was successfully designed for encapsulating and transporting oridonin to the tumor site. The drug loading of the prepared Ori@ZIF-8 was 26.78%, and the particles' mean size was 240.5 nm. In vitro, the release of Ori@ZIF-8 exhibited acid sensitivity, with a slow release under neutral conditions and rapid release of the drug under weakly acidic conditions. According to the in vitro anti-tumor experiments, Ori@ZIF-8 produced higher cytotoxicity than free Ori and induced apoptosis in A549 cancer cells. In conclusion, Ori@ZIF-8 could be a potential pH-responsive carrier to accurately release more oridonins at the tumor site.
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Diterpenos de Tipo Kaurano , Estructuras Metalorgánicas , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/farmacología , Estructuras Metalorgánicas/química , Humanos , Concentración de Iones de Hidrógeno , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Portadores de Fármacos/química , Células A549 , Línea Celular Tumoral , Zeolitas/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Antineoplásicos/farmacología , Antineoplásicos/química , Supervivencia Celular/efectos de los fármacos , ImidazolesRESUMEN
Sepsis-associated encephalopathy (SAE) is one of the most common types of organ dysfunction without overt central nervous system (CNS) infection. It is associated with higher mortality, low quality of life, and long-term neurological sequelae, its mortality in patients diagnosed with sepsis, progressing to SAE, is 9% to 76%. The pathophysiology of SAE is still unknown, but its mechanisms are well elaborated, including oxidative stress, increased cytokines and proinflammatory factors levels, disturbances in the cerebral circulation, changes in blood-brain barrier permeability, injury to the brain's vascular endothelium, altered levels of neurotransmitters, changes in amino acid levels, dysfunction of cerebral microvascular cells, mitochondria dysfunction, activation of microglia and astrocytes, and neuronal death. The diagnosis of SAE involves excluding direct CNS infection or other types of encephalopathies, which might hinder its early detection and appropriate implementation of management protocols, especially in paediatric patients where only a few cases have been reported in the literature. The most commonly applied diagnostic tools include electroencephalography, neurological imaging, and biomarker detection. SAE treatment mainly focuses on managing underlying conditions and using antibiotics and supportive therapy. In contrast, sedative medication is used judiciously to treat those showing features such as agitation. The most widely used medication is dexmedetomidine which is neuroprotective by inhibiting neuronal apoptosis and reducing a sepsis-associated inflammatory response, resulting in improved short-term mortality and shorter time on a ventilator. Other agents, such as dexamethasone, melatonin, and magnesium, are also being explored in vivo and ex vivo with encouraging results. Managing modifiable factors associated with SAE is crucial in improving generalised neurological outcomes. From those mentioned above, there are still only a few experimentation models of paediatric SAE and its treatment strategies. Extrapolation of adult SAE models is challenging because of the evolving brain and technical complexity of the model being investigated. Here, we reviewed the current understanding of paediatric SAE, its pathophysiological mechanisms, diagnostic methods, therapeutic interventions, and potential emerging neuroprotective agents.
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Encefalopatías , Encefalopatía Asociada a la Sepsis , Sepsis , Adulto , Humanos , Niño , Encefalopatía Asociada a la Sepsis/diagnóstico , Encefalopatía Asociada a la Sepsis/etiología , Encefalopatía Asociada a la Sepsis/terapia , Calidad de Vida , Encéfalo/metabolismo , Sepsis/metabolismo , Encefalopatías/etiología , Encefalopatías/complicacionesRESUMEN
Featured with its extraordinary super-resolution capability, the advent of stimulated emission depletion (STED) lithography has allowed for vastly reduced minimum feature size of a single pixel down to the deep sub-diffraction scale so as to produce unprecedented nanofeatures. However, the anticipated sub-diffraction pixel pitch down below 100â nm remains out of reach due to redundant polymerization of adjacent exposures at a short distance, so called memory effect. In this work, a nanoprinting-at-expansion/employments-at-recovery strategy is applied in the dual-beam STED lithography technique to surmount the memory effect and break adjacent-exposure limit imposed on minimizing the pixel pitch. The implementation of a femtosecond laser at a wavelength of 532â nm, the same as the inhibition laser beam, working as the initiation laser beam, can drastically reduce the saturated inhibition laser intensity by 74% for abating redundant polymerization subjected to multiple exposures in realizing nanoscale pixel pitch. The adjacent-exposure zone can be separated by isotropically expanding an elastic PDMS substrate for further diminishing redundant polymerization. Applying stretching ratio of 30%, a minimum super-resolved nanodots pixel pitch of 96â nm was achieved with single-dot size of 34â nm on both planar and hierarchical substrate, which offers a record-close distance for printing adjacent pixels. With its nanometer discernibility, this method holds great promise for future versatile utilization in advanced nanoimprinting, high density data storage, etc.
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Fiber-optic devices working in the visible and near-infrared windows are attracting attention due to the rapid development of biomedicine that involves optics. In this work, we have successfully realized the fabrication of near-infrared microfiber Bragg grating (NIR-µFBG), which was operated at the wavelength of 785â nm, by harnessing the fourth harmonic order of Bragg resonance. The NIR-µFBG provided the maximum sensitivity of axial tension and bending to 211â nm/N and 0.18â nm/deg, respectively. By conferring the considerably lower cross-sensitivity, such as response to temperature or ambient refractive index, the NIR-µFBG can be potentially implemented as the highly sensitive tensile force and curve sensor.
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The desorption mechanism of heavy metals (HMs) in soil around the mining region are complex and affected by multiple pollution sources, including sewage discharge and atmospheric deposition. Meanwhile, pollution sources would change soil physical and chemical properties (mineralogy and organic matter), thus affecting the bioavailability of HMs. This study aimed to investigate the pollution source of HMs (Cd, Co, Cu, Cr, Mn, Ni, Pb, and Zn) in soil near mining, and further evaluate influence mechanism of dust fall on HMs pollution in soil by desorption dynamics processes and pH-dependence leaching test. Result presented that dust fall is the primary pollution source to HMs accumulation in soil. Additionally, the result of mineralogical analysis in dust fall revealed that quartz, kaolinite, calcite, chalcopyrite, and magnetite are the major mineralogical phases by XRD and SEM-EDS. Meanwhile, the abundance of kaolinite and calcite in dust fall is higher than in soil, which is the primary reason of higher acid-base buffer capacity of dust fall. Correspondingly, the weakened or disappeared of hydroxyl after the adding acid extraction (0-0.4 mmol· g-1) demonstrated that hydroxyl is the main participants of HMs absorption in soil and dust fall. These combined findings suggested that atmospheric deposition not only increases the pollution loading of HMs in soil, but also changes the mineral phase composition of soil, which would increase the adsorption capacity and bioavailability of HMs in soil. This is very remarkable that heavy metals in soil influenced by dust fall pollution could be released preferentially when soil pH is changed. The present results of this study would provide efficient and scientific targeted strategies for pollution control of HMs in soil near mining areas.
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Monitoreo del Ambiente , Metales Pesados , Contaminantes del Suelo , Humanos , China , Cobre/análisis , Polvo/análisis , Monitoreo del Ambiente/métodos , Caolín , Metales Pesados/análisis , Medición de Riesgo , Suelo/química , Contaminantes del Suelo/análisisRESUMEN
Objective: This study aimed to investigate the protective mechanisms of melatonin in an in vitro model of sepsis-induced hepatocyte injury, specifically focusing on mitophagy and mitochondrial biogenesis. Methods: In this study, we utilized lipopolysaccharide (LPS)-treated AML12 cells to establish an in vitro model of sepsis-induced hepatocyte injury. The effects of melatonin pretreatment were examined through various analyses, including assessments of oxidative stress, inflammation, mitophagy, mitochondrial biogenesis, and adenosine triphosphate (ATP) levels. Results: The results revealed that LPS-treated AML12 cells exhibited elevated levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 protein, intracellular reactive oxygen species (ROS), and lipid peroxidation, specifically malondialdehyde (MDA). Moreover, the levels of key markers associated with mitophagy, including PTEN-induced putative kinase 1 (PINK1), parkin, and LC3, were significantly increased (P < .05). Similarly, markers of mitochondrial biogenesis, such as peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM), were also significantly increased (P < .05). Conversely, superoxide dismutase (SOD) activity and ATP levels were significantly decreased in LPS-treated AML12 cells compared to the control group (P < .05). However, melatonin pretreatment led to a significant decrease in TNF-α and IL-6 protein levels, intracellular ROS, and MDA levels (P < .05), along with a significant increase in SOD activity, ATP levels, and markers of mitophagy and mitochondrial. Conclusions: Our findings demonstrate that melatonin plays a role in regulating mitochondrial quality control in sepsis-induced hepatocytes. It achieves this result by promoting mitophagy and inducing mitochondrial biogenesis, thereby selectively eliminating dysfunctional mitochondria.
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Melatonina , Sepsis , Humanos , Melatonina/farmacología , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/farmacología , Mitofagia , Biogénesis de Organelos , Lipopolisacáridos , Hepatocitos/metabolismo , Superóxido Dismutasa , Adenosina Trifosfato/farmacología , Sepsis/tratamiento farmacológicoRESUMEN
Cancer stem cells (CSCs) have been identified and characterized in both hematopoietic and solid tumors. Their existence was first predicted by Virchow and Cohnheim in the 1870s. Later, many studies showed that CSCs can be identified and isolated by their expression of specific cell markers. The significance of CSCs with respect to tumor biology and anti-cancer treatment lies in their ability to maintain quiescence with very slow proliferation, indefinite self-renewal, differentiation, and trans-differentiation such as epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET). The ability for detachment, migration, extra- and intravasation, invasion and thereby of completing all necessary steps of the metastatic cascade highlights their significance for metastasis. CSCs comprise the cancer cell populations responsible for tumor growth, resistance to therapies and cancer metastasis. In this review, the history of the CSC theory, their identification and characterization and their biology are described. The contribution of the CSC ability to undergo EMT for cancer metastasis is discussed. Recently, novel strategies for drug development have focused on the elimination of the CSCs specifically. The unique functional and molecular properties of CSCs are discussed as possible therapeutic vulnerabilities for the development of novel anti-metastasis treatments. Prospectively, this may provide precise personalized anti-cancer treatments with improved therapeutic efficiency with fewer side effects and leading to better prognosis.
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Transición Epitelial-Mesenquimal , Neoplasias , Humanos , Neoplasias/metabolismo , Diferenciación Celular , Células Madre Neoplásicas/metabolismoRESUMEN
Compared with high-pressure water and reagent washing decontamination, foam decontamination has a promising application due to its ability to significantly reduce the volume of radioactive waste liquids and effectively decontaminate the inner surface of the pipes, the interior of the large cavities, and the vertical walls. However, the foam is less stable, leading to a low decontamination rate. Currently, three main types of stabilizers with different stabilizing mechanisms, namely nanoparticles, polymers, and cosurfactants, are used to improve foam stability and thus increase the decontamination rate. Nanosilica (NS), xanthan gum (XG), and n-tetradecanol (TD) were used as typical representatives of nanoparticles, polymers, and cosurfactants, respectively, to improve the stability of the foam detergent with pH < 2 and chelating agents. The differences in the effects of these three types of stabilizers on foam properties were investigated. Although NS, XG, and TD all increase the half-life of the foam from 7.2 min to about 40 min, the concentration of TD is much lower than that of NS and XG in the foaming solution, and TD foaming solution has the highest foaming ratio. Moreover, TD can markedly lower the surface tension, resulting in a significant reduction of the wetting contact angle on the surfaces of glass, ceramic tile, stainless steel, and paint, while NS and XG cannot signally change the surface tension and have no obvious effect on the wetting contact angle. At low shear rates, TD can increase the apparent viscosity of foam by two orders of magnitude, and the wall-hanging time of the foam on the vertical wall is more than 30 min. In contrast, NS and XG cause a limited increase in the apparent viscosity of the foam, and the wall-hanging times are both less than 5 min. In addition, TD foaming solution has excellent storage stability, and the storage time has no obvious effect on the performance of the foam. And after only three days of storage, NS undergoes severe agglomeration and precipitation in the foaming solution, resulting in a complete loss of the stabilizing effect. After 90 days of storage, the half-life of XG foam decreases by 26%. For simulated radioactive uranium contamination on both horizontal and vertical surfaces, TD can significantly improve the decontamination rate, especially for vertical surfaces, where TD can increase the single decontamination rate by more than 50%.
RESUMEN
Despite the decrease in anthropogenic emissions, haze episodes were still frequent in the Fenwei Plain, which was identified as one of the three key areas for air pollution control. Herein, PM2.5 samples were collected to investigate the influence of festival effect during the Chinese Spring Festival from February 2rd to 13th, 2019, in Linfen on the Fenwei Plain. The characteristics of element pollution, enrichment factor, source apportionment, regional transport of PM2.5, and health risk assessment were discussed. Meanwhile, the simulated lung fluid method (SLF) was carried out to accurately assess the inhalation risks of heavy metals (HMs). Results indicated that the average concentration of PM2.5 was 195.6 µg·m-3 during the studying period. Road fugitive dust (15.6%), firework burning source (25.6%), industrial emission (30.5%), and coal combustion (28.3%) were identified by positive matrix factorization (PMF) modeling. Using the HYSPLIT trajectory model, air masses from the central Shaanxi, southern Hebei, and northern Henan were the dominant transport paths during the Spring Festival, which contributed 21.9 and 41.2% of total trajectories, respectively. The findings that high PSCF and CWT levels were found in central Shaanxi, southern Hebei, and northern Henan were confirmed. The SLF mean bioaccessibility (%) of the solubility of particulate metals was in order of Mn > Ni > Sb > Ba > Zn > Pb > Cr. However, the carcinogenic risk value of Cr was the highest, exceeding the maximum acceptable risk. The present study provided important information for further analyzing the air pollution cause of Fenwei Plain.
Asunto(s)
Contaminantes Atmosféricos , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Carbón Mineral/análisis , Disponibilidad Biológica , Monitoreo del Ambiente/métodos , China , Estaciones del Año , Emisiones de Vehículos/análisisRESUMEN
OBJECTIVE: To explore the disease spectrum for abnormal 3-hydroxyisovalerylcarnitine (C5OH) metabolism identified through newborn screening and clinical diagnosis patients and the key points for differential diagnosis so as to raise the awareness of pediatricians for such diseases. METHODS: Clinical data of 85 neonates with abnormal C5OH metabolism identified from February 2004 to January 2022 at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were collected. Their clinical manifestations and results of tandem mass spectrometry (MS/MS), gas chromatography mass spectrometry (GC-MS) and genetic testing were retrospectively analyzed. RESULTS: Among the 85 cases, 46 (54.1%) were identified by neonate screening, whilst 39 (45.9%) were clinically diagnosed patients. Five diseases were diagnosed, including 28 cases with multiple carboxylase deficiency (MCD, 32.9%), 29 cases with 3-methylcrotonyl-coenzymeAcarboxylasedeficiency (MCCD, 34.1%), 4 cases with 3-methylglutaconic acid (3-MGA, 4.7%), 7 cases with 3-hydroxy-3-methylglutaric acid (3-HMG, 8.2%), and 17 cases with beta-ketothiolase deficiency (BKD, 20.0%). The disorders were characterized by sudden onset, anorexia, vomiting, diarrhea, abnormal breathing, consciousness disorder, spasm and developmental delay. CONCLUSION: Among newborns with abnormal C5OH metabolism, MCCD is the most common disorder, which was followed by BKD and MCD. For patients with abnormal C5OH metabolism, MCD is the most common, followed by BKD and 3-HMG. C5OH related diseases have great heterogeneity. Combination of blood acylcarnitine levels, urinary organic acid levels and genetic testing based on clinical characteristics can help to attain the diagnosis.