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1.
Bioorg Chem ; 145: 107214, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38417190

RESUMO

Four new drimane-type sesquiterpenoids and two new nucleoside derivatives (1-6), were isolated from the fungus Helicoma septoconstrictum. Their structures were determined based on the combination of the analysis of their HR-ESI-MS, NMR, ECD calculations data and acid hydrolysis. All the isolated compounds were detected for their bio-activities against MDA-MB-231, A549/DDP, A2780 and HepG2 cell lines. Helicoside C (4) exhibited superior cytotoxicity against the A2780 cell line with IC50 7.5 ± 1.5 µM. The analysis of reactive oxygen species (ROS) revealed that Helicoside C induced an increase in intracellular ROS. Furthermore, the flow cytometry and mitochondrial membrane potential (MMP) analyses unveiled that Helicoside C mediated mitochondrial-dependent apoptosis in A2780 cells. The western blotting test showed that Helicoside C could suppress the STAT3's phosphorylation. These findings offered crucial support for development of H. septoconstrictum and highlighted the potential application of drimane-type sesquiterpenoids in pharmaceuticals.


Assuntos
Ascomicetos , Neoplasias Ovarianas , Sesquiterpenos Policíclicos , Sesquiterpenos , Humanos , Feminino , Linhagem Celular Tumoral , Nucleosídeos , Neoplasias Ovarianas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/química , Ascomicetos/metabolismo , Apoptose
2.
BMC Med Imaging ; 24(1): 178, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030494

RESUMO

OBJECTIVE: To establish a machine learning model based on radiomics and clinical features derived from non-contrast CT to predict futile recanalization (FR) in patients with anterior circulation acute ischemic stroke (AIS) undergoing endovascular treatment. METHODS: A retrospective analysis was conducted on 174 patients who underwent endovascular treatment for acute anterior circulation ischemic stroke between January 2020 and December 2023. FR was defined as successful recanalization but poor prognosis at 90 days (modified Rankin Scale, mRS 4-6). Radiomic features were extracted from non-contrast CT and selected using the least absolute shrinkage and selection operator (LASSO) regression method. Logistic regression (LR) model was used to build models based on radiomic and clinical features. A radiomics-clinical nomogram model was developed, and the predictive performance of the models was evaluated using area under the curve (AUC), accuracy, sensitivity, and specificity. RESULTS: A total of 174 patients were included. 2016 radiomic features were extracted from non-contrast CT, and 9 features were selected to build the radiomics model. Univariate and stepwise multivariate analyses identified admission NIHSS score, hemorrhagic transformation, NLR, and admission blood glucose as independent factors for building the clinical model. The AUC of the radiomics-clinical nomogram model in the training and testing cohorts were 0.860 (95%CI 0.801-0.919) and 0.775 (95%CI 0.605-0.945), respectively. CONCLUSION: The radiomics-clinical nomogram model based on non-contrast CT demonstrated satisfactory performance in predicting futile recanalization in patients with anterior circulation acute ischemic stroke.


Assuntos
Procedimentos Endovasculares , AVC Isquêmico , Aprendizado de Máquina , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/cirurgia , AVC Isquêmico/terapia , Tomografia Computadorizada por Raios X/métodos , Procedimentos Endovasculares/métodos , Nomogramas , Futilidade Médica , Prognóstico , Radiômica
3.
Proc Natl Acad Sci U S A ; 118(34)2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34417297

RESUMO

Two independent structures of the proton-pumping, respiratory cytochrome bo3 ubiquinol oxidase (cyt bo3 ) have been determined by cryogenic electron microscopy (cryo-EM) in styrene-maleic acid (SMA) copolymer nanodiscs and in membrane scaffold protein (MSP) nanodiscs to 2.55- and 2.19-Å resolution, respectively. The structures include the metal redox centers (heme b, heme o3 , and CuB), the redox-active cross-linked histidine-tyrosine cofactor, and the internal water molecules in the proton-conducting D channel. Each structure also contains one equivalent of ubiquinone-8 (UQ8) in the substrate binding site as well as several phospholipid molecules. The isoprene side chain of UQ8 is clamped within a hydrophobic groove in subunit I by transmembrane helix TM0, which is only present in quinol oxidases and not in the closely related cytochrome c oxidases. Both structures show carbonyl O1 of the UQ8 headgroup hydrogen bonded to D75I and R71I In both structures, residue H98I occupies two conformations. In conformation 1, H98I forms a hydrogen bond with carbonyl O4 of the UQ8 headgroup, but in conformation 2, the imidazole side chain of H98I has flipped to form a hydrogen bond with E14I at the N-terminal end of TM0. We propose that H98I dynamics facilitate proton transfer from ubiquinol to the periplasmic aqueous phase during oxidation of the substrate. Computational studies show that TM0 creates a channel, allowing access of water to the ubiquinol headgroup and to H98I.


Assuntos
Grupo dos Citocromos b/química , Grupo dos Citocromos b/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Heme/metabolismo , Fosfolipídeos/metabolismo , Bombas de Próton , Ubiquinona/metabolismo , Sítios de Ligação , Microscopia Crioeletrônica , Heme/química , Oxirredução , Conformação Proteica
4.
J Basic Microbiol ; 64(1): 68-80, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37717245

RESUMO

Endophytic fungi are an important source of novel antitumor substances. Previously, we isolated an endophytic fungus, Alternaria alstroemeria, from the medicinal plant Artemisia artemisia, whose crude extracts strongly inhibited A549 tumor cells. We obtained a transformant, namely AaLaeAOE26 , which completely loses its antitumor activity due to overexpression of the global regulator AaLaeA. Re-sequencing analysis of the genome revealed that the insertion site was in the noncoding region and did not destroy any other genes. Metabolomics analysis revealed that the level of secondary antitumor metabolic substances was significantly lower in AaLaeAOE26 compared with the wild strain, in particular flavonoids were more downregulated according to the metabolomics analysis. A further comparative transcriptome analysis revealed that a gene encoding FAD-binding domain protein (Fla1) was significantly downregulated. On the other hand, overexpression of AaFla1 led to significant enhancement of antitumor activity against A549 with a sevenfold higher inhibition ratio than the wild strain. At the same time, we also found a significant increase in the accumulation of antitumor metabolites including quercetin, gitogenin, rhodioloside, liensinine, ginsenoside Rg2 and cinobufagin. Our data suggest that the global regulator AaLaeA negatively affects the production of antitumor compounds via controlling the transcription of AaFla1 in endophytic A. alstroemeria.


Assuntos
Alstroemeria , Alternaria , Alternaria/genética , Metabolismo Secundário , Flavonoides/metabolismo , Endófitos
5.
Prep Biochem Biotechnol ; : 1-9, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847777

RESUMO

Background: Recombinant myofibril-bound serine proteinase (rMBSP) was successfully expressed in Pichia pastoris GS115 in our laboratory. However, low production of rMBSP in shake flask constraints further exploration of properties.Methods: A 5-L high cell density fermentation was performed and the fermentation medium was optimized. Response surface methodology (RSM) was used to optimize the culture condition through modeling three selected parameter.Results: Under the optimized culture medium (LBSM, 1% yeast powder and 1% peptone) and culture conditions (induction pH 5.5, temperature 29 °C, time 40 h), the yield of rMBSP was 420 mg/L in a 5-L fermenter, which was a 6-fold increase over thar, expressed in flask cultivation. The desired enzyme was purified by two-step, which yielded a 33.7% recovery of a product that had over 85% purity. The activity of purified rMBSP was significantly inhibited by Ca2+, Mg2+, SDS, guanidine hydrochloeide, acetone, isopropanol, chloroform, n-hexane and n-heptane. Enzymatic analysis revealed a Km of 2.89 ± 0.09 µM and a Vmax of 14.20 ± 0.12 nM•min-1 for rMBSP. LC-MS/MS analysis demonstrated the specific cleavage of bovine serum albumin by rMPSP.Conclusion: These findings suggest that rMPSP has potential as a valuable enzyme for protein science research.

6.
Clin Lab ; 69(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36649509

RESUMO

BACKGROUND: COVID-19 and malaria share some similar symptoms such as fever, difficulty in breathing, fatigue, and headaches of acute onset. With overlapping symptoms and travel history significant for COVID-19 and malaria, healthcare systems and professionals will face a great challenge in the case of COVID-19 and malaria co-infection. METHODS: Here we presented a patient with COVID-19 infection and refractory anemia of unknown reason. A diagnostic test for malaria was later performed. RESULTS: The patient was ultimately diagnosed with COVID-19 and plasmodium falciparum malaria co-infection. He recovered gradually after receiving anti-malaria treatment. CONCLUSIONS: The present case highlights the danger of focusing only on a diagnosis of COVID-19, reminding clinicians to be vigilant about the possibility of co-infections.


Assuntos
Anemia , COVID-19 , Coinfecção , Malária Falciparum , Malária , Humanos , Masculino , Anemia/diagnóstico , Coinfecção/diagnóstico , COVID-19/complicações , População do Leste Asiático , Malária Falciparum/complicações , Malária Falciparum/diagnóstico , Plasmodium falciparum , China
7.
Chem Biodivers ; 20(5): e202300313, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37139628

RESUMO

A new spirostane, namely neohelicomyine B (1), together with six known steroids (2-7) were isolated from the fermentation of fungus Neohelicomyces hyalosporus. The structures of these compounds were elucidated by extensive analyses of spectroscopic methods including 1D and 2D NMR and HR-ESI-MS. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction. The bioactivities of compounds 1-7 were evaluated using cellular assays. Compound 1 displayed moderate cytotoxicity against HepG2 cells (hepatoma cells) with IC50 value of 8.4±2.1 µM. Compound 7 also exhibited cytotoxic activity against HepG2 cells with the IC50 value of 3.0±0.2 µM.


Assuntos
Antineoplásicos , Ascomicetos , Antineoplásicos/química , Esteroides , Espectroscopia de Ressonância Magnética , Estrutura Molecular
8.
Cell Tissue Bank ; 24(1): 181-190, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35794499

RESUMO

The process of generating type I/II collagen scaffolds is fraught with bubble formation, which can interfere with the three-dimensional structure of the scaffold. Herein, we applied low-temperature vacuum freeze-drying to remove mixed air bubbles under negative pressure. Type I and II rubber sponges were acid-solubilized via acid lysis and enzymolysis. Thereafter, vacuum negative pressure was applied to remove bubbles, and the cover glass press method was applied to shape the type I/II original scaffold. Vacuum negative pressure was applied for a second time to remove any residual bubbles. Subsequent application of carbamide/N-hydroxysuccinimide cross-linked the scaffold. The traditional method was used as the control group. The structure and number of residual bubbles and pore sizes of the two scaffolds were compared. Based on the relationship between the pressure and the number of residual bubbles, a curve was created, and the time of ice formation was calculated. The bubble content of the experimental group was significantly lower than that of the control group (P < 0.05). The pore diameter of the type I/II collagen scaffold was higher in the experimental group than in the control group. The time of icing effect of type I and II collagen solution was 136.54 ± 5.26 and 144.40 ± 6.45 s, respectively. The experimental scaffold had a more regular structure with actively proliferating chondrocytes that possessed adherent pseudopodia. The findings indicated that the vacuum negative pressure method did not affect the physical or chemical properties of collagen, and these scaffolds exhibited good biocompatibility with chondrocytes.


Assuntos
Colágeno , Alicerces Teciduais , Alicerces Teciduais/química , Sucção , Colágeno/química , Colágeno Tipo I , Colágeno Tipo II , Engenharia Tecidual/métodos
9.
FASEB J ; 35(1): e21207, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33368572

RESUMO

ß-barrel outer membrane proteins (ß-OMPs) play critical roles in nutrition acquisition, protein import/export, and other fundamental biological processes. The assembly of ß-OMPs in Gram-negative bacteria is mediated by the ß-barrel assembly machinery (BAM) complex, yet its precise mechanism remains elusive. Here, we report two structures of the BAM complex in detergents and in nanodisks, and two crystal structures of the BAM complex with bound substrates. Structural analysis indicates that the membrane compositions surrounding the BAM complex could modulate its overall conformations, indicating low energy barriers between different conformational states and a highly dynamic nature of the BAM complex. Importantly, structures of the BAM complex with bound substrates and the related functional analysis show that the first ß-strand of the BamA ß-barrel (ß1BamA ) in the BAM complex is associated with the last but not the first ß-strand of a ß-OMP substrate via antiparallel ß-strand interactions. These observations are consistent with the ß-signal hypothesis during ß-OMP biogenesis, and suggest that the ß1BamA strand in the BAM complex may interact with the last ß-strand of an incoming ß-OMP substrate upon their release from the chaperone-bound state.


Assuntos
Proteínas da Membrana Bacteriana Externa/química , Aprendizado de Máquina , Conformação Proteica em Folha beta , Domínios Proteicos
10.
J Wound Care ; 31(1): 40-46, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35077212

RESUMO

OBJECTIVE: Diabetic foot ulcers (DFUs) are one of the most serious diabetic consequences, leading to amputations. Various therapies have been used to treat DFUs; however, a combination of negative pressure suction, artificial skin and autogenous skin implantation have never been investigated. This study aimed to evaluate the effectiveness of a novel three-step therapy protocol using negative pressure wound therapy (NPWT), artificial skin and autogenous skin implantation in patients with DFUs. METHOD: At a single tertiary university hospital between 2015 and 2018, the three-step therapy protocol was applied to patients with DFUs and its safety and efficacy was investigated. RESULTS: A total of 21 patients took part in the study. The majority of the patients were female (62%), with a mean age of 65 years and a mean body mass index of 21kg/m2. A third (n=7) of operative sites experienced minor complications, with two requiring re-operation. At a median follow up of 24 months, the average time of complete wound healing was 46 days, and the wound healing rate was 71%. The first-stage wound healing rate was 90%. All patients had achieved remission without any further recurrence of disease. CONCLUSION: This comprehensive surgical technique for managing DFUs achieved a high local cure rate, minimal functional morbidity, and acceptable wound complication rates. The three-step therapy protocol has the potential to promote the healing process of DFUs, which is expected to serve as a new method for the treatment and cure of DFUs.


Assuntos
Diabetes Mellitus , Pé Diabético , Tratamento de Ferimentos com Pressão Negativa , Pele Artificial , Idoso , Amputação Cirúrgica , Pé Diabético/terapia , Feminino , Humanos , Masculino , Cicatrização
11.
J Basic Microbiol ; 62(11): 1402-1414, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36041052

RESUMO

The global regulatory factor LaeA has been shown to be involved in the biosynthesis of secondary metabolites in various fungi. In a previous work, we isolated an endophytic fungus from Artemisia annua, and its extract had a significant inhibitory effect on the A549 cancer cell line. Phylogenetic analysis further identified the strain as Alternaria alstroemeria. Overexpression of AalaeA gene resulted in significantly increased antitumor activity of this strain's extract. The 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay results showed that the inhibition rate of the AalaeAOE29 mutant extract on A549 cancer cells was significantly higher than that of the WT extract, as the IC50 decreased from 195.0 to 107.4 µg/ml, and the total apoptosis rate was enhanced. Overexpression of the AalaeA gene significantly increased the contents of myricetin, geraniol, ergosterol, and 18 other antitumor compounds as determined by metabolomic analysis. Transcriptomic analysis revealed significant changes in 95 genes in the mutant strain, including polyketide synthases, nonribosomal peptide synthases, cytochrome P450s, glycosyltransferases, acetyl-CoA acetyltransferases, and others. These results suggested that AaLaeA mediated the antitumor activity of the metabolites in A. alstroemeria by regulating multiple metabolic pathways.


Assuntos
Alstroemeria , Alternaria , Alternaria/genética , Filogenia , Metabolismo Secundário , Extratos Vegetais , Endófitos/metabolismo
12.
Surg Innov ; 29(5): 652-661, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36113416

RESUMO

Aim. To compare the safety and efficacy of computed tomography (CT)-assisted three-dimensional guiding templates (3DGTs) and free-hand (FH) technique for posterior cervical pedicle screw fixation in cervical spondylotic myelopathy (CSM) treatment. Methods. Thirty-five patients (216 screws) with CSM and developmental cervical stenosis were randomly divided into groups A (FH) and B (3DGTs). All patients underwent modified posterior surgery with cervical pedicle screw insertion (C1-7). Preoperative, postoperative, and intergroup comparisons of efficacy were evaluated using the visual analog scale (VAS), Japanese Orthopaedic Association (JOA), and Short Form 12 (SF-12) scores and JOA score improvement rate. Incidence of intra- and postoperative complications was analyzed. Postoperative cervical spine CT was performed to evaluate (i) the pedicle screws' deviation angle from the optimal path (sagittal deviation, α; coronal deviation angle, ß), screw insertion point's deviation distance (d), and screw accuracy and (ii) the deviation angle and distance of screw entrance point of pedicle screws from the optimal channel. Results. All patients successfully completed the procedures. Groups A and B did not significantly differ in age, sex ratio, body mass index, operative time, or intraoperative blood loss amount. Postoperative VAS, JOA, and SF-12 scores improved in both groups. VAS, JOA, or SF-12 scores did not significantly differ between the 2 groups. The α, ß, and d scores were lower in group B, but accuracy was higher in group B. Conclusions. 3DGTs and FH technique show comparable outcomes with respect to neurological improvement and safety.


Assuntos
Parafusos Pediculares , Humanos , Estudos Retrospectivos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Tomografia Computadorizada por Raios X/métodos , Duração da Cirurgia , Resultado do Tratamento
13.
Int Wound J ; 19(5): 1023-1038, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35266304

RESUMO

The cartilage repair and regeneration show inadequate self-healing capability and have some complications, which are inordinate challenges in clinical therapy. Biopolymeric injectable hydrogels, a prominent type of cell-carrier as well tissue engineering scaffolding materials, establish promising therapeutic potential of stem cell-based cartilage-regeneration treatment. In addition, injectable scaffolding biomaterial should have rapid gelation properties with adequate rheological and mechanical properties. In the present investigation, we developed and fabricated the macromolecular silk fibroin blended with polylysine modified chitosan polymer (SF/PCS) using thermal-sensitive glycerophosphate (GP), which contains effective gelation ability, morphology, porosity and also has enhanced mechanical properties to induce physical applicability, cell proliferation and nutrient exchange in the cell-based treatment. The developed and optimised injectable hydrogel group has good biocompatibility with human fibroblast (L929) cells and bone marrow-derived mesenchymal stem cells (BMSCs). Additionally, it was found that SF/PCS hydrogel group could sustainably release TGF-ß1 and efficiently regulate cartilage-specific and inflammatory-related gene expressions. Finally, the cartilage-regeneration potential of the hydrogel groups embedded with and without BMSCs were evaluated in SD rat models under histopathological analysis, which showed promising cartilage repair. Overall, we conclude that the TGF-ß1-SF/PCS injectable hydrogel demonstrates enhanced in vitro and in vivo tissue regeneration properties, which lead to efficacious therapeutic potential in cartilage regeneration.


Assuntos
Cartilagem Articular , Quitosana , Fibroínas , Nanopartículas , Animais , Células da Medula Óssea/metabolismo , Cartilagem Articular/fisiologia , Fibroínas/metabolismo , Fibroínas/farmacologia , Humanos , Hidrogéis , Ratos , Ratos Sprague-Dawley , Engenharia Tecidual , Alicerces Teciduais , Fator de Crescimento Transformador beta1/metabolismo
14.
Appl Opt ; 60(7): 1982-1986, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33690290

RESUMO

Nanosecond dissipative soliton resonance pulse is a demonstration of an all polarization-maintaining (PM) thulium-doped fiber laser in a nonlinear amplifying loop mirror (NALM)-based figure-eight configuration. Each loop of the apparatus includes a controllable power amplifier. With increased amplifier power, pulse width broadens linearly from 3.6 to 13.5 ns, and maximum single pulse energy can reach 27.5 nJ. Interestingly, the output peak power presents two completely opposite proportional effects in terms of the variation of settings for two amplifiers, respectively. The experimental results show that the NALM loop plays an important role for tunable pulse duration, and the unidirectional ring part makes a significant contribution for power scaling.

15.
Cutan Ocul Toxicol ; 40(3): 221-231, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34003048

RESUMO

INTRODUCTION: Oil body (OB), a subcellular organelle that stores oil in plant seeds, is considered a new transdermal drug delivery system. With the increasing understanding of the OB and its main protein (oleosin), numerous studies have been conducted on OB as "carrier" for the expression of exogenous proteins. In our previous study, oil body fused with aFGF (OLAF) was obtained using a plant oil body expression system that had been preliminarily proven to be effective in accelerating the healing of skin wounds. However, no dermal toxicological information on OLAF is available. OBJECTIVE: To ensure the dermal safety of OLAF, a series of tests (the acute dermal toxicity test, 21-day repeat dermal toxicity test, dermal irritation test and skin sensitisation test) were conducted after optimising the extraction protocol of OLAF. MATERIALS AND METHODS: To improve the extraction rate of OLAF, response surface methodology (RSM) was first employed to optimise the extraction conditions. Then, Wistar rats were exposed to OLAF (400 mg·kg-1 body weight) in two different ways (6 hours/time for 24 hours and 1 time/day for 21 days) to evaluate the acute dermal toxicity and 21-day repeated dermal toxicity of OLAF. In the acute dermal toxicity test, clinical observations were conducted to evaluate the toxicity, behaviour, and health of the animals for 14 consecutive days. Similarly, the clinical signs, body weight, haematological and biochemical parameters, histopathological changes and other indicators were also detected during the 21 days administration. For the dermal irritation test, single and multiple doses of OLAF (125 mg·kg-1 body weight) were administered to albino rabbits for 14 days (1 time/day). The irritation reaction on the skin of each albino rabbit was recorded and scored. Meanwhile, skin sensitisation to OLAF was conducted using guinea pigs for a period of 28 days. RESULTS: Suitable extraction conditions for OLAF (PBS concentration 0.01, pH of PBS 8.6, solid-liquid ratio 1:385 g·mL-1) were obtained using RSM. Under these conditions, the extraction rate and particle size of OLAF were 7.29% and 1290 nm, respectively. In the tests of acute dermal toxicity and 21-day repeated dermal toxicity, no mortality or significant differences were observed in terms of clinical signs, body weight, haematological parameters, biochemical parameters and anatomopathological analysis. With respect to the dermal irritation test and skin sensitisation test, no differences in erythema, oedema or other abnormalities were observed between treatment and control groups on gross and histopathological examinations. CONCLUSIONS: The results of this study suggest that OLAF does not cause obvious toxicity, skin sensitisation or irritation in animals.


Assuntos
Portadores de Fármacos/toxicidade , Fator 1 de Crescimento de Fibroblastos/administração & dosagem , Gotículas Lipídicas , Óleos de Plantas/isolamento & purificação , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Feminino , Fator 1 de Crescimento de Fibroblastos/toxicidade , Cobaias , Masculino , Óleos de Plantas/toxicidade , Coelhos , Ratos , Testes Cutâneos , Testes de Toxicidade Aguda , Cicatrização/efeitos dos fármacos
16.
Angew Chem Int Ed Engl ; 60(17): 9306-9310, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33523581

RESUMO

Developing advanced characterization techniques for single-atom catalysts (SACs) is of great significance to identify their structural and catalytic properties. Raman spectroscopy can provide molecular structure information, and thus, the technique is a promising tool for catalysis. However, its application in SACs remains a great challenge because of its low sensitivity. We develop a highly sensitive strategy that achieves the characterization of the structure of SACs and in situ monitoring of the catalytic reaction processes on them by shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) for the first time. Using the strategy, Pd SACs on different supports were identified by Raman spectroscopy and the nucleation process of Pd species from single atoms to nanoparticles was revealed. Moreover, the catalytic reaction processes of the hydrogenation of nitro compounds on Pd SACs were monitored in situ, and molecular insights were obtained to uncover the unique catalytic properties of SACs. This work provides a new spectroscopic tool for the in situ study of SACs, especially at solid-liquid interfaces.

17.
Cancer Cell Int ; 20: 219, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32518528

RESUMO

Increased expression of the small nucleolar RNA host gene 6 (SNHG6) has been reported in different cancers, such as hepatocellular carcinoma, colorectal cancer, and lung cancer. The high expression level of SNHG6 is associated with tumor progression and poor prognosis. This paper provides an overview of recent studies on the oncogenic role and potential clinical utilities of SNHG6. Upregulated SNHG6 arrests tumor cell cycle and reduces apoptosis but promotes migration, invasion, metastasis, epithelial-mesenchymal transition (EMT), and chemoresistance in tumors. Mechanically, SNHG6 primarily sponges tumor suppressor microRNA (miRNA), functioning as a competing endogenous RNA. Once sponged, miRNA is unable to degrade, silence, or hamper the translation of its downstream, mostly oncogenic genes, ultimately driving cancer-related processes. Thus, SNHG6 might serve as a biomarker for cancer diagnosis and prognosis.

18.
Biochemistry ; 58(14): 1931-1941, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30888187

RESUMO

The chaperone-usher secretion pathway is a conserved bacterial protein secretion system dedicated to the biogenesis of adhesive fibers. Usher, a multidomain-containing outer membrane protein, plays a central role in this process by acting as a molecular machine that recruits different chaperone-subunit complexes, catalyzes subunit polymerization, and forms a channel for secretion of the assembled subunits. While recent crystal structural studies have greatly advanced our understanding of the structure and function of ushers, the overall architecture of the full-length apo-usher, the molecular events that dictate conformational changes in usher during pilus biogenesis, and its activation by the specific chaperone-adhesin complex remain largely elusive. Using single-molecule fluorescence resonance energy transfer studies, we found that the substrate-free usher FimD (apo-FimD) adopts a contracted conformation that is distinct from its substrate-bound states; both the N-terminal domain (NTD) and the C-terminal domain (CTD) of apo-FimD are highly dynamic, and FimD coordinates its domain conformational changes via intramolecular domain conformation signaling. By combining these studies with in vitro photo-cross-linking studies, we further show that only the chaperone-bound adhesin (FimC:FimH) can be transferred to the CTD, dislocates the plug domain, and triggers conformational changes in the remaining FimD domains. Taken together, these studies delineate an overall architecture of the full-length apo-FimD, provide detailed mechanic insight into the activation of apo-FimD, and explain why FimD could adjust its conformational states to perform multiple functions in each cycle of pilus subunit addition and ensure that pilus assembly proceeds progressively in a cellular energy-free environment.


Assuntos
Proteínas de Escherichia coli/química , Proteínas de Fímbrias/química , Transferência Ressonante de Energia de Fluorescência/métodos , Chaperonas Moleculares/química , Conformação Proteica , Domínios Proteicos , Sistemas de Secreção Bacterianos/genética , Sistemas de Secreção Bacterianos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Fímbrias/genética , Proteínas de Fímbrias/metabolismo , Polarização de Fluorescência , Cinética , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Mutação , Ligação Proteica , Transdução de Sinais/genética
19.
Hum Brain Mapp ; 40(4): 1049-1061, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30593684

RESUMO

The processes involved in value evaluation and self-control are critical when making behavioral choices. However, the evidence linking these two types of processes to behavioral choices in intertemporal decision-making remains elusive. As the ventromedial prefrontal cortex (vmPFC), striatum, and dorsolateral prefrontal cortex (dlPFC) have been associated with these two processes, we focused on these three regions. We employed functional magnetic resonance imaging during a delayed discounting task (DDT) using a relatively large sample size, three independent samples. We evaluated how much information about a specific choice could be decoded from local patterns in each brain area using multivoxel pattern analysis (MVPA). To investigate the relationship between the dlPFC and vmPFC/striatum regions, we performed a psychophysiological interaction (PPI) analysis. In Experiment I, we found that the vmPFC and dlPFC, but not the striatum, could determine choices in healthy participants. Furthermore, we found that the dlPFC showed significant functional connectivity with the vmPFC, but not the striatum, when making decisions. These results could be replicated in Experiment II with an independent sample of healthy participants. In Experiment III, the choice-decoding accuracy in the vmPFC and dlPFC was lower in patients with addiction (smokers and participants with Internet gaming disorder) than in healthy participants, and decoding accuracy in the dlPFC was related to impulsivity in addicts. Taken together, our findings may provide neural evidence supporting the hypothesis that value evaluation and self-control processes both guide the intertemporal choices, and might provide potential neural targets for the diagnosis and treatment of impulsivity-related brain disorders.


Assuntos
Encéfalo/fisiologia , Comportamento de Escolha/fisiologia , Autocontrole , Adulto , Mapeamento Encefálico/métodos , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Adulto Jovem
20.
Analyst ; 144(2): 685-690, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30516176

RESUMO

In this work, copper/cuprous oxide (Cu/Cu2O) nanocomposites were electrodeposited on a fluorine doped tin oxide (FTO) glass substrate for sensitive determination of hydrogen peroxide (H2O2). The Cu/Cu2O nanocomposites were synthesized on FTO at a constant current density of -0.4 mA cm-2 in 0.3 M CuSO4 (pH 9.5) under magnetic agitation. The composition and morphology of Cu/Cu2O nanocomposites were characterized by X-ray diffraction, scanning electron microscopy, energy-dispersive spectroscopy and X-ray photoelectron spectroscopy. Taking advantage of the synergistic effects of Cu and Cu2O, the fabricated Cu/Cu2O/FTO electrode showed excellent electrocatalytic activity towards the oxidation of H2O2. The electrocatalytic performance of Cu/Cu2O/FTO was evaluated by linear sweep voltammetry and amperometry. Under optimized conditions, the developed sensor exhibited a wide linear range of 0.2-2000 µM for the determination of H2O2 with a detection limit of 0.04 µM (S/N = 3). In addition, the proposed H2O2 sensor was successfully applied for the determination of H2O2 in milk samples, indicating that the electrodeposited Cu/Cu2O nanocomposites are promising nanomaterials for electrochemical sensors.

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