Initial Experience of Long-Term Prophylaxis with Lanadelumab for Hereditary Angioedema in China: A Clinical Observation Study on Six Patients.

INTRODUCTION: Hereditary angioedema (HAE) is a rare genetic disorder caused by deficiency or dysfunction of C1-esterase inhibitor that is characterized by recurrent episodes of bradykinin-mediated edema. Lanadelumab has been the only available first-line therapy for long-term prophylaxis (LTP) of HAE in China since its approval in 2020. The present study aimed to investigate the clinical efficacy and safety of lanadelumab for LTP in Chinese patients. METHODS: A retrospective clinical data were collected for the 6 patients and used to examine the frequency of attack symptoms, disease-related loss of work days, and quality of life before and after LTP with lanadelumab. Health-related quality of life was assessed using the Dermatology Life Quality Index (DLQI) and the Angioedema Quality of Life Questionnaire (AE-QoL). RESULTS: Lanadelumab led to reductions of 97.8% and 98.5% in the attack rate and treated attack rate, respectively. All patients exhibited significant improvements in AE-QoL and DLQI scores (100% reduction rates) during the early treatment period (4 weeks and 2 weeks, respectively) and in missed work days/year (98.9% reduction rate). The efficacy of lanadelumab remained stable during COVID-19 vaccination and infection. No serious/severe treatment-emergent adverse events occurred during lanadelumab treatment. CONCLUSION: This study is the first report that demonstrates the clinical efficacy of lanadelumab and safety of LTP in HAE patients from Chinese mainland. A reasonable dosage plan can ensure a quick and long-lasting protective role of lanadelumab against HAE attacks, during COVID-19 pandemic period.

Multiparametric Magnetic Resonance Investigations on Acute and Long-Term Kidney Injury.

Acute kidney injury (AKI) is a frequent complication of critical illness and carries a significant risk of short- and long-term mortality. The prediction of the progression of AKI to long-term injury has been difficult for renal disease treatment. Radiologists are keen for the early detection of transition from AKI to long-term kidney injury, which would help in the preventive measures. The lack of established methods for early detection of long-term kidney injury underscores the pressing needs of advanced imaging technology that reveals microscopic tissue alterations during the progression of AKI. Fueled by recent advances in data acquisition and post-processing methods of magnetic resonance imaging (MRI), multiparametric MRI is showing great potential as a diagnostic tool for many kidney diseases. Multiparametric MRI studies offer a precious opportunity for real-time noninvasive monitoring of pathological development and progression of AKI to long-term injury. It provides insight into renal vasculature and function (arterial spin labeling, intravoxel incoherent motion), tissue oxygenation (blood oxygen level-dependent), tissue injury and fibrosis (diffusion tensor imaging, diffusion kurtosis imaging, T1 and T2 mapping, quantitative susceptibility mapping). The multiparametric MRI approach is highly promising but the longitudinal investigation on the transition of AKI to irreversible long-term impairment is largely ignored. Further optimization and implementation of renal MR methods in clinical practice will enhance our comprehension of not only AKI but chronic kidney diseases. Novel imaging biomarkers for microscopic renal tissue alterations could be discovered and benefit the preventative interventions. This review explores recent MRI applications on acute and long-term kidney injury while addressing lingering challenges, with emphasis on the potential value of the development of multiparametric MRI for renal imaging on clinical systems. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

The Effect of Acidic Residues on the Binding between Opicalcin1 and Ryanodine Receptor from the Structure-Functional Analysis.

Calcin is a group ligand with high affinity and specificity for the ryanodine receptors (RyRs). Little is known about the effect of its acidic residues on the spacial structure as well as the interaction with RyRs. We screened the opicalcin1 acidic mutants and investigated the effect of mutation on activity. The results indicated that all acidic mutants maintained the structural features, but their surface charge distribution underwent significant changes. Molecular docking and dynamics simulations were used to analyze the interaction between opicalcin1 mutants and RyRs, which demonstrated that all opicalcin1 mutants effectively bound to the channel domain of RyR1. This stable binding induced a pronounced asymmetry in the structure of the RyR tetramer, exhibiting a high degree of structural dissimilarity. [3H]Ryanodine binding to RyR1 was enhanced in D2A and D15A, which was similar to opicalcin1, but that effect was suppressed in E12A and E29A and reversed for the DE-4A, thereby inhibiting ryanodine binding. Opicalcin1 and DE-4A also exhibited the ability to form stable docking structures with RyR2. Acidic residues play a crucial role in the structure of calcin and its functional interaction with RyRs that is beneficial for the calcin optimization to develop more active peptide lead compounds for RyR-related diseases.

Compressed sensing 3D T2WI radiomics model: improving diagnostic performance in muscle invasion of bladder cancer.

BACKGROUND: Preoperative discrimination between non-muscle-invasive bladder cancer (NMIBC) and the muscle invasive bladder cancer (MIBC) is a determinant of management. The purpose of this research is to employ radiomics to evaluate the diagnostic value in determining muscle invasiveness of compressed sensing (CS) accelerated 3D T2-weighted-SPACE sequence with high resolution and short acquisition time. METHODS: This prospective study involved 108 participants who underwent preoperative 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted sequences. The cohort was divided into training and validation cohorts in a 7:3 ratio. In the training cohort, a Rad-score was constructed based on radiomic features selected by intraclass correlation coefficients, pearson correlation coefficient and least absolute shrinkage and selection operator . Multivariate logistic regression was used to develop a nomogram combined radiomics and clinical indices. In the validation cohort, the performances of the models were evaluated by ROC, calibration, and decision curves. RESULTS: In the validation cohort, the area under ROC curve of 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted models were 0.87(95% confidence interval (CI):0.73-1.00), 0.79(95%CI:0.63-0.96) and 0.77(95%CI:0.60-0.93), respectively. The differences in signal-to-noise ratio and contrast-to-noise ratio between 3D-CS-T2-weighted-SPACE and 3D-T2-weighted-SPACE sequences were not statistically significant(p > 0.05). While the clinical model composed of three clinical indices was 0.74(95%CI:0.55-0.94) and the radiomics-clinical nomogram model was 0.88(95%CI:0.75-1.00). The calibration curves confirmed high goodness of fit, and the decision curve also showed that the radiomics model and combined nomogram model yielded higher net benefits than the clinical model. CONCLUSION: The radiomics model based on compressed sensing 3D T2WI sequence, which was acquired within a shorter acquisition time, showed superior diagnostic efficacy in muscle invasion of bladder cancer. Additionally, the nomogram model could enhance the diagnostic performance.

Copper-induced oxidative stress inhibits asexual reproduction of Aurelia coerulea polyps.

OBJECTIVE: Our research aims to investigate the specific mechanisms by which copper inhibits the asexual proliferation of Aurelia coerulea polyps. METHODS: Aurelia coerulea polyps were exposed to various CuSO4 concentrations to study metamorphosis and budding proliferation. Oxidative stress markers (ROS, MDA, CAT, H2O2, T-AOC, SOD) were measured in polyps and early strobilae. Transcriptomic analysis were used to compare differences in gene expression and enrichment pathways between untreated and copper-exposed polyps. Additionally, RT-qPCR was used to analyze the expression of key molecules. Antioxidant L-Ascorbic acid was applied to determine the role of oxidative stress in asexual reproduction of Aurelia coerulea polyps when exposed to copper. RESULTS: Copper inhibited strobilization and budding of Aurelia coerulea polyps in a dose-dependent manner, in which oxidative stress was involved. Transcriptomic data suggested that the DNA replication pathway was significantly enriched in early strobilae compared to polyps. However, copper treatment repealed the difference of DNA replication pathway between early strobilae compared and polyps. Transcriptomic data suggested that alanine, aspartate, and glutamate metabolism pathways were enriched in untreated budding polyps compared to copper-exposed polyps. After applying the antioxidant L-Ascorbic acid to copper-exposed polyps, various oxidative indicators changed to different extents, with increases in ROS, MDA, CAT, H2O2, and SOD and a decrease in T-AOC. Further more, the time required for polyps to develop into early strobila was shortened, indicating that the delay in metamorphosis caused by copper exposure was effectively alleviated. And the budding rate increased, indicating that the inhibition of budding proliferation caused by copper exposure was effectively alleviated. The expression of key genes were consist with the transcriptomic sequencing results. CONCLUSION: Copper exposure causes oxidative stress resulting in the inhibition of asexual reproduction in Aurelia coerulea polyps, including metamorphosis and budding.

The value of elevated cerebrospinal fluid lactate concentrations in post-neurosurgical bacterial meningitis.

Bacterial meningitis is a serious complication after neurosurgery and has a high mortality rate. Early diagnosis and timely treatment are crucial or will have disastrous consequences. The classic triad of bacterial meningitis lacks sensitivity and specificity. Therefore, the diagnosis of post-neurosurgical bacterial meningitis relies on cerebrospinal fluid. But traditional cerebrospinal fluid parameters are not completely reliable in diagnosing post-neurosurgical bacterial meningitis. Previous studies have found that CSF lactate concentration is related to bacterial meningitis. But, after the craniocerebral operation, the cerebrospinal fluid of most patients is bloody. Whether red blood cells interfere with diagnosing PNBM based on lactate concentration is limited. In the current study, we further analysis on whether red blood cells interfere with diagnosing PNBM based on lactate concentration. This study aimed to investigate the value of cerebrospinal fluid lactate concentrations in post-neurosurgical bacterial meningitis. A prospective observational study was performed on 62 patients at Kunshan First People's Hospital's intensive care unit affiliated with Jiangsu University. We found that erythrocytes do not affect cerebrospinal fluid lactate, and elevated lactate concentrations can be used as a marker for postoperative bacterial meningitis.

Asprosin is positively associated with metabolic syndrome in hemodialysis patients: a cross-sectional study.

INTRODUCTION: Metabolic syndrome (MS) has a high prevalence in hemodialysis patients. High asprosin levels are associated with the accumulation of adiposity and an increase in body weight, which may drive the development of this syndrome. The relationship between asprosin and MS in patients on hemodialysis has not been investigated. MATERIALS AND METHODS: We enrolled hemodialysis patients at the hemodialysis center of one hospital in May 2021. MS was defined by the International Diabetes Federation. Fasting serum asprosin levels were measured. ROC curve, multivariate logistic regression and Spearman's rank correlation analyses were performed. RESULTS: In total, 134 patients were included, with 51 with MS and 83 without MS. Among the patients with MS, there was a significantly higher proportion of women (54.9%), prevalence of DM (p < 0.001), waist circumference (p < 0.001), BMI (p < 0.001), triglycerides (p < 0.001), and low-density lipoprotein cholesterol(p < 0.050), and PTH (p < 0.050) contents and a lower diastolic pressure(p < 0.050) and high-density lipoprotein cholesterol level (p < 0.001) than those in patients without MS. The patients with MS exhibited significantly higher serum asprosin levels than the non-MS patients [502.2 ± 153.3 ng/ml vs. 371.5 ± 144.9 ng/ml, p < 0.001]. The AUC for the serum asprosin level was 0.725 (95% confidence interval: 0.639, 0.811). Multivariate logistic regression analysis revealed that asprosin was independently and significantly positively associated with MS (OR = 1.008, p < 0.010). Asprosin levels tended to rise as the number of diagnostic criteria of MS increased (p for trend <0.001). CONCLUSIONS: Fasting serum asprosin is positively correlated with MS and could be an independent risk factor for MS in hemodialysis patients.

Construction of a predictive model for immunotherapy efficacy in lung squamous cell carcinoma based on the degree of tumor-infiltrating immune cells and molecular typing.

BACKGROUND: To construct a predictive model of immunotherapy efficacy for patients with lung squamous cell carcinoma (LUSC) based on the degree of tumor-infiltrating immune cells (TIIC) in the tumor microenvironment (TME). METHODS: The data of 501 patients with LUSC in the TCGA database were used as a training set, and grouped using non-negative matrix factorization (NMF) based on the degree of TIIC assessed by single-sample gene set enrichment analysis (GSEA). Two data sets (GSE126044 and GSE135222) were used as validation sets. Genes screened for modeling by least absolute shrinkage and selection operator (LASSO) regression and used to construct a model based on immunophenotyping score (IPTS). RNA extraction and qPCR were performed to validate the prognostic value of IPTS in our independent LUSC cohort. The receiver operating characteristic (ROC) curve was constructed to determine the predictive value of the immune efficacy. Kaplan-Meier survival curve analysis was performed to evaluate the prognostic predictive ability. Correlation analysis and enrichment analysis were used to explore the potential mechanism of IPTS molecular typing involved in predicting the immunotherapy efficacy for patients with LUSC. RESULTS: The training set was divided into a low immune cell infiltration type (C1) and a high immune cell infiltration type (C2) by NMF typing, and the IPTS molecular typing based on the 17-gene model could replace the results of the NMF typing. The area under the ROC curve (AUC) was 0.82. In both validation sets, the IPTS of patients who responded to immunotherapy were significantly higher than those who did not respond to immunotherapy (P = 0.0032 and P = 0.0451), whereas the AUC was 0.95 (95% CI = 1.00-0.84) and 0.77 (95% CI = 0.58-0.96), respectively. In our independent cohort, we validated its ability to predict the response to cancer immunotherapy, for the AUC was 0.88 (95% CI = 1.00-0.66). GSEA suggested that the high IPTS group was mainly involved in immune-related signaling pathways. CONCLUSIONS: IPTS molecular typing based on the degree of TIIC in the TME could well predict the efficacy of immunotherapy in patients with LUSC with a certain prognostic value.

A combined protein toxin screening based on the transcriptome and proteome of Solenopsis invicta.

BACKGROUND: Multi-omics technology provides a good tool to analyze the protein toxin composition and search for the potential pathogenic factors of Solenopsis invicta, under the great harm of the accelerated invasion in southern China. METHODS: Species collection, functional annotation, toxin screening, and 3D modeling construction of three interested toxins were performed based on the successfully constructed transcriptome and proteome of S. invicta. RESULTS: A total of 33,231 unigenes and 721 proteins were obtained from the constructed transcriptome and proteome, of which 9,842 (29.62%) and 4,844 (14.58%) unigenes, as well as 469 (65.05%) and 71 (99.45%) proteins were annotated against the databases of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, respectively. After comparing with the uniprot toxin database, a total of 316 unigenes and 47 proteins (calglandulin, venom allergen 3, and venom prothrombin activator hopsarin-D, etc.) were successfully screened. CONCLUSIONS: The update of annotations at the transcriptome and proteome levels presents a progression in the comprehension of S. invicta in China. We also provide a protein toxin list that could be used for further exploration of toxicity as well as its antagonistic strategy by S. invicta.

LncRNA LOXL1-AS1 Facilitates the Oncogenic Character in Cervical Cancer by the miR-526b-5p /LYPLA1 Axis.

Increasing reports demonstrate that long noncoding RNAs participate in the regulation of numerous malignancies, cervical cancer included. Although lncRNA LOXL1 antisense RNA 1 has been commonly accepted to be an oncogene in many cancers. Here, the role of LOXL1-AS1 in CC still need to be explored. In this study, LOXL1-AS1 was found elevated in CC tissues and cells. LOXL1-AS1 depletion restrained CC cell proliferation, migration, invasion, and angiogenesis in vivo. Furthermore, we found that LOXL1-AS1 upregulated Lysophospholipase 1 expression via sequestering miR-526b-5p. Rescue assays revealed that overexpression of LYPLA1 reversed the LOXL1-AS1 silencing-induced inhibitory effects on the malignant phenotypes of CC cells. To conclude, this study showed that LOXL1-AS1 facilitates cellular process in CC via functioning as a miR-526b-5p sponge.

Potential mechanism of oral baicalin treating psoriasis via suppressing Wnt signaling pathway and inhibiting Th17/IL-17 axis by activating PPARγ.

Psoriasis (PSO), an immune-mediated chronic inflammatory skin disease, has seriously affected the quality of patients' life. It is urgent to find effective medicines with lower costs and less side effects. Baicalin (HQG) is the main bioactive substance from Scutellaria baicalensis with effects of anti-inflammation and immunoregulation. Herein, we explored the effect of oral HQG treating PSO and its potential mechanism. Firstly, network pharmacology was used to predict that HQG may act on Estrogen, TNF-alpha (tumor necrosis factor, TNF), interleukin-17 (IL-17) signaling pathways and Th17 cell differentiation, especially the key targets including TNF, Proto-oncogene tyrosine-protein kinase Src, Peroxisome proliferator-activated receptor gamma and Matrix metalloproteinase-9. Imiquimod (IMQ)-induced mice were then used to study the effects of HQG treating PSO. HQG could significantly ameliorate the skin lesions, decrease the level of inflammatory factors and inhibit Th1/Th17 cell differentiation in IMQ-induced mice. Finally, transcriptome analysis of skin lesions integrated with the prediction of network pharmacology further demonstrated that the potential mechanism may be associated with suppressing Wnt signaling pathway and inhibiting Th17/IL-17 axis by activating PPARγ. In conclusion, this study suggested that HQG may be a promising agent for further studies in the search for therapeutic strategies to treat PSO in the future.

LncRNA NR2F1-AS1 Inhibits the Malignant Properties of Cervical Cancer Cells via Targeting miR-642a-3p/NR2F1 Axis.

Background: Cervical cancer (CC), as a serious menace to the health of women, has long been one of the most lethal gynecologic neoplasms throughout the world. Long non-coding RNA (LncRNA) NR2F1-AS1 has been documented to exert crucial functions in many malignant tumors. Nonetheless, the function and molecular mechanism of NR2F1-AS1 in CC remain completely unknown. Objectives: This study aimed to explore the function and molecular mechanism of NR2F1-AS1 in CC. Methods: The expression levels of NR2F1-AS1, miR-642a-3p, NR2F1 in CC tissues, and cell lines were examined by reverse transcription real-time quantitative polymerase chain reaction. Cell viability, proliferation, migration, and invasion were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, colony formation and Transwell assays. The protein levels of epithelial-mesenchymal transition markers and NR2F1 in CC cells were assessed by Western blot analysis. The correlations among NR2F1-AS1, miR-642a-3p, and NR2F1 were estimated through luciferase reporter and RNA immunoprecipitation assays. Results: NR2F1-AS1 expression was clearly downregulated in CC tissues and cell lines. Molecular mechanistic experiments showed that NR2F1-AS1 overexpression upregulated NR2F1 expression in CC cells by directly binding to miR-642a-3p, and inhibiting by this way cell viability, proliferation, migration, and invasion in CC. Rescue assays showed that NR2F1 knockdown or miR-642a-3p overexpression offset NR2F1-AS1 upregulation-induced inhibition on CC cell malignant phenotypes. Conclusions: These findings revealed that NR2F1-AS1 played a tumor suppressor role in CC by mediating the miR-642a-3p/NR2F1 axis.

Wogonin inhibits in vitro herpes simplex virus type 1 and 2 infection by modulating cellular NF-κB and MAPK pathways.

BACKGROUND: Wogonin, a natural flavonoid-like chemical compound, exhibits anti-inflammatory, antitumor, antiviral, neuroprotective, and anxiolytic effects by modulating a variety of cellular signaling pathways including PI3K-Akt, p53, nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK) pathways. In this study, its antiviral effect against herpes simplex virus (HSV) type 1 and 2 (HSV-1 and HSV-2) replication was investigated. RESULTS: Wogonin suppressed HSV-2-induced cytopathic effect (CPE) and reduced viral mRNA transcription, viral protein synthesis, and infectious virion particle titers in a dose-dependent manner. A time-of-drug-addition assay demonstrated that wogonin acted as a postentry viral inhibitor. Wogonin also significantly reduced HSV-induced NF-κB and MAPK pathway activation, which has previously been demonstrated to be important for viral replication. CONCLUSIONS: Our results suggest that the anti-herpes effect of wogonin may be mediated by modulation of cellular NF-κB and JNK/p38 MAPK pathways and imply that wogonin may be useful as an anti-HSV agent.

The bHLH transcription factor PPLS1 regulates the color of pulvinus and leaf sheath in foxtail millet (Setaria italica).

KEY MESSAGE: The bHLH transcription factor, PPLS1, interacts with SiMYB85 to control the color of pulvinus and leaf sheath by regulating anthocyanin biosynthesis in foxtail millet (Setaria italica). Foxtail millet (Setaria italica), a self-pollinated crop with numerous small florets, is difficult for cross-pollination. The color of pulvinus and leaf sheath with purple being dominant to green is an indicative character and often used for screening authentic hybrids in foxtail millet crossing. Deciphering molecular mechanism controlling this trait would greatly facilitate genetic improvement of cultivars in foxtail millet. Here, using the F2 bulk specific-locus amplified fragment sequencing approach, we mapped the putative causal gene for the purple color of pulvinus and leaf sheath (PPLS) trait to a 100 Kb region on chromosome 7. Expression analyses of the 15 genes in this region revealed that Seita.7G195400 (renamed here as PPLS1) was differentially expressed between purple and green cultivars. PPLS1 encodes a bHLH transcription factor and is localized in the nucleus with a transactivation activity. Furthermore, we observed that expression of a MYB transcription factor gene, SiMYB85 (Seita.4G086300) involved in anthocyanin biosynthesis, shows a totally positive association with that of PPLS1. Heterologous co-expression of both PPLS1 and SiMYB85 in tobacco leaves led to elevated anthocyanin accumulation and expression of some anthocyanin-related genes. Furthermore, PPLS1 physically interacts with SiMYB85. Taken together, our results suggest that PPLS1 interacts with SiMYB85 to control the color of pulvinus and leaf sheath by regulating anthocyanin biosynthesis in foxtail millet.

Correction to: KIF5B-RET fusion kinase promotes cell growth by multilevel activation of STAT3 in lung cancer.

After the publication of this work [1].

Blood Oxygen Level-Dependent Imaging and Intravoxel Incoherent Motion MRI of Early Contrast-Induced Acute Kidney Injury in a Rabbit Model.

BACKGROUND: To evaluate the application of blood oxygenation level-dependent (BOLD)imaging and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) on assessing early contrast-induced acute kidney injury (CIAKI). MATERIALS: Sixty rabbits were randomly chosen to undergo iohexol (1.0, 2.5, and 5.0 [gI/kg], respectively; n = 15 for each group) or saline injection (n = 15). In each group, 6 rabbits underwent MRI at 24 h before injection and after injection of iohexol or saline (1 h and 1, 2, 3, and 4 days); meanwhile, out of the remaining 9 rabbits, 3 were chosen for MRI acquisition, and then they were killed at specific time points (1 h, 1 day, and 3 days, respectively). RESULTS: The strong attenuation of pure molecular diffusion (D), apparent diffusion coefficient (ADC), and perfusion fraction (f) was observed at 1 day, while pseudodiffusion coefficient (D*) showed a significant decrease at 1 h after iohexol injection. A distinct elevation of apparent transverse relaxation rate (R2*) reached the maximum levels on day 1, which was consistent with the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor. ADC, D, and R2* correlated well with histopathological parameters and biochemical parameters. CONCLUSION: BOLD combined with IVIM is effective to monitor renal pathophysiology associated with CIAKI.

The effect of noise exposure on insulin sensitivity in mice may be mediated by the JNK/IRS1 pathway.

BACKGROUND: Epidemiological studies have suggested that noise exposure may increase the risk of type 2 diabetes mellitus (T2DM), and experimental studies have demonstrated that noise exposure can induce insulin resistance in rodents. The aim of the present study was to explore noise-induced processes underlying impaired insulin sensitivity in mice. METHODS: Male ICR mice were randomly divided into four groups: a control group without noise exposure and three noise groups exposed to white noise at a 95-dB sound pressure level for 4 h/day for 1, 10, or 20 days (N1D, N10D, and N20D, respectively). Systemic insulin sensitivity was evaluated at 1 day, 1 week, and 1 month post-noise exposure (1DPN, 1WPN, and 1MPN) via insulin tolerance tests (ITTs). Several insulin-related processes, including the phosphorylation of Akt, IRS1, and JNK in the animals' skeletal muscles, were examined using standard immunoblots. Biomarkers of inflammation (circulating levels of TNF-α and IL-6) and oxidative stress (SOD and CAT activities and MDA levels in skeletal muscles) were measured via chemical analyses. RESULTS: The data obtained in this study showed the following: (1) The impairment of systemic insulin sensitivity was transient in the N1D group but prolonged in the N10D and N20D groups. (2) Noise exposure led to enhanced JNK phosphorylation and IRS1 serine phosphorylation as well as reduced Akt phosphorylation in skeletal muscles in response to exogenous insulin stimulation. (3) Plasma levels of TNF-α and IL-6, CAT activity, and MDA concentrations in skeletal muscles were elevated after 20 days of noise exposure. CONCLUSIONS: Impaired insulin sensitivity in noise-exposed mice might be mediated by an enhancement of the JNK/IRS1 pathway. Inflammation and oxidative stress might contribute to insulin resistance after chronic noise exposure.

HPV11 E6 mutation by overexpression of APOBEC3A and effects of interferon-ω on APOBEC3s and HPV11 E6 expression in HPV11.HaCaT cells.

BACKGROUND: Condyloma acuminatum, infected by low-risk human papillomaviruses (e.g., HPV6 and HPV11), is one of the most widespread sexually transmitted diseases. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 proteins (APOBEC3s, A3s) are cellular cytidine deaminases acting as antiviral factors through hypermutation of viral genome. However, it remains unknown whether A3s results in HPV11 gene mutations and interferon-ω (IFN-ω) exhibits antiviral activities through the A3s system. Here we investigated whether enhanced APOBEC3A (A3A) resulted in the E6 gene mutations and explore the effects of recombinant human interferon-ω (rhIFN-ω) on A3s/E6 expression in HaCaT keratinocytes containing the genome of HPV 11 (HPV11.HaCaT cells). METHODS: A3A-overexpressed HPV11.HaCaT (A3A-HPV11.HaCaT) cells were established by lentiviral infection and verified by immunofluorescence and western-blotting. Cell cycle, E6 gene mutations, APOBEC3s/E6 gene expression and subcellular localization were detected by FACS, 3D-PCR and sequencing, qRT-PCR and immunofluorescence respectively. RESULTS: The results suggested that A3A-HPV11.HaCaT cells were successfully established. Enhanced A3A induced S-phase arrest, G > A/C > T mutations and obvious reduction of E6 mRNA expression. A3A/A3B mRNA expression was up-regulated at 6 h and 12 h and obvious A3A staining existed throughout HPV11.HaCaT cells after rhIFN-ω treatment. RhIFN-ω could also inhibit mRNA expression of HPV11 E6 significantly. CONCLUSIONS: Enhanced A3A repressed HPV11 E6 expression through gene hypermutation, and rhIFN-ω might be an effective agent against HPV11 infection by up-regulation of A3A.

Evolution of Phosphorus-Containing Groups on Activated Carbons during Heat Treatment.

Two types of activated carbons have been prepared by H3PO4 activation of lignocellulose and by H3PO4 modification of activated carbon, and then heat-treated at temperatures from 400 to 900 °C in an atmosphere of N2 or H2 to investigate the evolution of phosphorus-containing groups. Elemental analysis, X-ray photoelectron spectroscopy, 31P nuclear magnetic resonance, nitrogen adsorption, and scanning electron microscopy have been used to analyze the physicochemical properties of the activated carbons. The results show that C-O-P linkages of phosphorus-containing groups can progressively evolve into C-P-O, C3-P═O, C3-P, and eventually elemental phosphorus as a result of heat treatment. Phosphate-like groups are much more thermally stable in an N2 than in an H2 atmosphere. In N2, C-O-P linkages significantly evolve into C-P-O and C3-P═O at up to 800 °C, whereas C3-P linkages are not formed even at 900 °C. In H2, the corresponding evolution remarkably occurs at 500 °C, forming C3-P linkages and eventually elemental phosphorus. Moreover, the two activated carbons exhibit different evolution trends, suggesting that the evolution happens more easily for phosphorus-containing groups located on the edges of graphite-like crystallites than those in the lattice. Finally, we propose different evolution pathways of phosphorus-containing groups upon heat treatment in N2 and H2 atmospheres.