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1.
Plant Physiol ; 195(2): 1365-1381, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38471799

RESUMO

Several starch synthesis regulators have been identified, but these regulators are situated in the terminus of the regulatory network. Their upstream regulators and the complex regulatory network formed between these regulators remain largely unknown. A previous study demonstrated that NAM, ATAF, and CUC (NAC) transcription factors, OsNAC20 and OsNAC26 (OsNAC20/26), redundantly and positively regulate the accumulation of storage material in rice (Oryza sativa) endosperm. In this study, we detected OsNAC25 as an upstream regulator and interacting protein of OsNAC20/26. Both OsNAC25 mutation and OE resulted in a chalky seed phenotype, decreased starch content, and reduced expression of starch synthesis-related genes, but the mechanisms were different. In the osnac25 mutant, decreased expression of OsNAC20/26 resulted in reduced starch synthesis; however, in OsNAC25-overexpressing plants, the OsNAC25-OsNAC20/26 complex inhibited OsNAC20/26 binding to the promoter of starch synthesis-related genes. In addition, OsNAC20/26 positively regulated OsNAC25. Therefore, the mutual regulation between OsNAC25 and OsNAC20/26 forms a positive regulatory loop to stimulate the expression of starch synthesis-related genes and meet the great demand for starch accumulation in the grain filling stage. Simultaneously, a negative regulatory loop forms among the 3 proteins to avoid the excessive expression of starch synthesis-related genes. Collectively, our findings demonstrate that both promotion and inhibition mechanisms between OsNAC25 and OsNAC20/26 are essential for maintaining stable expression of starch synthesis-related genes and normal starch accumulation.


Assuntos
Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas , Amido , Fatores de Transcrição , Oryza/genética , Oryza/metabolismo , Amido/metabolismo , Amido/biossíntese , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Endosperma/metabolismo , Endosperma/genética
2.
Neuroimage ; 295: 120648, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38761882

RESUMO

BACKGROUND: Cerebellar intermittent theta burst stimulation (iTBS) modulates the excitability of the cerebral cortex and may enhance attentional performance. To date, few studies have conducted iTBS on healthy subjects for one week and used electroencephalography (EEG) to investigate the effect of multiple stimulation sessions on resting-state functional brain networks and the daily stimulation effect on attentional performance. METHODS: 16 healthy subjects participated in a one-week experiment, receiving bilateral cerebellar iTBS or sham stimulation and engaging in multi-task attentional training. The primary measures were the one-week attentional performance and pre- and post-experiment resting-state EEG activities. Amplitude Envelope Correlation (AEC) was used to construct the functional connectivity in the eye-open (EO) and eye-closed (EC) phases. RESULTS: At least three sessions of iTBS were required to enhance multi-task performance significantly, whereas only one or two sessions failed to elicit the improvement. Compared with the control group, iTBS induced significant changes in PSD, AEC functional connectivity, and AEC network properties during the EO phase, while it had little effect during the EC phase. During the EO phase, the network property changes of the iTBS subject were correlated with improved attentional performance. CONCLUSION: The multi-task performance requires multiple stimulations to enhance. iTBS affects the resting-state alpha band brain activities during the EO rather than the EC phase. The AEC network properties may serve as a biomarker to assess the attentional potential of healthy subjects.


Assuntos
Atenção , Cerebelo , Eletroencefalografia , Estimulação Magnética Transcraniana , Humanos , Atenção/fisiologia , Masculino , Feminino , Cerebelo/fisiologia , Cerebelo/diagnóstico por imagem , Adulto , Adulto Jovem , Estimulação Magnética Transcraniana/métodos , Rede Nervosa/fisiologia , Rede Nervosa/diagnóstico por imagem , Descanso/fisiologia , Voluntários Saudáveis
3.
Small ; : e2400326, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38813723

RESUMO

The latest research identifies that cysteine (Cys) is one of the key factors in tumor proliferation, metastasis, and recurrence. The direct depletion of intracellular Cys shows a profound antitumor effect. However, using nanozymes to efficiently deplete Cys for tumor therapy has not yet attracted widespread attention. Here, a (3-carboxypropyl) triphenylphosphonium bromide-derived hyaluronic acid-modified copper oxide nanorods (denoted as MitCuOHA) are designed with cysteine oxidase-like, glutathione oxidase-like and peroxidase-like activities to realize Cys depletion and further induce cellular ferroptosis and cuproptosis for synergistic tumor therapy. MitCuOHA nanozymes can efficiently catalyze the depletion of Cys and glutathione (GSH), accompanied by the generation of H2O2 and the subsequent conversion into highly active hydroxyl radicals, thereby successfully inducing ferroptosis in cancer cells. Meanwhile, copper ions released by MitCuOHA under tumor microenvironment stimulation directly bind to lipoylated proteins of the tricarboxylic acid cycle, leading to the abnormal aggregation of lipoylated proteins and subsequent loss of iron-sulfur cluster proteins, which ultimately triggers proteotoxic stress and cell cuproptosis. Both in vitro and in vivo results show the drastically enhanced anticancer efficacy of Cys oxidation catalyzed by the MitCuOHA nanozymes, demonstrating the high feasibility of such catalytic Cys depletion-induced synergistic ferroptosis and cuproptosis therapeutic concept.

4.
Ecotoxicol Environ Saf ; 280: 116541, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38848637

RESUMO

Although accumulating evidence indicates that endangered animals suffer from plastic pollution, this has been largely overlooked. Here, we explored the bacteria and eukaryotes living in the plastics gathered from the natural habitat of the highly endangered crocodile lizard. The results demonstrated that the bacterial and eukaryotic communities on plastics formed a unique ecosystem that exhibited lower diversity than those in the surrounding water and soil. However, microbes displayed a more complex and stable network on plastic than that in water or soil, implying unique mechanisms of stabilization. These mechanisms enhanced their resilience and contributed to the provision of stable ecological services. Eukaryotes formed a simpler and smaller network than bacteria, indicating different survival strategies. The bacteria residing on the plastics played a significant role in carbon transformation and sequestration, which likely impacted carbon cycling in the habitat. Furthermore, microbial exchange between plastics and the crocodile lizard was observed, suggesting that plastisphere serves as a mobile gene bank for the exchange of information, including potentially harmful substances. Overall, microbes on plastic appear to significantly impact the crocodile lizard and its natural habitat via various pathways. These results provided novel insights into risks evaluation of plastic pollution and valuable guidance for government efforts in plastic pollutant control in nature reserves.


Assuntos
Bactérias , Ecossistema , Espécies em Perigo de Extinção , Lagartos , Plásticos , Animais , Monitoramento Ambiental , Eucariotos , Fenótipo , Microbiologia do Solo
5.
Perfusion ; : 2676591241280163, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39196956

RESUMO

Extracorporeal membrane oxygenation (ECMO) has been widely used as a clinical bridge for cardiopulmonary failure. We recently used combined veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and haemoperfusion to successfully treat a patient with acute aconitine poisoning. The patient was admitted to the Emergency Intensive Care Unit (EICU) in a state of coma and shock. Her received comprehensive treatment, including haemoperfusion and anti-shock therapy. 40 minutes after admission, the patient experienced sudden respiratory and cardiac arrest. After conventional defibrillation and cardiopulmonary resuscitation proved ineffective, veno-arterial ECMO was immediately initiated. One hour after initiation of VA-ECMO, the patient's heart rhythm stabilised to sinus rhythm. After 33 h of supportive care, the patient was awake, haemodynamically stable and the VA-ECMO was successfully removed. The patient made full recovery 7 days after admission.

6.
J Transl Med ; 21(1): 349, 2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37237321

RESUMO

Gut microbiota is closely related to human health and disease because, together with their metabolites, gut microbiota maintain normal intestinal peristalsis. The use of antibiotics or opioid anesthetics, or both, during surgical procedures can lead to dysbiosis and affect intestinal motility; however, the underlying mechanisms are not fully known. This review aims to discuss the effect of gut microbiota and their metabolites on postoperative intestinal motility, focusing on regulating the enteric nervous system, 5-hydroxytryptamine neurotransmitter, and aryl hydrocarbon receptor.


Assuntos
Microbioma Gastrointestinal , Humanos , Intestinos/fisiologia , Motilidade Gastrointestinal , Disbiose
7.
Inorg Chem ; 62(3): 1156-1164, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36625518

RESUMO

Iridium/nickel (Ir/Ni) metallaphotoredox dual catalysis overcomes the challenging reductive elimination (RE) of Ni(II) species and has made a breakthrough progress to construct a wide range of C-X (X = C, N, S, and P) bonds. However, the corresponding reaction mechanisms are still ambiguous and controversial because the systematic research on the nature of this synergistic catalysis is not sufficient. Herein, IrIII/NiII and IrIII/Ni0 metallaphotoredox catalysis have been theoretically explored taking the aryl esterification reaction of benzoic acid and aryl bromide as an example by a combination of density functional theory (DFT), molecular dynamics, and time-dependent DFT computations. It is found that an electron-transfer mechanism is applicable to IrIII/NiII metallaphotoredox catalysis, but an energy-transfer mechanism is applicable to IrIII/Ni0 combination. The IrIII/NiII metallaphotoredox catalysis succeeds to construct a NiI-NiIII catalytic cycle to avoid the challenging RE of Ni(II) species, while the RE occurs from triplet excited-state Ni(II) species in the IrIII/Ni0 metallaphotoredox catalysis. In addition, the lower lowest unoccupied molecular orbital energy level of Ni(III) species than that of Ni(II) species accelerates RE from Ni(III) one. The triplet excited-state Ni(II) species can resemble a Ni(III) center, considering the metal-to-ligand charge transfer character to promote the RE.


Assuntos
Elétrons , Transporte de Elétrons
8.
Molecules ; 28(9)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37175209

RESUMO

Boron nitride nanosheet (BNNS) and graphene oxide (GO) as a single filler can effectively improve the thermal conductivity of the composites, and the synergistic mechanism of BNNS and GO was investigated in this paper. In this study, BNNS was first surface-functionalized and the multi-sized (50 nm, 200 nm, 500 nm) modified BNNS (A-BN) were attached to GO through non-covalent bonding interactions to form a cross-linked structure. Then, A-BN and GO were used as thermal fillers and support material adsorption eutectic phase change materials (PCMs) to prepare composite phase change material (CPCM). Characterization results show that small-size A-BN was more likely to form dense thermal networks with good compatibility and interface connectivity between PCMs, A-BN, and GO, ensuring that PCMs can be stored in the network without leaking. When the size of the BNNS was greater than 200 nm, the advantage of thermal conductivity obtained by A-BN was no longer obvious, and the phase change behavior of CPCM was inhibited. In general, the prepared CPCM has the ideal thermal response and thermal stability, which is very suitable for energy storage and thermal management applications.

9.
Molecules ; 28(19)2023 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-37836811

RESUMO

Recently, non-fullerene-based organic solar cells (OSCs) have made great breakthroughs, and small structural differences can have dramatic impacts on the power conversion efficiency (PCE). We take ITIC and its isomers as examples to study their effects on the performance of OSCs. ITIC and NFBDT only differed in the side chain position, and they were used as models with the same donor molecule, PBDB-T, to investigate the main reasons for the difference in their performance in terms of theoretical methods. In this work, a detailed comparative analysis of the electronic structure, absorption spectra, open circuit voltage and interfacial parameters of the ITIC and NFBDT systems was performed mainly by combining the density functional theory/time-dependent density functional theory and molecular dynamics simulations. The results showed that the lowest excited state of the ITIC molecule possessed a larger ∆q and more hybrid FE/CT states, and PBDB-T/ITIC had more charge separation paths as well as a larger kCS and smaller kCR. The reason for the performance difference between PBDB-T/ITIC and PBDB-T/NFBDT was elucidated, suggesting that ITIC is a superior acceptor based on a slight modulation of the side chain and providing a guiding direction for the design of superior-performing small molecule acceptor materials.

10.
Microb Pathog ; 157: 104960, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34022355

RESUMO

Carbapenem-resistant Acinetobacter baumannii (CRAB) is becoming a troublesome issue worldwide, and anti-CRAB drug research and development is urgently needed. To identify new anti-CRAB drug leads, we investigated seven scorpion venom-derived α-helical peptides that differ in their sequence composition and length. Three peptides, Hp1404, ctriporin and Im5, showed antimicrobial activities against Acinetobacter baumannii. Further antimicrobial assays revealed that Hp1404 exhibited the best cell selectivity with high anti-CRAB and low hemolytic activities. Fluorescence assays demonstrated that Hp1404 can induce dose-dependent disruptions of the bacterial cell membrane, implying a membrane-lytic mode of action. Taken together, our work sheds light on the potential of the scorpion venom-derived peptide Hp1404 for the development of novel antimicrobial agents against CRAB infections.


Assuntos
Acinetobacter baumannii , Anti-Infecciosos , Venenos de Escorpião , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Carbapenêmicos/farmacologia , Testes de Sensibilidade Microbiana , Proteínas Citotóxicas Formadoras de Poros , Venenos de Escorpião/farmacologia
11.
Chemistry ; 27(37): 9571-9579, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-33786898

RESUMO

Quantum mechanical and molecular dynamics simulations have been carried out on a series of anthracene-o-carborane derivatives (ANT-H, ANT-Ph, ANT-Me and ANT-TMS) with rare red-light emission in the solid state. The simulation of the heating process of the crystals and further comparison of the molecular structures and excited-state properties before and after heating help us to disclose the thermochromic behavior, that is, the red-shift emission is caused by elongation of the C1-C2 bond in the carborane moiety after heating. Thus, we believe that the molecular structure in the crystal is severely affected by heating. Transformation of the molecular conformation appears in the ANT-H crystal with increasing temperature. More specifically, the anthracene moiety moves from nearly parallel to the C1-C2 bond to nearly perpendicular, causing the short-wavelength emission to disappear after heating. As for the aggregation-induced emission phenomenon, the structures and photophysical properties were investigated comparatively in both the isolated and crystal states; the results suggested that the energy dissipation in crystal surroundings was greatly reduced through hindering structure relaxation from the excited to the ground state. We expect that discussion of the thermochromic behavior will provide a new analysis perspective for the molecular design of o-carborane derivatives.

12.
J Org Chem ; 86(1): 484-492, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33295780

RESUMO

Recent experimental work reported that visible-light photoredox catalysis coupled with primary sulfonamides and electron-deficient alkenes could efficiently construct C-C bonds at the α-position of primary amine derivatives under mild conditions. Here, a systematic study was conducted to explore the non-negligible excited-state single-electron-transfer (SET) processes and the catalytic cycle. Hydrogen atom transfer (HAT) catalysis containing different site-selective functionalization, involved as a critical process during the reaction, was computationally characterized. The superiorities of iridium-based photoredox catalysts in terms of photoabsorption properties, phosphorescence rates, and electron-transfer rates for SET processes were focused on. In addition, the function of quinuclidine in the entire photocatalytic reaction was also probed. These intrinsic properties and detailed insights into the mechanism are supposed to be helpful to the understanding of the C-C bond functionalization reaction and the future application of the iridium-based photoredox catalyst.

13.
J Bacteriol ; 203(1)2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33046561

RESUMO

The invasion and colonization of host plants by the destructive pathogen Ralstonia solanacearum rely on its cell motility, which is controlled by multiple factors. Here, we report that the LysR-type transcriptional regulator CrgA (RS_RS16695) represses cell motility in R. solanacearum GMI1000. CrgA possesses common features of a LysR-type transcriptional regulator and contains an N-terminal helix-turn-helix motif as well as a C-terminal LysR substrate-binding domain. Deletion of crgA results in an enhanced swim ring and increased transcription of flhDC In addition, the ΔcrgA mutant possesses more polar flagella than wild-type GMI1000 and exhibits higher expression of the flagellin gene fliC Despite these alterations, the ΔcrgA mutant did not have a detectable growth defect in culture. Yeast one-hybrid and electrophoretic mobility shift assays revealed that CrgA interacts directly with the flhDC promoter. Expressing the ß-glucuronidase (GUS) reporter under the control of the crgA promoter showed that crgA transcription is dependent on cell density. Soil-soaking inoculation with the crgA mutant caused wilt symptoms on tomato (Solanum lycopersicum L. cv. Hong yangli) plants earlier than inoculation with the wild-type GMI1000 but resulted in lower disease severity. We conclude that the R. solanacearum regulator CrgA represses flhDC expression and consequently affects the expression of fliC to modulate cell motility, thereby conditioning disease development in host plants.IMPORTANCERalstonia solanacearum is a widely distributed soilborne plant pathogen that causes bacterial wilt disease on diverse plant species. Motility is a critical virulence attribute of R. solanacearum because it allows this pathogen to efficiently invade and colonize host plants. In R. solanacearum, motility-defective strains are markedly affected in pathogenicity, which is coregulated with multiple virulence factors. In this study, we identified a new LysR-type transcriptional regulator (LTTR), CrgA, that negatively regulates motility. The mutation of the corresponding gene leads to the precocious appearance of wilt symptoms on tomato plants when the pathogen is introduced using soil-soaking inoculation. This study indicates that the regulation of R. solanacearum motility is more complex than previously thought and enhances our understanding of flagellum regulation in R. solanacearum.


Assuntos
Proteínas de Bactérias/fisiologia , Flagelos/fisiologia , Ralstonia solanacearum/fisiologia , Transativadores/fisiologia , Fatores de Transcrição/fisiologia , Ensaio de Desvio de Mobilidade Eletroforética , Solanum lycopersicum/microbiologia , Microscopia Eletrônica de Transmissão , Regiões Promotoras Genéticas/fisiologia , Ralstonia solanacearum/genética , Ralstonia solanacearum/patogenicidade , Ralstonia solanacearum/ultraestrutura , Reação em Cadeia da Polimerase em Tempo Real , Elementos Reguladores de Transcrição/fisiologia , Microbiologia do Solo , Técnicas do Sistema de Duplo-Híbrido , Virulência
14.
Mol Plant Microbe Interact ; 32(6): 697-707, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30540527

RESUMO

Ralstonia solanacearum is the causal agent of bacterial wilt disease. Here, we report that a large FAD-linked oxidase encoded by RSc0454 in GMI1000 is required for pathogenicity. The FAD-linked oxidase encoded by RSc0454 is composed of 1,345 amino acids, including DUF3683, lactate dehydrogenase (LDH), and succinate dehydrogenase (SDH) domains. The RSc0454 protein showed both LDH and SDH activities. To investigate its role in pathogenicity, a deletion mutant of the RSc0454 gene was constructed in GMI1000, which was impaired in its ability to cause bacterial wilt disease in tomato. A single DUF3683, LDH, or SDH domain was insufficient to restore bacterial pathogenicity. Mutagenesis of the RSc0454 gene did not affect growth rate but caused cell aggregation at the bottom of the liquid nutrient medium, which was reversed by exogenous applications of lactate, fumarate, pyruvate, and succinate. qRT-PCR and promoter LacZ fusion experiments demonstrated that RSc0454 gene transcription was induced by lactate and fumarate (both substrates of LDH). Compared with the downregulation of the succinate dehydrogenase gene sdhBADC and the lactate dehydrogenase gene ldh, RSc0454 gene transcription was enhanced in planta. This suggests that the oxidase encoded by RSc0454 was involved in a redox balance, which is in line with the different living conditions of R. solanacearum.


Assuntos
Oxirredutases , Ralstonia solanacearum , Virulência , Flavina-Adenina Dinucleotídeo/metabolismo , Oxirredutases/genética , Oxirredutases/metabolismo , Doenças das Plantas/microbiologia , Ralstonia solanacearum/enzimologia , Ralstonia solanacearum/genética , Ralstonia solanacearum/patogenicidade , Deleção de Sequência , Virulência/genética
15.
Anal Chem ; 91(9): 6097-6102, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-30966737

RESUMO

A variety of fluorophores have been designed and created to fabricate organic fluorescent probes. Among these fluorophores, benzopyran-coumarin (BC) based fluorescent platform has attracted increasing attention as it shows multiple appropriate fluorescent and imaging capacities. Nevertheless, the analytical potential of BC is still urgently needed to be further excavated as its detection performance is hindered by the inherent drawbacks of current BC skeleton, that is, limited number of reactive sites. As such, in this work, by simply introducing electron-withdrawing (EW) substituent groups, we reconstructed BC skeleton to afford two fluorescent probes, BCB (-Br substitued) and BCN (-NO2 substitued), both of which featured two highly reactive sites. These two probes were capable of detecting peroxynitrite (ONOO-) and biothiols (hydrogen sulfide, glutathione, cysteine, and homocysteine) through naked eye and UV-vis absorption analysis in buffer solution. In addition, BCB was able to specifically sense biothiols with fluorescent analysis while BCN, with - NO2 instead of -Br, displayed more prominent fluorescent specificity toward ONOO-. This work provided a new strategy for the reactivity regulation of fluorophore through EW group introduction, as well as an alternative approach and method for the construction of fluorescent probes for other important biological species.


Assuntos
Benzopiranos/química , Cumarínicos/química , Elétrons , Corantes Fluorescentes/química , Ácido Peroxinitroso/análise , Compostos de Sulfidrila/análise , Animais , Corantes Fluorescentes/síntese química , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Imagem Óptica , Células PC12 , Ratos
16.
Angew Chem Int Ed Engl ; 58(4): 1148-1152, 2019 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-30411835

RESUMO

A general and efficient protocol was developed for the synthesis of polysubstituted pyridines from propargyl amines and unsaturated carbonyl compounds through a tandem condensation/alkyne isomerization/6π 3-azatriene electrocyclization sequence. This process was found to be applicable to a wide range of readily available substrates (30 examples, up to 95 % yield) and could be readily performed on a preparative (20 g) scale. By taking advantage of this method for late-stage pyridine incorporation, we successfully completed the collective total synthesis of suveoline, norsuveoline, and macrophylline.

17.
Inorg Chem ; 56(8): 4569-4576, 2017 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-28345901

RESUMO

Ionic rare-earth metal complexes 1-4 bearing an imidazolium cation were synthesized, which, as single-component catalysts, showed good activity in catalyzing cyclic carbonate synthesis from epoxides and CO2. In the presence of 0.2 mol % catalyst, monosubstituted epoxides bearing different functional groups were converted into cyclic carbonates in 60-97% yields under atmospheric pressure. In addition, bulky/internal epoxides with low reactivity yielded cyclic carbonates in 40-95% yields. More importantly, the readily available samarium complex 2 was reused for six successive cycles without any significant loss in its catalytic activity. This is the first recyclable rare-earth metal-based catalyst in cyclic carbonate synthesis.

18.
J Biol Chem ; 289(24): 16914-23, 2014 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-24764303

RESUMO

Large conductance Ca(2+)- and voltage-activated potassium (BK) channels, composed of pore-forming α subunits and auxiliary ß subunits, play important roles in diverse physiological activities. The ß1 is predominately expressed in smooth muscle cells, where it greatly enhances the Ca(2+) sensitivity of BK channels for proper regulation of smooth muscle tone. However, the structural basis underlying dynamic interaction between BK mSlo1 α and ß1 remains elusive. Using macroscopic ionic current recordings in various Ca(2+) and Mg(2+) concentrations, we identified two binding sites on the cytosolic N terminus of ß1, namely the electrostatic enhancing site (mSlo1(K392,R393)-ß1(E13,T14)), increasing the calcium sensitivity of BK channels, and the hydrophobic site (mSlo1(L906,L908)-ß1(L5,V6,M7)), passing the physical force from the Ca(2+) bowl onto the enhancing site and S6 C-linker. Dynamic binding of these sites affects the interaction between the cytosolic domain and voltage-sensing domain, leading to the reduction of Mg(2+) sensitivity. A comprehensive structural model of the BK(mSlo1 α-ß1) complex was reconstructed based on these functional studies, which provides structural and mechanistic insights for understanding BK gating.


Assuntos
Cálcio/metabolismo , Ativação do Canal Iônico , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Magnésio/metabolismo , Potenciais de Ação , Sequência de Aminoácidos , Sítios de Ligação , Células HEK293 , Humanos , Gelo , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/química , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Simulação de Dinâmica Molecular , Dados de Sequência Molecular , Ligação Proteica , Subunidades Proteicas/química , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo
19.
Prep Biochem Biotechnol ; 45(2): 192-204, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24678584

RESUMO

A novel exopolysaccharide (EPS), namely, B4-EPS, is produced by Arthrobacter sp. B4. Response surface methodology (RSM) was employed to optimize the fermentation medium for increasing B4-EPS production. Based on Plackett-Burman design (PBD), glucose, yeast extract, and KH2PO4 were selected as significant variables, which were further optimized by a central composite design (CCD). According to response surface and canonical analysis, the optimal medium was composed of 16.94 g/L glucose, 2.33 g/L yeast extract, and 5.32 g/L KH2PO4. Under this condition, the maximum yield of B4-EPS reached about 8.54 g/L after 72 hr of batch fermentation, which was pretty close to the predicted value (8.52 g/L). Furthermore, B4-EPS was refined by column chromatography. The main homogeneous fraction (B4-EPS1) was collected and applied to assay of antibiofilm activity. B4-EPS1 exhibited a dose-dependent inhibitory effect on biofilm formation of Pseudomonas aeruginosa PAO1 without antibacterial activity. About 86.1% of biofilm formation of P. aeruginosa PAO1 was inhibited in the presence of 50 µg/mL B4-EPS1, which was more effective than the peer published data. Moreover, B4-EPS1 could prevent biofilm formation of other strains. These data suggest B4-EPS may represent a promising strategy to combat bacterial biofilms in the future.


Assuntos
Arthrobacter , Biofilmes/efeitos dos fármacos , Polissacarídeos Bacterianos , Pseudomonas aeruginosa/fisiologia , Arthrobacter/química , Arthrobacter/crescimento & desenvolvimento , Meios de Cultura/química , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/isolamento & purificação , Polissacarídeos Bacterianos/farmacologia
20.
Cancer Med ; 13(8): e7200, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38634194

RESUMO

BACKGROUND: Recently, increasing data have suggested that the lncRNA small nucleolar RNA host genes (SNHGs) were aberrantly expressed in hepatocellular carcinoma (HCC), but the association between the prognosis of HCC and their expression remained unclear. The purpose of this meta-analysis was to determine the prognostic significance of lncRNA SNHGs in HCC. METHODS: We systematically searched Embase, Web of Science, PubMed, and Cochrane Library for eligible articles published up to February 2024. The prognostic significance of SNHGs in HCC was evaluated by hazard ratios (HRs) and 95% confidence intervals (CIs). Odds ratios (ORs) were used to assess the clinicopathological features of SNHGs. RESULTS: This analysis comprised a total of 25 studies covering 2314 patients with HCC. The findings demonstrated that over-expressed SNHGs were associated with larger tumor size, multiple tumor numbers, poor histologic grade, earlier lymphatic metastasis, vein invasion, advanced tumor stage, portal vein tumor thrombosis (PVTT), and higher alpha-fetoprotein (AFP) level, but not with hepatitis B virus (HBV) infection, and cirrhosis. In terms of prognosis, patients with higher SNHG expression were more likely to have shorter overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS). CONCLUSIONS: In conclusion, upregulation of SNHGs expression correlates with shorter OS, RFS, DFS, tumor size and numbers, histologic grade, lymphatic metastasis, vein invasion, tumor stage, PVTT, and AFP level, suggesting that SNHGs may serve as prognostic biomarkers in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , alfa-Fetoproteínas , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Metástase Linfática , Recidiva Local de Neoplasia , Prognóstico , RNA Longo não Codificante/genética , RNA Nucleolar Pequeno
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