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Halogenated organic pollutants (HOPs) are causing a significant environmental and human health crisis due to their high levels of toxicity, persistence and bioaccumulation. Urgent action is required to develop effective approaches for the reduction and reuse of HOPs. Whereas current strategies focus primarily on the degradation of HOPs, repurposing them is an alternative approach, albeit a challenging task. Here we discover that alkyl bromide can act as a catalyst for the transfer of chlorine using alkyl chloride as the chlorine source. We demonstrate that this approach has a wide substrate scope, and we successfully apply it to reuse HOPs that include dichlorodiphenyltrichloroethane, hexabromocyclododecane, chlorinated paraffins, chloromethyl polystyrene and poly(vinyl chloride) (PVC). Moreover, we show that the synthesis of essential non-steroidal anti-inflammatory drugs can be achieved using PVC and hexabromocyclododecane, and we demonstrate that PVC waste can be used directly as a chlorinating agent. Overall, this methodology offers a promising strategy for repurposing HOPs.
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Massively parallel sequencing (MPS) has emerged as a promising technology for targeting multiple genetic loci simultaneously in forensic genetics. Here, a novel 193-plex panel was designed to target 28 A-STRs, 41 Y-STRs, 21 X-STRs, 3 sex-identified loci, and 100 A-SNPs by employing a single-end 400 bp sequencing strategy on the MGISEQ-2000™ platform. In the present study, a series of validations and sequencing of 1642 population samples were performed to evaluate the overall performance of the MPS-based panel and its practicality in forensic application according to the SWGDAM guidelines. In general, the 193-plex markers in our panel showed good performance in terms of species specificity, stability, and repeatability. Compared to commercial kits, this panel achieved 100% concordance for standard gDNA and 99.87% concordance for 14,560 population genotypes. Moreover, this panel detected 100% of the loci from 0.5 ng of DNA template and all unique alleles at a 1:4 DNA mixture ratio (0.2 ng minor contributor), and the applicability of the proposed approach for tracing and degrading DNA was further supported by case samples. In addition, several forensic parameters of STRs and SNPs were calculated in a population study. High CPE and CPD values greater than 0.9999999 were clearly demonstrated and these results could be useful references for the application of this panel in individual identification and paternity testing. Overall, this 193-plex MPS panel has been shown to be a reliable, repeatable, robust, inexpensive, and powerful tool sufficient for forensic practice.
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Genética Forense , Sequenciamento de Nucleotídeos em Larga Escala , Repetições de Microssatélites , Paternidade , Polimorfismo de Nucleotídeo Único , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Repetições de Microssatélites/genética , Genética Forense/métodos , Masculino , Feminino , Genótipo , Alelos , Genética Populacional/métodosRESUMO
BACKGROUND: Bile acid (BA) enterohepatic circulation disorders are a main feature of chronic cholestatic diseases. Promoting BA metabolism is thus a potential method of improving enterohepatic circulation disorders, and treat enterohepatic inflammation, oxidative stress and fibrosis due to cholestasis. PURPOSE: To investigate the effect of JiaGaSongTang (JGST) and its blood-absorbed ingredient 6-gingerol on α-naphthylisothiocyanate (ANIT)-induced chronic cholestasis, as well as elucidate the underlying regulatory mechanism. METHODS: Chronic cholestasis was induced in mice via subcutaneous injection of ANIT (50 mg/kg) every other day for 14 d. Treatment groups were administered JGST orally daily. Damage to the liver and intestine was observed using histopathological techniques. Biochemical techniques were employed to assess total BA (TBA) levels in the serum, liver, and ileum samples. Liquid chromatograph-mass spectrometry/mass spectrometry (LC-MS/MS) was used to analyze fecal BA components. Bioinformatic methods were adopted to screen the core targets and pathways. The blood-absorbed ingredients of JGST were scrutinized via LC-MS/MS. The effects of the major JGST ingredients on farnesoid X receptor (FXR) transactivation were validated using dual luciferase reporter genes. Lastly, the effects of the FXR inhibitor, DY268, on JGST and 6-gingerol pharmacodynamics were observed at the cellular and animal levels. RESULTS: JGST ameliorated pathological impairments in the liver and intestine, diminishing TBA levels in the serum, liver and gut. Fecal BA profiling revealed that JGST enhanced the excretion of toxic BA constituents, including deoxycholic acid. Bioinformatic analyses indicated that JGST engaged in anti-inflammatory mechanisms, attenuating collagen accumulation, and orchestrating BA metabolism via interactions with FXR and other pertinent targets. LC-MS/MS analysis identified six ingredients absorbed to the bloodstream, including 6-gingerol. Surface plasmon resonance (SPR) and dual luciferase reporter gene assays confirmed the abilities of 6-gingerol to bind to FXR and activate its transactivation. Ultimately, in both cellular and animal models, the therapeutic efficacy of JGST and 6-gingerol in chronic cholestasis was attenuated in the presence of FXR inhibitors. CONCLUSION: The findings, for the first time, demonstrated that 6-gingerol, a blood-absorbed ingredient of JGST, can activate FXR to affect BA metabolism, and thereby attenuate ANIT-induced liver and intestinal injury in chronic cholestasis mice model via inhibition of inflammation, oxidative stress, and liver fibrosis, in part in a FXR-dependent mechanism.
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1-Naftilisotiocianato , Ácidos e Sais Biliares , Catecóis , Colestase , Álcoois Graxos , Fígado , Receptores Citoplasmáticos e Nucleares , Animais , Ácidos e Sais Biliares/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Colestase/tratamento farmacológico , Colestase/metabolismo , Masculino , Camundongos , Catecóis/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Álcoois Graxos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Camundongos Endogâmicos C57BL , Humanos , Doença Crônica , Modelos Animais de DoençasRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The Timosaponin Bâ ¡ (TBâ ¡) is one of the main active components of the traditional Chinese medicine Anemarrhena asphodeloides, and it is a steroidal saponin with various pharmacological activities such as anti-oxidation, anti-inflammatory and anti-apoptosis. However, its role in acute ulcerative colitis remains unexplored thus far. AIM OF THE STUDY: This study aims to investigate the protective effect of TBâ ¡ against dextran sulfate sodium (DSS)-induced ulcerative colitis in mice and elucidate its underlying mechanisms. METHODS: Wild-type (WT) and NLRP3 knockout (NLRP3-/-) mice were applied to evaluate the protective effect of TBâ ¡ in DSS-induced mice colitis. Pharmacological inhibition of NLRP3 or adenovirus-mediated NLRP3 overexpression in bone marrow-derived macrophages (BMDM) from WT mice and colonic epithelial HCoEpiC cells was used to assess the role of TBâ ¡ in LPS + ATP-induced cell model. RNA-seq, ELISA, western blots, immunofluorescence staining, and expression analysis by qPCR were performed to examine the alterations of colonic NLRP3 expression in DSS-induced colon tissues and LPS + ATP-induced cells, respectively. RESULTS: In mice with DSS-induced ulcerative colitis, TBâ ¡ treatment attenuated clinical symptoms, repaired the intestinal mucosal barrier, reduced inflammatory infiltration, and alleviated colonic inflammation. RNA-seq analysis and protein expression levels demonstrated that TBâ ¡ could prominently inhibit NLRP3 signaling. TBâ ¡-mediated NLRP3 inhibition was associated with alleviating intestinal permeability and inflammatory response via the blockage of communication between epithelial cells and macrophages, probably in an NLRP3 inhibition mechanism. However, pharmacological inhibition of NLRP3 by MCC950 or Ad-NLRP3 mediated NLRP3 overexpression significantly impaired the TBâ ¡-mediated anti-inflammatory effect. Mechanistically, TBâ ¡-mediated NLRP3 inhibition may be partly associated with the suppression of NF-κB, a master pro-inflammatory factor for transcriptional regulation of NLRP3 expression in the priming step. Moreover, co-treatment TBâ ¡ with NF-κB inhibitor BAY11-7082 partly impaired TBâ ¡-mediated NLRP3 inhibition, and consequently affected the IL-1ß mature and secretion. Importantly, TBâ ¡-mediated amelioration was not further enhanced in NLPR3-/- mice. CONCLUSION: TBâ ¡ exerted a prominent protective effect against DSS-induced colitis via regulation of alleviation of intestinal permeability and inflammatory response via the blockage of crosstalk between epithelial cells and macrophages in an NLRP3-mediated inhibitory mechanism. These beneficial effects could make TBâ ¡ a promising drug for relieving colitis.
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Colite Ulcerativa , Colite , Saponinas , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , NF-kappa B/metabolismo , Lipopolissacarídeos/metabolismo , Inflamassomos/metabolismo , Colite/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Anti-Inflamatórios/efeitos adversos , Saponinas/farmacologia , Saponinas/uso terapêutico , Trifosfato de Adenosina/metabolismo , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Colo/metabolismoRESUMO
Diabetes is one of the foremost chronic non-communicable diseases worldwide, which significantly impacts people's quality of life. This study aimed to investigate the hypoglycemic effects of γ-polyglutamic acid (γ-PGA) on STZ-induced type II diabetes mice and its potential mechanisms. The results indicated that γ-PGA intervention contributed to reducing fasting blood glucose levels in diabetic mice, regulating lipid metabolism in type II diabetes mice, and improving insulin resistance. Additionally, γ-PGA could alleviate liver inflammation, enhancing the activity of hepatic antioxidant enzymes. Investigation into the insulin signaling pathway revealed that γ-PGA significantly increased the expression of INSR, IRS-1, Akt, PI3K in diabetic mice, thereby enhancing insulin sensitivity and improving insulin resistance to regulate glucose metabolism. High-throughput sequencing of mouse gut microbiota using 16S rRNA showed that γ-PGA increased the abundance and evenness of beneficial bacteria in the intestines of type II diabetic mice, inhibited the growth of harmful bacteria, and may exerted hypoglycemic effects by modulating and improving relevant metabolic pathways associated with diabetes symptoms. This study provides new insights into the treatment of type II diabetes and highlights the significant potential of γ-PGA in treating type II diabetes.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Ácido Poliglutâmico/análogos & derivados , Humanos , Camundongos , Animais , Hipoglicemiantes/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , RNA Ribossômico 16S , Qualidade de Vida , Insulina/metabolismo , Glicemia/metabolismoRESUMO
BACKGROUND AND PURPOSE: The mammalian target of rapamycin (mTOR) pathway plays critical roles in intrinsic chemoresistance by regulating Fanconi anaemia complementation group D2 (FANCD2) expression. However, the mechanisms by which mTOR regulates FANCD2 expression and related inhibitors are not clearly elucidated. Extracts of Centipeda minima (C. minima) showed promising chemosensitizing effects by inhibiting FANCD2 activity. Here, we have aimed to identify the bioactive chemosensitizer in C. minima extracts and elucidate its underlying mechanism. EXPERIMENTAL APPROACH: The chemosensitizing effects of arnicolide C (ArC), a bioactive compound in C. minima, on non-small cell lung cancer (NSCLC) were investigated using immunoblotting, immunofluorescence, flow cytometry, the comet assay, small interfering RNA (siRNA) transfection and animal models. The online SynergyFinder software was used to determine the synergistic effects of ArC and chemotherapeutic drugs on NSCLC cells. KEY RESULTS: ArC had synergistic cytotoxic effects with DNA cross-linking drugs such as cisplatin and mitomycin C in NSCLC cells. ArC treatment markedly decreased FANCD2 expression in NSCLC cells, thus attenuating cisplatin-induced FANCD2 nuclear foci formation, leading to DNA damage and apoptosis. ArC inhibited the mTOR pathway and attenuated mTOR-mediated expression of E2F1, a critical transcription factor of FANCD2. Co-administration of ArC and cisplatin exerted synergistic anticancer effects in the A549 xenograft mouse model by suppressing mTOR/FANCD2 signalling in tumour tissues. CONCLUSION AND IMPLICATIONS: ArC suppressed DNA cross-linking drug-induced DNA damage response by inhibiting the mTOR/E2F1/FANCD2 signalling axis, serving as a chemosensitizing agent. This provides insight into the anticancer mechanisms of ArC and offers a potential combinatorial anticancer therapeutic strategy.
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Carcinoma Pulmonar de Células não Pequenas , Anemia de Fanconi , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/farmacologia , Neoplasias Pulmonares/patologia , Serina-Treonina Quinases TOR/metabolismo , DNA , Mamíferos/metabolismo , Fator de Transcrição E2F1/metabolismo , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismoRESUMO
This case report discusses a diagnosis of pigmented vitreous cyst in a man aged 18 years who presented with a 2-week history of seeing a floater in his right eye.
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Cistos , Corpo Vítreo , Humanos , Seguimentos , Corpo Vítreo/patologia , Cistos/patologiaRESUMO
Herein, we present a novel method for the N-arylation of amino acid esters using α-bromoacetaldehyde acetal and acetoacetate via an I2-mediated metal-free benzannulation strategy, which disclosed the first synthetic application of N-arylation of amino acids using nonaromatic building blocks. The synthesized N-arylated amino acid derivatives were found to possess promising selective inhibition against human hepatocellular liver carcinoma cells, human melanoma cells, and human normal liver cells, with an IC50 value as low as 16.79 µg·mL-1.
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Aminoácidos , Ésteres , Humanos , Aminoácidos/química , Ésteres/química , MetaisRESUMO
Sulfur dioxide (SO2) derivatives are extensively utilized as both a preservative for foods and an active gaseous signal molecule in various physiological and pathological processes, but their excessive intake would bring harmful effects on human health; so, the determination of SO2 derivatives is of great importance. Herein, we developed a ratiometric fluorescent probe named 2-(2'-hydroxyphenyl)benzothiazole-3-ethyl-1,1,2-trimethyl-1H-benzo[e]indolium (HBT-EMBI) by introducing a hemicyanine unit of EMBI to an HBT group for the detection of SO2 derivatives via an excited-state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) effects. The probe displays some advantages, such as a colorimetric change from purple to colorless, a ratiometric fluorescence with zero cross-talk, and a remarkably large emission shift (Δλ = 164 nm) under a single-wavelength excitation. Accordingly, the probe HBT-EMBI has been successfully employed for the colorimetric and ratiometric determination of SO2 derivatives in real food samples and the quantitative visualization of SO2 derivative variations in HepG2 cells.
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Insertion/deletion polymorphisms (InDels) have particular characteristics, such as a relatively low mutation rate, small amplicon size, and no stutter artifacts when genotyped via the capillary electrophoresis platform. It would be an important complementary tool for individual identification and certain kinship analyses. At present, massively parallel sequencing (MPS) has shown excellent application value in forensic studies. Therefore, in this study, we developed a custom MPS InDel panel that contains 114 InDels [77 autosomal InDels (A-InDels), 32 X-chromosomal InDels (X-InDels), and 5 Y-chromosomal InDels) based on previous studies. To assess this panel's performance, several validation experiments were performed, including sensitivity, inhibitor, degraded DNA testing, species specificity, concordance, repeatability, case-type samples, and population studies. The results showed that the lowest DNA input was 0.25 ng. All genotypes were obtained in the presence of 80 ng/µL humic acid, 2000 µmol/L calcium, 3000 µmol/L EDTA and indigo. In degraded DNA testing, 90% of loci could be detected for 16-day-old formalin-fixed hearts. In addition, this panel has good species specificity. The values of combined power of discrimination and the combined power of exclusion for 77 A-InDels were 1-3.9951 × 10-32 and 1-4.2956 × 10-7 , respectively. The combined mean exclusion chance for 32 X-InDels was 0.99999 in trios and 0.99904 in duos. The validation results indicate that this newly developed MPS multiplex system is a robust tool for forensic applications.
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Genética Forense , Polimorfismo Genético , Humanos , Genótipo , Genética Forense/métodos , Impressões Digitais de DNA , DNA/análise , Mutação INDEL , Sequenciamento de Nucleotídeos em Larga Escala , Polimorfismo de Nucleotídeo Único , Genética PopulacionalRESUMO
Metallocenes are privileged backbones in the fields of synthetic chemistry, catalysis, polymer science, etc. Direct C-H functionalization is undoubtedly the simplest approach for tuning the properties of metallocenes. However, owing to the presence of multiple identical C(sp2 )-H sites, this protocol often suffers from low reactivity and selectivity issues, especially for the regioselective synthesis of 1,3-difunctionalized metallocenes. Herein, an efficient iridium-catalyzed meta-selective C-H borylation of metallocenes is reported. With no need of preinstalled directing groups, this approach enables a rapid synthesis of various boronic esters based on benzoferrocenes, ferrocenes, ruthenocene, and related half sandwich complex. A broad range of electron-deficient and -rich functional groups are all compatible with the process. Notably, C-H borylation of benzoferrocenes takes place exclusively at the benzene ring, which is likely ascribed to the shielding effect of pentamethylcyclopentadiene. The synthetic utility is further demonstrated by easy scalability to gram quantities, the conversion of boron to heteroatoms including N3 , SePh, and OAc, as well as diverse cross-coupling reactions.
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Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent health issues. The improvement of NAFLD is related to the activation of the farnesoid X receptor (FXR). Typhaneoside (TYP) is the main component of Typha orientalis Presl, which plays a positive role in the resistance of glucose and lipid metabolism disorders. This study aims to investigate the alleviative effect and the underlying mechanism of TYP on OAPA-induced cells and high-fat-diet (HFD)-induced mice with disorders of glucose and lipid metabolism, inflammation, oxidative stress and lower thermogenesis through FXR signaling. All the serum lipid, body weight, oxidative stress and inflammatory levels of WT mice were significantly increased after HFD administration. These mice were presented with pathological injury, liver tissue attenuation, energy expenditure, insulin resistance, and impaired glucose tolerance. These above-mentioned changes in HFD-induced mice were remarkably reversed by TYP, which improved HFD-induced energy expenditure, oxidative stress, inflammation, insulin resistance, and lipid accumulation in a dose-dependent manner by activating the expression of FXR. Furthermore, using a high throughput drug screening strategy based on fluorescent reporter genes, we found that TYP functions as a natural agonist of FXR.TYP-mediated FXR activation also significantly repressed TG hyperaccumulation in mouse primary Hepatocytes (MPHs). However, these beneficial effects of TYP were not observed in FXR-/- MPHs. Overall, activation of the FXR pathway by TYP is related to the improvement of metabolic parameters, such as blood glucose, lipid accumulation, insulin resistance, inflammation, oxidative stress and energy expenditure in vitro and in vivo.
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Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Fígado , Metabolismo dos Lipídeos , Inflamação/metabolismo , Glucose/metabolismo , Lipídeos/farmacologia , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversosRESUMO
Pachymic acid (Pac), a major bioactive constituent of Poria cocos, is an antioxidant that inhibits triglyceride (TG) accumulation. To the best of our knowledge, the present study investigated for the first time whether Pac activated sirtuin 6 (SIRT6) signaling to alleviate oleic acid (OA)-palmitic acid (PA)-induced lipid metabolism disorders in mouse primary hepatocytes (MPHs). In the present study, MPHs challenged with Pac were used to test the effects of Pac on intracellular lipid metabolism. Molecular docking studies were performed to explore the potential targets of Pac in defending against lipid deposition. MPHs isolated from liver-specific SIRT6-deficient mice were subjected to OA + PA incubation and treated with Pac to determine the function and detailed mechanism. It was revealed that Pac activated SIRT6 by increasing its expression and deacetylase activity. Pa prevented OA + PA-induced lipid deposition in MPHs in a dose-dependent manner. Pac (50 µM) administration significantly reduced TG accumulation and increased fatty acid oxidation rate in OA + PA-incubated MPHs. Meanwhile, as per the results of molecular docking and relative mRNA levels, Pac activated SIRT6 and increased SIRT6 deacetylation levels. Furthermore, SIRT6 deletions in MPHs abolished the protective effects of Pac against OA + PA-induced hepatocyte lipid metabolism disorders. The present study demonstrated that Pac alleviates OA + PA-induced hepatocyte lipid metabolism disorders by activating SIRT6 signaling. Overall, SIRT6 signaling increases oxidative stress burden and promotes hepatocyte lipolysis.
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Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.
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Copper plays a key role in the human body; meanwhile, excess Cu2+ ions can result in various diseases. Nanoclusters (NCs) are often used to measure Cu2+ ions, but there are two difficulties. On the one hand, a single probe of NCs is easily affected by environmental factors. On the other hand, it is difficult to mask the interference of Pb2+ ions and Cd2+ ions in the process of detecting Cu2+ ions. As a new type of quantum dots (QDs), tungsten disulfide quantum dots (WS2-QDs) have some advantages of simple synthesis and stable luminescence properties. Stable WS2-QDs with blue fluorescence are used as a reference probe, while gold silver nanoclusters (AuAgNCs) with red fluorescence are used as a response probe. A ratiometric fluorescent sensor was constructed by mixing the two styles of fluorescent probes, which is abbreviated as NCs/QDs. This nano-sensor can be used to detect the concentration of Cu2+ ions, in which the fluorescence of QDs does not change significantly, while the fluorescence of NCs can be quenched by Cu2+ ions. The concentration of Cu2+ ions can be determined as low as 0.12 µM with a linear range from 0.3 to 3 µM. The common interference caused by Pb2+ and Cd2+ ions can be eliminated by the phosphate buffer solution (PBS). This sensor was used to detect the concentration of Cu2+ in river water with satisfactory results.
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Despite the great potential in fabrication of biodegradable and eco-friendly air filters by electrospinning poly(lactic acid) (PLA) membranes, the filtering performance is frequently dwarfed by inadequate physical sieving or electrostatic adsorption mechanisms to capture airborne particulate matters (PMs). Here, using the parallel spinning approach, the unique micro/nanoscale architecture was established by conjugation of neighboring PLA nanofibers, creating bimodal fibers in electrospun PLA membranes for the enhanced slip effect to significantly reduce the air resistance. Moreover, the bone-like nanocrystalline hydroxyapatite bioelectret (HABE) was exploited to enhance the dielectric and polarization properties of electrospun PLA, accompanied by the controlled generation of junctions induced by the microaggregation of HABE (10-30 wt %). The incorporated HABE was supposed to orderly align in the applied E-field and largely promote the charging capability and surface potential, gradually increasing to 7.2 kV from the lowest level of 2.5 kV for pure PLA. This was mainly attributed to HABE-induced orientation of PLA backbone chains and CâO dipoles, as well as the interfacial charges trapped at the interphases of HABE-PLA and crystalline region-amorphous PLA. Given the multiple capturing mechanisms, the micro/nanostructured PLA/HABE membranes were characterized by excellent and sustainable filtering performance, e.g., the filtration efficiency of PM0.3 was promoted from 59.38% for pure PLA to 94.38% after addition of 30 wt % HABE at a moderate airflow capacity of 32 L/min and from 30.78 to 83.75% at the highest level of 85 L/min. It is of interest that the pressure drop was significantly decreased, mainly arising from the slip effect between the ultrafine nanofibers and conjugated microfibers. The proposed combination of the nanostructured electret and the multistructuring strategy offers the function integration of efficient filtration and low resistance that are highly useful to pursue fully biodegradable filters.
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In forensics, accurate identification of the origin of body fluids is essential for reconstructing a crime scene or presenting strong evidence in court. Microorganisms have demonstrated great potential in body fluid identification. We developed a multiplex PCR system for forensic salivary identification, which contains five types of bacteria:Streptococcus salivarius, Neisseria subflava, Streptococcus. mutans, Bacteroides thetaiotaomicron, and Bacteroides. uniformis. And the validated studies were carried out following the validation guidelines for DNA analysis methods developed by the Scientific Working Group on DNA Analysis Methods (SWGDAM), which included tests for sensitivity, species specificity, repeatability, stability, and mixed samples, trace samples, case samples, and a population study. Our result depicted that the lowest detection limit of the system was 0.01 ng template DNA. Moreover, the corresponding bacteria can still be detected when the amount of saliva input is low to 0.1 µL for DNA extraction. In addition, the target bacteria were not detected in the DNA of human, seven common animals, and seven bacteria DNA and in nine other body fluid samples (skin, semen, blood, menstrual blood, nasal mucus, sweat, tears, urine, and vaginal secretions). Six common inhibitors such as indigo, EDTA, hemoglobin, calcium ions, alcohol and humic acid were well tolerated by the system. What is more, the salivary identification system recognized the saliva component in all mixed samples and simulated case samples. Among 400 unrelated individuals from the Chinese Han population analyzed by this novel system, the detection rates of N. subflava, S. salivarius, and S. mutans were 97.75%, 70.75%, and 19.75%, respectively, with 100% identification of saliva. In conclusion, the salivary identification system has good sensitivity, specificity, stability, and accuracy, which can be a new effective tool for saliva identification.
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Líquidos Corporais , Reação em Cadeia da Polimerase Multiplex , Humanos , Feminino , Animais , Medicina Legal , Saliva/microbiologia , Sêmen , DNA , Genética Forense/métodosRESUMO
Importance: Parenteral enoxaparin is a preferred anticoagulant used in the acute phase for patients with acute coronary syndrome (ACS). The safety and efficacy of short-term low-dose rivaroxaban in this clinical setting remain unknown. Objective: To compare the safety and efficacy of rivaroxaban vs enoxaparin in the acute phase of ACS. Design, Setting, and Participants: This multicenter, prospective, open-label, active-controlled, equivalence and noninferiority trial was conducted from January 2017 through May 2021 with a 6-month follow-up at 21 hospitals in China. Participants included patients with ACS missing the primary reperfusion window or before selective revascularization. Data were analyzed from November 2021 to November 2022. Interventions: Participants were randomized 1:1:1 to oral rivaroxaban 2.5 mg or 5 mg or 1 mg/kg subcutaneous enoxaparin twice daily in addition to dual antiplatelet therapy (DAPT; aspirin 100 mg and clopidogrel 75 mg once daily) for a mean of 3.7 days. Main Outcomes and Measures: The primary safety end point was bleeding events, as defined by the International Society on Thrombosis and Haemostasis, and the primary efficacy end point was major adverse cardiovascular events (MACEs), including cardiac death, myocardial infarction, rerevascularization, or stroke during the 6-month follow-up. Results: Of 2055 enrolled patients, 2046 (99.6%) completed the trial (mean [SD] age 65.8 [8.2] years, 1443 [70.5%] male) and were randomized to enoxaparin (680 patients), rivaroxaban 2.5 mg (683 patients), or rivaroxaban 5 mg (683 patients). Bleeding rates were 46 patients (6.8%) in the enoxaparin group, 32 patients (4.7%) in the rivaroxaban 2.5 mg group, and 36 patients (5.3%)in the rivaroxaban 5 mg group (rivaroxaban 2.5 mg vs enoxaparin: noninferiority hazard ratio [HR], 0.68; 95% CI, 0.43 to 1.07; P = .005; rivaroxaban 5 mg vs enoxaparin: noninferiority HR, 0.88; 95% CI, 0.70 to 1.09; P = .001). The incidence of MACEs was similar among groups, and noninferiority was reached in the rivaroxaban 5 mg group (HR, 0.60; 95% CI, 0.31 to 1.16, P = .02) but not in the rivaroxaban 2.5 mg group (HR, 0.68; 95% CI, 0.36 to 1.30; P = .05) compared with the enoxaparin group. Conclusions and Relevance: In this equivalence and noninferiority trial, oral rivaroxaban 5 mg showed noninferiority to subcutaneous enoxaparin (1 mg/kg) for patients with ACS treated with DAPT during the acute phase. Results of this feasibility study provide useful information for designing future randomized clinical trials with sufficient sample sizes. Trial Registration: ClinicalTrials.gov Identifier: NCT03363035.
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Síndrome Coronariana Aguda , Rivaroxabana , Humanos , Masculino , Idoso , Feminino , Rivaroxabana/efeitos adversos , Enoxaparina/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Aspirina/uso terapêutico , Estudos Prospectivos , Hemorragia/induzido quimicamenteRESUMO
Biomimetic mineralization of high-strength apatite structure essentially relies on mimicking the inorganic building blocks of naturally occurring bones. However, conventional routes still have substantial function gaps in providing precision control over the geometrical dimensions and crystalline morphology of biomineralized apatite. Herein, we conceived the concept of microwave-assisted biomineralization (MAB) to customize 1D hydroxyapatite nanowhiskers (HANWs) at graphene templates, rendering the formation of graphene-hydroxyapatite (Gr-HA) nanohybrids. The HANWs essentially resembled bone apatite in elemental composition (Ca/P = 1.74), diameter (~20 nm), crystallinity (63 %), and rodlike geometry (aspect ratio of ~6). The Gr-HA nanohybrids were uniformly incorporated into poly(lactic acid) (PLA) microfibers (~1 µm) by electrospinning, engendering fibrous membranes with a set of Gr-HA loadings (10, 20 and 30 wt%). Intimate interactions were generated between Gr-HA and PLA matrix, contributing to significant promotion of the mechanical properties for PLA composite membranes. For example, the yield strength and elastic modulus of the PLA composite membranes loaded with 30 wt% Gr-HA achieved 5.4 and 66.4 MPa, increasing nearly 182 % and over 94 % compared to those of pure PLA, respectively. Moreover, the bone-like HANWs endowed PLA membranes with excellent cytocompatibility and good bioactivity, as demonstrated by over 38 % increase in cell viability and rapid apatite formation in mineral solution. The impressive combination of mechanical properties and biological characteristics make the PLA/Gr-HA scaffolds promising for guided tissue/bone regeneration therapy.
Assuntos
Durapatita , Grafite , Durapatita/química , Alicerces Teciduais/química , Biomineralização , Engenharia Tecidual/métodos , Poliésteres/químicaRESUMO
Uneven and insufficient encapsulation caused by surface tension between supporting and phase change materials (PCMs) can be theoretically avoided if the encapsulation process co-occurs with the formation of supporting materials in the same environment. Herein, for the first time, a one-pot one-step (OPOS) protocol is developed for synthesizing TiO2 -supported PCM composite, in which porous TiO2 is formed in situ in the solvent of melted PCMs and directly produces the desired thermal energy storage materials with the completion of the reaction. The preparation features straightforward operation and high environmental metrics with no emission, requires only stirring and heating without the addition of organic solvent or catalyst. Moreover, the preparation process can be easily scaled-up at the laboratory. Because of the OPOS protocol and porous TiO2 inside, the as-obtained PCM composite possesses a 66.5% encapsulation ratio and 166.8% thermal conductivity enhancement compared to pristine unsupported PCMs, with 94.7% light-to-thermal conversion efficiency and promising bacterial inhibition activity without any leakage.