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1.
Appl Environ Microbiol ; 90(2): e0146823, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38193675

RESUMEN

Bacillus spp., a class of aerobic bacteria, is widely used as a biocontrol microbe in the world. However, the reactive oxygen species (ROS) will accumulate once the aerobic bacteria are exposed to environmental stresses, which can decrease cell activity or lead to cell death. Hydroxyl radical (·OH), the strongest oxide in the ROS, can damage DNA directly, which is generated through Fenton Reaction by H2O2 and free iron. Here, we proved that the synthesis of pulcherriminic acid (PA), an iron chelator produced by Bacillus spp., could reduce DNA damage to protect cells from oxidative stress by sequestrating excess free iron, which enhanced the cell survival rates in stressful conditions (salt, antibiotic, and high temperature). It was worth noting that the synthesis of PA was found to be increased under oxidative stress. Thus, we demonstrated that the YvmB, a direct negative regulator of PA synthesis cluster yvmC-cypX, could be oxidized at cysteine residue (C57) to form a dimer losing the DNA-binding activity, which led to an improvement in PA production. Collectively, our findings highlight that YvmB senses ROS to regulate PA synthesis is one of the evolved proactive defense systems in bacteria against adverse environments.IMPORTANCEUnder environment stress, the electron transfer chain will be perturbed resulting in the accumulation of H2O2 and rapidly transform to ·OH through Fenton Reaction. How do bacteria deal with oxidative stress? At present, several iron chelators have been reported to decrease the ·OH generation by sequestrating iron, while how bacteria control the synthesis of iron chelators to resist oxidative stress is still unclear. Our study found that the synthesis of iron chelator PA is induced by reactive oxygen species (ROS), which means that the synthesis of iron chelator is a proactive defense mechanism against environment stress. Importantly, YvmB is the first response factor found to protect cells by reducing the ROS generation, which present a new perspective in antioxidation studies.


Asunto(s)
Bacillus licheniformis , Bacillus , Especies Reactivas de Oxígeno/metabolismo , Bacillus licheniformis/metabolismo , Peróxido de Hidrógeno , Estrés Oxidativo , Hierro/metabolismo , Quelantes del Hierro , Bacillus/metabolismo , ADN/metabolismo
2.
Am J Obstet Gynecol ; 230(4): 436.e1-436.e12, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38135094

RESUMEN

BACKGROUND: The influence of SARS-CoV-2 infection after embryo transfer on early pregnancy outcomes in in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment remains inadequately understood. This knowledge gap endures despite an abundance of studies investigating the repercussions of preceding SARS-CoV-2 infection on early pregnancy outcomes in spontaneous pregnancies. OBJECTIVE: This study aimed to investigate the association between SARS-CoV-2 infection within 10 weeks after embryo transfer and early pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. STUDY DESIGN: This prospective cohort study was conducted at a single public in vitro fertilization center in China. Female patients aged 20 to 39 years, with a body mass index ranging from 18 to 30 kg/m2, undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, were enrolled between September 2022 and December 2022, with follow-up extended until March 2023. The study tracked SARS-CoV-2 infection time (≤14 days, ≤28 days, and ≤10 weeks after embryo transfer), symptoms, vaccination status, the interval between vaccination and embryo transfer, and early pregnancy outcomes, encompassing biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate. The study used single-factor analysis and multivariate logistic regression to examine the association between SARS-CoV-2 infection status, along with other relevant factors, and the early pregnancy outcomes. RESULTS: A total of 857 female patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment were analyzed. In the first stage, SARS-CoV-2 infection within 14 days after embryo transfer did not have a significant negative association with the biochemical pregnancy rate (adjusted odds ratio, 0.74; 95% confidence interval, 0.51-1.09). In the second stage, SARS-CoV-2 infection within 28 days after embryo transfer had no significant association with the implantation rate (36.6% in infected vs 44.0% in uninfected group; P=.181). No statistically significant association was found with the clinical pregnancy rate after adjusting for confounding factors (adjusted odds ratio, 0.69; 95% confidence interval, 0.56-1.09). In the third stage, SARS-CoV-2 infection within 10 weeks after embryo transfer had no significant association with the early miscarriage rate (adjusted odds ratio, 0.77; 95% confidence interval, 0.35-1.71). CONCLUSION: Our study suggests that SARS-CoV-2 infection within 10 weeks after embryo transfer may not be negatively associated with the biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. It is important to note that these findings are specific to the target population of in vitro fertilization/intracytoplasmic sperm injection patients aged 20 to 39 years, without previous SARS-CoV-2 infection, and with a body mass index of 18 to 30 kg/m2. This information offers valuable insights, addressing current concerns and providing a clearer understanding of the actual risk associated with SARS-CoV-2 infection after embryo transfer.


Asunto(s)
Aborto Espontáneo , COVID-19 , Embarazo , Humanos , Masculino , Femenino , Resultado del Embarazo , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Estudios Prospectivos , COVID-19/terapia , COVID-19/etiología , SARS-CoV-2 , Semen , Fertilización In Vitro/efectos adversos , Transferencia de Embrión , Índice de Embarazo , Estudios Retrospectivos
3.
Int J Mol Sci ; 25(8)2024 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-38674126

RESUMEN

Toona ciliata, also known as Chinese mahogany, is a high-quality and fast-growing wood species with a high economic value. The wood properties of T. ciliata of different provenances vary significantly. In this study, we conducted comprehensive transcriptome and metabolome analyses of red and non-red T. ciliata wood cores of different provenances to compare their wood properties and explore the differential metabolites and genes that govern the variation in their wood properties. Through combined analyses, three differential genes and two metabolites were identified that are possibly related to lignin synthesis. The lignin content in wood cores from T. ciliata of different provenances shows significant variation following systematic measurement and comparisons. The gene Tci09G002190, one of the three differential genes, was identified as a member of the CAD (Cinnamyl alcohol dehydrogenase) gene family of T. ciliata, which is associated with lignin synthesis. Our data provide insights into the determinants of the wood properties in T. ciliata, providing a solid foundation for research into the subsequent mechanisms of the formation of T. ciliata wood.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Lignina , Metaboloma , Transcriptoma , Madera , Madera/metabolismo , Madera/genética , Lignina/biosíntesis , Lignina/metabolismo , Perfilación de la Expresión Génica/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oxidorreductasas de Alcohol/genética , Oxidorreductasas de Alcohol/metabolismo
4.
Phys Chem Chem Phys ; 25(45): 30897-30902, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37955266

RESUMEN

Two semiconducting borophenes with layer-dependent magnetism are predicted based on spin-polarized density functional theory. Both monolayer borophenes are ferromagnetic. One is composed of B3 and B15 triangular motifs, exhibiting bipolar spin polarization and a magnetic moment of 1.00 µB per primitive cell. The other consists of B15 triangular motifs, possessing a Curie temperature of about 437 K and a magnetic moment of 3.00 µB per primitive cell. B atoms located between the triangular motifs are essential for inducing ferromagnetism in monolayer borophenes. However, bilayer borophenes with high-symmetry stacking orders are nonmagnetic. Furthermore, magnetic boron nanotubes and fullerenes could be made of monolayer borophenes. Finally, we propose to fabricate these magnetic semiconducting borophenes from the buckled triangular structure of borophenes via selective electron beam ionization of B atoms by scanning transmission electron microscopy.

5.
World J Microbiol Biotechnol ; 39(7): 168, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37088857

RESUMEN

Lichenysin, a cyclic lipopeptide biosurfactant produced by Bacillus licheniformis, is composed of aspartate, glutamine, valine, leucine, isoleucine, and branched chain fatty acids. The synthesis of these amino acids and fatty acids requires pyruvate and NADPH as the primary precursor and cofactor. Therefore, a sufficient supply of pyruvate and NADPH is crucial for lichenysin production. This study aimed to increase lichenysin production by constructing a synthetic ED pathway in B. licheniformis WX02 through introducing phosphogluconate dehydratase (encoded by gene edd) and 2-keto-3-deoxygluconate 6-phosphate aldolase (encoded by gene eda) from Escherichia coli. Additionally, the NADP+-dependent glucose-6-phosphate dehydrogenase (encoded by gene zwf) was overexpressed, resulting in an engineered strain WX02/pHY-edda(Ec)-zwf. Analysis of the fermentation process revealed that the concentrations of pyruvate, aspartate, glutamine, valine, leucine, branched-chain fatty acids (iC15:0, aC15:0, iC16:0, iC17:0), and NADPH in WX02/pHY-edda(Ec)-zwf were increased by 77.21%, 80.41%, 85.31%, 141.64%, 44.94%, 35.08%, 38.08%, 19.33%, 21.16%, and 425%, respectively, compared to the control strain WX02/pHY300, which resulted in a 45.43% increase of lichenysin titer. This work took advantage of the ED pathway to increase lichenysin production for the first time, and provides a promising strategy for boosting the productivity of biochemicals that require pyruvate and NADPH as precursor and cofactor.


Asunto(s)
Bacillus licheniformis , Bacillus licheniformis/genética , Bacillus licheniformis/metabolismo , Glutamina/metabolismo , Ácido Aspártico/metabolismo , Leucina , NADP/metabolismo , Péptidos Cíclicos , Valina , Piruvatos/metabolismo , Ácidos Grasos/metabolismo
6.
Zhongguo Zhong Yao Za Zhi ; 48(13): 3546-3555, 2023 Jul.
Artículo en Zh | MEDLINE | ID: mdl-37474988

RESUMEN

The purpose of this study was to explore the effect and mechanism of Xihuang Pills on rats with precancerous lesions of the breast. Of 48 healthy female rats, 8 were randomly selected as blank group, and the other 40 were treated with 7,12-dimethylbenzanthracene(DMBA) combined with estrogen and progestin to establish a model of precancerous lesions of the breast. The successfully modeled rats were randomly divided into a model group, a tamoxifen group(1.8 mg·kg~(-1)·d~(-1)), a Xihuang Pills low-dose group(0.3 g·kg~(-1)·d~(-1)), a medium-dose group(0.6 g·kg~(-1)·d~(-1)) and a high-dose group(1.2 g·kg~(-1)·d~(-1)). After 30 days of admi-nistration, the histopathological changes of viscera and breast were observed by haematoxylin and eosin(HE) staining, and the visceral index was calculated. Enzyme linked immunosorbent assay(ELISA) was used to detect the contents of estradiol(E_2) and progesterone(P) in serum. The protein expressions of vascular endothelial growth factor(VEGF) and fibroblast growth factor 2(FGF2) were detected by immunohistochemistry. The protein expressions of VEGF, vascular endothelial growth factor receptor 2(VEGFR2), phosphorylated-vascular endothelial growth factor receptor 2(p-VEGFR2), B-cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) were detected by Western blot and the mRNA expressions of VEGF, FGF2, CXC-chemokine receptor 4(CXCR4), cysteine aspartic acid-specific protease(caspase-3), and stromal cell-derived factor 1(SDF-1) were detected by real-time polymerase chain reaction(RT-PCR). HE staining revealed that the model group had some liver and kidney damages and severe hyperplastic mammary tissue, while the Xihuang Pills high-dose group had mild hyperplasia. Compared with the model group, the Xihuang Pills groups had lo-wer ovarian coefficient(P<0.05 or P<0.01) and Xihuang Pills high-dose group had lower uterine coefficient(P<0.01). ELISA results showed that compared with the model group, expressions of E_2 and P in Xihuang Pills high-dose group were significantly decreased(P<0.05 or P<0.01). Immunohistochemistry, Western blot and RT-PCR indicated that compared with the conditions in the model group, the protein and mRNA expressions of VEGF and FGF2 in the Xihuang Pills groups were down-regulated(P<0.05 or P<0.01), and the protein expression of Bcl-2 was lowered(P<0.01); there was a decrease in the protein expressions of VEGFR2 and p-VEGFR2(P<0.01), a down-regulation in the mRNA expressions of CXCR4 and SDF-1(P<0.01), while an increase in the mRNA expression of caspase-3(P<0.01) in both Xihuang Pills medium-dose and high-dose groups; the protein expression of Bax in Xihuang Pills high-dose group was increased(P<0.01). The above results indicated that Xihuang Pills can effectively intervene in precance-rous lesions of the breast, and the mechanism may be related to the regulation of E_2 and P secretion as well as the inhibition of angiogenesis and chemokine receptor expression, thus controlling the occurrence of precancerous lesions of the breast in rats.


Asunto(s)
Lesiones Precancerosas , Factor A de Crecimiento Endotelial Vascular , Ratas , Femenino , Animales , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2 , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Caspasa 3 , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Factor 2 de Crecimiento de Fibroblastos , Proteínas Proto-Oncogénicas c-bcl-2 , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Hiperplasia , Receptores de Quimiocina , ARN Mensajero
7.
Zhongguo Zhong Yao Za Zhi ; 48(6): 1642-1651, 2023 Mar.
Artículo en Zh | MEDLINE | ID: mdl-37005852

RESUMEN

The UPLC-MS/MS was established for the determination of acetyl-11-keto-beta-boswellic acid(AKBA) and ß-boswellic acid(ß-BA), the main active components of Olibanum and Myrrha extracts in Xihuang Formula, in rat plasma and urine. The effects of compatibility on the pharmacokinetic behaviors of AKBA and ß-BA in rats were investigated, and the differences in pharmacokinetic behaviors between healthy rats and rats with precancerous lesions of breast cancer were compared. The results showed that compared with RM-NH and RM-SH groups, the AUC_(0-t) and AUC_(0-∞) of ß-BA increased(P<0.05 or P<0.01), T_(max) decreased(P<0.05 or P<0.01), and C_(max) increased(P<0.01) after compatibility. The trends of AKBA and ß-BA were the same. Compared with RM-SH group, the T_(max) decreased(P<0.05), C_(max) increased(P<0.01), and the absorption rate increased in the normal group of Xihuang Formula. The results of urinary excretion showed that there was a decreasing trend in the urinary excretion rate and total urinary excretion of ß-BA and AKBA after compatibility, but there was no statistical difference. Compared with normal group of Xihuang Formula, the AUC_(0-t) and AUC_(0-∞) of ß-BA increased(P<0.05), T_(max) increased(P<0.05), and the clearance rate decreased in the breast precancerous lesion group. AUC_(0-t) and AUC_(0-∞) of AKBA showed an increasing trend, the in vivo retention time was prolonged, and the clearance rate was reduced, but there was no significant difference compared with the normal group. The cumulative urinary excretion and urinary excretion rate of ß-BA and AKBA decreased under pathological conditions, indicating that pathological conditions could affect the in vivo process of ß-BA and AKBA, and reduce their excretion in the form of prototype drugs, showing different pharmacokine-tic characteristics from normal physiological conditions. In this study, UPLC-MS/MS analysis method was established, which was sui-table for in vivo pharmacokinetic analysis of ß-BA and AKBA. This study laid a foundation for the development of new dosage forms of Xihuang Formula.


Asunto(s)
Medicamentos Herbarios Chinos , Lesiones Precancerosas , Triterpenos , Ratas , Animales , Cromatografía Liquida , Espectrometría de Masas en Tándem , Triterpenos/farmacología
8.
Metab Eng ; 74: 108-120, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36257594

RESUMEN

Lichenysin, producted by Bacillus licheniformis, is an important cyclic lipopeptide biosurfactant, which has potential applications in oil exploitation, drug development, biological control of agriculture and bioremediation. While studies are lacking on metabolism regulation of lichenysin biosynthesis, which limits metabolic engineering and large-scale production of lichenysin. In this study, the yield of lichenysin was improved obviously by 13.6 folds to 2.18 ± 0.03 g/L in degU deletion strain (WX02△degU) compared with the wild-type strain (WX02) and completely inhibited in degU overexpressed strain (WX02/pHY-degU). We further proved that DegU, a transcription factor plays a significant role in multicellular behavior, is a key negative regulator of lichenysin synthesis lchA operon. But interestingly, lichenysin yield was still inhibited by overexpressing DegU in the promoter-substituted strain (WX02-PP43lch), in which promoter of lchA operon cannot be controlled by DegU. Thus, through 13C-metabolic flux analysis, we found that deletion of degU also enhanced glucose uptake, branched chain amino acid synthesis, and fatty acid synthesis, while decrease acetoin synthesis, which is beneficial for the supply of lichenysin precursors. Further experiments demonstrate that DegU regulates these pathways by binding to the promoter regions of related genes. Overall, we systematically investigated the multi-pathway regulation network mediated by DegU on lichenysin biosynthesis, which not only contributes to the further metabolic engineering for lichenysin high-production, but sheds light on studies of transcription factor regulation.


Asunto(s)
Bacillus licheniformis , Bacillus licheniformis/genética , Bacillus licheniformis/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Lipoproteínas/química , Lipoproteínas/genética , Lipoproteínas/metabolismo , Anilidas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Bacillus subtilis/metabolismo
9.
Zhongguo Zhong Yao Za Zhi ; 46(19): 4978-4985, 2021 Oct.
Artículo en Zh | MEDLINE | ID: mdl-34738392

RESUMEN

In this paper, co-processed lactose SuperTab 40 LL was selected as fillers to study the preparation of musk sustained-release mini-tablets in the Xihuang multiple-unit drug release system. Musk sustained-release tablets containing different proportions of SuperTab 40 LL and MCC were prepared under various pressures, and then the compressibility and compactibility of these prescriptions were evaluated by Walker, Heckel and Ryshkewitch-Duckworth equations. In addition, the fluidity of the prescriptions was evaluated by parameters of Kawakita equation. There was a comprehensive analysis of the effect of SuperTab 40 LL on musk sustained-release mini-tablets combined with the appearance of SuperTab 40 LL and their tensile strength. The results shown that SuperTab 40 LL had better compression process through the Heckel equation, and the direct compression process of drug powders with excipients can be analyzed by the Kawakita and Ryshkewitch-Duckworth equations. As a new type of co-processed lactose, SuperTab 40 LL had a good fluidity and compactibility. SuperTab 40 LL may undergo particle crushing and plastic deformation during the compression process, which increased the contact area and bonding sites between the particles, and aggregated and shaped the mixed powder easy. Moreover, MCC showed a synergistic effect, and the combined application with SuperTab 40 ll could effectively improve the fluidity and compressibility of the musk sustained-release powder. When the ratio of SuperTab 40 LL and MCC was 2∶1, musk sustained-release mini-tablets had a high drug loading capacity and good compactibility in line with the design objectives.


Asunto(s)
Excipientes , Modelos Teóricos , Preparaciones de Acción Retardada , Composición de Medicamentos , Ácidos Grasos Monoinsaturados , Polvos , Comprimidos
10.
Microb Cell Fact ; 19(1): 162, 2020 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-32778112

RESUMEN

BACKGROUND: Whey is a major pollutant generated by the dairy industry. To decrease environmental pollution caused by the industrial release of whey, new prospects for its utilization need to be urgently explored. Here, we investigated the possibility of using whey powder to produce 2,3-butanediol (BDO), an important platform chemical. RESULTS: Klebsiella oxytoca strain PDL-0 was selected because of its ability to efficiently produce BDO from lactose, the major fermentable sugar in whey. After deleting genes pox, pta, frdA, ldhD, and pflB responding for the production of by-products acetate, succinate, lactate, and formate, a recombinant strain K. oxytoca PDL-K5 was constructed. Fed-batch fermentation using K. oxytoca PDL-K5 produced 74.9 g/L BDO with a productivity of 2.27 g/L/h and a yield of 0.43 g/g from lactose. In addition, when whey powder was used as the substrate, 65.5 g/L BDO was produced within 24 h with a productivity of 2.73 g/L/h and a yield of 0.44 g/g. CONCLUSION: This study demonstrated the efficiency of K. oxytoca PDL-0 for BDO production from whey. Due to its non-pathogenicity and efficient lactose utilization, K. oxytoca PDL-0 might also be used in the production of other important chemicals using whey as the substrate.


Asunto(s)
Butileno Glicoles/metabolismo , Klebsiella oxytoca/genética , Klebsiella oxytoca/metabolismo , Suero Lácteo/metabolismo , Técnicas de Cultivo Celular por Lotes , Reactores Biológicos , Fermentación , Técnicas de Inactivación de Genes , Ingeniería Metabólica , Polvos
11.
Microbiol Res ; 287: 127843, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39024796

RESUMEN

Oxidative damage caused by the accumulation of reactive oxygen species (ROS) is one of the main obstacles to the improvement of microbial cell growth and fermentation characteristics under adverse environments. And the antioxidant capacity of cells will increase with the cell growth. Here, we found that a transition state transcription factor AbrB related to changes in cell growth status could regulate the accumulation of ROS and antioxidant capacity in Bacillus licheniformis. The results showed that the accumulation of intracellular ROS was reduced by 23.91 % and the cell survival rates were increased by 1.77-fold under 0.5 mM H2O2 when AbrB was knocked out. We further mapped regulatory target genes of AbrB related to ROS generation or clearance based on our previously analyzed transcriptome sequencing. It proved that AbrB could promote ROS generation via upregulating the synthesis of oxidase and siderophores, and negatively regulating the synthesis of iron chelators (pulcherriminic acid, and H2S). Additionally, AbrB could inhibit ROS clearance by negatively regulating the synthesis of antioxidase (superoxide dismutase, catalase, peroxidase, thioredoxin, thioredoxin reductase) and cysteine. Those results illustrated that the inactivation of AbrB during the stationary phase, along with its control over ROS generation and clearance, might represent a vital self-protection mechanism during cell evolution. Overall, the systematic investigation of the multi-pathway regulation network of ROS generation and clearance highlights the important function of AbrB in maintaining intracellular redox balance.


Asunto(s)
Antioxidantes , Bacillus licheniformis , Proteínas Bacterianas , Regulación Bacteriana de la Expresión Génica , Peróxido de Hidrógeno , Especies Reactivas de Oxígeno , Factores de Transcripción , Especies Reactivas de Oxígeno/metabolismo , Bacillus licheniformis/metabolismo , Bacillus licheniformis/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Peróxido de Hidrógeno/metabolismo , Antioxidantes/metabolismo , Estrés Oxidativo , Sideróforos/metabolismo
12.
Acta Biomater ; 181: 402-414, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38734282

RESUMEN

Tumor hypoxia, high oxidative stress, and low immunogenic create a deep-rooted immunosuppressive microenvironment, posing a major challenge to the therapeutic efficiency of cancer immunotherapy for solid tumor. Herein, an intelligent nanoplatform responsive to the tumor microenvironment (TME) capable of hypoxia relief and immune stimulation has been engineered for efficient solid tumor immunotherapy. The MnO2@OxA@OMV nanoreactor, enclosing bacterial-derived outer membrane vesicles (OMVs)-wrapped MnO2 nanoenzyme and the immunogenic cell death inducer oxaliplatin (OxA), demonstrated intrinsic catalase-like activity within the TME, which effectively catalyzed the endogenous H2O2 into O2 to enable a prolonged oxygen supply, thereby alleviating the tumor's oxidative stress and hypoxic TME, and expediting OxA release. The combinational action of OxA-caused ICD effect and Mn2+ from nanoreactor enabled the motivation of the cGAS-STING pathway to significantly improve the activation of STING and dendritic cells (DCs) maturation, resulting in metalloimmunotherapy. Furthermore, the immunostimulant OMVs played a crucial role in promoting the infiltration of activated CD8+T cells into the solid tumor. Overall, the nanoreactor offers a robust platform for solid tumor treatment, highlighting the significant potential of combining relief from tumor hypoxia and immune stimulation for metalloimmunotherapy. STATEMENT OF SIGNIFICANCE: A tailor-made nanoreactor was fabricated by enclosing bacterial-derived outer membrane vesicles (OMVs) onto MnO2 nanoenzyme and loading with immunogenic cell death inducer oxaliplatin (OxA) for tumor metalloimmunotherapy. The nanoreactor possesses intrinsic catalase-like activity within the tumor microenvironment, which effectively enabled a prolonged oxygen supply by catalyzing the conversion of endogenous H2O2 into O2, thereby alleviating tumor hypoxia and expediting OxA release. Furthermore, the TME-responsive release of nutritional Mn2+ sensitized the cGAS-STING pathway and collaborated with OxA-induced immunogenic cell death (ICD). Combing with immunostimulatory OMVs enhances the uptake of nanoreactors by DCs and promotes the infiltration of activated CD8+T cells. This nanoreactor offers a robust platform for solid tumor treatment, highlighting the significant potential of combining relief from tumor hypoxia and immune stimulation for metalloimmunotherapy.


Asunto(s)
Inmunoterapia , Microambiente Tumoral , Animales , Inmunoterapia/métodos , Ratones , Microambiente Tumoral/efectos de los fármacos , Línea Celular Tumoral , Hipoxia Tumoral/efectos de los fármacos , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Oxaliplatino/farmacología , Oxaliplatino/química , Óxidos/química , Óxidos/farmacología , Manganeso/química , Manganeso/farmacología , Humanos , Femenino , Neoplasias/terapia , Neoplasias/patología , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Células Dendríticas/inmunología , Ratones Endogámicos C57BL
13.
Photoacoustics ; 37: 100595, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38404402

RESUMEN

This paper reports a mini-resonant photoacoustic sensor for high-sensitivity trace gas sensing. The sensor primarily contains a sphere-cylinder coupled acoustic resonator, a cylindrical buffer chamber, and a fiber-optic acoustic sensor. The acoustic field distributions of this mini-resonant photoacoustic sensor and the conventional T-type resonant photoacoustic sensor have been carefully evaluated, showing that the first-order resonance frequency of the present mini-resonant photoacoustic sensor is reduced by nearly a half compared to that of the T-type resonant photoacoustic sensor. The volume of the developed photoacoustic cavity is only about 0.8 cm3. Trace methane is selected as the target analytical gas and a detection limit of 101 parts-per-billion at 100-s integration time has been achieved, corresponding to a normalized noise equivalent absorption (NNEA) coefficient of 1.04 × 10-8 W·cm-1·Hz-1/2. The developed mini-resonant photoacoustic sensor provides potential for high-sensitivity trace gas sensing in narrow spaces.

14.
Front Nutr ; 11: 1364841, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38765814

RESUMEN

Background: Nephritis is a pivotal catalyst in chronic kidney disease (CKD) progression. Although epidemiological studies have explored the impact of plasma circulating metabolites and drugs on nephritis, few have harnessed genetic methodologies to establish causal relationships. Methods: Through Mendelian randomization (MR) in two substantial cohorts, spanning large sample sizes, we evaluated over 100 plasma circulating metabolites and 263 drugs to discern their causal effects on nephritis risk. The primary analytical tool was the inverse variance weighted (IVW) analysis. Our bioinformatic scrutiny of GSE115857 (IgA nephropathy, 86 samples) and GSE72326 (lupus nephritis, 238 samples) unveiled anomalies in lipid metabolism and immunological characteristics in nephritis. Thorough sensitivity analyses (MR-Egger, MR-PRESSO, leave-one-out analysis) were undertaken to verify the instrumental variables' (IVs) assumptions. Results: Unique lipoprotein-related molecules established causal links with diverse nephritis subtypes. Notably, docosahexaenoic acid (DHA) emerged as a protective factor for acute tubulointerstitial nephritis (ATIN) (OR1 = 0.84, [95% CI 0.78-0.90], p1 = 0.013; OR2 = 0.89, [95% CI 0.82-0.97], p2 = 0.007). Conversely, multivitamin supplementation minus minerals notably increased the risk of ATIN (OR = 31.25, [95% CI 9.23-105.85], p = 0.004). Reduced α-linolenic acid (ALA) levels due to lipid-lowering drugs were linked to both ATIN (OR = 4.88, [95% CI 3.52-6.77], p < 0.001) and tubulointerstitial nephritis (TIN) (OR = 7.52, [95% CI 2.78-20.30], p = 0.042). While the non-renal drug indivina showed promise for TIN treatment, the use of digoxin, hydroxocobalamin, and liothyronine elevated the risk of chronic tubulointerstitial nephritis (CTIN). Transcriptome analysis affirmed that anomalous lipid metabolism and immune infiltration are characteristic of IgA nephropathy and lupus nephritis. The robustness of these causal links was reinforced by sensitivity analyses and leave-one-out tests, indicating no signs of pleiotropy. Conclusion: Dyslipidemia significantly contributes to nephritis development. Strategies aimed at reducing plasma low-density lipoprotein levels or ALA supplementation may enhance the efficacy of existing lipid-lowering drug regimens for nephritis treatment. Renal functional status should also be judiciously considered with regard to the use of nonrenal medications.

15.
ACS Appl Mater Interfaces ; 16(20): 25788-25798, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38716694

RESUMEN

Phototherapy, represented by photodynamic therapy (PDT) and photothermal therapy (PTT), has great potential in tumor treatment. However, the presence of antioxidant glutathione (GSH) and the heat shock proteins (HSPs) expression caused by high temperature can weaken the effects of PDT and PTT. Here, a multifunctional nanocomplex BT&GA@CL is constructed to realize enhanced synergistic PDT/PTT. Cinnamaldehyde liposomes (CLs) formed by cinnamaldehyde dimer self-assembly were loaded with in gambogic acid (GA) and an aggregation-induced emission molecule BT to obtain BT&GA@CL. As a drug carrier, CL can consume glutathione (GSH) and release drugs responsively. The released BT aggregates can simultaneously act as both a photothermal agent and photosensitizer to achieve PDT and PTT under 660 nm laser irradiation. Specifically, GA as an HSP90 inhibitor can attenuate PTT-induced HSP90 protein expression, thereby weakening the tolerance of tumor cells to high temperatures and enhancing PTT. Such a multifunctional nanocomplex simultaneously modulates the content of GSH and HSP90 in tumor cells, thus enhancing both PDT and PTT, ultimately achieving the goal of efficient combined tumor suppression.


Asunto(s)
Glutatión , Liposomas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Xantonas , Liposomas/química , Glutatión/metabolismo , Glutatión/química , Humanos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Xantonas/química , Xantonas/farmacología , Animales , Ratones , Terapia Fototérmica , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/patología , Neoplasias/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/química , Antineoplásicos/química , Antineoplásicos/farmacología
16.
J Colloid Interface Sci ; 671: 779-789, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38833910

RESUMEN

The modulation of microstructures in conjugated polymers represents a viable strategy for enhancing photocatalytic efficiency, albeit hampered by complex processing techniques. Here, we present an uncomplicated, template-free method to synthesize polymeric photocatalysts, namely BCN(x)@PPy, featuring a hollow nanotube-nanocluster core-shell superstructure. This configuration is realized through intramolecular covalent crosslinking and synergistic intermolecular donor-acceptor (D-A) interactions between phenylene pyrene (PPy, D) nanotubes and poly([1,1'-biphenyl]-3-carbonitrile) (PBCN, A) nanoclusters. Interestingly, the optimized BCN2@PPy composite demonstrates remarkably enhanced performance for photocatalytic hydrogen evolution, with an efficiency of 14.7-fold higher than that of unmodified PPy nanotubes. Experimental and density functional theory calculations revealed that BCN(x)@PPy composites are conducive to shortening photogenerated exciton migration, facilitating charge separation and transfer, reducing nanoclusters aggregation or re-stacking, and providing sufficient catalytically active sites, all contributing to the heightened efficiency in photocatalysis. These insights underscore the potential for precise molecular adjustments in conjugated polymers, advancing artificial photosynthesis.

17.
Front Bioeng Biotechnol ; 10: 955097, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35903792

RESUMEN

Sustainable and environment-friendly microbial fermentation processes have been developed to produce numerous chemicals. However, the high energy input required for sterilization and substantial fresh water consumption restrict the economic feasibility of traditional fermentation processes. To address these problems, Vibrio natriegens, a promising microbial chassis with low nutritional requirements, high salt tolerance and rapid growth rate can be selected as the host for chemical production. In this study, V. natriegens was metabolic engineered to produce 2,3-butanediol (2,3-BD), an important platform chemical, through non-sterilized fermentation with seawater-based minimal medium after expressing a 2,3-BD synthesis cluster and deleting two byproduct encoding genes. Under optimized fermentative conditions, 41.27 g/L 2,3-BD was produced with a productivity of 3.44 g/L/h and a yield of 0.39 g/g glucose by recombinant strain V. natriegensΔfrdAΔldhA-pETRABC. This study confirmed the feasibility of non-sterilized fermentation using seawater to replace freshwater and other valuable chemicals may also be produced through metabolic engineering of the emerging synthetic biology chassis V. natriegens.

18.
Comput Intell Neurosci ; 2022: 2526821, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35096037

RESUMEN

In the fields of traffic management, traffic health, and vehicle safety, vehicle speed prediction is an important research topic. The greater the difference between vehicle speed and average vehicle speed, or the more discrete the vehicle speed distribution, the higher the accident rate. This paper proposes a vehicle speed prediction method based on adaptive KF (Kalman filtering) in the ARMA (Autoregressive Moving Average) environment to address the problem of high-speed moving vehicle speed prediction. The ARMA theory is used to model the prediction of speed time series. The contribution rate of each coefficient representing the original time series is different after fitting the original time series with the ARMA model, so each coefficient must be given a certain weight. Multisource traffic data fusion and interval speed prediction are carried out on the basis of few-shot data preprocessing and traffic state division, according to different traffic states. The speed prediction accuracy is very high, according to the algorithm verification results.


Asunto(s)
Algoritmos , Proyectos de Investigación , Recolección de Datos , Modelos Estadísticos , Factores de Tiempo
19.
J Phys Chem A ; 115(35): 9987-92, 2011 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-21800870

RESUMEN

On the basis of density functional theory (DFT) methods, we study the magnetic properties and electronic structures of the armchair (4, 4) and zigzag (8, 0) single-wall SiC nanotubes with various vacancies and boron substitution. The calculation results indicate that a Si vacancy could induce the magnetic moments in both armchair (4, 4) and zigzag (8, 0) single-wall SiC nanotubes, which mainly arise from the p orbital of C atoms surrounding Si vacancy, leading to the ferromagnetic coupling. However, a C vacancy could only bring about the magnetic moment in armchair (4, 4) single-wall SiC nanotube, which mainly originates from the polarization of Si p electrons, leading to the antiferromagnetic coupling. In addition, for both kinds of single-wall SiC nanotubes, magnetic moments can be induced by a boron atom substituting for C atom. When two boron atoms locate nearest neighbored, both kinds of single-wall Si(C, B) nanotubes exhibit antiferromagnetic coupling.

20.
Environ Sci Pollut Res Int ; 28(39): 55233-55251, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34129162

RESUMEN

Based on the formaldehyde (HCHO) inversion data of OMI satellite sensor from 2009 to 2019, this paper discusses the spatial and temporal distribution of HCHO column concentration over the Qinghai-Tibet Plateau in the past 11 years and explores the factors affecting the dynamic distribution of atmospheric HCHO column concentration over the Qinghai-Tibet Plateau in combination with meteorological, aerosol, ozone, and other data. The results show that the average concentration of HCHO column in the Qinghai-Tibet Plateau is 8.84 × 1015 molec/cm2 in the past 11 years, which is relatively low, and the annual variation rate of HCHO column is 7.79%, showing a slight upward trend. The seasonal changes show a trend of Autumn < Winter < Spring < Summer. The monthly variation is more obvious than the seasonal variation. The spatial distribution showed a decreasing trend from southeast to northwest. Residual analysis showed that 83.77% of the area was frequently affected by natural factors. Correlation analysis found that the natural factors including precipitation, air temperature, and atmospheric activities for a greater influence on the column experiment the distribution of the concentration of the Qinghai-Tibet Plateau and human factors, such as biomass, the distribution of fossil fuel combustion, and emissions to HCHO, play a promoting role. Through the backward trajectory analysis, it can be seen that the transboundary atmospheric transport activity has a prominent contribution to the distribution of HCHO in the southern region of the Qinghai-Tibet Plateau. Hurst index study found that in the future, the concentration of HCHO column in 53.03% of the Qinghai-Tibet Plateau will decrease, but in some areas, such as the eastern and northern parts of the Qinghai-Tibet Plateau, it will increase.


Asunto(s)
Formaldehído , Meteorología , Humanos , Tibet
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