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1.
Sci Adv ; 10(3): eadl1015, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38232173

RESUMEN

Because of the nonequilibrium nature of thermal effects at the nanoscale, the characterization of local thermal effects within a single molecule is highly challenging. Here, we demonstrate a way to characterize the local thermal properties of a single fullerene (C60) molecule during current-induced heating processes through tip-enhanced anti-Stokes Raman spectroscopy. Although the measured vibron populations are far from equilibrium with the environment, we can still define an "effective temperature (Teff)" statistically via a Bose-Einstein distribution, suggesting a local equilibrium within the molecule. With increased current heating, Teff is found to rise up to about 1150 K until the C60 cage is decomposed. Such a decomposition temperature is similar to that reported for ensemble C60 samples, thus justifying the validity of our methodology. Moreover, the possible reaction pathway and product can be identified because of the chemical sensitivity of Raman spectroscopy. Our findings provide a practical method for noninvasively detecting the local heating effect inside a single molecule under nonequilibrium conditions.

2.
Redox Biol ; 64: 102787, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37392517

RESUMEN

INTRODUCTION: Irisin is a newly discovered myokine which links exercise to inflammation and inflammation-related diseases through macrophage regulation. However, the effect of irisin on the activity of inflammation related immune cells (such as neutrophils) has not been clearly described. OBJECTIVES: The objective of our study was to explore the effect of irisin on the neutrophil extracellular traps (NETs) formation. METHODS: Phorbol-12-myristate-13-acetate (PMA) was used to construct a classic neutrophil inflammation model that was used to observe the formation of NETs in vitro. We studied the effect of irisin on NETs formation and its regulation mechanism. Subsequently, acute pancreatitis (AP) was used to verify the protective effect of irisin in vivo, which was an acute aseptic inflammatory response disease model closely related to NETs. RESULTS: Our study found that addition of irisin significantly reduced the formation of NETs via regulation of the P38/MAPK pathway through integrin αVß5, which might be the one of key pathways in NETs formation, and which could theoretically offset the immunoregulatory effect of irisin. Systemic treatment with irisin reduced the severity of tissue damage common in the disease and inhibited the formation of NETs in pancreatic necrotic tissue of two classical AP mouse models. CONCLUSION: The findings confirmed for the first time that irisin could inhibit NETs formation and protect mice from pancreatic injury, which further elucidated the protective effect of exercise on acute inflammatory injury.


Asunto(s)
Trampas Extracelulares , Pancreatitis , Ratones , Animales , Trampas Extracelulares/metabolismo , Pancreatitis/metabolismo , Fibronectinas/farmacología , Fibronectinas/metabolismo , Enfermedad Aguda , Neutrófilos/metabolismo , Inflamación/metabolismo , Acetato de Tetradecanoilforbol/metabolismo , Acetato de Tetradecanoilforbol/farmacología
3.
Int Immunopharmacol ; 121: 110501, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37364326

RESUMEN

BACKGROUND: Acute pancreatitis (AP) is an inflammatory condition of the pancreas characterized by oxidative stress and inflammation in its pathophysiology. Acetyl-11-keto-ß-boswellic acid (AKBA) is an active triterpenoid with antioxidant activity. This article seeks to assess the impact of AKBA on AP and investigate its underlying mechanisms. METHODS: AP was induced in wild-type, Lyz2+/cre Nrf2fl/fl mice and Pdx1+/cre Nrf2fl/fl mice by caerulein. Serum amylase and lipase levels, along with histological grading, were utilized to evaluate the severity of AP. Murine bone marrow-derived macrophages (BMDMs) were isolated, cultured, and polarized to the M1 subtype. Flow cytometry and ELISA were utilized to identify the macrophage phenotype. Alterations in oxidative stress damage and intracellular ROS were observed. Nrf2/HO-1 signaling pathways were also evaluated. RESULTS: In a caerulein-induced mouse model of AP, treatment with AKBA reduced blood amylase and lipase activity and ameliorated pancreatic tissue histological and pathological features. Furthermore, AKBA significantly mitigated oxidative stress-induced damage and induced the expression of Nrf2 and HO-1 protein. Additionally, by using conditional knockout mice (Lyz2+/cre Nrf2fl/fl and Pdx1+/cre Nrf2fl/fl mice), we verified that Nrf2 primarily functions in macrophages rather than acinar cells. In vitro, AKBA inhibits pro-inflammatory M1-subtype macrophage polarization and reduces ROS generation through Nrf2/HO-1 oxidative stress pathway. Moreover, the protective effects of AKBA against AP were abolished in myeloid-specific Nrf2-deficient mice and BMDMs. Molecular docking results revealed interactions between AKBA and Nrf2. CONCLUSION: Our results confirm that AKBA exerts protective effects against AP in mice by inhibiting oxidative stress in macrophages through the Nrf2/HO-1 Pathway.


Asunto(s)
Pancreatitis , Animales , Ratones , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Pancreatitis/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ceruletida/farmacología , Enfermedad Aguda , Simulación del Acoplamiento Molecular , Estrés Oxidativo , Macrófagos/metabolismo , Lipasa , Amilasas
4.
J Clin Med ; 12(7)2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-37048616

RESUMEN

The inflammatory immune response mediated by neutrophils is closely related to the progression of acute pancreatitis. Previous studies confirmed that CD177 is a neutrophil-specific marker involved in the pathogenesis of conditions such as systemic vasculitis, asthma, and polycythemia vera. Neutrophil extracellular trap (NET) formation is a specific death program by which neutrophils release nuclear DNA covered with histones, granule proteins, etc. It also plays an important role in host defense and various pathological reactions. However, the function of CD177 in regulating the generation of NETs and the development of acute pancreatitis (AP) is unclear. In our manuscript, CD177 was significantly elevated in blood neutrophils in patients and positively correlated with the AP disease severity. Then, recombinant human CD177 protein (rhCD177) could significantly improve pancreatic injury and the inflammatory response in AP mice, and reduce AP-related lung injury. Mechanistically, we found that rhCD177 could inhibit the formation of NETs by reducing reactive oxygen species (ROS) and myeloperoxidase (MPO)/citrullinated histone H3 (CitH3) release. For the first time, we discovered the potential of rhCD177 to protect AP in mice and inhibit the NET formation of AP. CD177 may be a potential treatment strategy for preventing or inhibiting the aggravation of AP.

5.
Front Immunol ; 14: 1110843, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36860878

RESUMEN

Background: About a quarter of the world's population with latent tuberculosis infection (LTBI) are the main source of active tuberculosis. Bacillus Calmette Guerin (BCG) cannot effectively control LTBI individuals from developing diseases. Latency-related antigens can induce T lymphocytes of LTBI individuals to produce higher IFN-γ levels than tuberculosis patients and normal subjects. Herein, we firstly compared the effects of M. tuberculosis (MTB) ag85ab and 7 latent DNA vaccines on clearing latent MTB and preventing its activation in the mouse LTBI model. Methods: A mouse LTBI model was established, and then immunized respectively with PBS, pVAX1 vector, Vaccae vaccine, ag85ab DNA and 7 kinds of latent DNAs (including rv1733c, rv2660c, rv1813c, rv2029c, rv2628, rv2659c and rv3407) for three times. The mice with LTBI were injected with hydroprednisone to activate the latent MTB. Then, the mice were sacrificed for the bacterial count, histopathological examination, and immunological evaluation. Results: Using chemotherapy made the MTB latent in the infected mice, and then using hormone treatment reactivated the latent MTB, indicating that the mouse LTBI model was successfully established. After the mouse LTBI model was immunized with the vaccines, the lung colony-forming units (CFUs) and lesion degree of mice in all vaccines group were significantly decreased than those in the PBS group and vector group (P<0.0001, P<0.05). These vaccines could induce antigen-specific cellular immune responses. The number of IFN-γ effector T cells spots secreted by spleen lymphocytes in the ag85ab DNA group was significantly increased than those in the control groups (P<0.05). In the splenocyte culture supernatant, IFN-γ and IL-2 levels in the ag85ab, rv2029c, and rv2659c DNA groups significantly increased (P<0.05), and IL-17A levels in ag85ab and rv2659c DNA groups also significantly increased (P<0.05). Compared with the PBS and vector groups, the proportion of CD4+CD25+FOXP3+ regulatory T cells in spleen lymphocytes of ag85ab, rv2660c, rv2029c, and rv3407 DNA groups were significantly reduced (P<0.05). Conclusions: MTB ag85ab and 7 kinds of latent DNA vaccines showed immune preventive efficacies on a mouse model of LTBI, especially the rv2659c, and rv1733c DNA. Our findings will provide candidates for the development of new multi-stage vaccines against TB.


Asunto(s)
Tuberculosis Latente , Mycobacterium tuberculosis , Vacunas de ADN , Animales , Ratones , Tuberculosis Latente/prevención & control , Transporte Biológico , ADN , Modelos Animales de Enfermedad
6.
Curr Mol Med ; 23(6): 536-549, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35570540

RESUMEN

BACKGROUND: Verapamil enhances the sensitivity of Mycobacterium tuberculosis to anti-tuberculosis (TB) drugs, promotes the macrophage anti-TB ability, and reduces drug resistance, but its mechanism is unclear. Herein, we have investigated the effect of verapamil on cytokine expression in mouse peritoneal macrophages. METHODS: Macrophages from mice infected with M. tuberculosis or S. aureus were cultured with verapamil, the cytokines were detected by enzyme-linked immunosorbent assay, and the RNA was measured with quantitative real-time polymerase chain reaction and agarose gel electrophoresis. The intracellular calcium signaling was measured by confocal microscopy. RESULTS: Significantly higher levels of NF-κB, IL-12, TNF-α, and IL-1ß were observed after TB infection. The levels of NF-κB and IL-12 increased when verapamil concentration was less than 50 µg/ml, but decreased when verapamil concentration was greater than 50µg/ml. With the increase in verapamil concentration, TNF-α and IL-1ß expressed by macrophages decreased. The L-type calcium channel transcription significantly increased in M. tuberculosis rather than S. aureus-infected macrophages. Furthermore, during bacillus Calmette-Guerin (BCG) infection, verapamil stimulated a sharp peak in calcium concentration in macrophages, while calcium concentration increased mildly and decreased smoothly over time in the absence of verapamil. CONCLUSION: Verapamil enhanced macrophage immunity via the NF-κB pathway, and its effects on cytokine expression may be achieved by its regulation of intracellular calcium signaling.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Ratones , Animales , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Verapamilo/farmacología , Verapamilo/metabolismo , Calcio/metabolismo , Staphylococcus aureus/metabolismo , Macrófagos/metabolismo , Tuberculosis/tratamiento farmacológico , Tuberculosis/metabolismo , Citocinas/metabolismo , Interleucina-12/metabolismo
7.
Postgrad Med ; 134(7): 703-710, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35801388

RESUMEN

BACKGROUND: Acute pancreatitis (AP) is the most common pancreatic disease. Predicting the severity of AP is critical for making preventive decisions. However, the performance of existing scoring systems in predicting AP severity was not satisfactory. The purpose of this study was to develop predictive models for the severity of AP using machine learning (ML) algorithms and explore the important predictors that affected the prediction results. METHODS: The data of 441 patients in the Department of Gastroenterology in our hospital were analyzed retrospectively. The demographic data, blood routine and blood biochemical indexes, and the CTSI score were collected to develop five different ML predictive models to predict the severity of AP. The performance of the models was evaluated by the area under the receiver operating characteristic curve (AUC). The important predictors were determined by ranking the feature importance of the predictive factors. RESULTS: Compared to other ML models, the extreme gradient boosting model (XGBoost) showed better performance in predicting severe AP, with an AUC of 0.906, an accuracy of 0.902, a sensitivity of 0.700, a specificity of 0.961, and a F1 score of 0.764. Further analysis showed that the CTSI score, ALB, LDH, and NEUT were the important predictors of the severity of AP. CONCLUSION: The results showed that the XGBoost algorithm can accurately predict the severity of AP, which can provide an assistance for the clinicians to identify severe AP at an early stage.


Asunto(s)
Pancreatitis , Enfermedad Aguda , Humanos , Aprendizaje Automático , Pancreatitis/diagnóstico , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
8.
Infect Genet Evol ; 103: 105325, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35779785

RESUMEN

OBJECTIVE: The study investigated the clinical diagnostic value of long non-coding RNA (LncRNA) small nucleolar RNA host gene 16 (SNHG16) and explored its underlying molecular mechanism through Mycobacterium tuberculosis (M. tuberculosiinfection of macrophages. METHODS: RT-qPCR analysis of the serum SNHG16 levels of the 66 healthy individuals, 67 latent TB (LTB) patients, and 67 active TB (ATB) patients. The receiver-operating characteristic (ROC) curve to detect the clinical diagnostic value of SNHG16 in TB patients. In vitro, M. tuberculosis-infected macrophages, CCK-8 and ELISA to detect cell proliferation and inflammatory factor levels. Luciferase reported assay was performed to analyze the targeting relationship between SNHG16 and miR-140-5p. RESULTS: SNHG16 was significantly elevated in TB patients, and among them, ATB patients were higher than LTB patients. ROC confirmed that SNHG16 could distinguish LTB patients from healthy controls, and ATB patients from LTB patients, and can be used as a good diagnostic biomarker for TB. M. tuberculosis infection increased SNHG16 levels and promoted the proliferation and inflammation in macrophages. However, SNHG16 silencing significantly reversed the effect of infection. miR-140-5p, a direct target miRNA of SNHG16, was down-regulated in TB patients and was negatively correlated with SNHG16. When miR-140-5p was inhibited, the alleviating effect of SNHG16 silencing on M. tuberculosis infection proliferation and inflammation was significantly reversed. CONCLUSION: The present results suggested that SNHG16 may be a new diagnostic biomarker for TB patients and SNHG16 silencing may alleviate TB by inhibiting the proliferation of macrophages in TB by regulation miR-140-5p.


Asunto(s)
MicroARNs , ARN Largo no Codificante , Tuberculosis , Biomarcadores , Proliferación Celular/genética , Humanos , Inflamación/metabolismo , Macrófagos/metabolismo , MicroARNs/genética , Mycobacterium tuberculosis , ARN Largo no Codificante/genética , Tuberculosis/diagnóstico , Tuberculosis/genética
9.
Biochem Biophys Res Commun ; 600: 35-43, 2022 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-35182973

RESUMEN

The excessive inflammatory response mediated by macrophage is one of the key factors for the progress of acute pancreatitis (AP). Paeonol (Pae) was demonstrated to exert multiple anti-inflammatory effects. However, the role of Pae on AP is not clear. In the present study, we aimed to investigate the protective effect and mechanism of Pae on AP in vivo and vitro. In the caerulein-induced mild acute pancreatitis (MAP) model, we found that Pae administration reduced serum levels of amylase, lipase, IL-1ß and IL-6 and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. And Pae decrease the ROS generated, restore mitochondrial membrane potential (ΔΨm), inhibit M1 macrophage polarization and NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) in vitro. In addition, specific NLRP3 inhibitor MCC950 eliminated the protective effect of Pae on AP induced by caerulein in mice. Correspondingly, the inhibitory effect of Pae on ROS generated and M1 polarization was not observed in BMDMs with MCC950 in vitro. Taken together, our datas for the first time confirmed the protective effects of Pae on AP via the NLRP3 inflammasomes Pathway.


Asunto(s)
Inflamasomas , Pancreatitis , Acetofenonas , Enfermedad Aguda , Animales , Ceruletida/farmacología , Inflamasomas/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Especies Reactivas de Oxígeno/efectos adversos
10.
Front Cell Infect Microbiol ; 11: 763591, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34869066

RESUMEN

Tuberculosis (TB) is a serious public health problem worldwide. The combination of various anti-TB drugs is mainly used to treat TB in clinical practice. Despite the availability of effective antibiotics, effective treatment regimens still require long-term use of multiple drugs, leading to toxicity, low patient compliance, and the development of drug resistance. It has been confirmed that immune recognition, immune response, and immune regulation of Mycobacterium tuberculosis (Mtb) determine the occurrence, development, and outcome of diseases after Mtb infection. The research and development of TB-specific immunotherapy agents can effectively regulate the anti-TB immune response and provide a new approach toward the combined treatment of TB, thereby preventing and intervening in populations at high risk of TB infection. These immunotherapy agents will promote satisfactory progress in anti-TB treatment, achieving the goal of "ultra-short course chemotherapy." This review highlights the research progress in immunotherapy of TB, including immunoreactive substances, tuberculosis therapeutic vaccines, chemical agents, and cellular therapy.


Asunto(s)
Mycobacterium tuberculosis , Vacunas contra la Tuberculosis , Tuberculosis , Antituberculosos/uso terapéutico , Humanos , Inmunoterapia , Tuberculosis/tratamiento farmacológico , Vacunas contra la Tuberculosis/uso terapéutico
11.
Pharmacogenomics ; 22(18): 1185-1199, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34783250

RESUMEN

Aim: To identify novel genes associated with adverse effects of levonorgestrel (LNG) implants based on comparative whole-exome sequencing. Materials & methods: A cohort comprising 104 participants, including 52 controls and 52 women with LNG-related adverse effects, was recruited. Seven cases and eight controls were selected for whole-exome sequencing. We verified 13 single nucleotide variations (SNVs) related with integrin-mediated signaling pathway and cell proliferation using the MassARRAY platform. Results: Finally, we screened 49 cases and 52 controls for analyses. Two SNVs (rs7255721 and rs1042522) were located in ADAMTS10 and TP53, respectively, and significantly different between two groups. These two SNVs lead to changes in protein structure and physicochemical parameters. Conclusion: Here, we defined two pathogenic mutations related to adverse LNG effects.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Levonorgestrel/efectos adversos , Polimorfismo de Nucleótido Simple/genética , Adulto , Proliferación Celular/genética , Femenino , Humanos , Mutación/genética , Transducción de Señal/genética , Secuenciación del Exoma/métodos , Adulto Joven
12.
Adv Sci (Weinh) ; 8(17): e2101759, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34250756

RESUMEN

Renewable organic cathodes with abundant elements show promise for sustainable rechargeable batteries. Herein, for the first time, utilizing C60 fullerene as organic cathode for room-temperature lithium-ion battery is reported. The C60  cathode shows robust electrochemical performance preferably in ether-based electrolyte. It delivers discharge capacity up to 120 mAh g-1 and specific energy exceeding 200 Wh kg-1 with high initial Coulombic efficiency of 91%. The as-fabricated battery holds a capacity of 90 mAh g-1 after 50 cycles and showcases remarkable rate performance with 77 mAh g-1 retained at 500 mA g-1 . Noteworthily, three couples of unusual flat voltage plateaus recur at ≈2.4, 1.7, and 1.5 V, respectively. Diffusion-dominated three-electron-redox reactions are revealed by cyclic voltammogram and plateau capacities. Intriguingly, it is for the first time unveiled by in situ X-ray diffraction (XRD) that the C60 cathode underwent three reversible phase transitions during lithiation/delithiation process, except for the initial discharge when irreversible polymerization in between C60 nanoclusters existed as suggested by the characteristic irreversible peak shifts in both in situ XRD pattern and in situ Raman spectra. Cs-corrected transmission electron microscope corroborated these phase evolutions. Importantly, delithiation potentials derived from density-functional-theory simulation based on proposed phase structures qualitatively consists with experimental ones.

13.
J Immunol Res ; 2021: 6234560, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33575361

RESUMEN

BACKGROUND: The Traditional Chinese Medicine NiuBeiXiaoHe (NBXH) is a valid antituberculosis (TB) prescription from the experience of clinical practice. However, the mechanism of NBXH extracts' immunotherapy has been poorly understood. Herein, the immunotherapeutic efficacy and the differentially expressed (DE) genes of NBXH extracts were evaluated and identified in BALB/c mice. METHODS: The total RNA was extracted from peripheral blood mononuclear cells, and the DE genes were identified by gene chip. The enrichment and signaling pathway analyses were performed using Gene Ontology (GO) and KEGG database. RESULTS: It was shown that the treatment of NBXH extracts (high dose) significantly reduced mycobacteria loads and histopathological lesions in mice infected by Mycobacterium tuberculosis and resulted in 3,454 DE upregulated genes and 3,594 downregulated DE genes. Furthermore, NBXH extracts killed mycobacteria by inhibiting the supply of necessary ingredients for their growth and proliferation. They restored the disordered immune microenvironments by up- or downregulating immune and inflammation-related pathways. CONCLUSIONS: Taken together, NBXH extracts not only efficiently decreased the mycobacteria loads but also balanced the immune disorders in mice. These new findings provide a fresh perspective for elucidating the immunotherapeutic mechanism of NBXH extracts and pointed out the direction for improving the treatment efficacy of NBXH extracts.


Asunto(s)
Antituberculosos/farmacología , Medicamentos Herbarios Chinos/farmacología , Factores Inmunológicos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología , Animales , Antituberculosos/administración & dosificación , Carga Bacteriana , Biomarcadores , Biopsia , Biología Computacional , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Medicamentos Herbarios Chinos/administración & dosificación , Femenino , Perfilación de la Expresión Génica , Ontología de Genes , Factores Inmunológicos/administración & dosificación , Medicina Tradicional China , Ratones , Ratones Endogámicos BALB C , Especificidad de Órganos , Transducción de Señal
14.
Materials (Basel) ; 13(18)2020 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-32932863

RESUMEN

Using a new class of (BH4)- substituted argyrodite Li6PS5Z0.83(BH4)0.17, (Z = Cl, I) solid electrolyte, Li-metal solid-state batteries operating at room temperature have been developed. The cells were made by combining the modified argyrodite with an In-Li anode and two types of cathode: an oxide, LixMO2 (M = ⅓ Ni, ⅓ Mn, ⅓ Co; so called NMC) and a titanium disulfide, TiS2. The performance of the cells was evaluated through galvanostatic cycling and Alternating Current AC electrochemical impedance measurements. Reversible capacities were observed for both cathodes for at least tens of cycles. However, the high-voltage oxide cathode cell shows lower reversible capacity and larger fading upon cycling than the sulfide one. The AC impedance measurements revealed an increasing interfacial resistance at the cathode side for the oxide cathode inducing the capacity fading. This resistance was attributed to the intrinsic poor conductivity of NMC and interfacial reactions between the oxide material and the argyrodite electrolyte. On the contrary, the low interfacial resistance of the TiS2 cell during cycling evidences a better chemical compatibility between this active material and substituted argyrodites, allowing full cycling of the cathode material, 240 mAhg-1, for at least 35 cycles with a coulombic efficiency above 97%.

15.
Mil Med Res ; 7(1): 25, 2020 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-32493477

RESUMEN

BACKGROUND: Tuberculosis is a leading cause of death worldwide. BCG is an effective vaccine, but not widely used in many parts of the world due to a variety of issues. Mycobacterium vaccae (M. vaccae) is another vaccine used in human subjects to prevent tuberculosis. In the current study, we investigated the potential mechanisms of M. vaccae vaccination by determining differentially expressed genes in mice infected with M. tuberculosis before and after M. vaccae vaccination. METHODS: Three days after exposure to M. tuberculosis H37Rv strain (5 × 105 CFU), adult BALB/c mice randomly received either M. vaccae vaccine (22.5 µg) or vehicle via intramuscular injection (n = 8). Booster immunization was conducted 14 and 28 days after the primary immunization. Differentially expressed genes were identified by microarray followed by standard bioinformatics analysis. RESULTS: M. vaccae vaccination provided protection against M. tuberculosis infection (most prominent in the lungs). We identified 2326 upregulated and 2221 downregulated genes in vaccinated mice. These changes could be mapped to a total of 123 signaling pathways (68 upregulated and 55 downregulated). Further analysis pinpointed to the MyD88-dependent TLR signaling pathway and PI3K-Akt signaling pathway as most likely to be functional. CONCLUSIONS: M. vaccae vaccine provided good protection in mice against M. tuberculosis infection, via a highly complex set of molecular changes. Our findings may provide clue to guide development of more effective vaccine against tuberculosis.


Asunto(s)
Vacuna BCG/efectos adversos , Mycobacteriaceae/efectos de los fármacos , Tuberculosis/prevención & control , Adyuvantes Inmunológicos/efectos adversos , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/uso terapéutico , Animales , Vacuna BCG/farmacología , Vacuna BCG/uso terapéutico , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos BALB C , Tuberculosis/tratamiento farmacológico , Tuberculosis/inmunología , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética
16.
J Phys Condens Matter ; 32(41): 415804, 2020 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-32544890

RESUMEN

Hexagonal La2Ni7 and rhombohedral Y2Ni7 are weak itinerant antiferromagnet (wAFM) and ferromagnet (wFM), respectively. To follow the evolution between these two compounds, the crystal structure and magnetic properties of A 2 B 7 intermetallic compounds (A = La, Y, B = Ni) have been investigated combining x-ray powder diffraction and magnetic measurements. The La2-x Y x Ni7 intermetallic compounds with 0 ⩽ x ⩽ 1 crystallize in the hexagonal Ce2Ni7-type structure with Y preferentially located in the [A 2 B 4] units. The compounds with larger Y content (1.2 ⩽ x < 2) crystallize in both hexagonal and rhombohedral (Gd2Co7-type) structures with a substitution of Y for La in both [A 2 B 4] and [AB 5] units. Y2Ni7 crystallizes in the rhombohedral structure only. The average cell volume decreases linearly versus Y content, whereas the c/a ratio presents a minimum at x = 1 due to geometric constrains. The magnetic properties are strongly dependent on the structure type and the Y content. La2Ni7 displays a complex metamagnetic behavior with split AFM peaks. Compounds with x = 0.25 and 0.5 display a wAFM ground state and two metamagnetic transitions, the first one toward an intermediate wAFM state and the second one toward a FM state. T N and the second critical field µ 0 H c2 increase with the Y content, indicating a stabilization of the AFM state. LaYNi7, which is as the boundary between the two structure types, presents a very wFM state at low field and an AFM state as the applied field increases. All the compounds with x > 1, and which contains a rhombohedral phase are wFM with T C = 53(2) K. In addition to the experimental studies, first principles calculations using spin polarization have been performed to interpret the evolution of structural phase stability for 0 ⩽ x ⩽ 2.

17.
Infect Dis Poverty ; 9(1): 46, 2020 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-32349793

RESUMEN

BACKGROUND: Immune- and inflammation-related genes (IIRGs) play an important role in the pathogenesis of tuberculosis (TB). However, the relationship between IIRG polymorphisms and TB risk remains unknown. In this study, the gene polymorphisms and their association with tuberculosis were determined in a Chinese population. METHODS: We performed a case-control study involving 1016 patients with TB and 507 healthy controls of Han Chinese origin. Sixty-four single-nucleotide polymorphisms (SNPs) belonging to 18 IIRGs were genotyped by the PCR-MassArray assay, and the obtained data was analyzed with χ2-test, Bonferroni correction, and unconditional logistic regression analysis. RESULTS: We observed significant differences in the allele frequency of LTA rs2229094*C (P = 0.015), MBL2 rs2099902*C (P = 0.001), MBL2 rs930507*G (P = 0.004), MBL2 rs10824793*G (P = 0.004), and IL12RB1 rs2305740*G (P = 0.040) between the TB and healthy groups. Increased TB risk was identified in the rs930507 G/G genotype (Padjusted = 0.027) under a codominant genetic model as well as in the rs2099902 (C/T + C/C) vs T/T genotype (Padjusted = 0.020), rs930507 (C/G + G/G) vs C/C genotype (Padjusted = 0.027), and rs10824793 (G/A + G/G) vs A/A genotype (Padjusted = 0.017) under a dominant genetic model after Bonferroni correction in the analysis of the overall TB group rather than the TB subgroups. Furthermore, the rs10824793_rs7916582*GT and rs10824793_rs7916582*GC haplotypes were significantly associated with increased TB risk (P = 0.001, odds ratio [OR] = 1.421, 95% confidence interval [CI]: 1.152-1.753; and P = 0.018, OR = 1.364, 95% CI: 1.055-1.765, respectively). Moreover, the rs10824793_rs7916582*AT/AT or rs10824793_rs7916582*GT/GT diplotype showed a protective (P = 0.003, OR = 0.530, 95% CI: 0.349-0.805) or harmful (P = 0.009, OR = 1.396, 95% CI: 1.087-1.793) effect against the development of TB. CONCLUSIONS: This study indicated that MBL2 polymorphisms, haplotypes, and diplotypes were associated with TB susceptibility in the Han Chinese population. Additionally, larger sample size studies are needed to further confirm these findings in the future.


Asunto(s)
Lectina de Unión a Manosa/genética , Polimorfismo de Nucleótido Simple , Tuberculosis/genética , Adulto , Anciano , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
18.
Phys Chem Chem Phys ; 22(25): 13872-13879, 2020 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-32391527

RESUMEN

The properties of the mixed system LiBH4-LiCl-P2S5 are studied with respect to all-solid-state batteries. The studied material undergoes an amorphization upon heating above 60 °C, accompanied with increased Li+ conductivity beneficial for battery electrolyte applications. The measured ionic conductivity is ∼10-3 S cm-1 at room temperature with an activation energy of 0.40(2) eV after amorphization. Structural analysis and characterization of the material suggest that BH4 groups and PS4 may belong to the same molecular structure, where Cl ions interplay to accommodate the structural unit. Thanks to its conductivity, ductility and electrochemical stability (up to 5 V, Au vs. Li+/Li), this new electrolyte is successfully tested in battery cells operated with a cathode material (layered TiS2, theo. capacity 239 mA h g-1) and Li anode resulting in 93% capacity retention (10 cycles) and notable cycling stability under the current density ∼12 mA g-1 (0.05C-rate) at 50 °C. Further advanced characterisation by means of operando synchrotron X-ray diffraction in transmission mode contributes explicitly to a better understanding of the (de)lithiation processes of solid-state battery electrodes operated at moderate temperatures.

19.
Chem Biodivers ; 17(5): e2000137, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32207881

RESUMEN

Thermomyces lanuginosus and Scytalidium thermophilum are among the most ubiquitous thermophilic fungi in compost and soil. Chemical study on these two prevalent strains collected from Yunnan led to isolation of 23 metabolites, including one new metabolite, therlanubutanolide, and 15 known compounds, isolated from the YGP culture broth of Thermomyces lanuginosus and 7 known compounds isolated from Scytalidium thermophilum, respectively. Therlanubutanolide shared the quite similar features of the same carbon skeleton and saturation as natural hexadecanoic acids. This was the first reported discovery of such a lactone as natural occurring metabolite. All the compounds were reported for the first time from thermophilic fungi. Among them, N-[(2S,3R,4E,8E)-1,3-dihydroxy-9-methyloctadeca-4,8-dien-2-yl]acetamide was for the first time reported to be a naturally occurring metabolite and its NMR data was first provided in this study. A type of PKS-derived metabolites, three 3,4-dihydronaphthalen-1(2H)-ones, which were widely found in plant pathogenic fungi as phytotoxins and reported to have antimicrobial activity, were obtained from both dominant thermophilic fungi. The frequent occurrence of such PKS phytotoxins in these two thermophilic fungi might suggest particular ecological interest.


Asunto(s)
Ascomicetos/metabolismo , Naftalenos/metabolismo , Estructura Molecular , Naftalenos/química , Sintasas Poliquetidas/metabolismo , Especificidad de la Especie
20.
ACS Nano ; 14(2): 1600-1608, 2020 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-31961655

RESUMEN

Organic carbon materials, such as graphene and nanotubes, with a high specific capacity show promise in improving the energy density for lithium ion batteries (LiBs). Here, we report on the synthesis and characterization of C60(OH)12 and the C60(OH)12/graphene oxide (GO) composite and demonstrate their use as anode materials in LiBs. We find that the C60(OH)12/GO composite forms due to the chemical reactions between the carboxyl and epoxy groups of GO and the hydroxyl of C60(OH)12 nanoparticles and that C60(OH)12 uniformly grows on the surface of GO nanosheets. Using a suite of spectroscopy probes, we unequivocally show the mixing between C60(OH)12 and GO at the molecular level, which leads to superior battery performances. This composite has a reversible capacity of 1596 mAh g-1 at 0.2 A g-1, higher than the capacities of C60(OH)12 and GO. This composite has a superior cycling stability and excellent rate performance, making it a promising organic anode material for high-performance LiBs.

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