ABSTRACT
Avian pathogenic Escherichia coli (APEC) constitutes a significant cause of colibacillosis, a localized or systemic inflammatory disorder in avian species, resulting in considerable economic losses within the global poultry industry. SdiA (suppressor of division inhibitor) is a transcription factor recognized as a LuxR homolog in Escherichia coli, regulating various behaviors, including biofilm formation, multidrug resistance, and the secretion of virulence factors. However, the function of SdiA in APEC strains and its correlation with virulence and multidrug resistance remains unknown. This study probed into the function of SdiA by analyzing the effect of sdiA deletion on the transcription profile of an APEC strain. The microarray data revealed that SdiA upregulates 160 genes and downregulates 59 genes, exerting a particularly remarkable influence on the transcription of multiple virulence genes. A series of antibiotic sensitivity tests, biofilm formation assays, motility assays, and transcriptome analyses were performed, while a Normality test and t-test were conducted on the datasets. This research confirmed that SdiA inhibits biofilm formation by 1.9-fold (p-value < 0.01) and motility by 1.5-fold (p-value < 0.01). RT-qPCR revealed that SdiA positively regulates multidrug resistance by upregulating the expression of yafP, cbrA, and eamB. Collectively, the results of this study indicate the role of SdiA in the pathogenesis of APEC by controlling biofilm formation, motility, and multidrug resistance.
ABSTRACT
The role of serotonin in human behaviour is informed by approaches which allow in vivo modification of synaptic serotonin. However, characterising the effects of increased serotonin signalling in human models of behaviour is challenging given the limitations of available experimental probes, notably selective serotonin reuptake inhibitors. Here we use a now-accessible approach to directly increase synaptic serotonin in humans (a selective serotonin releasing agent) and examine its influence on domains of behaviour historically considered core functions of serotonin. Computational techniques, including reinforcement learning and drift diffusion modelling, explain participant behaviour at baseline and after week-long intervention. Reinforcement learning models reveal that increasing synaptic serotonin reduces sensitivity for outcomes in aversive contexts. Furthermore, increasing synaptic serotonin enhances behavioural inhibition, and shifts bias towards impulse control during exposure to aversive emotional probes. These effects are seen in the context of overall improvements in memory for neutral verbal information. Our findings highlight the direct effects of increasing synaptic serotonin on human behaviour, underlining its role in guiding decision-making within aversive and more neutral contexts, and offering implications for longstanding theories of central serotonin function.
Subject(s)
Serotonin , Humans , Serotonin/metabolism , Male , Female , Adult , Young Adult , Reinforcement, Psychology , Avoidance Learning/drug effects , Avoidance Learning/physiology , Emotions/physiology , Inhibition, Psychological , Selective Serotonin Reuptake Inhibitors/pharmacology , Learning/physiology , Decision Making/physiology , Memory/physiology , Memory/drug effectsABSTRACT
α-Actinins play crucial roles in cytoskeletal mechanobiology by acting as force-bearing structural modules that orchestrate and sustain the cytoskeletal framework, serving as pivotal hubs for diverse mechanosensing proteins. The mechanical stability of α-actinin dimer, a determinant of its functional state, remains largely unexplored. Here, we directly quantify the force-dependent lifetimes of homo- and hetero-dimers of human α-actinins, revealing an ultra-high mechanical stability of the dimers associated with > 100 seconds lifetime within 40 pN forces under shear-stretching geometry. Intriguingly, we uncover that the strong dimer stability is arisen from much weaker sub-domain pair interactions, suggesting the existence of distinct dimerized functional states of the dimer, spanning a spectrum of mechanical stability, with the spectrin repeats (SRs) in folded or unfolded conformation. In essence, our study supports a potent mechanism for building strength in biomolecular dimers through weak, multiple sub-domain interactions, and illuminates multifaceted roles of α-actinin dimers in cytoskeletal mechanics and mechanotransduction.
Subject(s)
Actinin , Protein Multimerization , Humans , Actinin/metabolism , Actinin/chemistry , Cytoskeleton/metabolism , Mechanotransduction, Cellular , Protein Domains , Single Molecule Imaging/methodsABSTRACT
This study aimed to compare the effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide content and quality characteristics of fried potato chips. The hydrolyzed pectin with molecular weight (Mw) of 8.81 ± 0.49 kDa was obtained through partial degradation of pectin (Mw: 747.57 ± 6.73 kDa) using pectinase. Results showed that both pectin and hydrolyzed pectin coating significantly inhibited acrylamide formation and inhibition rates exceeded 90 %. Hydrolyzed pectin had stronger inhibitory activity against acrylamide formation than pectin, especially when the concentration of hydrolyzed pectin was >2 %, its inhibitory rate exceeded 95 %. Compared to pectin coating, hydrolyzed pectin coating endow fried potato chips with smaller browning, higher crispness, less moisture but higher oil content. Overall, hydrolyzed pectin had better application prospects than pectin in inhibiting acrylamide formation of fried potato chips.
Subject(s)
Acrylamide , Pectins , Solanum tuberosum , Solanum tuberosum/chemistry , Pectins/chemistry , Acrylamide/chemistry , Hydrolysis , Cooking , Molecular WeightABSTRACT
Trimesic acid and o-phenylenediamine (OPD) were employed as precursors to synthesize yellow-green fluorescent carbon dots (Y-G-CDs) by solvothermal synthesis for the sensitive detection of Thiophanate-methyl (TM) in real agricultural products. The Y-G-CDs probe could specifically recognize the TM primarily through π-π stacking. Moreover, the fluorescence quenching of the probe was ultimately dominated by the PET effect, based on the interaction between the abundant carboxyl groups on the surface of the Y-G-CDs and the amino group of TM. A strong linear relationship between the fluorescence quenching of the probe and TM concentration in the range of 0-10 µmol/L was observed and the limit of detection (LOD) was calculated to be 50.7 nmol/L. Compared to the interference pesticides, the Y-G-CDs probe demonstrated exceptional selectivity toward TM, with satisfactory recoveries of 96.3 % - 104.2 % in spiked food samples. The Y-G-CDs probe enables simple pretreatment, cost-effective, and on-site detection of TM in fruits and vegetables with visual detection of the TM employing a smartphone-assisted sensing platform.
Subject(s)
Carbon , Quantum Dots , Thiophanate , Vegetables , Fruit , Smartphone , Fluorescent Dyes , Spectrometry, FluorescenceABSTRACT
Along with the demand for further miniaturization of high and pulsed power devices, it becomes more and more important to realize ultrahigh recoverable energy storage density (Wrec ) with high energy storage efficiency (η) and ultrahigh discharge energy storage density (Wd ) accompanied by high power density (Pd ) in dielectrics. To date, it remains, however, a big challenge to achieve high Wrec or Wd in glass ceramics compared to other dielectric energy storage materials. Herein, a strategy of defect formation modulation is applied to form "amorphous-disordered-ordered" microstructure in BaTiO3 -based glass ceramics so as to achieve a high Wrec of 12.04 J cm-3 with a high η of 81.1% and an ultrahigh Wd of 11.98 J cm-3 with a superb Pd of 973 MW cm-3 . This work demonstrates a feasible route to obtain glass ceramics with an outstanding energy storage performance and proves the enormous potential of glass ceramics in high and pulsed power applications.
ABSTRACT
BACKGROUND: Uridyl peptide compounds are renowned as a subclass of nucleoside antibiotics for their highly specific antibacterial activity against Gram-negative bacteria and the unique target of action. We previously activated the biosynthetic gene cluster of a uridyl peptide antibiotic, mureidomycin, in Streptomyces roseosporus NRRL 15998 by introducing an exogenous positive regulator gene ssaA, and the generated strain was designated as Sr-hA. This study aims to further explore mureidomycin analogs from Sr-hA as well as the collaborative roles of two wide-spread genes, SSGG-02980 and SSGG-03002 encoding putative nuclease/phosphatase and oxidoreductase respectively, in mureidomycin diversification. RESULTS: In order to understand how SSGG-02980 and SSGG-03002 contribute to mureidomycin biosynthesis, the gene disruption mutants and complementary strains were constructed. Mass spectrometry analyses revealed that two series of pairwise mureidomycin analogs were synthesized in Sr-hA with a two-dalton difference in molecular weight for each pair. By disruption of SSGG-03002, only mureidomycins with lower molecular weight (MRDs, 1-6) could be specifically accumulated in the mutant (∆03002-hA), whereas the other series of products with molecular weight plus 2 Da (rMRDs, 1'-6') became dominant in SSGG-02980 disruption mutant (∆02980-hA). Further comprehensive NMR analyses were performed to elucidate the structures, and three MRDs (3, 4, 5) with unsaturated double bond at C5-C6 of uracil group were characterized from ∆03002-hA. In contrast, the paired rMRDs analogs (3', 4', 5') from ∆SSGG-02980 corresponding to 3, 4 and 5 were shown to contain a single bond at this position. The results verified that SSGG-03002 participates in the reduction of uracil ring, whereas SSGG-02980 antagonizes the effect of SSGG-03002, which has been rarely recognized for a phosphatase. CONCLUSIONS: Overall, this study revealed the key roles of two wide-spread families of enzymes in Streptomyces. Of them, oxidoreductase, SSGG-03002, is involved in dihydro-mureidomycin biosynthesis of S. roseosporus, whereas nuclease/phosphatase, SSGG-02980, has an adverse effect on SSGG-03002. This kind of unusual regulation model between nuclease/phosphatase and oxidoreductase is unprecedented, providing new insights into the biosynthesis of mureidomycins in Streptomyces. The findings would be of significance for structural diversification of more uridyl peptide antibiotics against Gram-negative bacteria.
Subject(s)
Anti-Bacterial Agents , Streptomyces , Peptides/metabolism , Bacterial Proteins/metabolism , Streptomyces/metabolism , Oxidoreductases/metabolism , Uracil/metabolism , Phosphoric Monoester Hydrolases/genetics , Phosphoric Monoester Hydrolases/metabolism , Multigene FamilyABSTRACT
Staphylococcus aureus (S. aureus), as the main pathogen in milk and dairy products, usually causes intoxication with vomiting and various kinds of inflammation after entering the human body. CodY, an important transcriptional regulator in S. aureus, plays an important role in regulating metabolism, growth, and virulence. However, little is known about the role of CodY on environmental stress tolerance. In this research, we revealed the role of CodY in environmental stress tolerance in foodborne S. aureus RMSA24. codY mutation significantly reduced the tolerance of S. aureus to desiccation and oxidative, salt, and high-temperature stresses. However, S. aureus was more tolerant to low temperature stress due to mutation of codY. We found that the expressions of two important heat shock proteins-GroEL and DanJ-were significantly down-regulated in the mutant codY. This suggests that CodY may indirectly regulate the high- and low-temperature tolerance of S. aureus by regulating the expressions of groEL and danJ. This study reveals a new mechanism of environmental stress tolerance in S. aureus and provides new insights into controlling the contamination and harm caused by S. aureus in the food industry.
ABSTRACT
Mammalian DNA extracted from the invertebrates, especially blowfly-derived DNA, has been suggested as a useful tool to complement traditional field methods for terrestrial mammal monitoring. However, the accuracy of the estimated location of the target mammal detected from blowfly-derived DNA is largely dependent on the knowledge of blowflies' dispersal range. Presently, published data on adult blowfly dispersal capabilities remain scarce and mostly limited to temperate and subtropical regions, with no published report on the adult blowfly dispersal range in the Tropics. We seek to determine the blowfly flight range and dispersal activity in a tropical plantation in Malaysia by mark-release-recapture of approximately 3000 wild blowflies by use of rotten fish-baited traps for nine consecutive days. Out of the 3000 marked Chrysomya spp., only 1.5% (43) were recaptured during the 9-day sampling period. The majority of the blowflies (79%) were recaptured 1 km from the release point, while 20.9% were caught about 2-3 km from the release point. One individual blowfly travelled as far as 3 km and before being recaptured, which was the maximum dispersal distance recorded in this study. This result suggests that the estimated locations of the mammals detected from blowfly-derived iDNA is likely to be within 1-2 km radius from the origin of the blowfly sampling location. However, a more accurate estimated distance between the target mammal and the blowfly sampling location requires further investigation due to various factors, such as blowfly species, wind speed and direction that may potentially affect the blowfly dispersal activities. This study contributes further understanding on the development of a blowfly-derived DNA method as a mammalian monitoring tool in the tropical forests.
ABSTRACT
The present study proposes an evaluation method for the driving fragment ability of explosives, which aims to provide theoretical and technical support for the selection of explosives used in warheads. The evaluation method is proposed in the light of the dimensional method and the similarity principle, and it uses TNT equivalent as the evaluation indicator. To acquire the evaluation indicator, a test system for driving fragment ability of explosives is constructed, which includes a dynamite gun type driven device, a spherical fragment, and a multi-zone fragment velocity measurement system. TNT and thermobaric explosive were used to carry out the verification experiments of the evaluation method. On the basis of the evaluation method, the basic evaluation model for the driving fragment ability of explosives was established by the TNT mass and the corresponding fragment maximum velocity. Using the basic evaluation model, the TNT equivalent of the thermobaric explosive in driving fragment ability was calculated to be 1.29, which was 3.2% different from the ratio (1.25) of both explosives' Gurney-specific energy. The relative error of 3.2% falls within the allowable range of engineering error, confirming the feasibility of the proposed evaluation method. The result shows that the proposed evaluation method is effective and accurate in evaluating the driving fragment ability of explosives.
ABSTRACT
Background: Sterile inflammation contributes to the pathogenesis of cardiac dysfunction caused by various conditions including pressure overload in hypertension. Mitochondrial DNA (mtDNA) released from damaged mitochondria has been implicated in cardiac inflammation. However, the upstream mechanisms governing mtDNA release and how mtDNA activates sterile inflammation in pressure-overloaded hearts remain largely unknown. Here, we investigated the role of inducible NO synthase (iNOS) on pressure overload-induced cytosolic accumulation of mtDNA and whether mtDNA activated inflammation through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. Methods: To investigate whether the cGAS-STING cascade was involved in sterile inflammation and cardiac dysfunction upon pressure overload, cardiomyocyte-specific STING depletion mice and mice injected with adeno-associated virus-9 (AAV-9) to suppress the cGAS-STING cascade in the heart were subjected to transverse aortic constriction (TAC). iNOS null mice were used to determine the role of iNOS in cGAS-STING pathway activation in pressure-stressed hearts. Results: iNOS knockout abrogated mtDNA release and alleviated cardiac sterile inflammation resulting in improved cardiac function. Conversely, activating the cGAS-STING pathway blunted the protective effects of iNOS knockout. Moreover, iNOS activated the cGAS-STING pathway in isolated myocytes and this was prevented by depleting cytosolic mtDNA. In addition, disruption of the cGAS-STING pathway suppressed inflammatory cytokine transcription and modulated M1/M2 macrophage polarization, and thus mitigated cardiac remodeling and improved heart function. Finally, increased iNOS expression along with cytosolic mtDNA accumulation and cGAS-STING activation were also seen in human hypertensive hearts. Conclusion: Our findings demonstrate that mtDNA is released into the cytosol and triggers sterile inflammation through the cGAS-STING pathway leading to cardiac dysfunction after pressure overload. iNOS controls mtDNA release and subsequent cGAS activation in pressure-stressed hearts.
Subject(s)
DNA, Mitochondrial , Heart Diseases , Nitric Oxide Synthase Type II , Animals , Humans , Mice , Cytosol/metabolism , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Heart Diseases/metabolism , Inflammation/metabolism , Mice, Knockout , Mitochondria/metabolism , Myocytes, Cardiac/metabolism , Nucleotidyltransferases/genetics , Nucleotidyltransferases/metabolism , Nitric Oxide Synthase Type II/metabolismABSTRACT
BACKGROUND: Apathy, a disabling and poorly understood neuropsychiatric symptom, is characterised by impaired self-initiated behaviour. It has been hypothesised that the opportunity cost of time (OCT) may be a key computational variable linking self-initiated behaviour with motivational status. OCT represents the amount of reward which is foregone per second if no action is taken. Using a novel behavioural task and computational modelling, we investigated the relationship between OCT, self-initiation and apathy. We predicted that higher OCT would engender shorter action latencies, and that individuals with greater sensitivity to OCT would have higher behavioural apathy. METHODS: We modulated the OCT in a novel task called the 'Fisherman Game', Participants freely chose when to self-initiate actions to either collect rewards, or on occasion, to complete non-rewarding actions. We measured the relationship between action latencies, OCT and apathy for each participant across two independent non-clinical studies, one under laboratory conditions (n = 21) and one online (n = 90). 'Average-reward' reinforcement learning was used to model our data. We replicated our findings across both studies. RESULTS: We show that the latency of self-initiation is driven by changes in the OCT. Furthermore, we demonstrate, for the first time, that participants with higher apathy showed greater sensitivity to changes in OCT in younger adults. Our model shows that apathetic individuals experienced greatest change in subjective OCT during our task as a consequence of being more sensitive to rewards. CONCLUSIONS: Our results suggest that OCT is an important variable for determining free-operant action initiation and understanding apathy.
Subject(s)
Apathy , Adult , Humans , Cognition , Computer Simulation , Motivation , Reinforcement, PsychologyABSTRACT
BACKGROUND: Epidemiological surveys on heart failure (HF) in Chinese community are relatively lacking. This study aimed to estimate the prevalence and incidence of HF among community residents in southern China. METHODS: Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged ≥ 35 years in Guangzhou, China. The same survey process was carried out for individuals aged ≥ 65 years after a three-year follow-up. RESULTS: The overall prevalence of HF in community residents aged ≥ 35 years was 1.06%. Male had significantly higher risk of HF prevalence [odds ratio (OR) = 1.50, P = 0.027]. The gender-adjusted risk of HF was 1.48 times higher per 10 years aging. HF prevalence was statistically associated with atrial fibrillation, valvular heart disease, hypertension and chronic obstructive pulmonary disease after adjusting for age and gender (OR = 8.30, 5.17, 1.11, 2.28, respectively; all P < 0.05). HF incidence in individuals aged ≥ 65 years were 847 per 100,000 person-years. Baseline atrial fibrillation, valvular heart disease, and diabetes mellitus were risk factors for HF incidence for individuals aged ≥ 65 years adjusting for age and gender (OR = 5.05, 3.99, 2.11, respectively; all P < 0.05). Besides, residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF (OR = 14.41, 8.54, respectively; all P < 0.05). CONCLUSIONS: Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China. Management of related cardiovascular diseases may be helpful to reduce the incidence of HF.
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The laboratory mouse has provided tremendous insight to the underpinnings of mammalian central nervous system physiology. In recent years, it has become possible to image single neurons, glia and vascular cells in vivo by using head-fixed preparations combined with cranial windows to study local networks of activity in the living brain. Such approaches have also succeeded without the use of general anesthesia providing insights to the natural behaviors of the central nervous system. However, the same has not yet been developed for the eye, which is constantly in motion. Here we characterize a novel head-fixed preparation that enables high-resolution adaptive optics retinal imaging at the single-cell level in awake-behaving mice. We reveal three new functional attributes of the normal eye that are overlooked by anesthesia: 1) High-frequency, low-amplitude eye motion of the mouse that is only present in the awake state 2) Single-cell blood flow in the mouse retina is reduced under anesthesia and 3) Mouse retinae thicken in response to ketamine/xylazine anesthesia. Here we show key benefits of the awake-behaving preparation that enables study of retinal physiology without anesthesia to study the normal retinal physiology in the mouse.
Subject(s)
Ketamine , Wakefulness , Mice , Animals , Wakefulness/physiology , Retina/diagnostic imaging , Retina/physiology , Ketamine/pharmacology , Diagnostic Imaging , Xylazine/pharmacology , MammalsABSTRACT
JPEG compression will cause severe distortion to the shared compressed image, which brings great challenges to extracting messages correctly from the stego image. To address such challenges, we propose a novel end-to-end robust data hiding scheme for JPEG images. The embedding and extracting secret messages on the quantized discrete cosine transform (DCT) coefficients are implemented by the bi-directional process of the invertible neural network (INN), which can provide intrinsic robustness against lossy JPEG compression. We design a JPEG compression attack module to simulate the JPEG compression process, which helps the network automatically learn how to recover the secret message from JPEG compressed image. Experimental results have demonstrated that our method achieves strong robustness against lossy JPEG compression, and also significantly improves the security compared with the existing data hiding methods on the premise of ensuring image quality and high capacity. For example, the detection error of our method against XuNet has been increased by 3.45% over the existing data hiding methods.
Subject(s)
Data Compression , Data Compression/methods , Neural Networks, ComputerABSTRACT
Parametrial infiltration (PMI) is an essential factor in staging and planning treatment of cervical cancer. The purpose of this study was to develop a radiomics model for accessing PMI in patients with IB-IIB cervical cancer using features from 18 F-fluorodeoxy glucose (18 F-FDG) positron emission tomography (PET)/MR images. In this retrospective study, 66 patients with International Federation of Gynecology and Obstetrics stage IB-IIB cervical cancer (22 with PMI and 44 without PMI) who underwent 18 F-FDG PET/MRI were divided into a training dataset (n = 46) and a testing dataset (n = 20). Features were extracted from both the tumoral and peritumoral regions in 18 F-FDG PET/MR images. Single-modality and multimodality radiomics models were developed with random forest to predict PMI. The performance of the models was evaluated with F1 score, accuracy, and area under the curve (AUC). The Kappa test was used to observe the differences between PMI evaluated by radiomics-based models and pathological results. The intraclass correlation coefficient for features extracted from each region of interest (ROI) was measured. Three-fold crossvalidation was conducted to confirm the diagnostic ability of the features. The radiomics models developed by features from the tumoral region in T2 -weighted images (F1 score = 0.400, accuracy = 0.700, AUC = 0.708, Kappa = 0.211, p = 0.329) and the peritumoral region in PET images (F1 score = 0.533, accuracy = 0.650, AUC = 0.714, Kappa = 0.271, p = 0.202) achieved the best performances in the testing dataset among the four single-ROI radiomics models. The combined model using features from the tumoral region in T2 -weighted images and the peritumoral region in PET images achieved the best performance (F1 score = 0.727, accuracy = 0.850, AUC = 0.774, Kappa = 0.625, p < 0.05). The results suggest that 18 F-FDG PET/MRI can provide complementary information regarding cervical cancer. The radiomics-based method integrating features from the tumoral and peritumoral regions in 18 F-FDG PET/MR images gave a superior performance for evaluating PMI.
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BACKGROUND: The pathogenesis of depression is complex, with the brain's reward system likely to play an important role. The nucleus accumbens (NAc) is a key region in the brain that integrates reward signals. Lipopolysaccharides (LPS) can induce depressive-like behaviors and enhance neuroplasticity in NAc, but the underlying mechanism is still unknown. We previously found that eukaryotic translation initiation factor A1 (eIF5A1) acts as a ribosome-binding protein to regulate protein translation and to promote neuroplasticity. METHODS: In the present study, LPS was administered intraperitoneally to rats and the expression and cellular location of eIF5A1 was then investigated by RT-PCR, Western blotting and immunofluorescence. Subsequently, a neuron-specific lentivirus was used to regulate eIF5A1 expression in vivo and in vitro. Neuroplasticity was then examined by Golgi staining and by measurement of neuronal processes. Finally, proteomic analysis was used to identify proteins regulated by eIF5A1. RESULTS: The results showed that eIF5A1 expression was significantly increased in the NAc neurons of LPS rats. Following the knockdown of eIF5A1 in NAc neurons, the LPS-induced increases in neuronal arbors and spine density were significantly attenuated. Depression-like behaviors were also reduced. Neurite outgrowth of NAc neurons in vitro also increased or decreased in parallel with the increase or decrease in eIF5A1 expression, respectively. The proteomic results showed that eIF5A1 regulates the expression of many neuroplasticity-related proteins in neurons. CONCLUSIONS: These results confirm that eIF5A1 is involved in LPS-induced depression-like behavior by increasing neuroplasticity in the NAc. Our study also suggests the brain's reward system may play an important role in the pathogenesis of depression.
Subject(s)
Depression , Nucleus Accumbens , Peptide Initiation Factors , Animals , Rats , Depression/chemically induced , Lipopolysaccharides , Neuronal Plasticity , Proteomics , Peptide Initiation Factors/genetics , Eukaryotic Translation Initiation Factor 5AABSTRACT
BACKGROUND@#Epidemiological surveys on heart failure (HF) in Chinese community are relatively lacking. This study aimed to estimate the prevalence and incidence of HF among community residents in southern China.@*METHODS@#Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged ≥ 35 years in Guangzhou, China. The same survey process was carried out for individuals aged ≥ 65 years after a three-year follow-up.@*RESULTS@#The overall prevalence of HF in community residents aged ≥ 35 years was 1.06%. Male had significantly higher risk of HF prevalence [odds ratio (OR) = 1.50, P = 0.027]. The gender-adjusted risk of HF was 1.48 times higher per 10 years aging. HF prevalence was statistically associated with atrial fibrillation, valvular heart disease, hypertension and chronic obstructive pulmonary disease after adjusting for age and gender (OR = 8.30, 5.17, 1.11, 2.28, respectively; all P < 0.05). HF incidence in individuals aged ≥ 65 years were 847 per 100,000 person-years. Baseline atrial fibrillation, valvular heart disease, and diabetes mellitus were risk factors for HF incidence for individuals aged ≥ 65 years adjusting for age and gender (OR = 5.05, 3.99, 2.11, respectively; all P < 0.05). Besides, residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF (OR = 14.41, 8.54, respectively; all P < 0.05).@*CONCLUSIONS@#Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China. Management of related cardiovascular diseases may be helpful to reduce the incidence of HF.
ABSTRACT
Background: White matter hyperintensities (WMHs) are a subtype of cerebral small vessel disease and can be divided into periventricular WMHs (pvWMHs) and deep WMHs (dWMHs). pvWMHs and dWMHs were proved to be determined by different etiologies. This study aimed to develop a 2D Cascade U-net (Cascade U) for the segmentation and differentiation of pvWMHs and dWMHs on 2D T2-FLAIR images. Methods: A total of 253 subjects were recruited in the present study. All subjects underwent 2D T2-FLAIR scan on a 3.0 Tesla MR scanner. Both contours of pvWMHs and dWMHs were manually delineated by the observers and considered as the gold standard. Fazekas scale was used to evaluate the burdens of pvWMHs and dWMHs, respectively. Cascade U consisted of a segmentation U-net and a differentiation U-net and was trained with a combined loss function. The performance of Cascade U was compared with two other U-net models (Pipeline U and Separate U). Dice similarity coefficient (DSC), Matthews correlation coefficient (MCC), precision, and recall were used to evaluate the performances of all models. The linear correlations between WMHs volume (WMHV) measured by all models and the gold standard were also conducted. Results: Compared with other models, Cascade U exhibited a better performance on WMHs segmentation and pvWMHs identification. Cascade U achieved DSC values of 0.605 ± 0.135, 0.517 ± 0.263, and 0.510 ± 0.241 and MCC values of 0.617 ± 0.122, 0.526 ± 0.263, and 0.522 ± 0.243 on the segmentation of total WMHs, pvWMHs, and dWMHs, respectively. Cascade U exhibited strong correlations with the gold standard on measuring WMHV (R2 = 0.954, p < 0.001), pvWMHV (R2 = 0.933, p < 0.001), and dWMHV (R2 = 0.918, p < 0.001). A significant correlation was found on lesion volume between Cascade U and gold standard (r > 0.510, p < 0.001). Conclusion: Cascade U showed competitive results in segmentation and differentiation of pvWMHs and dWMHs on 2D T2-FLAIR images, indicating potential feasibility in precisely evaluating the burdens of WMHs.
ABSTRACT
The tsRNAs (tRNA-derived small RNAs) are new types of small noncoding RNAs derived from tRNAs. Gliomas are well-known malignant brain tumors. The study focused on tsRNA characterizations within gliomas. Datasets processing, bioinformatics analyses, and visualizations were performed with the packages of Python and R. Cell proliferations were demonstrated via CCK8 assays and colony formation assays, and in vivo xenograft experiments. Dual-luciferase reporter assay was performed to confirm the binding of tsRNA with its targets. Via using bioinformatics approaches, the hundreds of tsRNAs with available expression abundance were identified in gliomas dataset, most of them derived from D-loop or T-loop fragments of tRNAs. Among tsRNAs derived from tRNA-Cys-GCA, tRFdb-3003a and tRFdb-3003b (tRFdb-3003a/b) were remarkably down-regulated in gliomas. The survival outcome of gliomas patients with low tRFdb-3003a/b expressions was notably worse than that of high-expression patients. In glioma cells, tRFdb-3003a could suppress cells proliferation and colony formation ability. In vivo, tRFdb-3003a suppressed the tumor growth of xenograft gliomas. Enrichment analyses displayed the tRFdb-3003a-related mRNAs were enriched in the specific GO terms, spliceosome and autophagy pathways, and three GSEA molecular signatures. Mechanically, 3'-UTR regions of VAV2 mRNA were predicted to contain the binding positions of tRFdb-3003a/b, tRFdb-3003a and tRFdb-3003b was effective to reduce the relative luciferase activity of cells with VAV2 wild-type reporter. Overexpression of tRFdb-3003a/b could down-regulated the expression levels of VAV2 protein and mRNA in glioma cells. The tRNA-Cys-GCA derived tRFdb-3003a and tRFdb-3003b might act as key player in tumor progressions of gliomas; tRFdb-3003a/b might directly bind to VAV2 and regulate VAV2 expressions in gliomas.