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1.
Small ; 20(10): e2306713, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37919863

RESUMO

Luminescent metal clusters have attracted great interest in current research; however, the design synthesis of Al clusters with color-tunable luminescence remains challenging. Herein, an [Al8 (OH)8 (NA)16 ] (Al8 , HNA = nicotinic acid) molecular cluster with dual luminescence properties of fluorescence and room-temperature phosphorescence (RTP) is synthesized by choosing HNA ligand as phosphor. Its prompt photoluminescence (PL) spectrum exhibits approximately white light emission at room temperature. Considering that halogen atoms can be used to regulate the RTP property by balancing the singlet and triplet excitons, different CdX2 (X- = Cl- , Br- , I- ) are introduced into the reactive system of the Al8 cluster, and three new Al8 cluster-based metal-organic frameworks, {[Al8 Cd3 Cl5 (OH)8 (NA)17 H2 O]·2HNA}n (CdCl2 -Al8 ), {[Al8 Cd4 Br7 (OH)8 (NA)16 CH3 CN]·NA·HNA}n (CdBr2 -Al8 ) and {[Al8 Cd8 I16 (OH)8 (NA)16 ]}n (CdI2 -Al8 ) are successfully obtained. They realize the color tunability from blue to yellow at room temperature. The origination of fluorescence and phosphorescence has also been illustrated by structure-property analysis and theoretical calculation. This work provides new insights into the design of multicolor luminescent metal cluster-based materials and develops advanced photo-functional materials for multicolor display, anti-counterfeiting, and encryption applications.

2.
Bioorg Chem ; 144: 107166, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38308998

RESUMO

Twelve phthalideisoquinoline hemiacetal alkaloids including eight new ones (1-8) and one natural alkaloid characterized by an aziridine moiety with unassigned NMR data (9), were isolated and identified from the bulbs of Corydalis decumbens. Their structures were established by comprehensive analyses of HRESIMS, NMR, X-ray crystallography, and ECD analyses. The unambiguously established structures of the phthalideisoquinoline hemiacetal alkaloids indicated that the absolute configurations of C-1, C-9, and C-7' were confusable only relied on coupling constants. A summary of their ECD spectra was concluded and provided an insight for C-1, C-9, and C-7' absolute configuration assignment. These new compounds were evaluated to induce autophagy flux through flow cytometry analysis. Moreover, compounds 2 and 6 could significantly induce autophagy and inhibit Tau pathology by AMPK-ULK1 pathway activation, which provided an avenue for anti-AD lead compounds discovery.


Assuntos
Alcaloides , Corydalis , Corydalis/química , Proteínas Quinases Ativadas por AMP/metabolismo , Alcaloides/química , Espectroscopia de Ressonância Magnética , Autofagia
3.
Environ Geochem Health ; 46(8): 270, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954122

RESUMO

Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with 135Cs at approximately 2.3 million years and 87Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (Igeo), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.


Assuntos
Radioisótopos de Césio , Mineração , Poluentes Radioativos do Solo , Medição de Risco , China , Poluentes Radioativos do Solo/análise , Radioisótopos de Césio/análise , Humanos , Radioisótopos de Estrôncio/análise , Césio/análise , Cidades , Solo/química , Método de Monte Carlo , Monitoramento de Radiação
4.
Yi Chuan ; 46(3): 209-218, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38632099

RESUMO

Long interspersed elements-1(LINE-1) is the only autonomous transposon in human genome,and its retrotransposition results in change of cellular genome structure and function, leading occurrence of various severe diseases. As a central key intermediated component during life cycle of LINE-1 retrotransposition, the host modification of LINE-1 mRNA affects the LINE-1 transposition directly. N6-adenosine methylation(m6A), the most abundant epigenetic modification on eukaryotic RNA, is dynamically reversible. m6A modification is also found on LINE-1 mRNA, and it participants regulation of the whole LINE-1 replication cycle, with affecting LINE-1 retrotransposition as well as its adjacent genes expression, followed by influencing genomic stability, cellular self-renewal, and differentiation potential, which plays important roles in human development and diseases. In this review, we summarize the research progress in LINE-1 m6A modification, including its modification positions, patterns and related mechanisms, hoping to provide a new sight on the mechanism research and treatment of related diseases.


Assuntos
Adenosina/análogos & derivados , Genoma Humano , RNA , Humanos , Metilação , RNA/metabolismo , RNA Mensageiro/genética
5.
Opt Lett ; 48(1): 81-84, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36563374

RESUMO

Bolometers based on graphene have demonstrated outstanding performance with high sensitivity and short response time. In situ adjustment of bolometers is very important in various applications, but it is still difficult to implement in many systems. Here we propose a gate-tunable bolometer based on two strongly coupled graphene nanomechanical resonators. Both resonators are exposed to the same light field, and we can measure the properties of one bolometer by directly tracking the resonance frequency shifts, and indirectly measure the other bolometer through mechanical coupling. We find that the sensitivity and the response bandwidth of both bolometers can be independently adjusted by tuning the corresponding gate voltages. Moreover, the properties of the indirectly measured bolometer show a dependence on the coupling between the two resonators, with other parameters being fixed. Our method has the potential to optimize the design of large-scale bolometer arrays, and open new horizons in infrared/terahertz astronomy and communication systems.

6.
Inorg Chem ; 62(6): 2617-2624, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36716134

RESUMO

Metallic clusters, assembled by functional motifs, possess the attribute of regulating the properties by changing inorganic and organic components. In this work, a series of aluminum-oxo clusters, [Al6O(dmp)4(Hdmp)2]·2iPrOH [Al6-1, H3dmp = 2,2-bis(hydroxymethyl)propionic acid], [Al6(H2thmmg)6]·2DMF·2H2O [Al6-2, H5thmmg = N-tris(hydroxymethyl)methylglycine], [Al8(OH)4(NAP-OH)12(MeO)7(MeOH)]Cl·7MeCN·3MeOH (Al8, HNAP-OH = 3-hydroxy-2-naphthoic acid), and [Al10(NA)10(MeO)20] (Al10, HNA = nicotinic acid), were obtained based on different carboxylic acids, realizing metallic ring size enlargement from 5.91 to 9.32 Å. They all exhibit good chemical stability. Importantly, the Al8 cluster displays obvious photochromic behavior from pale yellow to orange yellow, originating from the generation of photoinduced radicals in the metal-assisted ligand-ligand electron transfer process of 3-hydroxy-2-naphthoic acid (HNAP-OH). This work enriches the metal ring cluster chemistry and reports the example of the aluminum-oxo cluster-based photochromic material, developing a novel system of photochromic materials.

7.
Environ Toxicol ; 38(4): 727-742, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36515635

RESUMO

Cyfluthrin is widely used in the field of sanitary pest control by its wide insecticidal spectrum, high efficiency and low toxicity, low residue, and good biodegradability. But, as a double-edged sword, a large amount of cyfluthrin remains are still in the environment. The residual cyfluthrin is absorbed into the food chain through vegetation and then poses a risk to soil organisms and human health. Several studies have suggested that cyfluthrin is one of the main factors causing testicular damage, but the mechanism remains unclear. In this study, we established in vivo and in vitro models of testicular injury in rats and GC-2 cells exposed to cyfluthrin to explore whether stimulator of interferon genes (STING) gene mediates the regulation of AMPK/mTOR/p70S6K autophagy pathway, which lays a foundation for further study of the mechanism of testicular injury induced by cyfluthrin. The results showed that the activity of super oxide dismutase in testis decreased and the activity of malonic dialdehyde increased with the increase of concentration in vivo and in vitro. At the same time, the levels of mitochondrial damage and inflammation in the testis also increased, which further activated autophagy. In this process, the increased level of inflammation is related to the increased expression of STING gene, and AMPK/mTOR/p70S6K autophagy pathway is also involved. To sum up, cyfluthrin has certain reproductive toxicity, and long-term exposure can induce testicular cell damage. STING gene can participate in cyfluthrin-induced testicular injury through AMPK/mTOR/P70S6K autophagy pathway.


Assuntos
Proteínas Quinases Ativadas por AMP , Transdução de Sinais , Masculino , Ratos , Humanos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Interferons
8.
Angew Chem Int Ed Engl ; 62(14): e202218669, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36762956

RESUMO

Proton transfer is crucial for electrocatalysis. Accumulating cations at electrochemical interfaces can alter the proton transfer rate and then tune electrocatalytic performance. However, the mechanism for regulating proton transfer remains ambiguous. Here, we quantify the cation effect on proton diffusion in solution by hydrogen evolution on microelectrodes, revealing the rate can be suppressed by more than 10 times. Different from the prevalent opinions that proton transport is slowed down by modified electric field, we found water structure imposes a more evident effect on kinetics. FTIR test and path integral molecular dynamics simulation indicate that proton prefers to wander within the hydration shell of cations rather than to hop rapidly along water wires. Low connectivity of water networks disrupted by cations corrupts the fast-moving path in bulk water. This study highlights the promising way for regulating proton kinetics via a modified water structure.

9.
J Appl Toxicol ; 42(3): 475-489, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34561900

RESUMO

Aflatoxin is a secondary metabolite secreted by Aspergillus flavus, parasitic Aspergillus, and other fungi through the polyketone pathway, and it can be detected in many foods. Aflatoxin has strong toxicity and carcinogenicity, and many studies have shown that aflatoxin is highly associated with liver cancer. In the present study, malignant transformation of L02 cells was induced by aflatoxin B1 (AFB1), and the gene expression, miRNA expression, and methylation level were detected by high-throughput sequencing. The gene and miRNA expression results showed that 2547 genes and 315 miRNAs were changed in the AFB1-treated group compared with the DMSO group. Among them, RSAD2 and SCIN were significantly upregulated, whereas TRAPPC3L and UBE2L6 were significantly downregulated. Has-miR-33b-3p was significantly upregulated, whereas Has-miR-3613-5p was significantly downregulated. The methylation results showed that 2832 CpG sites were methylated on the promoter or coding DNA sequence (CDS) of the gene, whereas the expression of DNMT3a and DNMT3b was significantly upregulated. Moreover, hypermethylation occurred in TRAPPC3L, CDH13, and SPINK13. The results of GO and KEGG pathway analyses showed that significantly changed genes and miRNAs were mainly involved in tumor formation, proliferation, invasion, and migration. The results of network map analysis showed that Hsa-miR-3613-5p, Hsa-miR-615-5p, Hsa-miR-615-3p, and Hsa-miR-3158-3p were the key miRNAs for malignant transformation of L02 cells induced by AFB1. In addition, the expression of ONECUT2, RAP1GAP2, and FSTL4 was regulated by DNA methylation and miRNAs. These results suggested that the gene expression network regulated by DNA methylation and miRNAs may play a vital role in AFB1-induced hepatocellular carcinoma.


Assuntos
Aflatoxina B1/toxicidade , Metilação de DNA , Redes Reguladoras de Genes/efeitos dos fármacos , MicroRNAs/genética , Linhagem Celular , Metilação de DNA/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/fisiologia
10.
Magn Reson Chem ; 60(1): 104-112, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34212405

RESUMO

The local structural, electronic, optical, and electron paramagnetic resonance (EPR) properties are uniformly studied for Cu2+ -doped rutile (TiO2 ) crystals by using the density functional theory (DFT) calculations. The local cation-oxygen bond lengths and planar bond angle, band gap, Mulliken charge and overlapping population, density of state (DOS), and UV-Vis absorption spectra are calculated for pure and copper-doped rutile. The smaller overlapping population of Cu-O bonds in the doped system than Ti-O bonds in pure rutile reflects weaker orbital admixtures or covalency of the former. Compared with pure rutile, Cu2+ doping leads to significant redshift of the UV-Vis absorption band and the narrow impurity band in visible and near-infrared regions arising from the Cu2+ d-d transitions and narrowing of the band gap by about 0.636 eV, possibly suggesting enhancement of visible light activity. The Cu dopant induces a spin magnetic moment of 0.74 µB for the doped rutile. The calculated UV-Vis absorption spectra and spin Hamiltonian parameters for copper-doped rutile show reasonable agreement with the experimental data and some improvement related to the previous perturbation formula calculations. Present systematic studies would be helpful to understand the mechanisms of the enhancement in the optical and magnetic properties of this material with transition-metal (especially Cu2+ ) dopants.

11.
Angew Chem Int Ed Engl ; 61(36): e202208473, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-35830204

RESUMO

Herein, we report the development of new Co complexes that have cyclopropane-based diphosphine ligands and can catalyze highly chemo-, regio-, and stereoselective hydroboration reactions of unsymmetrical internal alkynes. These reactions exhibited unusual regioselectivity: specifically, reactions of aryl alkyl internal alkynes showed excellent cis-ß-addition selectivity, and reactions of dialkyl internal alkynes gave excellent cis-α-addition selectivity. Highly regioselective hydroboration of unsymmetrical dialkyl internal alkynes cannot be achieved by other known methods. The reactions described herein are highly synthetically useful, particularly for the stereoselective synthesis of trisubstituted alkenylborates and alkenes. Mechanistic studies indicate that a CoI -H species is a plausible active catalyst and the rigid structure of the cyclopropane skeleton of the ligands and the crowded reaction pocket were responsible for the unprecedented regioselectivity.

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(1): 33-40, 2022 Jan 15.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-35177173

RESUMO

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS: There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.


Assuntos
Displasia Broncopulmonar , Síndrome do Desconforto Respiratório do Recém-Nascido , Displasia Broncopulmonar/epidemiologia , Feminino , Idade Gestacional , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Gravidez , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
13.
Oncologist ; 26(8): 649-e1313, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33749934

RESUMO

LESSONS LEARNED: MET overexpression is uncommon, and positive MET immunohistochemistry (1+/2+) was an independent positive prognostic factor for response rate and progression-free survival. Whether MET overexpression can be considered a potential predictive biomarker and be used as an inclusion criterion is worth investigating in a future study. BACKGROUND: Metatinib tromethamine tablet (metatinib) is a small molecule receptor kinase inhibitor targeting both c-MET and vascular endothelial growth factor receptor 2. This phase I trial aimed to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), pharmacokinetics, safety, and efficacy of metatinib in patients with advanced solid tumors. METHODS: Eligible patients received a single dose of metatinib in a 3 + 3 dose-escalation design with dose levels of 25-800 mg/day, after a single dose on day 1, then 2 days off, and then a multidose schedule of once-daily doses for 25 consecutive days (days 4-28). Primary endpoints were MTD and safety; secondary and exploratory endpoints included pharmacokinetics (PK), efficacy, and biomarkers. RESULTS: Eighteen patients (including nine patients with hepatocellular carcinoma [HCC]) received at least one dose of study drug (one patient quit the study without continuous multiple-dose administration after receiving a single dose of metatinib). Hand-foot skin reaction, diarrhea, and liver dysfunction were the DLTs, and 200 mg/day was the MTD. The most common treatment-related adverse events (TRAEs) were skin toxicity (50%), diarrhea (33.3%), and liver dysfunction (27.8%). Three patients (only one of six in the 200 mg/day cohort; the other two in the 300 mg/day cohort) experienced severe TRAEs: one patient with severe liver dysfunction and two patients with severe liver dysfunction and skin toxicity, respectively. Pharmacokinetics assessment indicated that metatinib was rapidly absorbed and metabolized to the formation of reactive metabolite, SCR-1510, after single-dose administration. The mean time taken to achieve maximum concentration and terminal elimination half-life of SCR-1510 was approximately 2.0-3.0 hours and ranged from 8 to 14 hours. Two patients had partial responses. The objective response rate and disease control rate (DCR) were 11.1% and 61.1%, respectively. The median progression-free survival (PFS) was 2.75 months. CONCLUSION: Metatinib administration of 200 mg/day was well tolerated, safe, and effective. The MTD was 200 mg/day, which should be recommended in further investigations.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Comprimidos , Trometamina , Fator A de Crescimento do Endotélio Vascular
14.
BMC Microbiol ; 21(1): 68, 2021 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-33639835

RESUMO

BACKGROUND: The genus Lactobacillus is an important component of the gastrointestinal tract of human and animals and commonly considered as probiotic. L. taiwanensis has long been proposed to be a probiotic whereas understanding on this species is still in its infancy. Genomic information of L. taiwanensis is fairly limited. Extensive characterization of its beneficial traits is needed. RESULTS: A new strain CLG01 of L. taiwanensis was isolated from mouse Peyer's patches. We established its probiotic profile through in vitro experiments. Complete genome of this strain was also sequenced and analyzed. L. taiwanensis CLG01 showed robust tolerance to acid and a degree of tolerance to bile salt with a promising antibacterial activity against a broad spectrum of pathogenic bacteria. In vitro treatment of mouse RAW 264.7 macrophage cells with heat-killed bacteria and bacterial supernatant of L. taiwanensis CLG01 resulted in enhancement of immune responses and upregulated expression of TNF-α and IL-6. The strain CLG01 also increased the IL-10 production of macrophages when co-treated with lipopolysaccharide (LPS). Complete genome of L. taiwanensis CLG01 contained a 1.89 Mb chromosome and two plasmids. Further genomic analysis revealed the presence of genes related to its resistance to different stresses and the beneficial effects mentioned above. Moreover, biosynthetic gene clusters (BGCs) encoding antimicrobial peptides, like bacteriocin, linear azol(in)e-containing peptide (LAP) and lanthipeptide, were also identified in the genome of L. taiwanensis CLG01. CONCLUSIONS: L. taiwanensis CLG01, isolated from mouse Peyer's patches, is the first L. taiwanensis strain with both phenotypes and genotypes systematically studied. These preliminary data confirmed the role of L. taiwanensis CLG01 as a potential probiotic candidate with antibacterial and immunomodulatory activity, which provide insight for further investigation to this species.


Assuntos
Antibacterianos , Genoma Bacteriano/genética , Fatores Imunológicos , Lactobacillus/genética , Lactobacillus/metabolismo , Nódulos Linfáticos Agregados/microbiologia , Probióticos , Animais , Antibacterianos/isolamento & purificação , Células Cultivadas , Regulação da Expressão Gênica/imunologia , Fatores Imunológicos/isolamento & purificação , Interleucina-6/genética , Camundongos , Fator de Necrose Tumoral alfa/genética
15.
J Bone Miner Metab ; 39(2): 237-244, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32876727

RESUMO

INTRODUCTION: Bone turnover markers (BTMs) can be used to monitor bone metabolism, while the actual clinical changing in hip fracture had not been certified to evaluate the changes of BTMs during the healing process after surgery of elderly hip fractures; and to get the effects of operation type, gender, serum 25(OH)D level, and age on bone turnover markers. MATERIALS AND METHODS: A total of 100 elderly cases with hip fracture were selected, including 74 females and 26 males, and the patients were followed to 180-230 days after surgery. Serum levels of N-propeptide of type 1 collagen (P1NP), C-terminal crosslinking telopeptides of type 1 collagen (CTX), Osteocalcin (OC), and 25 hydroxy vitamin D (25OHD) were investigated. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry (DXA). RESULTS: (1) P1NP and CTX showed peak time at 30-60 days after operation, while OC keep going even at 180-230 days; P1NP showed less than 4 times elevation during healing, CTX and OC only had less than 2 times rise. (2) Female had higher serum CTX and OC than male, intramedullary nailing for intertrochanteric fracture patients had higher P1NP than hip replacement for femoral neck fracture patients, and both the degrees of increase were less than 50%. (3) Serum average 25(OH)D level had no effect on BTMs during the fracture healing; different from the young old (65-84 years), serum OC level of eldest older patients(≥ 85 years) decreased early in the process of fracture healing. CONCLUSIONS: BTMs reached the peak level in 30-60 days after surgery, P1NP showed less than 4 times elevation, and CTX and OC had less than 2 times rise. It was not necessary to take gender into account when observing P1NP, and it was not necessary to take fracture and operation type into account when observing CTX and OC.


Assuntos
Biomarcadores/sangue , Remodelação Óssea , Fraturas do Quadril/sangue , Fraturas do Quadril/cirurgia , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Colágeno Tipo I/sangue , Feminino , Seguimentos , Fraturas do Quadril/fisiopatologia , Humanos , Masculino , Osteocalcina/sangue , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue
16.
Bioorg Med Chem ; 39: 116166, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33910157

RESUMO

Constitutive activation of Hedgehog (Hh) pathway is intimately related with the occurrence and development of several malignancies, such as medulloblastoma (MB) and other tumors. Therefore, small molecular inhibitors of Hh pathway are urgently needed. In this study, three new steroidal alkaloids, ⊿5 (20R, 24R) 23-oxo-24-methylsolacongetidine, ⊿5 (20S, 24R) 23-oxo-24-methylsolacongetidine and veralinine 3-O-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-D-glucopyranoside, together with six known alkaloids, 20-epi-verazine, verazine, protoverine 15-(l)-2'-methylbutyrate, jervine, veramarine and ß1-chaconine, were isolated and determined from Veratrum grandiflorum Loes. The dual-luciferase bioassay indicated that all compounds exhibited significant inhibitions of Hh pathway with IC50 values of 0.72-14.31 µM against Shh-LIGHT 2 cells. To determine whether these Hh pathway inhibitors act with the Smoothened (Smo) protein, which is an important oncoprotein and target for this pathway, BODIPY-cyclopamine (BC) competitive binding assay was preferentially performed. Compared with BC alone, all compounds obviously reduced the fluorescence intensities of BC binding with Smo in Smo-overexpression HEK293T cells through fluorescence microscope and flow cytometer. By directly interacting with Smo, it revealed that they were actually novel natural Smo inhibitors. Then, their anti-tumor effects were investigated against the human MB cell line DAOY, which is a typical pediatric brain tumor cells line with highly expressed Hh pathway. Interestingly, most of compounds had slight proliferation inhibitions on DAOY cells after treatment for 24 h same as vismodegib, while ß1-chaconine showed the strongest inhibitory effect on the growth of DAOY with IC50 value of 5.35 µM. In conclusion, our studies valuably provide several novel natural Smo inhibitors for potential targeting treatment of Hh-dependent tumors.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Proliferação de Células/efeitos dos fármacos , Meduloblastoma/patologia , Receptor Smoothened/antagonistas & inibidores , Esteroides/química , Veratrum/química , Alcaloides/química , Linhagem Celular Tumoral , Células HEK293 , Humanos , Estrutura Molecular , Análise Espectral/métodos
17.
J Chem Phys ; 155(23): 234303, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34937377

RESUMO

It is well known that structure determines property, but obtaining a pair of silver nanoclusters with comparable structures to understand the structure-property relationship is a very challenging task. A new 60-nuclei silver nanocluster (SD/Ag60a) protected by a mixed-ligand shell of tBuS- and o-CH3OPhCOO- was obtained and characterized. Single crystal x-ray diffraction reveals that SD/Ag60a has an identical metal nuclearity and core-shell structural type to SD/Ag1 previously reported by our group, whereas the compositions of the core and shell have undergone a rearrangement from an Ag12 cuboctahedron core and an Ag48 rhombicuboctahedron shell in SD/Ag1 to an Ag14 rhombic dodecahedron core and an oval Ag46 shell in SD/Ag60a. The core enlargement from Ag12 to Ag14 originates from the replacement of two S2- in Ag12S15 by two Ag+, which gives a new Ag14S13 core. This result indicates that the metal frameworks of silver nanoclusters have some extent flexibility despite the same nuclearity, which can be influenced by ligands, solvents, anion templates, and others in the embryonic stage of the assembly. Interestingly, different core-shell architectures of Ag60 nanoclusters also significantly endow the different optical absorption bands, photocurrent-generating properties, and luminesecent behaviors. This work not only realizes the regulation of the core-shell structure of silver nanoclusters with the same nuclearity but also provides a comparable model for investigating the relationship of structure-photoelectric properties.

18.
Magn Reson Chem ; 59(4): 439-446, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33084084

RESUMO

The local structure, d-d transition band, and spin Hamiltonian parameters (SHPs) are theoretically studied for the V4+ probe in Na2 O-PbO-Bi2 O3 -SiO2 (NPBS) glass ceramics containing V2 O5 dopant with various concentration x (0 ≤ x ≤ 5 mol%) by using the perturbation formulas of the SHPs for tetragonally compressed octahedral 3d1 clusters. The first decreasing (or increasing) and then increasing (or decreasing) d-d transition band (= 10 Dq ) and hyperfine structure constants A// and A⊥ (or g factors g// and g⊥ ) with x can be suitably simulated with the similarly varying Fourier type concentration functions of cubic field parameter Dq , covalence factor N, core polarization constant κ, and reduction factor H (or relative tetragonal compression ratio ρ), with the minima (or maxima) at the middle concentration x = 3 mol%, respectively. The above concentration variations of SHPs and the related quantities may originate from the modifications of local crystal field strength, tetragonal compression, and electron cloud distribution near the impurity V4+ with x, corresponding to the highest [V4+ ]/[V5+ ] ratio at 3 mol%. Present studies would be helpful to explore novel sodium lead bismuth silicate glass ceramics by modifying the concentration of V2 O5 dopant.

19.
Aust Crit Care ; 34(4): 388-394, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33097369

RESUMO

BACKGROUND: Numerous studies have demonstrated the benefits and safety of ultrasound guidance in comparison with conventional palpation for radial artery cannulation in adult patients. However, the current evidence for paediatric patients is not fully understood. OBJECTIVE: The objective of this study was to compare the efficiency and safety of ultrasound guidance with those of traditional palpation for radial artery cannulation in paediatric patients and provide convincing evidence for clinical practice. METHODS: PubMed, Cochrane Library, ClinicalTrials.gov (Min et al-2019, NCT02795468, Anantasit et al-2017, NCT02668471), China National Knowledge Infrastructure, and Wanfang Data were systematically searched from their inception until December 31, 2019, to identify relevant randomised controlled trials. Data were extracted from the included studies independently by two investigators. The primary outcome of interest was the first-attempt success rate. Review Manager Version 5.3 and trial sequential analysis (beta = 0.9) were applied to analyse the collected data. RESULTS: A total of eight randomised controlled trials involving 680 paediatric patients were included in this study. The pooled findings showed that ultrasound-guided radial artery cannulation, in comparison with traditional palpation, can significantly improve the first-attempt success rate (relative risk [RR] = 1.65, 95% confidence interval [CI] = 1.36-2.01, P < 0.00001). Trial sequential analysis indicated that this available evidence was conclusive. Moreover, ultrasound guidance was associated with an increased total success rate (RR = 1.38, 95% CI = 1.15-1.66, P = 0.0004), a decreased mean procedural time (standardised mean difference = -0.89, 95% CI = -1.52 to -0.25, P = 0.006), and incidence of haematoma (RR = 0.19, 95% CI = 0.10-0.35, P < 0.00001). CONCLUSION: Ultrasound-guided radial arterial cannulation in paediatric patients is associated with improved first-attempt success rates, total success rates, and mean procedural time and decreased incidence of haematoma. The current evidence suggests that ultrasound guidance should be the standard of care for radial artery cannulation in clinical practice.


Assuntos
Cateterismo Periférico , Artéria Radial , Adulto , Criança , Humanos , Palpação , Artéria Radial/diagnóstico por imagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Ultrassonografia , Ultrassonografia de Intervenção
20.
Yi Chuan ; 43(6): 571-579, 2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284988

RESUMO

Long interspersed element-1 (LINE-1), which is the only autonomous retrotransposon in human genome, makes up about 17% of the human genome. For LINE-1 retrotransposition may result in genome instability, it was strictly restricted by organisms, and its expression was therefore barely detected in normal somatic cells. However, the expression of LINE-1 is a common phenomenon in most tumor or cancer tissues, suggesting a close relationship between LINE-1 expression and cancer development. Differentially expressed LINE-1 in cancer tissues can be used as a biomarker for tumor diagnosis and an important indicator of prognosis after cancer therapeutics. Meanwhile, the feasibility of LINE-1 as a potential drug target for tumor treatment has also been evaluating and verifying in clinicals. In this review, we introduce the application of LINE-1 as a biomarker in tumor diagnosis and prognostic, as well as the research progress in LINE-1 as potential drug target for tumor treatment, in order to provide some references for clinical application in cancer treatment.


Assuntos
Elementos Nucleotídeos Longos e Dispersos , Neoplasias , Carcinogênese/genética , Transformação Celular Neoplásica , Genoma Humano , Humanos , Elementos Nucleotídeos Longos e Dispersos/genética , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia
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