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Objectives: To explore the effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on motor function and cortical excitability in stroke patients with different motor evoked potential (MEP) status. Methods: A total of 80 stroke patients were enrolled in this randomized controlled trial and divided into two groups according to MEP status (- or +) of lesioned hemisphere. Then, each group was randomly assigned to receive either active or sham LF-rTMS. In addition to conventional rehabilitation, all participants received 20 sessions of rTMS at 1 Hz frequency through the active or the sham coil over 4 weeks. Fugl-Meyer Assessment (FMA), National Institutes of Health Stroke Scale (NIHSS), Shoulder Abduction Finger Extension (SAFE) and Barthel Index (BI), bilateral resting motor threshold (rMT), amplitude of Motor evoked potential (MEP) and Central Motor Conduction Time (CMCT), and Interhemispheric asymmetry (IHA) were blindly assessed at baseline, 4 weeks and 8 weeks after treatment, respectively. Results: At 4 weeks after intervention, FMA and NIHSS changed scores in 1 Hz MEP(+) group were significantly higher than those in the other three groups (p < 0.001). After receiving 1 Hz rTMS, stroke patients with MEP(+) showed significant changes in their bilateral cortical excitability (p < 0.05). At 8 weeks after intervention, 1 Hz MEP(+) group experienced higher changes in NIHSS, FMA, SAFE, and BI scores than other groups (p < 0.001). Furthermore, 1 Hz rTMS intervention could decrease unaffected cortical excitability and enhance affected cortical excitability of stroke patients with MEP(+) (p < 0.05). The correlation analysis revealed that FMA motor change score was associated with decreased unaffected MEP amplitude (r = -0.401, p = 0.010) and decreased affected rMT (r = -0.584, p < 0.001) from baseline, which was only observed in the MEP(+) group. Conclusion: The effects of LF-rTMS on motor recovery and cortical excitability were more effective in stroke patients with MEP than those with no MEP.
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Background: The immunogenicity of allogeneic mesenchymal stem cells (MSCs) is significantly enhanced after transplantation or differentiation, and these cells can be recognized and cleared by recipient immune cells. Graft rejection has become a major obstacle to improving the therapeutic effect of allogeneic MSCs or, after their differentiation, transplantation in the treatment of diabetes and other diseases. Solving this problem is helpful for prolonging the time that cells play a role in the recipient body and for significantly improving the clinical therapeutic effect. Methods: In this study, canine adipose-derived mesenchymal stem cells (ADSCs) were used as seed cells, and gene editing technology was used to knock out the B2M gene in these cells and cooperate with the overexpression of the PD-L1 gene. Gene-edited ADSCs (GeADSCs), whose biological characteristics and safety are not different from those of normal canine ADSCs, have been obtained. Results: The immunogenicity of GeADSCs is reduced, the immune escape ability of GeADSCs is enhanced, and GeADSCs can remain in the body for a longer time. Using the optimized induction program, the efficiency of the differentiation of GeADSCs into new islet ß-cells was increased, and the maturity of the new islet ß-cells was increased. The immunogenicity of new islet ß-cells decreased, and their immune escape ability was enhanced after the cells were transplanted into diabetic dogs (the graft site was prevascularized by the implantation of a scaffold to form a vascularized pouch). The number of infiltrating immune cells and the content of immune factors were decreased at the graft site. Conclusions: New islet ß-cell transplantation, which has low immunogenicity, can reverse diabetes in dogs, and the therapeutic effect of cell transplantation is significantly enhanced. This study provides a new method for prolonging the survival and functional time of cells in transplant recipients and significantly improving the clinical therapeutic effect.
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Miscarriage poses a significant threat to both maternal and fetal health. Its etiology remains unknown, and there are no established effective identification or prevention strategies. A low oxygen environment in early pregnancy is a physiological necessity for embryonic and placental growth. Hypoxia-inducible factors (HIFs) are a family of classic hypoxia signaling molecules, whose expression level may fluctuate abnormally because of imbalance in oxygen levels. Its unusual fluctuations initiate multiple signaling pathways at the maternal-fetal interface and modulate a range of phenotypic changes, including proliferation, differentiation, migration, invasion, angiogenesis, endometrial decidualization, and immune tolerance. Notably, aberrant regulation of these processes may lead to miscarriage. This review aims to clarify how HIF-1α mediates the aberrant regulation of biological processes, including autophagy, metabolic reprogramming, immunity, epigenetics, and angiogenesis, and how these effects impact trophoblasts and other cells at the maternal-fetal interface. These findings provide new insights into potential therapeutic and preventive strategies for miscarriage.
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Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder affecting millions globally. It encompasses both motor and non-motor symptoms, with a notable impact on patients' quality of life. Electroencephalogram (EEG) is a non-invasive tool that is increasingly utilized to investigate neural mechanisms in PD, identify early diagnostic markers, and assess therapeutic responses. Methods: The data were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database, focusing on publications related to EEG research in PD from 2004 to 2023. A comprehensive bibliometric analysis was conducted using CiteSpace and VOSviewer software. The analysis began with an evaluation of the selected publications, identifying leading countries, institutions, authors, and journals, as well as co-cited references, to summarize the current state of EEG research in PD. Keywords are employed to identify research topics that are currently of interest in this field through the analysis of high-frequency keyword co-occurrence and cluster analysis. Finally, burst keywords were identified to uncover emerging trends and research frontiers in the field, highlighting shifts in interest and identifying future research directions. Results: A total of 1,559 publications on EEG research in PD were identified. The United States, Germany, and England have made notable contributions to the field. The University of London is the leading institution in terms of publication output, with the University of California closely following. The most prolific authors are Brown P, Fuhr P, and Stam C In terms of total citations and per-article citations, Stam C has the highest number of citations, while Brown P has the highest H-index. In terms of the total number of publications, Clinical Neurophysiology is the leading journal, while Brain is the most highly cited. The most frequently cited articles pertain to software toolboxes for EEG analysis, neural oscillations, and PD pathophysiology. Through analyzing the keywords, four research hotspots were identified: research on the neural oscillations and connectivity, research on the innovations in EEG Analysis, impact of therapies on EEG, and research on cognitive and emotional assessments. Conclusion: This bibliometric analysis demonstrates a growing global interest in EEG research in PD. The investigation of neural oscillations and connectivity remains a primary focus of research. The application of machine learning, deep learning, and task analysis techniques offers promising avenues for future research in EEG and PD, suggesting the potential for advancements in this field. This study offers valuable insights into the major research trends, influential contributors, and evolving themes in this field, providing a roadmap for future exploration.
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Fermentation with Bacillus subtilis significantly enhances the physiological activity and bioavailability of soymilk, but the resulting characteristic flavor seriously affects its industrial promotion. The objective of this study was to identify key proteins associated with characteristic flavors in B. subtilis BSNK-5-fermented soymilk using tandem mass tag (TMT) proteomics. The results showed that a total of 765 differentially expressed proteins were identified. Seventy differentially expressed proteins related to characteristic flavor were screened through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. After integrating metabolomics data, fifteen key proteases of characteristic flavor components in BSNK-5-fermented soymilk were further identified, and free ammonia was added. In addition, there were five main formation mechanisms, including the decomposition of urea to produce ammonia; the degradation of glutamate by glutamate dehydrogenase to produce ammonia; the degradation of threonine and non-enzymatic changes to form the derivative 2,5-dimethylpyrazine; the degradation of valine, leucine, and isoleucine to synthesize isovalerate and 2-methylbutyrate; and the metabolism of pyruvate and lactate to synthesize acetate. These results provide a theoretical foundation for the improvement of undesirable flavor in B. subtilis BSNK-5-fermented soy foods.
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Mesenchymal Stem Cells are ideal seed cells for tissue repair and cell therapy and have promising applications in regenerative medicine and tissue engineering. Using Platelet-Rich Plasma as an adjuvant to create and improve the microenvironment for Mesenchymal Stem Cells growth can enhance the biological properties of Mesenchymal Stem Cells and improve the efficacy of cell therapy. However, the mechanism by which Platelet-Rich Plasma improves the biological performance of Mesenchymal Stem Cells is still unknown. In this study, by examining the effects of Platelet-Rich Plasma on the biological performance of Mesenchymal Stem Cells, combined with multiomics analysis (Transcriptomics, Proteomics and Metabolomics) and related tests, we analyzed the specific pathways, related mechanisms and metabolic pathways of Platelet-Rich Plasma to improve the biological performance of Mesenchymal Stem Cells. In an in vitro cell culture system, the biological performance of Mesenchymal Stem Cells was significantly improved after replacing Foetal Bovine Serum with Platelet-Rich Plasma, and the genes (ESM1, PDGFB, CLEC7A, CCR1 and ITGA6 et al.) related to cell proliferation, adhesion, growth, migration and signal transduction were significantly upregulated. Platelet-Rich Plasma can enhance the secretion function of MSC exosomes, significantly upregulate many proteins related to tissue repair, immune regulation and anti-infection, and enhance the repair effect of exosomes on skin injury. After replacing Foetal Bovine Serum with Platelet-Rich Plasma, Mesenchymal Stem Cells underwent metabolic reprogramming, the metabolism of amino acids and fatty acids and various signaling pathways were changed, the anabolic pathways of various proteins were enhanced. These results provide a theoretical and technical reference for optimizing the Mesenchymal Stem Cells culture system, improving the biological characteristics and clinical application effects of Mesenchymal Stem Cells.
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Proliferación Celular , Células Madre Mesenquimatosas , Plasma Rico en Plaquetas , Proteómica , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Plasma Rico en Plaquetas/metabolismo , Humanos , Metabolómica , Animales , Células Cultivadas , Perfilación de la Expresión Génica , Exosomas/metabolismo , MultiómicaRESUMEN
Microbial nitrogen sources are promising, and soy protein as a plant-based nitrogen source has absolute advantages in creating microbial culture medium in terms of renewability, eco-friendliness, and greater safety. Soy protein is rich in variety due to different extraction technologies and significantly different in the cell growth and metabolism of microorganisms as nitrogen source. Therefore, different soy proteins (soy meal powder, SMP; soy peptone, SP; soy protein concentrate, SPC; soy protein isolate, SPI; and soy protein hydrolysate, SPH) were used as nitrogen sources to culture Bacillus subtilis, Streptococcus lactis, and Streptomyces clavuligerus to evaluate the suitable soy nitrogen sources of the above strains. The results showed that B. subtilis had the highest bacteria density in SMP medium; S. lactis had the highest bacteria density in SPI medium; and S. clavuligerus had the highest PMV in SPI medium. Nattokinase activity was the highest in SP medium; the bacteriostatic effect of nisin was the best in SPI medium; and the clavulanic acid concentration was the highest in SMP medium. Based on analyzing the correlation between the nutritional composition and growth metabolism of the strains, the results indicated that the protein content and amino acid composition were the key factors influencing the cell growth and metabolism of the strains. These findings present a new, high-value application opportunity for soybean protein.
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BACKGROUND: Alzheimer's Disease (AD) is the most prevalent type of dementia. The early change of gut microbiota is a potential biomarker for preclinical AD patients. OBJECTIVE: The study aimed to explore changes in gut microbiota characteristics in preclinical AD patients, including those with Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI), and detect the correlation between gut microbiota characteristics and cognitive performances. METHODS: This study included 117 participants [33 MCI, 54 SCD, and 30 Healthy Controls (HC)]. We collected fresh fecal samples and blood samples from all participants and evaluated their cognitive performance. We analyzed the diversity and structure of gut microbiota in all participants through qPCR, screened characteristic microbial species through machine learning models, and explored the correlations between these species and cognitive performances and serum indicators. RESULTS: Compared to the healthy controls, the structure of gut microbiota in MCI and SCD patients was significantly different. The three characteristic microorganisms, including Bacteroides ovatus, Bifidobacterium adolescentis, and Roseburia inulinivorans, were screened based on the best classification model (HC and MCI) having intergroup differences. Bifidobacterium adolescentis is associated with better performance in multiple cognitive scores and several serum indicators. Roseburia inulinivorans showed negative correlations with the scores of the Functional Activities Questionnaire (FAQ). CONCLUSION: The gut microbiota in patients with preclinical AD has significantly changed in terms of composition and richness. Correlations have been discovered between changes in characteristic species and cognitive performances. Gut microbiota alterations have shown promise in affecting AD pathology and cognitive deficit.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiología , Enfermedad de Alzheimer/microbiología , Femenino , Masculino , Estudios Transversales , Anciano , Disfunción Cognitiva/microbiología , Heces/microbiología , Persona de Mediana EdadRESUMEN
OBJECTIVE: Face memory impairment significantly affects social interactions and daily functioning in individuals with mild cognitive impairment (MCI). While deficits in recognizing familiar faces among individuals with MCI have been reported, their ability to learn and recognize unfamiliar faces remains unclear. This study examined the behavioral performance and event-related potentials (ERPs) of unfamiliar face memorization and recognition in MCI. METHODS: Fifteen individuals with MCI and 15 healthy controls learned and recognized 90 unfamiliar neutral faces. Their performance accuracy and cortical ERPs were compared between the two groups across the learning and recognition phases. RESULTS: Individuals with MCI had lower accuracy in identifying newly learned faces than healthy controls. Moreover, individuals with MCI had reduced occipitotemporal N170 and central vertex positive potential responses during both the learning and recognition phases, suggesting impaired initial face processing and attentional resources allocation. Also, individuals with MCI had reduced central N200 and frontal P300 responses during the recognition phase, suggesting impaired later-stage face recognition and attention engagement. CONCLUSION: These findings provide neurobehavioral evidence for impaired learning and recognition of unfamiliar faces in individuals with MCI. SIGNIFICANCE: Individuals with MCI may have face memory deficits in both early-stage face processing and later-stage recognition .
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Disfunción Cognitiva , Reconocimiento Facial , Humanos , Reconocimiento en Psicología/fisiología , Potenciales Evocados/fisiología , Aprendizaje , Reconocimiento Facial/fisiología , Disfunción Cognitiva/diagnóstico , Reconocimiento Visual de Modelos/fisiologíaRESUMEN
The brain's dynamic spontaneous neural activity is significant in supporting cognition; however, how brain dynamics go awry in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remains unclear. Thus, the current study aimed to investigate the dynamic amplitude of low-frequency fluctuation (dALFF) alterations in patients at high risk for Alzheimer's disease and to explore its correlation with clinical cognitive assessment scales, to identify an early imaging sign for these special populations. A total of 152 participants, including 72 SCD patients, 44 MCI patients and 36 healthy controls (HCs), underwent a resting-state functional magnetic resonance imaging and were assessed with various neuropsychological tests. The dALFF was measured using sliding-window analysis. We employed canonical correlation analysis (CCA) to examine the bi-multivariate correlations between neuropsychological scales and altered dALFF among multiple regions in SCD and MCI patients. Compared to those in the HC group, both the MCI and SCD groups showed higher dALFF values in the right opercular inferior frontal gyrus (voxel P < .001, cluster P < .05, correction). Moreover, the CCA models revealed that behavioural tests relevant to inattention correlated with the dALFF of the right middle frontal gyrus and right opercular inferior frontal gyrus, which are involved in frontoparietal networks (R = .43, P = .024). In conclusion, the brain dynamics of neural activity in frontal areas provide insights into the shared neural basis underlying SCD and MCI.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Imagen por Resonancia Magnética , Humanos , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/diagnóstico por imagen , Masculino , Femenino , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Anciano , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Pruebas Neuropsicológicas , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagenRESUMEN
Microbial fermentation emerges as a promising strategy to elevate the quality of soybean proteins in food industry. This study conducted a comprehensive assessment of the biotransformation of four types of soybean proteins by Bacillus subtilis BSNK-5, a proteinase-rich bacterium. BSNK-5 had good adaptability to each protein. Soluble protein, peptides and free amino acids increased in fermented soybean proteins (FSPs) and dominant after 48-84 h fermentation, enhancing nutritional value. Extensive proteolysis of BSNK-5 also improved antioxidant and antihypertensive activities, reaching peak level after 48 h fermentation. Furthermore, excessive proteolysis effectively enhanced the generation of beneficial spermidine without producing toxic histamine after fermentation, and formed the flavor profile with 56 volatiles in 48 h FSPs. Further degradation of amino acids showed a positive correlation with off-flavors, particularly the enrichment of 3-methylbutanoic acid. These findings establish a theoretical foundation for regulating moderate fermentation by BSNK-5 to enabling the high-value utilization of soybean protein.
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Bacillus subtilis , Proteínas de Soja , Proteínas de Soja/metabolismo , Bacillus subtilis/metabolismo , Glycine max , Aminoácidos/metabolismo , Antioxidantes/metabolismo , FermentaciónRESUMEN
The use of polysaccharides to recover soybean whey protein (SWP) from whey wastewater is recognized as an effective approach. However, the recovery rate can vary due to differences in the structure and compound ratios of the polysaccharides involved. The interaction between SWP and polysaccharides (sodium alginate, SA; chitosan, CHI; carrageenan, CAR) at different ratio was investigated. We harnessed these complexes to fabricate emulsions aimed at delivering soybean isoflavones. The results showed that the addition of polysaccharides unfolded the structure of SWP. The intermolecular hydrogen bonds within SWP-SA were stronger than those of the other complexes. These structural changes showed consistency across different ratios. The mean particle size of the complexes increased. SWP-SA exhibited the lowest interfacial tension. The emulsion with SWP-SA at 300 W demonstrated superior stability, and the bioavailability of soybean isoflavones increased by 3-6 %. These results shed light on the promising potential of polysaccharide-based strategies for SWP recovery and the effective delivery of soybean isoflavones.
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Isoflavonas , Suero Lácteo , Proteína de Suero de Leche/química , Glycine max , Proteínas de Soja , Polisacáridos/química , Emulsiones/químicaRESUMEN
Background: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are neurodegenerative processing stages of Alzheimer's disease (AD). Cognitive decline is thought to manifest in intrinsic brain activity changes, but research results yielded conflicting and few studies have explored the roles of brain regions in cognitive decline, and sensitivity of the cognitive field to changes in the altered intrinsic brain activity. Methods: In this cross-sectional study, 158 elderly participants were recruited from the memory clinic of the First Affiliated Hospital of Nanjing Medical University from July 2019 to May 2021, and grouped into SCD (n=73), MCI (n=46), and normal controls (NC) (n=39). The amplitude of low-frequency fluctuation (ALFF) was calculated and evaluated among the groups. Then canonical correlation analysis (CCA) was conducted to investigate the associations between imaging outcomes and cognitive behaviors. Results: Neuropsychological tests in different cognitive dimensions and ALFF values of the prefrontal, parietal, and temporal gyrus, were significantly different (P<0.05) among the three groups, with no appreciable decline in daily activity. The changes in intrinsic activities were closely related to the decline in cognitive function (R=0.73, P=0.002). ALFF values in the left middle occipital gyrus, right middle frontal gyrus, left superior frontal gyrus, left angular gyrus, and superior temporal gyrus played significant roles in the analysis, while the Montreal Cognitive Assessment (MoCA) and Auditory-Verbal Learning Test scores were found to be more sensitive to changes in ALFF values. Conclusions: Spontaneous brain activity is a stable imaging biomarker of cognitive impairment. ALFF changes of the prefrontal, occipital, left angular, and temporal gyrus were sensitive to identifying cognitive decline, and the scores of the Auditory-Verbal Learning Test and MoCA could predict the abnormal intrinsic activities.
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As a zoonotic parasite, Cryptosporidium spp. could cause severe diarrhea mainly in calves and children globally. Monitoring and prevention of Cryptosporidium spp.'s prevalence is of great significance in both economy and public health aspects. In this study, specific primers and probes were designed within the conserved region of 18S rRNA gene for Cryptosporidium spp. and recombinase polymerase amplification assays based on the fluorescence monitoring (real-time RPA) as well as combined with a lateral flow strip (LFS RPA) were developed. Both of the two RPA assays allowed the exponential amplification of the target fragment within 20 min. After incubation on a metal bath at 42 °C, the LFS RPA results were displayed on the lateral flow strip within 5 min while real-time RPA allowed the real-time observation of the results in Genie III at 39 °C. The RPA assays showed high specificity for Cryptosporidium spp. without any cross-reaction with other tested pathogens causing diarrhea in cattle. With the recombinant plasmid DNA containing the 18S rRNA gene of Cryptosporidium spp. serving as a template, the limit of detection for real-time RPA and LFS RPA assays were 14.6 and 12.7 copies/reaction, respectively. Moreover, the RPA assays were validated by testing diarrheic cattle fecal samples and compared with a real-time PCR. The positive ratio of Cryptosporidium spp. was 24.04 % (44/183) and 26.23 % (48/183) in both RPA assays and real-time PCR assay, respectively, and the kappa coefficient value was 0.942. The diagnostic specificity and diagnostic sensitivity of both RPA assays were 100 % and 91.67 %, respectively. Forty-one of 48 positive samples were successfully sequenced and four Cryptosporidium species were detected, including C. parvum (n = 20), C. andersoni (n = 17), C. bovis (n = 3) and C. ryanae (n = 1). The developed RPA assays are easy to operate and faster to obtain the detection results, and they are suiting for the point-of-care detection and facilitating the prevention and control of Cryptosporidium spp. infections.
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BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been well defined as a common chronic liver metabolism disorder. Statins as a first-line therapeutic treatment had some side effects. Here, we found that Fumigaclavine C (FC) was collected from endophytic Aspergillus terreus via the root of Rhizophora stylosa (Rhizophoraceae), had potential anti-adipogenic and hepatoprotective effects both in vitro and in vivo without obvious adverse side effects. However, the mechanisms of the prevention and management of FC for hepatic steatosis are incompletely delineated. METHODS: The pharmacodynamic effects of FC were measured in high-fat diet (HFD)-induced obese mice. Liver index and blood biochemical were examined. Histopathological examination in the liver was performed by hematoxylin & eosin or oil red O. The levels of serum TG, TC, LDL-c, HDL-c, FFA, T-bili, ALT, AST, creatinine, and creatine kinase were estimated via diagnostic assay kits. The levels of hepatic lipid metabolism-related genes were detected via qRT-PCR. The expression levels of hepatic de novo lipogenesis were quantitated with Western blot analysis. RESULTS: FC-treatment markedly reduced hepatic lipid accumulation in HFD-induced obese mice. FC significantly attenuated the hepatic lipid metabolism and ameliorated liver injury without obvious adverse side effects. Moreover, FC also could dose-dependently modulate the expressions of lipid metabolism-related transcription genes. Mechanically, FC notably suppressed sterol response element binding protein-1c mediated de novo lipogenesis via interfering with the RhoA/ROCK signaling pathway by decreasing the levels of geranylgeranyl diphosphate and farnesyl diphosphate. CONCLUSIONS: These findings suggested that FC could improve hepatic steatosis through inhibiting de novo lipogenesis via modulating the RhoA/ROCK signaling pathway.
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Alcaloides de Claviceps , Alcaloides Indólicos , Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Lipogénesis , Ratones Obesos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Transducción de Señal , Alcaloides de Claviceps/farmacología , Alcaloides Indólicos/farmacologíaRESUMEN
Background: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are preclinical stages of Alzheimer's disease (AD). Individual biomarkers are essential for evaluating altered neurological outcomes at both SCD and MCI stages for early diagnosis and intervention of AD. In this study, we aimed to investigate the relationships between topological properties of the individual brain morphological network and clinical cognitive performances among healthy controls (HCs) and patients with SCD or MCI. Methods: The topological measurements of individual morphological networks were analyzed using graph theory, and inter-group differences of standard graph topology were correlated and regressed to scores of clinical cognitive functions. Results: Compared with HCs, the topology of the individual morphological networks in SCD and MCI patients was significantly altered. At the global level, altered topology was characterized by lower global efficiency, shorter characteristics path length, and normalized characteristics path length [all P<0.05, false discovery rate (FDR) corrected]. In addition, at the regional level, SCD and MCI patients exhibited abnormal degree centrality in the caudate nucleus and nodal efficiency in the caudate nucleus, right insula, lenticular nucleus, and putamen (all P<0.05, FDR corrected). Conclusions: The topological features of individual gray matter morphological networks may serve as biomarkers to improve disease prognosis and intervention in the early stages of AD, namely SCD and MCI. Moreover, these findings may further elucidate the relationships between brain morphological alterations and cognitive dysfunctions in SCD and MCI.
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Mixed-valence compounds possess both intriguing chemical and physical properties such as the intervalence charge transfer band and thus have been excellent model systems for the investigation of fundamental electron- and charge-transfer phenomena. Herein, we show that valence stratification can be a source of symmetry breaking and generating ferroelectricity in two-dimensional (2D) materials. We present ab initio computation evidence of the monolayer Cu2Cl3 structure with Cu ions being stratified into two separated layers of Cu(I) and Cu(II). Chemically, this unique monolayer not only entails lower formation energy than the bulk CuCl + CuCl2, but also enables the swapping of two valences through vertical ferroelectric switching, leading to a hitherto unreported chemical valencing phenomenon. Notably, the Jahn-Teller distortion of the Cu(II) layer results in another source of symmetry breaking and thus in-plane ferroelectricity. Apart from the valence swapping and self-contained double ferroelectricity, the monolayer's ferroelasticity is also coupled with in-plane ferroelectricity, while the monolayer's ferromagnetism is coupled with vertical polarization owing to the distinct magnetization of each Cu(I) and Cu(II) layer, thereby evoking the long-sought 2D triferroicity as well as triferroic couplings.
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Low Ag lead-free Sn-Ag-Cu (SAC) solders have attracted great interest due to their good drop resistance, high welding reliability, and low melting point. However, low Ag may lead to the degradation of the mechanical properties. Micro-alloying is an effective approach to improving the properties of SAC alloys. In this paper, the effects of minor additions of Sb, In, Ni, and Bi on microstructure, thermal and mechanical properties of Sn-1 wt.%Ag-0.5 wt.%Cu (SAC105) were systematically investigated. It is found that the microstructure can be refined with intermetallic compounds (IMCs) distributed more evenly in the Sn matrix with additions of Sb, In, and Ni, which brings a combined strengthening mechanism, i.e., solid solution strengthening and precipitation strengthening, leading to the tensile strength improved of SAC105. When Ni is substituted by Bi, the tensile strength is further enhanced with a considerable tensile ductility higher than 25%, which still meets the practical demands. At the same time, the melting point is reduced, the wettability is improved, and the creep resistance is enhanced. Among all the investigated solders, SAC105-2Sb-4.4In-0.3Bi alloy possesses the optimized properties, i.e., the lowest melting point, the best wettability, and the highest creep resistance at room temperature, implying that element alloying plays a vital role in improving the performance of SAC105 solders.
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As the most common type of stroke, ischemic stroke, also known as cerebral infarction (CI), with its high mortality and disability rate, has placed a huge burden on social economy and public health. Treatment methods for CI mainly include thrombectomy, thrombolysis, drug therapy, and so on. However, these treatments have certain timeliness and different side effects. In recent years, the gut-brain axis has become a hot topic, and its role in nervous system diseases has been confirmed by increasing evidences. The intestinal microbiota, as an important part of the gut-brain axis, has a non-negligible impact on the progression of CI through mechanisms such as inflammatory response and damage-associated molecular patterns, and changes in the composition of intestinal microbiota can also serve as the basis for predicting CI. At the same time, the diagnosis of CI requires more high-throughput techniques, and the analysis method of metabolomics just fits this demand. This paper reviewed the changes of intestinal microbiota in patients within CI and the effects of the intestinal microbiota on the course of CI, and summarized the therapeutic methods of the intervention with the intestinal microbiota. Furthermore, metabolic changes of CI patients were also discussed to reveal the molecular characteristics of CI and to elucidate the potential pathologic pathway of its interference.
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Microbioma Gastrointestinal , Accidente Cerebrovascular , Humanos , Microbioma Gastrointestinal/fisiología , Heces , Infarto Cerebral , Metaboloma , Trasplante de Microbiota FecalRESUMEN
Nattokinase (NK) derived from food is a sustainable thrombolytic agent. In this study, to protect vulnerable biological activity of NK, the targeted modified W/O/W emulsions were fabricated from complexes of soybean isolate protein (SPI) and polyglutamic acid (PGA). The results showed that the SPI-PGA complex formed a tighter internal structure through non-covalent bonds. The secondary structure, α-helix and ß-sheet content of the 1:3 (v/v) ratio complex of SPI to PGA increased by 6.14% and 8.62%, respectively. The emulsification and stability of the complexes were improved by refining structural properties as against SPI. The W/O/W emulsions coated by complexes formed the stronger network structure with higher encapsulation efficiency, better interfacial features, and better storage stability. Moreover, the highest bioavailability was achieved by W/O/W emulsions coated with 1:3 ratio complex at 80.69%. This study provided a new strategy towards tailoring ideal emulsion vehicles and expanded the NK application in food formulations.