Mediation of FOXA2/IL-6/IL-6R/STAT3 signaling pathway mediates benzo[a]pyrene-induced airway epithelial mesenchymal transformation in asthma.

Benzo [a]pyrene (BaP), a toxic pollutant, increases the incidence and severity of asthma. However, the molecular mechanisms underlying the effects of BaP in asthma remain unclear. In terms of research methods, we used BaP to intervene in the animal model of asthma and the human bronchial epithelial (16HBE) cells, and the involved mechanisms were found from the injury, inflammation, and airway epithelial to mesenchymal transition (EMT) in asthma. We also constructed small interfering RNAs and overexpression plasmids to knockdown/overexpress IL-6R and FOXA2 in 16HBE cells and a serotype 9 adeno-associated viral vector for lung tissue overexpression of FOXA2 in mice to determine the mechanism of action of BaP-exacerbated asthma airway EMT. We observed that BaP aggravated inflammatory cell infiltration into the lungs, reduced the Penh value, increased collagen fibres in the lung tissue, and increased serum IgE levels in asthmatic mice. After BaP intervention, the expression of FOXA2 in the lung tissue of asthmatic mice decreased, the production and secretion of IL-6 were stimulated, and STAT3 phosphorylation and nuclear translocation increased, leading to changes in EMT markers. However, EMT decreased after increasing FOXA2 expression and decreasing that of IL-6R and was further enhanced after low FOXA2 expression. Our results revealed that BaP exacerbated airway epithelial cell injury and interfered with FOXA2, activating the IL-6/IL-6R/STAT3 signaling pathway to promote airway EMT in asthma. These findings provide toxicological evidence for the mechanism underlying the contribution of BaP to the increased incidence of asthma and its exacerbations.

CircPAPPA2 plays a role in preeclampsia pathogenesis via regulation of the miR-942/miR-5006-3p.

CircRNAs are a class of endogenous non-coding RNAs implicated in the pathogenesis of many pregnancy related diseases, one of which is pre-eclampsia (PE). This study aims to investigate the role of CircPAPPA2 (circbase ID: hsa_circ_0015382) in regulating the migration and invasion of trophoblast cells. RNA sequencing was used to identify the differentially expressed circRNAs in placenta of PE and normal pregnant women. Quantitative polymerase chain reaction (qRT-PCR) was used to verify the expression of circPAPPA2 and two miRNAs (miR-942-5p, 5006-3p) in placenta of PE and normal pregnant women. CCK8 and transwell experiments were performed to assess the function of circPAPPA2 in PE development.The interaction between circPAPPA2 and miR-942-5p/miR-5006-3p was verified by dual-luciferase reporter assay. Finally, bioinformatics analyzed with gene ontology, Kyoto Encyclopedia of the target genes. The results showed that the expression of circPAPPA2 was increased in placenta of PE pregnant women. Also, circPAPPA2 impedes trophoblasts cell proliferation and invasion. Moreover, the expression of circPAPPA2 was positively correlated with systolic blood pressure and urine protein. In addition, circPAPPA2 serves as a sponge of miR-942-5p and miR-5006-3p. In conclusion, CircPAPPA2 regulates trophoblasts cell proliferation and invasion by mediating the miR-942/miR-5006-3p.

Alterations in gut microbiota and inflammatory cytokines after administration of antibiotics in mice.

Antibiotics are widely used to treat bacterial infection and reduce the mortality rate, while antibiotic overuse can cause gut microbiota dysbiosis. The impact of antibiotics on gut microbiota is not fully understood. In our study, four commonly used antibiotics (ceftazidime, cefoperazone-sulbactam, imipenem-cilastatin, and moxifloxacin) were given subcutaneously to mice, and their impacts on the gut microbiota composition and serum cytokine levels were evaluated through 16S rRNA analysis and a multiplex immunoassay. Antibiotic treatment markedly reduced gut microbiota diversity and changed gut microbiota composition. Antibiotic treatment significantly increased and decreased the abundance of Firmicutes and Bacteroidota, respectively. The antibiotic treatments increased the abundance of opportunistic pathogens such as Enterococcus and decreased that of Lachnospiraceae and Muribaculaceae. For moxifloxacin, the significantly high abundance of Enterococcus and Klebsiella was observed after 14 and 21 days of treatment. However, a relatively low abundance of opportunistic pathogens was found after 14 days of imipenem-cilastatin treatment. Additionally, the serum levels of various pro-inflammatory cytokines, such as IL-1ß, IL-12 (p70), and IL-17, significantly increased after 21 days of antibiotic treatments. Overall, these results provide a guide for rational use of antibiotics in clinical settings: short-term use of moxifloxacin is recommended with regard to gut microbiota health, and the 14-day use of imipenem-cilastatin may have a less severe impact than other antibiotics.IMPORTANCEAntibiotic treatments are directly associated with changes in gut microbiota and are effective against both pathogens and beneficial bacteria. Gut microbiota dysbiosis induced by antibiotic treatment could increase the risk of some diseases. Therefore, an adequate understanding of gut microbiota changes after antibiotic use is crucial. In this study, we investigated the effects of continuous treatment with antibiotics on gut microbiota, serum cytokines, and intestinal inflammatory response. Our results suggest that short-term use of moxifloxacin is recommended, and the 14-day use of imipenem-cilastatin may have a less severe effect on gut microbiota health than cefoperazone-sulbactam. These results provide useful guidance on the rational use of antibiotics with regard to gut microbiota health.

Application of Hyperspectral Technology with Machine Learning for Brix Detection of Pastry Pears.

Sugar content is an essential indicator for evaluating crisp pear quality and categorization, being used for fruit quality identification and market sales prediction. In this study, we paired a support vector machine (SVM) algorithm with genetic algorithm optimization to reliably estimate the sugar content in crisp pears. We evaluated the spectral data and actual sugar content in crisp pears, then applied three preprocessing methods to the spectral data: standard normal variable transformation (SNV), multivariate scattering correction (MSC), and convolution smoothing (SG). Support vector regression (SVR) models were built using processing approaches. According to the findings, the SVM model preprocessed with convolution smoothing (SG) was the most accurate, with a correlation coefficient 0.0742 higher than that of the raw spectral data. Based on this finding, we used competitive adaptive reweighting (CARS) and the continuous projection algorithm (SPA) to select key representative wavelengths from the spectral data. Finally, we used the retrieved characteristic wavelength data to create a support vector machine model (GASVR) that was genetically tuned. The correlation coefficient of the SG-GASVR model in the prediction set was higher by 0.0321 and the root mean square prediction error (RMSEP) was lower by 0.0267 compared with those of the SG-SVR model. The SG-CARS-GASVR model had the highest correlation coefficient, at 0.8992. In conclusion, the developed SG-CARS-GASVR model provides a reliable method for detecting the sugar content in crisp pear using hyperspectral technology, thereby increasing the accuracy and efficiency of the quality assessment of crisp pear.

Factors influencing Frey syndrome after parotidectomy with acellular dermal matrix.

BACKGROUND: Frey syndrome, also known as ototemporal nerve syndrome or gustatory sweating syndrome, is one of the most common complications of parotid gland surgery. This condition is characterized by abnormal sensations in the facial skin accompanied by episodes of flushing and sweating triggered by cognitive processes, visual stimuli, or eating. AIM: To investigate the preventive effect of acellular dermal matrix (ADM) on Frey syndrome after parotid tumor resection and analyzed the effects of Frey syndrome across various surgical methods and other factors involved in parotid tumor resection. METHODS: Retrospective data from 82 patients were analyzed to assess the correlation between sex, age, resection sample size, operation time, operation mode, ADM usage, and occurrence of postoperative Frey syndrome. RESULTS: Among the 82 patients, the incidence of Frey syndrome was 56.1%. There were no significant differences in sex, age, or operation time between the two groups (P > 0.05). However, there was a significant difference between ADM implantation and occurrence of Frey syndrome (P < 0.05). ADM application could reduce the variation in the incidence of Frey syndrome across different operation modes. CONCLUSION: ADM can effectively prevent Frey syndrome and delay its onset.

Jiangqi Pingxiao formula regulates dendritic cell apoptosis in an autophagy-dependent manner through the AMPK/mTOR pathway in a murine model of OVA-induced asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Allergic asthma is a recurring respiratory condition that typically manifests during childhood or adolescence. It is characterized by a dominant type II immune response triggered by the identification and capturing of inhaled allergens by dendritic cells (DCs). Jiangqi Pingxiao Formula (JQPXF), a prescription medicine used for the treatment of pediatric asthma, has been clinically proven to be both safe and effective. However, its mechanism of action in the treatment of asthma has not been fully been fully elucidated. Recent research suggests that several natural compounds have the potential to target dendritic cells (DCs) and alleviate ovalbumin (OVA)-induced asthma, which may also be found within JQPXF. AIM OF THE STUDY: This study aimed to elucidate the effect of JQPXF on OVA-induced asthma model and its molecular mechanism targeting DCs. MATERIALS AND METHODS: The main constituents of JQPXF were analyzed by ultra performance liquid chromatography (UPLC). An asthma model was established by OVA. Hematoxylin-eosin staining and measurement of respiratory function was used to evaluate the treatment effect of JQPXF on asthmatic mice. Cytokine (IL-5, IL-13 and IgE) concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was employed to evaluate inflammatory cell infiltration (T helper 2 cells and DCs) in vivo and DC survival in vivo and vitro. Western blot and immunofluorescence were used to verify the molecular mechanisms. RESULTS: The results suggest that JQPXF can ameliorate pathological conditions and improve lung function in asthmatic mice, as well as the Th2 cells. Treatment with JQPXF significantly reduced the number of DCs and increased the number of Propidium iodide+ (PI) DCs. Furthermore, JQPXF upregulated protein levels of the pro-apoptotic factors Cleaved-caspase-3 and Bax, while downregulating the anti-apoptotic factor Bcl-2. Simultaneously, JQPXF increased autophagy levels by facilitating p62 degradation and promoting translation from LC3B I to LC3B II of DCs in vitro, as well as reducing the integrated optical density (IOD) of p62 within the CD11c-positive area in the lung. 3-Methyladenine (3-MA) was used to block autophagic flux and the apoptotic effect of JQPXF on DCs was abolished in vitro, with the number of DCs decreased by JQPXF being reversed in vivo. We further investigated the upstream key regulator of autophagy, the AMPK/mTOR pathway, and found that JQPXF increased AMPK phosphorylation while decreasing mTOR phosphorylation levels. Additionally, we employed Compound C (CC) as an AMPK inhibitor to inhibit this signaling pathway, and our findings revealed that both autophagic flux and apoptotic levels in DCs were abolished in vitro. CONCLUSIONS: In summary, we have demonstrated that JQPXF could alleviate type II inflammation in an asthmatic model by promoting the apoptosis of DCs through an autophagy-dependent mechanism, achieved by regulating the AMPK/mTOR signaling pathway.

Oral VV116 versus placebo in patients with mild-to-moderate COVID-19 in China: a multicentre, double-blind, phase 3, randomised controlled study.

BACKGROUND: Spread of SARS-CoV-2 led to a global pandemic, and there remains unmet medical needs in the treatment of Omicron infections. VV116, an oral antiviral agent that has potent activity against SARS-CoV-2, was compared with a placebo in this phase 3 study to investigate its efficacy and safety in patients with mild-to-moderate COVID-19. METHODS: This multicentre, double-blind, phase 3, randomised controlled study enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomisation to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2-5) or oral placebo (on the same schedule as VV116) for 5 days. Randomisation stratification factors included SARS-CoV-2 vaccination status and the presence of high-risk factors for progression to severe COVID-19. Inclusion criteria were a positive SARS-CoV-2 test, an initial onset of COVID-19 symptoms 3 days or less before the first study dose, and a score of 2 or more for any target COVID-19-related symptoms in the 24 h before the first dose. Patients who had severe or critical COVID-19 or who had taken any antiviral drugs were excluded from the study. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. Efficacy analyses were performed on a modified intention-to-treat population, comprising all patients who received at least one dose of VV116 or placebo, tested positive for SARS-CoV-2 nucleic acid, and did not test positive for influenza virus before the first dose. Safety analyses were done on all participants who received at least one dose of VV116 or placebo. This study was registered with ClinicalTrials.gov, NCT05582629, and has been completed. FINDINGS: A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04-1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04-1·33; p=0·0009), consistent with the interim analysis. The incidence of adverse events was similar between groups (242 [35·9%] of 674 patients vs 283 [42·1%] of 673 patients). INTERPRETATION: Among patients with mild-to-moderate COVID-19, VV116 significantly reduced the time to sustained clinical symptom resolution compared with placebo, with no observed safety concerns. FUNDING: Shanghai Vinnerna Biosciences, Shanghai Science and Technology Commission, and the National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Intravoxel incoherent motion diffusion-weighted MRI for predicting the efficacy of high-intensity focused ultrasound ablation for uterine fibroids.

Purpose: To evaluate the significance of magnetic resonance (MR) intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) quantitative parameters in predicting early efficacy of high-intensity focused ultrasound (HIFU) ablation of uterine fibroids before treatment. Method: 64 patients with 89 uterine fibroids undergoing HIFU ablation (51 sufficient ablations and 38 insufficient ablations) were enrolled in the study and completed MR imaging and IVIM-DWI before treatment. The IVIM-DWI parameters, including D (diffusion coefficient), D* (pseudo-diffusion coefficient), f (perfusion fraction) and relative blood flow (rBF) were calculated. The logistic regression (LR) model was constructed to analyze the predictors of efficacy. The receiver operating characteristic (ROC) curve was drawn to assess the model's performance. A nomograph was constructed to visualize the model. Results: The D value of the sufficient ablation group (931.0(851.5-987.4) × 10-6 mm2/s) was significantly lower than that of the insufficient ablation group (1052.7(1019.6-1158.7) × 10-6 mm2/s) (p<0.001). However, differences in D*, f, and rBF values between the groups were not significant (p>0.05). The LR model was constructed with D value, fibroid position, ventral skin distance, T2WI signal intensity, and contrast enhanced degree. The area under the ROC curve, specificity, and sensitivity of the model were 0.858 (95% confidence interval: 0.781, 0.935), 0.686, and 0.947. The nomogram and calibration curves confirmed that the model had excellent performance. Conclusion: The IVIM-DWI quantitative parameters can be used to predict early effects of HIFU ablation on uterine fibroids. A high D value before treatment may indicate that the treatment will be less effective in the early stages.

Lipid metabolism for predicting the recurrence of hypertriglyceridemic acute pancreatitis.

Rationale and objectives: To investigate the predictive value of lipid metabolism in predicting the recurrence of hypertriglyceridemic acute pancreatitis (HTG-AP). Materials and methods: A total of 892 patients were admitted to our hospital for acute pancreatitis (AP) from January 2017 to December 2020, of whom 198 diagnosed with HTG-AP were enrolled in this retrospective study. Demographic information, length of stay, smoking index, alcohol abuse, necrosis, severity, baseline lipid metabolism and other blood biochemical indicators were recorded. The risk factors of recurrence were evaluated using univariate and multivariate Cox proportional risk analyses, and the cumulative recurrence-free survival rate of patients were calculated using Kaplan Meier method and the differences between groups were compared using the log-rank test. Results: Univariate and multivariate analysis showed that triglyceride (hazard ratio, 2.421; 95% CI, 1.152-5.076; P = 0.020), non high-density lipoprotein (hazard ratio, 4.630; 95% CI, 1.692-12.658; P = 0.003) and apolipoprotein A1 (hazard ratio, 1.735; 95% CI, 1.093-2.754; P = 0.019) were important predictors for recurrence of HTG-AP. Subsequently, patients were divided into four groups according to the cut off values of triglyceride, non high-density lipoprotein and apolipoprotein A1. It was found that the cumulative recurrence-free survival rate of patients in highest-risk group or high-risk group was significantly lower than that of medium-risk group (P < 0.001, P = 0.003) or low risk group (P < 0.001). Conclusion: Serum triglycerides, non high-density lipoprotein and apolipoprotein A1 are independent predictors of recurrence in HTG-AP patients, which can provide reference for individualized treatment and prevention of recurrence in HTG-AP patients.

Neuroprotective Effect of Dexmedetomidine on Cerebral Ischemia-Reperfusion Injury in Rats.

Background: The number of patients having ischemic stroke is increasing year on year. The anesthetic adjuvant dexmedetomidine is neuroprotective in rats and has potential for use in the treatment of ischemic stroke. Objective: The neuroprotective mechanism of dexmedetomidine in cerebral ischemia-reperfusion injury was studied in relation to its regulation of the oxidative stress response, astrocyte response, microglia overactivation, and apoptosis-related protein expression. Methods: We randomly and equally divided 25 male Sprague-Dawley rats into 5 groups: a sham-operation group, an ischemia-reperfusion injury group, and low-, medium-, and high-dose dexmedetomidine groups. A rat model of focal cerebral ischemia-reperfusion injury was established by embolization of the right middle cerebral artery for 60 minutes and reperfusion for 2 hours. The volume of cerebral infarction was calculated by triphenyl tetrazolium chloride staining. The protein expression levels of caspase-3, methionyl aminopeptidase 2 (MetAP2 or MAP2), glial fibrillary acidic protein, and allograft inflammatory factor 1 (AIF-1) in the cerebral cortex were determined by Western blot and immunohistochemistry. Results: The volume of cerebral infarction in rats decreased with increasing dose of dexmedetomidine (P = .039, 95% CI = .027 to .044). The expression levels of caspase-3, glial fibrillary acidic protein, and allograft inflammatory factor 1 and the amount of 4-hydroxynonenal decreased with increasing doses of dexmedetomidine (P = .033, 95% CI = .021 to .037). Methionyl aminopeptidase 2 (MetAP2 or MAP2) expression increased with increasing doses of dexmedetomidine (P = .023, 95% CI = .011 to .028). Conclusion: Dexmedetomidine has a dose-dependent protective effect on cerebral ischemic injury in rats. The neuroprotective effects of dexmedetomidine are achieved, in part, by reducing the oxidative stress response, inhibiting glial overactivation, and inhibiting expression levels of apoptosis-related proteins.

BMAL1 regulates MUC1 overexpression in ovalbumin-induced asthma.

Asthma often presents with a daily rhythm; however, the underlying mechanisms remain unclear. Circadian rhythm genes have been proposed to regulate inflammation and mucin expression. Here, ovalbumin (OVA)-induced mice and serum shock human bronchial epidermal cells (16HBE) were used in in vivo and in vitro models, respectively. We constructed a brain and muscle ARNT-like 1 (BMAL1) knockdown 16HBE cell line to analyze the effects of rhythmic fluctuations on mucin expression. Serum immunoglobulin E (IgE) and circadian rhythm genes in asthmatic mice showed rhythmic fluctuation amplitude. Mucin (MUC) 1 and MUC5AC expression was increased in the lung tissue of the asthmatic mice. MUC1 expression was negatively correlated with that of the circadian rhythm genes, particularly BMAL1 (r = -0.546, P = 0.006). There was also a negative correlation between BMAL1 and MUC1 expression (r = -0.507, P = 0.002) in the serum shock 16HBE cells. BMAL1 knockdown negated the rhythmic fluctuation amplitude of MUC1 expression and upregulated MUC1 expression in the 16HBE cells. These results indicate that the key circadian rhythm gene, BMAL1, causes periodic changes in airway MUC1 expression in OVA-induced asthmatic mice. Targeting BMAL1 to regulate periodic changes in MUC1 expression may, therefore, improve asthma treatments.

Case Report: Parvovirus B19 infection complicated by hemophagocytic lymphohistiocytosis in a heart-lung transplant patient.

Immunosuppressed patients can contract parvovirus B19, and some may experience hemophagocytic lymphohistiocytosis (HLH). Herein, we describe the first report of hemophagocytic lymphohistiocytosis in a heart-lung transplant patient with concomitant parvovirus B19 infection. The patient was treated with intravenous immune globulin (IVIG) and the features of HLH were remission. This instance emphasizes the significance of parvovirus B19 monitoring in transplant patients with anemia; if HLH complicates the situation, IVIG may be an adequate remedy. Finally, a summary of the development in diagnosing and managing parvovirus B19 infection complicated by HLH is provided.

Radiomics analysis of contrast-enhanced T1W MRI: predicting the recurrence of acute pancreatitis.

To investigate the predictive value of radiomics based on T1-weighted contrast-enhanced MRI (CE-MRI) in forecasting the recurrence of acute pancreatitis (AP). A total of 201 patients with first-episode of acute pancreatitis were enrolled retrospectively (140 in the training cohort and 61 in the testing cohort), with 69 and 30 patients who experienced recurrence in each cohort, respectively. Quantitative image feature extraction was obtained from MR contrast-enhanced late arterial-phase images. The optimal radiomics features retained after dimensionality reduction were used to construct the radiomics model through logistic regression analysis, and the clinical characteristics were collected to construct the clinical model. The nomogram model was established by linearly integrating the clinically independent risk factor with the optimal radiomics signature. The five best radiomics features were determined by dimensionality reduction. The radiomics model had a higher area under the receiver operating characteristic curve (AUC) than the clinical model for estimating the recurrence of acute pancreatitis for both the training cohort (0.915 vs. 0.811, p = 0.020) and testing cohort (0.917 vs. 0.681, p = 0.002). The nomogram model showed good performance, with an AUC of 0.943 in the training cohort and 0.906 in the testing cohort. The radiomics model based on CE-MRI showed good performance for optimizing the individualized prediction of recurrent acute pancreatitis, which provides a reference for the prevention and treatment of recurrent pancreatitis.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Anti-C5a Antibody BDB-001 for Severe COVID-19: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Clinical Trial in Healthy Chinese Adults.

INTRODUCTION: Severe Coronavirus Disease 2019 (COVID-19) progresses with inflammation and coagulation, due to an overactive complement system. Complement component 5a (C5a) plays a key role in the complement system to trigger a powerful "cytokine and chemokine storm" in viral infection. BDB-001, a recombinant human immunoglobulin G4 (IgG4) that specially binds to C5a, has the potential to inhibit the C5a-triggered cytokine storm in treating COVID-19 patients and other inflammation diseases. Here, we have explored its safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy adults. This trial is registered with http://www.chinadrugtrials.org.cn/(CTR20200429 ). METHODS: Thirty-two enrolled participants were randomized into three single-dose cohorts (2, 4, and 8 mg/kg) and 1 multi-dose cohort (4 mg/kg), and received either BDB-001 or placebo (3:1) double-blindly. The safety and tolerability after administration were evaluated for 21 days for single-dose cohorts and 28 days for the multi-dose cohort. The pharmacokinetics of BDB-001 in plasma and pharmacodynamics as free C5a in plasma were analyzed. RESULTS: The incidence of drug-related adverse events (AEs) was low, and all AEs were mild or moderate: neither AEs ≥ 3 (NCI-Common Terminology Criteria For Adverse Events, CTCAE 5.0) nor serious adverse events (SAEs) were found. The area under the concentration-time curve from time zero to 480 h (AUC0-480h), that from time zero to infinity (AUCinf), and peak plasma concentration ©max) increased dose-dependently from 2 to 8 mg/kg in the single-dose cohorts and were characterized by a nonlinear pharmacokinetics of target-mediated drug disposal (TMDD). The accumulation index by AUC0-tau after five administrations (4 mg/kg) from the multi-dose cohort was 6.42, suggesting an accumulation effect. Furthermore, inhibition of C5a at the plasma level was observed. CONCLUSION: The results of this phase I study supported that BDB-001 is a potent anti-C5a inhibitor with safety, tolerability, and no immunogenicity. TRIAL REGISTRATION NUMBER: CTR20200429.

MicroRNA-155-5p Aggravates Adriamycin-Induced Focal Segmental Glomerulosclerosis through Targeting Nrf2.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix and usually associated with nephrotic range proteinuria. FSGS is a huge burden to society; however, the mechanisms remain unclear and treatment is still lacking. METHODS: Adriamycin nephropathy was induced by Adriamycin injection and some mice were also injected with Anti-miR-155-5p LNA or YC-1 (a pharmacological inhibitor of HIF-1). At 6 weeks, the mice were sacrificed, and kidneys, blood and urine samples were collected for further analysis. RESULTS: We demonstrated a significant increase of miR-155-5p in kidney tissues in Adriamycin-induced FSGS mouse models. We also found Adriamycin treatment led to the activation of HIF-1, and inhibition of HIF-1 using YC-1 partly prevented the induction of miR-155-5p. Functionally, anti-miR-155-5p attenuated kidney injury and delayed the progression of renal fibrosis. Further, anti-miR-155-5p also enhanced the expression of Nrf2 following Adriamycin treatment. Further, our luciferase microRNA target reporter assay verified Nrf2 as a direct target of miR-155-5p. Our further results indicated anti-miR-155-5p could suppress kidney oxidative stress and inflammation, also supporting Nrf2 was the direct target of miR-155-5p. Finally, we also found miR-155-5p did not increase in serum but significantly increased in urine, indicating urinary miR-155-5p may be useful for FSGS diagnosis. CONCLUSION: This study identified a HIF-1/miR-155-5p/Nrf2 axis which can promote kidney oxidative stress and inflammation, finally aggravating kidney injury and accelerating the progression of renal fibrosis in FSGS. Moreover, the increase in urinary miR-155-5p may be useful for the diagnosis of FSGS.

Development and validation of a combined model based on dual-sequence MRI radiomics for predicting the efficacy of high-intensity focused ultrasound ablation for hysteromyoma.

OBJECTIVES: To determine the value of dual-sequence magnetic resonance imaging (MRI)-based radiomics in predicting the efficacy of high-intensity focused ultrasound (HIFU) ablation for hysteromyoma. METHODS: A total of 142 patients with 172 hysteromyomas (95 hysteromyomas from the sufficient ablation group, and 77 hysteromyomas from the insufficient ablation group) were enrolled in the study. The clinical-radiological model was constructed with independent clinical-radiological risk factors, the radiomics model was constructed based on the optimal radiomics features of hysteromyoma from dual sequences, and the two groups of features were incorporated to construct the combined model. A fivefold cross validation procedure was adopted to validate these models. A nomogram was constructed, applying the combined model in the training cohort. The models were assessed with receiver operating characteristic (ROC) curves and integrated discrimination improvement (IDI). An independent test cohort comprising 40 patients was used to evaluate the performance of the optimal model. RESULTS: Among the three models, the average areas under the ROC curves (AUC) of the radiomics model and combined model were 0.803 (95% confidence interval (CI): 0.726-0.881) and 0.841 (95% CI: 0.772-0.909), which were better than the clinical-radiological model in the training cohort. The IDI showed that the combined model had the best prediction accuracy. The combined model also showed good discrimination in both the validation cohort (AUC = 0.834) and the independent test cohort (AUC = 0.801). CONCLUSION: The combined model based on the dual-sequence MRI radiomics is the most promising tool from our study to assist clinicians in predicting HIFU ablation efficacy.

Viral reactivation in the lungs of patients with severe pneumonia is associated with increased mortality, a multicenter, retrospective study.

Viral reactivation is widespread in patients with severe pneumonia, yet the landscape of viral reactivation in the lungs is not well-known. This study aims to assess the landscape and clinical features of viral reactivation in the early onset of severe pneumonia in ICU patients. The clinical data from 97 patients were collected retrospectively from the intensive care units of five teaching hospitals between June 2018 and July 2021. Metagenomic next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid (BALF) was performed at the onset of severe pneumonia. Cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), and Epstein-Barr virus (EBV) were the most common reactivated viruses in the lower respiratory tract of patients with severe pneumonia. After adjusting for the risk of confounding and competition of age, sex, sequential organ failure assessment, acute physiology chronic health assessment II and immunosuppression status, viral reactivation resulted in an overall 2.052-fold increase in 28-day all-cause mortality (95% CI: 1.004-4.194). This study showed that CMV, HSV-1, and EBV were the most common reactivated viruses in the lungs of patients with severe pneumonia. The existence of viral reactivations was associated with an increased risk of mortality. The simultaneous reactivation of multiple viruses needs to be considered in the design of clinical trials.

Optimization of photothermal conversion and catalytic sites for photo-assisted-catalytic degradation of volatile organic compounds.

Solar energy conversion is a promising strategy to enhance the elimination of volatile organic compounds (VOCs) and minimize power consumption. Herein, non-noble metal WC@WO3 as cocatalyst was composited with CeO2 to optimize photochemical and photothermal conversion for the catalytic ozonation of toluene and acetone. The photothermal conversion efficiencies of visible and infrared lights on 20%WC@WO3-CeO2 were 2.2 and 10.4 times higher than those on CeO2, respectively, which indicates that the equilibrium temperature of the catalyst remarkably increased under full-spectrum light irradiation. Moreover, WC@WO3 transferred electrons to CeO2 in 20%WC@WO3-CeO2 and thus remarkably improved the activity of catalytic sites. The synergy factor of light and O3 on 20%WC@WO3-CeO2 was 5.8, and the reaction rate of toluene and acetone reached 9274.5 and 35779.0 mg/(m3∙min), respectively. This work provides a low-cost and high-efficient catalyst for the utilization of solar energy for VOC control.