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The application of the DMSO/SOCl2 system enabled the intramolecular cyclization/chlorination of N,N-disubstituted 2-alkynylanilines, leading to the synthesis of a series of 3-chloroindoles with moderate to good yields. Differing from the previously reported interrupted Pummerer reaction featuring the introduction of SMe moiety, the current approach adopted an alternative pathway that realized the incorporation of chlorine atom to the indole skeleton via a desulfonylative chlorocyclization process.
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The combining use of BnSCF2D, mCPBA and Tf2O serves as an efficient multi-component reagents system (MCRS) for the synthesis of deuteriodifluoromethylthiolated isocoumarins-1-imines/isocoumarins via intramolecular cyclization/deuteriodifluoromethylthiolation of 2-alkynylbenzamides/2-alkynylbenzoates. The approach features the generation of the crucial reactive electrophilic sulfonium salt through a sequence process involving the oxidation of BnSCF2D by mCPBA followed by Tf2O promoted activation.
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Hexabromocyclododecane (HBCD), as a monitored chemical of the Chemical Weapons Convention, the Stockholm Convention and the Action Plan for New Pollutants Treatment in China, raises significant concerns on its impact of human health and food security. This study investigated enantiomer-specific biomarkers of HBCD in maize (Zea mays L.). Upon exposure to HBCD enantiomers, the maize root tip cell wall exhibited thinning, uneven cell gaps, and increased deposition on the cell outer wall. Elevated malondialdehyde (MDA) indicated lipid peroxidation, with higher mitochondrial membrane potential (MMP) inhibition in (+)-enantiomer treatments (47.2%-57.9%) than (-)-enantiomers (14.4%-37.4%). The cell death rate significantly increased by 37.7%-108.8% in roots and 16.4%-62.4% in shoots, accompanied by the upregulation of superoxide dismutase isoforms genes. Molecular docking presenting interactions between HBCD and target proteins, suggested that HBCD has an affinity for antioxidant enzyme receptors with higher binding energy for (+)-enantiomers, further confirming their stronger toxic effects. All indicators revealed that oxidative damage to maize seedlings was more severe after treatment with (+)-enantiomers compared to (-)-enantiomers. This study elucidates the biomarkers of phytotoxicity evolution induced by HBCD enantiomers, providing valuable insights for the formulation of more effective policies to safeguard environmental safety and human health in the future.
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Biomarcadores , Hidrocarburos Bromados , Simulación del Acoplamiento Molecular , Zea mays , Zea mays/efectos de los fármacos , Zea mays/genética , Hidrocarburos Bromados/toxicidad , Estereoisomerismo , Retardadores de Llama/toxicidad , Peroxidación de Lípido/efectos de los fármacosRESUMEN
A series of 4-thio/seleno-cyanated pyrazoles was conveniently synthesized from 4-unsubstituted pyrazoles using NH4SCN/KSeCN as thio/selenocyanogen sources and PhICl2 as the hypervalent iodine oxidant. This metal-free approach was postulated to involve the in situ generation of reactive thio/selenocyanogen chloride (Cl-SCN/SeCN) from the reaction of PhICl2 and NH4SCN/KSeCN, followed by an electrophilic thio/selenocyanation of the pyrazole skeleton.
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Aptamer-based lateral flow assay (Apt-LFA) has shown promising applications for small-molecule detection. However, the design of the AuNP (gold nanoparticle)-cDNA (complementary DNA) nanoprobe is still a big challenge due to the moderate affinity of the aptamer to small molecules. Herein, we report a versatile strategy to design a AuNPs@polyA-cDNA (poly A, a repeat sequence with 15 A bases) nanoprobe for small-molecule Apt-LFA. The AuNPs@polyA-cDNA nanoprobe contains a polyA anchor blocker, complementary DNA segment to DNA on the control line (cDNAc), partial complementary DNA segment with aptamer (cDNAa), and auxiliary hybridization DNA segment (auxDNA). Using adenosine 5'-triphosphate (ATP) as a model target, we optimized the length of auxDNA and cDNAa and achieved a sensitive detection of ATP. In addition, kanamycin was used as a model target to verify the universality of the concept. Therefore, this strategy can be easily extended to other small molecules; therefore, high application potential in Apt-LFAs can be envisaged.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Nanopartículas del Metal , ADN Complementario , Oro , ADN , Adenosina Trifosfato , Poli A , Límite de DetecciónRESUMEN
A metal-free synthesis of a series of fluoroalkyl-containing oxazoles from ß-monosubstituted enamines was developed. This fluoroacyloxylation/cyclization cascade process was mediated by fluoroalkyl-containing hypervalent iodine(III) species formed in situ from the reaction of phenyliodine(III) diacetate (PIDA) and RCF2CO2H (R = H, Cl, Br, F, CF3, CH3, Ph, SAr, OAr).
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Antipsychotic medications are commonly used to treat schizophrenia, but they can have negative effects on lipid metabolism, leading to an increased risk of cardiovascular diseases, reduced life expectancy, and difficulties with treatment adherence. The specific mechanisms by which antipsychotics disrupt lipid metabolism are not well understood. Sterol regulatory element-binding proteins (SREBPs) are important transcriptional factors that regulate lipid metabolism. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a gene regulated by SREBPs, plays a critical role in controlling levels of low-density lipoprotein cholesterol (LDL-C) and has become a focus of research on lipid-lowering drugs. Recent studies have shown that antipsychotic drugs can affect lipid metabolism through the SREBP/PCSK9 pathway. A deep understanding of the mechanism for this pathway in antipsychotic drug-related metabolic abnormalities will promote the prevention of lipid metabolism disorders in patients with schizophrenia and the development and application of new drugs.
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Antipsicóticos , Trastornos del Metabolismo de los Lípidos , Humanos , Antipsicóticos/efectos adversos , Metabolismo de los Lípidos , Proproteína Convertasa 9/genética , Proteína 1 de Unión a los Elementos Reguladores de EsterolesRESUMEN
Aflatoxin B1 (AFB1) is a mycotoxin and is the most carcinogenic of all known chemicals. In view of the AFB1 characteristics of widespread distribution, serious pollution, great harm to humans, and animals and difficult to remove, it is urgent to develop a convenient and sensitive detection method. Moreover, chromatographic test strips (CTSs) are a rapid detection technology that combines labeling technology with chromatography technology. CTSs have been widely used in the fields of environmental monitoring, medical diagnosis, and food safety analysis in recent years. Different from other immune assays, they have the advantages of short measuring time, low cost, high efficiency and no need for professionals to operate. In addition, the introduction of nanomaterials has laid a good foundation for the detection of high sensitivity, high specificity and high efficiency via CTSs. Herein, we tend to comprehensively introduce the applications of chromatographic methods in AFB1 detection and pay attention to the signal detection modes based on nanomaterials in antibody-based immunochromatographic strips (ICSs), such as colorimetric, fluorescent, chemiluminescent, and Raman scattering sensing. Some typical examples are also listed in this review. In the end, we make a summary and put forward prospects for the development of CTSs.
This review is the first systematic review about the applications of antibody-/aptamer-based chromatographic methods for rapid AFB1 detection.Pay attention to the signal detection modes based on nanomaterials in antibody-ICSs, such as colorimetric, fluorescent, chemiluminescent and Raman scattering sensing.Make a summary about some typical examples and put forward prospects for the development of CTSs.
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Ochratoxin A (OTA) is a widely distributed mycotoxin that often contaminates food, grains and animal feed. It poses a serious threat to human health because of its high toxicity and persistence. Therefore, the development of an inexpensive, highly sensitive, accurate and rapid method for OTA detection is imperative. In recent years, various nanomaterials used in the establishment of aptasensors have attracted great attention due to their large surface-to-volume ratio, good stability and facile preparation. This review summarizes the development of nanomaterial-based aptasensors for OTA determination and sample treatment over the past 5 years. The nanomaterials used in OTA aptasensors include metal, carbon, luminescent, magnetic and other nanomaterials. Finally, the limitations and future challenges in the development of nanomaterial-based OTA aptasensors are reviewed and discussed.
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Técnicas Biosensibles , Nanoestructuras , Ocratoxinas , Alimentación Animal , AnimalesRESUMEN
(R)-3-aminopiperidine ((R)-APD), a key intermediate for alogliptin, trelagliptin, and linagliptin, was successfully resolved from racemic 3-aminopiperidine with an enantiomerically pure resolving agent, namely, (R)-4-(2-chlohydroxy-1.3.2-dioxaphosphorinane 2-oxide ((R)-CPA), via diastereomeric salt formation. By this resolution approach, (R)-3-aminopiperidine was obtained in 99.5% yield with 99.6%e.e.
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BACKGROUND: This study aims to analyze the trends of premature mortality caused from four major non-communicable diseases (NCDs), namely cardiovascular disease (CVD), cancer, chronic respiratory diseases, and diabetes in Nanjing between 2007 and 2018 and project the ability to achieve the "Healthy China 2030" reduction target. METHODS: Mortality data of four major NCDs for the period 2007-2018 were extracted from the Death Information Registration and Management System of Chinese Center for Disease Control and Prevention. Population data for Nanjing were provided by the Nanjing Bureau of Public Security. The premature mortality was calculated using the life table method. Joinpoint regression model was used to estimate the average annual percent changes (AAPC) in mortality trends. RESULTS: From 2007 to 2018, the premature mortality from four major NCDs combined in Nanjing decreased from 15.5 to 9.5%, with the AAPC value at - 4.3% (95% CI [- 5.2% to - 3.4%]). Overall, it can potentially achieve the target, with a relative reduction 28.6%. The premature mortality from cancer, CVD, chronic respiratory diseases and diabetes all decreased, with AAPC values at - 4.2, - 5.0%, - 5.9% and - 1.6% respectively. A relative reduction of 40.6 and 41.2% in females and in rural areas, but only 21.0 and 12.8% in males and in urban areas were projected. CONCLUSION: An integrated approach should be taken focusing on the modifiable risk factors across different sectors and disciplines in Nanjing. The prevention and treatment of cancers, diabetes, male and rural areas NCDs should be enhanced.
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Diabetes Mellitus , Enfermedades no Transmisibles , China/epidemiología , Diabetes Mellitus/epidemiología , Femenino , Humanos , Tablas de Vida , Masculino , Mortalidad Prematura , Enfermedades no Transmisibles/epidemiologíaRESUMEN
The construction of the biologically interesting chromone skeleton was realized by PhIO-mediated dehydrogenation of chromanones under mild conditions. Interestingly, this method also found application in the synthesis of the naturally occurring frutinone A.
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Bisphenol A (BPA) is an important industrial chemical used as a plasticizer in polycarbonate and epoxy resins in the plastic and paper industries. Because of its estrogenic properties, BPA has attracted increasing attention from many researchers. This review focuses primarily on analytical methods for BPA detection that have emerged in recent years. We present and discuss the advantages and disadvantages of sample preparation techniques (e.g., solvent extraction, solid-phase extraction, molecularly imprinted polymer solid-phase extraction, and micro-extraction techniques) and analytical methods (e.g., liquid chromatography, liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, capillary electrophoresis, immunoassay, and several novel sensors). We also discuss expected future developments for the detection of BPA. Graphical Abstract This review focuses primarily on the recent development in the detection of bisphenol A including sample pre-treatment and analytical methods.
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Compuestos de Bencidrilo/análisis , Técnicas de Química Analítica/métodos , Disruptores Endocrinos/análisis , Contaminantes Ambientales/análisis , Fenoles/análisis , Plastificantes/análisis , Animales , Aptámeros de Nucleótidos/química , Compuestos de Bencidrilo/aislamiento & purificación , Técnicas Biosensibles/métodos , Cromatografía de Afinidad/métodos , Cromatografía Liquida/métodos , Electroforesis Capilar/métodos , Disruptores Endocrinos/aislamiento & purificación , Contaminantes Ambientales/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Extracción Líquido-Líquido/métodos , Espectrometría de Masas/métodos , Impresión Molecular/métodos , Fenoles/aislamiento & purificación , Plastificantes/aislamiento & purificación , Polímeros/química , Extracción en Fase Sólida/métodosRESUMEN
This study presents a novel analytical method for the detection of oxytetracycline (OTC) in complex food matrices based on a direct competitive enzyme-linked aptamer assay and magnetic separation technology. In this protocol, free OTC competed with horseradish peroxidase labeled OTC (OTC-HRP) for binding to the OTC aptamer immobilized on magnetic beads. The parameters that can affect the response, such as avidin concentration, aptamer concentration, OTC-HRP concentration, incubation temperature, incubation time, blocking agent, and binding buffer, were optimized. Under the optimal conditions, the linear range for the OTC concentration detection is 0.5-100 ng mL(-1), with a concentration of OTC needed to obtain 50 % of the maximum signal of 14.47 ng mL(-1). The limit of detection and the limit of quantitation were 0.88 and 3.40 ng mL(-1), respectively. There was no obvious cross-reactivity with most of the tetracycline pesticides. The recovery rates ranged from 71.0 to 91.2 % for the food samples, including chicken, milk, and honey, and the relative standard deviation was less than 15.0 %. The proposed method was applied to measure OTC in real samples, and was validated using high-performance liquid chromatography. This method has the advantages of magnetic separation and the concentration effect of magnetic nanoparticles, the specificity of the aptamer, and the high-throughput of microtiter plates; it offers a promising approach for the screening of OTC because it is simple, rapid, highly sensitive, and has low cost.
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Antibacterianos/química , Aptámeros de Nucleótidos/química , Residuos de Medicamentos/química , Análisis de los Alimentos/métodos , Imanes , Nanoestructuras , Oxitetraciclina/química , Avidina/química , Biotinilación , Contaminación de Alimentos , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: To observe the clinical efficacy of comprehensive Western medical treatment plus Compound Yindan Decoction (CYD) in treatment of acute cholestatic hepatitis (ACH). METHODS: Using randomized controlled study, 60 ACH patients in line with inclusive criteria were randomly assigned to the treatment group (treated by comprehensive Western medical treatment plus CYD) and the control group (treated by comprehensive Western medical treatment alone), 30 in each group. Scores for symptoms and levels of liver functions [total bilirubin (TBIL), direct bilirubin (DBIL), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), total biliary acid (TBA)] were observed before and after treatment. RESULTS: Compared with before treatment in the same group, total scores for symptoms decreased in the treatment group and the control group at the end of the 1st and the 4th week after treatment (all P < 0.05). Compared with the control group, total scores for symptoms decreased in the treatment group at the end of the 1st week (P < 0.05). Compared with before treatment, serum levels of TBIL, DBIL, ALP, GGT, and TBA all decreased in the two groups at the end of the 4th week after treat- ment (P < 0.01). Compared with the control group, serum levels of TBIL, DBIL, ALP, GGT, and TBA all decreased in the treatment group at the end of the 1st and the 2nd week after treatment (P < 0.05). Compared with the control group, the average time for TBIL and DBIL decreasing to the level less than five times the normal value was significantly shorter in the treatment group (P < 0.05). CONCLUSION: CYD could significantly improve clinical symptoms of ACH patients, decrease serum levels of TBIL and DBIL, reduce serum levels of ALP, GGT, and TBA, obviously improve cholestasis, and promote the recovery.
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Medicamentos Herbarios Chinos/uso terapéutico , Hepatitis/tratamiento farmacológico , Fosfatasa Alcalina , Bilirrubina , Colestasis , Terapia Combinada , Humanos , gamma-GlutamiltransferasaRESUMEN
Highly diastereoselective intramolecular trapping of ammonium ylides with enones has been developed through a Rh(II)/Brønsted acid cocatalytic strategy. This process allows rapid and efficient construction of N-unprotected polyfunctional 2,2,3-trisubstituted indolines in moderate to good yields with excellent diastereoselectivity.
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Ácidos/química , Compuestos de Amonio/química , Indoles/síntesis química , Rutenio/química , Catálisis , Indoles/química , Estructura Molecular , EstereoisomerismoRESUMEN
Alcaligenes faecalis strain JBW4, a strain of bacteria that is capable of degrading endosulfan, was inoculated into sterilized and natural soils spiked with endosulfan. JBW4 degraded 75.8 and 87.0 % of α-endosulfan and 58.5 and 69.5 % of ß-endosulfan in sterilized and natural soils, respectively, after 77 days. Endosulfan ether and endosulfan lactone were the major metabolites that were detected by gas chromatography-mass spectrometry. This result suggested that A. faecalis strain JBW4 degrades endosulfan using a non-oxidative pathway in soils. The ability of strain JBW4 to colonize endosulfan-contaminated soils was confirmed by polymerase chain reaction-denaturing gradient gel electrophoresis. This result suggested that strain JBW4 competed with the original inhabitants in the soil to establish a balance and successfully colonize the soils. In addition, the detoxification of endosulfan by strain JBW4 was evaluated using single-cell gel electrophoresis and by determining the soil microbial biomass carbon and enzymatic activities. The results showed that the genotoxicity and ecotoxicity of endosulfan in soil were reduced after degradation. The natural degradation of endosulfan in soil is inadequate; therefore, JBW4 shows potential for the bioremediation of industrial soils that are contaminated with endosulfan residues.
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Alcaligenes faecalis/crecimiento & desarrollo , Alcaligenes faecalis/metabolismo , Endosulfano/metabolismo , Microbiología del Suelo , Contaminantes del Suelo/metabolismo , Biotransformación , Electroforesis en Gel de Gradiente Desnaturalizante , Cromatografía de Gases y Espectrometría de Masas , Redes y Vías Metabólicas , Reacción en Cadena de la Polimerasa , ARN Bacteriano/genéticaRESUMEN
Fomesafen is a diphenyl ether herbicide that has an important role in the removal of broadleaf weeds in bean and fruit tree fields. However, very little information is known about the effects of this herbicide on soil microbial community structure and activities. In the present study, laboratory experiments were conducted to examine the effects of different concentrations of fomesafen (0, 10, 100, and 500 µg/kg) on microbial community structure and activities during an exposure period of 60 days, using soil enzyme assays, plate counting, and denaturing gradient gel electrophoresis (DGGE). The results of enzymatic activity experiments showed that fomesafen had different stimulating effects on the activities of acid phosphatase, alkaline phosphatase, and dehydrogenase, with dehydrogenase being most sensitive to fomesafen. On the tenth day, urease activity was inhibited significantly after treatment of different concentrations of fomesafen; this inhibiting effect then gradually disappeared and returned to the control level after 30 days. Plate counting experiments indicated that the number of bacteria and actinomycetes increased in fomesafen-spiked soil relative to the control after 30 days of incubation, while fungal number decreased significantly after only 10 days. The DGGE results revealed that the bacterial community varied in response to the addition of fomesafen, and the intensity of these six bands was greater on day 10. Sequencing and phylogenetic analyses indicated that the six excised DGGE bands were closely related to Emticicia, Bacillus, and uncultured bacteria. After 10 days, the bacterial community exhibited no obvious change compared with the control. Throughout the experiment, we concluded that 0-500 µg/kg of fomesafen could not produce significant toxic effects on soil microbial community structure and activities.
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Bacterias/crecimiento & desarrollo , Benzamidas/toxicidad , Herbicidas/toxicidad , Microbiología del Suelo , Contaminantes del Suelo/toxicidad , Bacterias/clasificación , Bacterias/efectos de los fármacos , Benzamidas/análisis , Monitoreo del Ambiente , Hongos/crecimiento & desarrollo , Herbicidas/análisis , Filogenia , Suelo/química , Contaminantes del Suelo/análisisRESUMEN
OBJECTIVE: To evaluate the renal function of 298 liver cirrhosis cases among the patient population of Beijing Ditan Hospital. METHODS: The medical database of Beijing Ditan Hospital was retrospectively searched for patients with liver cirrhosis (compensated and decompensated). Patients were excluded from the study according to the presence of concomitant serious diseases, such as hypertension, diabetes, and malignancies.The consistency of renal insufficiency was evaluated by the glomerular filtration rate (eGFR) or serum creatinine (SCr) level, which were applied to the simplified modification of diet in renal disease (MDRD) equation.The renal function was compared between groups stratified according to compensated/decompensated status, sex, and age.The factors affecting renal insufficiency were screened.Measurement data were compared using the t-test and count data were compared using the chi-square test.Multiple sets of data were compared using analysis of variance.Correlations were assessed using multivariate logistic regression analysis, and the confounding variables were controlled with the Mantel-Haenszel method. RESULTS: A total of 298 hospitalized patients with liver cirrhosis were included in the study, among which 41 had compensated cirrhosis and 257 had decompensated cirrhosis.Twenty patients (6.7%) with renal insufficiency were identified by SCr measurement and 62 patients (20.8%) were identified by eGFR, and the number identified was significantly different between the two groups (x2=42.00, P less than 0.05).Fifty-six (21.8%) patients had decompensated cirrhosis and 6 (14.6%) patients had decompensated cirrhosis with renal dysfunction; the eGFR levels for these two groups were (117.75 +/- 32.60) ml/min/(1.73 m2)-1 and (112.72 +/- 24.01) ml/min/(1.73 m2) respectively and the difference was not statistically significant (P more than 0.05).The incidence of renal dysfunction among female patients was 22.7% (17/75), and the incidence among male patients was 20.2% (45/223); the eGFR levels for these two groups were (110.07 +/- 26.60) ml/min/(1.73 m2)1 and (112.49 +/- 33.05) ml/min/(l.73 m2) respectively, and the difference was not statistically significant (P more than 0.05).The rate of renal dysfunction among patients aged 20 to 40 years-old, more than 40 to 60 years-old, and more than 60 years years-old was 5.7% (4/70), 22.5% (40/178), and 36.0%(18/50) respectively; the eGFR values for these two groups were (123.43 +/- 24.42) ml min/(l.73 m2), (111.18+/- 33.57) ml/min/(1.73 m2), and (98.20 +/- 27.04) ml/min/(1.73 m2), and the differences were not statistically significant (P less than 0.05).After stratification of the study population by age, the patient sex and the cirrhosis stage were not significantly different (P more than 0.05).Multivariate logistic regression analysis identified age as a risk factor of hepatitis B-related cirrhosis and renal dysfunction (P less than 0.05). CONCLUSION: The simplified MDRD equation can help clinicians determine whether patients have kidney injury.Development of renal dysfunction in patients with liver cirrhosis is not associated with patient sex and cirrhosis stage, but is precisely correlated with patient age.
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Enfermedades Renales/fisiopatología , Cirrosis Hepática , Adulto , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To evaluate the clinical efficacy and safety of integrative medical program based on blood cooling and detoxification recipe (BCDR) in treating patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) of heat-toxicity accumulation syndrome (HTAS). METHODS: Adopting randomized controlled clinical design, a total of 105 HBV-ACLF patients of HTAS were randomly assigned to the trial group (64 cases) and the control group (41 cases). Patients in the control group were treated with comprehensive Western therapy, while those in the trial group were treated with comprehensive Western therapy plus BCDR. All were treated for 8 weeks and followed up for 40 weeks. Effect and safety of the treatment were assessed, including fatality, liver functions [total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), and aspartate transaminase (AST)], and prothrombin activity (PTA) after treatment and at week 48 of follow-ups. RESULTS: After 8-week treatment, there was statistical difference in the overall fatality rate (15.63% vs 34.15%), the fatality rate in the mid-term (25.0% vs 64.7%), TBIL at week 8 (64.54 +/- 79.75), AST [at week 2: (178.97 +/- 44.24) U/L vs (288.48 +/- 58.49) U/L; at week 4: (61.65 +/- 27.36) U/L vs (171.12 +/- 89.11) U/L] and PTA [at week 4: (58.30 +/- 15.29) vs (42.56 +/- 15.27); at week 6: (60.77 +/- 20.40) vs (43.08 +/- 12.79)] (all P < 0.05). At week 48 of the followup, the fatality rate of the trial group (21.88%) decreased by 17. 14% when compared with that of the control group (39.02%; P < 0.05). No obvious adverse event occurred in the two groups during the 8-week treatment period. CONCLUSION: BCDR could significantly reduce the mortality of HBV-ACLF patients.