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Transition-metal-catalyzed enantioselective nitrene transfer to sulfides has emerged as one of the most powerful strategies for rapid construction of enantioenriched sulfimides. However, achieving stereocontrol over highly active earth-abundant transition-metal nitrenoid intermediates remains a formidable challenge compared with precious metals. Herein, we disclose a chiral iron(II)/N,N'-dioxide-catalyzed enantioselective imidation of dialkyl and alkyl aryl sulfides using iminoiodinanes as nitrene precursors. A series of chiral sulfimides were obtained in moderate-to-good yields with high enantioselectivities (56 examples, up to 99% yield, 98:2 e.r.). The utility of this methodology was demonstrated by late-stage modification of complex molecules and synthesis of the chiral insecticide sulfoxaflor and the intermediates of related bioactive compounds. Based on experimental studies and theoretical calculations, a water-bonded high-spin iron nitrenoid species was identified as the key intermediate. The observed stereoselectivity was original from the steric repulsion between the amide unit of the ligand in the chiral cave and the bulky substituent of sulfides. Additionally, dioxazolones proved to be suitable acylnitrene precursors in the presence of an iron(III)/N,N'-dioxide complex, resulting in the formation of enantioselectivity-reversed sulfimides (14 examples, up to 81% yield, 97:3 e.r.).
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The severe deterioration of the marine ecosystem significantly negatively impacts the performance of solar-driven steam generation (SSG) and the quality of the obtained freshwater. Herein, a bifunctional Ag/MgFe2O4@SCW reactor with a sandwich structure is designed for efficient SSG and Cr(VI) reduction, which is constructed via in situ deposit Ag nanoparticles (NPs) and MgFe2O4 onto surface carbonized wood (SCW). Owing to the advanced sandwich structure and strong interfacial interactions between each component, an ultra-high evaporation rate of 1.55 kg m-2 h-1 and the efficiency of 88.6% are achieved using Ag/MgFe2O4@SCW under 1 sun. The system exhibits the long-term evaporation performance in the simulated sewage and strong acid/base solutions along with water-harvesting capacity in outdoor solar desalination. The quality of distilled water after desalination of actual seawater and NaCl solutions with different concentrations meets the WHO-recommended drinkable water standards. Furthermore, Ag/MgFe2O4@SCW shows outstanding antibacterial property, self-desalting capacity, as well as reusability and structure stability. Most importantly, the fast carrier separation endows Ag/MgFe2O4@SCW with superior photocatalytic activity and Cr(VI) photoreduction of up to 96.1% after 180 min of illumination. The bifunctional Ag/MgFe2O4@SCW reactor provides an advanced synergistic mechanism for improving SSG and photocatalytic performance, while being promising for solar-powered production of clean water.
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Phthalate esters (PAEs), accompanied by phthalate monoesters as hydrolysis metabolites in humans, have been widely used as plasticizers and exhibited disruptive effects on the endocrine and metabolic systems. The present study aims to investigate the inhibition behavior of PAEs and phthalate monoesters on the activity of the important hydrolytic enzymes, carboxylesterases (CESs), to elucidate the toxicity mechanism from a new perspective. The results showed significant inhibition on CES1 and CES2 by most PAEs, but not by phthalate monoesters, above which the activity of CES1 was strongly inhibited by DCHP, DEHP, DiOP, DiPP, DNP, DPP and BBZP, with inhibition ratios exceeding 80%. Kinetic analyses and in vitro-in vivo extrapolation were conducted, revealing that PAEs have the potential to disrupt the metabolism of endogenous substances catalyzed by CES1 in vivo. Molecular docking results revealed that hydrogen bonds and hydrophobic contacts formed by ester bonds contributed to the interaction of PAEs towards CES1. These findings will be beneficial for understanding the adverse effect of PAEs and phthalate monoesters.
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Dietilhexil Ftalato , Ácidos Ftálicos , Humanos , Hidrolasas de Éster Carboxílico , Simulación del Acoplamiento Molecular , Ácidos Ftálicos/toxicidad , Plastificantes/toxicidad , Ésteres/química , Dibutil Ftalato , Dietilhexil Ftalato/toxicidad , Dietilhexil Ftalato/química , ChinaRESUMEN
Maintaining a vacuum when applying negative pressure wound therapy (NPWT) is the key to its function, which is a challenge in the perineum, buttocks, and sacrococcygeal region. A retrospective cohort study was conducted to assess the effect of hydrocolloid dressings on preventing air leakage when applying NPWT in these regions. There were 61 patients in Group A (without the aid of hydrocolloid dressings) and 65 patients in Group B (with the aid of hydrocolloid dressings). The hydrocolloid dressing-assisted NPWT significantly reduced the incidence of air leakage compared with conventional NPWT placement (24.6% vs. 7.7%; risk ratio, 3.20; 95% confidence interval, 1.24-8.27; p = 0.009), while decreasing the number of open NPWT applications (2.2 vs. 1.7; difference, 0.43; 95% confidence interval, 0.19-0.66; p < 0.001), shortening hospital stays (20.1 vs. 16.1; difference, 4.07; 95% confidence interval, 1.68-6.46; p = 0.01), and reducing the incidence of adverse skin events (18.0% vs. 4.6%; risk ratio, 3.91; 95% confidence interval, 1.14-13.34; p = 0.017). These findings support the routine use of hydrocolloid dressing-assisted NPWT placement in the perineum, buttocks, and sacrococcygeal region.
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Vendas Hidrocoloidales , Terapia de Presión Negativa para Heridas , Humanos , Perineo , Nalgas , Región Sacrococcígea , Estudios Retrospectivos , Cicatrización de HeridasRESUMEN
The dissolution of silica and transparent exopolymer particles (TEP) can deposit on the membrane surface and cause serious membrane fouling in reverse osmosis (RO) technology. Coagulation, as a common pretreatment process for RO, can effectively intercept pollutants and alleviate membrane fouling. In this study, FeCl3 and AlCl3 coagulants and polyacrylamide (PAM) flocculants were used to explore the optimal coagulation conditions to reduce the concentration of silica and TEP in the RO process. The results showed that the two coagulants had the best removal effect on pollutants when the pH was 7 and the dosage was 50 mg/L. Considering the proportion of reversible fouling after coagulation, the removal rate of pollutants, and the residual amount of coagulation metal ions, the best PAM dosage was 5 mg/L for FeCl3 and 1 mg/L for AlCl3. After coagulation pretreatment, the Zeta potential decreased, and the particle size distribution increased, making pollutants tend to aggregate, thus effectively removing foulants. The removal mechanisms of pollutants by coagulation pretreatment were determined to be adsorption, electric neutralization and co-precipitation. This study determined the best removal conditions of silica and TEP by coagulation and explored the removal mechanism.
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Contaminantes Ambientales , Purificación del Agua , Dióxido de Silicio , Matriz Extracelular de Sustancias Poliméricas , Purificación del Agua/métodos , Filtración/métodos , ÓsmosisRESUMEN
The textbook alkene halogenation reaction establishes straightforward access to vicinal dihaloalkanes. However, a robust catalytic method for dihalogenizing electron-deficient olefins in an enantioselective manner is still under development, and its mechanism remains controversial. Herein, we disclose efficient regio-, anti-diastereo-, and enantioselective dibromination, bromochlorination, and dichlorination reactions of enones catalyzed by a chiral N,N'-dioxide/Yb(OTf)3 complex. With the combination of electrophilic halogen and halide salts as halogenating agents, an array of homo- and heterodihalogenated derivatives is achieved in moderate to good enantioselectivities. Moreover, DFT calculations reveal that a novel triplet halo-radical pylon intermediate is probable in accounting for the exclusive regio- and anti-diastereoselectivity.
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It is crucial to design efficient adsorbents for uranium from natural seawater with wide adaptability, effectiveness, and environmental safety. Porous organic polymers (POPs) provide superb tunable porosity and stability among developed porous materials. In this work, two new POPs, i.e., HCCP-P5-1 and HCCP-P5-2 were rationally designed and constructed by linked with macrocyclic pillar[5]arene as the monomer and hexachlorophosphate as the core via a macrocycle-to-framework strategy. Both pillar[5]arene-containing POPs exhibited high uranium adsorption capacity compared with previously reported macrocycle-free counterparts. The isothermal adsorption curves and kinetic studies showed that the adsorption of POPs on uranium was consistent with the Langmuir model and the pseudo-second-order kinetic model. Especially, HCCP-P5-1 has reached 537.81 mg/g, which is greater than most POPs that have been reported. Meanwhile, the comparison between both HCCP-P5-1 and HCCP-P5-2 can illustrate that the adsorption capacity and stability could be adjusted by the monomer ratio. This work provides a new idea for the design and construction of uranium adsorbents from macrocycle-derived POPs.
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The C-C bond lengths of the linear magnetic neutral CnSb, CnSb+ cations and CnSb- anions are within 1.255-1.336 Å, which is typical for cumulene structures with moderately strong double-bonds. In this report, we found that the adiabatic ionization energy (IE) of CnSb decreased with n. When comparing the IE~n relationship of CnSb with that of pure Cn, we found that the latter exhibited a stair-step pattern (n ≥ 6), but the IE~n relationship of CnSb chains took the shape of a flat curve. The IEs of CnSb were lower than those of corresponding pure carbon chains. Different from pure carbon chains, the adiabatic electron affinity of CnSb does not exhibit a parity effect. There is an even-odd alternation for the incremental binding energies of the open chain CnSb (for n = 1-16) and CnSb+ (n = 1-10, when n > 10, the incremental binding energies of odd (n) chain of CnSb+ are larger than adjacent clusters). The difference in the incremental binding energies between the even and odd chains of both CnSb and pure Cn diminishes with the increase in n. The incremental binding energies for CnSb- anions do not exhibit a parity effect. For carbon chain clusters, the most favorable binding site of atomic antimony is the terminal carbon of the carbon cluster because the terminal carbon with a large spin density bonds in an unsaturated way. The C-Sb bond is a double bond with Wiberg bond index (WBI) between 1.41 and 2.13, which is obviously stronger for a carbon chain cluster with odd-number carbon atoms. The WBI of all C-C bonds was determined to be between 1.63 and 2.01, indicating the cumulene character of the carbon chain. Generally, the alteration of WBI and, in particular, the carbon chain cluster is consistent with the bond length alteration. However, the shorter C-C distance did not indicate a larger WBI. Rather than relying on the empirical comparison of bond distance, the WBI is a meaningful quantitative indicator for predicting the bonding strength in the carbon chain.
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Compared with the common synthesis methods of metal-organic frameworks (MOFs), Co/Cu-based bi-MOFs composite catalyst CoXCu(10-X)-MOFs (X = 2, 4, 6, and 8) was prepared by a facile synthesis method at room temperature. The bi-MOFs composite catalyst was characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The removal ability of sulfamethoxazole (SMX) by different Co:Cu rate bi-MOFs composite catalysts, single Co-based MOFs (zeolitic imidazolate framework-67, ZIF-67), and Cu-based MOFs (Hong Kong University of Science and Technology-1, HKUST-1) were investigated and the effects of peracetic acid (PAA) concentration, catalyst dosage, the common interfering substances (Cl-, HCO3-, SO42-, HA) in water, and SMX removal were investigated. Through the analysis of different free radical scavengers and the changes of surface elements before and after the reaction, the oxidation mechanism was further explored, and the stability of Co4Cu6-MOFs was explored through repeated recycling. The experimental results demonstrate that Co4Cu6-MOFs have a high catalytic activity for PAA. Co4Cu6-MOFs/PAA show the best removal effect of SMX under neutral conditions and the presence of Cl- and HCO3- can promote the removal of SMX.
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Estructuras Metalorgánicas , Contaminantes Químicos del Agua , Sulfametoxazol , Ácido Peracético , Estructuras Metalorgánicas/química , Contaminantes Químicos del Agua/química , Oxidación-ReducciónRESUMEN
N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is a common alkylating agent, which can be experimentally used as a chemical mutagen and carcinogen, extensively existing in the environment. Folic acid (FA), part of the B group of vitamins, plays an important role in defending against inflammation and reducing the risk of cancers. Nevertheless, there is little research on the protective effects of FA against MNNG-induced esophageal inflammation, and its underlying mechanism still remains elusive. Hence, in the present study, we exposed MNNG to SD rats and esophageal cells to establish the esophageal inflammation models. Our research aims to explore the protective roles of FA against esophageal inflammation induced by MNNG via NF-κB pathway by CCK-8, EdU, RT-qPCR, ELISA, H&E, Western blot. Our results revealed that MNNG decreased the viability of esophageal cells, which was restored under FA intervention. Besides, FA relieved the elevation of IL-6, IL-8 and TNF-α in MNNG-induced esophageal inflammation. Moreover, histopathological analysis showed that epithelial spinous cells proliferated in mucous layer, and inflammatory cells were locally infiltrated in the submucosa after MNNG exposure, while the pathological damage of esophageal tissues was gradually alleviated along with increasing FA doses. And Western blot results demonstrated that FA could relieve the rise of phosphorylated IκBα (p-IκBα) and phosphorylated p65 (p-p65) proteins induced by MNNG. Therefore, it is reasonable to believe that FA has a crucial role in preventing MNNG-induced esophageal inflammation through inhibiting the NF-κB pathway, thereby down-regulating the expressions of IL-6, IL-8 and TNF-α.
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Metilnitronitrosoguanidina , FN-kappa B , Animales , Ácido Fólico/farmacología , Ácido Fólico/uso terapéutico , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/prevención & control , Interleucina-6 , Interleucina-8 , Metilnitronitrosoguanidina/toxicidad , Inhibidor NF-kappaB alfa , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfaRESUMEN
OBJECTIVE: Congenital microtia is a common congenital disease in newborns. The specific cause of congenital microtia is currently unknown. The main objective of this study is to elucidate the epidemiological characteristics of congenital microtia and explore the possible etiology of congenital microtia. METHODS: Part of the newborn data from 2011 to 2020 in Shandong Province Birth Defects Monitoring Hospitals were randomly selected. The software GraphPad Prism 9 was used to analyze the data and draw figures. RESULTS: A total of 4247 infants were diagnosed with congenital malformation among 149,525 newborns randomly selected from the Shandong Province Birth Defects Monitoring Hospitals. Among them, a total of 115 infants were diagnosed with congenital microtia. The mean incidence of microtia during 10 years was 76.14±21.93 per 100,000 infants. The mean incidence of microtia in infants with congenital malformation was 2.67±0.75%. The average incidence of male and female infants with microtia during 10 years were 86.93±23.22 and 64.18±32.71 per 100,000 infants, respectively. In terms of maternal age, the older the mother, the higher the incidence of microtia. In terms of the place of residence, rural infants have a higher incidence of microtia than urban infants. CONCLUSIONS: The average incidence of microtia was 76.14±21.93 per 100,000 infants in Shandong Province, China, 2011-2020. The female-to-male incidence ratio was 1.45:1. The authors recommend that women choose to give birth at the age of 25 to 29. They hope that the government will take measures to improve the medical and health conditions in rural areas and improve parenting knowledge in rural areas. This can effectively reduce the prevalence of microtia in infants.
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Anomalías Congénitas , Microtia Congénita , Lactante , Femenino , Recién Nacido , Masculino , Humanos , Microtia Congénita/epidemiología , China/epidemiología , Edad Materna , Incidencia , Prevalencia , Estudios Epidemiológicos , Anomalías Congénitas/epidemiologíaRESUMEN
Deep sternal wound infection (DSWI) is a fatal complication after median sternotomy. This study was to assess the effect of vacuum-assisted closure (VAC) combined with bi-pectoral muscle advancement flap therapy on rehabilitation for the treatment of DSWI. Fifty-two patients with DSWI underwent treatment of VAC and bi-pectoral muscle flap. These patients were followed-up 12 months postoperation. The patient characteristics, duration of VAC therapy, the mean hospital stay, and postoperative complications were retrospectively analysed. All patients underwent 1 to 3 VAC treatment sessions before closure. Fifty-one of 52 DSWI patients were cured to discharge; the mean hospital stay was 26.5 days. The drainage tube continued to drain a large amount of bloody fluid in three patients after the wound was closed. Respiratory failure occurred in one patient with severe mediastinal and pulmonary infections and died eventually in hospital. One patient died of acute cerebral haemorrhage during the12-month follow-up. VAC therapy combined with bi-pectoral muscle flap is a simple and effective treatment for DSWIs with short hospital stays and few complications. However, this is a retrospective case series presentation with no comparison group; further large-scale controlled studies are needed.
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Desbridamiento/métodos , Terapia de Presión Negativa para Heridas/métodos , Músculos Pectorales/trasplante , Esternotomía/efectos adversos , Esternón/cirugía , Colgajos Quirúrgicos , Infección de la Herida Quirúrgica/terapia , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: There is controversy over the optimal timing of microtia reconstruction. The eighth costal cartilage, which is used to shape the helix framework, can be one of the key factors determining surgical timing of microtia reconstruction. Nevertheless, it is difficult to predict the length of the eighth costal cartilage preoperatively. The aim of the present study was to discuss different methods of fabricating cartilaginous ear framework in children with microtia according to different lengths of the eighth costal cartilage. METHODS: Based on the actual length of the eighth costal cartilage in microtia children, there are 2 methods to fabricate auricular framework. In method I, the eighth costal cartilage was divided into 2 parts. Part A was used to fashion the helix, while part B was used to protrude the antihelix, superior, and inferior crus. The seventh rib was used to form the main body and the sixth rib was used to form the base of the framework. In method II, the seventh costal cartilage was used to fashion the helix and extrude the antihelix, superior, and inferior crus as method I did. The sixth rib was used to form the main body and the eighth rib was used to form the base of the framework. RESULTS: A total of 68 microtia children underwent auricular reconstruction adopting the modified techniques between 2015 and 2016. The great majority of patients (66 patients) were satisfied with the reconstructed ears. Two patients were relatively satisfied with the reconstructed ears. Three cases have been selected to illustrate the favorable result achieved. They revealed that the helix, antihelix, superior crus, and inferior crus all appeared distinct and presented a favorable result of the contour of the reconstructed auricle. CONCLUSIONS: Based on different lengths of eighth costal cartilage in children, different methods of fabricating ear framework make full use of the autogenous costal cartilage and elevate anatomical details, demonstrating that personalized treatment is necessary.
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Microtia Congénita/cirugía , Cartílago Costal/trasplante , Niño , Pabellón Auricular/cirugía , Cartílago Auricular/cirugía , Oído Externo/cirugía , Humanos , Masculino , Satisfacción Personal , Procedimientos de Cirugía Plástica/métodos , Costillas/cirugíaRESUMEN
PURPOSE: Medial closing-wedge distal femoral osteotomy (MCWDFO) was used to treat valgus knee malalignment combined with lateral compartment disease. The clinical outcome of the osteotomy depends on the accurate correction of valgus malalignment. The aim of this study was to evaluate the accuracy of a MCWDFO assisted by three-dimensional (3D)-printed cutting guides and locking guides. PATIENTS AND METHODS: Thirty-three consecutive patients (33 knees) were operated on using the same MCWDFO. 3D-printed cutting guides and locking guides were used to locate the osteotomy cut plane and to facilitate closing the wedge in 12 patients (3D-guide group). Another 21 patients (conventional group) underwent MCWDFO following the conventional technique. The desired correction was defined as a weight-bearing line (WBL) coordinate 50% of the width of the tibial plateau from the medial tibial margin. The deviation between the planned and executed WBL coordinate, surgical time and fluoroscopic time were compared. RESULTS: The mean deviation between the planned and executed WBL coordinate was 4.9% in the 3D-guide group and 7.6% in the conventional group (P = 0.024). Shorter surgical time was found in the 3D-guide group (mean, 77.7 minutes vs. mean, 96.5 minutes; P < 0.001), while the mean number of intra-operative fluoroscopic images was 6.1, compared with 34.7 in the conventional group (P < 0.001). CONCLUSION: The use of 3D-printed cutting guides and locking guides can increase the precision of the MCWDFO in patients with lateral compartment disease and valgus deformity, making our surgery more efficiency and occupying less fluoroscopic time.
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Desviación Ósea/cirugía , Fémur/cirugía , Genu Valgum/cirugía , Osteoartritis de la Rodilla/cirugía , Osteotomía/instrumentación , Impresión Tridimensional , Adulto , Femenino , Humanos , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Osteotomía/métodosRESUMEN
Circular RNAs (circRNAs) are widespread and diverse endogenous RNAs distinct from traditional linear RNAs, which may regulate gene expression in eukaryotes. However, the function of human circRNAs, including their potential role in lung cancer, remains largely unknown. We screened the circRNA circ0006916, which was evidently down-regulated in 16HBE-T cells (anti-benzopyrene-trans-7, 8-dihydrodiol-9, 10-epoxide-transformed human bronchial epithelial cells), and in A549 and H460 cell lines. Silencing of circ0006916, but not its parental gene homer scaffolding protein 1 (HOMER1), promoted cell proliferation via speeding up the cell cycle process rather than by inhibiting apoptosis; conversely, overexpression of circ0006916 had the opposite effect. Luciferase-screening assay indicated that circ0006916 bound to miR-522-3p and inhibited pleckstrin homology domain and leucine rich repeat protein phosphatase 1 (PHLPP1) activity. We also explored the effect of the RNA-binding protein trinucleotide repeat-containing 6A (TNRC6A) on circ0006916 production. Circ0006916 expression was decreased after silencing TNRC6A. TNRC6A bound to the intron regions around the circRNA-forming exons of circ0006916, as shown by RNA immunoprecipitation assay combined with sequencing analysis. The association of circ0006916 with TNRC6A was further verified by RNA pull-down assays. We then constructed a carrier and confirmed that TNRC6A binding to the flanked intron region of circ0006916 was necessary for generation of circ0006916. These results demonstrate that TNRC6A regulates the biogenesis of the circRNA circ0006916, which has a regulatory role in cell growth.
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Autoantígenos/metabolismo , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Proteínas de Unión al ARN/metabolismo , ARN/metabolismo , Células A549 , Autoantígenos/genética , Silenciador del Gen , Proteínas de Andamiaje Homer/genética , Humanos , Neoplasias Pulmonares/patología , MicroARNs/metabolismo , Proteínas Nucleares/genética , Fosfoproteínas Fosfatasas/genética , ARN/genética , ARN Circular , Proteínas de Unión al ARN/genéticaRESUMEN
Previously, double helix nanowire was reported by coating Pd/Pt/Au onto Au-Ag alloy nanowire. Here, straight oleylamine-stabilized ultrathin Au nanowires with single crystalline fcc lattice are surprisingly converted into double helix helices upon reacting with Ag in tetrahydrofuran (THF). The obtained Au-Ag helical nanowires contain lattice distinctively different from the fcc lattice and are different in many aspects with the previous system. The discovery may expand the scope of nanoscale double helix formation and the understanding of lattice transformation among ultrafine nanostructures.
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Resistance to trastuzumab, which specifically target HER2-positive breast and gastric cancer, can develop ultimately in cancer patients. However, the underlying mechanisms of resistance in gastric cancer have not been fully elucidated. Here, we established trastuzumab-resistant MKN45 and NCI N87 gastric cancer sublines from their parental cells. The resistant cells exhibited characteristics of epithelial-mesenchymal transition (EMT) and acquired higher migratory and invasive capacities. To exploit the activated pathways and develop new strategies to overcome trastuzumab resistance, we investigated MKN45 and MKN45/R cells via label-free quantitative proteomics, and found pathways that were altered significantly in MKN45/R cells, with the Wnt/ß-catenin pathway being the most significant. We further confirmed the activation of this pathway by detecting its key molecules in MKN45/R and NCI N87/R cells via Western blot, in which Wnt3A, FZD6, and CTNNB1 increased, whereas GSK-3ß decreased, manifesting the activation of the Wnt/&-catenin pathway. Correspondingly, inhibition of Wnt/ß-catenin pathway by ICG-001, a specific Wnt/&-catenin inhibitor, preferentially reduced proliferation and invasion of trastuzumab-resistant cells and reversed EMT. Concurringly, CTNNB1 knockdown in stable cell lines potently sensitized cells to trastuzumab and induced more apoptosis. Taken together, our study demonstrates that the Wnt/ß-catenin pathway mediates trastuzumab resistance, and the combination of Wnt/ß-catenin inhibitors with trastuzumab may be an effective treatment option.
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Antineoplásicos Inmunológicos/farmacología , Resistencia a Antineoplásicos , Proteómica , Neoplasias Gástricas/tratamiento farmacológico , Trastuzumab/farmacología , Vía de Señalización Wnt/efectos de los fármacos , Antineoplásicos Inmunológicos/uso terapéutico , Apoptosis/efectos de los fármacos , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Invasividad Neoplásica , Pirimidinonas/farmacología , Trastuzumab/uso terapéuticoRESUMEN
Lead is a metal that has toxic effects on the developing nervous system. However, the mechanisms underlying lead-induced neurotoxicity are not well understood. Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation, but few studies have examined the function of ncRNAs in lead-induced neurotoxicity. We addressed this in the present study by evaluating the functions of a long non-coding RNA (named lncRpa) and a circular RNA (named circRar1) in a mouse model of lead-induced neurotoxicity. High-throughput RNA sequencing showed that both lncRpa and circRar1 promoted neuronal apoptosis. We also found that lncRpa and circRar1 induced the upregulation of apoptosis-associated factors caspase8 and p38 at the mRNA and protein levels via modulation of their common target microRNA miR-671. This is the first report of a regulatory interaction among a lncRNA, circRNA, and miRNA mediating neuronal apoptosis in response to lead toxicity.
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Apoptosis/efectos de los fármacos , Neuronas/efectos de los fármacos , Síndromes de Neurotoxicidad/etiología , Compuestos Organometálicos/toxicidad , Animales , Apoptosis/genética , Caspasa 8/genética , Línea Celular Tumoral , Modelos Animales de Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Ratones , MicroARNs/genética , Neuroblastoma/genética , Síndromes de Neurotoxicidad/genética , ARN/genética , ARN Circular , ARN Largo no Codificante/genética , Regulación hacia Arriba/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genéticaRESUMEN
A photoresponsive amphiphilic gold nanoparticle (AuNP) is achieved through the decoration of AuNP with hydrophilic poly(ethylene glycol) (PEG) and hydrophobic photoresponsive polymethacrylate containing spiropyran units (PSPMA). Owing to the photoresponsive property of spiropyran units, the amphiphilic AuNPs can easily achieve the controllable assembly/disassembly behaviors under the trigger by light. Under visible light, spiropyran units provide weak intermolecular interactions between neighbored AuNPs, leading to isolated AuNPs in the solution. While under UV light irradiation, spiropyran units in the polymer brushes transform into merocyanine isomer with conjugated structure and zwitterionic state, promoting the integration of adjacent AuNPs through π-π stacking and electrostatic attractions, further leading to the formation of Au oligomers. The smart reversible AuNP oligomers exhibited switchable plasmonic coupling for tuning surface-enhanced Raman scattering (SERS) activity, which is promising for the application of SERS based sensors and optical imaging.
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Synchrotron radiation nanoscale computed tomography (SR nano-CT) is a powerful analysis tool and can be used to perform chemical identification, mapping, or speciation of carbon and other elements together with X-ray fluorescence and X-ray absorption near edge structure (XANES) imaging. In practical applications, there are often challenges for SR nano-CT due to the misaligned geometry caused by the sample stage axial vibration. It occurs quite frequently because of experimental constraints from the mechanical error of manufacturing and assembly and the thermal expansion during the time-consuming scanning. The axial vibration will lead to the structure overlap among neighboring layers and degrade imaging results by imposing artifacts into the nano-CT images. It becomes worse for samples with complicated axial structure. In this work, we analyze the influence of axial vibration on nano-CT image by partial derivative. Then, an axial vibration calibration method for SR nano-CT is developed and investigated. It is based on the cross correlation of plane integral curves of the sample at different view angles. This work comprises a numerical study of the method and its experimental verification using a dataset measured with the full-field transmission X-ray microscope nano-CT setup at the beamline 4W1A of the Beijing Synchrotron Radiation Facility. The results demonstrate that the presented method can handle the stage axial vibration. It can work for random axial vibration and needs neither calibration phantom nor additional calibration scanning. It will be helpful for the development and application of synchrotron radiation nano-CT systems.