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1.
Artigo em Inglês | MEDLINE | ID: mdl-34533926

RESUMO

Poor cyclic stability and low rate performance due to dramatic volume change and low intrinsic electronic conductivity are the two key issues needing to be urgently solved in silicon (Si)-based anodes for lithium-ion batteries. Herein, a novel tin (Sn)-bonded Si anode is proposed for the first time. Sn, which has a high electronic conductivity, is used to bond the Si-anode material and copper (Cu) current collector together using a hot-pressed method with a temperature slightly above the melting point of Sn. The cycling performance of the electrode is studied using a galvanostatic method. Nanoindentation and peeling tests are conducted to measure the mechanical strength of the electrodes. Direct current polarization and galvanostatic intermittent titration techniques are applied to assess the conductivity of the composites. Electrochemical impedance spectroscopy and X-ray photoelectron spectroscopy are conducted to evaluate the effect of the coating layer on the cycling ability of the composites. The Sn-bonded Si anodes show superior cycling stability and high rate performance with an improved initial Coulombic efficiency. Analyses reveal that the low-melting-point Sn helps to markedly improve the electronic conductivity of the electrodes and serves as a metallic binder as well to enhance the adhesive strength of the electrode. It is hopeful that this novel Sn-bonded Si anode provides a new insight for the development of advanced Si-based anodes for LIBs.

2.
Colloids Surf B Biointerfaces ; 207: 112024, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34384973

RESUMO

In this study, we aim to develop the pH-sensitive and tumor-targeting nanogels based on the co-polymerization of three terminal allyl-functionalized components, including ortho ester-conjugated mPEG (mPEG-MOE), ortho ester crosslinker (OEAM) and phenylboronic acid (APBA). The hybrid nanogels displayed a typical spherical structure with a diameter around 200 nm observed by dynamic light scattering (DLS) and scanning electron microscopy (SEM). The prepared nanogels possessed a good stability in neutral conditions, while displayed pH-triggered drug release profiles. Furthermore, in vitro study of cellular uptake and cytotoxicity indicated that the nanogels possessed the highest drug accumulation and cytotoxicity against EMT6 cells. In vivo antitumor examination suggested that these nanogels brought out excellent efficacy in enhancing drug concentration, restraining tumor growth, and prolonged the survival time of tumor-bearing mice. Thus, the prepared multi-functional nanogels possess great potentials for drug delivery in tumor treatment.


Assuntos
Doxorrubicina , Ésteres , Animais , Doxorrubicina/farmacologia , Portadores de Fármacos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Camundongos , Nanogéis , Polietilenoglicóis
3.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34360535

RESUMO

The aims of this study were to develop the magnolol-chitosan films and study the positive effect of the combination of magnolol and chitosan. The addition of magnolol made the magnolol-chitosan films exhibit higher density (1.06-1.87 g/cm3), but the relatively lower water vapor permeability (12.06-7.36 × 10-11·g·m-1·s-1·Pa-1) and water content (16.10-10.64%). The dense and smooth surface and cross-section of magnolol-chitosan films were observed by environmental scanning electron microscopy (ESEM) images. The interaction of magnolol and chitosan was observed by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). After the addition of magnolol, the antioxidant capacity of magnolol-chitosan films was increased from 18.99 to 82.00%, the growth of P. aeruginosa was inhibited and the inhibition percentage of biofilm formation was increased from 30.89 to 86.04%. We further verified that the application of magnolol-chitosan films on chilled pork significantly reduced the increases in pH value, inhibited the growth of microorganisms and extended the shelf life. Results suggest that magnolol had a positive effect on magnolol-chitosan films and could be effectively applied to pork preservation.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Compostos de Bifenilo/farmacologia , Quitosana/química , Conservação de Alimentos/métodos , Lignanas/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Embalagem de Alimentos/métodos , Carne de Porco/análise , Infecções por Pseudomonas/microbiologia , Suínos
4.
Environ Microbiol ; 23(9): 5463-5480, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34288342

RESUMO

Pyricularia oryzae is a multi-host pathogen causing cereal disease, including the devastating rice blast. Panicle blast is a serious stage, leading to severe yield loss. Thirty-one isolates (average 4.1%) were collected from the rice panicle lesions at nine locations covering Jiangsu province from 2010 to 2017. These isolates were characterized as Pyricularia sp. jiangsuensis distinct from known Pyricularia species. The representative strain 18-2 can infect rice panicle, root and five kinds of grasses. Intriguingly, strain 18-2 can co-infect rice leaf with P. oryzae Guy11. The whole genome of P. sp. jiangsuensis 18-2 was sequenced. Nine effectors were distributed in translocation or inversion region, which may link to the rapid evolution of effectors. Twenty-one homologues of known blast-effectors were identified in strain 18-2, seven effectors including the homologues of SLP1, BAS2, BAS113, CDIP2/3, MoHEG16 and Avr-Pi54, were upregulated in the sample of inoculated panicle with strain 18-2 at 24 hpi compared with inoculation at 8 hpi. Our results provide evidences that P. sp. jiangsuensis represents an addition to the mycobiota of blast disease. This study advances our understanding of the pathogenicity of P. sp. jiangsuensis to hosts, which sheds new light on the adaptability in the co-evolution of pathogen and host.

5.
Food Chem ; 365: 130464, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34252624

RESUMO

Carbon nanoparticles (CNPs) extensively present in thermal-processed foods. Sodium nitrite (NaNO2) and tea polyphenols (TP) are commonly used in meat processing, while the properties and cytotoxicity of CNPs existed in fried pork added NaNO2 and TP remain unknown. The results showed that compared with no addition (NA, 4.008 ± 0.43 nm) in soaked pork, the smaller diameters of CNPs (0.968 ± 0.44 nm) were found in CNPs-NaNO2-20 group (addition 20 mg/kg NaNO2), the larger (155.8 ± 7.30 nm) in CNPs-TP-100 group (addition 100 mg/kg TP). The diameter of CNPs was positively correlated with the added concentration. CNPs decreased the viability of HL-7702 cells. Compared with NA group, cell viability in CNPs-NaNO2-80 group was obviously (p < 0.05) decreased by 3.17%, while the CNPs-TP-200 group was 13.84% higher. CNPs could block cells growth by arresting cells in S-phase and increasing cellular ROS levels. CNPs generated in fired pork added 200 mg/kg TP in soaking showed less cytotoxicity.


Assuntos
Nanopartículas , Carne de Porco , Carne Vermelha , Animais , Carbono , Nanopartículas/toxicidade , Polifenóis/toxicidade , Nitrito de Sódio/toxicidade , Suínos , Chá
6.
Int J Biol Macromol ; 185: 620-628, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34216663

RESUMO

Mandarin (Citrus reticulata L.) essential oil (MEO) reportedly displays excellent antimicrobial properties. In this study, MEO was loaded into chitosan nanoparticles (CSNPs). The characteristics, antibacterial properties and benefit in pork preservation of MEO-CSNPs were evaluated. The MEO-CSNPs displayed an excellent encapsulation efficiency (EE) (67.32%-82.35%), the particle size values of 131.3 nm-161.9 nm, and the absolute zeta potential values above 30 mV. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) analysis, and thermogravimetric analysis (TGA) revealed that the MEO was incorporated into CSNPs without requiring a chemical reaction, the antibacterial activity of the MEO remained. Furthermore, the damage of MEO-chitosan nanoemulsions (MEO-CSs) to the cell membranes of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was confirmed by the change of bacterial cell morphology. The anti-biofilm assays verified that the MEO-CSs substantially inhibited biofilm formation and destroyed the mature biofilms. MEO-CSs were also applied to pork, proving a great potential for pork preservation. This study provides a potential approach for developing and utilizing MEO-CSs as natural antimicrobial agents in the food industry.


Assuntos
Quitosana/química , Citrus/química , Conservação de Alimentos/métodos , Óleos Voláteis/farmacologia , Carne de Porco , Animais , Membrana Externa Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Nanopartículas , Óleos Voláteis/química , Tamanho da Partícula , Óleos Vegetais/química , Óleos Vegetais/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Suínos , Termogravimetria , Difração de Raios X
7.
J Agric Food Chem ; 69(31): 8828-8837, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34314156

RESUMO

Goat milk and oligosaccharides play important roles in gastrointestinal health. A combination of goat milk with three oligosaccharides, stachyose (STS), fructo-oligosaccharide (FOS), and a prebiotics mixture (FGS), was fed to mice. Changes and functions of the microbiota, short chain fatty acid (SCFA) concentrations, and immune gene expression in the small intestines were determined. The FOS treatment increased the beneficial bacteria Lactobacillus and Bifidobacterium, the FGS treatment helped stabilize the microbial community, and the STS treatment significantly enhanced microbial diversity and the growth of Bacteroidetes. The oligosaccharide treatments regulated the gene expression levels of the immune factors tumor necrosis factor alpha (Tnfα), granzyme B (Gzmb), perforin (Prf), and aryl hydrocarbon receptor (Ahr). Stachyose significantly increased the concentrations of acetate and propionate compared with other treatments. These findings demonstrate that STS is the preferred carbon source for microbiota, slightly modulates SCFA production, and results in low immunogenicity in the small intestines of mice.


Assuntos
Microbiota , Leite , Animais , Ácidos Graxos Voláteis , Fezes , Cabras , Imunidade , Intestino Delgado , Intestinos , Camundongos , Oligossacarídeos , Prebióticos
8.
Neuropharmacology ; 195: 108673, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34153316

RESUMO

Positive allosteric modulators (PAMs) of the µ-opioid receptor (MOR) have been proposed to exhibit therapeutic potential by maximizing the analgesic properties of clinically used opioid drugs while limiting their adverse effects or risk of overdose as a result of using lower drug doses. We herein report in vitro and in vivo characterization of two small molecules from a chemical series of MOR PAMs that exhibit: (i) MOR PAM activity and receptor subtype selectivity in vitro, (ii) a differential potentiation of the antinociceptive effect of oxycodone, morphine, and methadone in mouse models of pain that roughly correlates with in vitro activity, and (iii) a lack of potentiation of adverse effects associated with opioid administration, such as somatic withdrawal, respiratory depression, and analgesic tolerance. This series of MOR PAMs holds promise for the development of adjuncts to opioid therapy to mitigate against overdose and opioid use disorders.

9.
Proc Natl Acad Sci U S A ; 118(20)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33990467

RESUMO

Cardiac arrhythmias are the most common cause of sudden cardiac death worldwide. Lengthening the ventricular action potential duration (APD), either congenitally or via pathologic or pharmacologic means, predisposes to a life-threatening ventricular arrhythmia, Torsade de Pointes. IKs (KCNQ1+KCNE1), a slowly activating K+ current, plays a role in action potential repolarization. In this study, we screened a chemical library in silico by docking compounds to the voltage-sensing domain (VSD) of the IKs channel. Here, we show that C28 specifically shifted IKs VSD activation in ventricle to more negative voltages and reversed the drug-induced lengthening of APD. At the same dosage, C28 did not cause significant changes of the normal APD in either ventricle or atrium. This study provides evidence in support of a computational prediction of IKs VSD activation as a potential therapeutic approach for all forms of APD prolongation. This outcome could expand the therapeutic efficacy of a myriad of currently approved drugs that may trigger arrhythmias.

10.
Nat Commun ; 12(1): 2451, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33907187

RESUMO

Many pathogens infect hosts through specific organs, such as Ustilaginoidea virens, which infects rice panicles. Here, we show that a microbe-associated molecular pattern (MAMP), Ser-Thr-rich Glycosyl-phosphatidyl-inositol-anchored protein (SGP1) from U. virens, induces immune responses in rice leaves but not panicles. SGP1 is widely distributed among fungi and acts as a proteinaceous, thermostable elicitor of BAK1-dependent defense responses in N. benthamiana. Plants specifically recognize a 22 amino acid peptide (SGP1 N terminus peptide 22, SNP22) in its N-terminus that induces cell death, oxidative burst, and defense-related gene expression. Exposure to SNP22 enhances rice immunity signaling and resistance to infection by multiple fungal and bacterial pathogens. Interestingly, while SGP1 can activate immune responses in leaves, SGP1 is required for U. virens infection of rice panicles in vivo, showing it contributes to the virulence of a panicle adapted pathogen.


Assuntos
Proteínas Fúngicas/imunologia , Hypocreales/patogenicidade , Oryza/imunologia , Doenças das Plantas/imunologia , Folhas de Planta/imunologia , Proteínas de Plantas/imunologia , Sequência de Aminoácidos , Morte Celular/genética , Morte Celular/imunologia , Proteínas Fúngicas/genética , Regulação da Expressão Gênica , Glicosilfosfatidilinositóis/química , Glicosilfosfatidilinositóis/metabolismo , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Hypocreales/genética , Hypocreales/crescimento & desenvolvimento , Hypocreales/imunologia , Inflorescência/genética , Inflorescência/imunologia , Inflorescência/microbiologia , Oryza/genética , Oryza/microbiologia , Padrões Moleculares Associados a Patógenos/imunologia , Padrões Moleculares Associados a Patógenos/metabolismo , Peptídeos/genética , Peptídeos/imunologia , Células Vegetais/imunologia , Células Vegetais/patologia , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Imunidade Vegetal/genética , Folhas de Planta/genética , Folhas de Planta/microbiologia , Proteínas de Plantas/genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transdução de Sinais , Virulência
11.
BMC Infect Dis ; 21(1): 376, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882850

RESUMO

BACKGROUND: The manifestation of Talaromyces marneffei infection in some HIV-infected patients may be atypical. Cases with gastrointestinal involvement have rarely been reported. It is hard to make a diagnosis when patients are lacking the characteristic rash and positive blood culture. CASE PRESENTATION: Here, we described a patient living with HIV who complained of fever and abdominal pain, and was rapidly diagnosed with Talaromyces marneffei infection by metagenomic next-generation sequencing (mNGS) using formalin-fixation and paraffin-embedded (FFPE) samples of omentum majus tissue. We also reviewed reported related cases. CONCLUSIONS: Talaromyces marneffei is an unusual cause of clinical presentations involving obvious abdominal pain and lower gastrointestinal bleeding, but can be included in the differential diagnosis. As an important diagnostic tool, the significance of mNGS using FFPE samples of lesions provides a more targeted diagnosis.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Hemorragia Gastrointestinal/microbiologia , HIV/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Metagenômica/métodos , Micoses/complicações , Micoses/fisiopatologia , Talaromyces/genética , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Antifúngicos/uso terapêutico , China , Diagnóstico Diferencial , Seguimentos , Humanos , Masculino , Micoses/tratamento farmacológico , Micoses/microbiologia , RNA Viral/sangue , Resultado do Tratamento
13.
Small ; : e2008132, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33768716

RESUMO

Poor cycling stability and rate capability are two key issues needing to be solved for Li- and Mn-rich oxide cathode material for lithium-ion batteries (LIBs). Herein, a novel perovskite electron-ion mixed conductor Nd0.6 Sr0.4 CoO3 (NSCO) is used as the coating layer on Li1.2 Ni0.13 Co0.13 Mn0.54 O2 (LNCMO) to simultaneously enhance its cycling stability and rate capability. By coating 3 wt% NSCO, LNCMO-3NSCO exhibits an optimal cycling performance with a capacity retention of 99% at 0.1C (1C = 200 mA g-1 ) after 60 cycles, 91% at 1C after 300 cycles, and 54% at 20C after 1000 cycles, much better than 78%, 63%, and 3% of LNCMO, respectively. Even at a high charge and discharge rate of 50C, LNCMO-3NSCO exhibits a discharge capacity of 53 mAh g-1 and a mid-point discharge voltage of 2.88 V, much higher than those of LNCMO (24 mA h g-1 and 2.40 V, respectively). Benefiting from the high electronic conductivity (1.46 S cm-1 ) and ionic conductivity (1.48 × 10-7  S cm-1 ), NSCO coating not only suppresses transition metals dissolution and structure transformation, but also significantly enhances electronic conductivity and Li+ diffusion coefficient of LNCMO by an order of magnitude.

14.
ACS Nano ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33666431

RESUMO

Room-temperature sodium-sulfur (RT Na-S) batteries are widely considered as one of the alternative energy-storage systems with low cost and high energy density. However, the both poor cycle stability and capacity are two critical issues arising from low conversion kinetics and sodium polysulfides (NaPSs) dissolution for sulfur cathodes during the charge/discharge process. Herein, we report a highly stable RT Na-S battery cathode via building heterostructures in multichannel carbon fibers. The TiN-TiO2@MCCFs, fabricated by electrospinning and nitriding techniques, are loaded with the active material S, forming S/TiN-TiO2@MCCFs as the cathode in a RT Na-S battery. At 0.1 A g-1, the cathode produces the capacity of more than 640 mAh g-1 within 100 cycles with a high Coulombic efficiency of nearly 100%. Even at 5 A g-1, the battery still exhibites a capacity of 257.1 mAh g-1 after 1000 cycles. Combining structural and electrochemical analyses with the first-principles calculations reveals that the incorporation of the highly electrocatalytic activity of TiN with the powerful chemisorption of TiO2 well stabilizes S and also alleviates the shuttle effects of polysulfides. This work with simple processes and low cost is expected to promote the further development and application of metal-S batteries.

15.
Cell ; 184(4): 931-942.e18, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33571431

RESUMO

The D1- and D2-dopamine receptors (D1R and D2R), which signal through Gs and Gi, respectively, represent the principal stimulatory and inhibitory dopamine receptors in the central nervous system. D1R and D2R also represent the main therapeutic targets for Parkinson's disease, schizophrenia, and many other neuropsychiatric disorders, and insight into their signaling is essential for understanding both therapeutic and side effects of dopaminergic drugs. Here, we report four cryoelectron microscopy (cryo-EM) structures of D1R-Gs and D2R-Gi signaling complexes with selective and non-selective dopamine agonists, including two currently used anti-Parkinson's disease drugs, apomorphine and bromocriptine. These structures, together with mutagenesis studies, reveal the conserved binding mode of dopamine agonists, the unique pocket topology underlying ligand selectivity, the conformational changes in receptor activation, and potential structural determinants for G protein-coupling selectivity. These results provide both a molecular understanding of dopamine signaling and multiple structural templates for drug design targeting the dopaminergic system.


Assuntos
Receptores de Dopamina D1/química , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/química , Receptores de Dopamina D2/metabolismo , Transdução de Sinais , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/análogos & derivados , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/farmacologia , Sequência de Aminoácidos , Sequência Conservada , Microscopia Crioeletrônica , AMP Cíclico/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Células HEK293 , Humanos , Ligantes , Modelos Moleculares , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Receptores de Dopamina D1/ultraestrutura , Receptores de Dopamina D2/ultraestrutura , Homologia Estrutural de Proteína
16.
J Dairy Sci ; 104(4): 4108-4118, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33612218

RESUMO

Frozen milk can help producers overcome the seasonality of goat milk production, low goat production and short lactation periods, and avoid discarding milk during some special periods. We investigated effects of combination between freezing (cryogenic refrigerator of -16 to -20°C or ultra-cryogenic refrigerator of -76 to -80°C) and thawing (homeothermy of 20 to 25°C or refrigeration of 2 to 4°C) on nutritive compositions and physicochemical characteristics of raw goat milk during storage period (80 d). Compared with fresh goat milk, the frozen-thawed milk decreased contents of fat, protein, and lactose, as well as surface tension and stability coefficient, whereas increased effective diameter and polydispersity index. The average values of color values (L*, a*, and b*) in 4 group samples changed from 83.01 to 82.25, -1.40 to -1.54, 3.51 to 3.81, respectively, and the ΔE of most samples did not exceed 2. In contrast to the other 3 frozen-thawed treatments, goat milk treated with ultra-cryogenic freezing-homeothermic thawing (UFHT) possessed higher fat (5.20 g/100 g), smaller effective particle diameter (0.32 µm), and the lowest polydispersity index value (0.26). The color and confocal laser scanning microscopy images of UFHT were similar to those of fresh goat milk, illustrating UFHT was the optimal approach to maintain the natural quality of goat milk. Our finding provides a theoretical basis for producers to freeze surplus milk.


Assuntos
Leite , Refrigeração , Animais , Feminino , Congelamento , Cabras , Lactação , Refrigeração/veterinária
17.
Eur J Med Res ; 26(1): 15, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546770

RESUMO

BACKGROUND: Hypothermic machine perfusion (HMP) improves the quality of donor livers for transplantation, both in animal models and in clinical practice. Treatment with SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), can suppress the JNK signaling pathway to alleviate donor liver ischemia-reperfusion injury (IRI). We performed the present study with the objective of exploring the protective effects exerted by a combination of HMP and SP600125 on liver xenograft viability for donation after cardiac death (DCD) in a porcine model. METHODS: 54 adult BAMA mini-pigs were randomly assigned to 5 groups, including sham, cold storage for 4 h (CS 4 h), CS 4 h + SP600125, CS 2 h + HMP 2 h, and CS 2 h + HMP 2 h + SP600125 groups. Donor livers in the CS 4 h and CS 4 h + SP600125 groups were conventionally cold preserved for 4 h, whereas donor livers in the CS 2 h + HMP 2 h and CS 2 h + HMP 2 h + SP600125 groups were cold preserved for 2 h and then treated with HMP for 2 h. The preservation and perfusion solutions contained SP600125 (20 µM). Follow-up was conducted for 5 days after liver transplantation to compare the surgical outcomes by means of serological examination, pathological results, and survival rate. RESULTS: The most satisfactory outcome after liver transplantation was observed in the CS 2 h + HMP 2 h + SP600125 group, which presented with minimal damage of donor livers during 5 days' follow-up. Additionally, serological examination, pathological results, and survival rate concurred in showing better results in the CS 2 h + HMP 2 h ± SP600125 group than in the CS 4 h ± SP600125 group. CONCLUSION: HMP in combination with SP600125 has hepatoprotective properties and improves the quality and viability of porcine livers collected after DCD, thus improving prognosis after liver transplantation.


Assuntos
Aloenxertos/efeitos dos fármacos , Antracenos/farmacologia , Transplante de Fígado , Preservação de Órgãos/métodos , Perfusão/métodos , Animais , Temperatura Baixa , Morte , Modelos Animais de Doenças , Traumatismo por Reperfusão/prevenção & controle , Suínos , Porco Miniatura
18.
Mol Cell ; 81(6): 1147-1159.e4, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33548201

RESUMO

The dopamine system, including five dopamine receptors (D1R-D5R), plays essential roles in the central nervous system (CNS), and ligands that activate dopamine receptors have been used to treat many neuropsychiatric disorders. Here, we report two cryo-EM structures of human D3R in complex with an inhibitory G protein and bound to the D3R-selective agonists PD128907 and pramipexole, the latter of which is used to treat patients with Parkinson's disease. The structures reveal agonist binding modes distinct from the antagonist-bound D3R structure and conformational signatures for ligand-induced receptor activation. Mutagenesis and homology modeling illuminate determinants of ligand specificity across dopamine receptors and the mechanisms for Gi protein coupling. Collectively our work reveals the basis of agonist binding and ligand-induced receptor activation and provides structural templates for designing specific ligands to treat CNS diseases targeting the dopaminergic system.


Assuntos
Microscopia Crioeletrônica , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/química , Modelos Moleculares , Complexos Multiproteicos/ultraestrutura , Receptores de Dopamina D3/química , Benzopiranos/química , Células HEK293 , Humanos , Complexos Multiproteicos/química , Oxazinas/química , Pramipexol/química , Domínios Proteicos , Relação Estrutura-Atividade
19.
Appl Environ Microbiol ; 87(7)2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33452032

RESUMO

Pseudomonas chlororaphis YL-1 has extensive antimicrobial activities against phytopathogens, and its genome harbors a pyoverdine (PVD) biosynthesis gene cluster. The alternative sigma factor PvdS in Pseudomonas aeruginosa PAO1 acts as a critical regulator in response to iron starvation. The assembly of the PVD backbone starts with peptide synthetase enzyme PvdL. PvdF catalyzes formylation of l-OH-Orn to produce l-N 5-hydroxyornithine. Here, we describe the characterization of PVD production in YL-1 and its antimicrobial activity in comparison with that of its PVD-deficient ΔpvdS, ΔpvdF, and ΔpvdL mutants, which were obtained using a sacB-based site-specific mutagenesis strategy. Using in vitro methods, we examined the effect of exogenous iron under low-iron conditions and an iron-chelating agent under iron-sufficient conditions on PVD production, antibacterial activity, and the relative expression of the PVD transcription factor gene pvdS in YL-1. We found that strain YL-1, the ΔpvdF mutant, and the ΔpvdS(pUCP26-pvdS) complemented strain produced visible PVDs and demonstrated a wide range of inhibitory effects against Gram-negative and Gram-positive bacteria in vitro under low-iron conditions and that with the increase of iron, its PVD production and antibacterial activity were reduced. The antibacterial compounds produced by strain YL-1 under low-iron conditions were PVDs based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Moreover, the antibacterial activity observed in vitro was correlated with in vivo control efficacies of strain YL-1 against rice bacterial leaf blight (BLB) disease caused by Xanthomonas oryzae pv. oryzae. Collectively, PVDs are responsible for the antibacterial activities of strain YL-1 under both natural and induced low-iron conditions.IMPORTANCE The results demonstrated that PVDs are essential for the broad-spectrum antibacterial activities of strain YL-1 against both Gram-positive and Gram-negative bacteria under low-iron conditions. Our findings also highlight the effect of exogenous iron on the production of PVD and the importance of this bacterial product in bacterial interactions. As a biocontrol agent, PVDs can directly inhibit the proliferation of the tested bacteria in addition to participating in iron competition.


Assuntos
Antibacterianos/farmacologia , Ferro/metabolismo , Oligopeptídeos/farmacologia , Pseudomonas chlororaphis/metabolismo , Antibacterianos/química , Cromatografia Líquida , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Oligopeptídeos/química , Pseudomonas chlororaphis/química , Pseudomonas chlororaphis/genética , Espectrometria de Massas em Tandem
20.
Complement Ther Clin Pract ; 41: 101253, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33186824

RESUMO

BACKGROUND: Acupuncture has been found to be an effective treatment for insomnia. but it is not clear whether acupuncture is just a placebo effect. We aimed to compare the efficacy and safety of acupuncture and sham/placebo acupuncture. METHODS: We searched the Central Register of Controlled Trials of Medline, EMBASE, and Cochrane from database inception through March 16, 2020 for randomized controlled trials (RCTs) that compared acupuncture therapy with sham/placebo acupuncture or no treatment. Restricted to English language. Cochrane risk of bias tool was used to analyze risk of bias of the included randomized controlled trials (RCT). Data analysis was performed with Review Manager 5.3. RESULTS: A total of 15 studies involving 1108 patients. Meta-analysis results showed that acupuncture therapy was superior to sham/placebo acupuncture in terms of improving Pittsburgh sleep quality index (PSQI), insomnia severity index (ISI), total sleep time (TST), sleep-onset latency (SOL), wake after sleep onset (WASO), sleep efficiency (SE), even during the follow-up period, acupuncture therapy was superior to sham/placebo acupuncture on PSQI. Due to the obvious heterogeneity of the study, (1) for primary outcome (PSQI):subgroup analysis based on the type of acupuncture and placebo acupuncture showed that acupuncture was superior to placebo acupuncture lower PSQI: acupuncture was superior to placebo acupuncture (3RCTs,MD = -7.34,95% [-8.02,-6.66],I2 = 86%) and minimal acupuncture (5RCTs,MD = -3.29,95% [-3.95, -2.63],I2 = 53%), Auricular acupressure was superior to placebo acupuncture (1RCT,MD = -4.16,95% [-6.57, -1.75]), minimal acupuncture was superior to electroacupuncture (2RCTs, MD = 0.70,95%CI [0.52, 0.87],I2 = 0%), while there was no significant difference between auricular acupressure and minimal acupuncture, between electroacupuncture and placebo acupuncture. trials). (2) for secondary outcome (ISI,TST,WASO,SE,SOL).ISI, the ISI score of minimal acupuncture was lower than that of electroacupuncture (2RCTs,MD = 0.80,95%CI [0.55, 1.04],I2 = 0), acupuncture was lower placebo acupuncture (1RCT, MD = -7.89,95%CI [-10.15, -5.63]), There was no significant difference between electroacupuncture and minimal acupuncture. Conclusion: Based on the outcomes included in this study, the efficacy of acupuncture was superior to that of placebo acupuncture in treating insomnia. Types of acupuncture therapy and placebo may underestimate the efficacy of acupuncture in different ways.


Assuntos
Terapia por Acupuntura , Distúrbios do Início e da Manutenção do Sono , Acupressão , Eletroacupuntura , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Distúrbios do Início e da Manutenção do Sono/terapia
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