ABSTRACT
BACKGROUND: Neuropathic pain (NP) is the primary symptom of various neurological conditions. Patients with NP often experience mood disorders, particularly depression and anxiety, that can severely affect their normal lives. Microglial cells are associated with NP. Excessive inflammatory responses, especially the secretion of large amounts of pro-inflammatory cytokines, ultimately lead to neuroinflammation. Microglial pyroptosis is a newly discovered form of inflammatory cell death associated with immune responses and inflammation-related diseases of the central nervous system. AIM: To investigate the effects of botulinum toxin type A (BTX-A) on microglial pyroptosis in terms of NP and associated mechanisms. METHODS: Two models, an in vitro lipopolysaccharide (LPS)-stimulated microglial cell model and a selective nerve injury model using BTX-A and SPP1 knockdown treatments, were used. Key proteins in the pyroptosis signaling pathway, NLRP3-GSDMD, were assessed using western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence. Inflammatory factors [interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α] were assessed using enzyme-linked immunosorbent assay. We also evaluated microglial cell proliferation and apoptosis. Furthermore, we measured pain sensation by assessing the delayed hind paw withdrawal latency using thermal stimulation. RESULTS: The expression levels of ACS and GSDMD-N and the mRNA expression of TNF-α, IL-6, and IL-1ß were enhanced in LPS-treated microglia. Furthermore, SPP1 expression was also induced in LPS-treated microglia. Notably, BTX-A inhibited SPP1 mRNA and protein expression in the LPS-treated microglia. Additionally, depletion of SPP1 or BTX-A inhibited cell viability and induced apoptosis in LPS-treated microglia, whereas co-treatment with BTX-A enhanced the effect of SPP1 short hairpin (sh)RNA in LPS-treated microglia. Finally, SPP1 depletion or BTX-A treatment reduced the levels of GSDMD-N, NLPRP3, and ASC and suppressed the production of inflammatory factors. CONCLUSION: Notably, BTX-A therapy and SPP1 shRNA enhance microglial proliferation and apoptosis and inhibit microglial death. It improves pain perception and inhibits microglial activation in rats with selective nerve pain.
ABSTRACT
The surface chemistry of CeO2 is dictated by the well-defined facets, which exert great influence on the supported metal species and the catalytic performance. Here we report Pt1/CeO2 catalysts exhibiting specific structures of Pt-O coordination on different facets by using adequate preparation methods. The simple impregnation method results in Pt-O3 coordination on the predominantly exposed {111} facets, while the photo-deposition method achieves oriented atomic deposition for Pt-O4 coordination into the "nano-pocket" structure of {100} facets at the top. Compared to the impregnated Pt1/CeO2 catalyst showing normal redox properties and low-temperature activity for CO oxidation, the photo-deposited Pt1/CeO2 exhibits uncustomary strong metal-support interaction and extraordinary high-temperature stability. The preparation methods dictate the facet-dependent diversity of Pt-O coordination, resulting in the further activity-selectivity trade-off. By applying specific preparation routes, our work provides an example of disentangling the effects of support facets and coordination environments for nano-catalysts.
ABSTRACT
Insoluble dietary fiber (IDF) in soybean meal, due to the insolubility, is one of the major impediments to upcycle the soybean meal for its value-added use. This study converted IDF to soluble dietary fiber (SDF) using ball milling and enzymatic hydrolysis of the IDF. The impact of ball milling and enzymatic hydrolysis on the physicochemical and functional properties of SDF was evaluated. Cellulase, hemicellulase, xylanase, galacturonase, and arabinofuranosidase were employed for hydrolyzing IDF. The results showed that ball milling significantly reduced the particle size of IDF, facilitating enhanced enzymatic hydrolysis and resulting in SDF with lower molecular weight and varied monosaccharide composition. The synergistic effect of ball milling and enzymatic processes with combination of cellulase-xylanase-galacturonase was evident by the improved conversion rates (69.8%) and altered weight-averaged molecular weight (<5900 Da) of the resulting SDF. Rheological and microstructural analyses of the SDF gel indicated that specific enzyme combinations led to SDF gels with distinct viscoelastic properties, pore sizes, and functional capabilities, suitable for varied applications in the food and pharmaceutical sectors. This comprehensive evaluation demonstrates the potential of optimized physical bioprocessing techniques in developing functional ingredients with tailored properties for industrial use.
Subject(s)
Dietary Fiber , Food Handling , Glycine max , Particle Size , Solubility , Dietary Fiber/analysis , Glycine max/chemistry , Hydrolysis , Food Handling/methods , Molecular Weight , Rheology , Glycoside Hydrolases/metabolism , Cellulase/metabolism , Cellulase/chemistry , ViscosityABSTRACT
This study was conducted to comprehensively characterize, metabolites, lipids, and volatile flavor compounds of NingXiang (NX) pigs, Berkshire (BKS) pigs, and their crossbred (Berkshire × Ningxiang, BN) pigs using multi-omics technique. The results showed that NX had high intramuscular fat (IMF) content and meat redness. The metabolite and lipid compositions were varied greatly among three pig breeds. The NX pigs exhibited distinctive sweet, fruity, and floral aroma while BN pigs have inherited this flavor profile. 2-pentylfuran, pentanal, 2-(E)-octenal, and acetic acid were the key volatile flavor compounds (VOC) of NX and BKS pork. The VOCs were influenced by the composition and content of metabolites and lipids. The NX pigs have excellent meat quality traits, unique flavor profiles, and high degree of genetic stability regarding flavor. The study deepens our understanding of the flavor of Chinese indigenous pigs, providing theoretical basis to understand the meat flavor regulation under different feeding conditions.
Subject(s)
Lipids , Meat , Taste , Volatile Organic Compounds , Animals , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/metabolism , Volatile Organic Compounds/analysis , Swine/metabolism , Lipids/chemistry , Lipids/analysis , Meat/analysis , Flavoring Agents/chemistry , Flavoring Agents/metabolism , Odorants/analysis , Metabolomics , MultiomicsABSTRACT
The Guohe River Basin in Anhui Province was selected as the research area for this study. By collecting surface water, shallow groundwater, and middle-deep groundwater samples, various hydrochemical parameters and stable isotopes of water in different water bodies were analyzed using methods such as the Gibbs diagram, ion ratios, and MixSIAR model to reveal and quantify the transformation relationships between these water bodies. The results indicated that both surface water and groundwater in the study area were predominantly neutral to weakly alkaline. The hydrochemical types of surface water were mainly characterized by Cl·SO4·HCO3-Na and Cl·SO4-Na types, whereas the shallow groundwater exhibited HCO3-Ca·Mg and HCO3-Mg·Na types, and the middle-deep groundwater was of the Cl·HCO3-Na type. The hydrochemical characteristics of various water bodies were influenced by multiple factors such as rock weathering, evaporation concentration, and positive cation exchange. The distribution characteristics of δ18O and δ2H values in surface water and groundwater indicated that atmospheric precipitation was the main water source. The δ18O and δ2H in groundwater were significantly correlated with K+, Na+, Cl-, SO42-, and NO3-. According to the analysis using the MixSIAR model, the contribution of atmospheric precipitation to surface water was 46.5 %, whereas the contribution from shallow groundwater was 53.5 %. The sources of shallow groundwater were identified as atmospheric precipitation (57.4 %) and surface water (42.6 %), and the main source of supply for middle-deep groundwater was lateral flow from upstream groundwater.
ABSTRACT
BACKGROUND: Despite the widespread use of immune checkpoint inhibitors (ICIs) in cancer treatment, disease progression remains common in the majority of patients and subsequent therapeutic options for this population are limited. ICI rechallenge has been validated favorably in terms of efficacy and safety in many cancer types, while data in esophageal squamous cell carcinoma (ESCC) are still lacking. METHODS: Clinical and pathological characteristics of advanced ESCC patients who received ICI rechallenge were collected retrospectively. The primary outcomes of interest were the disease control rate (DCR) and progression-free survival (PFS). Treatment-related adverse events were also recorded. We categorized patients into primary resistance and secondary resistance based on a 6-month disease control duration following the initial immunotherapy and further conducted exploratory analyses. RESULTS: A retrospective cohort study spanning January 2018 and October 2023, at Peking University Cancer Hospital, scrutinized 45 advanced ESCC patients undergoing two lines of ICI-based therapies (ICI-1 and ICI-2). The initial therapeutic approach involved combining ICIs with chemotherapy, and the ICI rechallenge primarily comprised ICIs and angiogenesis inhibitors. The median PFS for ICI-1 was 6.7 months with a disease control rate of 88.9 %. Following the ICI rechallenge, the median PFS and disease control rate remained at 3.2 months and 73.3 %, respectively. It is noteworthy that patients with secondary resistance to ICI-1 exhibited a higher 6-month PFS rate (29.6 % v.s. 11.1 %) in the ICI-2 stage. Any grade of treatment-related adverse events was observed in 29 (64.4 %) and 18 (40.0 %) patients at ICI-1 and ICI-2. The incidence of treatment-related adverse events in grades 3-4 was 9.1 % at ICI-1 and 9.1 % at ICI-2. CONCLUSION: ICI rechallenge may offer a potential survival benefit and a favorable safety profile for patients with ESCC who have progressed after initial immunotherapy. Patients exhibiting acquired resistance during initial immunotherapy are more likely to achieve prolonged disease control after undergoing rechallenge therapy. Prospective studies are required to further explore the optimal combined therapy and select targeted population.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Immune Checkpoint Inhibitors , Humans , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Male , Female , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/mortality , Esophageal Squamous Cell Carcinoma/immunology , Middle Aged , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/mortality , Retrospective Studies , Aged , Adult , Drug Resistance, Neoplasm , Progression-Free SurvivalABSTRACT
Background: The combination therapy of immunotherapy and drug-eluting bead bronchial artery chemoembolization (DEB-BACE) or microwave ablation (MWA) has been attempted as an effective and safe approach for advanced non-small cell lung cancer (NSCLC). However, the outcomes of immunotherapy plus multiple interventional techniques for advanced NSCLC remain unclear. This retrospective study thus aimed to investigate the effectiveness and safety of the maintenance treatment of programmed cell death protein 1 (PD-1) blockade after MWA plus DEB-BACE for advanced NSCLC. Methods: This retrospective cohort study consists of 95 patients with advanced NSCLC who were treated with DEB-BACE between April 2017 and October 2022 and who were allocated to three groups: group A (MWA + DEB-BACE + PD-1 blockade; n=15), group B (MWA + DEB-BACE; n=25), and group C (DEB-BACE alone; n=55). The adverse events (AEs) were compared between the three groups. The outcomes were compared via Kaplan-Meier methods, including median progression-free survival (PFS) and overall survival (OS). Survival analyses were performed via the univariate and multivariate analyses to investigate the prognostic predictors. Results: The overall incidence of AEs in the groups A-C was 53.3% (8/15), 36.0% (9/25), and 32.7% (18/55), respectively, which did not represent a significant difference (P=0.42). No severe AEs (SAEs) occurred. Group A, compared with group B and group C, had a significantly longer estimated median PFS (33.0 vs. 7.0 vs. 3.0 months; P<0.001) and OS (33.0 vs. 13.0 vs. 6.0 months; P=0.002). PD-1 blockade (P=0.006), tumor number (P=0.01), and DEB-BACE/bronchial artery infusion (BAI) chemotherapy cycles (P=0.04) were identified as the predictors of PFS, while the predictors of OS were PD-1 blockade (P<0.001), number of metastases (P<0.001), tumor diameter (P<0.001), and DEB-BACE/BAI cycles (P=0.02). Conclusions: Compared with that of advanced NSCLC treated with MWA plus DEB-BACE or DEB-BACE alone, the maintenance treatment of immunotherapy after MWA plus DEB-BACE might provide a superior prognosis without increasing the risk of AEs.
ABSTRACT
The quality of pork is significantly impacted by intramuscular fat (IMF). However, the regulatory mechanism of IMF depositions remains unclear. We performed whole-transcriptome sequencing of the longissimus dorsi muscle (IMF) from the high (5.1 ± 0.08) and low (2.9 ± 0.51) IMF groups (%) to elucidate potential mechanisms. In summary, 285 differentially expressed genes (DEGs), 14 differentially expressed miRNAs (DEMIs), 83 differentially expressed lncRNAs (DELs), and 79 differentially expressed circRNAs (DECs) were identified. DEGs were widely associated with IMF deposition and liposome differentiation. Furthermore, competing endogenous RNA (ceRNA) regulatory networks were constructed through co-differential expression analyses, which included circRNA-miRNA-mRNA (containing 6 DEMIs, 6 DEGs, 47 DECs) and lncRNA-miRNA-mRNA (containing 6 DEMIs, 6 DEGs, 36 DELs) regulatory networks. The circRNAs sus-TRPM7_0005, sus-MTUS1_0004, the lncRNAs SMSTRG.4269.1, and MSTRG.7983.2 regulate the expression of six lipid metabolism-related target genes, including PLCB1, BAD, and GADD45G, through the binding sites of 2-4068, miR-7134-3p, and miR-190a. For instance, MSTRG.4269.1 regulates its targets PLCB1 and BAD via miRNA 2_4068. Meanwhile, sus-TRPM7_0005 controls its target LRP5 through ssc-miR-7134-3P. These findings indicate molecular regulatory networks that could potentially be applied for the marker-assisted selection of IMF to enhance pork quality.
Subject(s)
Gene Regulatory Networks , MicroRNAs , RNA, Long Noncoding , Transcriptome , Animals , Swine/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Transcriptome/genetics , Muscle, Skeletal/metabolism , Gene Expression Profiling/methods , RNA, Circular/genetics , Lipid Metabolism/genetics , Adipose Tissue/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolismSubject(s)
Antibodies, Monoclonal, Humanized , Axial Spondyloarthritis , Epilepsy , Female , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Anticonvulsants/adverse effects , Anticonvulsants/therapeutic use , Axial Spondyloarthritis/diagnosis , Axial Spondyloarthritis/drug therapy , Epilepsy/drug therapy , Epilepsy/diagnosis , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/diagnosis , Treatment OutcomeABSTRACT
Objective: This study aimed to assess the efficacy and safety of traditional Chinese medicine decoction as an adjunctive treatment for diabetic nephropathy in systematic evaluations. Methods: A comprehensive search was conducted in PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases, covering the period from January 2013 to July 2023. The search was restricted to randomized controlled trials (RCTs) conducted within the past decade that investigated the use of TCM decoction as an adjunctive treatment for diabetic nephropathy. The control group received western medicine treatment, while the intervention group received TCM decoction in addition to the conventional treatment. Endnote and Excel were employed for literature management and data organization, and Revman 5.3 and Stata 16 software were used for the analyses. Results: 66 RCTs involving 6,951 participants were included in this study. The clinical efficacy of TCM decoction as an adjunctive treatment for diabetic nephropathy was found to be significantly higher than that of the control group (OR = 3.12, 95% CI [2.70, 3.60], I2 = 0%, p < 0.00001). The incidence of adverse events did not differ significantly between the intervention group and the control group (OR = 0.94, 95% CI [0.60, 1.48], I2 = 0%, p = 0.94). According to the secondary outcomes of renal function and blood glucose indicators, the intervention group showed better therapeutic efficacy compared to the control group. The most frequently used TCM categories were tonifying medicine, blood-activating medicine, astringent medicine, diuretic medicine, heat-clearing medicine, and laxative medicine. Among them, the top five frequently used Chinese medicine were Astragalus mongholicus Bunge [Fabaceae; Astragali mongholici radix](58 times), Salvia miltiorrhiza Bunge [Lamiaceae; Radix et rhizoma salviae miltiorrhizae] (42 times), Dioscorea oppositifolia L. [Dioscoreaceae; Dioscoreae rhizoma] (38 times), Poria cocos (Schw.) Wolf [Polyporaceae; Poria] (38 times), and Cornus officinalis Siebold & Zucc. [Cornaceae; Corni fructus] (35 times). Conclusion: The combined use of TCM decoction with western medicine in the treatment of diabetic nephropathy can enhance clinical effectiveness and 2 This is a provisional file, not the final typeset article achieve superior therapeutic effects in comparison to western medicine alone, without significant risks. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier [CRD42022529144].
ABSTRACT
Glass microfluidic chips are suitable for coupling with mass spectrometry (MS) due to their flexible design, optical transparency and resistance to organic reagents. However, due to the high hardness and brittleness of glass, there is a lack of simple and feasible technology to manufacture a monolithic nanospray ionization (nESI) emitter on a glass microchip, which hinders its coupling with mass spectrometry. Here, a continuous fluid-assisted etching strategy is proposed to fabricate monolithic three-dimensional (3D) nESI emitters integrated into glass microchips. A continuous fluid of methanol is adopted to protect the inner wall of the channels and the bonding interface of the glass microfluidic chip from being wet-etched, forming sharp 3D nESI emitters. The fabricated 3D nESI emitter can form a stable electrospray plume, resulting in consistent nESI detection of acetylcholine with an RSD of 4.5% within 10 min. The fabricated 3D emitter is integrated on a glass microfluidic chip designed with a T-junction droplet generator, which can realize efficient analysis of acetylcholine in picoliter-volume droplets by nESI-MS. Stability testing of over 20 000 droplets detected by the established system resulted in an RSD of 9.1% over approximately 180 min. The detection of ten neurochemicals in rat cerebrospinal fluid droplets is achieved. The established glass droplet microfluidic chip-MS system exhibits potential for broad applications such as in vivo neurochemical monitoring and single-cell analysis in the future.
ABSTRACT
Objective: This study was to evaluate the performance of noninvasive prenatal testing (NIPT) in detecting fetal chromosome disorders in pregnant women. Methods: From October 1st, 2017, to December 31th, 2022, a total of 15,304 plasma cell free DNA-NIPT samples were collected for fetal chromosome disorders screening. The results of NIPT were validated by confirmatory invasive testing or clinical outcome follow-up. Further, NIPT performance between low-risk and high-risk groups, as well as singleton pregnancy and twin pregnancy groups was compared. Besides, analysis of 111 false-positive cases was performed. Results: Totally, NIPT was performed on 15,086 eligible venous blood samples, of which 179 (1.19%) showed positive NIPT results and 68 were further validated to be true positive samples via confirmatory invasive testing or follow-up of clinical outcomes. For common chromosome aneuploidies, sex chromosome abnormalities (SCA) and other chromosomal aneuploidies, the detection sensitivities of NIPT were all 100%, the specificities were 99.87%, 99.70%, and 99.68% and the positive predictive values (PPVs) were 65.45%, 31.82%, and 10.91%, respectively. No statistically significant variance in detection performance was observed among 2987 high-risk and 12,099 low-risk subjects, as well as singleton and twin pregnancy subjects. The concentration of cell-free fetal DNA of 111 false-positive cases ranged from 5.5% to 33.7%, which was higher than the minimum requirement of NIPT. Conclusion: With stringent protocol, NIPT shows high sensitivity and specificity for detecting fetal chromosome disorders in a large-scale clinical service, helping improving overall pregnancy management.
ABSTRACT
Background: Due to the limited role of chronic pain medication in military personnel and the distress caused to the military population, mindfulness-based therapy has been considered for the follow-up treatment of military personnel with chronic pain. The purpose of this review is to explore the effect and the implementation of mindfulness-based therapy for the military population with chronic pain. Methods: The keywords for the search included "mindfulness" AND ("pain" OR "chronic pain") AND ("military" OR "veteran"). The PubMed, Embase, and Cochrane Library databases were searched. The Cochrane Collaboration tool was used to independently assess the risk of bias of the included randomized controlled trials, and the Newcastle-Ottawa Scale was used to independently assess the risk of bias of the included case-control studies. Results: A total of 175 papers were identified; 65 duplicates were excluded, and 59 papers that did not meet the inclusion criteria were excluded after reading the titles and abstracts. The remaining 51 papers were read in full, 42 of which did not meet the inclusion criteria. Nine papers met the inclusion criteria and were included in the study. The nine studies included 507 veterans and 56 active-duty female military personnel. All pain interventions were mindfulness-based therapy, and all of them were integrated into or adapted from standard mindfulness courses. The results all showed that after mindfulness-based therapy, the relevant indicators improved. Conclusions: Mindfulness-based therapy is an effective treatment method for the military population with chronic pain. The review indicates that future research should focus on the best setting for mindfulness-based therapy, including the course content and time.
ABSTRACT
We theoretically study the crossed Andreev reflection (CAR) of the normal metal-superconductor-normal metal (NSN) heterojunction based on Kekulé-Y patterned graphene with two doping types, i.e.nSnandnSpconfigurations. It is found that the enhanced CAR is more likely to occur in thenSpjunction rather than thenSnjunction. To be concrete, the almost perfect CAR occurs in a large range of incident angle in the single Dirac cone phase when the incident energy is inside the gap of the nonlinear band. Furthermore, the roles of the length of superconductor and pseudospin-valley coupling on conductance are also evaluated.
ABSTRACT
6-mercaptopurine (6-MP) as the effective anti-cancer drug was used for the treatment of Crohn's disease and acute lymphoblastic leukaemia, but the response to maintenance therapy was variable with individual differences. In order to control the dosage and decrease the side effects of 6-MP, a sensitive and stable assay was urgently needed for 6-MP monitoring. Herein, RuZn NPs with electrochemical oxidation property and oxidase-like activity was proposed for dual-mode 6-MP monitoring. Burr-like RuZn NPs were prepared and explored to not only exhibit an electrochemical oxidation signal at 0.78 V, but also displayed excellent oxidase-like performances. RuZn NPs were utilized for the dual-mode monitoring of 6-MP, attributing to the formation of Ru-SH covalent bonding. The colorimetric method showed good linearity from 10 µM to 5 mM with the limit of detection (LOD) of 300 nM, while the electrochemical method provided a higher sensitivity with the LOD of 37 nM in range from 100 nM to 200 µM. This work provided a new way for the fabrication of dual-functional nanotags with electroactivity and oxidase-like property, and opened a dual-mode approach for the 6-MP detection applications with complementary and satisfactory results.
Subject(s)
Metal Nanoparticles , Ruthenium Compounds/chemistry , Zinc Compounds/chemistry , Electrons , Oxidation-Reduction , Metal Nanoparticles/chemistry , Metal Nanoparticles/ultrastructure , Antineoplastic Agents/chemistryABSTRACT
In contrast to the kinetically favored outward isomerization-hydrocarbonylation of alkenes, the disfavored inward isomerization-hydrocarbonylation of alkenes remains an important challenge. Herein, we have developed a novel and effective palladium-catalyzed inward isomerization-hydroaminocarbonylation of unactivated alkenes and aniline hydrochlorides for the formation of synthetically valuable α-aryl carboxylic amides in high yields and high site-selectivities. The high efficiency of the reaction is attributed to a relay catalysis strategy, in which the Markovnikov-favored [PdH]-PtBu3 catalyst is responsible for inward isomerization, while the [PdH]-Ruphos catalyst is responsible for hydroaminocarbonylation of the resulting conjugated aryl alkenes. The reaction exhibits highly functional group tolerance and provides a new method for formal carbonylation of remote C(sp3)-H bond.
ABSTRACT
E2F transcription factor 5 (E2F5) gene is a transcription factor, plays an important role in the development of a variety of cells. E2F5 is expressed in human and mouse adipocytes, but its specific function in adipogenesis is unclear. Krüppel-like factor 7 (KLF7) facilitates proliferation and inhibits differentiation in chicken preadipocytes. Our previous KLF7 chromatin immunoprecipitation-sequencing analysis revealed a KLF7-binding peak in the 3' flanking region of the E2F5, indicating a regulatory role of KLF7 in this region. In the present study, we investigated E2F5 potential role, the overexpression and knockdown analyses revealed that E2F5 inhibited the differentiation and promoted the proliferation of chicken preadipocytes. Moreover, we identified enhancer activity in the 3' flanking region (nucleotides +22661/+22900) of E2F5 and found that KLF7 overexpression increased E2F5 expression and luciferase activity in this region. Deleting the putative KLF7-binding site eliminated the promoting effect of KLF7 overexpression on E2F5 expression. Further, E2F5 reversed the KLF7-induced decrease in preadipocyte differentiation and increase in preadipocyte proliferation. Taken together, our findings demonstrate that KLF7 inhibits differentiation and promotes proliferation in preadipocytes by enhancing E2F5 transcription.
Subject(s)
Adipocytes , Adipogenesis , Cell Differentiation , Cell Proliferation , Chickens , Kruppel-Like Transcription Factors , Animals , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , Adipogenesis/physiology , Chickens/genetics , Adipocytes/metabolism , Adipocytes/physiology , E2F5 Transcription Factor/metabolism , E2F5 Transcription Factor/genetics , E2F5 Transcription Factor/physiology , Avian Proteins/metabolism , Avian Proteins/geneticsABSTRACT
BACKGROUND: The neural cells in the brains of patients with Parkinson's disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson's disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson's disease based on the central-peripheral-central theory. METHODS: The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson's disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. DISCUSSION: The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023.
Subject(s)
Parkinson Disease , Transcranial Direct Current Stimulation , Humans , Middle Aged , Aged , Parkinson Disease/diagnosis , Parkinson Disease/therapy , Parkinson Disease/complications , Transcranial Direct Current Stimulation/adverse effects , Transcranial Direct Current Stimulation/methods , Quality of Life , Exercise Therapy/methods , Double-Blind Method , Randomized Controlled Trials as TopicABSTRACT
Cu2+ as an important trace element plays an essential role in various biologic processes due to the unique redox active nature. For this reason, much effort has been made to develop effective methods for Cu2+ detection. In this study, a novel structure fluorescent chemosensor, 1-(6-(((5-(5, 5-difluoro-1, 3, 7, 9-tetramethyl-5H-4λ4, 5λ4-dipyrrolo[1, 2-c:2', 1'-f][1, 3, 2] diazaborinin-10-yl)quinolin-8-yl)oxy)methyl)pyridin-2-yl)-N, N-bis(pyridin-2-ylmethyl)methanamine (1), was synthesized and characterized by 1H and 13C nuclear magnetic resonance spectroscopy, and electrospray ionization mass spectrometry. Sensor 1 showed an obviously "on-off" fluorescence response to Cu2+ with a 1:1 binding stoichiometry by UV-vis and fluorescence spectrophotometry. The detection limit of sensor 1 to Cu2+ was determined to be 1.9 µM, and the stable pH range for Cu2+ detection was from 3 to 13. Sensor 1 can be used for recognition and detection of tyrosinase in potatoes.
Subject(s)
Copper , Fluorescent Dyes , Monophenol Monooxygenase , Solanum tuberosum , Spectrometry, Fluorescence , Copper/chemistry , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Hydrogen-Ion Concentration , Solanum tuberosum/chemistry , Monophenol Monooxygenase/metabolism , Monophenol Monooxygenase/chemistry , Limit of DetectionABSTRACT
Nanosized Pt catalysts are the catalyst-of-choice for proton exchange membrane fuel cell (PEMFC) anode, but are limited by their extreme sensitivity to CO in parts per million (ppm) level, thereby making the use of ultrapure H2 a prerequisite to ensure acceptable performance. Herein, we confront the CO poisoning issue by bringing the Ir/Rh single atom sites to synergistically working with their metallic counterparts. In presence of 1000 ppm CO, the catalyst represents not only undisturbed H2 oxidation reaction (HOR) catalytic behavior in electrochemical cell, but also unparalleled peak power density at 643 mW cm-2 in single cell, 27-fold in mass activity of the best PtRu/C catalysts available. Pre-poisoning experiments and surface-enhanced Raman scattering spectroscopy (SERS) and calculation results in combine suggest the presence of adjacent Ir/Rh single atom sites (SASs) to the nanoparticles (NPs) as the origin for this prominent catalytic behavior. The single sites not only exhibit superb CO oxidation performance by themselves, but can also scavenge the CO adsorbed on approximated NPs via supplying reactive OH* species. We open up a new route here to conquer the formidable CO poisoning issue through single atom and nanoparticle synergistic catalysis, and pave the way towards a more robust PEMFC future.