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1.
JACS Au ; 1(8): 1178-1186, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34467356

RESUMO

Two-dimensional (2D) perovskites are emerging as promising candidates for diverse optoelectronic applications because of low cost and excellent stability. In this work, we explore the electronic structures and interfacial properties of (4Tm)2PbI4 with both the collinear and noncollinear DFT (PBE and HSE06) methods. The results evidently manifest that explicitly considering the spin-orbit coupling (SOC) effects is necessary to attain correct band alignment of (4Tm)2PbI4 that agrees with recent experiments (Nat. Chem.2019, 11, 1151; Nature2020, 580, 614). The subsequent time-domain noncollinear DFT-based nonadiabatic carrier dynamics simulations with the SOC effects reveal that the photoinduced electron and hole transfer processes are asymmetric and associated with different rates. The differences are mainly ascribed to considerably different nonadiabatic couplings in charge of the electron and hole transfer processes. Shortly, our current work sheds important light on the mechanism of the interfacial charge carrier transfer processes of (4Tm)2PbI4. The importance of the SOC effects on correctly aligning the band states of (4Tm)2PbI4 may be generalized to similar organic-inorganic hybrid 2D perovskites having heavy Pb atoms.

2.
Angew Chem Int Ed Engl ; 60(36): 19912-19920, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34227724

RESUMO

Developing Type-I photosensitizers is considered as an efficient approach to overcome the deficiency of traditional photodynamic therapy (PDT) for hypoxic tumors. However, it remains a challenge to design photosensitizers for generating reactive oxygen species by the Type-I process. Herein, we report a series of α,ß-linked BODIPY dimers and a trimer that exclusively generate superoxide radical (O2 -. ) by the Type-I process upon light irradiation. The triplet formation originates from an effective excited-state relaxation from the initially populated singlet (S1 ) to triplet (T1 ) states via an intermediate triplet (T2 ) state. The low reduction potential and ultralong lifetime of the T1 state facilitate the efficient generation of O2 -. by inter-molecular charge transfer to molecular oxygen. The energy gap of T1 -S0 is smaller than that between 3 O2 and 1 O2 thereby precluding the generation of singlet oxygen by the Type-II process. The trimer exhibits superior PDT performance under the hypoxic environment.

3.
Am J Pathol ; 191(8): 1431-1441, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34294192

RESUMO

Glomeruli instance segmentation from pathologic images is a fundamental step in the automatic analysis of renal biopsies. Glomerular histologic manifestations vary widely among diseases and cases, and several special staining methods are necessary for pathologic diagnosis. A robust model is needed to segment and classify glomeruli with different staining methods and apply in cases with various glomerular pathologic changes. Herein, pathologic images from renal biopsy slides stained with three basic special staining methods were used to build the data sets. The snapshot group included 1970 glomeruli from 516 patients, and the whole-slide image group included 8665 glomeruli from 148 patients. Cascade Mask region-based convolutional neural net architecture was trained to detect, classify, and segment glomeruli into three categories: i) GN, structural normal; ii) global sclerosis; and iii) glomerular with other lesions. In the snapshot group, total glomeruli, GN, global sclerosis, and glomerular with other lesions achieved an F1 score of 0.914, 0.896, 0.681, and 0.756, respectively, which were comparable with those in the whole-slide image group (0.940, 0.839, 0.806, and 0.753, respectively). Among the three categories, GN achieved the best instance segmentation effect in both groups, as determined by average precision, average recall, F1 score, and Mask mean Intersection over Union. The present model segments and classifies multistained glomeruli with efficiency and robustness. It can be applied as the first step for more detailed glomerular histologic analysis.


Assuntos
Aprendizado Profundo , Interpretação de Imagem Assistida por Computador/métodos , Nefropatias/diagnóstico , Glomérulos Renais/patologia , Biópsia , Humanos , Nefropatias/patologia , Coloração e Rotulagem
4.
J Phys Chem Lett ; 12(25): 5944-5950, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34156849

RESUMO

The Pd complex PdN3N exhibits an unusual dual emission of room-temperature phosphorescence (RTP) and thermally activated delayed fluorescence (TADF), but the mechanism is elusive. Herein, we employed both density functional theory (DFT) and time-dependent DFT (TD-DFT) methods to explore excited-state properties of this Pd complex, which shows that the S0, S1, T1, and T2 states are involved in the luminescence. Both the S1 → T1 and S1 → T2 intersystem crossing (ISC) processes are more efficient than the S1 fluorescence and insensitive to temperature. However, the direct T1 → S1 and T2-mediated T1 → T2 → S1 reverse ISC (rISC) processes change remarkably with temperature. At 300 K, these two processes are more efficient than the T1 phosphorescence and therefore enable TADF. Importantly, the T1 → S1 rISC and T1 phosphorescence rates are comparable at 300 K, which leads to dual emissions of TADF and RTP, whereas these two channels become blocked at 100 K so that only the T1 phosphorescence is recorded experimentally.


Assuntos
Complexos de Coordenação/química , Teoria da Densidade Funcional , Fluorescência , Paládio/química , Temperatura , Modelos Moleculares , Conformação Molecular
5.
Phys Chem Chem Phys ; 23(19): 11528-11537, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-33960343

RESUMO

Ni-rich layered oxides, like LiNi0.8Co0.1Mn0.1O2 (NCM811), have been widely investigated as cathodes due to their high energy density. However, gradual structural transformation during cycling can lead to capacity degradation and potential decay of cathode materials. Herein, we doped high-valence transition metal (TM) ions (V5+, Nb5+, and Zr4+) at the Ni site of NCM811 by first principles simulations and explored the mechanism of doping TMs in NCMs for enhancing the electrochemical performance. Analysis of the calculations shows that doping V, Nb and Zr has an efficient influence on alleviating the Ni oxidation, reducing the loss of oxygen, and facilitating Li+ migration. Moreover, V doping can further suppress the lattice distortion due to the radius of V5+ being close to the radius of Mn4+. In particular, compared with the barrier of the pristine NCM in Li divacancy, the barrier of V-doped NCM reaches the lowest. In conclusion, V is the most favorable dopant for NCM811 to improve the electrochemical properties and achieve both high capacity and cycling stability.

6.
Front Physiol ; 12: 597449, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33927635

RESUMO

Nonalcoholic fatty liver disease is the most common hepatic disease in western countries and is even more ubiquitous in Asian countries. Our study determined that TH17/Treg cells were imbalanced in animal models. Based on our interest in the mechanism underlying TH17/Treg cell imbalance in nonalcoholic fatty liver mice, we conducted a joint bioinformatics analysis to further investigate this process. Common gene sequencing analysis was based on one trial from one sequencing platform, where gene expression analysis and enrichment analysis were the only analyses performed. We compared different sequencing results from different trials performed using different sequencing platforms, and we utilized the intersection of these analytical results to perform joint analysis. We used a bioinformatics analysis method to perform enrichment analysis and map interaction network analysis and predict potential microRNA sites. Animal experiments were also designed to validate the results of the data analysis based on quantitative polymerase chain reaction (qPCR) and western blotting. Our results revealed 8 coexisting differentially expressed genes (DEGs) and 7 hinge genes. The identified DEGs may influence nonalcoholic steatosis hepatitis through the interleukin-17 pathway. We found that microRNA-29c interacts with FOS and IGFBP1. Polymerase chain reaction analyses revealed both FOS and microRNA-29c expression in NASH mice, and western blot analyses indicated the same trend with regard to FOS protein levels. Based on these results, we suggest that microRNA-29c acts on FOS via the interleukin-17 signaling pathway to regulate TH17/Treg cells in NASH patients.

7.
Gene ; 787: 145639, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33848576

RESUMO

Anomopoda is the widespread planktonic microcrustacean, which plays a crucial role in aquatic ecosystem. There are few studies about the evolutionary relationships among various Anomopoda basing on molecular data. In the present study, phylogenetic analysis of eight Anomopoda was carried out. Firstly, the culture system was developed to breed cladocerans. By using this system, eight species (Daphnia magna, D. pulex, D. sinensis, Ceriodaphnia reticulata, Moina micrura, Scapholeberis kingi, Simocephalus vetulus and Eurycercus lamellatus) were purified and cultured stably in the laboratory. Then, transcriptomic sequences and partial mitochondrial DNA sequences were both used to reconstruct the phylogenetic tree among 8 species. Transcriptomic sequences were sequenced on Illumina Hiseq 2500 platform. After assembly and annotation, transcriptomic sequences were spliced together and aligned for phylogenetic analysis. Basing on the orthologous genes derived from transcriptomic sequences, the phylogenetic analysis showed that 4 genera of Daphniidae were clustered into one group, and among the 4 genera, Ceriodaphnia was closer to Daphnia than Simocephalus, while Scapholeberis was farthest from other species. In addition, Eurycercidae was closer to Daphniidae than Moinidae. The phylogenetic trees based on both 12S rRNA and 16S rRNA sequences were similar with that based on transcriptomic sequences. Meanwhile, the phylogenetic tree based on 16S rRNA sequences was more suitable than that based on 12S rRNA sequences. These results suggested that the phylogenetic analysis basing on the transcriptomic sequences was available in cladocerans, which will help us to effectively understand the phylogenetic relationships among various cladocerans.


Assuntos
Cladóceros/classificação , Cladóceros/genética , DNA Mitocondrial , Animais , Anotação de Sequência Molecular , Tipagem Molecular , Filogenia , Análise de Sequência de DNA , Especificidade da Espécie , Transcriptoma
8.
Phys Chem Chem Phys ; 23(9): 5143-5151, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33624671

RESUMO

Based on first-principle calculations, we proposed a one two-dimensional (2D) blue AsP (b-AsP) monolayer as an ideal anode material for lithium/sodium-ion (Li/Na-ion) batteries for the first time. The b-AsP monolayer possesses thermal and dynamic stabilities. The system undergoes the transition from semiconductor to metal after Li/Na atoms are embedded, which ensures good electric transportation. Most remarkably, our results indicate that the b-AsP monolayer exhibits high theoretical capacities of 1011.2 mA h g-1 (for Li) and 1769.6 mA h g-1 (for Na), low average open circuit voltages of 0.17 eV for Li4AsP and 0.14 eV for Na7AsP systems and ultrafast diffusivity with the low energy barriers of 0.17/0.15 eV and 0.08/0.07 eV of the P/As sides for Li and Na, respectively. Given these exceptional properties, the synthesis of a buckled b-AsP monolayer is desired to achieve a promising electrode material for Li- and Na-ion batteries.

9.
J Chem Phys ; 154(5): 054703, 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33557547

RESUMO

Density functional theory calculations have been performed to study the reaction mechanism of N2 thermal reduction (N2TR) over a single metal atom incorporated nitrogen-doped graphene. Our results reveal that the type of metal atoms and their coordination environments have a significant effect on the catalytic activity of N2TR. Regarding CoN4- and FeN4-embedded graphene sheets that the metal atom is fourfold coordinated, they are inactive for N2TR owing to the poor stability of the adsorbed H2 and N2 molecules. In contrast, if the monodisperse metal atom is surrounded by three N atoms, namely, CoN3/G and FeN3/G show activity toward N2TR, and catalytic conversion of N2 into ammonia is achieved through the associative mechanism rather than the dissociative mechanism. Further investigations show that the synthesis of NH3 over the two surfaces is mainly through the formation of an NHNH* intermediate; however, the detailed reaction mechanisms are sensitive to the type of metal atom introduced into N-doped graphene. Based on the calculated kinetic barriers, FeN3/G exhibits a better catalytic activity for N2TR. The superior performance of FeN3/G can be attributed to the fact that this surface prefers a high spin-polarized state during the whole process of N2TR, while the non-spin polarized state is predicted as the ground state for most of the elementary steps of N2-fixation over CoN3/G. The present study provides theoretical insights into developing graphene-based single atom catalysts with a high activity toward ammonia synthesis through N2TR.

10.
J Phys Chem Lett ; 12(4): 1131-1137, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33475363

RESUMO

In this work, we explore the interfacial properties of the C60-Py@MAPbI3 heterojunction of the PbI-terminated MAPbI3(001) surface and pyridine-functionalized C60-Py fullerene derivative through both collinear and noncollinear density functional theory calculations with and without spin-orbit coupling (SOC) effects. C60-Py is bound to the MAPbI3 surface through interfacial Pb-O and Pb-N bonds. Although C60-Py@MAPbI3 is predicted to be the same type II heterojunction at all of the computational levels considered, the SOC effects largely decrease the energy gap of the first conduction bands of C60-Py and MAPbI3, thereby accelerating the interfacial electron transfer. Further dynamics simulations show that the inclusion of the SOC effects induces the transfer of approximately 80% of electrons from MAPbI3 to C60-Py within 1 ps. The work demonstrates that the SOC effects are indispensable for the interfacial properties of C60-Py@MAPbI3 and could also play a non-negligible role in tuning the optoelectronic properties of fullerene-based or similar perovskite devices.

11.
Neuroscience ; 457: 27-40, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32795555

RESUMO

Acute neuroinflammation is the major detrimental factor that causes secondary tissue damage after spinal cord injury (SCI). Curbing neuroinflammation would reduce the neuronal death and benefit functional recovery. In the current study, we used a HO-1-encoding lentivirus to transduce microglia, and adoptively transferred these microglia into injured rat spinal cords. Lentivirus-induced overexpression of exogenous HO-1 significantly inhibited microglia-mediated inflammatory response after SCI, as demonstrated by lower expression of pro-inflammatory mediators in transferred microglia. In addition, the overall post-SCI neuroinflammation was also suppressed by HO-1-overexpressing microglia, as indicated by less leukocyte infiltration and lower pro-inflammatory cytokine production in the spinal cord. Consistently, the tissue damage and neuronal apoptosis were decreased in injured spinal cords, while the locomotor function was moderately improved. We further identified that adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling was involved in the regulatory effect of HO-1 on microglia, because HO-1 overexpression increased the activating phosphorylation of AMPKα. Moreover, the AMPK inhibitor compound C diminished the anti-inflammatory effect of HO-1 in lipopolysaccharide-stimulated microglia in vitro. Taken together, we proved that microglial HO-1 reduced acute post-SCI neuroinflammation. Our study might provide a promising therapeutic approach to benefit SCI recovery.


Assuntos
Microglia , Traumatismos da Medula Espinal , Animais , Heme Oxigenase-1/metabolismo , Microglia/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico
12.
Phys Chem Chem Phys ; 22(38): 21872-21880, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32966445

RESUMO

On the basis of the electron "acceptance-donation" concept, a boron decorated melon-based carbon nitride (CN) is studied as a metal-free photocatalyst to efficiently reduce N2 to NH3 under visible light irradiation. The results revealed that a boron-interstitial (Bint)-decorated melon-based CN has an outstanding N2 reduction capacity through the enzymatic mechanism with a rather low overpotential (0.32 V). The excellent efficiency and selectivity of Bint-decorated melon-based CN in N2 reduction reaction (NRR) are attributed to the concentrated spin polarization on the B atom, the significant enhancement of visible and infrared light absorption, and the effective inhibition of the competitive hydrogen evolution reaction (HER). Importantly, B-doped melon-based CN has been successfully synthesized in the experiments, so obtaining Bint-decorated melon is promising, while proton transfer from the -NH2 group in CN to the B atom surely will affect the functionality of the catalyst through deactivation of the N2 adsorption site. Our study provides a novel single atom metal-free photocatalyst with high efficiency for NRR, which is conducive to the sustainable synthesis of ammonia.

13.
Sci Rep ; 10(1): 15351, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948816

RESUMO

Agricultural management techniques such as mulching with crop straw can impact soil properties and may in turn change the structure and function of the soil food web. We investigated different straw mulching types and straw mulching coverage levels on soil nematodes community structure in walnut orchards. We set up a randomized experimental design with three straw mulch types, and three straw mulch distance treatments in a walnut plantation. The results indicated that the number of soil nematodes after straw mulching was lower than that found in the control (CK). However, the metabolic and structure footprints of the omnivore-predator nematodes showed higher values as compared to CK. The abundances of plant parasite and omnivore-predator nematodes were negatively correlated with ammonium nitrogen (NH4+-N) and dissolved organic nitrogen (DON), whereas soil moisture content (SM) had a negative correlation with the abundance of total nematodes. High structure index (SI), maturity index (MI) and low enrichment index (EI) values revealed a structured soil food web, medium soil enrichment, and fungal decomposition channel under the mix straw mulching treatments. Soil nematodes should be used as an indicator of soil functional changes resulting from straw mulching.


Assuntos
Agricultura/métodos , Juglans , Nematoides , Animais , Biodiversidade , Brassica napus , Carbono/análise , China , Nitrogênio/análise , Caules de Planta , Solo/química , Solo/parasitologia
14.
J Neuroinflammation ; 17(1): 202, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631435

RESUMO

BACKGROUND: Spinal cord injury (SCI) triggers the primary mechanical injury and secondary inflammation-mediated injury. Neuroinflammation-mediated insult causes secondary and extensive neurological damage after SCI. Microglia play a pivotal role in the initiation and progression of post-SCI neuroinflammation. METHODS: To elucidate the significance of LRCH1 to microglial functions, we applied lentivirus-induced LRCH1 knockdown in primary microglia culture and tested the role of LRCH1 in microglia-mediated inflammatory reaction both in vitro and in a rat SCI model. RESULTS: We found that LRCH1 was downregulated in microglia after traumatic SCI. LRCH1 knockdown increased the production of pro-inflammatory cytokines such as IL-1ß, TNF-α, and IL-6 after in vitro priming with lipopolysaccharide and adenosine triphosphate. Furthermore, LRCH1 knockdown promoted the priming-induced microglial polarization towards the pro-inflammatory inducible nitric oxide synthase (iNOS)-expressing microglia. LRCH1 knockdown also enhanced microglia-mediated N27 neuron death after priming. Further analysis revealed that LRCH1 knockdown increased priming-induced activation of p38 mitogen-activated protein kinase (MAPK) and Erk1/2 signaling, which are crucial to the inflammatory response of microglia. When LRCH1-knockdown microglia were adoptively injected into rat spinal cords, they enhanced post-SCI production of pro-inflammatory cytokines, increased SCI-induced recruitment of leukocytes, aggravated SCI-induced tissue damage and neuronal death, and worsened the locomotor function. CONCLUSION: Our study reveals for the first time that LRCH1 serves as a negative regulator of microglia-mediated neuroinflammation after SCI and provides clues for developing novel therapeutic approaches against SCI.


Assuntos
Mediadores da Inflamação/metabolismo , Proteínas dos Microfilamentos/antagonistas & inibidores , Proteínas dos Microfilamentos/metabolismo , Microglia/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Células Cultivadas , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Masculino , Microglia/efeitos dos fármacos , Microglia/patologia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/patologia
15.
J Phys Chem A ; 124(27): 5684-5695, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32530626

RESUMO

Recently, we have developed a multilayer energy-based fragment (MLEBF) method to describe excited states of large systems in which photochemically active and inert regions are separately treated with multiconfigurational and single-reference electronic structure method and their mutual polarization effects are naturally described within the many-body expansion framework. This MLEBF method has been demonstrated to provide highly accurate energies and gradients. In this work, we have further derived the MLEBF method with which highly accurate excited-state Hessian matrices of large systems are efficiently constructed. Moreover, in combination with recently proposed embedded atom neural network (EANN) model we have developed a machine learning (ML) accelerated MLEBF method (i.e., ML-MLEBF) in which photochemically inert region is entirely replaced with trained ML models. ML-MLEBF is found to improve computational efficiency of Hessian matrices in particular for large systems. Furthermore, both MLEBF and ML-MLEBF methods are highly parallel and exhibit low-scaling computational cost with multiple CPUs. The present developments could motivate combining various ML techniques with fragment-based electronic structure methods to explore Hessian-matrix-based excited-state properties of large systems.

16.
Molecules ; 25(7)2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32260278

RESUMO

Obesity is commonly associated with hyperglycemia and type 2 diabetes and negatively affects chromium accumulation in tissues. Exercise prevents and controls obesity and type 2 diabetes. However, little information is available regarding chromium changes for regulating glucose homeostasis in high-fat diet (HFD)-fed animals/humans who exercise. Therefore, this study explored the effects of exercise and whether it alters chromium distribution in obese mice. Male C57BL6/J mice aged 4 weeks were randomly divided into two groups and fed either an HFD or standard diet (SD). Each group was subgrouped into two additional groups in which one subgroup was exposed to treadmill exercise for 12 weeks and the other comprised control mice. HFD-fed mice that exercised exhibited significant lower body weight gain, food/energy intake, daily food efficiency, and serum leptin and insulin levels than did HFD-fed control mice. Moreover, exercise reduced fasting glucose and enhanced insulin sensitivity and pancreatic ß-cell function, as determined by homeostasis model assessment (HOMA)-insulin resistance and HOMA-ß indices, respectively. Exercise also resulted in markedly higher chromium levels within the muscle, liver, fat tissues, and kidney but lower chromium levels in the bone and bloodstream in obese mice than in control mice. However, these changes were not noteworthy in SD-fed mice that exercised. Thus, exercise prevents and controls HFD-induced obesity and may modulate chromium distribution in insulin target tissues.


Assuntos
Glicemia/análise , Cromo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Teste de Esforço/métodos , Obesidade/prevenção & controle , Animais , Modelos Animais de Doenças , Ingestão de Energia , Homeostase , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/induzido quimicamente , Obesidade/metabolismo , Distribuição Aleatória , Distribuição Tecidual
17.
J Phys Chem Lett ; 10(24): 7836-7841, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31786927

RESUMO

In this work we have combined machine learning techniques with our recently developed multilayer energy-based fragment method for studying excited states of large systems. The photochemically active and inert regions are separately treated with the complete active space self-consistent field method and the trained models. This method is demonstrated to provide accurate energies and gradients leading to essentially the same excited-state potential energy surfaces and nonadiabatic dynamics compared with full ab initio results. Furthermore, in conjunction with the use of machine learning models, this method is highly parallel and exhibits low-scaling computational cost. Finally, the present work could encourage the marriage of machine learning with fragment-based electronic structure methods to explore photochemistry of large systems.

18.
Phys Chem Chem Phys ; 21(41): 22695-22699, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31595910

RESUMO

We developed a multi-layer energy-based fragment (MLEBF) method within the many-body energy expansion framework. It supplies accurate energies and gradients, and accurately reproduces excited-state topological structures. Moreover, MLEBF-based nonadiabatic dynamics simulations give nearly the same results compared with full ab initio ones. The present work could stimulate developing energy-based fragment methods for photochemistry of large systems.

19.
Am J Transl Res ; 11(9): 5703-5715, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632541

RESUMO

The gut microbiota has been shown to play an important role in chronic liver disease. It has been found that both Lactobacillus rhamnosus and its culture supernatant have the potential to mitigate alcoholic steatohepatitis. However, the exact mechanism is still not fully understood. Bone marrow mesenchymal stem cells have immunosuppressive effects with few side effects. The synergistic effect between Lactobacillus rhamnosus culture supernatant and bone marrow mesenchymal stem cells (BMMSCs) deserves further observation. In this study, a mouse model of chronic alcoholic hepatitis was established by eight weeks of Lieber-DeCarli liquid diet feeding; and LGG-s, BMMSCs or a combination of the two were used to explore a new therapeutic method for alcoholic liver disease and to study the mechanism. The results showed that the combined LGG-s and BMMSC treatment might have a synergistic effect and could improve the symptoms of alcoholic hepatitis by regulating inflammation, autophagy and lymphocyte subsets through the PI3k/NF-kB and PI3K/mTOR pathways. With the treatment, the autophagy rate accelerated, and alcohol-induced natural killer B (NKB) cell and follicular helper T (TFH) cell numbers decreased. These findings suggest that the development of alcoholic hepatitis may occur via PI3K/NF-kB and PI3K/mTOR pathway overactivation as well as through NKB and TFH cell imbalances. Moreover, LGG-s and BMMSCs can regulate these factors and alleviate the disease.

20.
Immunology ; 158(4): 362-374, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31559637

RESUMO

The neuroinflammation following traumatic spinal cord injury (SCI) is a critical process that impacts both the injury and the recovery of spinal cord parenchyma. Infiltrating regulatory T (Treg) cells are potent anti-inflammatory cells that restrain post-SCI neuroinflammation. To understand the molecular mechanisms underlying the activity of infiltrating Treg cells, we used a mouse spinal cord compression injury model to analyze the role of Sirtuins (SIRTs) in the modulation of infiltrating Treg cell functions. We found that the expressions of SIRT4 and SIRT6 were up-regulated in infiltrating Treg cells. Using lentivirus-mediated gene expression or RNA interference, we revealed that SIRT4 substantially inhibited the expression of Foxp3, interleukin-10, and transforming growth factor-ß in Treg cells, whereas SIRT6 had little effect on Treg cells. Consistently, SIRT4 overexpression weakened the suppressive effect of Treg cells on lipopolysaccharide-stimulated spinal cord CD11b+ myeloid cells. Knock-down of SIRT4 enhanced the anti-inflammatory activity of infiltrating Treg cells in the parenchyma of injured spinal cords. Additionally, SIRT4 overexpression blocked in vitro Treg cell generation from conventional T cells. Furthermore, SIRT4 down-regulated 5' AMP-activated protein kinase (AMPK) signaling in Treg cells, whereas the AMPK agonist AICAR restored the expression of Foxp3 and interleukin-10 in SIRT4-overexpressing Treg cells. In conclusion, our research unveils a new mechanism by which the post-SCI neuroinflammation is regulated.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Proteínas Mitocondriais/metabolismo , Sirtuínas/metabolismo , Traumatismos da Medula Espinal/metabolismo , Linfócitos T Reguladores/imunologia , Adenilato Quinase/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/genética , Humanos , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Mitocondriais/genética , Inflamação Neurogênica , RNA Interferente Pequeno/genética , Transdução de Sinais , Sirtuínas/genética , Traumatismos da Medula Espinal/imunologia , Regulação para Cima
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