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The preparation of coordination polymer (CP) alloys is demonstrated by the use of two meltable, one-dimensional crystal structures via melt-kneading. The polymer structures of the alloys are studied by synchrotron X-ray absorption and scattering, solid-state NMR spectroscopy, DSC, and viscoelastic measurements. Crystalline and amorphous domains and thermal properties (melting and glass transition) in the alloys depend on the ratio of the two constituent CPs. The glassy alloy composed of an equivalent amount of two CPs shows high plastic deformation properties, and the fracture point reaches 128% without a filler or compatibilizing agent, hence behaving as ductile materials.
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Separating ethane (C2H6) from ethylene (C2H4) is an essential and energy-intensive process in the chemical industry. Here, we report two flexible diamondoid coordination networks, X-dia-1-Ni and X-dia-1-Ni0.89Co0.11, that exhibit gate-opening between narrow-pore (NP) and large-pore (LP) phases for C2H6, but not for C2H4. X-dia-1-Ni0.89Co0.11 thereby exhibited a type F-IV isotherm at 273 K with no C2H6 uptake and a high uptake (111 cm3 g-1, 1 atm) for the NP and LP phases, respectively. Conversely, the LP phase exhibited a low uptake of C2H4 (12.2 cm3 g-1). This C2H6/C2H4 uptake ratio of 9.1 for X-dia-1-Ni0.89Co0.11 far surpassed those of previously reported physisorbents, many of which are C2H4-selective. In situ variable-pressure X-ray diffraction and modeling studies provided insight into the abrupt C2H6-induced structural NP to LP transformation. The promise of pure gas isotherms and, more generally, flexible coordination networks for gas separations was validated by dynamic breakthrough studies, which afforded high-purity (99.9%) C2H4 in one step.
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Drought and water scarcity are two of the world's major problems. Solar-powered sorption-based atmospheric water harvesting technology is a promising solution in this category. The main challenge is to design materials with high water harvesting performance while achieving fast water vapor adsorption/desorption rates. Here, a superhydrophilic photothermic hollow nanocapsule (SPHN) is represented that achieves efficient atmospheric water harvesting in outdoor climates. In SPHN, the hollow mesoporous silica (HMS) is grafted with polypyrrole (PPy) and also loaded with lithium chloride (LiCl). The hollow structure is used to store water while preventing leakage. The hydrophilic spherical nanocapsule and the trapped water produce more free and weakly adsorbed water. Significantly lower the heat of desorption compared to pure LiCl solution. Such SPHN significantly improves the adsorption/desorption kinetics, e.g., absorbs 0.78-2.01 g of water per gram of SPHN at 25 °C, relative humidity (RH) 30-80% within 3 h. In particular, SPHN has excellent photothermal properties to achieve rapid water release under natural sunlight conditions, i.e., 80-90% of water is released in 1 h at 0.7-1.0 kW m-2 solar irradiation, and 50% of water is released even at solar irradiation as low as 0.4 kW m-2 . The water collection capacity can reach 1.2 g g-1 per cycle by using the self-made atmospheric water harvesting (AWH) device. This finding provides a way to design novel materials for efficient water harvesting tasks, e.g., water engineering, freshwater generator, etc.
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Clarithromycin (CLA) has been widely used in the treatment of bacterial infection. Research reveals the adverse effects on the central nervous system among patients receiving CLA treatment; whereas, a relevant underlying mechanism remains considerably unclear. According to our research, an integrated lipidomic and transcriptomic analysis was applied to explore the effect of CLA on neurobehavior. CLA treatment caused anxiety-like behaviors dose-dependently during open field as well as elevated plus maze trials on mice. Transcriptomes and LC/MS-MS-based metabolomes were adopted for investigating how CLA affected lipidomic profiling as well as metabolic pathway of the cerebral cortex. CLA exposure greatly disturbed glycerophospholipid metabolism and the carbon chain length of fatty acids. By using whole transcriptome sequencing, we found that CLA significantly downregulated the mRNA expression of CEPT1 and CHPT1, two key enzymes involved in the synthesis of glycerophospholipids, supporting the findings from the lipidomic profiling. Also, CLA causes changes in neuronal morphology and function in vitro, which support the existing findings concerning neurobehavior in vivo. We speculate that altered glycerophospholipid metabolism may be involved in the neurobehavioral effect of CLA. Our findings contribute to understanding the mechanisms of CLA-induced adverse effects on the central nervous system. 1. Clarithromycin treatment caused anxiety-like behavior with dose-dependent response both in the open field and elevated plus maze test in mice; 2. Clarithromycin exposing predominately disturbed the metabolism of glycerophospholipids in the cerebral cortex of mice; 3. Clarithromycin application remarkably attenuated CEPT1 and CHPT1 gene expression, which participate in the last step in the synthesis of glycerophospholipids; 4. The altered glycerophospholipid metabolomics may be involved in the abnormal neurobehavior caused by clarithromycin.
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Claritromicina , Lipidómica , Animales , Ratones , Claritromicina/farmacología , Transcriptoma , Glicerofosfolípidos/metabolismo , Corteza Cerebral/metabolismoRESUMEN
Oxidative stress response is closely related to neurodegenerative diseases. This study aimed to investigate the cytoprotective effects of luteolin on glutamate-induced oxidative stress injury in PC12 cells. GC-MS combined with multivariate statistical approaches was used to perform metabolomics studies to assess the possible mechanisms. Our results identified 23 metabolites as differential expressed metabolites in the glutamate group, including cysteine content in cells that decreased drastically. This suggests that glutathione synthesis, which balances the redox state of cells, was affected. Luteolin inhibits the reduction in viability in glutamate-induced PC12 cells and regulates 13 differential expressed metabolites in glutamate-induced cell damage. These metabolites associated with luteolin included glycine, serine, and threonine metabolism; glyoxylate and dicarboxylate metabolism; aminoacyl-tRNA biosynthesis; cysteine and methionine metabolism; inositol phosphate metabolism; and starch and sucrose metabolism. In summary, the systemic antioxidant capacity of luteolin in PC12 cells is related to its regulation of amino acid, glucose, and nucleotide metabolism pathways.
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Ácido Glutámico , Luteolina , Ratas , Animales , Células PC12 , Luteolina/farmacología , Cromatografía de Gases y Espectrometría de Masas , Cisteína , MetabolómicaRESUMEN
Boron (B) is a required micronutrient that is crucial for the growth and development of vascular plants. A deficiency in B is generally regarded as a limiting factor affecting agricultural production in many parts of the world. Boron is involved in the metabolism of plant lignin and additionally, B deficiency can lead to the excessive accumulation of lignin in plant leaves/roots, resulting in corking symptoms and inhibited growth. However, the effect of B on lignin biosynthesis is not as well characterized as the specific function of B in the cell wall. In this article, recent studies on the regulation of lignin biosynthesis in plants under low-B stress conditions are reviewed. Moreover, the following possible mechanisms underlying the lignin synthesis promoted by B deficiency are discussed: (1) the accumulation of phenolic substances during B deficiency directly enhances lignin synthesis; (2) excess H2 O2 has a dual function to the enhancement of lignin under boron deficiency conditions, serving as a substrate and a signaling molecule; and (3) B deficiency regulates lignin synthesis through the expression of genes encoding transcription factors such as MYBs. Finally, future studies regarding physiology, molecules, and transcriptional regulation may reveal the mechanism(s) mediating the relationship between lignin synthesis and B deficiency. This review provides new insights and important references for future research and the enhancement of plant B nutrition.
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Boro , Lignina , Boro/metabolismo , Lignina/metabolismo , Plantas/metabolismo , Factores de Transcripción/metabolismo , Hojas de la Planta/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Arlivirus is currently the only genus in the newly established viral family Lispiviridae. In this study, the complete genome sequence of a novel arlivirus, tentatively named "Nbu stink bug virus 1" (NbuSBV-1), was identified in an individual yellow spotted stink bug, Erthesina fullo (family Pentatomidae, order Hemiptera), which is a widely distributed phytophagous pest in Asia. NbuSBV-1 has a single negative-stranded RNA genome of 13,605 nucleotides in length, and it was predicted to contain six open reading frames (ORFs). Conserved domains of NbuSBV-1 were predicted in ORF1 (a nucleoprotein), ORF4 (a glycoprotein domain), ORF5 (a zinc-finger domain), and ORF6 (an RNA-directed RNA polymerase [RdRP] domain, an mRNA cap domain, and a methyltransferase domain). NbuSBV-1 shares 50.54% amino acid sequence identity in the RdRP region with its closest homolog, Lishì spider virus 2. In RdRP-based phylogenetic analysis, NbuSBV-1 was clearly clustered in a clade with other arliviruses. Furthermore, NbuSBV-1-derived small interfering RNAs (siRNAs) showed typical patterns of virus-derived siRNAs produced by the host antiviral RNA interference pathway. As far as we know, NbuSBV-1 is the first arlivirus identified in an insect of the family Pentatomidae.
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Heterópteros , Virus ARN , Animales , Genoma Viral , Sistemas de Lectura Abierta , Filogenia , Virus ARN/genética , ARN Viral/genéticaRESUMEN
Methotrexate, a folic acid antitumor drug, is widely used to treat childhood acute lymphoblastic leukemia. Therapeutic drug monitoring is crucial for adjusting the dosage of methotrexate according to its plasma concentration and reducing adverse effects. Micro-sampling strategies, like dried plasma spot, is an attractive but underutilized method that has the desired features of easy collection, storage, and transport, and overcomes known hematocrit issues in dried blood spot analysis. This study describes a dried plasma spot-based liquid chromatography-tandem mass spectrometry method for quantification of methotrexate. The assay showed good linearity over 30-2000 ng/mL (R2 ≥ 0.995) as well as excellent precision (0.6-9.3%) and accuracy (89.2-108.3%). Methotrexate was extracted from dried plasma spot and wet plasma samples with recoveries greater than 92.1%, and no significant matrix effect was observed. A comparison of dried plasma spot and wet plasma concentrations was assessed in 27 patients treated with methotrexate and Passing-Bablok regression coefficients showed that no significant difference between the two methods. The Bland-Altman plots showed similar agreement between the methods, indicating that the proposed dried plasma spot sampling method is an effective way to monitor the concentration of methotrexate in human plasma.
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Monitoreo de Drogas , Espectrometría de Masas en Tándem , Niño , Cromatografía Liquida , Pruebas con Sangre Seca/métodos , Monitoreo de Drogas/métodos , Humanos , Metotrexato , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/métodosRESUMEN
Ischemic stroke is a disease with high mortality. Circular RNA_0010729 (hsa_circ_0010729) has been reported to be involved in ischemic heart disease. However, it is not clear whether hsa_circ_0010729 is involved in the regulation of ischemic stroke. In this study, we used oxygen-glucose deprivation/reoxygenation (OGD/R) to stimulate human brain microvascular endothelial cells (HBMECs) model to investigate the potential role of hsa_circ_0010729 in stroke in vitro. The expression levels of hsa_circ_0010729, miR-665, and ING5 in ischemic stroke were detected by quantitative real-time polymerase chain reaction (qRT-PCR). HBMECs proliferation was detected by CCK-8. Cell apoptosis was detected by flow cytometry. The levels of inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the related protein expression. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were used to examine the target relationship between miR-665 and hsa_circ_0010729 or ING5. Compared with the control group, hsa_circ_0010729 and ING5 were highly expressed in OGD/R-induced HBMECs, while miR-665 was lowly expressed. Hsa_circ_0010729 silencing promoted OGD/R-induced cell proliferation and inhibited apoptosis. However, the effect of hsa_circ_0010729 down-regulation on OGD/R-induced cell was partially restored after co-transfection with miR-665 inhibitor. Overexpression of miR-665 can promote the proliferation and inhibit apoptosis of OGD/R-induced HBMECs by inhibiting ING5 expression. In OGD/R-induced HBMECs, hsa_circ_0010729 silencing decreased ING5 expression by upregulating miR-665. Hsa_circ_0010729 regulated miR-665/ING5 axis in OGD/R-induced HBMECs. Therefore, hsa_circ_0010729 may be a new therapeutic target for ischemic stroke.
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Accidente Cerebrovascular Isquémico , MicroARNs , ARN Circular , Humanos , Apoptosis/genética , Proliferación Celular/genética , Células Endoteliales/metabolismo , Glucosa/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Oxígeno/metabolismo , Factores de Transcripción , Proteínas Supresoras de Tumor/genética , ARN Circular/genéticaRESUMEN
Ochratoxin A (OTA) is a mycotoxin found in a variety of foods and herbal medicines, and several governmental bodies around the world have set maximum allowable levels of OTA in different foods and herbal medicines. This study aims to evaluate the health risk of OTA in Astragali Radix (AR) in China, and to evaluate the effects of different limit levels on the risk control of OTA in AR. The concentrations of OTA in 187 samples of AR were investigated, and 61 (32.6%) samples were positive. The mean, 50th and 95th percentile values of OTA in positive samples were 56.2, 5.1 and 304.5 µg/kg, respectively. A margin of exposure (MOE) approach was applied to assess the risk. Considering other food sources, long-term consumers have a relatively high risk of OTA exposure due to the ingestion of AR. Theoretical limit levels of OTA in AR were evaluated from two dimensions by weighing the costs and the benefits. The results indicated that the limit levels that might be applied to the management of OTA contamination in AR in China could be screened out through risk-based evaluation of limit levels.
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Planta del Astrágalo , Micotoxinas , Ocratoxinas , China , Contaminación de Alimentos/análisis , Ocratoxinas/análisisRESUMEN
Meropenem (MER) is widely used to treat complicated and serious infections. Therapeutic drug monitoring (TDM) provides a valid clinical tool to avoid suboptimal concentrations and dose−related adverse reactions. However, TDM seems to face challenges since the limited stability of MER in plasma makes transport difficult between clinics and laboratories. Dried plasma spot (DPS) sampling is an attractive but underutilized method for TDM that has the desired features of easy collection, storage, and transport, and overcomes known hematocrit (HCT) issues in dried blood spot (DBS) analysis. This study was designed to investigate a DPS−based liquid chromatography−tandem mass spectrometry (LC−MS/MS) method for quantification of MER. The method was developed and validated for DPS and wet plasma samples. Calibration curves were linear (R2 > 0.995) over the concentration range of 0.5−50 µg/mL. Overall accuracy and precision did not exceed 15% and no significant matrix effect was observed. MER has been more stable in DPS than in wet plasma samples. A comparison of DPS and wet plasma concentrations was assessed in 32 patients treated with MER. The results showed that there was no significant difference between the two methods. So the DPS method developed in this study is appropriate and practical for the monitor of MER in the daily clinical laboratory practice.
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Pruebas con Sangre Seca , Espectrometría de Masas en Tándem , Cromatografía Liquida/métodos , Pruebas con Sangre Seca/métodos , Humanos , Meropenem , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/métodosRESUMEN
The enrichment and purification of coal-bed methane provides a source of energy and helps offset global warming. In this work, we demonstrate a strategy involving the regulation of the pore size and pore chemistry to promote the separation of CH4 /N2 mixtures in four nickel-based coordination networks, named Ni(ina)2 , Ni(3-ain)2 , Ni(2-ain)2 , and Ni(pba)2 , (where ina=isonicotinic acid, 3-ain=3-aminoisonicotinic acid, 2-ain=2-aminoisonicotinic acid, and pba=4-(4-pyridyl)benzoic acid). Among them, Ni(ina)2 and Ni(3-ain)2 can effectively separate CH4 from N2 with top-performing performance because of the suitable pore size (≈0.6 and 0.5â nm) and pore environment. Explicitly, Ni(ina)2 exhibits the highest ever reported CH4 /N2 selectivity of 15.8 and excellent CH4 uptake (40.8â cm3 g-1 ) at ambient conditions, thus setting new benchmarks for all reported MOFs and traditional adsorbents. The exceptional CH4 /N2 separation performance of Ni(ina)2 is confirmed by dynamic breakthrough experiments. Under different CH4 /N2 ratios, Ni(ina)2 selectively extracts methane from the gaseous blend and produces a high purity of CH4 (99 %). Theoretical calculations and CH4 -loading single-crystal structure analysis provide critical insight into the adsorption/separation mechanism. Ni(ina)2 and Ni(3-ain)2 can form rich intermolecular interactions with methane, indicating a strong adsorption affinity between pore walls and CH4 molecules. Importantly, Ni(ina)2 has good thermal and moisture stability and can easily be scaled up at a low cost ($25 per kilogram), which will be valuable for potential industrial applications. Overall, this work provides a powerful approach for the selective adsorption of CH4 from coal-bed methane.
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In the electronics industry, the efficient recovery and capture of sulfur hexafluoride (SF6 ) from SF6 /N2 mixtures is of great importance. Herein, three metal-organic frameworks with fine-tuning pore structures, Cu(peba)2 , Ni(pba)2 , and Ni(ina)2 , were designed for SF6 capture. Among them, Ni(ina)2 has perfect pore sizes (6â Å) that are comparable to the kinetic diameter of sulfur hexafluoride (5.2â Å), affording the benchmark binding affinity for SF6 gas. Ni(ina)2 exhibits the highest SF6 /N2 selectivity (375.1 at 298â K and 1â bar) and ultra-high SF6 uptake capacity (53.5â cm3 g-1 at 298â K and 0.1â bar) at ambient conditions. The remarkable separation performance of Ni(ina)2 was verified by dynamic breakthrough experiments. Theoretical calculations and the SF6 -loaded single-crystal structure provided critical insight into the adsorption/separation mechanism. This porous coordination network has the potential to be used in industrial applications.
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GC/MS coupled metabolomics analysis, using a simplified and much less expensive silylation process with trimethylsilyl cyanide (TMSCN), was conducted to investigate metabolic abnormalities in stomach cancer cells. Under optimized conditions for derivatization by TMSCN and methanol extraction, 228 metabolites were detected using GC/MS spectrometry analysis, and 89 metabolites were identified using standard compounds and the NIST database. Ten metabolite levels were found to be lower in stomach cancer cells relative to normal cells. Among those ten metabolites, four metabolites-ribose, proline, pyroglutamic acid, and glucose-were known to be linked to cancers. In particular, pyroglutamic acid level showed a drastic reduction of 22-fold in stomach cancer cells. Since glutamine and glutamic acid are known to undergo cyclization to pyroglutamic acid, the 22-fold reduction might be the actual reduction in the levels of glutamine and/or glutamic acid-both known to be cancer-related. Hence, the marked reduction in pyroglutamic acid level might serve as a biomarker to aid early detection of stomach cancer. Graphical abstract.
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Cromatografía de Gases y Espectrometría de Masas/métodos , Ácido Glutámico/análisis , Glutamina/análisis , Metabolómica/métodos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Ácido Glutámico/metabolismo , Glutamina/metabolismo , Humanos , Peso Molecular , Células Tumorales CultivadasRESUMEN
BACKGROUND: Congenital thrombotic thrombocytopenic purpura (TTP) is rare and is prone to misdiagnosis or missed diagnosis in clinical. The relationship between genotype and phenotype needs further study. METHODS: A 15-hour-old Chinese girl develops jaundice. Her platelet counts suddenly decreases with bleeding spots on the left side of chest, upper abdomen, and bilateral groin on the fourth day after birth. The plasma ADAMTS13 activity and inhibitor are detected by residual collagen binding assay. ADAMTS 13 gene is detected by next generation sequencing. RESULTS: The plasma ADAMTS13 activity of the patient is shown to be severely deficient, but without inhibitor. Gene sequencing analysis shows that the patient carries a compound heterozygote mutation of ADAMTS13 gene, one is c.1564T>C, p.(Cys522Arg) on exon 13 of the ADAMTS13 gene, a heterozygote missense mutation. It is identified as a de novo suspected pathological variation. The other is c.330+1G>A on intron 3 of the ADAMTS13 gene, a heterozygote splicing mutation. Her father and elder sister carry c.1564T>C, p.(Cys522Arg) on exon 13 of the ADAMTS13 gene, a heterozygote missense mutations. Her mother carries c.330+1G>A on intron 3 of the ADAMTS13 gene, a heterozygote splicing mutation. CONCLUSIONS: The deficiency of ADAMTS13 caused by one heterozygote missense mutation and the other heterozygote splicing mutation are responsible for the episode of this congenital TTP patient.
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Proteína ADAMTS13/genética , Mutación Missense , Púrpura Trombocitopénica Trombótica/diagnóstico , Púrpura Trombocitopénica Trombótica/genética , Proteína ADAMTS13/sangre , Proteína ADAMTS13/metabolismo , Análisis Mutacional de ADN/métodos , Femenino , Heterocigoto , Humanos , Recién NacidoRESUMEN
OBJECTIVE: To analyze the zearalenone(ZEN) level in coix seed, and assess the risk of dietary exposure of ZEN in coix seed in Shanghai. METHODS: The ZEN contents of 147 coix seed samples collected in Shanghai were determined. The consumption data of 730 adults in Shanghai was collected by questionnaire survey with random sampling method. Dietary intake of ZEN from coix seed in Shanghai was simulated by Monte Carlo simulation. RESULTS: The total detection rate of ZEN in coix seed was 69. 39 %(102/147), with the content range of <1. 0-9361 µg/kg and the average value of 327. 7 µg/kg. The average exposure level of populations to ZEN in coix seed was 0. 0216 µg/(kg·d), which was much lower than the tolerable daily intake(TDI). The high exposure level(P95) of populations to ZEN in coix seed was 0. 0609 µg/(kg·d), which accounted for about 24% of TDI. There were about 1. 1% people with the dietary exposure to ZEN exceeding TDI on the basis of the ZEN contents in coix seed and consumption data of coix seed in Shanghai. CONCLUSION: The health risk of ZEN exposure of coix seed in Shanghai population is lower when taking coix seed regularly, and there are potential health risks when taking coix seed highly contaminated with ZEN at a higher dose for a long time.
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Coix , Zearalenona , China , Exposición Dietética , Contaminación de Alimentos/análisis , Semillas/química , Zearalenona/análisis , Zearalenona/toxicidadRESUMEN
Inorganic arsenic is an environmental carcinogen that poses a major global public health risk. A high percentage of drinking water from wells in the U.S. contains higher-than-normal levels of arsenic, suggesting an increased risk of arsenic-induced deleterious effects. In addition to primary preventive measures, therapeutic strategies need to effectively address and integrate multiple molecular mechanisms underlying arsenic-induced carcinogenesis. We previously showed that the loss of miR-199a-5p in arsenic-transformed cells is pivotal to promote arsenic-induced angiogenesis and tumor growth in lung epithelial cells. In this study, we further showed that subacute or chronic exposure to arsenic diminished miR-199a-5p levels largely due to DNA methylation, which was achieved by increased DNA methyltransferase-1 (DNMT1) activity, mediated by the formation of specific protein 1 (Sp1)/DNMT1 complex. In addition to the DNA hypermethylation, arsenic exposure also repressed miR-199a transcription through a transcriptional repressor Sp1. We further identified an association between miR-199a-5p repression and the arsenic-mediated energy metabolic shift, as reflected by mitochondria defects and a switch to glycolysis, in which a glycolytic enzyme pyruvate kinase 2 (PKM2) was a functional target of miR-199a-5p. Taken together, the repression of miR-199a-5p through both Sp1-dependent DNA methylation and Sp1 transcriptional repression promotes an arsenic-mediated metabolic shift from mitochondria respiration to aerobic glycolysis via PKM2.
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Arsénico/efectos adversos , Metilación de ADN/efectos de los fármacos , MicroARNs/genética , Factor de Transcripción Sp1/genética , Activación Metabólica/efectos de los fármacos , Carcinogénesis/efectos de los fármacos , Línea Celular , Glucólisis/efectos de los fármacos , HumanosRESUMEN
Fe(II) and α-ketoglutarate-dependent fat mass and obesity associated protein (FTO)-dependent demethylation of m6A is important for regulation of mRNA splicing and adipogenesis. Developing FTO-specific inhibitors can help probe the biology of FTO and unravel novel therapeutic targets for treatment of obesity or obesity-associated diseases. In the present paper, we have identified that 4-chloro-6-(6'-chloro-7'-hydroxy-2',4',4'-trimethyl-chroman-2'-yl)benzene-1,3-diol (CHTB) is an inhibitor of FTO. The crystal structure of CHTB complexed with human FTO reveals that the novel small molecule binds to FTO in a specific manner. The identification of the novel small molecule offers opportunities for further development of more selective and potent FTO inhibitors.
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Fármacos Antiobesidad/farmacología , Obesidad , Proteínas/antagonistas & inhibidores , Proteínas/química , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Fármacos Antiobesidad/química , Fármacos Antiobesidad/uso terapéutico , Cristalización , Células HEK293 , Humanos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Proteínas/metabolismoRESUMEN
BACKGROUND: Colonic neuroendocrine neoplasms (NENs) are relatively rare tumors with an incidence rate of 0.11-0.21/100,000. NENs account for approximately 0.4% of colorectal neoplasms. Cutaneous metastases of colonic neuroendocrine carcinomas (NECs) are very infrequent, while cases of scalp metastasis are even fewer. Cutaneous metastases are more rare than visceral metastases and usually develop later; therefore, cutaneous metastases as initial distant metastases can be easily overlooked. This is the second case report of a colonic NEC with scalp metastasis. Compared with the previous case, in this instance scalp metastasis developed before visceral metastasis, and the cutaneous lesions were confined to the scalp alone. CASE PRESENTATION: A 62-year-old Chinese man, who had undergone radical surgery for a "locoregional" colonic NEC one and half months before, came to our hospital for adjuvant chemotherapy. We found multiple scalp nodules during physical examination. Moreover, these nodules had occurred and had not been detected prior to the patient undergoing radical surgery. The scalp nodules proved to be metastases from colonic NEC as determined using pathological and immunohistochemical examinations following lumpectomy. After one and half months, visceral metastases were detected in this patient. Ultimately, the patient died two months later. CONCLUSIONS: In this report an unusual case of a colonic NEC with initial distant metastasis confined to the scalp is presented. This case is unusual because of the development of cutaneous metastasis before visceral metastasis. The scalp metastasis were initially overlooked, leading to inaccurate staging and radical surgery that was not curative. This demonstrates that distant metastasis can occur during the early phase of tumor growth in these aggressive lesions. Thus, the possibility of distant metastases should be assessed in the initial work up to avoid mistaken clinical staging especially when distant metastases occur only in skin.
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Carcinoma Neuroendocrino/patología , Neoplasias del Colon/patología , Metástasis de la Neoplasia/patología , Cuero Cabelludo/patología , Carcinoma Neuroendocrino/cirugía , Neoplasias del Colon/cirugía , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Emerging organophosphate flame retardants (eOPFRs) have attracted attention in recent times and are expected to gain extensive usage in the coming years. However, they may have adverse effects on organisms. Due to their novel nature, there are few relevant articles dealing with toxicological studies of the above eOPFRs, especially their information on the perturbation of cellular metabolism, which is, thus far, marginally understood. Our research initially assessed the cytotoxicity of eOPFRs, which include compounds like cresyl diphenyl phosphate (CDP), resorcinol bis(diphenyl phosphate) (RDP), triallyl phosphate (TAP), and pentaerythritol phosphate alcohol (PEPA). This evaluation was conducted using the methyl thiazolyl tetrazolium (MTT) assay. Subsequently, we utilized a gas chromatography/mass spectrometry (GC/MS)-based metabolomic approach to investigate the metabolic disruptions induced by these four eOPFRs in A549 cells. The MTT results showed that, at high concentrations of 1 mM, their cytotoxicity was ranked as CDP > TAP > RDP > PEPA. In addition, metabolic studies at low concentrations of 10 µM showed that the metabolic interference of CDP, TAP, and PEPA focuses on oxidative stress, amino acid metabolism, and energy metabolism, while RDP mainly affects energy metabolism-galactose metabolism and gluconeogenesis. Therefore, from the perspective of cytotoxicity and metabolic analysis, RDP may be a more promising alternative. Our experiments provide important insights into the possible metabolic effects of potential toxic substances and complement the evidence on the human health risks of eOPFRs.