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JOURNAL/nrgr/04.03/01300535-202502000-00027/figure1/v/2024-05-28T214302Z/r/image-tiff Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury. Low-density lipoprotein receptor, a classic cholesterol regulatory receptor, has been found to inhibit NLR family pyrin domain containing protein 3 (NLRP3) inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer's disease. However, little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke. To address this issue in the present study, we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models. First, we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis. We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation. Second, we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus. Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype. Finally, we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin, an NLRP3 agonist, restored the neurotoxic astrocyte phenotype. These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.
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Background: Most studies have indicated that peripheral insulin-like growth levels factor-1 (IGF-1) is valuable in diagnosing heart failure, although the results have been inconsistent. To help solve the debate, we performed a meta-analysis to explore the relationship between IGF-1 and heart failure (HF). Methods: We conducted an extensive search across various databases such as Embase, Cochrane Library, Pubmed, Medline, and Web of Science on May 30, 2023. From the extensive pool of studies, we selected 16 relevant articles, encompassing a total of 1,380 cases and 1,153 controls, to conduct a rigorous meta-analysis. Results: The total results indicated that there is an association between lower IGF-1 level and HF. The random-effects model yielded a pooled standardized mean difference (SMD) of -0.598 (95% CI: -1.081 to -0.116, P = 0.015). Further subgroup analysis also showed that IGF-1 levels were associated with HF in the age difference ≥5 years subgroup and body mass index difference >1 subgroup. Additionally, significant association between IGF-1 levels and HF were detected in the "serum" samples and "Europe" subgroups. Importantly, we observed IGF-1 showed significant lower levels in patients with reduced ejection fraction (HFrEF) compared to the controls, not in patients with preserved ejection fraction (HFpEF). The Begg's and Egger's tests revealed no indication of publication bias. Conclusions: Our meta-analysis has provided evidence suggesting a substantial correlation between reduced levels of IGF-1 and the occurrence of HF. Further prospective studies are necessary to ascertain the use of IGF-1 as a reliable biomarker for diagnosing HF, especially for HFrEF. But the diagnosis of HFpEF should be cautious.
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Significant pharmacokinetic variation occurs in critically ill patients, leading to underexposure to antibiotics and poor prognosis. In this study, we developed a simple, sensitive, and fast liquid chromatography tandem mass spectrometry (LCMS/MS) platform for the simultaneous quantification of 8 antibacterial and 2 antifungal drugs, which is optimally suited for clinically efficient, real-time therapeutic drug monitoring (TDM). Multiple reaction monitoring (MRM) mass spectrometry was used in this method, and samples were prepared via protein precipitation with methanol. Chromatographic separation was accomplished on a BGIU Column-U02 (2.1ï½50â¯mm, 3⯵m), with six stable isotopes and one analog as an internal standard. The overall turnaround time of the assay was 5â¯minutes. All the drugs tested (piperacillin, cefoperazone, meropenem, levofloxacin, moxifloxacin, daptomycin, linezolid, vancomycin, fluconazole and voriconazole) were linear in the test concentration range (r ≥ 0.9900), the accuracy was 95â¯%-111â¯%, the precision variation coefficient was greater than or equal to 10â¯%, the lower limit of quantitation was 0.31-7.51â¯mg/L, and the coefficient of variation of the matrix factor was less than 10â¯%. The recovery rates ranged from 85â¯% to 115â¯%, and the antibiotics were stable at 4°C and -20°C for 6 days, with an offset of greater than or equal to 15â¯%. This method was successfully applied to routine TDM in 252 elderly critically ill patients.
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Two Co(II) metal-organic frameworks (Co-MOFs), namely, [Co(DMTDC)(bimb)]n (Co-MOF-1) and {[Co(DPTDC)(bimb)(H2O)]·2DMF}n (Co-MOF-2) (H2DMTDC = 3,4-dimethylthieno[2,3-b]thiophene-2,5-dicarboxylic acid, H2DPTDC = 3,4-diphenylthieno[2,3-b]thiophene-2,5-dicarboxylic acid, bimb = 1,4-bis((1H-imidazol-1-yl)methyl)benzene), were obtained by the reaction of flexible N-containing ligand bimb and two structurally related thiophene-containing ligands H2DMTDC and H2DPTDC, respectively. These Co-MOFs displayed a 3D framework and porous structure, respectively. Co-MOF-1 and the activated sample Co-MOF-2' could act as green heterogeneous catalysts for the one-pot multicomponent Biginelli reaction, specifically the dehydration condensation process involving aldehydes, acetoacetates, and urea to yield dihydropyrimidin-2(1H)-ones. The reaction has advantages such as solvent-free conditions, water as only byproduct, readily accessible starting materials, excellent functional group compatibility, and simple operation. Both catalysts exhibited a wide substrate scope and maintained significant catalytic activity over five cycles. The special catalytic performance may be ascribed to functional groups within the ligand.
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OBJECTIVE: To investigate the effects of ligustrazine on neuropathic pain (NPP) in rats with sciatic nerve injury and to provide new scientific insight for broadening the clinical application of ligustrazine. METHODS: Human spinal cord cell line STR cells were transfected with TLR4-mimic or mimic negative control (mimic-NC). After transfection, the STR cells were treated with different concentrations of ligustrazine (0, 0.25, 0.5, 1, 2 µm) for 24 h or 48 h. Cell proliferation was detected by MTT assay and colony formation assay. A rat model was further constructed to evaluate mechanical and cold pain sensitivity behaviors by fiber mechanical stimulation and freezing spray. The extracellular fluids of medial prefrontal cortex (mPFC) and central amygdala (CeA) were collected by intracranial dual-site simultaneous microdialysis. The contents of glutamic acid (Glu), aspartate (Asp), glycine (Gly), and γ-aminobutyric acid (GABA) in extracellular fluids were detected by HPLC. RESULTS: Compared to the 0 µm group, ligustrazine concentration at 0.5 µm significantly decreased the relative cell viability of STR cells and promoted the cell apoptosis rate. Ligustrazine at 0.25 µm significantly reduced the colony number of STR cells (all P<0.05). Compared to the control group, 1 µM ligustrazine significantly increased the protein expression of Bax and cleaved caspase 3 in STR cells but decreased the protein expression of Bcl-2 (all P<0.001). Compared to the control group, 2 µM ligustrazine treatments significantly reduced the protein levels of TLR4 and p-Akt in STR cells (all P<0.001). However, 2 µM ligustrazine treatments did not change the protein expression of Akt (P>0.05). Compared to the control group, the level of TLR4 in STR cells transfected with TLR4-mimic was significantly increased (P<0.001). Compared to the control group, transfection of TLR4-mimic reversed the anti-proliferative and pro-apoptotic effects of ligustrazine on STR cells (all P<0.001). CONCLUSION: The analgesic effect of Ligustrazine on neuropathic pain caused by spinal cord injury may be related to its inhibition of the release of excitatory amino acid transmitters Glu and Gly through the TLR4/NF-κB pathway, regulation of the dynamic balance of excitatory and inhibitory amino acid neurotransmitters, and alleviation of the central sensitization effect caused by the excitotoxicity of Glu.
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T-2 toxin, a highly toxic trichothecene mycotoxin widely found in food and feed, poses a significant threat to human health as well as livestock and poultry industry. Liver, being a crucial metabolic organ, is particularly susceptible to T-2 toxin induced damage characterized by inflammation and oxidative stress. Despite the role of Sirtuin 5 (SIRT5) in mitigating liver injury has been confirmed, its specific impact on T-2 toxin induced liver injury remains to be elucidated. The objective of this study was to investigate the protective role of SIRT5 against T-2 toxin induced liver injury in mice. Following the oral administration of 1 mg/kg.bw of T-2 toxin for 21 consecutive days to SIRT5 knockout (SIRT5-/-) and wild-type (WT) male mice, liver assessments were conducted. Our findings demonstrated that aggravated hepatic pathological injury was observed in SIRT5-/- mice, accompanied by elevated malondialdehyde (MDA) and Fe levels, as well as enhanced expression of glutathione peroxidase 4 (GPX4), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, Gasdermin-D (GSDMD), tumour necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1ß). These results indicated that SIRT5 alleviated hepatic structural damage and dysfunction, while inhibiting oxidative stress, iron accumulation, and NLRP3 inflammasome activation. Analysis revealed a positive correlation among NLRP3 inflammasome activation, iron accumulation, and oxidative stress. Overall, our study demonstrated that SIRT5 mitigated liver injury induced by T-2 toxin through inhibiting iron accumulation, oxidative stress, and NLRP3 inflammasome activation, providing novel insights into the management and prevention of T-2 toxin poisoning.
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Nuomin virus (NOMV), an emerging tick-borne virus (TBVs) identified in 2020, has been associated with fever, headache, and potential liver dysfunction in infected individuals. This study presents a novel TaqMan real-time quantitative PCR method designed for the rapid, sensitive, and specific detection of NOMV, facilitating early diagnosis. Utilizing Beacon Designer software 8.0, we optimized the PCR assay including the development of primers and probes to precisely target the conserved region of the NOMV genome, followed by optimization of primer and probe concentrations and annealing temperature. The resulting assay demonstrated robust performance, with standard curve represented by the equation y=-3.29x+39.42, a high correlation coefficient (R2 = 0.995) and an efficiency 99.53â¯%. Importantly, the method exhibited exceptional specificity, which did not yield cross-reacting signals from other TBVs, including Songling virus (SGLV), Beiji virus (BJNV), tick-borne encephalitis virus (TBEV), Yezo virus (YEZV), Alongshan virus (ALSV), and severe fever with thrombocytopenia syndrome bunyavirus (SFTSV). The assay's detection limit was remarkably low, reaching 10 copies/µL, representing a 100-fold increase compared to semi-nested RT-PCR. Additionally, it demonstrated excellent repeatability, with coefficients of variation for intra- and inter-group tests consistently below 3â¯%. Clinical evaluations confirmed the assay's superior performance, highlighting its high specificity, sensitivity, and reproducibility for NOMV detection. In conclusion, the method developed in this study provides a valuable tool to support timely management of NOMV infections, with significant implications for clinical practice.
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This study improves the Logistic chaotic system and combines it with the hyperchaotic Chen system to create a dual chaotic system. The algorithm encrypts images in three stages. In the first stage, a plaintext-related key generation scheme is designed to generate the parameters and initial values of the dual chaotic system. In the second stage, the chaotic sequences generated by the dual chaotic system are used for dynamic DNA encoding and computation. In the third stage, the chaotic sequences generated by the improved Logistic chaotic system are used to perform row-column permutations, completing the scrambling. The security analysis of the encrypted images shows that the algorithm described in this paper is robust and secure, capable of resisting most known attacks. The algorithm is fast in encryption, provides high-quality image reconstruction, and is suitable for scenarios with high comprehensive performance and image quality requirements.
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Algoritmos , Cor , Segurança Computacional , DNA , Processamento de Imagem Assistida por Computador , DNA/genética , Processamento de Imagem Assistida por Computador/métodos , Dinâmica não LinearRESUMO
Contrast-enhanced magnetic resonance neurography (CE-MRN) holds promise for diagnosing brachial plexopathy by enhancing nerve visualization and revealing additional imaging features in various lesions. This study aims to validate CE-MRN's efficacy in improving brachial plexus (BP) imaging across different patient cohorts. Seventy-one subjects, including 19 volunteers and 52 patients with BP compression/entrapment, injury, and neoplasms, underwent both CE-MRN and plain MRN. Two radiologists assessed nerve visibility, with inter-reader agreement evaluated. Quantitative parameters such as signal intensity (SI), contrast-to-noise ratio (CNR), and contrast ratio (CR) of the C7 nerve were measured. Both qualitative scoring and quantitative metrics were compared between CE-MRN and plain MRN within each patient group. Patient classification followed the Neuropathy Score Reporting and Data System (NS-RADS), summarizing additional imaging features for each brachial plexopathy type. Inter-reader agreement for qualitative assessment was strong. CE-MRN significantly enhanced BP visualization and nerve-tissue contrast across all cohorts, particularly in volunteers and patients with injuries. It also uncovered additional imaging features such as hypointense signals in ganglia, compressed nerve sites, and neoplastic enhancements. CE-MRN effectively mitigated muscle edema and vascular contamination, enabling precise classification of BP injuries. Overall, CE-MRN consistently enhances BP visualization and provides valuable imaging features for accurate diagnosis.
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Neuropatias do Plexo Braquial , Plexo Braquial , Meios de Contraste , Imageamento por Ressonância Magnética , Humanos , Neuropatias do Plexo Braquial/diagnóstico por imagem , Neuropatias do Plexo Braquial/diagnóstico , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Plexo Braquial/diagnóstico por imagem , Plexo Braquial/patologia , Idoso , Adulto JovemRESUMO
The stress hyperglycemia ratio (SHR) is established as a reliable marker for assessing the severity of stress-induced hyperglycemia. While its effectiveness in managing patients with Acute Ischemic Stroke (AIS) remains to be fully understood. We aim to explore the relationship between SHR and clinical prognosis in AIS patients and to assess how diabetes status influences this relationship. In this study, we analyzed data from the Medical Information Mart for Intensive Care (MIMIC-IV) database, selecting patients with AIS who required ICU admission. These patients were categorized into tertiles based on their SHR levels. We applied Cox hazard regression models and used restricted cubic spline (RCS) curves to investigate relationships between outcomes and SHR. The study enrolled a total of 2029 patients. Cox regression demonstrated that a strong correlation was found between increasing SHR levels and higher all-cause mortality. Patients in the higher two tertiles of SHR experienced significantly elevated 30-day and 90-day mortality rates compared to those in the lowest tertile. This pattern remained consistent regardless of diabetes status. Further, RCS analysis confirmed a progressively increasing risk of all-cause mortality with higher SHR levels. The findings indicate that SHR is association with increased 30-day and 90-day mortality among AIS patients, underscoring its potential value in risk stratification. Although the presence of diabetes may weaken this association, significant correlations persist in diabetic patients.
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Hiperglicemia , AVC Isquêmico , Humanos , Masculino , Feminino , Idoso , AVC Isquêmico/mortalidade , AVC Isquêmico/sangue , AVC Isquêmico/complicações , Hiperglicemia/mortalidade , Hiperglicemia/complicações , Hiperglicemia/sangue , Pessoa de Meia-Idade , Prognóstico , Idoso de 80 Anos ou mais , Modelos de Riscos Proporcionais , Glicemia/análise , Fatores de RiscoRESUMO
BACKGROUND: Paediatric traumatic duodenal hematoma is a rare type of blunt abdominal injury for which treatment strategies are controversial. This study aimed to evaluate the application value of nonoperative management of paediatric duodenal hematoma caused by trauma. METHODS: A retrospective analysis was conducted on patients with duodenal hematoma with a confirmed history of abdominal trauma admitted to our hospital between January 2010 and December 2022. General patient information, including age, sex, cause of injury, clinical manifestations, and treatment outcomes, was recorded. RESULTS: A total of 11 cases were included in this study, with 6 males and 5 females. School-age children (≥6 years) accounted for 72.7% (8/11) of the cases. Bicycle handlebar injuries accounted for 63.6% (7/11) of cases. Among these cases, 5 (45.5%) were classified as American Association for the Surgery of Trauma grade I, while the remaining were classified as grade II. The median history time was 1 day (range: 2 h-12 days). All patients were successfully treated using non-operative methods. The median time to oral feeding after injury was 17 days (range: 9-32 days). Oral feeding was initiated within 2 weeks in 2 patients (18.2%), within 3 weeks in 6 patients (54.5%), and within 4 weeks in 10 patients (90.9%). CONCLUSION: Paediatric traumatic duodenal hematoma is more common in school-aged children, mainly due to bicycle handlebar injuries. Nonoperative treatment is proven to be safe and effective, with duodenal obstruction symptoms typically resolving within 4 weeks.
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PURPOSE: The prevalence of biliary tract diseases, which are common gastrointestinal disorders, is steadily rising. If it progresses to sepsis or septic shock, it can endanger the patient's life. Therefore, it is crucial to promptly diagnose bacterial infection in individuals suffering from biliary diseases and comprehend the risk factors associated with infection. The objective of this study was to examine the types of bacteria present in the bile of patients with biliary tract diseases, assess any alterations in their susceptibility to antimicrobial agents, and identify the risk factors contributing to the development of infection in these patients. PATIENTS AND METHODS: From June 2019 to November 2022, 317 patients of biliary tract diseases with positive bile culture were included in this hospital-based descriptive analysis. The hospital's computerized medical records were used to collect data on demographic information (including gender, age, and occupation), laboratory, and clinical findings, physical examination results, comorbidities, basic diseases, treatment history, complications, and in-hospital outcomes. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) principles. RESULTS: Of the 317 patients with positive biliary tract diseases, 247 had benign diseases and 70 had malignant diseases. Patients with benign disease experienced a higher prevalence of statistically significant symptoms such as abdominal pain (81.4% vs. 57.1%, P = 0.000), nausea (31.2% vs. 14.3%, P = 0.005), vomiting (30.0% vs. 12.9%, P = 0.004), and chills (10.9% vs. 2.9%, P = 0.039), while jaundice (12.6% vs. 37.1%, P = 0.000) was more common in patients with malignant disease. At the species level, Escherichia coli (105; 40.5%), Klebsiella pneumoniae (41; 15.8%), and Pseudomonas aeruginosa (30; 11.6%) were the most commonly found Gram-negative bacterial strains in biliary tract infection. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were most susceptible to tigecycline, ertapenem and ceftazidime/avibactam, respectively. CONCLUSION: Gram-negative bacteria are the most commonly isolated biliary bacteria. Clinical doctors should pay attention to patients with malignant diseases with low hemoglobin, high total bilirubin and high alkaline phosphatase. Carbapenems, tigecycline, and minocycline are the recommended antibiotics for Enterobacteriaceae. In recent years, the proportion of enterococcus has gradually increased, and clinical attention should be paid to enterococcus infection. Linezolid and vancomycin were recommended for the treatment of Enterococci infections. Overall, this work can provide reference for clinical diagnosis, treatment and effective interventions.
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Antibacterianos , Bile , Doenças Biliares , Centros de Atenção Terciária , Humanos , Masculino , Feminino , Doenças Biliares/microbiologia , Doenças Biliares/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Adulto , Bile/microbiologia , Antibacterianos/uso terapêutico , Fatores de Risco , Idoso de 80 Anos ou mais , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/tratamento farmacológico , Prevalência , Adulto JovemRESUMO
Speech emotion recognition (SER) is not only a ubiquitous aspect of everyday communication, but also a central focus in the field of human-computer interaction. However, SER faces several challenges, including difficulties in detecting subtle emotional nuances and the complicated task of recognizing speech emotions in noisy environments. To effectively address these challenges, we introduce a Transformer-based model called MelTrans, which is designed to distill critical clues from speech data by learning core features and long-range dependencies. At the heart of our approach is a dual-stream framework. Using the Transformer architecture as its foundation, MelTrans deciphers broad dependencies within speech mel-spectrograms, facilitating a nuanced understanding of emotional cues embedded in speech signals. Comprehensive experimental evaluations on the EmoDB (92.52%) and IEMOCAP (76.54%) datasets demonstrate the effectiveness of MelTrans. These results highlight MelTrans's ability to capture critical cues and long-range dependencies in speech data, setting a new benchmark within the context of these specific datasets. These results highlight the effectiveness of the proposed model in addressing the complex challenges posed by SER tasks.
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Emoções , Fala , Humanos , Emoções/fisiologia , Fala/fisiologia , Algoritmos , Interface para o Reconhecimento da FalaRESUMO
OBJECTIVES: Despite the potential spillover effect, the optimal duration of dual antiplatelet therapy for minor stroke within 72 hours of symptom onset is still uncertain. METHODS: Safety and Efficacy of Aspirin-Clopidogrel in Acute Noncardiogenic Minor Ischemic Stroke (National Institutes of Health Stroke Scale (NIHSS) score≤5) is a prospective cohort study involving patients with minor ischaemic stroke within 72 hours of symptom onset. The DAPT group was further categorised into three subgroups: shorter duration (<10 days), short duration (10-21 days) and long duration (>21 days). The primary efficacy and safety outcomes were composite vascular event and severe bleeding during 90 days. RESULTS: Among 3061 eligible patients (age was 61.7±12.0 years, 73.3% were men, median (IQR) NIHSS score, 2 (1-3)), 2977 (97.4%) completed the follow-up. Dual antiplatelet therapy (DAPT) and single antiplatelet therapy (SAPT) were administered in 61.0% and 39.0% of patients. Among them, 305 patients (16.8%) received a shorter duration of DAPT, 937 patients (51.7%) received a short duration and 572 patients (31.5%) received a long duration. In the propensity-weighted Cox proportional hazards regression analysis, the use of DAPT in the short-duration group was associated with a lower risk of the primary vascular event outcome (HR (HR)=0.66, 95% CI 0.46 to 0.94, p=0.02) compared with SAPT group. The incidence of severe bleeding events at 90 days was similar. Similar findings were obtained from the propensity score-matching analysis. CONCLUSION: Short duration of DAPT (10-21 days) is superior to SAPT in minor stroke within 72 hours, reducing 90-day composite vascular events without increasing bleeding risk.
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Background: Community-acquired pneumonia (CAP) is a common infectious disease characterized by inflammation of the lung parenchyma in individuals who have not recently been hospitalized. It remains a significant cause of morbidity and mortality worldwide. Aspirin is a widely used drug, often administered to CAP patients. However, the benefits of aspirin remain controversial. Objective: We sought to determine whether aspirin treatment has a protective effect on the outcomes of CAP patients. Methods: We selected patients with CAP from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching (PSM) balanced baseline differences. A multivariate Cox regression model assessed the relationship between aspirin treatment and 28-day mortality. Results: A total of 3,595 patients were included, with 2,261 receiving aspirin and 1,334 not. After PSM, 1,219 pairs were matched. The 28-day mortality rate for aspirin users was 20.46%, lower than non-users. Multivariate Cox regression indicated aspirin use was associated with decreased 28-day mortality (HR 0.75, 95% CI 0.63-0.88, p < 0.001). No significant differences were found between 325 mg/day and 81 mg/day aspirin treatments in terms of 28-day mortality, hospital mortality, 90-day mortality, gastrointestinal hemorrhage, and thrombocytopenia. However, intensive care unit (ICU) stay was longer for the 325 mg/day group compared to the 81 mg/day group (4.22 vs. 3.57 days, p = 0.031). Conclusion: Aspirin is associated with reduced 28-day mortality in CAP patients. However, 325 mg/day aspirin does not provide extra benefits over 81 mg/day and may lead to longer ICU stays.
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Background/purpose: Rho GTPase activating protein 11A (ARHGAP11A) can facilitate GTP hydrolysis in RhoA. The functions of ARHGAP11A in oral squamous cell carcinoma (OSCC) have not yet been explored. This study aimed to investigate the expression profile of ARHGAP11A in OSCC, its correlation with patient prognosis, its effect on cell-cycle progression, and the mechanisms by which it is dysregulated. Materials and methods: Bioinformatics analysis was conducted using data from The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma (TCGA-HNSC). Lentiviruses carrying ARHGAP11A shRNAs were employed to determine the effects of ARHGAP11A knockdown on tumor cell proliferation and cell-cycle progression. Dual-luciferase reporter assays were utilized to examine how FOXM1 transcriptionally regulates ARHGAP11A expression. Results: ARHGAP11A upregulation was associated with unfavorable overall survival (OS) in patients with TSCC (HR: 2.142, 95%CI: 1.224-3.749, P = 0.007), but not in patients with OSCC of sites other than the tongue. ARHGAP11A knockdown inhibited the proliferation of TSCC cells in vitro and in vivo, and induced G1 phase arrest. ARHGAP11A knockdown increased GTP-RhoA but decreased p-RB levels, while it did not affect the total expression of RhoA and RB. ARHGAP11A knockdown increased p27 and decreased cyclin E1 expression. ARHGAP11A is transcriptionally activated by FOXM1 via multiple FOXM1 binding sites in the promoter regions in TSCC cells. Conclusion: This study revealed the oncogenic role of ARHGAP11A in TSCC, highlighting its impact on cell-cycle control and tumor proliferation. Furthermore, the regulatory relationship between FOXM1 and ARHGAP11A provides new insights into the transcriptional networks in TSCC.
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INTRODUCTION: Presently, numerous studies have demonstrated that long-term cardiovascular changes after Coronavirus Disease 2019(COVID-19) infection should be considered. The study was aimed to explore the risk factors for post COVID-19 long-term cardiovascular symptoms. METHODS: This retrospective observational cross-sectional study involved 204 COVID-19 patients who were admitted to Yantaishan Hospital from January 1, 2023 to January 31, 2023. Demographic and laboratory data were collected and compared between patients who experienced post COVID-19 long-term cardiovascular symptoms and those who did not. Logistic regression analysis was used to identify the risk factors associated with the occurrence of post COVID-19 long-term cardiovascular symptoms. RESULTS: Fifty-two participants presented Post COVID-19 cardiovascular symptoms, while the remaining 152 individuals did not show any such symptoms including chest pain, chest tightness, shortness of breath, palpitations, dyspnea, exercise intolerance, and postural tachycardia syndrome. In comparison to the group without post COVID-19 long-term cardiovascular symptoms, the group with post COVID-19 long-term cardiovascular symptoms exhibited a significantly higher prevalence of anxiety and depression (25.0% vs. 4.6%, p = 0.000), as well as significantly elevated C-reactive protein (42.3 mg/L vs. 20.3 mg/L, p = 0.014) and D-dimer (0.3 mg/L vs. 0.22 mg/L, p = 0.024). Anxiety and depression (odds ratio [OR] = 6.403, 95% confidence interval [CI]:2.180-18.809, p = 0.001), C-reactive protein (OR = 1.009, 95%CI:1.003-1.015, p = 0.006), D-dimer (OR = 1.455, 95%CI:1.004-2.109, p = 0.048), and LDL-C (OR = 1.780, 95%CI:1.043-3.040, p = 0.035) were identified as independent risk factors for post COVID-19 long-term cardiovascular symptoms. CONCLUSION: Anxiety and depression, C-reactive protein, D-dimer, and LDL-C levels are associated with the development of post COVID-19 long-term cardiovascular symptoms.
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COVID-19 , Doenças Cardiovasculares , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Estudos Retrospectivos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco , Idoso , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Adulto , Ansiedade/epidemiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Depressão/epidemiologia , China/epidemiologia , Síndrome de COVID-19 Pós-AgudaRESUMO
BACKGROUND: Which cell populations that determine the fate of bacteria in infectious granulomas remain unclear. Leprosy, a granulomatous disease with a strong genetic predisposition, caused by Mycobacterium leprae infection, exhibits distinct sub-types with varying bacterial load and is considered an outstanding disease model for studying host-pathogen interactions. METHODS: We performed single-cell RNA and immune repertoire sequencing on 11 healthy controls and 20 patients with leprosy, and integrated single-cell data with genome-wide genetic data on leprosy. Multiplex immunohistochemistry, and in vitro and in vivo infection experiments were conducted to confirm the multimodal omics findings. FINDINGS: Lepromatous leprosy (L-LEP) granulomas with high bacterial burden were characterised by exhausted CD8+ T cells, and high RGS1 expression in CD8+ T cells was associated with L-LEP. By contrast, tuberculoid leprosy (T-LEP) granulomas with low bacterial burden displayed enrichment in resident memory IFNG+ CD8+ T cells (CD8+ Trm) with high GNLY expression. This enrichment was potentially attributable to the communication between IL1B macrophages and CD8+ Trm via CXCL10-CXCR3 signalling. Additionally, IL1B macrophages in L-LEP exhibited anti-inflammatory phenotype, with high APOE expression contributing to high bacterial burden. Conversely, IL1B macrophages in T-LEP were distinguished by interferon-γ induced GBP family genes. INTERPRETATION: The state of IL1B macrophages and functional CD8+ T cells, as well as the relationship between them, is crucial for controlling bacterial persistence within granulomas. These insights may indicate potential targets for host-directed immunotherapy in granulomatous diseases caused by mycobacteria and other intracellular bacteria. FUNDING: The Key research and development program of Shandong Province (2021LCZX07), Natural Science Foundation of Shandong Province (ZR2023MH046), Youth Science Foundation Cultivation Funding Plan of Shandong First Medical University (Shandong Academy of Medical Sciences) (202201-123), National Natural Science Foundation of China (82471800, 82230107, 82273545, 82304039), the China Postdoctoral Science Foundation (2023M742162), Shandong Province Taishan Scholar Project (tspd20230608), Joint Innovation Team for Clinical & Basic Research (202410), Central guidance for local scientific and technological development projects of Shandong Province (YDZX2023058).
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The thermochemical conversion technology for anaerobic digestate from food waste (ADFW) can reduce waste volume, eliminate pathogens, and recover energy through incineration, pyrolysis, gasification, and hydrothermal transformation. This paper comprehensively reviews the physicochemical features of anaerobically fermented digestate from food waste (FW), digestate treatment methods, and their advantages and disadvantages. In addition, the analysis and application of associated by-products from ADFW thermochemical conversion are also discussed. The main products include biochar, bio-oil, and biogas. Biochar can be used for soil improvement and biomedicine and bio-oil can be used forliquid fuel. Meanwhile, biogas mainly consists of CH4, CO2, and H2 and CO, which can be used in petrochemicals, metallurgy, and other fields. The catalytic pyrolysis/gasification for plastic-containing ADFW is proposed by adding iron-based industrial waste (red mud/copper) as catalysts under the CO2/CH4 atmosphere. This review helps to provide new guidelines for the ADFW utilization of desired products.
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Iminosugars, a class of polyhydroxylated cyclic alkaloids with intriguing properties, hold promising therapeutic potentials against a broad spectrum of enveloped viruses, including DENV, HCV, HIV, and influenza viruses. Mechanistically, iminosugars act as the competitive inhibitors of host endoplasmic reticular α-glucosidases I and II to disrupt the proper folding of viral nascent glycoproteins, which thereby exerts antiviral effects. Remarkably, the glycoproteins of many enveloped viruses are significantly more dependent on the calnexin pathway of the protein folding than most host glycoproteins. Therefore, extensive interests and efforts have been devoted to exploit iminosugars as broad-spectrum antiviral agents. This review provides the summary and insights into the recent advancements in the development of novel iminosugars as effective and selective antiviral agents against a variety of enveloped viruses, as well as the understandings of their antiviral mechanisms.