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Alismatis Rhizoma (AR), a traditional Chinese medicine for treating obesity in traditional Chinese medicine clinic, is recognized as a promising source of lead compounds of lipase inhibitors. Ultrafiltration centrifugal combined with liquid chromatography-mass spectrometry (UF-LC-MS) was used for screening potential lipase inhibitors from AR, and the result indicated the binding capacity between compound 7 and lipase (92.3⯱â¯1.28â¯%) was significantly higher than other triterpenoids, and was identified as alisol C 23-acetate. It exhibited a mixed-type inhibitory behavior with an IC50 value of 84.88⯱â¯1.03⯵M. Subsequently, the binding pockets of alisol C 23-acetate to lipase were predicted, and their binding mechanism was explored with molecular simulation. Pocket 1 (active center) and pocket 4 might be the orthosteric and allosteric binding sites of alisol C 23-acetate to lipase, respectively. The interaction between alisol C 23-acetate and lipase was identified to involve key amino acid residues such as GLY-77, PHE-78, TYR-115, LEU-154, PRO-181, PHE-216, LEU-264, ASP-278, GLN-306, ARG-313, and VAL-426. Meanwhile, alisol C 23-acetate remained stable during the intestinal digestive but degraded in the gastric digestion. Overall, alisol C 23-acetate is expected to be the lead compound of lipase inhibitors for treating obesity.
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A method for simultaneous determination of 12 mycotoxins in Pericarpium Citri Reticulataeby HPLC-MS/MS was established to analyze the residues of mycotoxins, inwhich from Three Gorges Reservoir area of China, including AFB1, AFB2, AFG1, AFG2, T-2, FB1, FB2, FB3, ZEN, OTA, OTB and DON.In addition, a probabilistic assessment model based on Monte Carlo simulation method was established in combination with pollution data, and the health risk assessment was carried out by the exposure limit method (MOE).The results showed that the method with strong specificity, good linearity and accurate recovery was established and could be used for the determination of 12 mycotoxins in Pericarpium Citri Reticulatae.In general, the total pollution rate of different degrees of pollution in the 36 batches of Pericarpium Citri Reticulatae sampleswas 75 %. It should be noted thatthe proportion of positive samplescontaminated by one toxin was the highest (59.26 %), and the detection rate of FB3 in Pericarpium Citri Reticulataewas the highest (66.67%), followed by AFG1 (44.44 %), indicating that the medicinal material polluted by AFG1 and AFB3 alone or simultaneously was more serious. Specifically, the detection rate of mycotoxins in Chongqing was the highest (92.31%) on account of the high temperature and humidity in Chongqing, followed by Southeast of Sichuan (83.33%) and West of Hubei (45.45%).On the other hand, the MOE of AFB1 and AFB2 calculated were both greater than 10000, indicating that the health risk of AFB1 and AFB2 exposure caused by taking Pericarpium Citri Reticulatae was low, but the risk of high intake population was higher than that of conventional intake population, which needed to be paid attention to. This study can provide a reference for the safety assessment of clinical medication of Pericarpium Citri Reticulatae inThree Gorges Reservoir area.
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Citrus , Contaminação de Alimentos , Micotoxinas , China , Medição de Risco , Micotoxinas/análise , Citrus/química , Contaminação de Alimentos/análise , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Humanos , Exposição Dietética/análiseRESUMO
Deep dewatering of Waste Activated Sludge (WAS) through mechanical processes remains inefficient, primarily due to the formation of a stable hydrogen bonding network between the biopolymers and water, which consequently leads to significant water trapped by Extracellular Polymeric Substances (EPS). In this study, a novel and recyclable treatment for WAS based on Ionic Liquids (ILs) was established, named IL-biphasic aqueous system (IL-ABS) treatment. Specifically, the IL-ABS formed in WAS facilitated rapid and efficient in-situ deep dewatering while concurrently recovering hydroxyapatite. The water content decreased from an initial 98.27 % to 65.35 % with IL-ABS, formed by 1-Butyl-3-methylimidazolium bromide (BmimBr) and K3PO4 synthesized from waste H3PO4. Moreover, the recycled BmimBr maintaining the water content of the dewatered sludge consistently between 65.61 % and 67.25 % across five cycles, exhibited remarkable reproducibility. Through three-dimensional excitation-emission matrix, lactate dehydrogenase analyses and confocal laser scanning microscopy, the high concentration of BmimBr in the upper phase effectively disrupted the cells and EPS, which exposed protein and polysaccharide on the EPS surface. Subsequently, the K3PO4 in the lower phase led to an enhanced salting-out effect in WAS. Furthermore, FT-IR analysis revealed that K3PO4 disrupted the original hydrogen bonds between EPS and water. Then, BmimBr formed numerous hydrogen bonds with the sludge flocs, leading to deep dewatering and agglomeration of the sludge flocs during the unique phase separation process of IL-ABS. Notably, sludge-derived hydroxyapatite product exhibited remarkable adsorption capacity for prevalent heavy metal contaminants such as Pb2+, Cd2+ and Cu2+, with efficiencies comparable to those of commercial hydroxyapatite, thereby achieving the resource utilization of waste H3PO4. Moreover, economic calculations demonstrated the suitability of this novel treatment. This innovative treatment exhibits potential for practical applications in the non-mechanical deep dewatering of WAS.
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Sludge is an inevitable waste product of sewage treatment with a high water content and large volume, it poses a significant threat of secondary pollution to both water and the atmosphere without proper disposal. In this regard, dewatering has emerged as an attractive method in sludge treatment, as it can reduce the sludge volume, enhance its transportability and calorific value, and even decrease the production of landfill leachate. In recent years, physical conditioning methods including non-chemical conditioners or energy input alone, have been extensively researched for their potential to enhance sludge dewatering efficiency, such as thermal treatment, freeze-thaw, microwave, ultrasonic, skeleton builders addition, and electro-dewatering, as well as combined methods. The main objective of this paper is to comprehensively evaluate the dewatering capacity of various physical conditioning methods, and identify key factors affecting sludge dewatering efficiency. In addition, future research anticipated directions and outlooks are proposed. This work is expected to provide valuable insights for developing efficient, eco-friendly, and low-energy consumption techniques for deep sludge dewatering.
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Esgotos , Eliminação de Resíduos Líquidos , Eliminação de Resíduos Líquidos/métodos , Água/químicaRESUMO
Polysaccharides are generally considered to have immune enhancing functions, and mulberry leaf polysaccharide is the main active substance in mulberry leaves, while there are few studies on whether mulberry leaf polysaccharide (MLP) has an effect on immunosuppression and intestinal damage caused by cyclophosphamide (CTX), we investigated whether MLP has an ameliorative effect on intestinal damage caused by CTX. A total of 210 1-day-old Mahuang cocks were selected for this experiment. Were equally divided into six groups and used to evaluate the immune effect of MLP. Our results showed that MLP significantly enhanced the growth performance of chicks and significantly elevated the secretion of cytokines (IL-1ß, IL-10, IL-6, TNF-α, and IFN-γ), immunoglobulins and antioxidant enzymes in the serum of immunosuppressed chicks. It attenuated jejunal damage and elevated the expression of jejunal tight junction proteins Claudin1, Zo-1 and MUC2, which protected intestinal health. MLP activated TLR4-MyD88-NF-κB pathway and enhanced the expression of TLR4, MyD88 and NF-κB, which served to protect the intestine. 16S rDNA gene high-throughput sequencing showed that MLP increased species richness, restored CTX-induced gut microbiome imbalance, and enhanced the abundance of probiotic bacteria in the gut. MLP improves cyclophosphamide-induced growth inhibition and intestinal damage in chicks by modulating intestinal flora and enhancing immune regulation and antioxidant capacity. In conclusion, this study provides a scientific basis for MLP as an immune enhancer to regulate chick intestinal flora and protect chick intestinal mucosal damage.
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As a Chinese folk health product, Abrus cantoniensis exhibits good immunomodulatory activity because of its polysaccharide components (ACP), and carboxymethylation of polysaccharides can often further improve the biological activity of polysaccharides. In this study, we explored the impact of prophylactic administration of carboxymethylated Abrus cantoniensis polysaccharide (CM-ACP) on immunosuppression and intestinal damage induced by cyclophosphamide (CTX) in mice. Our findings demonstrated that CM-ACP exhibited a more potent immunomodulatory activity compared to ACP. Additionally, CM-ACP effectively enhanced the abundance of short-chain fatty acid (SCFA)-producing bacteria in immunosuppressed mice and regulated the gene expression of STAT6 and STAT3 mediated pathway signals. In order to further explore the relationship among polysaccharides, intestinal immunity and intestinal flora, we performed a pseudo-sterile mouse validation experiment and fecal microbiota transplantation (FMT) experiment. The findings suggest that CM-FMT and butyrate attenuate CTX-induced immunosuppression and intestinal injury. CM-FMT and butyrate show superior immunomodulatory ability, and may effectively regulate intestinal cell metabolism and repair the damaged intestine by activating STAT6 and STAT3-mediated pathways. These findings offer new insights into the mechanisms by which CM-ACP functions as functional food or drug, facilitating immune response regulation and maintaining intestinal health.
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Abrus , Microbioma Gastrointestinal , Camundongos , Animais , Ácido Butírico , Terapia de Imunossupressão , Intestinos , Polissacarídeos/farmacologiaRESUMO
Selenium is an essential nutrient for biological function. However, there is a detrimental effect on the aquatic environment associated with higher concentrations of > 40 µg/L. The utilization of waste shrimp shells for the removal of high-concentrated selenium from wastewater is a commendable strategy in both the pollution control and waste management sectors. In the present study, a chitin-iron polymer complex hybrid material (Fe@SHC) was prepared from shrimp shell-derived hydrochar (SHC), and the synthesized composite was successfully employed to uptake selenium from wastewater. The highest removal performance of 79.18 mg/g was attained by Fe@SHC, whereas the capacity of SHC was 15.30 mg/g. It was found that the calcium content of Fe@SHC (1.98%) was lower than that of SHC (25.20%) and pHzpc of Fe@SHC was extended to 7.78 compared with that of SHC (2.00). The abundance of protonated hydroxyl (-OH2+) and amine (-NH3+) functional groups that developed through the iron co-precipitations resulted in the improved adsorption performance of Fe@SHC. XPS analysis demonstrated that the captured Se(IV) species were converted into less hazardous Se(0), which is accompanied by the electron transfer with both N-C = O (acetyl amine) and -NH2 (amine) functional groups. Adsorption kinetics disclosed that the adsorption process was governed by chemical sorption, and the Sips isotherm model provided the most accurate description of the isotherm equilibrium. This study proposed an inexpensive and environmentally friendly method for effective decontamination of Se from wastewater.
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Nanopartículas , Selênio , Poluentes Químicos da Água , Ferro/química , Águas Residuárias , Selênio/análise , Adsorção , Quitina , Cinética , Nanopartículas/química , Aminas , Poluentes Químicos da Água/análiseRESUMO
Catheter-related bloodstream infection (CRBSI) is a significant complication among patients on haemodialysis (HD) who are dependent on a central venous catheter (CVC) for an extended period. Catheter removal as first-line treatment can induce accelerated venous access site depletion in patients on HD who rely on it to survive. It is possible to retain the catheter in stable patients without septic syndrome while administering systemic antibiotics and antibiotic lock therapy. Herein, we report the case of a patient on HD with CRBSI who was successfully treated with intravenous levofloxacin- and urokinase-based antibiotic lock, without catheter removal prior to kidney transplantation. The use of urokinase in combination with antibiotics in lock solutions for treating catheter infections is rare. We verified the physical compatibility of levofloxacin and urokinase by visual inspection, turbidimetric measurements, and particle count. To our knowledge, this was a rare case demonstrating the effective use of urokinase and levofloxacin in a catheter lock for CRBSI in a patient on HD. Considering the need for highly concentrated antimicrobials and the availability of various antibiotics, the compatibility and stability of the lock solution is a matter of concern. Further studies are warranted to assess the stability and compatibility of various antibiotics in combination with urokinase.
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Excited-state intermolecular proton transfer (inter-ESPT) fluorescent probes responsive to specific bioactive molecules should be greatly promising for protein sensing, DNA mutation simulating and cellular process regulating. However, the inter-ESPT molecules are recessive ESPT fluorophores, which need the assistance of other molecules with both hydrogen-bond accepting and donating abilities to turn on the tautomeric fluorescence. Valid design strategies to create powerful inter-ESPT fluorescent probes are poorly developed, particularly for proteins as targets. We recently reported a unique supramolecular strategy to trigger the inter-ESPT process based on the probe-protein recognition by H-bonding and to image protein-based subcellular structures in live cells. Herein, we found that our inter-ESPT probes (inter-ESPT-01) bearing a 2-amino-3-cyanopyridine scaffold can anchor proteins and light up the "invisible" ESPT state, so as to image the proteins or the protein-based subcellular organelles. More importantly, the inter-ESPT emission of inter-ESPT-01 can be significantly enhanced by the FRET process between amino and imino tautomers, endowing the inter-ESPT-01 probes with super-bright tautomeric fluorescence. The expressed proteins Ecallantide and MarTX were selected as the models to light up the inter-ESPT fluorescence of the probes and revealed that the inter-ESPT process can be triggered by the specific probe-protein recognition events. In the use of the super-bright inter-ESPT fluorescence, not only the proteins, but also the protein-based cilia and tunneling nanotubes (TNTs) can be specifically visualized in living cancer cells. Furthermore, such recognition-driven strategy allows us to construct a unique inter-ESPT probe to track and image specific endogenous proteins in live cells, highlighting the potential of inter-ESPT fluorogens as novel intelligent biomaterials.
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Corantes Fluorescentes , Prótons , Corantes Fluorescentes/química , Transferência Ressonante de Energia de Fluorescência , CíliosRESUMO
Lack of highly efficient, inexpensive, and easily available catalysts severely limits the practical applicability of electrochemically sensing assay towards 5-hydroxytryptamine (5-HT). Herein, four kinds of Fe-Co bimetallic Prussian blue analogues (FeCo-PBAs) with different molar ratios of Fe to Co were prepared using a simple coprecipitation method. Interestingly, Fe(III) in K3 [Fe(CN)6] can be reduced to Fe(II) by adding trisodium citrate dehydrate, which could offer a new clue to synthesize PBAs with Fe(II) core ions. With the optimizational FeCo-PBA synthesized at a 0.5/1 M ratio of Fe to Co as an electrocatalyst, the constructed sensor shows excellent comprehensive performance for the 5-HT assay with a high sensitivity of 0.856 µA µM-1 and an ultralow detection limit of 8.4 nM. Under the optimum conditions, linearity was obtained in the ranges of 0.1-10.0 µM and 10.0-200.0 µM and preferable recoveries ranged from 97.8% to 103.0% with relative standard deviation (RSD) < 4.0%. The integrated properties of FeCo-PBA can be comparable to previously reported electrocatalysts for the 5-HT assay including noble metal-based and expensive carbon (graphene and carbon nanotubes)-based electrocatalysts. The proposed sensor also exhibits outstanding selectivity, reproducibility, and practicality for real sample analyses. This work is the first report on the PBA-based sensor for the 5-HT assay, verifying the practicability of this high-performance sensor for the 5-HT assay.
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Compostos Férricos , Nanotubos de Carbono , Reprodutibilidade dos Testes , Serotonina , FerrocianetosRESUMO
Tripterygium wilfordii-a traditional Chinese herbal medicine-is used to treat several diseases, including chronic kidney disease, rheumatic autoimmune disorder, and skin disorders. With the development of modern pharmacology, scientists have gradually realized that T. wilfordii has side effects on several organs and systems of the human body, including the liver, kidney, reproductive system, hematopoietic system, and immune system. Our understanding of its toxicity remains unclear. The incidence of problems in the hematopoietic system is not low but few related studies have been conducted. The serious consequences need to be of concern to clinicians and scientists. To ensure the safety of patients, it is important to elucidate the mechanism underlying the damage to the hematopoietic system caused by T. wilfordii and strategies to reduce its toxicity. Routine blood and biochemical tests should be conducted when administering T. wilfordii, and in case of any abnormality, the medication should be terminated in time along with a comprehensive symptomatic treatment. Herein, we report the case of a 50-year-old Chinese female with end-stage renal disease (ESRD) who developed severe bone marrow suppression after taking a short-term normal dose of a T. wilfordii-containing decoction. She died of sepsis and septic shock, although timely therapeutic measures (e.g., stimulating hematopoiesis, anti-infection treatment, and hemodialysis) were administered. To the best of our knowledge, this is the first report of death by T. wilfordii-induced myelosuppression from a short term, conventional dose in an adult female with ESRD. Although the underlying mechanism remains unclear, this case contradicts the notion that side effects on the hematopoietic system are non-lethal.
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Established a model of lipopolysaccharide (LPS)-induced mastitis in mice, pathological sections and myeloperoxidase were used to detect the degree of tissue damage, enzyme-linked immunosorbent assay (ELISA) was performed to detect the expression of pro-inflammatory cytokines, meanwhile fluorescence quantitative PCR experiments were performed to detect the mRNA expression of CD14/TLR4/NF-κB/MAPK signalling pathway, and the faeces of mice were collected for 16S measurement of flora. The results showed that Abrus cantoniensis total flavonoids (ATF) could significantly reduce the damage of LPS on mammary tissue in mice and inhibit the secretion of inflammatory factors such as TNF-α, IL-1ß and IL-6. At the mRNA level, ATF inhibited the expression of CD14/TLR4/NF-κB/MAPK pathway and enhanced the expression of tight junction proteins in the blood-milk barrier. In the results of the intestinal flora assay, ATF were found to be able to regulate the relative abundance of the dominant flora from the phylum level to the genus level, restoring LPS-induced gut microbial dysbiosis. In summary, ATF attenuated the inflammatory response of LPS on mouse mammary gland by inhibiting the expression of CD14/TLR4/NF-κB/MAPK pathway, enhancing the expression of tight junction proteins and restoring LPS-induced gut microbial dysbiosis. This suggests that ATF could be a potential herbal remedy for mastitis.
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Nitrite (NO2-) is a common pollutant and is widely present in the environment and in human bodies. The development of a rapid and accurate method for NO2- detection is always a very important task. Herein, we synthesized a partnered excited-state intermolecular proton transfer (ESIPT) fluorophore using the "multi-component one pot" method, and used this as a probe (ESIPT-F) for sensing NO2-. ESIPT-F exhibited bimodal emission in different solvents because of the solvent-mediated ESIPT reaction. The addition of NO2- caused an obvious change in colors and tautomeric fluorescence due to the graft of NO2- into the ESIPT-F molecules. From this basis, highly sensitive and selective analysis of NO2- was developed using tautomeric emission signaling, achieving sensitive detection of NO2- in the concentration range of 0~45 mM with a detection limit of 12.5 nM. More importantly, ESIPT-F showed the ability to anchor proteins and resulted in a recognition-driven "on-off" ESIPT process, enabling it to become a powerful tool for fluorescence imaging of proteins or protein-based subcellular organelles. MTT experimental results revealed that ESIPT-F is low cytotoxic and has good membrane permeability to cells. Thus, ESIPT-F was further employed to image the tunneling nanotube in vitro HEC-1A cells, displaying high-resolution performance.
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Nitratos , Prótons , Corantes Fluorescentes , Humanos , Dióxido de Nitrogênio , Óxidos de Nitrogênio , Solventes , Espectrometria de FluorescênciaRESUMO
Abrus cantoniensis is a Chinese herbal medicine with efficacy in clearing heat and detoxification, as well as relieving liver pain. The whole plant, except the seeds, can be used and consumed. Flavonoids have been found in modern pharmacological studies to have important biological activities, such as anti-inflammatory, antibacterial and antioxidant properties. The antibacterial and antioxidant bioactivities of the total flavonoids of Abrus cantoniensis (ATF) have been widely reported in national and international journals, but there are fewer studies on their anti-inflammatory effects. The present study focused on the optimization of the ultrasonic extraction process of ATF by response surface methodology and the study of its anti-inflammatory effects in vitro and in vivo. The results showed that the factors that had a great impact on the ATF extraction were the material-to-liquid ratio, ultrasonic extraction cycles and ethanol concentration. The best extraction process used a material-to-liquid ratio of 1:47, ultrasonic extraction cycles of 4 times, an ethanol concentration of 50%, an ultrasonic extraction time of 40 min and an ultrasonic power of 125 W. Under these conditions, the actual extraction rate of total flavonoids was 3.68%, which was not significantly different from the predicted value of 3.71%. In an in vitro anti-inflammatory assay, ATF was found to be effective in alleviating LPS (lipopolysaccharide)-induced inflammation in mouse peritoneal macrophages. In an in vivo anti-inflammatory assay, ATF was found to have a significant inhibitory effect on xylene-induced ear swelling in mice and cotton ball granuloma in mice, and the inhibitory effect was close to that of the positive control drug dexamethasone. This may provide a theoretical basis for the further development of the medicinal value of Abrus cantoniensis.
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Abrus , Animais , Antibacterianos , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Etanol , Flavonoides/farmacologia , Camundongos , Extratos Vegetais/farmacologia , UltrassomRESUMO
Constructing excited-state intermolecular proton transfer (ESIPT-e) fluorophores represents significant challenges due to the harsh requirement of bearing a proton donor-acceptor (D-A) system and their matching proton donating-accepting ability in the same molecule. Herein, we synthesized a new-type ESIPT-e fluorophor (2-APC) using the "four-component one-pot" reaction. By the installing of a cyano-group on pyridine scaffold, the proton donating ability of -NH2 was greatly enhanced, enabling 2-APC to undergo ESIPT-e process. Surprisingly, 2-APC exhibited dual-emissions in protic solvents ethanol and normal fluorescence in aprotic solvents, which is vastly different from that of conventional ESIPT-a dyes. The ESIPT emission can be obviously suppressed by Fe3+ due to the coordination reaction of Fe3+ with the A-D system in 2-APC. From this basis, a highly sensitive and selective method was established using 2-APC as a fluorescent probe, which offers the sensitive detection of Fe3+ ranging from 0 to 13 µM with the detection limit of 7.5 nM. The recovery study of spiked Fe3+ measured by the probe showed satisfactory results (97.2103.4%) with the reasonable RSD ranging from 3.1 to 3.8%. Moreover, 2-APC can also exhibit aggregation-induced effect in poor solvent or solid-state, eliciting strong red fluorescence. 2-APC was also applied to cell-imaging, exhibiting good cell-permeability, biocompatibility and color rendering. This multi-mode emission of 2-APC is significant departure from that of conventional extended p-conjugated systems and ESIPT dyes based on a flat and rigid molecular design. The "one-pot synthesis" strategy for the construction of ESIPT molecules pioneered a new route to achieve tricolor-emissive fluorophores.
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Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Ferro/análise , Neoplasias Pulmonares/metabolismo , Prótons , Solventes/química , Poluentes Químicos da Água/análise , Células A549 , Proliferação de Células , Transferência de Energia , Humanos , Neoplasias Pulmonares/patologia , Imagem Molecular , Espectrometria de Fluorescência/métodosRESUMO
Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the galactosidase A (GLA) gene that result in deficiency of α-GLA activity, leading to major organ failure and premature mortality. According to different disease courses, FD can be divided into classical and nonclassical phenotypes. The nonclassical FD phenotype is always absent of characteristic symptoms, which makes identifying it challenging. This article presents a 49-year-old man with a 10-year history of proteinuria and decreased glomerular filtration rate. An electrocardiogram showed a complete right bundle branch block and abnormal Q waves in high lateral, accompanied by dramatically elevated ST segment. Consequently, a renal biopsy was performed. Vacuolation was found in many podocytes in light microscopic examinations. Similarly, a myelin-like structure was detected by electron microscopy. Pathological findings were most consistent with FD. Consequently, genetic analysis, p.R301Q (c.902G>A [p.Arg301Gln]), confirmed the FD diagnosis. Angiotensin receptor blocker and traditional Chinese medicine, but not enzyme replacement therapy, were prescribed due to financial constraints. The patient had stabilization of kidney disease 6 months later. The case showed that renal biopsy should be performed in patients with cardiac and renal symptoms, which could contribute toward the correct diagnosis for nonclassical FD type.
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Doença de Fabry/diagnóstico , Rim/patologia , Biópsia , Eletrocardiografia , Doença de Fabry/fisiopatologia , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
MicroRNAs (miRNAs/miRs) are highly conserved single-stranded small non-coding RNAs, which are involved in the physiological and pathological processes of breast cancer, and affect the prognosis of patients with breast cancer. The present study used the Gene Expression Omnibus (GEO)2R tool to detect miR-100 expression in breast cancer tissues obtained from GEO breast cancer-related datasets. Bioinformatics analysis revealed that miR-100 expression was downregulated in different stages, grades and lymph node metastasis stages of breast cancer, and patients with high miR-100 expression had a more favorable prognosis. Based on these analyses, Cell Counting Kit-8, wound healing and Transwell assays were performed, and the results demonstrated that overexpression of miR-100 inhibited the proliferation, migration and invasion of breast cancer cells. To verify the tumor-suppressive effect of miR-100 in breast cancer, the LinkedOmics and PITA databases were used to assess the association between miR-100 and forkhead box A1 (FOXA1). The results demonstrated that miR-100 had binding sites within the FOXA1 gene, and FOXA1 expression was negatively associated with miR-100 expression in breast cancer tissues. Similarly, a negative association was observed between miR-100 and FOXA1 expression, using the StarBase V3.0 database. The association between miR-100 and FOXA1 was further verified via reverse transcription-quantitative PCR and western blot analyses, and the dual-luciferase reporter assay. The results demonstrated that miR-100 targeted the 3'-untranslated region of FOXA1 in breast cancer cells. Furthermore, rescue experiments were performed to confirm whether miR-100 exerts its antitumor effects by regulating FOXA1. The results demonstrated that overexpression of FOXA1 promoted the proliferation, migration and invasion of breast cancer cells; thus, the antitumor effects of miR-100 in breast cancer were reversed following overexpression of FOXA1. Taken together, the results of the present study suggest that miR-100 inhibits the proliferation, migration and invasion of breast cancer cells by targeting FOXA1 expression. These results may provide a novel insight and an experimental basis for identifying effective therapeutic targets of high specificity for breast cancer.
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A solvent-assisted ESIPT fluorescent dye was synthesized and used as a probe (2-PPN) for the detection of F-/Ag+ and high-resolution imaging of the cilia in live cells. The developed ESIPT fluorophore exhibited strong tautomeric fluorescence in protic solvents and normal emission in aprotic solvents, which is a significant departure from that of conventional intramolecular ESIPT compounds. The H-binding interaction of F- and the chelation of Ag+ with the ESIPT module of 2-PPN resulted in significant tautomeric emission quenching. From this basis, the 2-PPN-based assays for the detection of F- and Ag+ were established. The detection limit for F- and Ag+ sensing is 2.4 nM and 1.5 nM, respectively. The selective experimental results showed that no tautomeric fluorescence change of 2-PPN could be observed in the presence of the other inorganic ions in the same medium, revealing high selectivity of 2-PPN to F- and Ag+. Furthermore, MTT assay experiments proved that the probe 2-PPN exhibited low cytotoxicity and good cell membrane permeability. The probe was also further successfully utilized to image the cilia in vitro MCF7 cells, displaying its high-resolution imaging performance.Graphical abstract.
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Cílios , Corantes Fluorescentes/síntese química , Flúor/química , Nitrilas/síntese química , Pirenos/síntese química , Prata/química , Corantes Fluorescentes/química , Humanos , Células MCF-7 , Estrutura Molecular , Nitrilas/química , Pirenos/químicaRESUMO
A portable, cheap and sensitive paper type electrochemical immunosensor was developed with conductive nanobiochar paper as the conductive layer and utilized for sensitive detection of microcystin-LR (MCLR) toxin in water. The paper immunosensor was constructed by coating of highly conductive and dispersible nanobiochar particle (nBC) and anti-MCLR antibody on the filter paper via dipping-drying method. The presence of MCLR could be specifically quantified amperometrically by the nBC-paper immunosensor with the response time of less than 5 min, and the lowest detection limit of 17 pM (0.017 µg/L) was achieved. Moreover, the proposed immunosensor exhibited high selectivity, reproducibility and storage stability, and was also used for environmental water detection with satisfactory recovery. The successful fabrication of low cost and ubiquitous biochar based paper type electrochemical immunosensing system would have significant value for the development of highly cost-effective electrochemical device.