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1.
Breast Cancer Res ; 26(1): 105, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937788

ABSTRACT

Circular RNAs (circRNAs) are a new group of endogenous RNAs recently found to be involved in the development of various diseases, including their confirmed involvement in the progression of several types of cancers. Unluckily, the abnormal expression and functions of circRNAs in breast cancer shall be further investigated. This work aims to elucidate the action and molecular mechanism of circHSDL2 in the malignant progression of breast cancer. Differential expression profiles of circRNAs in breast cancer tissues relative to normal breast tissues and in the exosomes of breast cancer patients compared to healthy women were analyzed from databases to identify potentially functional circRNAs. CircHSDL2 was selected for further investigation. Cell proliferation, migration and invasion assays were done to assess the effect of circHSDL2 overexpression on breast cancer cells. Bioinformatics test and dual-luciferase reporter experiments were done to explore the interaction between circHSDL2 and miRNA. Downstream target genes were further investigated through proteomics analysis and Western blotting. The influence of circHSDL2 on breast cancer in vivo was evaluated through xenograft experiments in nude mice. Functional analysis demonstrated circHSDL2 overexpression promoted the division, movement, and invasion of breast cancer cells both in vivo and in vitro. Mechanistically, circHSDL2 acted as a sponge for miR-7978 to affect ZNF704 expression and thereby regulate the Hippo pathway in breast cancer cells. In conclusion, circHSDL2 regulates the Hippo pathway through the miR-7978/ZNF704 axis to facilitate the malignancy of breast cancer. This may be a potential biomarker and treatment target.


Subject(s)
Breast Neoplasms , Cell Proliferation , Disease Progression , Gene Expression Regulation, Neoplastic , Hippo Signaling Pathway , MicroRNAs , Protein Serine-Threonine Kinases , RNA, Circular , Signal Transduction , Humans , Female , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , RNA, Circular/genetics , MicroRNAs/genetics , Animals , Mice , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Signal Transduction/genetics , Cell Proliferation/genetics , Cell Line, Tumor , Cell Movement/genetics , Mice, Nude
2.
Front Immunol ; 15: 1374390, 2024.
Article in English | MEDLINE | ID: mdl-38868768

ABSTRACT

Immunotherapy for hematological malignancies is a rapidly advancing field that has gained momentum in recent years, primarily encompassing chimeric antigen receptor T-cell (CAR-T) therapies, immune checkpoint inhibitors, and other modalities. However, its clinical efficacy remains limited, and drug resistance poses a significant challenge. Therefore, novel immunotherapeutic targets and agents need to be identified. Recently, N6-methyladenosine (m6A), the most prevalent RNA epitope modification, has emerged as a pivotal factor in various malignancies. Reportedly, m6A mutations influence the immunological microenvironment of hematological malignancies, leading to immune evasion and compromising the anti-tumor immune response in hematological malignancies. In this review, we comprehensively summarize the roles of the currently identified m6A modifications in various hematological malignancies, with a particular focus on their impact on the immune microenvironment. Additionally, we provide an overview of the research progress made in developing m6A-targeted drugs for hematological tumor therapy, to offer novel clinical insights.


Subject(s)
Adenosine , Hematologic Neoplasms , Tumor Microenvironment , Humans , Tumor Microenvironment/immunology , Hematologic Neoplasms/immunology , Hematologic Neoplasms/therapy , Adenosine/analogs & derivatives , Adenosine/immunology , Adenosine/metabolism , Animals , Immunotherapy/methods
3.
World J Clin Cases ; 12(16): 2881-2886, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38899312

ABSTRACT

BACKGROUND: Granulomatosis with polyangiitis (GPA) is one of the most prevalent forms of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis. The diagnosis of GPA depends on clinical presentation, serological evidence of a positive ANCA, and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation. Cytoplasmic ANCA (c-ANCA) is positive in 65%-75% of GPA patients, accompanied by proteinase 3 (PR3), the main target antigen of c-ANCA, another 5% of GPA patients had negative ANCA. CASE SUMMARY: The patient, a 52-year-old male, presented with unexplained nasal congestion, tinnitus, and hearing loss. After a duration of 4 months experiencing these symptoms, the patient subsequently developed fever and headache. The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis, and the ANCA results were negative. The anti-infective therapy proved to be ineffective, but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day. However, after continuous use of methylprednisolone tablets for 3 months, the patient experienced a recurrence of fever accompanied by right-sided migraine, positive c-ANCA and PR3, and increased total protein in cerebrospinal fluid. The patient was diagnosed with GPA. After receiving a treatment regimen of intravenous methylprednisolone 40 mg/d and cyclophosphamide 0.8 g monthly, the patient experienced alleviation of fever and headache. Additionally, the ANCA levels became negative and there has been no recurrence. CONCLUSION: For GPA patients with negative ANCA, there is a potential for early missed diagnosis. The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.

4.
Brief Funct Genomics ; 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38912767

ABSTRACT

RNA interference (RNAi) technology is widely used in the biological prevention and control of terrestrial insects. One of the main factors with the application of RNAi in insects is the difference in RNAi efficiency, which may vary not only in different insects, but also in different genes of the same insect, and even in different double-stranded RNAs (dsRNAs) of the same gene. This work focuses on the last question and establishes a bioinformatics software that can help researchers screen for the most efficient dsRNA targeting target genes. Among insects, the red flour beetle (Tribolium castaneum) is known to be one of the most sensitive to RNAi. From iBeetle-Base, we extracted 12 027 efficient dsRNA sequences with a lethality rate of ≥20% or with experimentation-induced phenotypic changes and processed these data to correspond to specific silence efficiency. Based on the first complied novel benchmark dataset, we specifically designed a deep neural network to identify and characterize efficient dsRNA for RNAi in insects. The dna2vec word embedding model was trained to extract distributed feature representations, and three powerful modules, namely convolutional neural network, bidirectional long short-term memory network, and self-attention mechanism, were integrated to form our predictor model to characterize the extracted dsRNAs and their silencing efficiencies for T. castaneum. Our model dsRNAPredictor showed reliable performance in multiple independent tests based on different species, including both T. castaneum and Aedes aegypti. This indicates that dsRNAPredictor can facilitate prescreening for designing high-efficiency dsRNA targeting target genes of insects in advance.

5.
Angew Chem Int Ed Engl ; : e202405905, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771269

ABSTRACT

The replacement of a CC unit with an isoelectronic BN unit in aromatic systems can give rise to molecules and materials with fascinating properties. We report here the synthesis, characterization, and reactivity of a 1,4,2,3-diazadiborole species, 2, featuring an unprecedented 6π-aromatic BN-heterocyclic moiety that is isoelectronic to cyclopentadienide (Cp-). Bearing an unsymmetrical B=B entity, 2 exhibits reactivity toward oxidants, protic reagents, electrophiles, and unsaturated substrates. This reactivity facilitates the synthesis of a variety of novel mono- and bicyclic organoboron derivatives through mechanisms including ring retention, cleavage/recombination, annulation, and expansion. These findings reveal innovative synthetic routes to BN-embedded aromatic compounds via desymmetrization, affording unique building blocks for synthetic chemistry.

6.
Ren Fail ; 46(1): 2355354, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38785302

ABSTRACT

Serum magnesium levels exceeding 0.9 mmol/L are associated with increased survival rates in patients with CKD. This retrospective study aimed to identify risk factors for cardio-cerebrovascular events among patients receiving continuous ambulatory peritoneal dialysis (CAPD) and to examine their correlations with serum magnesium levels. Sociodemographic data, clinical physiological and biochemical indexes, and cardio-cerebrovascular event data were collected from 189 patients undergoing CAPD. Risk factors associated with cardio-cerebrovascular events were identified by univariate binary logistic regression analysis. Correlations between the risk factors and serum magnesium levels were determined by correlation analysis. Univariate regression analysis identified age, C-reactive protein (CRP), red cell volume distribution width standard deviation, red cell volume distribution width corpuscular volume, serum albumin, serum potassium, serum sodium, serum chlorine, serum magnesium, and serum uric acid as risk factors for cardio-cerebrovascular events. Among them, serum magnesium ≤0.8 mmol/L had the highest odds ratio (3.996). Multivariate regression analysis revealed that serum magnesium was an independent risk factor, while serum UA (<440 µmol/L) was an independent protective factor for cardio-cerebrovascular events. The incidence of cardio-cerebrovascular events differed significantly among patients with different grades of serum magnesium (χ2 = 12.023, p = 0.002), with the highest incidence observed in patients with a serum magnesium concentration <0.8 mmol/L. High serum magnesium levels were correlated with high levels of serum albumin (r = 0.399, p < 0.001), serum potassium (r = 0.423, p < 0.001), and serum uric acid (r = 0.411, p < 0.001), and low levels of CRP (r = -0.279, p < 0.001). In conclusion, low serum magnesium may predict cardio-cerebrovascular events in patients receiving CAPD.


Subject(s)
Magnesium , Peritoneal Dialysis, Continuous Ambulatory , Humans , Male , Female , Peritoneal Dialysis, Continuous Ambulatory/adverse effects , Middle Aged , Magnesium/blood , Retrospective Studies , Risk Factors , Adult , Aged , Cardiovascular Diseases/etiology , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Incidence , Cerebrovascular Disorders/etiology , Cerebrovascular Disorders/blood , Cerebrovascular Disorders/epidemiology , Logistic Models , C-Reactive Protein/analysis , Uric Acid/blood , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/blood
7.
Metallomics ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38772737

ABSTRACT

Accumulating evidence indicates that plasma metals levels may associate with Type 2 diabetes mellitus (T2DM) incident risk. Mitochondrial function such as mitochondrial DNA copy number (mtDNA-CN) might be linked metal exposure and physiological metabolism. Mediation analysis was conducted to determine the mediating roles of mtDNA-CN in the associations of plasma metals with diabetes risk. In the present study, we investigated associations between plasma metals levels, mtDNA-CN and T2DM incident in elderly population with 6-year follow-up (2 times) study. Ten plasma metals (i.e. manganese (Mg), aluminium (Al), calcium (Ca), ferrum (Fe), barium (Ba), arsenic (As), copper (Cu), selenium (Se), titanium (Ti) and cesium (Sr) were measured by using inductively coupled plasma mass spectrometry (ICP-MS). Mitochondrial DNA copy number was measured by real-time PCR. Multivariable linear regression and logistic regression models were carried out to estimate the relationship between plasma metal concentrations, mtDNA-CN and T2DM incident risk in the current work. Plasma Ba deficiency and mtDNA-CN decline associated with T2DM incident risk during aging process. Meanwhile plasma Ba found to be positively associated with mtDNA-CN. Mitochondrial function mtDNA-CN demonstrated mediating effects in association between plasma Ba deficiency and T2DM incident risk, and 49.8% of the association was mediated by mtDNA-CN. These findings extend the knowledge of T2DM incident risk factors and highlight the point that mtDNA-CN may be linked metals element and T2DM incident risk.

8.
Angew Chem Int Ed Engl ; 63(26): e202400441, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38587149

ABSTRACT

Nickel-catalyzed transannulation reactions triggered by the extrusion of small gaseous molecules have emerged as a powerful strategy for the efficient construction of heterocyclic compounds. However, their use in asymmetric synthesis remains challenging because of the difficulty in controlling stereo- and regioselectivity. Herein, we report the first nickel-catalyzed asymmetric synthesis of N-N atropisomers by the denitrogenative transannulation of benzotriazones with alkynes. A broad range of N-N atropisomers was obtained with excellent regio- and enantioselectivity under mild conditions. Moreover, density functional theory (DFT) calculations provided insights into the nickel-catalyzed reaction mechanism and enantioselectivity control.

9.
Clin Immunol ; 263: 110228, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38663494

ABSTRACT

Asthma is a heterogeneous disease characterized by chronic airway inflammation, reversible airflow limitation, and airway remodeling. Eosinophil peroxidase (EPX) is the most abundant secondary granule protein unique to activated eosinophils. In this study, we aimed to illustrate the effect of EPX on the epithelial-mesenchymal transition (EMT) in BEAS-2B cells. Our research found that both EPX and ADAM33 were negatively correlated with FEV1/FVC and FEV1%pred, and positively correlated with IL-5 levels. Asthma patients had relatively higher levels of ADAM33 and EPX compared to the healthy control group. The expression of TSLP, TGF-ß1 and ADAM33 in the EPX intervention group was significantly higher. Moreover, EPX could promote the proliferation, migration and EMT of BEAS-2B cells, and the effect of EPX on various factors was significantly improved by the PI3K inhibitor LY294002. The findings from this study could potentially offer a novel therapeutic target for addressing airway remodeling in bronchial asthma, particularly focusing on EMT.


Subject(s)
Airway Remodeling , Asthma , Bronchi , Eosinophil Peroxidase , Epithelial Cells , Epithelial-Mesenchymal Transition , Transforming Growth Factor beta1 , Humans , Asthma/metabolism , Asthma/pathology , Asthma/physiopathology , Asthma/immunology , Male , Female , Epithelial Cells/metabolism , Eosinophil Peroxidase/metabolism , Transforming Growth Factor beta1/metabolism , Middle Aged , Adult , Bronchi/pathology , Interleukin-5/metabolism , Chromones/pharmacology , Cytokines/metabolism , Cell Line , Thymic Stromal Lymphopoietin , Cell Proliferation , Cell Movement , Morpholines/pharmacology , ADAM Proteins
10.
J Org Chem ; 89(8): 5675-5682, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38569117

ABSTRACT

As important π-skeletons, benzosiloles often possess unique electronic and optical properties and have been widely used in semiconductor materials. Therefore, great attention has been drawn to the area of developing novel synthetic methods for various benzosiloles. However, the synthesis of enantioenriched silicon-stereogenic benzosiloles is still at an early stage and remains to be explored. Herein, we performed systematic density functional theory studies on the recently reported nickel-catalyzed asymmetric synthesis of silicon-stereogenic benosiloles, which was enabled by an enantioselective desymmetrization of (2-alkenyl)aryl-substituted silacyclobutanes. Our computational study shows that the reaction mechanism involves ligand exchange, oxidative addition, alkene insertion, and hydrogen-transfer coupled reductive-demetalation steps. The proposed transmetalation and ß-hydride elimination mechanism was not found, which might be due to the unfavorable ring strain of the multicyclic intermediates. The novel hydrogen-transfer coupled reductive-demetalation mechanism was shown to be reasonable for the generation of the silicon-stereogenic benzosilole. Noncovalent interactions (including C-H···π and hydrogen bonding) in the rate-determining alkene insertion transition state account for the origins of the enantioselectivity. Our computational study sheds light on the detailed reaction mechanism and also provides insights for the development of novel approaches for synthesis of high-value silicon-stereogenic compounds.

11.
Virology ; 594: 110032, 2024 06.
Article in English | MEDLINE | ID: mdl-38467094

ABSTRACT

Many viruses employ a process known as superinfection exclusion (SIE) to block subsequent entry or replication of the same or closely related viruses in the cells they occupy. SIE is also referred to as Cross-protection refers to the situation where a host plant infected by a mild strain of a virus or viroid gains immunity against a more severe strain closely related to the initial infectant. The mechanisms underlying cross-protection are not fully understood. In this study, we performed a comparative transcriptomic analysis of potato (Solanum tuberosum L.) leaves. The strains PVYN-Wi-HLJ-BDH-2 and PVYNTN-NW-INM-W-369-12 are henceforth designated as BDH and 369, respectively. In total, 806 differentially expressed genes (DEGs) were detected between the Control and JZ (preinfected with BDH and challenge with 369) treatment. Gene Ontology (GO) analysis showed that the response to external biological stimulation, signal transduction, kinase, immunity, redox pathways were significantly enriched. Among these pathways, we identified numerous differentially expressed metabolites related to virus infection. Moreover, our data also identified a small set of genes that likely play important roles in the establishment of cross-protection. Specifically, we observed significant differential expression of the A1-II gamma-like gene, elongation factor 1-alpha-like gene, and subtilisin-like protease StSBT1.7 gene, with StSBT1.7 being the most significant in our transcriptome data. These genes can stimulate the expression of defense plant genes, induce plant chemical defense, and participate in the induction of trauma and pathogenic bacteria. Our findings provided insights into the mechanisms underlying the ability of mild viruses to protect host plants against subsequent closely related virus infection in Solanum tuberosum L.


Subject(s)
Potyvirus , Solanum tuberosum , Virus Diseases , Potyvirus/genetics , Gene Expression Profiling , Transcriptome , Plant Diseases
12.
Ren Fail ; 46(1): 2324071, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38494197

ABSTRACT

INTRODUCTION: The study presented here aimed to establish a predictive model for heart failure (HF) and all-cause mortality in peritoneal dialysis (PD) patients with machine learning (ML) algorithm. METHODS: We retrospectively included 1006 patients who initiated PD from 2010 to 2016. XGBoost, random forest (RF), and AdaBoost were used to train models for assessing risk for 1-year and 5-year HF hospitalization and mortality. The performance was validated using fivefold cross-validation. The optimal ML algorithm was used to construct the models to predictive the risk of the HF and all-cause mortality. The prediction performance of ML methods and Cox regression was compared. RESULTS: Over a median follow-up of 49 months. Two hundred and ninety-eight patients developed HF required hospitalization; 199 patients died during the follow-up. The RF model (AUC = 0.853) was the best performing model for predicting HF, and the XGBoost model (AUC = 0.871) was the best model for predicting mortality. Baseline moderate or severe renal disease, systolic blood pressure (SBP), body mass index (BMI), age, Charlson Comorbidity Index (CCI) score were strongly associated with HF hospitalization, whereas age, CCI score, creatinine, age, high-density lipoprotein cholesterol (HDL-C), total cholesterol, baseline estimated glomerular filtration rate (eGFR) were the most significant predictors of mortality. For all the above endpoints, the ML models demonstrated better discrimination than Cox regression. CONCLUSIONS: We developed and validated a novel method to predict the risk factors of HF and all-cause mortality that integrates readily available clinical, laboratory, and electrocardiographic variables to predict the risk of HF among PD patients.


Subject(s)
Heart Failure , Peritoneal Dialysis , Humans , Nomograms , Retrospective Studies , Risk Assessment/methods , Hospitalization , Heart Failure/epidemiology , Heart Failure/etiology , Peritoneal Dialysis/adverse effects , Machine Learning , Cholesterol
13.
Cell Transplant ; 33: 9636897241236586, 2024.
Article in English | MEDLINE | ID: mdl-38469823

ABSTRACT

Systemic lupus erythematosus (SLE) is a multi-organ and systemic autoimmune disease characterized by an imbalance of humoral and cellular immunity. The efficacy and side effects of traditional glucocorticoid and immunosuppressant therapy remain controversial. Recent studies have revealed abnormalities in mesenchymal stem cells (MSCs) in SLE, leading to the application of bone marrow-derived MSCs (BM-MSCs) transplantation technique for SLE treatment. However, autologous transplantation using BM-MSCs from SLE patients has shown suboptimal efficacy due to their dysfunction, while allogeneic mesenchymal stem cell transplantation (MSCT) still faces challenges, such as donor degeneration, genetic instability, and immune rejection. Therefore, exploring new sources of stem cells is crucial for overcoming these limitations in clinical applications. Human amniotic epithelial stem cells (hAESCs), derived from the eighth-day blastocyst, possess strong characteristics including good differentiation potential, immune tolerance with low antigen-presenting ability, and unique immune properties. Hence, hAESCs hold great promise for the treatment of not only SLE but also other autoimmune diseases.


Subject(s)
Hematopoietic Stem Cell Transplantation , Lupus Erythematosus, Systemic , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Humans , Amnion , Lupus Erythematosus, Systemic/therapy , Mesenchymal Stem Cell Transplantation/methods
14.
Nat Commun ; 15(1): 2028, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38459051

ABSTRACT

Copine proteins are highly conserved and ubiquitously found in eukaryotes, and their indispensable roles in different species were proposed. However, their exact function remains unclear. The phytohormone brassinosteroids (BRs) play vital roles in plant growth, development and environmental responses. A key event in effective BR signaling is the formation of functional BRI1-SERK receptor complex and subsequent transphosphorylation upon ligand binding. Here, we demonstrate that BONZAI (BON) proteins, which are plasma membrane-associated copine proteins, are critical components of BR signaling in both the monocot maize and the dicot Arabidopsis. Biochemical and molecular analyses reveal that BON proteins directly interact with SERK kinases, thereby ensuring effective BRI1-SERK interaction and transphosphorylation. This study advances the knowledge on BR signaling and provides an important target for optimizing valuable agronomic traits, it also opens a way to study steroid hormone signaling and copine proteins of eukaryotes in a broader perspective.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Carrier Proteins , Arabidopsis/metabolism , Brassinosteroids/metabolism , Zea mays/genetics , Zea mays/metabolism , Protein Kinases/metabolism , Arabidopsis Proteins/metabolism , Membrane Proteins/metabolism
15.
J Colloid Interface Sci ; 661: 957-965, 2024 May.
Article in English | MEDLINE | ID: mdl-38330667

ABSTRACT

Constructing in-plane heterojunctions with high interfacial density using two-dimensional materials represents a promising yet challenging avenue for enhancing the hydrogen evolution reaction (HER) in water electrolysis. In this work, we report that three-dimensional porous MoS2-ReS2 in-plane heterojunctions, fabricated via chemical vapor deposition, exhibit robust electrocatalytic activity for the water splitting reaction. The optimized MoS2-ReS2 in-plane heterojunction achieves superior HER performance across a wide pH range, requiring an overpotential of only 200 mV to reach a current density of 10 mA cm-2 in alkaline seawater. Thus, it outperforms standalone MoS2 and ReS2. Furthermore, the catalyst exhibits remarkable stability, enduring up to 200 h in alkaline seawater. Experimental results coupled with density functional theory calculations confirm that electron redistribution at the MoS2-ReS2 heterointerface is likely driven by disparities in in-plane work functions between the two phases. This leads to charge accumulation at the interface, thereby enhancing the adsorptive activity of S atoms toward H* intermediates and facilitating the dissociation of water molecules at the interface. This discovery offers valuable insights into the electrocatalytic mechanisms at the interface and provides a roadmap for designing high-performance, earth-abundant HER electrocatalysts suitable for practical applications.

16.
Heliyon ; 10(3): e25482, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38352747

ABSTRACT

Food has become a crucial factor in attracting tourists to destinations. Providing tourists with satisfying food experiences has become a significant concern for tourist destinations. This study examines how tourists' food experiences contribute to their subjective well-being. After conducting a questionnaire survey of 360 tourists who experienced Zibo barbecue food, and analyzing the data using structural equation modeling, it was found that: tourists' food sensory experience, service experience, and environmental experience positively affect their satisfaction and subjective well-being; The effect of these experiences on tourists' satisfaction is mediated by tourist attitude; Tourist attitude and satisfaction play a chain mediating role in the effect of sensory experience, service experience, and environmental experience on tourists' subjective well-being. The research findings help to deepen the understanding of the relationship between food tourism experience and subjective well-being, enrich the theoretical research on food experience and tourists' well-being, and have insightful significance for the development and construction of other tourist destinations.

17.
Int J Mol Sci ; 25(2)2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38279212

ABSTRACT

Animal models of metabolic disorders are essential to studying pathogenic mechanisms and developing therapies for diabetes, but the induction protocols vary, and sexual dimorphism often exists. In a chronic diabetic model of diet-induced obesity (DIO) and low-dose streptozotocin (STZ)-induced hyperglycemia, blood glucose and lipid profiles were measured. The high-fat (HF) diet damaged insulin sensitivity and increased triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, and liver lipid deposition. STZ increased blood glucose and liver fibrosis with less effects on blood lipids or liver lipid deposition. The combination of DIO and STZ treatments led to significant liver lipid deposition and fibrosis. Female mice showed delayed body weight gain on HF diet and resisted STZ-induced hyperglycemia. However, once they developed DIO, which occurs around 26 weeks of HF diet, the female mice were prone to STZ-induced hyperglycemia. In hindlimb ischemia, male mice in the DIO-STZ group showed significantly worse neovascularization compared with DIO or STZ groups. The DIO-STZ females showed significantly worse recovery than the DIO-STZ males. Our observations suggest that DIO-STZ is a plausible model for studying metabolic and cardiovascular disorders in obesity and diabetes. Moreover, the findings in female animals stress the need to assess sexual dimorphism and investigate the underlying mechanisms that contribute to the worse vasculopathy manifestations in females in metabolic models.


Subject(s)
Diabetes Mellitus, Experimental , Hyperglycemia , Male , Female , Mice , Animals , Blood Glucose/metabolism , Insulin/metabolism , Diabetes Mellitus, Experimental/drug therapy , Obesity/complications , Disease Models, Animal , Lipids , Hyperglycemia/drug therapy , Diet, High-Fat/adverse effects , Stress, Physiological
18.
Anal Chem ; 96(5): 2217-2226, 2024 02 06.
Article in English | MEDLINE | ID: mdl-38262909

ABSTRACT

Circulating tumor cells (CTCs) have emerged as powerful biomarkers for diagnosis of prostate cancer. However, the effective identification and concurrently accurate imaging of CTCs for early screening of prostate cancer have been rarely explored. Herein, we reported a multifunctional gold nanoprobe-based thermophoretic assay for simultaneous specific distinguishing of prostate cancer CTCs and sensitive imaging of intracellular microRNA (miR-21), achieving the rapid and precise detection of prostate cancer. The multifunctional gold nanoprobe (GNP-DNA/Ab) was modified by two types of prostate-specific antibodies, anti-PSMA and anti-EpCAM, which could effectively recognize the targeting CTCs, and meanwhile linked double-stranded DNA for further visually imaging intracellular miR-21. Upon the specific internalization of GNP-DNA/Ab by PC-3 cells, target aberrant miR-21 could displace the signal strand to recover the fluorescence signal for sensitive detection at the single-cell level, achieving single PC-3 cell imaging benefiting from the thermophoresis-mediated signal amplification procedure. Taking advantage of the sensitive miR-21 imaging performance, GNP-DNA/Ab could be employed to discriminate the PC-3 and Jurkat cells because of the different expression levels of miR-21. Notably, PC-3 cells were efficiently recognized from white blood cells, exhibiting promising potential for the early diagnosis of prostate cancer. Furthermore, GNP-DNA/Ab possessed good biocompatibility and stability. Therefore, this work provides a great tool for aberrant miRNA-related detection and specific discrimination of CTCs, achieving the early and accurate diagnosis of prostate cancer.


Subject(s)
MicroRNAs , Neoplastic Cells, Circulating , Prostatic Neoplasms , Male , Humans , Neoplastic Cells, Circulating/pathology , Gold , Prostatic Neoplasms/pathology , DNA
19.
Plant Physiol ; 194(4): 2616-2630, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38206190

ABSTRACT

The plant cuticle is essential in plant defense against biotic and abiotic stresses. To systematically elucidate the genetic architecture of maize (Zea mays L.) cuticular wax metabolism, 2 cuticular wax-related traits, the chlorophyll extraction rate (CER) and water loss rate (WLR) of 389 maize inbred lines, were investigated and a genome-wide association study (GWAS) was performed using 1.25 million single nucleotide polymorphisms (SNPs). In total, 57 nonredundant quantitative trait loci (QTL) explaining 5.57% to 15.07% of the phenotypic variation for each QTL were identified. These QTLs contained 183 genes, among which 21 strong candidates were identified based on functional annotations and previous publications. Remarkably, 3 candidate genes that express differentially during cuticle development encode ß-ketoacyl-CoA synthase (KCS). While ZmKCS19 was known to be involved in cuticle wax metabolism, ZmKCS12 and ZmKCS3 functions were not reported. The association between ZmKCS12 and WLR was confirmed by resequencing 106 inbred lines, and the variation of WLR was significant between different haplotypes of ZmKCS12. In this study, the loss-of-function mutant of ZmKCS12 exhibited wrinkled leaf morphology, altered wax crystal morphology, and decreased C32 wax monomer levels, causing an increased WLR and sensitivity to drought. These results confirm that ZmKCS12 plays a vital role in maize C32 wax monomer synthesis and is critical for drought tolerance. In sum, through GWAS of 2 cuticular wax-associated traits, this study reveals comprehensively the genetic architecture in maize cuticular wax metabolism and provides a valuable reference for the genetic improvement of stress tolerance in maize.


Subject(s)
Genome-Wide Association Study , Zea mays , Zea mays/genetics , Zea mays/metabolism , Quantitative Trait Loci/genetics , Phenotype , Water/metabolism , Plant Leaves/genetics
20.
Nano Lett ; 24(2): 566-575, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-37962055

ABSTRACT

Optical biosensors based on micro/nanofibers are highly valuable for probing and monitoring liquid environments and bioactivity. Most current optical biosensors, however, are still based on glass, semiconductors, or metallic materials, which might not be fully suitable for biologically relevant environments. Here, we introduce biocompatible and flexible microfibers from lotus silk as microenvironmental monitors that exhibit waveguiding of intrinsic fluorescence as well as of coupled light. These features make single-filament monitors excellent building blocks for a variety of sensing functions, including pH probing and detection of bacterial activity. These results pave the way for the development of new and entirely eco-friendly, potentially multiplexed biosensing platforms.


Subject(s)
Biosensing Techniques , Nanofibers , Biosensing Techniques/methods , Silk , Semiconductors , Bacteria
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