ABSTRACT
Based on the polynomial theory, the error propagation characteristics of the widely used N-step discrete Fourier transform (N-DFT) phase-shift algorithm were analyzed via theoretical analysis, under the effect of Gamma distortion and phase detuning. The results showed that the N-DFT algorithm could not simultaneously suppress both types of error. A robust linear phase-shift (RLPS) algorithm was designed, the performance of the RLPS and 8-DFT algorithms in terms of spectral response, detuning robustness, and G S / N was briefly analysis by Manuel Servin method. The Simulation analysis and comparison of the results show that the RLPS algorithm could suppress both types of error simultaneously, which exhibited better stability and accuracy than N-DFT and exponential algorithms, particularly in gradient measurement stability, peak-to-valley (PV) and root-mean-square (RMS) error suppression. Moreover, a physical experiment apparatus was built to test unidirectionally inclined plane mirror and concave mirror using the RLPS, N-DFT, and exponential algorithms. The results showed that the RLPS algorithm could significantly improve the measurement stability and accuracy in the presence of detuning and without screen Gamma calibration.
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The aim of this study was to investigate the effect of hesperidin on the liver and kidney dysfunctions induced by nickel. The mice were divided into six groups: nickel treatment with 80 mg/kg, 160 mg/kg, 320 mg/kg hesperidin groups, 0.5% CMC-Na group, nickel group, and blank control group. Histopathological techniques, biochemistry, immunohistochemistry, and the TUNEL method were used to study the changes in structure, functions, oxidative injuries, and apoptosis of the liver and kidney. The results showed that hesperidin could alleviate the weight loss and histological injuries of the liver and kidney induced by nickel, and increase the levels of lactate dehydrogenase (LDH), alanine aminotransferase (GPT), glutamic oxaloacetic transaminase (GOT) in liver and blood urea nitrogen (BUN), creatinine (Cr) and N-acetylglucosidase (NAG) in kidney. In addition, hesperidin could increase the activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) in the liver and kidney, decrease the content of malondialdehyde (MDA) and inhibit cell apoptosis. It is suggested that hesperidin could help inhibit the toxic effect of nickel on the liver and kidney.
ABSTRACT
The disruption of circadian rhythms (CRs) has been linked to metabolic disorders, yet the role of hepatic BMAL1, a key circadian regulator, in the whole-body metabolism and the associated lipid metabolic phenotype in the liver remains unclear. Bmal1 floxed (Bmal1f/f) and hepatocyte-specific Bmal1 knockout (Bmal1hep-/-) C57BL/6J mice underwent a regular feeding regimen. Hepatic CR, lipid content, mitochondrial function, and systemic metabolism were assessed at zeitgeber time (ZT) 0 and ZT12. Relevant molecules were examined to elucidate the metabolic phenotype. Hepatocyte-specific knockout of Bmal1 disrupted the expression of rhythmic genes in the liver. Bmal1hep-/- mice exhibited decreased hepatic TG content at ZT0, primarily due to enhanced lipolysis, reduced lipogenesis, and diminished lipid uptake. The ß-oxidation function of liver mitochondria decreased at both ZT0 and ZT12. Our findings on the metabolic profile and associated hepatic lipid metabolism in the absence of Bmal1 in hepatocytes provides new insights into metabolic syndromes from the perspective of liver CR disturbances.
Subject(s)
ARNTL Transcription Factors , Circadian Rhythm , Hepatocytes , Lipid Metabolism , Liver , Mice, Inbred C57BL , Mice, Knockout , Animals , ARNTL Transcription Factors/genetics , ARNTL Transcription Factors/metabolism , Lipid Metabolism/genetics , Mice , Liver/metabolism , Circadian Rhythm/genetics , Hepatocytes/metabolism , Phenotype , Male , Metabolome , Gene Deletion , Lipogenesis/geneticsABSTRACT
Pseudomonas aeruginosa is one of the most common pathogens causing hemorrhagic pneumonia in Chinese forest musk deer. Multidrug-resistant P. aeruginosa is frequently isolated from the lungs of affected musk deer in Shaanxi Province, China. With the increasing bacterial drug resistance, commonly used antibiotics have shown limited efficacy against drug-resistant P. aeruginosa. Therefore, phages have garnered attention as a promising alternative to antibiotics among researchers. In this study, phages vB_PaeP_YL1 and vB_PaeP_YL2 (respectively referred to as YL1 and YL2) were isolated from mixed sewage samples from a farm. YL1 and YL2 exhibit an icosahedral head and a non-contractile short tail, belonging to the Podoviridae family. Identification results demonstrate good tolerance to low temperatures and pH levels, with minimal variation in potency within 30 min of UV irradiation. The MOI for both YL1 and YL2 was 0.1, and their one-step growth curve latent periods were 10 min and 20 min, respectively. Moreover, both single phage and phage cocktail effectively inhibited the growth of the host bacteria in vitro, with the phage cocktail showing superior inhibitory effects compared to the single phage. YL1 and YL2 possess double-stranded DNA genomes, with YL1 having a genome size of 72,187 bp and a total G + C content of 55.02%, while YL2 has a genome size of 72,060 bp and a total G + C content of 54.98%. YL1 and YL2 are predicted to have 93 and 92 open reading frames (ORFs), respectively, and no ORFs related to drug resistance or lysogeny were found in both phages. Genome annotation and phylogenetic analysis revealed that YL1 is closely related to vB_PaeP_FBPa1 (ON857943), while YL2 is closely related to vB_PaeP_FBPa1 (ON857943) and Phage26 (NC041907). In a mouse model of hemorrhagic pneumonia, phage cocktail treatment showed better control of the disease and significantly reduced lung bacterial load compared to single phage treatment. Therefore, YL1 and YL2 have the potential for the prevention and treatment of multidrug-resistant P. aeruginosa infections.
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Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly transmissible disease of significant concern in the pig industry. Previous studies have demonstrated that the XM-2020 strain (a lineage 1.8 PRRSV IA/2012/NADC30) can induce special hemorrhagic injury in the small intestines. However, the specific mechanism underlying this injurious effect remains incompletely understood. In this study, we examined the pathogenic properties of XM-2020 and YC-2020 strains (a lineage 1.5 PRRSV IA/2014/NADC34) in piglets. Animal pathogenic tests revealed that with either Lineage 1 PRRSVs strains XM-2020 or YC-2020 demonstrated pronounced intestinal hemorrhage and suppression of peripheral immunological organs, comparing to JXA1 infection. Transcriptome analysis of diseased small intestines unveiled that PRRSV infection stimulated oxidative and inflammatory reactions. Remarkably, we also observed activation of the complement system alongside a notable down-regulation of complement and coagulation cascade pathways in the Lineage 1 PRRSVs infection group. Based on these findings, we propose that the primary mechanism driving the hemorrhagic injury of the small intestine caused by Lineage 1 PRRSVs is the suppression of complement and coagulation cascades resulting from immunosuppression. This discovery deepens our understanding of the pathogenicity of PRRSV in the small intestine and provides promising ways out for the development of innovative strategies aimed at controlling PRRSV.
Subject(s)
Complement System Proteins , Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Animals , Swine , Complement System Proteins/immunology , Complement System Proteins/metabolism , Porcine respiratory and reproductive syndrome virus/pathogenicity , Porcine Reproductive and Respiratory Syndrome/virology , Porcine Reproductive and Respiratory Syndrome/pathology , Blood Coagulation , Intestine, Small/virology , Intestine, Small/pathology , Intestines/virology , Intestines/pathology , Gene Expression Profiling , HemorrhageABSTRACT
The leaching process of uranium tailings is a typical water-rock interaction. The release of 226Ra from uranium tailings depends on the nuclides outside the intrinsic properties of uranium tailings on the one hand, and is influenced by the water medium on the other. In this paper, a uranium tailings repository in southern China was used as a research object, and uranium tailings at different depths were collected by drilling samples and mixed to analyze the 226Ra occurrence states. Static dissolution leaching experiments of 226Ra under different pH conditions, solid-liquid ratio conditions, and ionic strength conditions were carried out, and the adsorption and desorption behaviours of 226Ra in five representative stratigraphic media were investigated. The results show that 226Ra has a strong adsorption capacity in representative strata, with adsorption distribution coefficient Kd values ranging from 1.07E+02 to 1.29E+03 (mL/g) and desorption distribution coefficients ranging from 4.97E+02 to 2.71E+03 (mL/g), but the adsorption is reversible. The 226Ra in uranium tailings exists mainly in the residual and water-soluble states, and the release of 226Ra from uranium tailings under different conditions is mainly from the water-soluble and exchangeable state fractions. Low pH conditions, low solid-liquid ratio conditions and high ionic strength conditions are favourable to the release of 226Ra from uranium tailings, so the release of 226Ra from uranium tailings can be reduced by means of adjusting the pH in the tailings and setting up a water barrier. The results of this research have important guiding significance for the management of existing uranium tailings ponds and the control of 226Ra migration in groundwater, which is conducive to guaranteeing the long-term safety, stability and sustainability of uranium mining sites.
Subject(s)
Radium , Uranium , Uranium/chemistry , Adsorption , Radium/analysis , Radium/chemistry , China , Soil Pollutants, Radioactive/analysis , Radiation Monitoring , Mining , Water Pollutants, Radioactive/chemistry , Water Pollutants, Radioactive/analysisABSTRACT
BACKGROUND: Previous literature has explored the relationship between chronic atrophic gastritis (CAG) and isolated cancers within the upper gastrointestinal cancers; However, an integrative synthesis across the totality of upper gastrointestinal cancers was conspicuously absent. The research objective was to assess the relationship between CAG and the risk of incident upper gastrointestinal cancers, specifically including gastric cancer, oesophageal cancer, and oesophagogastric junction cancer. METHODS: Rigorous systematic searches were conducted across three major databases, namely PubMed, Embase and Web of Science, encompassing the timeline from database inception until August 10, 2023. We extracted the necessary odds ratio (OR) and their corresponding 95% confidence interval (CI) for subsequent meta-analysis. Statistical analyses were conducted using Stata 17.0 software. RESULTS: This meta-analysis included a total of 23 articles encompassing 5858 patients diagnosed with upper gastrointestinal cancers. CAG resulted in a statistically significant 4.12-fold elevated risk of incident gastric cancer (OR = 4.12, 95% CI 3.20-5.30). Likewise, CAG was linked to a 2.08-fold increased risk of incident oesophageal cancer (OR = 2.08, 95%CI 1.60-2.72). Intriguingly, a specific correlation was found between CAG and the risk of incident oesophageal squamous cell carcinoma (OR = 2.29, 95%CI 1.77-2.95), while no significant association was detected for oesophageal adenocarcinoma (OR = 0.62, 95%CI 0.17-2.26). Moreover, CAG was correlated with a 2.77-fold heightened risk of oesophagogastric junction cancer (OR = 2.77, 95%CI 2.21-3.46). Notably, for the same type of upper gastrointestinal cancer, it was observed that diagnosing CAG through histological methods was linked to a 33-77% higher risk of developing cancer compared to diagnosing CAG through serological methods. CONCLUSION: This meta-analysis indicated a two- to fourfold increased risk of gastric cancer, oesophageal cancer, and oesophagogastric junction cancer in patients with CAG. Importantly, for the same upper gastrointestinal cancer, the risk of incident cancer was higher when CAG was diagnosed histologically compared to serological diagnosis. Further rigorous study designs are required to explore the impact of CAG diagnosed through both diagnostic methods on the risk of upper gastrointestinal cancers.
Subject(s)
Gastritis, Atrophic , Gastrointestinal Neoplasms , Humans , Gastritis, Atrophic/complications , Gastritis, Atrophic/epidemiology , Risk Factors , Gastrointestinal Neoplasms/epidemiology , Gastrointestinal Neoplasms/pathology , Chronic Disease , Incidence , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/pathology , Stomach Neoplasms/epidemiology , Stomach Neoplasms/pathology , Male , Odds Ratio , Female , Publication BiasABSTRACT
A pterygium is a wedge-shaped fibrovascular growth of the conjunctiva membrane that extends onto the cornea, which is the outer layer of the eye. It is also known as surfer's eye. Growth of a pterygium can also occur on the either side of the eye, attaching firmly to the sclera. Pterygia are one of the world's most common ocular diseases. However, the pathogenesis remains unsolved to date. As the pathogenesis of pterygium is closely related to finding the ideal treatment, a clear understanding of the pathogenesis will lead to better treatment and lower the recurrence rate, which is notably high and more difficult to treat than a primary pterygium. Massive studies have recently been conducted to determine the exact causes and mechanism of pterygia. We evaluated the pathogenetic factors ultraviolet radiation, viral infection, tumor suppressor genes p53, growth factors, oxidative stress, apoptosis and neuropeptides in the progression of the disease. The heightened expression of TRPV1 suggests its potential contribution in the occurrence of pterygium, promoting its inflammation and modulating sensory responses in ocular tissues. Subsequently, the developmental mechanism of pterygium, along with its correlation with dry eye disease is proposed to facilitate the identification of pathogenetic factors for pterygia, contributing to the advancement of understanding in this area and may lead to improved surgical outcomes.
Subject(s)
Pterygium , Pterygium/etiology , Pterygium/metabolism , Humans , Risk Factors , Oxidative Stress , Ultraviolet Rays/adverse effects , Apoptosis , Conjunctiva/pathologyABSTRACT
Low rate distributed denial of service attack (LR-DDoS) is a special type of distributed denial of service (DDoS) attack, which uses the vulnerability of HTTP protocol to send HTTP requests to applications or servers at a slow speed, resulting in long-term occupation of server threads and affecting the normal access of legitimate users. Since LR-DDoS attacks do not need to send flooding or a large number of HTTP requests, it is difficult for traditional intrusion detection methods to detect such attacks, especially when HTTP traffic is encrypted. To overcome the above problems, we proposed an encrypted LR-DDoS attack detection and mitigation method based on the multi-granularity feature fusion (MFFLR-DDoS) for software defined networking (SDN). This method analyzes the encrypted session flow from the time sequence of packets and the spatiality of session flow and uses different deep learning methods to extract features, to obtain more effective features for abnormal traffic detection. In addition, we used the advantages of SDN architecture to perform real-time defense against LR-DDoS attacks by the way of SDN controller issuing flow rules. The experimental results showed that the MFFLR-DDoS model had a higher detection rate than advanced methods, and could mitigate LR-DDoS attack traffic online and in real-time.
ABSTRACT
Detecting changes in the dynamics of secreted proteins in serum has been a challenge for proteomics. Enter secreted protein database (SEPDB), an integrated secretory proteomics database offering human, mouse and rat secretory proteomics datasets collected from serum, exosomes and cell culture media. SEPDB compiles secreted protein information from secreted protein database, UniProt and Human Protein Atlas databases to annotate secreted proteomics data based on protein subcellular localization and disease markers. SEPDB integrates the latest predictive modeling techniques to measure deviations in the distribution of signal peptide structures of secreted proteins, extends signal peptide sequence prediction by excluding transmembrane structural domain proteins and updates the validation analysis pipeline for secreted proteins. To establish tissue-specific profiles, we have also created secreted proteomics datasets associated with different human tissues. In addition, we provide information on heterogeneous receptor network organizational relationships, reflective of the complex functional information inherent in the molecular structures of secreted proteins that serve as ligands. Users can take advantage of the Refreshed Search, Analyze, Browse and Download functions of SEPDB, which is available online at https://sysomics.com/SEPDB/. Database URL: https://sysomics.com/SEPDB/.
Subject(s)
Proteins , Proteomics , Animals , Mice , Rats , Humans , Databases, Protein , Proteins/chemistry , Proteomics/methods , Protein Sorting SignalsABSTRACT
Bacterial wilt is the leading disease of sesame and alters the bacterial community composition, function, and metabolism of sesame rhizosphere soil. However, its pattern of change is unclear. Here, the purpose of this study was to investigate how these communities respond to three differing severities of bacterial wilt in mature continuously cropped sesame plants by metagenomic and metabolomic techniques, namely, absence (WH), moderate (WD5), and severe (WD9) wilt. The results indicated that bacterial wilt could significantly change the bacterial community structure in the rhizosphere soil of continuously cropped sesame plants. The biomarker species with significant differences will also change with increasing disease severity. In particular, the gene expression levels of Ralstonia solanacearum in the WD9 and WD5 treatments increased by 25.29% and 33.61%, respectively, compared to those in the WH treatment (4.35â¯log10 copies g-1). The occurrence of bacterial wilt significantly altered the functions of the bacterial community in rhizosphere soil. KEEG and CAZy functional annotations revealed that the number of significantly different functions in WH was greater than that in WD5 and WD9. Bacterial wilt significantly affected the relative content of metabolites, especially acids, in the rhizosphere soil, and compared with those in the rhizosphere soil from WH, 10 acids (including S-adenosylmethionine, N-acetylleucine, and desaminotyrosine, etc.) in the rhizosphere soil from WD5 or WD9 significantly increased. In comparison, the changes in the other 10 acids (including hypotaurine, erucic acid, and 6-hydroxynicotinic acid, etc.) were reversed. The occurrence of bacterial wilt also significantly inhibited metabolic pathways such as ABC transporter and amino acid biosynthesis pathways in rhizosphere soil and had a significant impact on two key enzymes (1.1.1.11 and 2.6.1.44). In conclusion, sesame bacterial wilt significantly alters the rhizosphere soil bacterial community structure, function, and metabolites. This study enhances the understanding of sesame bacterial wilt mechanisms and lays the groundwork for future prevention and control strategies against this disease.
Subject(s)
Sesamum , Soil , Soil/chemistry , Rhizosphere , Soil Microbiology , Biodiversity , Bacteria/geneticsABSTRACT
Background: The associations of two novel inflammation biomarkers, systemic inflammation response index (SIRI) and systemic immune inflammation index (SII), with mortality risk in patients with chronic heart failure (CHF) are not well-characterized. Methods: This retrospective cohort study included patients with CHF in two medical centers of Chinese People's Liberation Army General Hospital, Beijing, China. The outcomes of this study included in-hospital mortality and long-term mortality. Associations of SIRI and SII with mortality were assessed using multivariable regressions and receiver operating characteristic (ROC) analyses. Results: A total of 6232 patients with CHF were included in the present study. We documented 97 cases of in-hospital mortality and 1738 cases of long-term mortality during an average 5.01-year follow-up. Compared with patients in the lowest quartile of SIRI, those in the highest quartile exhibited 134% higher risk of in-hospital mortality (adjusted odds ratio, 2.34; 95% confidence interval [CI], 1.16-4.72) and 45% higher risk of long-term mortality (adjusted hazard ratio, 1.45; 95% CI, 1.25-1.67). Compared with patients in the lowest quartile of SII, those in the highest quartile exhibited 27% higher risk of long-term mortality (adjusted hazard ratio, 1.27; 95% CI, 1.11-1.46). In ROC analyses, SIRI showed better prognostic discrimination than C-reactive protein (area under the curve: 69.39 vs 60.91, P = 0.01, for in-hospital mortality; 61.82 vs 58.67, P = 0.03, for 3-year mortality), whereas SII showed similar prognostic value with C-reactive protein. Conclusion: SIRI and SII were significantly associated with mortality risk in patients with CHF. SIRI may provide better prognostic discrimination than C-reactive protein.
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Fungal keratitis (FK) is a dangerous corneal infection that is common in tropical and subtropical areas. Its incidence is extremely high, and ocular trauma and contact lenses can lead to FK, but its common treatment such as using topical antifungal eye drop instillation is often less effective because of several drawbacks of the drugs typically used, including limited ocular penetration, high frequency of dosing, poor biocompatibility, and the potential for severe drug reactions. Therefore, the development of novel drug delivery devices for the treatment of FK is urgent. The urgent need for novel drug delivery devices to treat FK has led to the development of several techniques, including nanoparticles (NPs), in situ forming hydrogels, contact lenses, and microneedles (MNs). However, it is important to note that the main mechanisms differ between these techniques. NPs can transport large amounts of drugs and be taken up by cells owing to their large surface area and small size. In situ forming hydrogels can significantly extend the residence time of drugs because of their strong adhesive properties. Contact lenses, with their comfortable shape and drug-carrying capacity, can also act as drug delivery devices. MNs can create channels in the cornea, bypassing its barrier and enhancing drug bioavailability. This article will go over novel medication delivery techniques for treating FK and make a conclusion about their advantages and limitations in anticipation to serve the best option for the individual therapy of FK.
Subject(s)
Corneal Ulcer , Eye Infections, Fungal , Keratitis , Humans , Corneal Ulcer/drug therapy , Drug Delivery Systems/methods , Keratitis/drug therapy , Keratitis/microbiology , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/microbiology , HydrogelsABSTRACT
BACKGROUND: Patients with diabetes mellitus (DM) caused by obesity have increased in recent years. The impact of obesity on long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) with or without DM remains unclear. METHODS: We retrospectively analysed data from 1918 patients who underwent PCI. Patients were categorized into four groups based on body mass index (BMI, normal weight: BMI < 25 kg/m2; overweight and obese: BMI ≥ 25 kg/m2) and DM status (presence or absence). The primary endpoint was the occurrence of major adverse cardiac and cerebrovascular events (MACCE; defined as all-cause death, myocardial infarction, stroke, and unplanned repeat revascularization). RESULTS: During a median follow-up of 7.0 years, no significant differences in MACCE, myocardial infarction, or stroke were observed among the four groups. Overweight and obese individuals exhibited lower all-cause mortality rates compared with normal-weight patients (without DM: hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.37 to 0.78; with DM: HR: 0.57, 95% CI: 0.38 to 0.86). In non-diabetic patients, the overweight and obese group demonstrated a higher risk of unplanned repeat revascularization than the normal-weight group (HR:1.23, 95% CI:1.03 to 1.46). After multivariable adjustment, overweight and obesity were not significantly associated with MACCE, all-cause death, myocardial infarction, stroke, or unplanned repeat revascularization in patients with and without diabetes undergoing PCI. CONCLUSION: Overweight and obesity did not demonstrate a significant protective effect on long-term outcomes in patients with and without diabetes undergoing PCI.
Subject(s)
Coronary Artery Disease , Diabetes Mellitus , Myocardial Infarction , Percutaneous Coronary Intervention , Stroke , Humans , Overweight , Retrospective Studies , Body Mass Index , Percutaneous Coronary Intervention/adverse effects , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Myocardial Infarction/etiology , Obesity/complications , Obesity/diagnosis , Stroke/diagnosis , Stroke/epidemiology , Stroke/complications , Treatment Outcome , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Coronary Artery Disease/complicationsABSTRACT
BACKGROUND: The use of histogram analysis of computed tomography (CT) values is a potential method for differentiating between benign osteoblastic lesions (BOLs) and malignant osteoblastic lesions (MOLs). PURPOSE: To explore the diagnostic efficacy of histogram analysis in accurately distinguishing between BOLs and MOLs based on CT values. MATERIAL AND METHODS: A total of 25 BOLs and 25 MOLs, which were confirmed through pathology or imaging follow-up, were included in this study. FireVoxel software was used to process the lesions and obtain various histogram parameters, including mean value, standard deviation, variance, coefficient of variation, skewness, kurtosis, entropy value, and percentiles ranging from 1st to 99th. Statistical tests, such as two independent-sample t-tests and the Mann-Whitney U test with Bonferroni correction, were employed to compare the differences in histogram parameters between BOLs and MOLs. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of each parameter. RESULTS: Significant differences were observed in several histogram parameters between BOLs and MOLs, including the mean value, coefficient of variation, skewness, and various percentiles. Notably, the 25th percentile demonstrated the highest diagnostic efficacy, as indicated by the largest area under the curve in the ROC curve analysis. CONCLUSION: Histogram analysis of CT values provides valuable diagnostic information for accurately differentiating between BOLs and MOLs. Among the different parameters, the 25th percentile parameter proves to be the most effective in this discrimination process.
Subject(s)
Bone Neoplasms , Tomography, X-Ray Computed , Humans , Diagnosis, Differential , Tomography, X-Ray Computed/methods , Female , Male , Bone Neoplasms/diagnostic imaging , Middle Aged , Adult , Aged , Adolescent , Young Adult , Retrospective StudiesABSTRACT
Short-chain fatty acids (SCFAs), particularly propionate and butyrate, have been reported in many cancers. However, the relationship between propionate and acute myeloid leukemia (AML) remains unclear. Additionally, Acyl-CoA synthetase long chain family member 4 (ACSL4) has been reported to regulate immunity in solid tumors, but there are still many gaps to be filled in AML. Here, we discovered the underlying mechanism of propionate and ACSL4-mediated ferroptosis for immunotherapy. Our results showed that the level of propionate in the AML patients' feces was decreased, which was correlated to gut microbiota dysbiosis. Moreover, we demonstrated that propionate suppressed AML progression both in vivo and in vitro. In mechanism, propionate induced AML cells apoptosis and ferroptosis. The imbalance of reactive oxygen species (ROS) and redox homeostasis induced by propionate caused mitochondrial fission and mitophagy, which enhanced ferroptosis and apoptosis. Furthermore, ACSL4-mediated ferroptosis caused by propionate increased the immunogenicity of AML cells, induced the release of damage-associated molecular patterns (DAMPs), and promoted the maturation of dendritic cells (DCs). The increased level of immunogenicity due to ferroptosis enable propionate-based whole-cell vaccines to activate immunity, thus further facilitating effective killing of AML cells. Collectively, our study uncovers a crucial role for propionate suppresses AML progression by inducing ferroptosis and the potential mechanisms of ACSL4-mediated ferroptosis in the regulation of AML immunity.
Subject(s)
Ferroptosis , Leukemia, Myeloid, Acute , Humans , Propionates/pharmacology , Mitophagy , Apoptosis , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathologyABSTRACT
In China, several problems were common in the telemedicine systems, such as the poor network stability and difficult interconnection. A new telemedicine system jointly driven by multinetwork integration and remote control has been designed to address these problems. A multilink aggregation algorithm and an overlay network for telemedicine system (ONTMS) were developed to improve network stability, and a non-intervention remote control method was designed for Internet of Things (IoT) devices/systems. The authors monitored the network parameters, and distributed the questionnaire to participants, for evaluating the telemedicine system and services. Under a detection bandwidth of 8 Mbps, the aggregation parameters of Unicom 4G, Telecom 4G, and China Mobile 4G were optimal, with an uplink bandwidth, delay, and packet loss ratio (PLR) of 7.93 Mbps, 58.80 ms, and 0.06%, respectively. These parameters were significantly superior to those of China Mobile 4G, the best single network (p < 0.001). Through the ONTMS, the mean round-trip transporting delay from Beijing to Sanya was 76 ms, and the PLR was 0 at vast majority of time. A total of 1988 participants, including 1920 patients and 68 doctors, completed the questionnaires. More than 97% of participants felt that the audio and video transmission and remote control were fluent and convenient. 96% of patients rated the telemedicine services with scores of 4 or 5. This system has shown robust network property and excellent interaction ability, and satisfied the needs of patients and doctors.
ABSTRACT
Recent studies have shown a strong correlation between ambient fine particulate matter (PM2.5) exposure and diabetes risk, including abnormal lipid accumulation and systemic insulin resistance (IR). Hawthorn total flavonoids (HF) are the main groups of active substances in Hawthorn, which showed anti-hyperlipidemic and anti-hyperglycemic effects. Therefore, we hypothesized that HF may attenuate PM2.5-induced IR and abnormal lipid accumulation. Female C57BL/6 N mice were randomly assigned to the filtered air exposure (FA) group, concentrated PM2.5 exposure (PM) group, PM2.5 exposure maintained on a low-dose HF diet (LHF) group, and PM2.5 exposure maintained on a high-dose HF diet (HHF) group for an 8-week PM2.5 exposure using a whole-body exposure device. Body glucose homeostasis, lipid profiles in the liver and serum, and enzymes responsible for hepatic lipid metabolism were measured. We found that exposure to PM2.5 impaired glucose tolerance and insulin sensitivity. In addition, triacylglycerol (TAG) in serum elevated, whereas hepatic TAG levels were decreased after PM2.5 exposure, accompanied by inhibited fatty acid uptake, lipogenesis, and lipolysis in the liver. HF administration, on the other hand, balanced the hepatic TAG levels by increasing fatty acid uptake and decreasing lipid export, leading to alleviated systemic IR and hyperlipidemia in PM2.5-exposed mice. Therefore, HF administration may be an effective strategy to protect against PM2.5-induced IR and metabolic abnormalities of lipids.