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1.
Heliyon ; 10(11): e31932, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38867959

RESUMEN

Background and objectives: The efficacy of rituximab (RTX) in treating steroid-resistant Graves' orbitopathy (GO) has been limitedly studied in Asians. Moreover, RTX has been considered even less for patients with steroid-resistant dysthyroid optic neuropathy (DON) who failed to undergo orbital decompression surgery for physical or financial reasons, or who responded poorly to the procedure. This study aimed to investigate the efficacy of RTX in treating steroid-resistant active moderate-to-severe and sight-threatening GO in a Chinese population. Methods: Data from 28 patients with steroid-resistant GO prescribed a single dose of 500 mg RTX were retrospectively retrieved. Treatment responses and contributing factors were analyzed. Results: The median follow-up time was 22 (8-34) weeks. 23 (82.1 %) patients had a positive objective outcome recommended by the European Group on Graves' Orbitopathy (EUGOGO), while 25 (92.6 %) had a decrease in 7-item clinical activity score (CAS) by at least 2. Diplopia, visual dysfunction, and MRI-detected T2 relaxation time of the involved extraocular muscles improved significantly at the last follow-up compared to baseline (81.0 % vs. 47.6 %, 38.9 % vs. 16.7 %, and 87.8 (8.64) vs. 75.8 (10.9) ms, respectively; all p values < 0.05). No significant improvement was seen in terms of proptosis and eye muscle duction. Notably, a higher baseline IgG4 to IgG ratio was a predictor for RTX-induced positive EUGOGO outcomes. After RTX treatment, all 8 patients with DON demonstrated inactivation, and 4 improved in visual acuity by ≥ 1 line. No patient with DON experienced obvious deterioration. Conclusion: A single dose of 500 mg RTX seemed to be an effective and tolerable treatment for steroid-resistant GO. However, larger-scale studies with a control group are required for a more solid conclusion. The role of RTX in steroid-resistant DON management where surgery is unavailable or ineffective should be further explored.

2.
Arch Gynecol Obstet ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38814453

RESUMEN

BACKGROUND: Gestational diabetes mellitus (GDM) poses significant health risks for both mothers and children, contributing to long-term complications such as type 2 diabetes and cardiovascular disease. This study explores the potential of microRNAs (miRNAs) as biomarkers for GDM by analyzing peripheral blood samples from GDM patients. METHOD: Ten samples, including peripheral blood from 5 GDM patients and 5 controls, were collected to perform the RNA sequencing analysis. Differentially expressed miRNAs were further validated by quantitative real-time polymerase chain reaction. RESULTS: A total of 2287 miRNAs were identified, 229 of which showed differential expression. Validation by qRT-PCR confirmed significant up-regulation of miR-5193, miR-5003-3p, miR-3127-5p, novel-miR-96, miR-6734-5p, and miR-122-5p, while miR-10395-3p was down-regulated. Bioinformatics analyses revealed the involvement of these miRNAs in pathways associated with herpes simplex virus 1 infection. CONCLUSION: This study provides insights into the differential expression of miRNAs in GDM patients and their potential roles in disease pathogenesis. It suggests that the differentially expressed miRNAs could serve as potential biomarkers for GDM, shedding light on the complex molecular mechanisms involved.

3.
Nat Commun ; 15(1): 4300, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773134

RESUMEN

The chromatin modifier GRAIN WEIGHT 6a (GW6a) enhances rice grain size and yield. However, little is known about its gene network determining grain size. Here, we report that MITOGEN-ACTIVED PROTEIN KINASE 6 (OsMAPK6) and E3 ligase CHANG LI GENG 1 (CLG1) interact with and target GW6a for phosphorylation and ubiquitylation, respectively. Unexpectedly, however, in vitro and in vivo assays reveal that both of the two post-translational modifications stabilize GW6a. Furthermore, we uncover two major GW6a phosphorylation sites (serine142 and threonine186) targeted by OsMAPK6 serving an important role in modulating grain size. In addition, our genetic and molecular results suggest that the OsMAPK6-GW6a and CLG1-GW6a axes are crucial and operate in a non-additive manner to control grain size. Overall, our findings identify a previously unknown mechanism by which phosphorylation and ubiquitylation non-additively stabilize GW6a to enhance grain size, and reveal correlations and interactions of these posttranslational modifications during rice grain development.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Oryza , Proteínas de Plantas , Ubiquitinación , Oryza/metabolismo , Oryza/genética , Oryza/crecimiento & desarrollo , Fosforilación , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Grano Comestible/metabolismo , Grano Comestible/crecimiento & desarrollo , Procesamiento Proteico-Postraduccional , Plantas Modificadas Genéticamente , Cromatina/metabolismo
4.
Nat Commun ; 15(1): 3046, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589370

RESUMEN

Sintering of active metal species often happens during catalytic reactions, which requires redispersion in a reactive atmosphere at elevated temperatures to recover the activity. Herein, we report a simple method to redisperse sintered Cu catalysts via O2-H2O treatment at room temperature. In-situ spectroscopic characterizations reveal that H2O induces the formation of hydroxylated Cu species in humid O2, pushing surface diffusion of Cu atoms at room temperature. Further, surface OH groups formed on most hydroxylable support surfaces such as γ-Al2O3, SiO2, and CeO2 in the humid atmosphere help to pull the mobile Cu species and enhance Cu redispersion. Both pushing and pulling effects of gaseous H2O promote the structural transformation of Cu aggregates into highly dispersed Cu species at room temperature, which exhibit enhanced activity in reverse water gas shift and preferential oxidation of carbon monoxide reactions. These findings highlight the important role of H2O in the dynamic structure evolution of supported metal nanocatalysts and lay the foundation for the regeneration of sintered catalysts under mild conditions.

5.
Angew Chem Int Ed Engl ; 63(5): e202316888, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38078622

RESUMEN

Supported metal catalysts are widely used for chemical conversion, in which construction of high density metal-oxide or oxide-metal interface is an important means to improve their reaction performance. Here, Cu@ZnOx encapsulation structure has been in situ constructed through gas-phase migration of Zn species from ZnO particles onto surface of Cu nanoparticles under CO2 hydrogenation atmosphere at 450 °C. The gas-phase deposition of Zn species onto the Cu surface and growth of ZnOx overlayer is self-limited under the high temperature and redox gas (CO2 /H2 ) conditions. Accordingly, high density ZnOx -Cu interface sites can be effectively tailored to have an enhanced activity in CO2 hydrogenation to methanol. This work reveals a new route for the construction of active oxide-metal interface and classic strong metal-support interaction state through gas-phase migration of support species induced by high temperature redox reaction atmosphere.

6.
Phys Chem Chem Phys ; 26(2): 974-984, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38088058

RESUMEN

The quantity of surface oxygen vacancies/defects is critical to promote the reactivity of metal oxide catalysts. Therefore, for the controlled engineering of Bi2Zr2O7 with rich surface defects for soot combustion, four different methods have been adopted. Bi2Zr2O7 compounds with a defective fluorite phase but with varied surface vacancy concentrations have been successfully synthesized by various methods. The best catalyst (Bi2Zr2O7-CP) was fabricated by a facile co-precipitation method. Both O2- and O22- were the active surface sites whose number positively correlated to the number of surface oxygen vacancies and determined the activity. Moreover, a sample with more surface vacancies usually had weaker Zr-O bonds, which could be the intrinsic factor to enhance the activity. In addition, a novel and simple method has been developed to accurately titrate the absolute amount of soot reactive oxygen sites and calculate the TOF values. In conclusion, by optimizing the preparation methods, Bi2Zr2O7 catalysts with rich surface defects can be tuned, which may help in designing more applicable soot oxidation catalysts.

7.
J Nutr Biochem ; 124: 109491, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37865382

RESUMEN

Weaning is one of the major factors that cause stress and intestinal infection in infants and in young animals due to an immature intestine and not fully developed immune functions. Pectin (PEC), a prebiotic polysaccharide, has attracted considerable attention in intestinal epithelial signaling and function via modulation of the microbial community. A total of 16 weaned piglets (21-d-old) were randomly assigned into two groups: control group and PEC group. Supplementation of 5% pectin improved intestinal mucosal barrier function by modulating the composition of the bile acid pool in piglets. Specifically, piglets in PEC group had less serum D-lactate content and alkaline phosphatase activity. In the ileum, dietary pectin increased the number of crypt PAS/AB-positive goblet cells and the mRNA expressions of MUC2, ZO-1, and Occludin. Piglets in PEC group displayed a decreased abundance of Enterococcus (2.71 vs. 65.92%), but the abundances of Lactobacillus (30.80 vs. 7.93%), Streptococcus (21.41 vs. 14.81%), and Clostridium_sensu_stricto_1 (28.34 vs. 0.01%) were increased. Elevated concentrations of bile acids especially hyocholic acid species (HCAs) including HCA, HDCA, and THDCA were also observed. Besides, correlation analysis revealed that dietary pectin supplementation may have beneficial effects through stimulation of the crosstalk between gut microbes and bile acid synthesis within the enterohepatic circulation. Thus, dietary pectin supplementation exhibited a further positive effect on the healthy growth and development of weaned piglets. These findings suggest pectin supplementation as the prebiotic is beneficial for gut health and improvement of weaned stress via regulating microbiota and bile acid metabolism.


Asunto(s)
Suplementos Dietéticos , Funcion de la Barrera Intestinal , Humanos , Animales , Porcinos , Suplementos Dietéticos/análisis , Pectinas/farmacología , Dieta , Ácidos y Sales Biliares , Destete
8.
Front Endocrinol (Lausanne) ; 14: 1206368, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38107521

RESUMEN

Background: The clinical manifestations of multiple myeloma (MM) and bone metastatic tumor are both systemic bone pain, which is difficult to distinguish from imaging manifestations, leading to misdiagnosis and missed diagnosis. Case summary: We reported a man with a unique case whose tumors were MM with bone metastatic tumor of clear cell renal cell carcinoma (CCRCC). Computed tomography (CT) showed multifocal osteolytic bone destruction, while magnetic resonance imaging (MRI) showed multifocal bone marrow infiltration with soft tissue mass. Pathology and immunohistochemistry established the diagnosis of the coexistence of myeloma with bone metastatic tumor of CCRCC in the spine. Immunotherapy and systemic chemotherapy were adopted in the clinic, and vertebral decompression was performed after anemia was corrected. This case with MM and bone metastatic tumor of CCRCC received radiotherapy and immunotherapy and acquired satisfying outcome after 1 year of follow-up. Conclusion: It is difficult to differentiate MM and bone metastatic tumor on imaging, especially when there are bone lesions at the same time, which is an easily missed diagnosis and needs to be comprehensively evaluated in combination with functional procedures, clinical laboratory tests, and histopathology.


Asunto(s)
Neoplasias Óseas , Carcinoma de Células Renales , Neoplasias Renales , Mieloma Múltiple , Masculino , Humanos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnóstico por imagen , Mieloma Múltiple/terapia , Carcinoma de Células Renales/complicaciones , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/terapia , Neoplasias Óseas/complicaciones , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/terapia , Médula Ósea/patología , Neoplasias Renales/complicaciones , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/terapia
9.
J Vis Exp ; (201)2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37982524

RESUMEN

This study aims to solve the problem of the cell temperature rise and performance decline caused by dusty particulate matter covering the surface of the cell through the allocation of airflow velocities at the inlets of the battery cooling box under the goal of low energy consumption. We take the maximum temperature of the battery pack at a specified airflow velocity and dust-free environment as the expected temperature in a dusty environment. The maximum temperature of the battery pack in a dusty environment is solved at different inlet airflow velocities, which are the boundary conditions of the analysis model constructed in the simulation software. The arrays representing the different airflow velocity combinations of inlets are generated randomly through the optimal Latin hypercube algorithm (OLHA), where the lower and upper limits of velocities corresponding to the temperatures above the desired temperature are set in the optimization software. We establish an approximate QRSM between the velocity combination and the maximum temperature using the fitting module of the optimization software. The QRSM is optimized based on the ASAM, and the optimal result is in good agreement with the analysis result obtained by the simulation software. After optimization, the flow rate of the middle inlet is changed from 5.5 m/s to 5 m/s, and the total airflow velocity is decreased by 3%. The protocol here presents an optimization method simultaneously considering energy consumption and thermal performance of the battery management system that has been established, and it can be widely used to improve the life cycle of the battery pack with minimum operating cost.


Asunto(s)
Polvo , Material Particulado , Calor , Litio , Temperatura , Iones
10.
Mol Med ; 29(1): 118, 2023 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-37667187

RESUMEN

BACKGROUND: Type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD). Exendin-4 (Ex-4), a widely used glucagon-like peptide-1 receptor agonist drug in the treatment of T2D, has been demonstrated the therapeutic effects on diabetic encephalopathy (DE). Especially, the Ex-4 ameliorates the tau hyperphosphorylation and cognitive impairment in DE. And these crucial alterations are also important bridge between T2D and AD. However, its unique mechanism is unclear. METHODS: The db/db mice, high-fat-diet (HFD) / streptozotocin (STZ)-induced diabetic (HF-diabetic) mice, and high-glucose-damaged (HGD) HT-22 hippocampal cells were enrolled to examine the effects of Ex-4 on AD-like changes in T2D. The Novel object recognition test (NORT) and Morris water maze test (MWMT) were conducted to evaluate the cognitive impairment. The Dickkopf-1 (DKK1) was employed to weaken the activation of the Wnt/ß-catenin pathway to explore the mechanism of Ex-4 in protecting the brain functions. The JASPAR was based to predict the interaction between NeuroD1 and the promoter region of Ins2. Moreover, the chromatin immunoprecipitation coupled with quantitative polymerase chain reaction (ChIP-qPCR) and luciferase reporter assays were performed. RESULTS: Ex-4 alleviated the tau hyperphosphorylation, increased the brain-derived insulin, and improved the PI3K/AKT/GSK3-ß signalling in db/db mice, HF-diabetic mice, and HGD HT-22 hippocampal neuronal cells. The NORT and MWMT indicated that Ex-4 alleviated the learning and memory deficits in HF-diabetic mice. The inhibitor Dickkopf-1 (DKK1) of the Wnt/ß-catenin pathway significantly blocked the protective effects of Ex-4. Regarding further molecular mechanisms, NeuroD1 was affected by Ex-4 in vivo and in vitro, and the knockdown or overexpression of NeuroD1 suggested its crucial role in promoting the brain insulin by Ex-4. Meanwhile, the ChIP‒qPCR and luciferase reporter assays confirmed the combination between NeuroD1 and the promoter region of the insulin-encoding gene Ins2. And this interaction could be promoted by Ex-4. CONCLUSIONS: Our study proposes that Ex-4 alleviates tau hyperphosphorylation and cognitive dysfunction by increasing Ins2-derived brain insulin through the Wnt/ß-catenin/NeuroD1 signaling in T2D. And its also show new lights on part of the progress and mechanism on treatment targets for the DE in T2D.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animales , Ratones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Exenatida/farmacología , beta Catenina , Diabetes Mellitus Experimental/tratamiento farmacológico , Glucógeno Sintasa Quinasa 3 , Fosfatidilinositol 3-Quinasas , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Insulina , Enfermedad de Alzheimer/tratamiento farmacológico
11.
Foods ; 12(17)2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37685202

RESUMEN

The intramuscular fat (IMF) content is considered an important factor for assessing meat quality, and is highly related to meat flavor. However, in donkey meat, the influences of IMF content on lipid and volatile profiles remain unclear. Thus, we conducted lipidomic and volatilomic investigations on high- and low-IMF samples from donkey longissimus dorsi muscle. When the IMF level increased, the monounsaturated fatty acid (especially oleic acid) content significantly increased but the saturated fatty acid content decreased (p < 0.05). Twenty-nine of 876 lipids showed significant differences between the two groups. Volatile profiles from differential IMF content samples were also distinct. Five differential volatile odorants were identified in the two groups: 2-acetyl-2-thiazoline, octanal, 2-pentylfuran, pentanal, and 1-(2-pyridinyl) ethanone. Additionally, strong correlations were found between differential fatty acids and lipids with differential odorants. Thus, the difference in volatile odorants may result from the change in the fatty acid composition and lipid profiles induced by different IMF contents, highlighting the urgent need to increase IMF levels in donkey meat.

12.
PLoS One ; 18(8): e0289209, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37590218

RESUMEN

Small mammal species play an important role influencing vegetation primary productivity and plant species composition, seed dispersal, soil structure, and as predator and/or prey species. Species which experience population dynamics cycles can, at high population phases, heavily impact agricultural sectors and promote rodent-borne disease transmission. To better understand the drivers behind small mammal distributions and abundances, and how these differ for individual species, it is necessary to characterise landscape variables important for the life cycles of the species in question. In this study, a suite of Earth observation derived metrics quantifying landscape characteristics and dynamics, and in-situ small mammal trapline and transect survey data, are used to generate random forest species distribution models for nine small mammal species for study sites in Narati, China and Sary Mogul, Kyrgyzstan. These species distribution models identify the important landscape proxy variables driving species abundance and distributions, in turn identifying the optimal conditions for each species. The observed relationships differed between species, with the number of landscape proxy variables identified as important for each species ranging from 3 for Microtus gregalis at Sary Mogul, to 26 for Ellobius tancrei at Narati. Results indicate that grasslands were predicted to hold higher abundances of Microtus obscurus, E. tancrei and Marmota baibacina, forest areas hold higher abundances of Myodes centralis and Sorex asper, with mixed forest-grassland boundary areas and areas close to watercourses predicted to hold higher abundances of Apodemus uralensis and Sicista tianshanica. Localised variability in vegetation and wetness conditions, as well as presence of certain habitat types, are also shown to influence these small mammal species abundances. Predictive application of the Random Forest (RF) models identified spatial hot-spots of high abundance, with model validation producing R2 values between 0.670 for M. gregalis transect data at Sary Mogul to 0.939 for E. tancrei transect data at Narati. This enhances previous work whereby optimal habitat was defined simply as presence of a given land cover type, and instead defines optimal habitat via a combination of important landscape dynamic variables, moving from a human-defined to species-defined perspective of optimal habitat. The species distribution models demonstrate differing distributions and abundances of host species across the study areas, utilising the strengths of Earth observation data to improve our understanding of landscape and ecological linkages to small mammal distributions and abundances.


Asunto(s)
Directivas Anticipadas , Mamíferos , Humanos , Animales , Agricultura , Arvicolinae , Benchmarking , Marmota , Murinae
13.
J Vis Exp ; (196)2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37358274

RESUMEN

This study aims to solve the problems of air flow chaos and poor performance in a vented box caused by the heterogeneous distribution of airflow through the design of the internal structure of the vented box with constant energy consumption. The final goal is to evenly distribute the airflow inside the vented box. Sensitivity analysis was performed for three structural parameters: the number of pipes, the number of holes in the middle pipe, and the number of each increment from the inside to the outside pipe. A total of 16 random array sets of three structural parameters with four levels were determined using the orthogonal experimental design. Commercial software was used for the construction of a 3D model for the selected experimental points, and this data was used to obtain the airflow velocities, which were then used to obtain the standard deviation of each experimental point. According to the range analysis, the combination of the three structural parameters was optimized. In other words, an efficient and economical optimization method considering the performance of the vented box was established, and it could be widely used to extend the storage time of fresh food.

14.
Cell Rep ; 42(3): 112187, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36871218

RESUMEN

Grain size is a key component of grain yield and quality in crops. Several core players of auxin signaling have been revealed to modulate grain size; however, to date, few genetically defined pathways have been reported, and whether phosphorylation could boost degradation of Aux/IAA proteins is uncertain. Here, we show that TGW3 (also called OsGSK5) interacts with and phosphorylates OsIAA10. Phosphorylation of OsIAA10 facilitates its interaction with OsTIR1 and subsequent destabilization, but this modification hinders its interaction with OsARF4. Our genetic and molecular evidence identifies an OsTIR1-OsIAA10-OsARF4 axis as key for grain size control. In addition, physiological and molecular studies suggest that TGW3 mediates the brassinosteroid response, the effect of which can be relayed through the regulatory axis. Collectively, these findings define a auxin signaling pathway to regulate grain size, in which phosphorylation of OsIAA10 enhances its proteolysis and potentiates OsIAA10-OsARF4-mediated auxin signaling.


Asunto(s)
Ácidos Indolacéticos , Oryza , Ácidos Indolacéticos/metabolismo , Fosforilación , Oryza/genética , Proteolisis , Transducción de Señal , Proteínas de Plantas/genética , Regulación de la Expresión Génica de las Plantas
15.
Int J Mol Sci ; 24(3)2023 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-36768620

RESUMEN

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important human pathogen causing severe diseases, such as hemorrhagic colitis and lethal hemolytic uremic syndrome. The signal-sensing capability of EHEC O157:H7 at specific host colonization sites via different two-component systems (TCSs) is closely related to its pathogenicity during infection. However, the types of systems involved and the regulatory mechanisms are not fully understood. Here, we investigated the function of the TCS BarA/UvrY regulator UvrY in the pathogenicity regulation of EHEC O157:H7. Our results showed that UvrY acts as a positive regulator of EHEC O157:H7 for cellular adherence and mouse colonization through the transcriptional activation of the locus for enterocyte effacement (LEE) pathogenic genes. Furthermore, this regulation is mediated by the LEE island master regulator, Ler. Our results highlight the significance of UvrY in EHEC O157:H7 pathogenicity and underline the unknown importance of BarA/UvrY in colonization establishment and intestinal adaptability during infection.


Asunto(s)
Infecciones por Escherichia coli , Escherichia coli O157 , Proteínas de Escherichia coli , Animales , Humanos , Ratones , Enterocitos , Infecciones por Escherichia coli/genética , Escherichia coli O157/genética , Proteínas de Escherichia coli/genética , Proteínas de la Membrana , Fosfotransferasas , Virulencia/genética
16.
mSphere ; 8(1): e0058122, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36511706

RESUMEN

Fecal microbiota transplantation (FMT) is an effective means of modulating gut microbiota for the treatment of many diseases, including Clostridioides difficile infections. The gut-spleen axis has been established, and this is involved in the development and function of the spleen. However, it is not understood whether gut microbiota can be used to improve spleen function, especially in spleens disrupted by a disease or an anti-cancer treatment. In the current investigation, we established that alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue anticancer drug busulfan-disrupted spleen vasculature and spleen function. A10-FMT improved the gene and/or protein expression of genes involved in vasculature development, increased the cell proliferation rate, enhanced the endothelial progenitor cell capability, and elevated the expression of the cell junction molecules to increase the vascularization of the spleen. This investigation found for the first time that the reestablishment of spleen vascularization restored spleen function by improving spleen immune cells and iron metabolism. These findings may be used as a strategy to minimize the side effects of anti-cancer drugs or to improve spleen vasculature-related diseases. IMPORTANCE Alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue busulfan disrupted spleen vasculature. A10-FMT improved the cell proliferation rate, endothelial progenitor cell capability, and cell junction molecules to increase vasculature formation in the spleen. This reestablishment restored spleen function by improving spleen immune cells and iron metabolism. These findings are useful for the treatment of spleen vasculature-related diseases.


Asunto(s)
Busulfano , Microbiota , Bazo , Hierro
17.
Gut Microbes ; 14(1): 2143216, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36369865

RESUMEN

Vibrio cholerae (V. cholerae), one of the most important bacterial pathogens in history, is a gram-negative motile bacterium that causes fatal pandemic disease in humans via oral ingestion of contaminated water or food. This process involves the coordinated actions of numerous regulatory factors. The MerR family regulators, which are widespread in prokaryotes, have been reported to be associated with pathogenicity. However, the role of the MerR family regulators in V. cholerae virulence remains unknown. Our study systematically investigated the influence of MerR family regulators on intestinal colonization of V. cholerae within the host. Among the five MerR family regulators, MlrA was found to significantly promote the colonization capacity of V. cholerae in infant mice. Furthermore, we revealed that MlrA increases bacterial intestinal colonization by directly enhancing the expression of tcpA, which encodes one of the most important virulence factors in V. cholerae, by binding to its promoter region. In addition, we revealed that during infection, mlrA is activated by anaerobic signals in the small intestine of the host through Fnr. In summary, our findings reveal a MlrA-mediated virulence regulation pathway that enables V. cholerae to sense environmental signals at the infection site to precisely activate virulence gene expression, thus providing useful insights into the pathogenic mechanisms of V. cholerae.


Asunto(s)
Cólera , Microbioma Gastrointestinal , Vibrio cholerae , Humanos , Ratones , Animales , Vibrio cholerae/metabolismo , Regulación Bacteriana de la Expresión Génica , Anaerobiosis , Proteínas Bacterianas/metabolismo , Intestino Delgado/metabolismo , Cólera/microbiología
18.
Proc Natl Acad Sci U S A ; 119(48): e2212436119, 2022 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-36409903

RESUMEN

Riboflavin is produced by most commensal bacteria in the human colon, where enterohemorrhagic Escherichia coli (EHEC) colonizes and causes diseases. Sensing environmental signals to site-specifically express the type-III secretion system (T3SS), which injects effectors into host cells leading to intestinal colonization and disease, is key to the pathogenesis of EHEC. Here, we reveal that EHEC O157:H7, a dominant EHEC serotype frequently associated with severe diseases, acquired a previously uncharacterized two-component regulatory system rbfSR, which senses microbiota-produced riboflavin to directly activate the expression of LEE genes encoding the T3SS in the colon. rbfSR is present in O157:H7 and O145:H28 but absent from other EHEC serotypes. The binding site of RbfR through which it regulates LEE gene expression was identified and is conserved in all EHEC serotypes and Citrobacter rodentium, a surrogate for EHEC in mice. Introducing rbfSR into C. rodentium enabled bacteria to sense microbiota-produced riboflavin in the mouse colon to increase the expression of LEE genes, causing increased disease severity in mice. Phylogenic analysis showed that the O55:H7 ancestor of O157:H7 obtained rbfSR which has been kept in O157:H7 since then. Thus, acquiring rbfSR represents an essential step in the evolution of the highly pathogenic O157:H7. The expression of LEE genes and cell attachment ability of other EHEC serotypes in the presence of riboflavin significantly increased when rbfSR was introduced into them, indicating that those serotypes are ready to use RbfSR to increase their pathogenicity. This may present a potential public health issue as horizontal gene transfer is frequent in enteric bacteria.


Asunto(s)
Escherichia coli Enterohemorrágica , Escherichia coli O157 , Microbiota , Animales , Humanos , Ratones , Escherichia coli Enterohemorrágica/genética , Escherichia coli O157/genética , Riboflavina , Virulencia/genética , Intestinos
19.
Materials (Basel) ; 15(19)2022 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-36234291

RESUMEN

Reducing the local stress in the vicinity of the grain boundaries is a favorable way to improve the super-elastic properties of super-elastic alloys. The crystal plasticity finite element method (CPFEM) was applied in this study to simulate the deformation behavior and local stress of a super-elastic Cu-8Al-11Mn (wt.%) alloy containing single grains with various orientations, columnar grains with different misorientation angles, and tri-crystals with distinct grain boundary morphologies. The results indicated that the stress distribution of single grains presented obvious orientation dependence during deformation. Uniformly distributed stress was observed in grains with orientations of 0° and 90° when more slip systems were activated during deformation. With the increase in the misorientation angles of columnar grains, the stresses in the vicinity of the grain boundaries increased, which was related to the difference in the shear stress of the slip systems in adjacent grains. When the difference in the shear stress of the slip systems in two adjacent grains was large, a local stress concentration formed in the vicinity of the grain boundary. Compared with the triple-junction grain boundaries, the local stresses of the straight and vertical grain boundaries were smaller, which was closely related to the number of activated slip systems on both sides of the grain boundary. The above results were obtained experimentally and could be used to design super-elastic alloys with high performance.

20.
Metabolites ; 12(10)2022 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-36295879

RESUMEN

Frozen storage is an important strategy to maintain meat quality for long-term storage and transportation. Lipid oxidation is one of the predominant causes of the deterioration of meat quality during frozen storage. Untargeted lipidomic and targeted metabolomics were employed to comprehensively evaluate the effect of frozen duration on pork lipid profiles and lipid oxidative products including free fatty acids and fatty aldehydes. A total of 688 lipids, 40 fatty acids and 14 aldehydes were successfully screened in a pork sample. We found that ether-linked glycerophospholipids, the predominant type of lipids, gradually decreased during frozen storage. Of these ether-linked glycerophospholipids, ether-linked phosphatidylethanolamine and phosphatidylcholine containing more than one unsaturated bond were greatly influenced by frozen storage, resulting in an increase in free polyunsaturated fatty acids and fatty aldehydes. Among these lipid oxidative products, decanal, cis-11,14-eicosenoic acid and cis-5,8,11,14,17-dicosapentaenoic acid can be considered as potential indicators to calculate the freezing time of unknown frozen pork samples. Moreover, over the three-month frozen storage, the first month was a rapid oxidation stage while the other two months were a slow oxidation stage.

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