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1.
Adv Mater ; : e2409904, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39254348

RESUMEN

The positive electrodes of non-aqueous aluminum ion batteries (AIBs) frequently encounter significant issues, for instance, low capacity in graphite (mechanism: anion de/intercalation and large electrode deformation induced) and poor stability in inorganic positive electrodes (mechanism: multi-electron redox reaction and dissolution of active materials induced). Here, metallo-porphyrin compounds (employed Fe2+, Co2+, Ni2+, Cu2+, and Zn2+ as the ion centers) are introduced to effectively enhance both the cycling stability and reversible capacity due to the formation of stable conjugated metal-organic coordination and presence of axially coordinated active sites, respectively. With the regulation of electronic energy levels, the d-orbitals in the redox reactions and electron transfer pathways can be rearranged. The 5,10,15,20-tetraphenyl-21H,23H-porphine nickle(II) (NiTPP) presents the highest specific capacity (177.1 mAh g-1), with an increment of 32.1% and 77.1% in comparison with the capacities of H2TPP and graphite, respectively, which offers a new route for developing high-capacity positive electrodes for stable AIBs.

2.
Curr Alzheimer Res ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39136501

RESUMEN

Alzheimer's disease (AD) is the most common type of dementia among middle-aged and elderly individuals. Accelerating the prevention and treatment of AD has become an urgent problem. New technology including Computer-aided drug design (CADD) can effectively reduce the medication cost for patients with AD, reduce the cost of living, and improve the quality of life of patients, providing new ideas for treating AD. This paper reviews the pathogenesis of AD, the latest developments in CADD and other small-molecule docking technologies for drug discovery and development; the current research status of small-molecule compounds for AD at home and abroad from the perspective of drug action targets; and the development trend of new drug development for AD in the future.

3.
Angew Chem Int Ed Engl ; : e202410110, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38972839

RESUMEN

Nonaqueous organic aluminum batteries are considered as promising high-safety energy storage devices due to stable ionic liquid electrolytes and Al metals. However, the stability and capacity of organic positive electrodes are limited by their inherent high solubility and low active organic molecules. To address such issues, here porphyrin compounds with rigid molecular structures present stable and reversible capability in electrochemically storing AlCl2 +. Comparison between the porphyrin molecules with electron-donating groups (TPP-EDG) and with electron-withdrawing groups (TPP-EWG) suggests that EDG is responsible for increasing both highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels, resulting in decreased redox potentials. On the other hand, EWG is associated with decreasing both HOMO and LUMO energy levels, leading to promoted redox potentials. EDG and EWG play critical roles in regulating electron density of porphyrin π bond and electrochemical energy storage kinetics behavior. The competitive mechanism between electrochemical redox reaction and de/adsorption processes suggests that TPP-OCH3 delivers the highest specific capacity ~171.8 mAh g-1, approaching a record in the organic Al batteries.

4.
ACS Nano ; 18(29): 18852-18869, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38993077

RESUMEN

Vanadium redox flow battery (VRFB) has garnered significant attention due to its potential for facilitating the cost-effective utilization of renewable energy and large-scale power storage. However, the limited electrochemical activity of the electrode in vanadium redox reactions poses a challenge in achieving a high-performance VRFB. Consequently, there is a pressing need to assess advancements in electrodes to inspire innovative approaches for enhancing electrode structure and composition. This work categorizes three-dimensional (3D) electrodes derived from materials such as foam, biomass, and electrospun fibers. By employing a flexible electrode design and compositional functionalization, high-speed mass transfer channels and abundant active sites for vanadium redox reactions can be created. Furthermore, the incorporation of 3D electrocatalysts into the electrodes is discussed, including metal-based, carbon-based, and composite materials. The strong interaction and ordered arrangement of these nanocomposites have an influence on the uniformity and stability of the surface charge distribution, thereby enhancing the electrochemical performance of the composite electrodes. Finally, the challenges and perspectives of VRFB are explored through advancements in 3D electrodes, 3D electrocatalysts, and mechanisms. It is hoped that this review will inspire the development of methodology and concept of 3D electrodes in VRFB, so as to promote the future development of scientific energy storage and conversion technology.

5.
Fundam Res ; 4(1): 86-94, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38933837

RESUMEN

Despite its existence for more than 80 years, the titanium industry is still challenged by massive carbon emissions, high production costs, and large resource waste. More than one hundred million tons of Ti-bearing blast furnace slag (TB-slag) has been discarded in China because of the difficulty of reutilization, which requires efficient titanium extraction and recovery technologies. This paper describes a low-cost, carbon-emission-free method for Ti extraction and oxygen evolution via molten oxide electrolysis (MOE) vacuum distillation. After a comprehensive analysis of the binding energies and activities of liquid metals, the highlights of our study are as follows. 1) Sb has the best preferential deposition of Ti among a series of high-Ti-affinitive liquid metal cathodes (Cu, Ni, Pb, Sn, and Sb). 2) The Ir anode was first used in TB-slag with IrO2 formed on its surface to protect it from further corrosion. 3) An alloy containing Ti and Ca can be obtained by MOE, and Ti and Ca metals can be refined by further vacuum distillation. 4) A closed loop is formed in the overall process owing to the recyclable Sb cathode and continuous feeding of TB-slag into the electrolyte. This simple, low-cost, and environmentally friendly method can realize the efficient utilization of Ti resources and achieve carbon neutrality.

6.
Int Immunopharmacol ; 137: 112468, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38906004

RESUMEN

Prolonged or excessive oxidative stress can lead to premature cellular and body aging. Mannan-binding lectin (MBL) is synthesized by the liver and plays an important role in innate immunity, anti-inflammation, and anti-oxidation, and has a positive impact on health and longevity. To date, few studies investigated the role of MBL in attenuating oxidative stress-induced senescence. In this study, we evaluated the role of MBL in oxidative stress-induced premature aging and explored its underlying mechanism in C57BL/6 mice and mouse embryonic fibroblasts (NIH/3T3). First, we established an oxidative premature senescence model induced by D-galactose in C57BL/6 mice. We found that MBL-deficient mice had a marked aging-like appearance, reduced learning and spatial exploration abilities, severe liver pathological damage, and significantly upregulated expression of Senescence-associated proteins (p53 and p21), inflammatory kinesins (IL-1ß and IL-6), and the senescence ß-galactosidase (SA-ß-Gal) positive rate as compared with WT mice. In the H2O2-induced oxidative senescence model of NIH/3T3 cells, consistent results were obtained after MBL intervention. In addition, MBL effectively inhibited G1 phase arrest, ROS levels, DNA damage, and mitochondrial dysfunction in premature senescent cells. Mechanistically, we found that oxidative stress inhibited the nicotinamide adenine dinucleotide (NAD+)/ silent information regulator 1 (Sirt1) signaling pathway, while MBL activated the NAD+/Sirt1 signaling pathway inhibited by oxidative stress. In addition, MBL could activate the NAD+/Sirt1 pathway by upregulating NAMPT, which in turn inhibited p38 phosphorylation by activating the NAD+/Sirt1 pathway. In conclusion, MBL inhibits oxidative aging, which may facilitate the development of therapeutics to delay oxidative aging.


Asunto(s)
Senescencia Celular , Galactosa , Lectina de Unión a Manosa , Ratones Endogámicos C57BL , NAD , Estrés Oxidativo , Transducción de Señal , Sirtuina 1 , Animales , Sirtuina 1/metabolismo , Sirtuina 1/genética , Estrés Oxidativo/efectos de los fármacos , Ratones , Senescencia Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Células 3T3 NIH , NAD/metabolismo , Lectina de Unión a Manosa/metabolismo , Lectina de Unión a Manosa/genética , Ratones Noqueados , Peróxido de Hidrógeno/metabolismo , Masculino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo
7.
Adv Mater ; 36(24): e2401008, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38446734

RESUMEN

Quasi-solid-state potassium-ion batteries (SSPIBs) are of great potential for commercial use due to the abundant reserves and cost-effectiveness of resources, as well as high safety. Gel polymer electrolytes (GPEs) with high ionic conductivity and fast interfacial charge transport are necessary for SSPIBs. Here, the weak electrostatic force between K+ and electronegative functional groups in the ethoxylated trimethylolpropane triacrylate (ETPTA) polymer chains, which can promote fast migration of free K+, is revealed. To further enhance the interfacial reaction kinetics, a multilayered GPE by in situ growth of poly(vinylidenefluoride-co-hexafluoropropylene) (PVDF-HFP) on ETPTA (PVDF-HFP|ETPTA|PVDF-HFP) is constructed to improve the interface contact and provide sufficient K+ concentration in PVDF-HFP. A high ion transference number (0.92) and a superior ionic conductivity (5.15 × 10-3 S cm-1) are achieved. Consequently, the SSPIBs with both intercalation-type (PB) and conversion-type (PTCDA) cathodes show the best battery performance among all reported SSPIBs of the same cathode. These findings demonstrate that potassium-ion batteries have the potential to surpass Li/Na ion batteries in solid-state systems.

8.
Angew Chem Int Ed Engl ; 63(12): e202317203, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38286752

RESUMEN

The two-dimensional (2D) MXenes with sufficient interlayer spacing are promising cathode materials for aluminum-ion batteries (AIBs), yet the electrostatic repulsion effect between the surface negative charges and the active anions (AlCl4 - ) hinders the intercalation of AlCl4 - and is usually ignored. Here, we propose a charge regulation strategy for MXene cathodes to overcome this challenge. By doping N and Co, the zeta potential is gradually transformed from negative (Ti3 C2 Tx ) to near-neutral (Ti3 CNTx ), and finally positive (Ti3 CNTx @Co). Therefore, the electrostatic repulsion force can be greatly weakened between Ti3 CNTx and AlCl4 - , or even formed a strong electrostatic attraction between Ti3 CNTx @Co and AlCl4 - , which can not only accommodate more AlCl4 - ions in the Ti3 CNTx @Co interlayers to increase the capacity, but also solve the stacking and expansion problems. As a result, the optimized Al-MXene battery exhibits an ultrahigh capacity of up to 240 mAh g-1 (2-4 times the capacity of graphite cathode, 60-120 mAh g-1 ) and a potential ultrahigh energy density (432 Wh kg-1 , 2-4 times the value of graphite, 110-220 Wh kg-1 ) based on the mass of cathode materials, comparable to LiFePO4 -based lithium-ion batteries (350-450 Wh kg-1 , based on the mass of LiFePO4 ).

9.
Osteoporos Int ; 35(2): 243-253, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37857915

RESUMEN

Iron is a necessary trace element in the human body, and it participates in many physiological processes. Disorders of iron metabolism can cause lesions in many tissues and organs, including bone. Recently, iron has gained attention as an independent factor influencing bone metabolism disorders, especially the involvement of iron overload in osteoporosis. The aim of this review was to summarize the findings from clinical and animal model research regarding the involvement of iron in bone metabolism disorders and to elucidate the mechanisms behind iron overload and osteoporosis. Lastly, we aimed to describe the association between bone loss and iron overload. We believe that a reduction in iron accumulation can be used as an alternative treatment to assist in the treatment of osteoporosis, to improve bone mass, and to improve the quality of life of patients.


Asunto(s)
Sobrecarga de Hierro , Osteoporosis , Animales , Humanos , Hierro/metabolismo , Calidad de Vida , Sobrecarga de Hierro/complicaciones , Huesos/metabolismo , Osteoporosis/tratamiento farmacológico , Osteoporosis/etiología , Osteoporosis/metabolismo
10.
Small ; 20(22): e2309823, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38109127

RESUMEN

Electrocatalysts with low Pt loading mass to achieve high current density (≥1 A cm-2) for hydrogen evolution reaction (HER) are still extremely challenging due to the limited intrinsic activity and weak stability of catalytic sites. The modulation of the electronic microenvironment of the support-Pt structure is crucial to enhance the intrinsic activity and stability of catalytic sites. Herein, an innovative titanium oxycarbide (TiVCO) solid solution with Ti vacancies (TiV) is proposed as support to anchor sub-nanoscale Pt atomic clusters (Pt ACs) and a stable "TiV-Pt ACs" structure is carefully designed. The electronic microenvironment of "TiV-Pt ACs" is indirectly optimized by an unsaturated C/O site near TiV. Thanks to this, novel "TiV-Pt ACs" structure (Pt@TiVCO) with low Pt loading mass (2.44 wt.%) exhibits excellent HER activity in acidic solution and the mass activity is more than ten times that of commercial 20% Pt/C at the overpotentials of 50 and 100 mV. Particularly, Pt@TiVCO shows amazing stability at high and fluctuating current density of 1-2 A cm-2 for 120 h. This work provides a novel and promising method to develop stable and low-loading Pt-based catalysts adapting to high current density.

11.
Heliyon ; 9(11): e21882, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38034794

RESUMEN

Mannan-binding lectin (MBL) is a pattern-recognition molecule that plays a crucial role in innate immunity. MBL deficiency correlates with an increased risk of chronic kidney disease (CKD). However, the molecular mechanisms are not fully defined. Here, we established a CKD model in wild-type (WT) and MBL-deficient (MBL-/-) mice via unilateral ureteral obstruction (UUO). The result showed that MBL deficiency aggravated the pathogenesis of renal fibrosis in CKD mice. Strikingly, the in vivo macrophage depletion investigation revealed that macrophages play an essential role in the MBL-mediated suppression of renal fibrosis. We found that MBL limited the progression of macrophage-to-myofibroblast transition (MMT) in kidney tissues of UUO mice. Further in vitro study showed that MBL-/- macrophages exhibited significantly increased levels of fibrotic-related molecules compared with WT cells upon transforming growth factor beta (TGF-ß) stimulation. We demonstrated that MBL inhibited the MMT process by suppressing the production of matrix metalloproteinase 9 (MMP-9) and activation of Akt signaling. In summary, our study revealed an expected role of MBL on macrophage transition during renal fibrosis, thus offering new insight into the potential of MBL as a therapeutic target for CKD.

12.
J Phys Chem B ; 127(40): 8669-8680, 2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37781882

RESUMEN

Molten salt electrochemistry has been widely used in many fields, especially for metal extraction/refinement. The understanding of mass transfer in molten salts under harsh operation conditions is of great importance to reveal reaction mechanisms and advance fine technologies. It has been generally assumed that natural convection is negligible in stagnant molten salt electrochemistry. Herein, we report an abnormal natural convection in molten LiCl-KCl, with the arising time from 2.37 s at 873 K to 10.13 s at 673 K. Using the concentration correction factor, the derived thickness of the natural convection-diffusion layer (δconv.) was found to be ranging from 128 to 163 µm, much thinner than those in aqueous solutions (∼200 µm). The simulations showed that the notable natural convection resulted from convection-diffusion layer (CDL) convection dominated over the density-driven convection even at high redox concentrations, implying the severe vibration of molten salt systems. To suppress the intense natural convection, we predicted that the use of microelectrodes (with radii less than 23.2 µm for δconv. = 150 µm) would be a promising tool, regardless of their inferior stabilities in high-temperature molten salts at this stage. These innovative findings offer insights into the impact of natural convection on mass transfer in molten salts that have not been previously revealed.

13.
Proc Natl Acad Sci U S A ; 120(28): e2301780120, 2023 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-37399420

RESUMEN

Nearly half of the elements in the periodic table are extracted, refined, or plated using electrodeposition in high-temperature melts. However, operando observations and tuning of the electrodeposition process during realistic electrolysis operations are extremely difficult due to severe reaction conditions and complicated electrolytic cell, which makes the improvement of the process very blind and inefficient. Here, we developed a multipurpose operando high-temperature electrochemical instrument that combines operando Raman microspectroscopy analysis, optical microscopy imaging, and a tunable magnetic field. Subsequently, the electrodeposition of Ti-which is a typical polyvalent metal and generally shows a very complex electrode process-was used to verify the stability of the instrument. The complex multistep cathodic process of Ti in the molten salt at 823 K was systematically analyzed by a multidimensional operando analysis strategy involving multiple experimental studies, theoretical calculations, etc. The regulatory effect and its corresponding scale-span mechanism of the magnetic field on the electrodeposition process of Ti were also elucidated, which would be inaccessible with existing experimental techniques and is significant for the real-time and rational optimization of the process. Overall, this work established a powerful and universal methodology for in-depth analysis of high-temperature electrochemistry.

14.
Adv Mater ; 35(35): e2303943, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37402138

RESUMEN

Al batteries have great potential for renewable energy storage owing to their low cost, high capacity, and safety. High energy density and adaptability to fluctuating electricity are major challenges. Here, a lightweight Al battery for fast storage of fluctuating energy is constructed based on a novel hierarchical porous dendrite-free carbon aerogel film (CAF) anode and an integrated graphite composite carbon aerogel film (GCAF) cathode. A new induced mechanism by the O-containing functional groups on the CAF anode is con-firmed for uniform Al deposition. The GCAF cathode possesses a higher mass utilization ratio due to the extremely high loading mass (9.5-10.0 mg cm-2 ) of graphite materials compared to conventional coated cathodes. Meanwhile, the volume expansion of the GCAF cathode is almost negligible, resulting in better cycling stability. The lightweight CAF‖GCAF full battery can adapt well to large and fluctuating current densities owing to its hierarchical porous structure. A large discharge capacity (115.6 mAh g-1 ) after 2000 cycles and a short charge time (7.0 min) at a high current density are obtained. The construction strategy of lightweight Al batteries based on carbon aerogel electrodes can promote the breakthrough of high-energy-density Al batteries adapted to the fast storage of fluctuating renewable energy.

15.
Exploration (Beijing) ; 3(1): 20210186, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37323618

RESUMEN

Graphite has been used in a wide range of applications since the discovery due to its great chemical stability, excellent electrical conductivity, availability, and ease of processing. However, the synthesis of graphite materials still remains energy-intensive as they are usually produced through a high-temperature treatment (>3000°C). Herein, we introduce a molten salt electrochemical approach utilizing carbon dioxide (CO2) or amorphous carbons as raw precursors for graphite synthesis. With the assistance of molten salts, the processes can be conducted at moderate temperatures (700-850°C). The mechanisms of the electrochemical conversion of CO2 and amorphous carbons into graphitic materials are presented. Furthermore, the factors that affect the graphitization degree of the prepared graphitic products, such as molten salt composition, working temperature, cell voltage, additives, and electrodes, are discussed. The energy storage applications of these graphitic carbons in batteries and supercapacitors are also summarized. Moreover, the energy consumption and cost estimation of the processes are reviewed, which provides perspectives on the large-scale synthesis of graphitic carbons using this molten salt electrochemical strategy.

16.
Parasit Vectors ; 16(1): 210, 2023 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-37344876

RESUMEN

BACKGROUND: Trichomonas vaginalis is a widespread and important sexually transmitted pathogen. Adherence to the surface of the host cell is the precondition for the parasitism and pathogenicity of this parasite. Trichomonas vaginalis adhesion protein 33 (TvAP33) plays a key role in the process of adhesion, but how this protein mediates the adhesion and pathogenicity of T. vaginalis to host cells is unclear. METHODS: The expression of TvAP33 in trophozoites was knocked down by small interfering RNA. VK2/E6E7 cells and mice infected with T. vaginalis were used to evaluate the pathogenicity of T. vaginalis. We constructed a complementary DNA library of VK2/E6E7 cells and screened the protein molecules interacting with TvAP33 by the yeast two-hybrid system. The interaction between TvAP33 and BNIP3 (Bcl-2 interacting protein 3) was analyzed by co-immunoprecipitation and colocalization. RESULTS: Following knockdown of TvAP33 expression, the number of T. vaginalis trophozoites adhering to VK2/E6E7 cells decreased significantly, and the inhibition of VK2/E6E7 cell proliferation and VK2/E6E7 cell apoptosis and death induced by T. vaginalis were reduced. Animal challenge experiments showed that the pathogenicity of trophozoites decreased following passive immunization with TvAP33 antiserum or blocking of the TvAP33 protein. Immunofluorescence analysis revealed that TvAP33 could bind to VK2/E6E7 cells. Eighteen protein molecules interacting with TvAP33 were identified by the yeast two-hybrid system. The interaction between TvAP33 and BNIP3 was further confirmed by co-immunoprecipitation and colocalization. When the expression of both TvAP33 and BNIP3 in trophozoites was knocked down by small RNA interference, the number of T. vaginalis adhering to VK2/E6E7 cells and the inhibition of VK2/E6E7 cell proliferation were significantly lower compared to trophozoites with only knockdown of TvAP33 or only BNIP3. Therefore, the interaction of TvAP33 and BNIP3 in the pathogenesis of T. vaginalis infecting host cells is not unique and involves other molecules. CONCLUSIONS: Our study showed that the interaction between TvAP33 and BNIP3 mediated the adhesion and pathogenicity of T. vaginalis to host cells, providing a basis for searching for drug targets for T. vaginalis as well as new ideas for the prevention and treatment of trichomoniasis.


Asunto(s)
Tricomoniasis , Trichomonas vaginalis , Animales , Ratones , Trichomonas vaginalis/genética , Virulencia , Trofozoítos
17.
Anal Chem ; 95(22): 8596-8604, 2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37227698

RESUMEN

C2H2 and H2, as important chemical and energy raw materials, can be produced effectively and environmentally friendly by the partial oxidation (POX) of CH4. Simultaneous analysis of intermediate gas compositions in the multiprocess (cracking, recovery, degassing, etc) of POX can regulate product generation and improve production efficiency. To overcome the disadvantage of common gas chromatography, we propose a fluorescence noise eliminating fiber-enhanced Raman spectroscopy (FNEFERS) technique for simultaneous and multiprocess analysis of the POX process, in which the fluorescence noise eliminating (FNE) method can effectively eliminate the horizontal and vertical spatial noise to ensure ppm level limits of detection (LOD). The vibration modes of gas compositions related to each POX process such as cracked gas, synthesis gas, and product acetylene are analyzed. Meanwhile, the composition of three-process intermediate sample gases from Sinopec Chongqing SVW Chemical Co., Ltd is quantitatively and qualitatively analyzed simultaneously, along with the ppm level LODs (H2: 11.2 ppm, C2H2: 3.1 ppm, CO2: 9.4 ppm, C2H4: 4.8 ppm, CH4: 1.5 ppm, CO: 17.9 ppm, allene: 1.5 ppm, methyl acetylene: 2.6 ppm, 1,3-butadiene: 2.8 ppm) with a laser power of 180 mW, exposure time of 30 s, and accuracy of higher than 95.2%. This study fully demonstrates the ability of FNEFERS to replace gas chromatography to achieve simultaneous and multiprocess analysis of intermediate compositions for C2H2 and H2 production and to monitor other chemical and energy production processes.

18.
Food Funct ; 14(10): 4647-4661, 2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37102320

RESUMEN

Parkinson's disease (PD) is a tricky neurodegenerative disease characterized with motor deficits and gastrointestinal (GI) dysfunction. Gut microbiota disturbance is reported to be involved in the clinical phenotypes of PD and its pathogenesis through the brain-gut-microbiota axis. Resveratrol is a natural polyphenol that possesses various biological activities in alleviating many diseases, including PD. The present study was aimed to investigate the role of gut microbiota in resveratrol-treated PD mice. A chronic mouse model of PD was generated via the injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probenecid (MPTP/P) for 5 consecutive weeks. Resveratrol was orally administered once a day (30 mg kg-1 d-1) for a total of 8 weeks. From the 6th week to the 8th week, fecal microbiota transplantation (FMT) was performed from resveratrol-treated PD mice to PD mice to evaluate the contribution of resveratrol-shaped microbiota in the alleviation of PD. The results showed that FMT from resveratrol-shaped microbiota remarkably alleviated the mice phenotype from PD progression, including increased latency in the rotarod, shortened beam walking time, increased the number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta (SNpc) and enriched TH-positive fiber density in the striatum. Further experiments revealed that FMT could ameliorate the GI dysfunction by increasing the small intestinal transport rate and the colon length, decreasing the relative abundances of inflammatory cytokines (TNF-α, IL-6 and IL-1ß) in colon epithelial tissue. The 16S rDNA sequencing indicated that FMT attenuated the gut microbial dysbiosis in PD mice by increasing the abundances of Prevotellaceae, Rikenellaceae, Erysipelotrichaceae, Blautia and Alistipes, lowering the ratio of Fimicutes/Bacteroidetes, and decreasing the abundances of Lachnospiraceae and Akkermansia. Therefore, results in this study demonstrated that gut microbiota played a vital role in the prevention of PD progression, and the shaping of the gut microbiota was the pharmacological mechanism of resveratrol in alleviating the phenotype of Parkinson's disease in PD mice.


Asunto(s)
Microbioma Gastrointestinal , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Animales , Ratones , Enfermedad de Parkinson/tratamiento farmacológico , Resveratrol/uso terapéutico , Tirosina 3-Monooxigenasa , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina
19.
Curr Mol Pharmacol ; 16(8): 881-893, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36999419

RESUMEN

BACKGROUND: Melanoma, a highly malignant skin cancer, is a hot topic in oncology treatment research. Nowadays, tumor immunotherapy, especially immunotherapy combined with other therapies, has attracted more and more attention. Indoleamine 2,3-dioxygenase 2 (IDO2), a ratelimiting enzyme of the tryptophan metabolism pathway in the urine of dogs with immunosuppression, is highly expressed in melanoma tissue. Additionally, IDO2 significantly inhibits the anti-tumor immunity of the body and has become a novel target of melanoma treatment. Nifuroxazide, as an intestinal antibacterial agent, was found to be able to inhibit Stat3 expression and exert an anti-tumor effect. Therefore, the present study aimed to examine the therapeutic effect of a self-designed IDO2-small interfering RNA (siRNA) delivered by attenuated Salmonella combined with nifuroxazide on melanoma- bearing mice, as well as determine its underlying mechanism. METHODS: The effect of nifuroxazide on melanoma was detected by flow cytometry, CCK-8 and colony- forming ability assays, respectively, in vitro. The plasmid of siRNA-IDO2 was constructed, and the mice-bearing melanoma model was established. After the treatment, the tumor growth and survival rate were monitored, and the morphological changes of tumor tissue were detected by HE staining. The expression of related proteins was detected by Western blotting, and the expression of CD4 and CD8 positive T cells in tumor tissue was detected by IHC and IF, and the proportion of CD4 and CD8 positive T cells in spleen was detected by flow cytometry. RESULTS: The results demonstrated that the combination therapy effectively inhibited the phosphorylation of Stat3 and the expression level of IDO2 in melanoma cells, which effectively inhibited tumor growth and prolonged the survival time of tumor-bearing mice. The mechanistic study revealed that, compared with control groups and monotherapy groups, the combination treatment group reduced the atypia of tumor cells, increased the apoptotic rate, enhanced the infiltration of T lymphocytes in tumor tissue and increased the CD4+ and CD8+ T lymphocytes in the spleen, suggesting that the mechanism may be associated with the inhibition of tumor cell proliferation, the increase of apoptosis and the enhancement of the cellular immunity. CONCLUSION: In conclusion, IDO2-siRNA combined with nifuroxazide therapy could serve a significant role in the treatment of melanoma-bearing mice, enhance the tumor immunity and provide an experimental basis for identifying a novel combination method for the treatment of melanoma clinically.


Asunto(s)
Melanoma , Nitrofuranos , Animales , Ratones , Perros , ARN Interferente Pequeño/genética , Melanoma/tratamiento farmacológico , Nitrofuranos/farmacología , Nitrofuranos/uso terapéutico , Hidroxibenzoatos/farmacología , Hidroxibenzoatos/uso terapéutico , Línea Celular Tumoral
20.
Adv Sci (Weinh) ; 10(8): e2205269, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36683158

RESUMEN

The petroleum coke (PC) has been widely used as raw materials for the preparation of electrodes in aluminium electrolysis and lithium-ion batteries (LIB), during which massive CO2 gases are produced. To meet global CO2 reduction, an environmentally friendly route for utilizing PC is highly required. Here, a simple, scalable, catalyst-free process that can directly convert high-sulfur PC into graphitic nanomaterials under cathodic polarization in molten CaCl2 -LiCl at mild temperatures is proposed. The energy consumption of the proposed process is calculated to be 3 627.08 kWh t-1 , half that of the traditional graphitization process (≈7,825.21 kWh t-1 graphite). When applied as a negative electrode for LIBs, the as-converted graphite materials deliver a competitive specific capacity of ≈360 mAh g-1 (0.2 C) compared with commercial graphite. This approach has great potential to scale up for sustainably converting low-value PC into high-quality graphite for energy storage.

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