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OBJECTIVES: Pseudomonas aeruginosa and Acinetobacter baumannii are ranked as top-priority organisms by WHO. Antimicrobial peptides (AMPs) are promising antimicrobial agents that are highly effective against serious bacterial infections. METHODS: In our previous study, a series of α-helical AMPs were screened using a novel multiple-descriptor strategy. The current research suggested that S24 exhibited strong antimicrobial activity against major pathogenic bacteria, and displayed minimal haemolysis, good serum stability and maintained salt resistance. RESULTS: We found that S24 exerted an antimicrobial effect by destroying outer membrane permeability and producing a strong binding effect on bacterial genomic DNA that inhibits genomic DNA migration. Furthermore, S24 exerted a strong ability to promote healing in wound infected by P. aeruginosa, A. baumannii and mixed strains in a mouse model. CONCLUSIONS: Overall, S24 showed good stability under physiological conditions and excellent antimicrobial activity, suggesting it may be a potential candidate for the development of serious bacterial infection treatment.
Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Anti-Bacterial Agents , Microbial Sensitivity Tests , Pseudomonas Infections , Pseudomonas aeruginosa , Wound Infection , Acinetobacter baumannii/drug effects , Pseudomonas aeruginosa/drug effects , Animals , Wound Infection/drug therapy , Wound Infection/microbiology , Mice , Acinetobacter Infections/drug therapy , Acinetobacter Infections/microbiology , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Anti-Bacterial Agents/pharmacology , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry , Disease Models, Animal , Cell Membrane Permeability/drug effects , Humans , DNA, Bacterial/geneticsABSTRACT
The regulation of circadian rhythms and the sleep-wake states involves in multiple neural circuits. The suprachiasmatic nucleus (SCN) is a circadian pacemaker that controls the rhythmic oscillation of mammalian behaviors. The basal forebrain (BF) is a critical brain region of sleep-wake regulation, which is the downstream of the SCN. Retrograde tracing of cholera toxin subunit B showed a direct projection from the SCN to the horizontal limbs of diagonal band (HDB), a subregion of the BF. However, the underlying function of the SCN-HDB pathway remains poorly understood. Herein, activation of this pathway significantly increased non-rapid eye movement (NREM) sleep during the dark phase by using optogenetic recordings. Moreover, activation of this pathway significantly induced NREM sleep during the dark phase for first 4 h by using chemogenetic methods. Taken together, these findings reveal that the SCN-HDB pathway participates in NREM sleep regulation and provides direct evidence of a novel SCN-related pathway involved in sleep-wake states regulation.
Subject(s)
Efferent Pathways , Optogenetics , Suprachiasmatic Nucleus , Animals , Suprachiasmatic Nucleus/physiology , Male , Mice , Efferent Pathways/physiology , Mice, Inbred C57BL , Sleep Stages/physiology , Basal Forebrain/physiology , Circadian Rhythm/physiology , ElectroencephalographyABSTRACT
Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist with sedative effects on sleep homeostasis. Oxytocin-expressing (OXT) neurons in the paraventricular nucleus (PVN) of the hypothalamus (PVNOXT) regulate sexual reproduction, drinking, sleep-wakefulness, and other instinctive behaviors. To investigate the effect of DEX on the activity and signal transmission of PVNOXT in regulating the sleep-wakefulness cycle. Here, we employed OXT-cre mice to selectively target and express the designer receptors exclusively activated by designer drugs (DREADD)-based chemogenetic tool hM3D(Gq) in PVNOXT neurons. Combining chemogenetic methods with electroencephalogram (EEG) /electromyogram (EMG) recordings, we found that cannula injection of DEX in PVN significantly increased the duration of non-rapid eye movement (NREM) sleep in mice. Furthermore, the chemogenetic activation of PVNOXT neurons using i.p. injection of clozapine N-oxide (CNO) after cannula injection of DEX to PVN led to a substantial increase in wakefulness. Electrophysiological results showed that DEX decreased the frequency of action potential (AP) and the spontaneous excitatory postsynaptic current (sEPSC) of PVNOXT neurons through α2-adrenoceptors. Therefore, these results identify that DEX promotes sleep and maintains sleep homeostasis by inhibiting PVNOXT neurons through the α2-adrenoceptor.
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Chemotherapy failure and resistance are the leading causes of mortality in patients with acute myeloid leukemia (AML). However, the role of m6A demethylase FTO and its inhibitor rhein in AML and AML drug resistance is unclear. Therefore, this study aimed to investigate the antileukemic effect of rhein on AML and explore its potential mechanisms underlying drug resistance. Bone marrow fluid was collected to assess FTO expression in AML. The Cell Counting Kit 8 reagent was used to assess cell viability. Migration assays were conducted to assess the cell migration capacity. Flow cytometry was used to determine the apoptotic effects of rhein and western blot analysis was used to detect protein expression. Online SynergyFinder software was used to calculate the drug synergy scores. The in-vivo antileukemic effect of rhein was assessed in an AML xenograft mouse model. We analyzed different types of AML bone marrow specimens to confirm that FTO is overexpressed in AML, particularly in cases of multidrug resistance. Subsequently, we conducted in-vivo and in-vitro investigations to explore the pharmacological activity and mechanism of rhein in AML and AML with multidrug resistance. The findings demonstrated that rhein effectively suppressed the proliferation and migration of AML cells in a time- and dose-dependent manner and induced apoptosis. Rhein targets FTO, inhibits the AKT/mTOR pathway, and exhibits synergistic antitumor effects when combined with azacitidine. This study elucidates the significant role of FTO and its inhibitor rhein in AML and AML with multidrug resistance, providing new insights for overcoming multidrug resistance in AML.
Subject(s)
Alpha-Ketoglutarate-Dependent Dioxygenase FTO , Anthraquinones , Apoptosis , Drug Resistance, Neoplasm , Leukemia, Myeloid, Acute , Proto-Oncogene Proteins c-akt , TOR Serine-Threonine Kinases , Xenograft Model Antitumor Assays , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/metabolism , Animals , Mice , Anthraquinones/pharmacology , Drug Resistance, Neoplasm/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , TOR Serine-Threonine Kinases/metabolism , Apoptosis/drug effects , Drug Resistance, Multiple/drug effects , Cell Proliferation/drug effects , Female , Male , Cell Movement/drug effects , Cell Line, Tumor , Mice, Nude , Middle Aged , Mice, Inbred BALB C , Signal Transduction/drug effectsABSTRACT
OBJECTIVES: The study aimed to explore the value of texture analysis of radiomics based on the short tau inversion recovery (STIR) sequence to evaluate the activity of bone marrow oedema of sacroiliac joints in early AS. METHODS: 43 patients with early AS whose data were randomly divided into the training cohort (n=116) and verification cohort (n=56) according to the ratio of 7:3. The optimal feature subsets were obtained by Mann-Whitney U-test, the minimum-Redundancy Maximum-Relevancy (mRMR), and then least absolute shrinkage and selection operator (LASSO) using these texture feature parameters, which were used to construct the final prediction model and obtained the Radscore. The ROC curve was performed to evaluate the performance of the model. The Spearman correlation test was used to analyse the correlation of various indicators. RESULTS: In the training cohort, to differentiate early AS sacroiliac joint bone marrow oedema between the active and stable groups, the AUCs of the Radscore, SPARCC and ADC were 0.81, 0.91, 0.78, respectively. In the validation cohort, the AUCs were 0.87, 0.89, 0.85. In the two cohorts, there were no significant differences in AUCs between values of the Radscore and SPARCC, ADC (p>0.05). There was a significant difference in AUC between SPARCC and ADC in the training cohort (p<0.05), with no statistical significance in the validation cohort (p>0.05). The correlations were all low between the Radscore values and the values of ESR, CRP, tI, ASDAS-ESR and ASDAS-CRP (p<0.05). CONCLUSIONS: Radiomics analysis based on STIR texture analysis has a good prediction for the evaluation of bone marrow oedema activity of sacroiliac joints in AS. It can be a new non-invasive and objective evaluation method for AS activity.
Subject(s)
Edema , Magnetic Resonance Imaging , Predictive Value of Tests , Sacroiliac Joint , Spondylitis, Ankylosing , Humans , Male , Female , Spondylitis, Ankylosing/diagnostic imaging , Sacroiliac Joint/diagnostic imaging , Adult , Edema/diagnostic imaging , Edema/etiology , Reproducibility of Results , Middle Aged , Bone Marrow Diseases/diagnostic imaging , ROC Curve , Bone Marrow/diagnostic imaging , Young Adult , Early Diagnosis , Retrospective Studies , Severity of Illness Index , RadiomicsABSTRACT
Three organic-inorganic metal iodides, namely, (NH4)(l-hp)ZnI3 (1), [Cd(l-hp)4]Cd3I8 (2), and (l-Hhp)(l-hp)PbI3 (3), have been synthesized using l-homoproline (l-hp) as the structure-directing agent. These compounds feature different noncentrosymmetric structures and optical properties. In particular, compound 3 shows a large second-harmonic-generation response of 3.4 times that of KH2PO4. Density functional theory calculations were performed to gain insight into its structure-property relationship.
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Three new homochiral metal bromides, namely, (l-Htp)2Cu2Br4 (1), (l-Htp)(l-tp)CdBr3 (2), and (l-tp)2ZnBr2 (3), were prepared using l-thioproline as the chiral template. These compounds feature dimeric, chainlike, and monomeric structures. Their second-harmonic-generation (SHG) efficiencies are 0.1, 0.3, and 2.0 times that of KH2PO4, respectively. Density functional theory calculations were performed to reveal the origin of the SHG response of compound 3.
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Ascites syndrome (AS) in broiler chickens, also known as pulmonary arterial hypertension (PAH), is a significant disease in the poultry industry. It is a nutritional metabolic disease that is closely associated with hypoxia-inducible factors and rapid growth. The rise in pulmonary artery pressure is a crucial characteristic of AS and is instrumental in its development. Hypoxia-inducible factor 1α (HIF-1α) is an active subunit of a key transcription factor in the oxygen-sensing pathway. HIF-1α plays a vital role in oxygen homeostasis and the development of pulmonary hypertension. Studying the effects of HIF-1α on pulmonary hypertension in humans or mammals, as well as ascites in broilers, can help us understand the pathogenesis of AS. Therefore, this review aims to (1) summarize the mechanism of HIF-1α in the development of pulmonary hypertension, (2) provide theoretical significance in explaining the mechanism of HIF-1α in the development of pulmonary arterial hypertension (ascites syndrome) in broilers, and (3) establish the correlation between HIF-1α and pulmonary arterial hypertension (ascites syndrome) in broilers. HIGHLIGHTSExplains the hypoxic mechanism of HIF-1α.Linking HIF-1α to pulmonary hypertension in broilers.Explains the role of microRNAs in pulmonary arterial hypertension in broilers.
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BACKGROUND: Acute kidney injury (AKI) is a common and serious condition, particularly among elderly patients. It is associated with high morbidity and mortality rates, further compounded by the need for continuous renal replacement therapy in severe cases. To improve clinical decision-making and patient management, there is a need for accurate prediction models that can identify patients at a high risk of mortality. METHODS: Data were extracted from the Dryad Digital Repository. Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a predictive nomogram for mortality within 28 days after continuous renal replacement therapy in elderly patients with acute kidney injury. The discrimination of the model was evaluated in the validation cohort using the area under the receiver operating characteristic curve (AUC), and calibration was evaluated using a calibration curve. The clinical utility of the model was assessed using decision curve analysis (DCA). RESULTS: A total of 606 participants were enrolled and randomly divided into two groups: a training cohort (n = 424) and a validation cohort (n = 182) in a 7:3 proportion. A risk prediction model was developed to identify independent predictors of 28-day mortality in elderly patients with AKI. The predictors included age, systolic blood pressure, creatinine, albumin, phosphorus, age-adjusted Charlson Comorbidity Index (CCI), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score. These predictors were incorporated into a logistic model and presented in a user-friendly nomogram. In the validation cohort, the model demonstrated good predictive performance with an AUC of 0.799. The calibration curve showed that the model was well calibrated. Additionally, DCA revealed significant net benefits of the nomogram for clinical application. CONCLUSION: The development of a nomogram for predicting 28-day mortality in elderly patients with AKI receiving continuous renal replacement therapy has the potential to improve prognostic accuracy and assist in clinical decision-making.
Subject(s)
Acute Kidney Injury , Continuous Renal Replacement Therapy , Nomograms , Humans , Female , Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , Male , Aged , Retrospective Studies , Aged, 80 and over , Cohort Studies , Risk Factors , Risk Assessment/methodsABSTRACT
This study aims to observe the effects of the traditional Chinese medicine prescription Dahuang Zhechong Pills(DHZCP on renal aging and explore its potential multi-target effects. Rats were assigned into the normal, model, DHZCP, and vitamin E(VE)groups. Firstly, the rat model of D-galactose(D-gal)-induced renal aging was established. During the modeling period, the rats in the 4 groups were administrated with double distilled water, double distilled water, DHZCP suspension, and VE suspension, respectively,by gavage every day. On day 60 of intervention, the indicators of renal aging and injury in rats were measured, including the function,histopathological characteristics, senescence-associated ß-galactosidase( SA-ß-gal) staining, and expression levels of Klotho and proteins associated with cell cycle arrest and senescence-associated secretory phenotype(SASP) in the renal tissue. Moreover, nontargeted metabolomic analysis of the renal tissue was performed for the 4 groups of rats to screen out the potential biomarkers and metabolic pathways. Finally, the signaling pathways of key targets were preliminarily validated. The results showed that DHZCP and VE significantly improved the renal function, histopathological features of renal tubular/interstitial tissue, and degree of SA-ß-gal staining, up-regulated the expression level of Klotho, and down-regulated the expression levels of proteins associated with cell cycle arrest and SASP in the renal tissue of the aging rats. In addition, DHZCP and VE regulated the metabolites in the renal tissue of the aging rats. There were 21 common differential metabolites. Among them, 5 differential metabolites were significantly increased in the aging rats and recovered after DHZCP or VE treatment, and they were involved in the lipid metabolism and energy metabolism pathways. The areas under the curves of the groups in comparison varied within the range of 0. 88-1. DHZCP regulated multiple signaling pathways, such as the adenosine monophosphate-activated protein kinase(AMPK), cyclic guanosine monophosphate-protein kinase G( c GMP-PKG), cyclic adenylic acid( c AMP), phosphatidylinositol-3-kinase-protein kinase B( PI3K-Akt), mammalian target of rapamycin(mTOR), and autophagy signaling pathways. In addition, it affected the multiple metabolic pathways, such as renin secretion, longevity regulation pathway, diabetic cardiomyopathy, and niacin and nicotinamide metabolism. DHZCP and VE significantly up-regulated the expression level of the key proteins in the AMPK signaling pathway in the renal tissue of the aging rats. In all, DHZCP and VE could mitigate renal aging and injury. DHZCP exerted multi-target effects via multiple signaling pathways and metabolic pathways in the kidney, in which the AMPK signaling pathway may be one of the key targets for action.
Subject(s)
Aging , Drugs, Chinese Herbal , Kidney , Metabolomics , Rats, Sprague-Dawley , Animals , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacology , Rats , Kidney/drug effects , Kidney/metabolism , Aging/drug effects , Aging/metabolism , Male , Signal Transduction/drug effectsABSTRACT
Achieving tunable emissions spanning the spectrum, from blue to near-infrared (NIR) light, within a single component is a formidable challenge with significant implication, particularly in tailoring multicolor luminescence for anti-counterfeiting purposes. In this study, we demonstrate a broad spectrum of emissions, covering blue to red and extending into NIR light in [BPy]2CdX4 : xSb3+ (BPy=Butylpyridinium; X=Cl, Br; x=0 to 0.08) through precise multisite structural fine-tuning. Notably, the multicolor emissions from [BPy]2CdBr4 : Sb3+ manifest a distinctive pattern, transitioning from blue to yellow in tandem with the host [BPy]2CdBr4 and further extending from yellow to NIR with its homologous [BPy]2CdCl4 : Sb3+, resulting in the simultaneous presence of intersecting and independent emission colors. Detailed modulation of chemical composition enables partial luminescence switching, facilitating the creation of diverse patterns with multicolor luminescence by employing [BPy]2CdX4 : xSb3+ as phosphors. This study for the first time successfully implements several groups of tunable emission colors in a single matrix via multisite fine-tuning. Such an effective strategy not only develops the specific relationships between tunable emissions and adjustable compositions, but also introduces a cost-effective and straightforward approach to achieving unique, high-level, plentiful-color and multiple-information-storage labels for advanced anti-counterfeiting applications.
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Homochiral halide perovskites have gained increasing attention because of their fascinating optoelectronic properties and prospective applications in laser technologies. However, the limited choice of chiral organic templates severely restricts their structural diversity and second-harmonic generation (SHG) effects. Here, we present an in situ chiral template approach for the synthesis of one-dimensional (1D) homochiral lead iodides. A chiral imine (L-ipp) template was generated in situ by reacting L-proline (L-pro) and acetone under ambient conditions. Notably, L-ipp can cooperate with L-pro to direct the formation of a homochiral lead iodide with dual chiral templates, which is unprecedented in crystalline metal halides. The homochiral lead iodide containing both L-ipp and L-pro shows a strong SHG response of 8.0â times that of KH2 PO4 (8.0×KDP). The SHG efficiency is one of the largest values reported to date for any homochiral lead halides under 1064â nm laser irradiation. A comparative study shows that homochiral 1D lead iodides containing either L-ipp or L-pro exhibit relatively weak SHG responses (≤1.0×KDP). This work demonstrates the advantage of using two different chiral templates over a single chiral template in enhancing the SHG responses of halide materials.
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BACKGROUND: Small extracellular vesicles (sEV) play a crucial role in immune responses to viral infection. However, the composition of sEV derived from children with viral pneumonia remains ill defined. METHODS: First, we performed mass spectrometry-based label-free proteomic analysis of urinary sEV in 7 children with viral pneumonia, 4 children with Mycoplasma pneumoniae pneumonia and 20 healthy children. Then a total of 33 proteins were selected to validate by multiple reaction monitoring analysis in an independent cohort of 20 healthy children and 29 children with pneumonia. RESULTS: In the discovery phase, a total of 1621 proteins were identified, while 260 proteins have differential expression in children with viral pneumonia compared to healthy children. Biological pathways primarily associated with neutrophil degranulation, carbohydrate metabolism and endocytosis were enriched in children with viral pneumonia. Finally, the abundance of eight proteins was verified to be significantly higher in children with viral pneumonia than in healthy children. CONCLUSIONS: This pilot study with proteomic profiles of urinary sEV provided insights to the host response to viral pathogen exposure and potential diagnostic biomarkers for children with viral pneumonia, and served as the basis for understanding the fundamental biology of infection. IMPACT: There were significant differences in the proteomic features of urinary sEV between children with viral pneumonia and those with Mycoplasma pneumoniae pneumonia. Many viral infection-related proteins were identified in urinary sEV and overrepresented in children with viral pneumonia, which facilitates our understanding of the fundamental biology of viral infection. A total of eight proteins (ANPEP, ASAH1, COL11A1, EHD4, HEXB, LGALS3BP, SERPINA1 and SERPING1) were verified as potential biomarkers for the diagnosis of viral pneumonia in children.
Subject(s)
Extracellular Vesicles , Pneumonia, Viral , Humans , Child , Pilot Projects , Proteomics , Proteins/metabolism , Extracellular Vesicles/metabolism , Biomarkers/metabolismABSTRACT
Three homochiral organic-inorganic hybrid antimony halides, namely, (L-Hhis)2Sb2Cl8 (1), L-H2his·SbBr5·H2O (2), and (L-H2his)2·Sb3I13·4H2O (3), were prepared to investigate the structure-directing roles of l-histidine (l-his). These compounds feature dimeric, chainlike, and trimeric structures with different optical bandgaps. They display second-harmonic-generation (SHG) responses of 0.1, 2.6, and 0.05 times that of KH2PO4, respectively. Theoretical calculations for compound 2 were carried out to get insights into its structure-property relationship.
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Objective To understand the relationship between psychological resilience in social support and anxiety/depression in people living with HIV/AIDS and to verify whether there is a mediating effect. Methods The questionnaire was administered to 161 people living with HIV/AIDS in a hospital. The questionnaire contained a general questionnaire, the Hospital Anxiety and Depression Scale (HADS), the Psychological Resilience Inventory (CD-RICS), and the Social Collaborative Support Scale (PSSS), and Pearson correlation analyses were used to explore the correlation between the factors and anxiety/depression, stratified linear regression analyses were used to validate the mediation model, and the bootstrap method was used to test for mediating effects. Results Anxiety was negatively correlated with psychological resilience and social support (r=-0.232, P < 0.01; r=-0.293, P < 0.01); depression was negatively correlated with psychological resilience and social support (r=-0.382, P < 0.01; r=-0.482, P < 0.01); there was a mediation effect model of social support between psychological resilience and anxiety/depression; psychological resilience played a fully mediating role in social support and anxiety/depression, with an effect contribution of 68.42%/59.34% and a 95% CI(-0.256~-0.036)/(-0.341 to~-0.106). Conclusion Psychological resilience plays a complete mediating effect between social support and anxiety/depression. It is recommended that more channels of social support be provided to patients with HIV/AIDS, thereby enhancing their psychological resilience and reducing anxiety/depression levels.
Subject(s)
Acquired Immunodeficiency Syndrome , Resilience, Psychological , Humans , Depression/epidemiology , Depression/psychology , Acquired Immunodeficiency Syndrome/psychology , Anxiety/epidemiology , Anxiety/psychology , Social Support , China/epidemiologyABSTRACT
BACKGROUND AND OBJECTIVES: Dexmedetomidine (DEX) is widely used in clinical sedation which has little effect on cardiopulmonary inhibition, however the mechanism remains to be elucidated. The basal forebrain (BF) is a key nucleus that controls sleep-wake cycle. The horizontal limbs of diagonal bundle (HDB) is one subregions of the BF. The purpose of this study was to examine whether the possible mechanism of DEX is through the α2 adrenergic receptor of BF (HDB). METHODS: In this study, we investigated the effects of DEX on the BF (HDB) by using whole cell patch clamp recordings. The threshold stimulus intensity, the inter-spike-intervals (ISIs) and the frequency of action potential firing in the BF (HDB) neurons were recorded by application of DEX (2 µM) and co-application of a α2 adrenergic receptor antagonist phentolamine (PHEN) (10 µM). RESULTS: DEX (2 µM) increased the threshold stimulus intensity, inhibited the frequency of action potential firing and enlarged the inter-spike-interval (ISI) in the BF (HDB) neurons. These effects were reversed by co-application of PHEN (10 µM). CONCLUSION: Taken together, our findings revealed DEX decreased the discharge activity of BF (HDB) neuron via α2 adrenergic receptors.
Subject(s)
Dexmedetomidine , Mice , Animals , Dexmedetomidine/pharmacology , Receptors, Adrenergic, alpha-2 , Signal Transduction , Neurons , Adrenergic alpha-2 Receptor Agonists/pharmacologyABSTRACT
Pelvic organ prolapse (POP) seriously affects elderly patients' quality of life, and new repair materials are urgently needed. To solve this problem, we synthesized methacrylated gelatin (GelMA) hydrogels and incorporated photothermally active Prussian blue nanoparticles (PBNPs) to synthesize PBNP@GelMA. Then, MSCs were encapsulated in the PBNP@GelMA and exposed to a 1.0 W/cm2 of 808 nm laser for 10 min to perform heat shock pretreatment for the implantation of mesenchymal stem cells (MSCs). Next, we tested the repair efficacy of scaffold-cell complexes both in vitro and in vivo. Our results reveal that the heat shock treatment induced by PBNP@GelMA improved the viability of MSCs, and the underlying mechanism may be related to HSP70. Furthermore, 2 weeks after implantation in the SD rat model, the collagen content increased in the MSC implantation group and PBNP@GelMA implantation group. However, the muscle regeneration at the implanting position was mostly enhanced after the implantation of the heat-shock-pretreated MSCs, which illustrates that heat shock treatment can further promote the MSC-mediated muscle regeneration. Therefore, manipulating the cell environment and providing proper heat stimulus by using PBNP@GelMA with NIR is a novel strategy to enhance the regenerative potential of MSCs and to promote pelvic tissue repair.
Subject(s)
Mesenchymal Stem Cells , Nanoparticles , Rats , Animals , Biocompatible Materials , Gelatin/pharmacology , Pelvic Floor , Prospective Studies , Quality of Life , Rats, Sprague-Dawley , Hydrogels/pharmacology , Tissue EngineeringABSTRACT
BACKGROUND: The growth and development of muscle stem cells (MuSCs) are significant events known to affect muscle plasticity, disease, meat production, and meat quality, which involves the types and functions of mRNA and non-coding RNA. Here, MuSCs were cultured from Guangxi fetal cattle. RNA sequencing was used to analyze the RNA expression of mRNA and non-coding RNAs during the cell proliferation and differentiation phases. RESULTS: Two thousand one hundred forty-eight mRNAs and 888 non-coding RNAs were differentially expressed between cell proliferation and differentiation phases, including 113 miRNAs, 662 lncRNAs, and 113 circRNAs. RT-qPCR verified the differential expression levels of mRNAs and non-coding RNAs, and the differentially expressed circUBE2Q2 was subsequently characterized. Expression profile analysis revealed that circUBE2Q2 was abundant in muscle tissues and intramuscular fat. The expression of cricUBE2Q2 was also significantly upregulated during MuSCs myogenic differentiation and SVFs adipogenic differentiation and decreased with age in cattle muscle tissue. Finally, the molecular mechanism of circUBE2Q2 regulating MuSCs function that affects skeletal muscle development was investigated. The results showed that circUBE2Q2 could serve as a sponge for miR-133a, significantly promoting differentiation and apoptosis of cultured MuSCs, and inhibiting proliferation of MuSCs. CONCLUSIONS: CircUBE2Q2 is associated with muscle growth and development and induces MuSCs myogenic differentiation through sponging miR-133a. This study will provide new clues for the mechanisms by which mRNAs and non-coding RNAs regulate skeletal muscle growth and development, affecting muscle quality and diseases.
Subject(s)
MicroRNAs , Muscle Development , Animals , Cattle , Cell Differentiation/genetics , China , MicroRNAs/genetics , MicroRNAs/metabolism , Muscle Development/genetics , Muscle, Skeletal/metabolism , Muscles/metabolism , Myoblasts/metabolism , RNA, Messenger/geneticsABSTRACT
Although natural sunlight-mediated photocatalysis is a clean, efficient, and green approach to access organic products, its application in the synthesis of covalent organic frameworks (COFs), however, is still unprecedented. Herein, we first report the sunlight photocatalytic synthesis of COF under ambient conditions. Furthermore, this "window ledge" reaction generated benzoxazole-linked COF is stable and can be applied as a reusable photocatalyst to highly promote visible-light-driven aerobic oxidation of sulfides to sulfoxides. These results not only enrich the COF synthetic methodology but also open a new route to access COFs in a green and sustainable way.
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The prominent pathological feature of fatty liver disease lesions is excessive fat accumulation in lipid droplets in hepatocytes. Thus, developing fluorescent lipid droplet-specific probes with high permeability and a high imaging contrast provides a robust tool for diagnosing fatty liver diseases. Herein, we rationally developed a novel donor-acceptor lipophilic fluorescent probe ANI with high photostability for wash-free visualization of lipid droplets and fatty liver disease characteristics. ANI showed a typical twisted intramolecular charge transfer effect with very faint fluorescence in high-polar solvents, but dramatically boosted emissions in low-polar environments. The solvatochromic probe can selectively light up lipid droplets with a high contrast in a wash-free manner. Further use of ANI to reveal the excessive accumulation of lipid droplets with a significantly large size in the liver tissues from the fatty liver disease model mice was successfully demonstrated. The remarkable imaging performances rendered ANI an alternative tool for accurately evaluating fatty liver disease in intraoperative diagnosis.