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With strong reducibility and high redox potential, the hydride ion (H-) is a reactive hydrogen species and an energy carrier. Materials that conduct pure H- at ambient conditions will be enablers of advanced clean energy storage and electrochemical conversion technologies1,2. However, rare earth trihydrides, known for fast H migration, also exhibit detrimental electronic conductivity3-5. Here we show that by creating nanosized grains and defects in the lattice, the electronic conductivity of LaHx can be suppressed by more than five orders of magnitude. This transforms LaHx to a superionic conductor at -40 °C with a record high H- conductivity of 1.0 × 10-2 S cm-1 and a low diffusion barrier of 0.12 eV. A room-temperature all-solid-state hydride cell is demonstrated.
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Metal nanoparticles have attracted considerable scientific and technological interest in recent years, most related explorations and reports are focused on transition and noble metals. However, the synthesis and application of light metal nanoparticles represented by Mg have not been fully exploited, limited by their ultrahigh reactivity in air and preparation in harsh conditions. In this work, a simple and effective one-step organic solvent-assisted ball-milling process is developed to synthesize Mg and Li nanoparticles, which permits the formation of MgH2 in a hydrogen atmosphere in a one-step reaction process at ambient temperature. Further studies suggest that acetone chemisorbs on defects/surfaces of Mg during ball milling leading to the formation of a metastable magnesium complex, which significantly alters the physical and chemical characteristics of Mg grains. The formation of metastable complexes provides an attractive strategy to produce light metal nanoparticles and inspires the authors to study the interaction of organic solvents with light metals.
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OBJECTIVES: Malignancy is related to idiopathic inflammatory myopathies (IIM) and leads to a poor prognosis. Early prediction of malignancy is thought to improve the prognosis. However, predictive models have rarely been reported in IIM. Herein, we aimed to establish and use a machine learning (ML) algorithm to predict the possible risk factors for malignancy in IIM patients. METHODS: We retrospectively reviewed the medical records of 168 patients diagnosed with IIM in Shantou Central hospital, from 2013 to 2021. We randomly divided patients into two groups, the training sets (70%) for construction of the prediction model, and the validation sets (30%) for evaluation of model performance. We constructed six types of ML algorithms models and the AUC of ROC curves were used to describe the efficacy of the model. Finally, we set up a web version using the best prediction model to make it more generally available. RESULTS: According to the multi-variable regression analysis, three predictors were found to be the risk factors to establish the prediction model, including age, ALT<80U/L, and anti-TIF1-γ, and ILD was found to be a protective factor. Compared with five other ML algorithms models, the traditional algorithm logistic regression (LR) model was as good or better than the other models to predict malignancy in IIM. The AUC of the ROC using LR was 0.900 in the training set and 0.784 in the validation set. We selected the LR model as the final prediction model. Accordingly, a nomogram was constructed using the above four factors. A web version was built and can be visited on the website or acquired by scanning the QR code. CONCLUSIONS: The LR algorithm appears to be a good predictor of malignancy and may help clinicians screen, evaluate and follow up high-risk patients with IIM.
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Miosite , Neoplasias , Humanos , Modelos Logísticos , Estudos Retrospectivos , Neoplasias/diagnóstico , Neoplasias/terapia , Aprendizado de Máquina , Miosite/diagnósticoRESUMO
The development of efficient, stable, and visible-light-responsive photocatalysts is crucial to address the pollution of water bodies by toxic heavy metal ions and organic antibiotics. Herein, a series of LaNi1-xFexO3/g-C3N4 heterojunction photocatalysts are prepared by a simple wet chemical method. Moreover, LaNi0.8Fe0.2O3/g-C3N4 composites are characterized by various methods, including structure, morphology, optical, and electrochemical methods and tetracycline degradation and photocatalytic reduction of Cr(VI) under visible light irradiation. Then, the photocatalytic performance of as-prepared LaNi0.8Fe0.2O3/g-C3N4 composites is evaluated. Compared with pure LaNi0.8Fe0.2O3 and g-C3N4, the LaNi0.8Fe0.2O3/g-C3N4 composite photocatalysts exhibit excellent photocatalytic performance due to synergy of doping and constructing heterojunctions. The results show that the doping of Fe ions can increase the concentration of oxygen vacancies, which is ultimately beneficial to the formation of electron traps. Moreover, the type-II heterojunction formed between LaNi0.8Fe0.2O3 and g-C3N4 effectively strengthens the separation and transfer of photoinduced carriers, thereby promoting photocatalytic activity. Furthermore, the photocatalytic activity of the LaNi0.8Fe0.2O3/g-C3N4 photocatalyst remains almost unchanged after three cycles, indicating long-term stability. Ultimately, the photocatalytic mechanism of the LaNi0.8Fe0.2O3/g-C3N4 composites is proposed.
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Antibacterianos , Tetraciclina , Catálise , LuzRESUMO
INTRODUCTION: To describe the clinical and laboratory features of systemic lupus erythematosus (SLE) enteritis and to establish a predictive model of risk and severity of lupus enteritis (LE). METHODS: Records of patients with SLE complaining about acute digestive symptoms were reviewed. The predictive nomogram for the diagnosis of LE was constructed by using R. The accuracy of the model was tested with correction curves. The receiver operating characteristic curve (ROC curve) program and a Decision curve analysis (DCA) were used for the verification of LE model. Receiver operating characteristic curve was also employed for evaluation of factors in the prediction of severity of LE. RESULTS: During the eight year period, 46 patients were in the LE group, while 32 were in the non-LE group. Abdominal pain, emesis, D-dimer >5 µg/mL, hypo-C3, and anti-SSA positive remained statistically significant and were included into the prediction model. Area under the curve (AUC) of ROC curve in this model was 0.909. Correction curve indicated consistency between the predicted rate and actual diagnostic rates. The DCA showed that the LE model was of benefit. Forty-four patients were included in developing the prediction model of LE severity. Infection, SLE disease activity index (SLEDAI), CT score, and new CT score were validated as risk factors for LE severity. The AUC of the combined SLEDAI, infection and new CT score were 0.870. CONCLUSION: The LE model exhibits good predictive ability to assess LE risk in SLE patients with acute digestive symptoms. The combination of SLEDAI, infection, and new CT score could improve the assessment of LE severity.
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Enterite , Lúpus Eritematoso Sistêmico , Dor Abdominal/etiologia , Enterite/diagnóstico , Enterite/etiologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Curva ROC , Índice de Gravidade de DoençaRESUMO
In this study, a novel MXene (Ti3C2Tx)-based nanocarrier was developed for drug delivery. MXene nanosheets were functionalized with 3, 3'-diselanediyldipropionic acid (DSeDPA), followed by grafting doxorubicin (DOX) as a model drug to the surface of functionalized MXene nanosheets (MXene-Se-DOX). The nanosheets were characterized using scanning electron microscopy, atomic force microscopy (AFM), transmission electron microscopy, energy-dispersive X-ray spectroscopy (EDX), nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and zeta potential techniques. The drug-loading capacity (17.95%) and encapsulation efficiency (41.66%) were determined using ultraviolet-visible spectroscopy. The lateral size and thickness of the MXene nanosheets measured using AFM were 200 nm and 1.5 nm, respectively. The drug release behavior of the MXene-Se-DOX nanosheets was evaluated under different medium conditions, and the nanosheets demonstrated outstanding dual (reactive oxygen species (ROS)- and pH-) responsive properties. Furthermore, the MXene-Se-DOX nanosheets exhibited excellent antibacterial activity against both Gram-negative E. coli and Gram-positive B. subtilis.
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Sistemas de Liberação de Medicamentos , Escherichia coli , Doxorrubicina/farmacologia , Doxorrubicina/química , Antibacterianos/farmacologia , Antibacterianos/química , Liberação Controlada de Fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Concentração de Íons de HidrogênioRESUMO
In a previous study, we demonstrated the role of polydatin (PD) in protecting against multiple organ dysfunction in sepsis. The aim of this study is to investigate whether PD protects against lipopolysaccharide (LPS)-induced endothelial barrier disruption through SIRT3 activation and to disclose the underlying mechanisms. Wild-type mice were injected with LPS and Evans Blue assay was performed to evaluate vascular permeability. Primary human umbilical vein endothelial cells (HUVECs) were stimulated with LPS. Endothelial permeability was evaluated by transendothelial electrical resistance (TER) and FITC-dextran leakage. SIRT3 activity was determined by a Deacetylase Fluorometric kit, and protein expression level of SIRT3 was detected by western blotting. Mitochondrial function was evaluated by determination of ROS level, mitochondrial membrane potential and mPTP opening. In endotoxemic mice, PD pretreatment attenuated vascular leakage in multiple organs while SIRT3 inhibition with 3-TYP reversed the effects of PD. PD treatment in late sepsis also exhibited barrier protective effects. In HUVECs, PD alleviated LPS-induced F-actin rearrangement, cadherin-catenin complex dissociation and endothelial hyperpermeability, whereas 3-TYP or SIRT3 siRNA attenuated the protective effects of PD. PD enhanced SIRT3 deacetylase activity, and attenuated LPS-induced decrease in SIRT3 expression as well. Furthermore, gain-of-function and loss-of-function strategies also confirmed the role of SIRT3 in enhancing endothelial barrier integrity. It was further ascertained that PD enhanced SIRT3-mediated deacetylation of SOD2 and cyclophilin D (CypD), thus suppressing mitochondrial dysfunction and subsequent endothelial barrier dysfunction. In addition, it was revealed that RAGE was involved in LPS-regulated SIRT3 signaling. Our results suggest that polydatin protects against LPS-induced endothelial barrier disruption dependent on SIRT3 and can be applied as a potential therapy for sepsis.
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Endotélio Vascular/efeitos dos fármacos , Glucosídeos/farmacologia , Lipopolissacarídeos/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Sirtuína 3/metabolismo , Estilbenos/farmacologia , Animais , Permeabilidade Capilar/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Substâncias ProtetorasRESUMO
Researches involving arterial pressure measurements in mice have primarily relied on carotid arterial catheterization. However, in some circumstances, measuring arterial pressure through the carotid arterial impairs accuracy. This study was aimed to evaluate whether femoral artery could displace carotid artery for the blood pressure (BP) measurements in mice. Fifty-six Swiss mice (n = 14 in each group) were randomized into four groups: control, left femoral artery, right femoral artery, and union group, in which BP was measured through left carotid, left femoral, right femoral artery, and simultaneously from right femoral artery and left carotid artery, respectively. Arterial pressure was recorded for 5 min after catheterization. There was no significant difference of the success rate and mortality rate among four groups (P > 0.05), and no obvious difference (P > 0.05) of catheterization time among the first three groups. For intergroup comparison of arterial pressure, there was no significant difference (P > 0.05) of the systolic blood pressure (SBP), diastolic BP, mean arterial pressure, and pulse pressure among the first three groups. For intragroup comparison, SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP) monitored from right femoral artery were similar (P > 0.05) with those from left carotid artery, with significantly positive correlation. The mean values of difference of SBP, DBP, and MAP were -1.3, 1.2, and 0.5 mmHg, respectively. Our results indicated that femoral artery catheterization could be a safe, feasible, reliable, and accuracy alternative for the direct measurement of arterial pressure in anesthesia mice.
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Pressão Arterial/fisiologia , Artérias Carótidas/fisiopatologia , Artéria Femoral/fisiologia , Hipertensão/fisiopatologia , Monitorização Fisiológica/métodos , Animais , Determinação da Pressão Arterial/métodos , Cateterismo Periférico , Modelos Animais de Doenças , Hipertensão/diagnóstico , Masculino , CamundongosRESUMO
BACKGROUND/AIMS: Disruption of endothelial barrier integrity in response to advanced glycation end products (AEGs) stimulation contributes to vasculopathy associated with diabetes mellitus. Mammalian diaphanous-related formin (mDia1) has been reported to bind to the cytoplasmic domain of the receptor for advanced glycation end products (RAGE), which induces a series of cellular processes. This study directly evaluated the participation of mDia1 in AGE-induced hyperpermeability and revealed the precise intracellular signal transductions of this pathological process. METHODS: Human umbilical vein endothelial cells (HUVECs) were used in the in vitro studies. Trans-endothelial electric resistance and permeability coefficient for dextran (Pd) were measured to analyze cell permeability. Western blotting, immunofluorescence staining and flow cytometry assay were performed to investigate the underlying mechanism. Dextran flux across the mesentery in mice was monitored to investigate in vivo microvascular permeability. RESULTS: we found that AGEs evoked Nox4 membrane translocation, reactive oxygen species production, phosphorylation of Src and VE-cadherin, dissociation of adherens junctions and eventual endothelial hyperpermeability through RAGE-mDia1 binding. Cells overexpressing mDia1 by recombinant adenovirus infection showed stronger cellular responses induced by AGEs. Down-regulation of mDia1 by infection with an adenovirus encoding siRNA or blockade of RAGE-mDia1 binding by transfection with RAGE mutant plasmids into HUVECs abolished these AGE-induced effects. Furthermore, knockdown of mDia1 using an adenovirus or genetical knockout of RAGE in C57 mice rescued AGE-evoked microvascular hyperpermeability. CONCLUSION: Our study revealed that mDia1 plays a critical role in AGE-induced microvascular hyperpermeability through binding to RAGE.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Permeabilidade Capilar/efeitos dos fármacos , Produtos Finais de Glicação Avançada/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Antígenos CD/metabolismo , Caderinas/metabolismo , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Forminas , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , NADPH Oxidase 4/metabolismo , Fosforilação/efeitos dos fármacos , Interferência de RNA , Espécies Reativas de Oxigênio/metabolismo , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismoRESUMO
Complex hydrides have played important roles in energy storage area. Here a complex hydride made of Li2 NH and LiBH4 was synthesized, which has a structure tentatively indexed using an orthorhombic cell with a space group of Pna21 and lattice parameters of a=10.121, b=6.997, and c=11.457â Å. The Li2 NH-LiBH4 sample (in a molar ratio of 1:1) shows excellent hydrogenation kinetics, starting to absorb H2 at 310â K, which is more than 100â K lower than that of pristine Li2 NH. Furthermore, the Li+ ion conductivity of the Li2 NH-LiBH4 sample is about 1.0×10-5 â S cm-1 at room temperature, and is higher than that of either Li2 NH or LiBH4 at 373â K. Those unique properties of the Li2 NH-LiBH4 complex render it a promising candidate for hydrogen storage and Li ion conduction.
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Endoplasmic reticulum (ER) stress-induced endothelial cell (EC) apoptosis has been implicated in a variety of human diseases. In addition to being regarded as an NADPH oxidase (NOX) inhibitor, apocynin (APO) exhibits an anti-apoptotic effect in various cells. The present study aimed to identify the protective role of apocynin in ER stress-mediated EC apoptosis and the underlying mechanisms. We found that ER stress resulted in a significant increase in c-Jun N-terminal kinase phosphorylation, and elicited caspase 3 cleavage and apoptosis. However, apocynin obviously attenuated EC apoptosis and this effect was partly dependent on ER stress sensor inositol-requiring enzyme 1α (IRE1α). Importantly, apocynin upregulated IRE1α expression in both protein and mRNA levels and promoted the pro-survival XBP1 splicing. Our results suggest that apocynin protects ECs against ER stress-induced apoptosis via IRE1α involvement. These findings may provide a novel mechanistic explanation for the anti-apoptotic effect of apocynin in ER stress.
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Acetofenonas/farmacologia , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Caspase 3/metabolismo , Humanos , Splicing de RNA/efeitos dos fármacos , Proteína 1 de Ligação a X-Box/biossínteseRESUMO
Mg2FeH6 with a purity of up to 94.5 wt% was synthesized and its interaction with LiNH2 was investigated in this study. It was found that Li4FeH6, normally synthesized by hydriding a mixture of LiH and Fe at 700 °C and 5.5 GPa H2 pressure, can be formed via ball-milling Mg2FeH6 and LiNH2 under ambient conditions following the reaction of Mg2FeH6 + 4LiNH2 â Li4FeH6 + 2Mg(NH2)2, ΔH = -92.8 kJ mol-1. The formation of Li4FeH6 was confirmed by XRD, FTIR and Mössbauer spectroscopic characterization. Li4FeH6 further reacts with 2Mg(NH2)2 releasing ca. 4.8 wt% H2 at 225 °C and reabsorbing 3.7 wt% H2 at 200 °C and 50 bar H2 pressure. Mg(NH2)2, LiH and Fe are the hydrogenated products.
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The disruption of endothelial integrity and the occurrence of angiogenesis in response to AGEs contribute greatly to micro- and macrovascular complications associated with DM. Among human dermal, brain, and retinal vascular ECs, activation of ERM, moesin, by phosphorylation of Thr-558 is involved in AGE-induced hyperpermeability and angiogenesis via the Rho and ROCK (Rho/ROCK) and p38 pathways. Src also plays an important role in AGE-induced endothelial barrier dysfunction by phosphorylating moesin, VE-cadherin, and FAK. Furthermore, recent studies have demonstrated that ROS serve as a key mediator of the AGE-induced endothelial response. ROS inhibition would greatly benefit ECs. This review focuses on the role of moesin in microvascular permeability and angiogenesis, and on the involvement of Src and ROS in endothelial barrier disruption.
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Endotélio Vascular/fisiopatologia , Produtos Finais de Glicação Avançada/fisiologia , Proteínas dos Microfilamentos/fisiologia , Permeabilidade Capilar , Humanos , Neovascularização Patológica , Espécies Reativas de Oxigênio/metabolismo , Quinases da Família src/metabolismoRESUMO
The doping effect of Sr(OH)2 on the Mg(NH2)2-2LiH system is investigated considering different amounts of added Sr(OH)2 in the range of 0.05 to 0.2 mol. Experimental results show that both the thermodynamic and the kinetic properties of Mg(NH2)2-2LiH are influenced by the presence of Sr(OH)2. The addition of 0.1 mol Sr(OH)2 leads to a decrease in both the dehydrogenation onset and peak temperatures of ca. 70 and 13 °C, respectively, and an acceleration in the de/re-hydrogenation rates of one time at 150 °C compared to Mg(NH2)2-2LiH alone. Based on differential scanning calorimetry (DSC) analysis, the overall reaction enthalpy of the 0.1 Sr(OH)2-doped sample is calculated to be 44 kJ per mol-H2 and there are two absorption events occurring in the doped sample instead of one in the pristine sample. For the applied experimental conditions, according to the in situ synchrotron radiation powder X-ray diffraction (SR-PXD) and Fourier Transform Infrared spectroscopy (FT-IR) analysis, the reaction mechanism has been finally defined: Sr(OH)2, Mg(NH2)2 and LiH react with each other to form SrO, MgO and LiNH2 during ball milling. After heating, SrO interacts with Mg(NH2)2 producing MgO and Sr(NH2)2. Then Mg(NH2)2, LiNH2 and Sr(NH2)2 react with LiH to produce Li2NH, SrNH, Li2Mg(NH)2 and Li2Mg2(NH)3 in traces. After re-hydrogenation, LiSrH3, LiH and LiNH2 are formed along with amorphous Mg(NH2)2. The reasons for the improved kinetics are: (a) during dehydrogenation, the in situ formation of SrNH appears to increase the interfacial contacts between Mg(NH2)2 and LiH and also weakens the N-H bond of Mg(NH2)2; (b) during absorption, the formation of LiSrH3 at around 150 °C could be the key factor for improving the hydrogenation properties.
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The 6Mg(NH2)2-9LiH-LiBH4 composite system has a maximum reversible hydrogen content of 4.2 wt% and a predicted dehydrogenation temperature of about 64 °C at 1 bar of H2. However, the existence of severe kinetic barriers precludes the occurrence of de/re-hydrogenation processes at such a low temperature (H. Cao, G. Wu, Y. Zhang, Z. Xiong, J. Qiu and P. Chen, J. Mater. Chem. A, 2014, 2, 15816-15822). In this work, Li3N and YCl3 have been chosen as co-additives for this system. These additives increase the hydrogen storage capacity and hasten the de/re-hydrogenation kinetics: a hydrogen uptake of 4.2 wt% of H2 was achieved in only 8 min under isothermal conditions at 180 °C and 85 bar of H2 pressure. The re-hydrogenation temperature, necessary for a complete absorption process, can be lowered below 90 °C by increasing the H2 pressure above 185 bar. Moreover, the results indicate that the hydrogenation capacity and absorption kinetics can be maintained roughly constant over several cycles. Low operating temperatures, together with fast absorption kinetics and good reversibility, make this system a promising on-board hydrogen storage material. The reasons for the improved de/re-hydrogenation properties are thoroughly investigated and discussed.
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A diverse array of cellular stresses can lead to accumulation of misfolded or unfolded proteins in endoplasmic reticulum (ER), which subsequently elicits ER stress. Inositol-requiring enzyme 1α (IRE1α) is the most sensitive of the three unfolded protein response (UPR) branches which are triggered to cope with ER stress in mammalian cells. IRE1α signaling is quite context-specific on account of many adaptor and modulator proteins that directly interact with it, including heat shock proteins (HSPs), RING finger protein 13 (RNF13), poly (ADP-ribose) polymerase 16 (PARP16), Bax/Bak, and Bax inhibitor-1 (BI-1). The activated IRE1α triggers different downstream pathways depending on the UPRosome formed by distinct modulator proteins. At the initial phase of ER stress, IRE1α-XBP1 axis functions as an adaptive response. While ER stress sustains or intensifies, signals shift to apoptotic responses. Furthermore, IRE1α signaling can be exploited to the development of a wide range of prevalent human diseases, with cancer the most characterized. Here we provide an overview of recent insights into the complex IRE1α signaling network which makes IRE1α an intriguing cell fate switch. Besides, the functional relevance is presented since IRE1α activation also participates in some other physiological processes beyond protein-folding status.
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Endorribonucleases/metabolismo , Transdução de Sinais , Animais , Apoptose , Diferenciação Celular , Sobrevivência Celular , Estresse do Retículo Endoplasmático , Humanos , Resposta a Proteínas não DobradasRESUMO
Fangji Huangqi decoction (FHD), as a classic traditional Chinese medicine formula, has been clinically proven effective against rheumatoid arthritis (RA), yet its therapeutic mechanism remains unclear. This study employed network pharmacology and molecular docking methods to explore the major active components, biological targets, and signaling pathways of FHD. Subsequently, lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used as the in vitro model to validate the modulating effects of FHD on molecules/inflammatory mediators using various biomedical techniques/kits such as MTT assay, Griess reagents, flow cytometry, RT-qPCR, and immunoblotting. Network pharmacology analyses indicated a total of 20 major active components and 30 core biological targets of FHD against RA. Pathway enrichment analyses demonstrated the involvement of mitogen-activated protein kinase (MAPK) signaling pathways in the efficacy of the formula. Furthermore, experimental evidence demonstrated that FHD dose-dependently and significantly inhibited the productions of nitric oxide (NO) and reactive oxygen species; lowered the mRNA expression levels of proinflammatory mediators including iNOS, COX-2, TNF-α, ΙL-1ß, and IL-6; decreased protein levels of the phosphorylated forms of p38, ERK, JNK, and NF-κB p65. Additionally, the results of molecular docking showed that tetrandrine, licochalcone A, oxonantenine, isorhamnetin, and kaempferol in FHD exerted the potent capability of binding to target molecules in the focused signaling pathway, probably being the potential effective substances for FHD. Our network pharmacology study integrated with cellular validation has elucidated that FHD exerts downregulating effects of the MAPK and NF-κB signaling pathway, ultimately leading to inhibitory effects on the productions of proinflammatory mediators in LPS-stimulated RAW264.7 cells. This work comprehensively demonstrated the effective substances, key targets, and signaling pathways involved in the anti-RA effects of the formula, and these findings provide a further understanding of the underlying mechanism of FHD in managing RA.
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Introduction: Combination therapy provides better outcomes than a single therapy and becomes an efficient strategy for cancer treatment. In this study, we designed a hypoxia- and singlet oxygen-responsive polymeric micelles which contain azo and nitroimidazole groups for enhanced cellular uptake, repaid cargo release, and codelivery of photosensitizer Ce6 and hypoxia-activated prodrug tirapazamine TPZ (DHM-Ce6@TPZ), which could be used for combining Ce6-mediated photodynamic therapy (PDT) and PDT-activated chemotherapy to enhance the therapy effect of cancer. Methods: The hypoxia- and singlet oxygen-responsive polymeric micelles DHM-Ce6@TPZ were prepared by film hydration method. The morphology, physicochemical properties, stimuli responsiveness, in vitro singlet oxygen production, cellular uptake, and cell viability were evaluated. In addition, the in vivo therapeutic effects of the micelles were verified using a tumor xenograft mice model. Results: The resulting dual-responsive micelles not only increased the concentration of intracellular photosensitizer and TPZ, but also facilitated photosensitizer and TPZ release for enhanced integration of photodynamic and chemotherapy therapy. As a photosensitizer, Ce6 induced PDT by generating toxic singlet reactive oxygen species (ROS), resulting in a hypoxic tumor environment to activate the prodrug TPZ to achieve efficient chemotherapy, thereby evoking a synergistic photodynamic and chemotherapy therapeutic effect. The cascade synergistic therapeutic effect of DHM-Ce6@TPZ was effectively evaluated both in vitro and in vivo to inhibit tumor growth in a breast cancer mice model. Conclusion: The designed multifunctional micellar nano platform could be a convenient and powerful vehicle for the efficient co-delivery of photosensitizers and chemical drugs for enhanced synergistic photodynamic and chemotherapy therapeutic effect of cancer.
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Nanopartículas , Fotoquimioterapia , Pró-Fármacos , Humanos , Animais , Camundongos , Fármacos Fotossensibilizantes/química , Micelas , Oxigênio Singlete , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Hipóxia/tratamento farmacológico , Polímeros/química , Pró-Fármacos/farmacologiaRESUMO
Machine learning (ML), a powerful artificial intelligence tool, can effectively assist and guide the production of bio-oil from hydrothermal liquefaction (HTL) of wet biomass. However, for hydrothermal co-liquefaction (co-HTL), there is a considerable lack of application of experimentally verified ML. In this work, two representative wet biomasses, sewage sludge and algal biomass, were selected for co-HTL. The Gradient Boosting Regression (GBR) and Random Forest (RF) algorithms were employed for regression and feature analyses on yield (Yield_oil, %), nitrogen content (N_oil, %), and energy recovery rate (ER_oil, %) of bio-oil. The single-task results revealed that temperature (T, °C) was the most significant factor. Yield_oil and ER_oil reached their maximum values around 350 °C, while that of N_oil was around 280 °C. The multi-task results indicated that the GBR-ML model of the dataset#4 (n_estimators = 40, and max_depth = 7,) owed the highest average test R2 (0.84), which was suitable for developing a prediction application. Subsequently, through experimental validation with actual biomass, the best GBR multi-task ML model (T ≥ 300 °C, Yield_oil error < 11.75 %, N_oil error < 2.40 %, and ER_oil error < 9.97 %) based on the dataset#6 was obtained for HTL/co-HTL. With these steps, we developed an application for predicting the multi-object of bio-oil, which is scarcely reported in co-hydrothermal liquefaction studies.
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Nitrogênio , Óleos de Plantas , Polifenóis , Esgotos , Biomassa , Inteligência Artificial , Biocombustíveis , Temperatura , Aprendizado de Máquina , ÁguaRESUMO
BACKGROUND: Sulfate-reducing bacteria (SRB) is a potential pathogen usually detected in patients with gastrointestinal diseases. Hydrogen sulfide (H2S), a metabolic byproduct of SRB, was considered the main causative agent that disrupted the morphology and function of gut epithelial cells. Associated study also showed that flagellin from Desulfovibrio vulgaris (DVF), the representative bacterium of the Desulfovibrio genus, could exacerbate colitis due to the interaction of DVF and LRRC19, leading to the secretion of pro-inflammatory cytokines. However, we still have limited understanding about the change of gut microbiota (GM) composition caused by overgrowth of SRB and its exacerbating effects on colitis. RESULTS: In this study, we transplanted D. vulgaris into the mice treated with or without DSS, and set a one-week recovery period to investigate the impact of D. vulgaris on the mice model. The outcomes showed that transplanted D. vulgaris into the normal mice could cause the gut inflammation, disrupt gut barrier and reduce the level of short-chain fatty acids (SCFAs). Moreover, D. vulgaris also significantly augmented DSS-induced colitis by exacerbating the damage of gut barrier and the secretion of inflammatory cytokines, for instance, IL-1ß, iNOS, and TNF-α. Furthermore, results also showed that D. vulgaris could markedly change GM composition, especially decrease the relative abundance of SCFAs-producing bacteria. Additionally, D. vulgaris significantly stimulated the growth of Akkermansia muciniphila probably via its metabolic byproduct, H2S, in vivo. CONCLUSIONS: Collectively, this study indicated that transplantation of D. vulgaris could cause gut inflammation and aggravate the colitis induced by DSS.