ABSTRACT
Using budding yeast, we have studied Rad51-dependent break-induced replication (BIR), where the invading 3' end of a site-specific double-strand break (DSB) and a donor template share 108 bp of homology that can be easily altered. BIR still occurs about 10% as often when every 6th base is mismatched as with a perfectly matched donor. Here we explore the tolerance of mismatches in more detail, by examining donor templates that each carry 10 mismatches, each with different spatial arrangements. Although 2 of the 6 arrangements we tested were nearly as efficient as the evenly-spaced reference, 4 were significantly less efficient. A donor with all 10 mismatches clustered at the 3' invading end of the DSB was not impaired compared to arrangements where mismatches were clustered at the 5' end. Our data suggest that the efficiency of strand invasion is principally dictated by thermodynamic considerations, i.e., by the total number of base pairs that can be formed; but mismatch position-specific effects are also important. We also addressed an apparent difference between in vitro and in vivo strand exchange assays, where in vitro studies had suggested that at a single contiguous stretch of 8 consecutive bases was needed to be paired for stable strand pairing, while in vivo assays using 108-bp substrates found significant recombination even when every 6th base was mismatched. Now, using substrates of either 90 or 108 nt-the latter being the size of the in vivo templates-we find that in vitro D-loop results are very similar to the in vivo results. However, there are still notable differences between in vivo and in vitro assays that are especially evident with unevenly-distributed mismatches. Mismatches in the donor template are incorporated into the BIR product in a strongly polar fashion up to ~40 nucleotides from the 3' end. Mismatch incorporation depends on the 3'â 5' proofreading exonuclease activity of DNA polymerase δ, with little contribution from Msh2/Mlh1 mismatch repair proteins, or from Rad1-Rad10 flap nuclease or the Mph1 helicase. Surprisingly, the probability of a mismatch 27 nt from the 3' end being replaced by donor sequence was the same whether the preceding 26 nucleotides were mismatched every 6th base or fully homologous. These data suggest that DNA polymerase δ "chews back" the 3' end of the invading strand without any mismatch-dependent cues from the strand invasion structure. However, there appears to be an alternative way to incorporate a mismatch at the first base at the 3' end of the donor.
Subject(s)
Saccharomyces cerevisiae Proteins , DNA Polymerase III/genetics , DNA Repair/genetics , DNA Replication/genetics , Exonucleases/genetics , MutS Homolog 2 Protein/genetics , Nucleotides/metabolism , Rad51 Recombinase/genetics , Rad51 Recombinase/metabolism , Recombination, Genetic , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolismABSTRACT
PURPOSE: We studied changes in the choroid, particularly variation in blood flow, during the development of myopia. The hemodynamic mechanism in play remains unclear. We evaluated blood flow by quantitating indocyanine green (ICG) fluorescence in a guinea pig model of form-deprivation myopia. METHODS: Guinea pigs were divided into form-deprivation myopia (FDM) and normal control (NC) groups. Ocular biometric and choroidal hemodynamics parameters were quantitatively derived via ICG imaging, and included the maximal ICG fluorescence intensity (Imax), rising time (Trising), blood flow index (BFI), and mean transit time (MTT). RESULTS: Form deprivation was associated with significant interocular differences in terms of both refractive error and axial length. ICG fluorescence hemodynamic maps of fundal blood flow and vasculature density were evident. In deprived eyes, the fluorescence signals exhibited significantly longer Trising and MTT but lower Imax and BFI than fellow eyes and NC group. The interocular differences in terms of the ocular biometric and hemodynamic parameters were significantly correlated. Hemodynamic analysis of choriocapillaris lobules revealed weakened fluorescence intensity and prolonged arrival and filling times in deprived eyes. Form deprivation reduced the number of lobulated choriocapillaris structures. CONCLUSION: Form-deprivation myopia triggered changes in the hemodynamic and vascular network structures of the choroid and choriocapillaris. The ICG fluorescence imaging/analysis method provides a unique tool for further myopia research.
Subject(s)
Myopia , Refractive Errors , Animals , Guinea Pigs , Diagnostic Imaging , Choroid/diagnostic imaging , HemodynamicsABSTRACT
We examined the lipid profiles in the aqueous humor (AH) of myopic patients to identify differences and investigate the relationships among dissertating lipids. Additionally, we assessed spherical equivalents and axial lengths to explore the pathogenesis of myopia. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed to qualitatively and quantitatively analyze the lipid composition of samples from myopic patients with axial lengths <26 mm (Group A) and >28 mm (Group B). Differences in lipid profiles between the two groups were determined using univariate and multivariate analyses. Receiver operator characteristic (ROC) curves were used to identify discriminating lipids. Spearman correlation analysis explored the associations between lipid concentrations and biometric parameters. Three hundred and nine lipids across 21 lipid classes have been identified in this study. Five lipids showed significant differences between Group B and Group A (VIP >1, P < 0.05): BMP (20:3/22:3), PG (22:1/24:0), PS (14:1/22:4), TG (44:2)_FA18:2, and TG (55:3)_FA18:1. The area under the curve (AUC) for these lipids was >0.75. Notably, the concentrations of BMP (20:3/22:3), PS (14:1/22:4), and TG (55:3)_FA18:1 were correlated with spherical equivalents, while BMP (20:3/22:3) and PS (14:1/22:4) correlated with axial lengths. Our study identified five differential lipids in myopic patients, with three showing significant correlations with the degree of myopia. These findings enhance our understanding of myopia pathogenesis through lipidomic alterations, emphasizing changes in cell membrane composition and function, energy metabolism and storage, and pathways involving inflammation, peroxisome proliferator-activated receptors (PPAR), and metabolic processes related to phosphatidylserine, phosphatidylglycerol, triglycerides, polyunsaturated fatty acids, and cholesterol.
Subject(s)
Aqueous Humor , Lipids , Myopia , Tandem Mass Spectrometry , Humans , Aqueous Humor/metabolism , Myopia/metabolism , Male , Female , Lipids/analysis , Adult , Chromatography, High Pressure Liquid , Young Adult , ROC Curve , Lipid Metabolism/physiology , Middle Aged , Axial Length, Eye/pathology , Biometry , LipidomicsABSTRACT
INTRODUCTION: Numerous studies have found an association between autoimmune diseases of the nervous system (ADNS) and schizophrenia (SCZ), but the findings remain controversial. We conducted the first meta-analysis to summarize the current evidence from cohort studies that evaluated the association between ADNS and SCZ. METHODS: PubMed, Web of Science, and Embase were comprehensively searched until May 30, 2022 for articles on the association between ADNS and SCZ. Every included study was reported effect size with 95% CIs for the association between ADNS and SCZ. Meta-regression and subgroup analysis were used to assess the heterogeneity. RESULTS: A total of 8 cohort studies with 12 cohorts were included in the meta-analysis. We observed a significant association between ADNS and SCZ (RR = 1.42; 95%CI, 1.18-1.72). Subgroup analysis showed that the risk of SCZ was significantly increased when ADNS were used as exposure factors (RR = 1.48; 95%CI, 1.15-1.89), whereas with SCZ did not observe an increased risk of subsequent ADNS (RR = 1.33; 95%CI, 0.92-1.92); multiple sclerosis (MS) was positively associated with SCZ (RR = 1.36; 95%CI, 1.12-1.66), but no significant association was found between Guillain-Barre syndrome (GBS) and SCZ (RR = 1.90; 95%CI, 0.87-4.17). Meanwhile, we found location was the source of heterogeneity. LIMITATIONS: High heterogeneity was observed (I2 = 92.0%), and only English literature was included in the meta-analysis. CONCLUSIONS: We found a positive association between ADNS and SCZ, and the association was different across the different types of ADNS. The results of the study are helpful for clinicians to carry out targeted preventive measures for ADNS and SCZ.
Subject(s)
Autoimmune Diseases of the Nervous System , Schizophrenia , Humans , Cohort StudiesABSTRACT
S-Adenosylmethionine (SAM) is a crucial small-molecule metabolite widely used in food and medicine. The development of high-throughput biosensors for SAM biosynthesis can significantly improve the titer of SAM. This paper constructed a synthetic transcription factor (TF)-based biosensor for SAM detecting in Saccharomyces cerevisiae. The synthetic TF, named MetJ-hER-VP16, consists of an Escherichia coli-derived DNA-binding domain MetJ, GS linker, the human estrogen receptor binding domain hER, and the viral activation domain VP16. The synthetic biosensor is capable of sensing SAM in a dose-dependent manner with fluorescence as the output. Additionally, it is tightly regulated by the inducer SAM and ß-estradiol, which means that the fluorescence output is only available when both are present together. The synthetic SAM biosensor could potentially be applied for high-throughput metabolic engineering and is expected to improve SAM production.
Subject(s)
Biosensing Techniques , S-Adenosylmethionine , Saccharomyces cerevisiae , Transcription Factors , Humans , Escherichia coli/metabolism , Etoposide/metabolism , S-Adenosylmethionine/metabolism , Saccharomyces cerevisiae/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
In antibody preparation, the immunogenicity of small molecules is limited due to the instability of adjuvant/hapten emulsions. Nanoparticle-based adjuvants overcome instability and effectively improve immune responses. Immunogenicity and antigenicity are fundamentally important, yet understudied, facets of nanoparticle formulations themselves. Herein, we studied the immunogenicity and antigenicity of nanoparticle formulations. In experiments in a rabbit model, simple inorganic nanoparticle (e.g., gold nanoparticle (AuNP) and silver nanoparticle (AgNP)) immunogens induced higher titers of antiserum. Moreover, several promising nanoparticle drug carrier immunogens (e.g., SiO2, oleylamine graft polysuccinimide (PSIOAm), oleylamine and N-(3-aminopropyl)imidazole cograft polysuccinimide (PSIOAm-NAPI), Fe3O4@O-dextran, etc.) showed excellent immunogenicity. Cross-reactivity calculations revealed that the antigenicity properties of AgNP and AuNP antigens are highly size-dependent. Meanwhile, four nanoparticle drug carriers generate antibody-specific immune responses to their antigens. The reactivity of the anti-NP antibodies with nanoparticle antigens was confirmed using immunoassays. This study systematically identified the immunogenicity and antigenicity of the nanoparticle formulation itself. These findings provide insights into the immunological properties of the nanoparticle formulation itself in an organism.
Subject(s)
Antigens/immunology , Immunity/immunology , Nanoparticle Drug Delivery System , Nanoparticles , Animals , Antibodies/immunology , Enzyme-Linked Immunosorbent Assay , Gold , Male , Metal Nanoparticles , Rabbits , SilverABSTRACT
BACKGROUND: To assess the feasibility and clinical utility of artificial intelligence (AI)-based screening for diabetic retinopathy (DR) and macular edema (ME) by combining fundus photos and optical coherence tomography (OCT) images in a community hospital. METHODS: Fundus photos and OCT images were taken for 600 diabetic patients in a community hospital. Ophthalmologists graded these fundus photos according to the International Clinical Diabetic Retinopathy (ICDR) Severity Scale as the ground truth. Two existing trained AI models were used to automatically classify the fundus images into DR grades according to ICDR, and to detect concomitant ME from OCT images, respectively. The criteria for referral were DR grades 2-4 and/or the presence of ME. The sensitivity and specificity of AI grading were evaluated. The number of referable DR cases confirmed by ophthalmologists and AI was calculated, respectively. RESULTS: DR was detected in 81 (13.5%) participants by ophthalmologists and in 94 (15.6%) by AI, and 45 (7.5%) and 53 (8.8%) participants were diagnosed with referable DR by ophthalmologists and by AI, respectively. The sensitivity, specificity and area under the curve (AUC) of AI for detecting DR were 91.67%, 96.92% and 0.944, respectively. For detecting referable DR, the sensitivity, specificity and AUC of AI were 97.78%, 98.38% and 0.981, respectively. ME was detected from OCT images in 49 (8.2%) participants by ophthalmologists and in 57 (9.5%) by AI, and the sensitivity, specificity and AUC of AI were 91.30%, 97.46% and 0.944, respectively. When combining fundus photos and OCT images, the number of referrals identified by ophthalmologists increased from 45 to 75 and from 53 to 85 by AI. CONCLUSION: AI-based DR screening has high sensitivity and specificity and may feasibly improve the referral rate of community DR.
Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , Artificial Intelligence , Diabetic Retinopathy/diagnostic imaging , Hospitals, Community , Humans , Macular Edema/diagnostic imaging , Mass Screening/methods , Photography/methods , Tomography, Optical Coherence/methodsABSTRACT
In this study, we explored the individual and combined effects of ammonia-N and sulfide stress (1â¯mg/L sulfide and 15â¯mg/L ammonia-N) on the oxidation resistance, immune response and intestinal health of Litopenaeus vannamei during 72â¯h exposure. The total antioxidant capacity (T-AOC), malonaldehyde (MDA) and nitric oxide (NO) content, superoxide dismutase (SOD) and catalase activity (CAT), the immune-relative gene (caspase-3, hsp70 and IMD) expression in hepatopancreas and intestine of L.vannamei and the intestinal microbiota were measured. The result showed that MDA and NO contents in hepatopancreas of L. vannamei in all treatment groups increased and remain were at high levels at the end of the stress exposure. The L. vannamei employ antioxidant defense system by increasing the activities of T-AOC, SOD and CAT enzymes in hepatopancereas and intestine to reduce oxidant damage. More severe damages with combined ammonia-N and sulfide stress to antioxidant systems were observed. The gene expression results also demonstrated that antioxidant capacity of L. vannamei was severely impaired and the apoptosis cell was initiated under the ammonia-N and sulfide stress. In addition, the environmental stress also reshaped the intestinal microbial community structure of L. vannamei that a number of original genera decreased, such as Cellvibrio, Vibrio and Rheinheimera; some new genera increased or appeared, such as Photobacterium in all treatment groups, Arcobacter and Fusibacter in sulfide stress group. Therefore, the health of L. vannamei was severely impacted when exposed to the stress of ammonia nitrogen and sulfide and these two factors can have weak synergic effects.
Subject(s)
Ammonia/adverse effects , Gastrointestinal Microbiome/drug effects , Immunity, Innate/drug effects , Nitrogen/adverse effects , Penaeidae/drug effects , Sulfides/adverse effects , Animals , Arthropod Proteins/genetics , Arthropod Proteins/metabolism , Oxidation-Reduction , Penaeidae/genetics , Penaeidae/immunology , Penaeidae/microbiology , Stress, PhysiologicalABSTRACT
Bone morphogenetic proteins (BMPs) play important roles in skeletal development and repair. Previously, we found fibroblast growth factor 2 (FGF2) induced up-regulation of BMP2, 3, 4 in the process of rabbit articular cartilage repair, which resulted in satisfactory repair effects. As BMP2/4 show a clearly positive effect for cartilage repair, we investigated the functions of BMP3 in rabbit articular cartilage repair. In this paper, we find that BMP3 inhibits the repair of partial-thickness defect of articular cartilage in rabbit by inducing the degradation of extracellular matrix, interfering with the survival of chondrocytes surrounding the defect, and directly inhibiting the expression of BMP2 and BMP4. Meanwhile BMP3 suppress the repair of full-thickness cartilage defect by destroying the subchondral bone through modulating the proliferation and differentiation of bone marrow stem cells (BMSCs), and directly increasing the expression of BMP4. Although BMP3 has different functions in the repair of partial and full-thickness defects of articular cartilage in rabbit, the regulation of BMP expression is involved in both of them. Together with our previous findings, we suggest the regulation of the BMP signaling pathway by BMP3 is essential in articular cartilage repair.
Subject(s)
Bone Morphogenetic Protein 3/genetics , Bone Morphogenetic Protein 3/metabolism , Cartilage, Articular/physiology , Wound Healing , Animals , Cartilage, Articular/surgery , Cell Differentiation , Cell Proliferation , Chondrocytes/cytology , Chondrocytes/metabolism , Extracellular Matrix/metabolism , Gene Expression , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Rabbits , Signal TransductionABSTRACT
Suicide is a severe public health issue globally. Accurately identifying high-risk lung cancer patients for suicidal behavior and taking timely intervention measures has become a focus of current research. This study intended to construct dynamic prediction models for identifying suicide risk among lung cancer patients. Patients were sourced from the Surveillance, Epidemiology, and End Results database, while meteorological data was acquired from the Centers for Disease Control and Prevention. This cohort comprised 455, 708 eligible lung cancer patients from January 1979 to December 2011. A Cox proportional hazard regression model based on landmarking approach was employed to explore the impact of meteorological factors and clinical characteristics on suicide among lung cancer patients, and to build dynamic prediction models for the suicide risk of these patients. Additionally, subgroup analyses were conducted by age and sex. The model's performance was evaluated using the C-index, Brier score, area under curve (AUC) and calibration plot. During the study period, there were 666 deaths by suicide among lung cancer patients. Multivariable Cox results from the dynamic prediction model indicated that age, marital status, race, sex, primary site, stage, monthly average daily sunlight, and monthly average temperature were significant predictors of suicide. The dynamic prediction model demonstrated well consistency and discrimination capabilities. Subgroup analyses revealed that the association of monthly average daily sunlight and monthly average temperature with suicide remained significant among female and younger lung cancer patients. The dynamic prediction model can effectively incorporate covariates with time-varying to predict lung cancer patients' suicide death. The results of this study have significant implications for assessing lung cancer individuals' suicide risk.
Subject(s)
Lung Neoplasms , SEER Program , Suicide , Humans , Male , Female , Lung Neoplasms/mortality , Lung Neoplasms/epidemiology , Lung Neoplasms/psychology , Middle Aged , Suicide/statistics & numerical data , Suicide/psychology , Aged , Adult , Risk Factors , Proportional Hazards Models , Risk Assessment/methods , United States/epidemiology , Meteorological Concepts , Cohort StudiesABSTRACT
We have previously shown that radiation increases HIF-1 activity in tumors, causing significant radioprotection of the tumor vasculature. The impact that HIF-1 activation has on overall tumor radiosensitivity, however, is unknown. We reveal here that HIF-1 plays an important role in determining tumor radioresponsiveness through regulating four distinct processes. By promoting ATP metabolism, proliferation, and p53 activation, HIF-1 has a radiosensitizing effect on tumors. Through stimulating endothelial cell survival, HIF-1 promotes tumor radioresistance. As a result, the net effect of HIF-1 blockade on tumor radioresponsiveness is highly dependent on treatment sequencing, with "radiation first" strategies being significantly more effective than the alternative. These data provide a strong rationale for pursuing sequence-specific combinations of HIF-1 blockade and conventional therapeutics.
Subject(s)
DNA-Binding Proteins/antagonists & inhibitors , Neoplasms/radiotherapy , Nuclear Proteins/antagonists & inhibitors , Radiation Tolerance , Transcription Factors/antagonists & inhibitors , Adenosine Triphosphate/metabolism , Animals , Apoptosis , Cell Proliferation , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Endothelium, Vascular/metabolism , Endothelium, Vascular/radiation effects , Energy Metabolism , Humans , Hypoxia-Inducible Factor 1 , Hypoxia-Inducible Factor 1, alpha Subunit , Mice , Neoplasms/metabolism , Neovascularization, Pathologic/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , RNA Interference , Radiation Tolerance/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Tumor Suppressor Protein p53/metabolismABSTRACT
As an excellent hosting matrices for enzyme immobilization, metal-organic framework (MOFs) provides superior physical and chemical protection for biocatalytic reactions. In recent years, the hierarchical porous metal-organic frameworks (HP-MOFs) have shown great potential in enzyme immobilization due to their flexible structural advantages. To date, a variety of HP-MOFs with intrinsic or defective porous have been developed for the immobilization of enzymes. The catalytic activity, stability and reusability of enzyme@HP-MOFs composites are significantly enhanced. This review systematically summarized the strategies for developing enzyme@HP-MOFs composites. In addition, the latest applications of enzyme@HP-MOFs composites in catalytic synthesis, biosensing and biomedicine were described. Moreover, the challenges and opportunities in this field were discussed and envisioned.
Subject(s)
Metal-Organic Frameworks , Metal-Organic Frameworks/chemistry , Porosity , Enzymes, Immobilized/chemistry , Biocatalysis , CatalysisABSTRACT
Recent studies have discovered that functional connections are impaired in patients with Parkinson's disease (PD) accompanied by hallucinations (PD-H), even at the preclinical stage. The cerebellum has been implicated in playing a role in cognitive processes. However, the functional connectivity (FC) between the cognitive sub-regions of the cerebellum in PD patients with hallucinations needs further clarification. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from three groups (17 PD-H patients, 13 patients with Parkinson's disease not accompanied by hallucinations (PD-NH), and 26 healthy controls (HC)). The data were collected in this study to investigate the impact of cerebellar FC changes on cognitive performance. Additionally, we define cerebellar FC as a training feature for classifying all subjects using Support Vector Machines (SVMs). We found that in the PD-H patients, there was an increase in FC within the left side of the precuneus (PCUN) compared to the HC. Additionally, there was an increase in FC within the bilateral opercular part of the inferior frontal gyrus (IFGoprec) and triangular part of the inferior frontal gyrus (IFCtriang), as well as the left side of the postcentral gyrus (PoCG), inferior parietal lobe (IPL), and PCUN compared to the PD-NH patients. In the machine learning training results, cerebellar FC has also been proven to be an effective biomarker feature, achieving a recognition rate of over 90% for PD-H. These findings indicate that the cortico-cerebellar FC in PD-H and PD-NH patients was significantly disrupted, with different patterns of distribution. The proposed pipeline offers a promising, low-cost alternative for diagnosing preclinical PD-H and may also be beneficial for other degenerative brain disorders.
ABSTRACT
Objective: Previous studies have demonstrated an association between anxiety and metabolic syndrome (MetS). However, the association is still controversial. This updated meta-analysis aimed to reanalyze the association between anxiety and MetS. Methods: We comprehensively searched PubMed, Embase and Web of Science for all related studies published before January 23, 2023. Observational studies that informed effect size with 95% confidence interval (CI) for the association between anxiety and MetS were included. According to heterogeneity between studies, fixed or random effects models were applied to calculate the pooled effect size. Publication bias was examined by funnel plots. Results: The research included 24 cross-sectional studies: 20 studies used MetS as the dependent variable with a pooled OR of 1.07 (95% CI: 1.01-1.13) and four studies used anxiety as the dependent variable with a pooled OR of 1.14 (95% CI: 1.07-1.23). Three cohort studies were found: two studies detected the association of baseline anxiety with the risk of MetS, one of the studies demonstrated a significant association, but a similar result was not found in another study; one study showed no significant association between baseline MetS and the risk of anxiety. Conclusion: Cross-sectional studies indicated an association between anxiety and MetS. The results from cohort studies are still inconsistent and limited. More large-scale prospective studies are needed to further reveal the causal relationship of anxiety with MetS.
ABSTRACT
Introduction: Visual hallucination is a prevalent psychiatric disorder characterized by the occurrence of false visual perceptions due to misinterpretation in the brain. Individuals with Parkinson's disease often experience both minor and complex visual hallucinations. The underlying mechanism of complex visual hallucinations in Parkinson's patients is commonly attributed to dysfunction in the visual pathway and attention network. However, there is limited research on the mechanism of minor hallucinations. Methods: To address this gap, we conducted an experiment involving 13 Parkinson's patients with minor hallucinations, 13 Parkinson's patients without hallucinations, and 13 healthy elderly individuals. We collected and analyzed EEG and MRI data. Furthermore, we utilized EEG data from abnormal brain regions to train a machine learning model to determine whether the abnormal EEG data were associated with minor hallucinations. Results: Our findings revealed that Parkinson's patients with minor hallucinations exhibited excessive activation of cortical excitability, an imbalanced interaction between the attention network and the default network, and disruption in the connection between these networks. These findings is similar to the mechanism observed in complex visual hallucinations. The visual reconstruction of one patient experiencing hallucinations yields results that differ from those observed in subjects without such symptoms. Discussion: The visual reconstruction results demonstrated significant differences between Parkinson's patients with hallucinations and healthy subjects. This suggests that visual reconstruction techniques may offer a means of evaluating hallucinations.
ABSTRACT
Through a poorly understood mechanism, tumors respond to radiation by secreting cytokines capable of inhibiting apoptosis in endothelial cells, thereby diminishing treatment response by minimizing vascular damage. We reveal here that this pathway is governed by a major angiogenesis regulator, HIF-1. Following radiotherapy, tumor reoxygenation leads to: (1) nuclear accumulation of HIF-1 in response to reactive oxygen, and (2) enhanced translation of HIF-1-regulated transcripts secondary to stress granule depolymerization. The resulting increase in HIF-1-regulated cytokines enhances endothelial cell radioresistance. Inhibiting postradiation HIF-1 activation significantly increases tumor radiosensitivity as a result of enhanced vascular destruction. These data describe novel pathways contributing significantly to our understanding of HIF-1 regulation which may be major determinants of tumor radiosensitivity, potentially having high clinical relevance.
Subject(s)
DNA-Binding Proteins/metabolism , Mammary Neoplasms, Experimental/radiotherapy , Nuclear Proteins/metabolism , Oxidative Stress/radiation effects , Oxygen/physiology , Radiation Tolerance , Transcription Factors , Animals , Apoptosis/radiation effects , Cell Hypoxia/physiology , Cesium Radioisotopes , Cytokines/metabolism , DNA-Binding Proteins/genetics , Endothelium, Vascular/metabolism , Endothelium, Vascular/radiation effects , Female , Free Radicals , Gamma Rays , Gene Expression Regulation, Neoplastic , Green Fluorescent Proteins , Hypoxia-Inducible Factor 1 , Hypoxia-Inducible Factor 1, alpha Subunit , Luminescent Proteins/metabolism , Mammary Neoplasms, Experimental/blood supply , Mammary Neoplasms, Experimental/metabolism , Mice , Neovascularization, Pathologic/metabolism , Nuclear Proteins/genetics , Protein Biosynthesis/radiation effectsABSTRACT
Purpose: The present study was performed to compare the optical quality of the eyes of myopic children before and after treatment with atropine eye drops of different concentrations. Methods: In the study population of 71 patients (131 eyes), 34 patients (63 eyes) were given 0.01% atropine eye drops and 37 patients (68 eyes) were given 0.05% atropine eye drops. The modulation transfer function (MTF) cutoff frequency, Strehl ratio, objective scattering index (OSI), and predicted visual acuities (PVAs 100%, 20%, and 9%) under different lighting conditions were measured before and after two weeks of atropine treatment. Results: After using 0.05% atropine eye drops for two weeks, the Strehl ratio decreased from 0.27 ± 0.07 to 0.23 ± 0.07 (P = 0.0026), PVA 20% decreased from 1.15 ± 0.32 to 1.03 ± 0.36 (P = 0.0344), and PVA 9% decreased from 0.74 ± 0.23 to 0.64 ± 0.23 (P = 0.0073). The OSI was significantly higher after using 0.05% than 0.01% atropine eye drops (P = 0.0396), while both the Strehl ratio and PVA 20% were lower after using 0.05% than 0.01% atropine eye drops (P = 0.0087 and P = 0.0492, respectively). Conclusion: The children's optical quality did not change significantly after using 0.01% atropine eye drops, whereas it decreased after using 0.05% atropine eye drops.
Subject(s)
Atropine , Myopia , Child , Eye , Humans , Myopia/diagnosis , Myopia/drug therapy , Ophthalmic Solutions , Visual AcuityABSTRACT
BACKGROUND: The odontogenic jaw cyst is a cavity containing liquid, semifluid or gaseous components, with the development of the disease. In recent years, with the rapid development of oral materials and the transformation of treatment of jaw cysts, more options are available for treatment of postoperative bone defect of jaw cysts. Guided bone regeneration (GBR) places biomaterials in the bone defect, and then uses biofilm to separate the proliferative soft tissue and the slow-growing bone tissue to maintain the space for bone regeneration, which is widely used in the field of implantology. AIM: To observe the clinical effect of GBR in repairing bone defect after enucleation of small and medium-sized odontogenic jaw cysts. METHODS: From June 2018 to September 2020, 13 patients (7 male, 6 female) with odontogenic jaw cysts were treated in the Department of Oral Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Adults without hypertension, heart disease, diabetes or other systemic diseases were selected. The diagnosis was based on the final pathological results: 11 cases were diagnosed as apical cysts, one as primordial cyst, and one as dentigerous cyst. The lesions were located in the maxilla in seven cases, and in the mandible in six cases. All cases were treated with the same method of enucleation combined with GBR. RESULTS: Three to four months after the operation, the boundary between the implant site and the surrounding normal stroma was not obvious in patients with small-sized odontogenic jaw cysts. The patients with tooth defects were treated with implant after 6 mo. For the patients with medium-sized odontogenic jaw cysts, the density of the center of the implant area was close to the normal mass at 6 mo after surgery, and there was a clear boundary between the periphery of the implant area and the normal mass. The boundary between the periphery of the implant area and the normal mass was blurred at 8-9 mo after surgery. Patients with tooth defects were treated with implants at > 6 mo after the operation. CONCLUSION: Enucleation combined with guided bone regeneration in small and medium-sized odontogenic jaw cysts can shorten the time of osteogenesis, increase the amount of new bone formation, reduce complications, and improve quality of life.
ABSTRACT
Purpose: To identify differentially expressed (DE) microRNAs (miRNAs) in the aqueous humor (AH) of keratoconus (KC) eyes using next-generation sequencing and to explore whether DE miRNAs might play roles in KC pathophysiology. Methods: The small RNAs in the AH of 15 KC eyes and 15 myopia eyes (the control group) were sequenced on an Illumina NovaSeq 6000 platform. Gene Oncology and Kyoto Encyclopedia of Genes and Genome enrichment analyses were performed. Receiver operating characteristic curves were used to identify potential KC biomarkers. Results: We identified 204 miRNAs in the AH of the KC group and 200 in the AH of the control group. Fourteen miRNAs were differentially expressed between the two groups; four miRNAs were upregulated and 10 downregulated in KC AH. The possible pathways regulated by the DE miRNAs included antigen processing and presentation, endocytosis, mismatch repair, and Hippo signaling. The AH concentrations of miR-222-3p, miR-363-3p, and miR-423-5p exhibited areas under the curves of 1. Conclusions: We profiled the DE miRNAs of the AH of KC eyes. These miRNAs may be associated with KC pathogenesis and could serve as KC biomarkers. Translational Relevance: Data on aberrantly expressed miRNAs in KC combined with bioinformatics analyses suggest possible roles for specific miRNAs. The DE miRNAs may serve as diagnostic KC biomarkers.
Subject(s)
Computational Biology , MicroRNAs , MicroRNAs/geneticsABSTRACT
Visible-light (VL) photocatalysis has been regarded as an intriguing technology for the control of persistent environmental pollutants. In this study, the novel homogeneous Co doped-Bi/BiOBr nanocomposites (CB-X) were prepared via a facile one-step hydrothermal method, featured with a uniform 0D Bi nanodots distribution on 2D Co-doped BiOBr nanosheets, and the photocatalytic performance was evaluated by decomposing the BPA as a prototype contaminant. The degradation experiment indicated that the optimal CB-2 nanocomposite exhibited the best photocatalytic activity with a 94% removal efficiency of BPA under the VL irradiation of 30 min; And the corresponding apparent rate constant (k) was as high as 0.107 min-1, which was 10.7 times greater than that of Bi/BiOBr (0.010 min-1). Benefiting from the modulation effect of Co-doping on the intrinsic electron configuration of Bi/BiOBr, the elevated VL adsorption capacity and accelerated h+/e- pairs separation rate were achieved, which were evidenced by photoluminescence (PL) spectroscopy, photo-electrochemical measurements and density functional theory (DFT) calculation. Moreover, the major reactive species in CB-X/VL system were uncovered to be â¢O2- and 1O2, whereas â¢OH and h+ presented a secondary contribution in the BPA elimination. Finally, the possible photocatalytic mechanism involved in CB-X nanocomposites and BPA degradation pathways were proposed on the basis of the various intermediates and products detected by LC-MS/MS.