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1.
Proc Natl Acad Sci U S A ; 121(14): e2321615121, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38530892

RESUMEN

Polymethoxyflavones (PMFs) are a class of abundant specialized metabolites with remarkable anticancer properties in citrus. Multiple methoxy groups in PMFs are derived from methylation modification catalyzed by a series of hydroxylases and O-methyltransferases (OMTs). However, the specific OMTs that catalyze the systematic O-methylation of hydroxyflavones remain largely unknown. Here, we report that PMFs are highly accumulated in wild mandarins and mandarin-derived accessions, while undetectable in early-diverging citrus species and related species. Our results demonstrated that three homologous genes, CreOMT3, CreOMT4, and CreOMT5, are crucial for PMF biosynthesis in citrus, and their encoded methyltransferases exhibit multisite O-methylation activities for hydroxyflavones, producing seven PMFs in vitro and in vivo. Comparative genomic and syntenic analyses indicated that the tandem CreOMT3, CreOMT4, and CreOMT5 may be duplicated from CreOMT6 and contributes to the genetic basis of PMF biosynthesis in the mandarin group through neofunctionalization. We also demonstrated that N17 in CreOMT4 is an essential amino acid residue for C3-, C5-, C6-, and C3'-O-methylation activity and provided a rationale for the functional deficiency of OMT6 to produce PMFs in early-diverging citrus and some domesticated citrus species. A 1,041-bp deletion in the CreOMT4 promoter, which is found in most modern cultivated mandarins, has reduced the PMF content relative to that in wild and early-admixture mandarins. This study provides a framework for reconstructing PMF biosynthetic pathways, which may facilitate the breeding of citrus fruits with enhanced health benefits.


Asunto(s)
Citrus , Citrus/química , Domesticación , Fitomejoramiento , Metilación , Metiltransferasas/metabolismo
2.
Small ; : e2402035, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38770746

RESUMEN

Solid-state batteries (SSBs) are under development as high-priority technologies for safe and energy-dense next-generation electrochemical energy storage systems operating over a wide temperature range. Solid-state electrolytes (SSEs) exhibit high thermal stability and, in some cases, the ability to prevent dendrite growth through a physical barrier, and compatibility with the "holy grail" metallic lithium. These unique advantages of SSEs have spurred significant research interests during the last decade. Garnet-type SSEs, that is, Li7La3Zr2O12 (LLZO), are intensively investigated due to their high Li-ion conductivity and exceptional chemical and electrochemical stability against lithium metal anodes. However, poor interfacial contact with cathode materials, undesirable lithium plating along grain boundaries, and moisture-induced chemical degradation greatly hinder the practical implementation of LLZO-based SSEs for SSBs. In this review, the recent advances in synthesis methods, modification strategies, corresponding mechanisms, and applications of garnet-based SSEs in SSBs are critically summarized. Furthermore, a comprehensive evaluation of the challenges and development trends of LLZO-based electrolytes in practical applications is presented to accelerate their development for high-performance SSBs.

3.
Small ; 20(16): e2307579, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38044290

RESUMEN

The design and fabrication of novel carbon hosts with high conductivity, accelerated electrochemical catalytic activities, and superior physical/chemical confinement on sulfur and its reaction intermediates polysulfides are essential for the construction of high-performance C/S cathodes for lithium-sulfur batteries (LSBs). In this work, a novel biofermentation coupled gel composite assembly technology is developed to prepare cross-linked carbon composite hosts consisting of conductive Rhizopus hyphae carbon fiber (RHCF) skeleton and lamellar sodium alginate carbon (SAC) uniformly implanted with polarized nanoparticles (V2O3, Ag, Co, etc.) with diameters of several nanometers. Impressively, the RHCF/SAC/V2O3 composites exhibit enhanced physical/chemical adsorption of polysulfides due to the synergistic effect between hierarchical pore structures, heteroatoms (N, P) doping, and polar V2O3 generation. Additionally, the catalytic conversion kinetics of cathodes are effectively improved by regulating the 3D carbon structure and optimizing the V2O3 catalyst. Consequently, the LSBs assembled with RHCF/SAC/V2O3-S cathode show exceptional cycle stability (capacity retention rate of 94.0% after 200 cycles at 0.1 C) and excellent rate performance (specific capacity of 578 mA h g-1 at 5 C). This work opens a new door for the fabrication of hyphae carbon composites via fermentation for electrochemical energy storage.

4.
Small ; 20(15): e2306381, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38013253

RESUMEN

All-solid-state lithium metal batteries (LMBs) are regarded as one of the most viable energy storage devices and their comprehensive properties are mainly controlled by solid electrolytes and interface compatibility. This work proposes an advanced poly(vinylidene fluoride-hexafluoropropylene) based gel polymer electrolyte (AP-GPEs) via functional superposition strategy, which involves incorporating butyl acrylate and polyethylene glycol diacrylate as elastic optimization framework, triethyl phosphate and fluoroethylene carbonate as flameproof liquid plasticizers, and Li7La3Zr2O12 nanowires (LLZO-w) as ion-conductive fillers, endowing the designed AP-GPEs/LLZO-w membrane with high mechanical strength, excellent flexibility, low flammability, low activation energy (0.137 eV), and improved ionic conductivity (0.42 × 10-3 S cm-1 at 20 °C) due to continuous ionic transport pathways. Additionally, the AP-GPEs/LLZO-w membrane shows good safety and chemical/electrochemical compatibility with the lithium anode, owing to the synergistic effect of LLZO-w filler, flexible frameworks, and flame retardants. Consequently, the LiFePO4/Li batteries assembled with AP-GPEs/LLZO-w electrolyte exhibit enhanced cycling performance (87.3% capacity retention after 600 cycles at 1 C) and notable high-rate capacity (93.3 mAh g-1 at 5 C). This work proposes a novel functional superposition strategy for the synthesis of high-performance comprehensive GPEs for LMBs.

5.
Small ; : e2401491, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38751305

RESUMEN

The design and fabrication of a lithiophilic skeleton are highly important for constructing advanced Li metal anodes. In this work, a new lithiophilic skeleton is reported by planting metal sulfides (e.g., Ni3S2) on vertical graphene (VG) via a facile ultrafast Joule heating (UJH) method, which facilitates the homogeneous distribution of lithiophilic sites on carbon cloth (CC) supported VG substrate with firm bonding. Ni3S2 nanoparticles are homogeneously anchored on the optimized skeleton as CC/VG@Ni3S2, which ensures high conductivity and uniform deposition of Li metal with non-dendrites. By means of systematic electrochemical characterizations, the symmetric cells coupled with CC/VG@Ni3S2 deliver a steady long-term cycle within 14 mV overpotential for 1800 h (900 cycles) at 1 mA cm-2 and 1 mAh cm-2. Meanwhile, the designed CC/VG@Ni3S2-Li||LFP full cell shows notable electrochemical performance with a capacity retention of 92.44% at 0.5 C after 500 cycles and exceptional rate performance. This novel synthesis strategy for metal sulfides on hierarchical carbon-based materials sheds new light on the development of high-performance lithium metal batteries (LMBs).

6.
Opt Express ; 32(10): 16913-16924, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38858887

RESUMEN

What we believe to be a novel reconfigurable multi-channel microwave photonic (MWP) receiver for multi-band RF signal is demonstrated for the first time, to the best of our knowledge. A reconfigurable MWP signal processing chip based on two cascaded microring filter banks is employed in the proposed receiver, which slices the multi-band RF input into several narrow band signals and selects optical frequency comb lines for frequency converting of each channel. Due to the significant reconfigurability of the signal processing chip, the proposed receiver can flexibly choose the output frequency band of each channel, and thus different frequency components of the multi-band RF input can be down converted to the intermediate frequency (IF) band for receiving or converted to other frequency band for forwarding. A multi-band RF signal composed of a linear frequency modulation (LFM) signal with 2 GHz bandwidth and a quad-phase shift keyed (QPSK) signal with 100 Mbit/s rate is experimentally received and reconstructed by the proposed receiver, where the reconstructed LFM component exhibits a signal to noise ratio (SNR) of 10.2 dB, and the reconstructed QPSK component reaches a high SNR of 26.1 dB and a great error vector magnitude (EVM) of 11.73%. On the other hand, the QPSK component of the multi-band RF signal centered at 13.5 GHz is successfully converted to 3.1 GHz.

7.
Chemistry ; 30(19): e202304168, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38264940

RESUMEN

"Carbon Peak and Carbon Neutrality" is an important strategic goal for the sustainable development of human society. Typically, a key means to achieve these goals is through electrochemical energy storage technologies and materials. In this context, the rational synthesis and modification of battery materials through new technologies play critical roles. Plasma technology, based on the principles of free radical chemistry, is considered a promising alternative for the construction of advanced battery materials due to its inherent advantages such as superior versatility, high reactivity, excellent conformal properties, low consumption and environmental friendliness. In this perspective paper, we discuss the working principle of plasma and its applied research on battery materials based on plasma conversion, deposition, etching, doping, etc. Furthermore, the new application directions of multiphase plasma associated with solid, liquid and gas sources are proposed and their application examples for batteries (e. g. lithium-ion batteries, lithium-sulfur batteries, zinc-air batteries) are given. Finally, the current challenges and future development trends of plasma technology are briefly summarized to provide guidance for the next generation of energy technologies.

8.
Cerebrovasc Dis ; 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38185108

RESUMEN

INTRODUCTION The efficacy and safety of low- and standard-dose alteplase for acute ischemic stroke (AIS) have not been consistently compared in previous studies. Nevertheless, the distinctions in the effects of low- and standard-dose alteplase, particularly within the context of bridging therapy (BT) for large vessel occlusion (LVO), warrant further exploration. This study compared clinical outcomes between BT with low- and standard-dose alteplase in patients with LVO-related AIS. METHODS We performed a search for randomized controlled trials and prospective or retrospective cohort studies investigating the clinical outcomes of BT in AIS in the PubMed, Embase, and Cochrane Library databases from inception to November 2022. The outcomes of interest were 90-day functional independence, successful recanalization, symptomatic intracerebral hemorrhage (sICH) and mortality; these outcomes were compared between patients who received BT with low- (primarily 0.6 mg/kg) and standard-dose alteplase (0.9 mg/kg). We used the standard-dose group as the reference and calculated the odds ratio (OR) and its 95% confidence interval (CI) from the raw numbers. Meta-analysis and ethnicity-based subgroup analysis (Asian and non-Asian) were performed. RESULTS Five observational studies, published after 2017 and including 408 patients, were included. The meta-analysis results demonstrated that compared with BT with standard-dose alteplase, BT with low-dose alteplase did not improve 90-day functional independence (odds ratio, [OR] 1.02; 95% confidence interval [CI], 0.58-1.80). Nevertheless, BT with low-dose alteplase was associated with a comparable successful recanalization rate (OR, 1.35; 95% CI, 0.68-2.67) and similar sICH incidence (OR 0.36; 95% CI, 0.10-1.36), and mortality (OR, 0.64; 95% CI, 0.27-1.54) compared with BT with standard-dose alteplase; however, the above three results were nonsignificant. In the ethnicity-based subgroup analyses, no differences were noted between Asian and non-Asian participants. CONCLUSIONS In patients with LVO-related AIS, BT with low- or standard-dose alteplase may provide similar efficacy, with no significant differences in sICH incidence and mortality. Additional well-designed prospective studies are required to confirm this result.

9.
Acta Pharmacol Sin ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811775

RESUMEN

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor precursor homologous domain A (EGF-A) of low-density lipoprotein receptor (LDLR) in the liver and triggers the degradation of LDLR via the lysosomal pathway, consequently leading to an elevation in plasma LDL-C levels. Inhibiting PCSK9 prolongs the lifespan of LDLR and maintains cholesterol homeostasis in the body. Thus, PCSK9 is an innovative pharmacological target for treating hypercholesterolemia and atherosclerosis. In this study, we discovered that E28362 was a novel small-molecule PCSK9 inhibitor by conducting a virtual screening of a library containing 40,000 compounds. E28362 (5, 10, 20 µM) dose-dependently increased the protein levels of LDLR in both total protein and the membrane fraction in both HepG2 and AML12 cells, and enhanced the uptake of DiI-LDL in AML12 cells. MTT assay showed that E28362 up to 80 µM had no obvious toxicity in HepG2, AML12, and HEK293a cells. The effects of E28362 on hyperlipidemia and atherosclerosis were evaluated in three different animal models. In high-fat diet-fed golden hamsters, administration of E28362 (6.7, 20, 60 mg·kg-1·d-1, i.g.) for 4 weeks significantly reduced plasma total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and PCSK9 levels, and reduced liver TC and TG contents. In Western diet-fed ApoE-/- mice (20, 60 mg·kg-1·d-1, i.g.) and human PCSK9 D374Y overexpression mice (60 mg·kg-1·d-1, i.g.), administration of E28362 for 12 weeks significantly decreased plasma LDL-C levels and the area of atherosclerotic lesions in en face aortas and aortic roots. Moreover, E28362 significantly increased the protein expression level of LDLR in the liver. We revealed that E28362 selectively bound to PCSK9 in HepG2 and AML12 cells, blocked the interaction between LDLR and PCSK9, and induced the degradation of PCSK9 through the ubiquitin-proteasome pathway, which finally resulted in increased LDLR protein levels. In conclusion, E28362 can block the interaction between PCSK9 and LDLR, induce the degradation of PCSK9, increase LDLR protein levels, and alleviate hyperlipidemia and atherosclerosis in three distinct animal models, suggesting that E28362 is a promising lead compound for the treatment of hyperlipidemia and atherosclerosis.

10.
Molecules ; 29(8)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38675552

RESUMEN

Exploiting novel materials with high specific capacities is crucial for the progress of advanced energy storage devices. Intentionally constructing functional heterostructures based on a variety of two-dimensional (2D) substances proves to be an extremely efficient method for capitalizing on the shared benefits of these materials. By elaborately designing the structure, a greatly escalated steadiness can be achieved throughout electrochemical cycles, along with boosted electron transfer kinetics. In this study, chemical vapor deposition (CVD) was utilized to alter the surface composition of multilayer Ti3C2Tx MXene, contributing to contriving various layered heterostructure materials through a precise adjustment of the reaction temperature. The optimal composite materials at a reaction temperature of 500 °C (defined as MX500), incorporating MXene as the conductive substrate, exhibited outstanding stability and high coulombic efficiency during electrochemical cycling. Meanwhile, the reactive sites are increased by using TiS2 and TiO2 at the heterogeneous interfaces, which sustains a specific capacity of 449 mAh g-1 after 200 cycles at a current density of 0.1 A g-1 and further demonstrates their exceptional electrochemical characteristics. Additionally, the noted pseudocapacitive properties, like MXene materials, further highlight the diverse capabilities of intuitive material design. This study illuminates the complex details of surface modification in multilayer MXene and offers a crucial understanding of the strategic creation of heterostructures, significantly impacting sophisticated electrochemical applications.

11.
Small ; 19(24): e2208164, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36916700

RESUMEN

Solid-state lithium-sulfur batteries (SSLSBs) have attracted tremendous research interest due to their large theoretical energy density and high safety, which are highly important indicators for the development of next-generation energy storage devices. Particularly, safety and "shuttle effect" issues originating from volatile and flammable liquid organic electrolytes can be fully mitigated by switching to a solid-state configuration. However, their road to thecommercial application is still plagued with numerous challenges, most notably the intrinsic electrochemical instability of solid-state electrolytes (SSEs) materials and their interfacial compatibility with electrodes and electrolytes. In this review, a critical discussion on the key issues and problems of different types of SSEs as well as the corresponding optimization strategies are first highlighted. Then, the state-of-the-art preparation methods and properties of different kinds of SSE materials, and their manufacture, characterization and performance in SSLSBs are summarized in detail. Finally, a scientific outlook for the future development of SSEs and the avenue to commercial application of SSLSBs is also proposed.

12.
Anim Biotechnol ; 34(4): 986-993, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34865600

RESUMEN

The DNA copy number variations (CNVs) are widely involved in affecting various kinds of biological functions, such as environmental adaptation. Tibetan sheep and White Suffolk sheep are two representative indigenous and exotic breeds raised in Sichuan, China, and both of them have many contrasting biological characteristics. In this study, we employed high-throughput sequencing approach to investigate genome-wide CNVs between the two sheep breeds. A total of 11,135 CNV regions (CNVRs) consisting of 6,488 deletions and 4,647 duplications were detected, whose length ranged from 1,599 bp to 0.56 Mb with the mean of 4,658 bp. There were 281 CNVRs segregated between Tibetan sheep and White Suffolk sheep, and 18 of them have been fixed within both breeds. Functional analyses of candidate genes within the segregating CNVRs revealed the thyroid hormone signaling pathway and CTNNB1 gene that would be responsible for differential biological characteristics of breeds, such as energy metabolism, seasonal reproduction, and litter size. Furthermore, the segregating CNVRs identified in this study were overlapped with many known quantitative trait loci that are associated with growth, testis weight, and reproductive seasonality. In conclusion, these results help us better understanding differential biological characteristics between Tibetan sheep and White Suffolk sheep.


Asunto(s)
Variaciones en el Número de Copia de ADN , Sitios de Carácter Cuantitativo , Masculino , Animales , Ovinos/genética , Variaciones en el Número de Copia de ADN/genética , Tibet , China , Transducción de Señal
13.
J Asian Nat Prod Res ; 25(8): 796-802, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36272140

RESUMEN

In this paper, we present the discovery of a novel salicylic acid derivative, moldavica acid A (1), and a new natural dibenzo[b,f]oxepin, moldavica acid B (2), together with four known phenylpropionic acids (3-6) and protocatechuic acid (7) that were isolated from Dracocephalum moldavica L. Their structures were elucidated by comprehensive spectroscopic methods, including infrared and nuclear magnetic resonance. Compound 1 is the first example of salicylic acid linking a carboxylated α-pyrone via an ethyl bridge. Beyond expanding the knowledge of the chemical diversity of D. moldavica, both compounds 1 and 2 were shown to upregulate the expression of Kruppel-like factor 2, which could serve as a prospective therapeutic target for the treatment of atherosclerosis.

14.
Small ; 18(7): e2106074, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34862735

RESUMEN

Nickel sulfides with high theoretical capacitance have aroused tremendous attention for next-generation supercapacitors. Unfortunately, the structural durability of nickel sulfides is insufficient to support the long-term working situation. Herein, Ni3 S4-x hollow microspheres with sulfur vacancies (Ni3 S4-x HMs) are constructed by a liquid-phase anion exchange process using the Ni-MOF as the precursor. Both experimental investigation and theoretical analysis suggest that the deliberately introduced sulfur vacancies effectively improve the anionic adsorptive ability of nickel sulfides in the KOH electrolyte, significantly enhancing the reversible capacitance and structural durability (1884 F g-1 at 2 A g-1 , capacity retention of 97.9% after 10 000 cycles). In addition, an asymmetrical solid-state supercapacitor consisting of Ni3 S4-x HMs cathode and activated carbon anode shows infusive energy/power density (33.05 Wh kg-1 /1.68 kW kg-1 ) and remains 82.4% over 10 000 repeated charging/discharging processes in the KOH-PVA gel electrolyte. The strategies can be developed to enlighten the structural design of various metal sulfides materials adopted in electrochemical energy storage devices including alkali ion batteries, supercapacitors, and electrocatalysts.

15.
Opt Express ; 30(17): 30420-30429, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-36242146

RESUMEN

Narrow linewidth and fast-chirped frequency are essential in frequency-modulated continuous-wave lasers. We introduce a laser that meets these requirements by coupling a distributed feedback laser with an external high-Q microring resonator, where a bulky stacked piezoelectric chip is attached to the resonator for fast tuning. The laser demonstrates an ultranarrow intrinsic linewidth of 22 Hz in the self-injection-locked state. Actuated by the bulky piezoelectric chip, the maximum triangular actuation bandwidth can reach 100 kHz. The driving voltage is filtered to avoid a resonant mechanical mode, obtaining the minimum residual linearity error at 10 kHz with a 4.2 GHz tuning range. A light detection and ranging system was set up for a proof-of-concept experiment, demonstrating a high detection precision with standard deviations of 2.7 and 4.0 cm for targets at 15 and 30 m, respectively.

16.
Opt Express ; 30(26): 46626-46648, 2022 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-36558611

RESUMEN

In this paper, we put forward a data-driven fiber model based on the deep neural network with multi-head attention mechanism. This model, which predicts signal evolution through fiber transmission in optical fiber telecommunications, can have advantages in computation time without losing much accuracy compared with conventional split-step fourier method (SSFM). In contrast with other neural network based models, this model obtains a relatively good balance between prediction accuracy and distance generalization especially in cases where higher bit rate and more complicated modulation formats are adopted. By numerically demonstration, this model can have ability of predicting up to 16-QAM 160Gbps signals with any transmission distances ranging from 0 to 100 km under both circumstances of the signals without or with the noise.

17.
Opt Express ; 30(21): 39111-39128, 2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36258459

RESUMEN

Snapshot compressive imaging (SCI) encodes high-speed scene video into a snapshot measurement and then computationally makes reconstructions, allowing for efficient high-dimensional data acquisition. Numerous algorithms, ranging from regularization-based optimization and deep learning, are being investigated to improve reconstruction quality, but they are still limited by the ill-posed and information-deficient nature of the standard SCI paradigm. To overcome these drawbacks, we propose a new key frames assisted hybrid encoding paradigm for compressive video sensing, termed KH-CVS, that alternatively captures short-exposure key frames without coding and long-exposure encoded compressive frames to jointly reconstruct high-quality video. With the use of optical flow and spatial warping, a deep convolutional neural network framework is constructed to integrate the benefits of these two types of frames. Extensive experiments on both simulations and real data from the prototype we developed verify the superiority of the proposed method.

18.
J Nat Prod ; 85(4): 972-979, 2022 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-35385664

RESUMEN

MS/MS-based molecular networking strain prioritization led to the discovery of a group of cyclic depsipeptides from an endolichenic Xylaria sp. The main component, xylaroamide A (1), was obtained by LC-MS-guided isolation. The planar structure of compound 1 was elucidated via 1D and 2D NMR, as well as MS/MS data. The configurations were fully determined by the combination of advanced Marfey's analysis, partial hydrolysis, Mosher's reaction, and GIAO NMR calculation based on a restricted conformational search. A plausible biosynthetic pathway for xylaroamide A (1) involving a rare trans-acting N-methyltransferase is proposed based on bioinformatics analysis. Xylaroamide A (1) exhibited inhibitory activity against cancer cell lines BT-549 and RKO with IC50 values of 2.5 and 9.5 µM, respectively.


Asunto(s)
Depsipéptidos , Xylariales , Depsipéptidos/química , Conformación Molecular , Estructura Molecular , Péptidos Cíclicos/química , Espectrometría de Masas en Tándem , Xylariales/química
19.
Bioorg Chem ; 127: 105971, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35749855

RESUMEN

Liver fibrosis is an important process in chronic liver disease and is strongly related to poor prognosis. Dehydromevalonolactone (C8) is a natural product isolated from a fungus of Fusarium sp. CPCC 401218, and its pharmacological activity has never been reported before. In this study, the potential of C8 as an anti-hepatic fibrosis agent was investigated. In human hepatic stellate cell (HSC) line LX-2, C8 suppressed the increased expression of COL1A1 and α-SMA induced by TGFß1, which indicated that C8 could repress the activation of HSCs. In bile duct ligated rats, C8 administration (100 mg/kg, i.p.) markedly attenuated liver injury, fibrosis, and inflammation, and suppressed the expression of the macrophage surface marker F4/80. In terms of mechanism, C8 treatment blocked the activation of the NLRP3 inflammasome, which was stimulated by LPS and nigericin in bone marrow-derived macrophages (BMDMs) and companied by the release of active IL-1ß. In addition, the activation of LX-2 cells induced by IL-1ß released from BMDMs was also inhibited after C8 administration, which indicated that C8 repressed HSCs activation by inhibiting the activation of NLRP3 inflammasome in macrophages. Furthermore, C8 exhibited the effects of anti-fibrosis and inhibiting the expression of NLRP3 inflammasome in non-alcoholic steatohepatitis (NASH) mice. Finally, C8 can be commendably absorbed in vivo and was safe for mice at the concentration of 1000 mg/kg (p.o.). In summary, our study reveals that C8 ameliorates HSCs activation and liver fibrosis in cholestasis rats and NASH mice by inhibiting NLRP3 inflammasome in macrophages, and C8 might be a safe and effective candidate for the treatment of liver fibrosis.


Asunto(s)
Inflamasomas , Ácido Mevalónico/análogos & derivados , Enfermedad del Hígado Graso no Alcohólico , Animales , Fibrosis , Humanos , Inflamasomas/metabolismo , Inflamación/metabolismo , Hígado/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Ácido Mevalónico/análisis , Ácido Mevalónico/farmacología , Ácido Mevalónico/uso terapéutico , Ratones , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Ratas
20.
J Asian Nat Prod Res ; : 1-13, 2022 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-35749256

RESUMEN

Four new lignans (1-4) and one new neolignan (5), along with two known lignan derivatives (6 and 7), were isolated from an aqueous extract of the Isatis indigotica root (ban lan gen). Their structures were determined by spectroscopic data analysis, chemical method, and theoretical calculation, for which 1 was proved by single-crystal X-ray diffraction. Compound 2 exhibited antiviral activity against influenza virus A/Hanfang/359/95 (H3N2) with an IC50 value of 11.1 µM and a selective index (SI) > 9, while 1 and 5 are the first examples of sulfonated lignan and neolignan from nature.

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