High expression of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) associated with Diquat-induced damage.

Diquat (DQ) is a commonly used bipyridine herbicide known for its toxic properties and adverse effects on individuals. However, the mechanism underlying DQ-induced damage remain elusive. Our research aimed to uncover the regulatory network involved in DQ-induced damage. We analyzed publicly accessible gene expression patterns and performed research using a DQ-induced damage animal model. The GSE153959 dataset from the Gene Expression Omnibus collection and the animal model of DQ-induced kidney injury were used to identify differentially expressed genes (DEGs). Pathways including the regulation of DNA-templated transcription in response to stress, RNA polymerase II transcription regulator complex and transcription coregulatory activity were shown to be enriched in 21 DEGs. We used least absolute shrinkage and selection operator (LASSO) regression analysis to find possible diagnostic biomarkers for DQ-induced damage. Then, we used an HK-2 cell model to confirm these results. Additionally, we confirmed that 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) was the major gene associated with DQ-induced damage using multi-omics screening. The sample validation strongly suggested that HMGCS2 has promise as a diagnostic marker and may provide new targets for therapy in the context of DQ-induced damage.

Multi-Omics Analysis Reveals the Toxicity of Polyvinyl Chloride Microplastics toward BEAS-2B Cells.

Polyvinyl chloride microplastics (PVC-MPs) are microplastic pollutants widely present in the environment, but their potential risks to human lung health and underlying toxicity mechanisms remain unknown. In this study, we systematically analyzed the effects of PVC-MPs on the transcriptome and metabolome of BEAS-2B cells using high-throughput RNA sequencing and untargeted metabolomics technologies. The results showed that exposure to PVC-MPs significantly reduced the viability of BEAS-2B cells, leading to the differential expression of 530 genes and 3768 metabolites. Further bioinformatics analyses showed that PVC-MP exposure influenced the expression of genes associated with fluid shear stress, the MAPK and TGF-ß signaling pathways, and the levels of metabolites associated with amino acid metabolism. In particular, integrated pathway analysis showed that lipid metabolic pathways (including glycerophospholipid metabolism, glycerolipid metabolism, and sphingolipid metabolism) were significantly perturbed in BEAS-2B cells following PVC-MPs exposure. This study provides new insights and targets for a deeper understanding of the toxicity mechanism of PVC-MPs and for the prevention and treatment of PVC-MP-associated lung diseases.

Flexible Wearable Strain Sensors Based on Laser-Induced Graphene for Monitoring Human Physiological Signals.

Flexible wearable strain sensors based on laser-induced graphene (LIG) have attracted significant interest due to their simple preparation process, three-dimensional porous structure, excellent electromechanical characteristics, and remarkable mechanical robustness. In this study, we demonstrated that LIG with various defects could be prepared on the surface of polyimide (PI) film, patterned in a single step by adjusting the scanning speed while maintaining a constant laser power of 12.4 W, and subjected to two repeated scans under ambient air conditions. The results indicated that LIG produced at a scanning speed of 70 mm/s exhibited an obvious stacked honeycomb micropore structure, and the flexible strain sensor fabricated with this material demonstrated stable resistance. The sensor exhibited high sensitivity within a low strain range of 0.4-8.0%, with the gauge factor (GF) reaching 107.8. The sensor demonstrated excellent stability and repeatable response at a strain of 2% after approximately 1000 repetitions. The flexible wearable LIG-based sensor with a serpentine bending structure could be used to detect various physiological signals, including pulse, finger bending, back of the hand relaxation and gripping, blinking eyes, smiling, drinking water, and speaking. The results of this study may serve as a reference for future applications in health monitoring, medical rehabilitation, and human-computer interactions.

Modeling study for predicting altered cellular activity induced by nanomaterials based on Dlk1-Dio3 gene expression and structural relationships.

Nanomaterials have been widely applied and developed due to its unique physicochemical characteristics, such as their small size. The environmental and biological effects caused by nanomaterials have raised concerns. In particular, some nanometal oxides have obvious biological toxicity and pose a major safety problem. The prediction model established by combining the expression levels of key genes with quantitative structure-activity relationship (QSAR) studies can predict the biotoxicity of nanomaterials by relying on both structural information and gene regulation information. This model can fill the gap of missing mechanisms in QSAR studies. In this study, we exposed A549 cells and BEAS-2B cells to 21 nanometal oxides for 24 h. Cell viability was assessed by measuring absorbance values using the CCK8 assay, and the expression levels of the Dlk1-Dio3 gene cluster were measured. By using the theoretical basis of the nano-QSAR model and the improved principles of the SMILES-based descriptors to combine specific gene expression and structural factors, new models were constructed using Monte Carlo partial least squares (MC-PLS) for the biotoxicity of the nanometal oxides on two different lung cells. The overall quality of the nano-QSAR models constructed by combining specific gene expression and structural parameters for A549 and BEAS-2B cells was better than that of the models constructed based on structural parameters only. The coefficient of determination (R2) of the A549 cell model increased from 0.9044 to 0.9969, and the Root Mean Square Error (RMSE) decreased from 0.1922 to 0.0348. The R2 of the BEAS-2B cell model increased from 0.9355 to 0.9705, and the RMSE decreased from 0.1206 to 0.0874. The model validation proved the proposed models have a good prediction, generalization ability and model stability. This study offers a new research perspective for the toxicity assessment of nanometal oxides, contributing to a more systematic safety evaluation of nanomaterials.

Multi-Omics Analyses Reveal the Mechanisms of Early Stage Kidney Toxicity by Diquat.

Diquat (DQ), a widely used bipyridyl herbicide, is associated with significantly higher rates of kidney injuries compared to other pesticides. However, the underlying molecular mechanisms are largely unknown. In this study, we identified the molecular changes in the early stage of DQ-induced kidney damage in a mouse model through transcriptomic, proteomic and metabolomic analyses. We identified 869 genes, 351 proteins and 96 metabolites that were differentially expressed in the DQ-treated mice relative to the control mice (p < 0.05), and showed significant enrichment in the PPAR signaling pathway and fatty acid metabolism. Hmgcs2, Cyp4a10, Cyp4a14 and Lpl were identified as the major proteins/genes associated with DQ-induced kidney damage. In addition, eicosapentaenoic acid, linoleic acid, palmitic acid and (R)-3-hydroxybutyric acid were the major metabolites related to DQ-induced kidney injury. Overall, the multi-omics analysis showed that DQ-induced kidney damage is associated with dysregulation of the PPAR signaling pathway, and an aberrant increase in Hmgcs2 expression and 3-hydroxybutyric acid levels. Our findings provide new insights into the molecular basis of DQ-induced early kidney damage.

Impact of connecting methods of continuous renal replacement therapy device on patients underwent extracorporeal membrane oxygenation: A retrospectively observational study.

OBJECTIVE: The objective of this study was to compare the safety and efficiency of different extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) connection methods. BACKGROUND: The number of patients receiving ECMO is increasing, and the fields of application are getting wider. However, patients receiving ECMO are prone to acute kidney injury and fluid overload requiring CRRT. There are few comparative studies of two different systems of connecting CRRT device and ECMO from safety and efficacy perspective. METHODS: This retrospective observational study included patients receiving ECMO in the extracorporeal life support centre of the First Affiliated Hospital of Nanjing Medical University from June, 2015, to December, 2020. Patients were divided into the parallel system group and integrated system group according to the connecting method between ECMO circuit and CRRT line. The outcomes were discharge survival rate, CRRT therapeutic dose completion rate, CRRT catheterisation time, CRRT initiating time, local bleeding at the CRRT catheter site, mean filter life, ECMO circuit thrombosis, ECMO air leakage, or blood leakage due to CRRT. RESULTS: Thirty patients in the parallel system group and 70 patients in the integrated system group were finally included. The discharge survival rate and CRRT therapeutic dose completion rate were not significantly different between the two groups. The parallel system group had significant longer CRRT initiating time (49.0 ± 12.1 min vs. 14.6 ± 2.1 min, P < 0.001) and shorter filter life (11.5 ± 3.2 h vs. 47.3 ± 14.0 h, P < 0.001) than the integrated system group. The occurrence rate of local bleeding was 93.3% in the parallel system group, and there is no bleeding case in the integrated system group. There was no case of ECMO circuit thrombosis from CRRT as well as ECMO air or blood leakage caused by CRRT in either group. ECMO therapy can be adapted by adjusting the position of the CRRT outlet in the integrated system. CONCLUSIONS: Connecting CRRT and ECMO as an integrated system might accelerate CRRT initiation, avoid local bleeding, and prolong filter life compared to the parallel system. The chance of developing CRRT-related ECMO circuit leak and thrombosis is manageable.

Machine Learning for Evaluating the Cytotoxicity of Mixtures of Nano-TiO2 and Heavy Metals: QSAR Model Apply Random Forest Algorithm after Clustering Analysis.

With the development and application of nanomaterials, their impact on the environment and organisms has attracted attention. As a common nanomaterial, nano-titanium dioxide (nano-TiO2) has adsorption properties to heavy metals in the environment. Quantitative structure-activity relationship (QSAR) is often used to predict the cytotoxicity of a single substance. However, there is little research on the toxicity of interaction between nanomaterials and other substances. In this study, we exposed human renal cortex proximal tubule epithelial (HK-2) cells to mixtures of eight heavy metals with nano-TiO2, measured absorbance values by CCK-8, and calculated cell viability. PLS and two ensemble learning algorithms are used to build multiple QSAR models for data sets, and the test set R2 is increased from 0.38 to 0.78 and 0.85, and RMSE is decreased from 0.18 to 0.12 and 0.10. After selecting the better random forest algorithm, the K-means clustering algorithm is used to continue to optimize the model, increasing the test set R2 to 0.95 and decreasing the RMSE to 0.08 and 0.06. As a reliable machine algorithm, random forest can be used to predict the toxicity of the mixture of nano-metal oxides and heavy metals. The cluster analysis can effectively improve the stability and predictability of the model, and provide a new idea for the prediction of cytotoxicity model in the future.

The regulation of LPCAT3 by miR-124-3p.1 in acute kidney injury suppresses cell proliferation by disrupting phospholipid metabolism.

Sepsis-associated acute renal injury (SA-AKI) is a common critical clinical disease. It is associated with increased mortality and increased risk of progression to chronic kidney disease. However, its pathogenesis is not fully known. We hypothesized that metabolic interactions mediate cell apoptosis and AKI. We found that phosphatidylcholine content in human renal tubular epithelial cells following lipopolysaccharide-induced injury was increased. The activity of lysophosphatidylcholine acyltransferase 3 (LPCAT3), a key enzyme in phospholipid metabolism, was increased, while the expression of miR-124-3p.1, which targets LPCAT3, was decreased. We also found that in the serum of SA-AKI patients, LPCAT3 activity was increased, and miR-124-3p.1 expression was decreased. Further experiments confirmed the specific binding of exocrine miR-124-3p.1 to LPCAT3. Our data reveal the molecular mechanisms of phospholipid metabolic disorder in early SA-AKI as well as the role of the miR-124-3p.1/LPCAT3 pathway in SA-AKI, which leads to ferroptosis. These results could provide the scientific basis for early diagnosis and renal replacement therapy in SA-AKI.

Preliminary Study of Resistance Mechanism of Botrytis cinerea to SYAUP-CN-26.

SYAUP-CN-26 (1S, 2R-((3-bromophenethyl)amino)-N-(4-chloro-2-trifluoromethylphenyl) cyclohexane-1-sulfonamide) is a novel sulfonamide compound with excellent activity against Botrytis cinerea. The present study sought to explore the mutant of B.cinerea resistant to SYAUP-CN-26 using SYAUP-CN-26 plates. Moreover, the cell membrane functions of B.cinerea, histidine kinase activity, relative conductivity, triglyceride, and cell membrane structure were determined, and the target gene histidine kinase Bos1 (AF396827.2) of procymidone was amplified and sequenced. The results showed that compared to the sensitive strain, the cell membrane permeability, triglyceride, and histidine kinase activity of the resistant strain showed significant changes. The relative conductivity of the sensitive strain increased by 6.95% and 9.61%, while the relative conductivity of the resistant strain increased by 0.23% and 1.76% with 26.785 µg/mL (EC95) and 79.754 µg/mL (MIC) of SYAUP-CN-26 treatment. The triglyceride inhibition rate of the resistant strain was 23.49% and 37.80%, which was 0.23% and 1.76% higher than the sensitive strain. Compared to the sensitive strain, the histidine kinase activity of the resistant strain was increased by 23.07% and 35.61%, respectively. SYAUP-CN-26 significantly damaged the cell membrane structure of the sensitive strain. The sequencing of the Bos1 gene of the sensitive and resistant strains indicated that SYAUP-CN-26 resistance was associated with a single point mutation (P348L) in the Bos1 gene. Therefore, it was inferred that the mutant of B.cinerea resistant to SYAUP-CN-26 might be regulated by the Bos1 gene. This study will provide a theoretical basis for further research and development of sulfonamide compounds for B. cinerea and new agents for the prevention and control of resistant B. cinerea.

Regulation of lung epithelial cell senescence in smoking-induced COPD/emphysema by microR-125a-5p via Sp1 mediation of SIRT1/HIF-1a.

Chronic obstructive pulmonary disease (COPD) affects the health of more than 300 million people worldwide; at present, there is no effective drug to treat COPD. Smoking is the most important risk factor, but the molecular mechanism by which smoking causes the disease is unclear. The senescence of lung epithelial cells is related to development of COPD. Regulation of miRNAs is the main epigenetic mechanism related to aging. ß-Galactose staining showed that the lung tissues of smokers have a higher degree of cellular senescence, and the expression of miR-125a-5p is high. This effect is obvious for smokers with COPD/emphysema, and there is a negative correlation between miR-125a-5p levels and values for forced expiratory volume in one second (FEV1)/forced vital capacity (FVC). After Balb/c mice were chronically exposed to various concentrations of cigarette smoke (CS), plethysmography showed that lung function was impaired, lung tissue senescence was increased, and the senescence-associated secretory phenotype (SASP) in bronchoalveolar lavage fluid was increased. For mouse lung epithelial (MLE)-12 cells treated with cigarette smoke extract (CSE), Sp1 and SIRT1 levels were low, HIF-1α acetylation levels were high, and cell senescence and secretion of SASP factors were elevated. Down-regulation of miR-125a-5p or up-regulation of Sp1 reversed these effects. In addition, compared with mice exposed to CS, knockdown of miR-125a-5p reduced lung epithelial cell senescence and COPD/emphysema. Therefore, in smoking-induced COPD, elevated miR-125a-5p participates in the senescence of lung epithelial cells through Sp1/SIRT1/HIF-1α. These findings provide evidence related to the pathogenesis of COPD/emphysema caused by chronic smoking.

Average mean arterial pressure in the first 6 hours of extracorporeal cardiopulmonary resuscitation in the prediction of the prognosis of neurological outcome: a single-center retrospective study.

OBJECTIVE: To study the correlation between the mean arterial pressure (MAP) level in the first 6 hours of extracorporeal cardiopulmonary resuscitation (ECPR) and patients' neurological outcomes. METHODS: Sex, age, basic comorbidities, the time from the first cardiac arrest to the start of CPR, the time from the first cardiac arrest to extracorporeal membrane oxygenation (ECMO), standardized ECMO flow, and the pH value at the beginning of ECMO and after 6 hours were recorded. MAP was recorded every 2 hours during the first 6 hours, and the average was calculated. The lactic acid clearance rate of the first 6 hours was calculated. Evaluated the neurological prognosis of patients at discharge. Then the patients were divided into groups according to their average MAP, and the above variables were compared in groups. RESULTS: Enrolled 63 adult ECPR patients. There were no statistically significant differences in sex, age, basic comorbidities, the time from the first cardiac arrest to the start of conventional CPR, the time from the first cardiac arrest to the start of ECMO, standardized ECMO flow, 6-hour lactic acid clearance rate, pH value at the sixth hour of operation between two groups. The pH value at the start of ECMO, survival rate, and good prognosis rate in low average MAP group were significantly lower. Low average MAP was associated with poor neurological outcomes (relative risk (RR) 1.50, 95% CI 1.17, 1.92). The RR of good neurological outcome for patients with average MAP ⩾65 mmHg was 5.91 (95% CI 1.45, 24.06), and the RR for average MAP ⩾100 mmHg was 1.18 (95% CI 0.19, 7.52). CONCLUSION: For ECPR patients, average MAP <65 mmHg in the first 6 hours of ECPR indicates a poor neurological prognosis. However, whether higher average MAP levels can improve the neurological prognosis of ECPR patient remains to be further studied.

Development of a LAMP method for detecting F129L mutant in azoxystrobin-resistant Pyricularia oryzae.

Azoxystrobin has been widely used since 1996 to control rice blast caused by Pyricularia oryzae. Azoxystrobin resistance related to mutations at the P. oryzae target protein (F129L of Cytb) has been reported worldwide. To quickly identify and detect resistant strains in the field, this research established a rapid loop-mediated isothermal amplification (LAMP) detection system for the F129L mutation. The system could detect the P. oryzae F129L (TTC-TTA) mutation at 62 °C within 60 min, with a detection limit of 100 fg/µL, which is 10 times higher than for conventional PCR. The method had high specificity and repeatability and could detect the F129L (TTC-TTA) mutation in plant tissues within 3 h. The LAMP method established in this study will be useful to detect azoxystrobin-resistant P. oryzae F129L mutant strains and generate significant data for the management of resistant P. oryzae isolates.

Can Cardiopulmonary Rehabilitation Facilitate Weaning of Extracorporeal Membrane Oxygenation (CaRe-ECMO)? Study Protocol for a Prospective Multidisciplinary Randomized Controlled Trial.

Background: Mortality of patients suffering from critical illness has been dramatically improved with advanced technological development of extracorporeal membrane oxygenation (ECMO) therapy. However, the majority of ECMO-supported patients failed to wean from ECMO therapy. As one of several options, cardiopulmonary rehabilitation serves as effective intervention in the improvement of cardiovascular and respiratory function in various major critical illness. Nonetheless, its role in facilitating ECMO weaning has not yet been explored. The purpose of this study is to investigate the effectiveness of cardiopulmonary rehabilitation on rate of ready for ECMO weaning in ECMO-supported patients (CaRe-ECMO). Methods: The CaRe-ECMO trial is a randomized controlled, parallel group, clinical trial. This trial will be performed in a minimum number of 366 ECMO-supported eligible patients. Patients will be randomly assigned to either: (1) the CaRe-ECMO group, which will be treated with usual care including pharmacotherapy, non-pharmacotherapy, and specific nursing for ECMO therapy and the CaRe-ECMO program; or (2) the control group, which will receive usual care only. The CaRe-ECMO program consists of protocolized positioning, passive range of motion (PROM) training, neuromuscular electrical stimulation (NMES), surface electrical phrenic nerve stimulation (SEPNS), and pulmonary rehabilitation. The primary outcome of the CaRe-ECMO trial is the rate of ready for ECMO weaning at CaRe-ECMO day 7 (refers to 7 days after the CaRe-ECMO program initiation). Secondary outcomes include rate of ECMO and mechanical ventilation weaning, total length in day of ready for ECMO weaning, ECMO weaning and mechanical ventilation, all-cause mortality, rate of major post-ECMO complications, ECMO unit length of stay (LOS) and hospital LOS, total cost for hospitalization, cerebral performance category (CPC), activities of daily living (ADL), and health-related quality of life (HRQoL). Discussion: The CaRe-ECMO is designed to answer the question "whether cardiopulmonary rehabilitation can facilitate weaning of ECMO (CaRe-ECMO)." Should the implementation of the CaRe-ECMO program result in superior primary and secondary outcomes as compared to the controls, specifically the add-on effects of cardiopulmonary rehabilitation to the routine ECMO practice for facilitating successful weaning, the CaRe-ECMO trial will offer an innovative treatment option for ECMO-supported patients and meaningfully impact on the standard care in ECMO therapy. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT05035797.

[Value of cardiac troponin T in predicting the prognosis of patients with cardiogenic shock receiving veno-arterial extracorporeal membrane oxygenation treatment: a consecutive 5-year retrospective study].

OBJECTIVE: To explore the changing trend of cardiac troponin T (cTnT) in patients with cardiogenic shock (CS) receiving veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and its predictive value. METHODS: A retrospective study was conducted. The data of patients with CS receiving V-A ECMO admitted to the First Affiliated Hospital of Nanjing Medical University from March 2015 to May 2020 were enrolled. The baseline data, ECMO related parameters, serum cTnT levels at 1, 2, 3 days after ECMO and intensive care unit (ICU) prognosis were recorded. The parameters with clinical significance and significant difference in univariate analysis were analyzed by binary multivariate Logistic regression analysis. Meanwhile, receiver operating characteristic (ROC) curve was drawn, area under ROC curve (AUC) was analyzed, and the threshold, sensitivity and specificity of serum cTnT level and its reduction rate for predicting clinical outcome were evaluated. RESULTS: A total of 72 patients were enrolled, of which 42 survived and 30 died at ICU discharge, and the ICU mortality was 41.7%. Univariate analysis results: compared with the survival group, the patients in the death group had higher acute physiology and chronic health evaluation II (APACHE II) score [32 (30, 34) vs. 29 (25, 30)], and the incidence of cardiac arrest before ECMO (70.0% vs. 31.0%), the ratios of invasive mechanical ventilation and continuous renal replacement therapy during ECMO were higher (96.7% vs. 66.7%, 83.3% vs. 42.9%), and the differences were statistically significant (all P < 0.05). Serum cTnT levels (ng/L) at 2 days and 3 days after ECMO in the death group were significantly higher than those in the survival group [2 days: 6 373.5 (898.3, 15 251.5) vs. 1 760.5 (933.0, 4 257.8), 3 day: 6 202.0 (758.9, 16 554.3) vs. 1 678.0 (623.3, 3 407.8), both P < 0.05], and the decrease rates of cTnT within 2 days and 3 days after ECMO were significantly lower than those in the survival group [2 days: 17.3% (-44.2%, 34.7%) vs. 36.8% (18.1%, 60.6%), 3 days: 32.4% (-30.0%, 55.5%) vs. 53.2% (38.3%, 72.3%), both P < 0.05]. Binary multivariate Logistic regression analysis showed that cardiac arrest before ECMO [odds ratio (OR) = 4.564, 95% confidence interval (95%CI) was 1.212-17.193, P = 0.025] and the decrease rate of cTnT level within 2 days after ECMO (OR = 1.617, 95%CI was 1.144-4.847, P = 0.026) were independent prognostic risk factors for the ICU death of CS patients receiving V-A ECMO. ROC curve analysis showed that the decline rate of cTnT within 2 days after ECMO transfer had a certain predictive value for the ICU death of CS patients receiving V-A ECMO. The AUC was 0.704 (95%CI was 0.584-0.824). The optimal diagnostic threshold was 40.0%, the sensitivity was 86.7%, the specificity was 52.4%, the positive predictive value was 66.9%, and the negative predictive value was 89.1%. CONCLUSIONS: The early decline rate of cTnT in CS patients who received V-A ECMO treatment in death group was lower than that of survival patients. The cTnT decline rate 2 days after ECMO was an independent risk factor for the death of such patients.

Is the blood pressure different between the paralyzed and unaffected arms or legs?

OBJECTIVES: To investigate whether the blood pressure (BP) levels are similar between the paralyzed and unaffected arms or legs. METHODS: This study enrolled 236 post-stroke patients with hemiplegic paralysis. Simultaneous four-limb BP was measured using four automatic BP devices for three times, and the average was used as final value. The inter-arm difference (IAD) and inter-ankle difference (IAND) were the BP difference between the arms or ankles, respectively. The difference between maximal BP reading and minimal BP reading was calculated as △BP to reflect the variation of three BP readings. RESULTS: The paralyzed arm had similar mean SBP (134.8 ± 18.7 vs. 135.1 ± 19.0 mmHg, NS) and DBP (79.5 ± 11.3 vs 78.1 ± 10.4 mmHg, NS) levels as compared with the unaffected arm. Similarly, the mean ankle SBP (143.6 ± 19.1 vs. 143.7 ± 18.6 mmHg, NS) and DBP (77.9 ± 17.7 vs. 75.8 ± 11.1 mmHg, NS) in the paralyzed legs were also similar to those in the unaffected legs. The detection rate of systolic IAD ≥10 mmHg was 5.9% and that for systolic IAND ≥15 mmHg was 20.3%. Meanwhile, △SBP levels were similar between two arms or ankles. CONCLUSION: In the post-stroke patients with hemiplegic paralysis, the SBP and DBP levels of the paralyzed and unaffected arms or ankles were similar.

The Effect of (1S,2R-((3-bromophenethyl)amino)-N-(4-chloro-2-trifluoromethylphenyl) cyclohexane-1 -sulfonamide) on Botrytis cinerea through the Membrane Damage Mechanism.

In recent years, Botrytis cinerea has led to serious yield losses because of its resistance to fungicides. Many sulfonamides with improved properties have been used. (1S,2R-((3-bromophenethyl)amino)-N-(4-chloro-2-trifluoromethylphenyl)cyclohexane-1-sulfonamide) (abbreviation: SYAUP-CN-26) is a new sulfonamide compound that has excellent activity against B. cinerea. This study investigated the effect of SYAUP-CN-26 on electric conductivity, nucleic acids leakage, malondialdehyde (MDA) content, and reducing sugars and membrane structure reduction of B. cinerea. The results showed that the cell membrane permeability of B. cinerea increased with increasing concentrations of SYAUP-CN-26; meanwhile, the sugar content decreased, the malondialdehyde content increased, and relative electric conductivity and nucleic acid substance leakage were observed in the cell after exposure to 19.263 mg/L SYAUP-CN-26 for 24 h. After 48 h of exposure to 1.823 mg/L and 19.263 mg/L SYAUP-CN-26, the cell membranes of B. cinerea mycelia were observed to be damaged under propidium iodide (PI) and transmission electron microscopy (TEM) observations. It is assumed that SYAUP-CN-26 was responsible for the damage of cell membrane. Overall, the results indicate that SYAUP-CN-26 could inhibit the growth of B. cinerea cells by damaging the cell membranes.

Adenomatous polyposis coli as a predictor of environmental chemical-induced transgenerational effects related to male infertility.

Exposure to toxic environmental chemicals during pregnancy is a ubiquitous threat to health with potentially transgenerational consequences. However, the underlying mechanism of how transgenerational effects occur as part of environmental chemical exposure are not well understood. We investigated the potential molecular changes associated with dibutyl phthalate exposure that induced transgenerational effects, using a rat model. Through the analysis of the Gene Expression Omnibus database, we found some similar studies of environmental exposure induced transgenerational effects. Then, we analyzed one of the studies and our results to identify the adenomatous polyposis coli (APC) gene. This gene participated the most of the pathways and was upregulated in both studies. We used the miRWALK data set to predict the microRNAs which targeted the APC gene. We confirmed the miR-30 family were significantly downregulated in F3 testis tissues and targeted the APC gene. In conclusion, the miR-30 family/APC interaction is a potential mechanism for the transgenerational effects induced by the environmental chemical.

Effect of Nano-SiO2 on Expression and Aberrant Methylation of Imprinted Genes in Lung and Testis.

Nanotechnology has been developing rapidly and is now used in many cutting-edge medical therapeutics. However, there is increasing concern that exposure to nanoparticles (NPs) may induce different systemic diseases as epigenetic mechanisms are associated with more and more disease. The role of NP epigenomic modification is important to disease etiology. Our study aimed to determine the epigenetic mechanisms of damage in lung and testis cells by exposing cells to SiO2 NPs. We used male C57BL/6 mice to characterize the damaging effect of SiO2 NPs on lung and testis cells as well as the resulting methylation state at the imprinted Dlk1/Dio3 domain region. The A549 cells exposed to SiO2 NPs had cell apoptosis, and male mice exposed to SiO2 NPs had altered lung and testis tissues. The genes in the imprinted domains Dlk1/Dio3 region changed in both tissues; Dlk1, Rtl1, and Dio3 are upregulated in testis while Dlk1 and Dio3 are also upregulated in lung tissues. Bisulfite sequencing PCR of male adult lung and testis were mostly hypomethylated, with a few hypermethylated CpGs. These findings indicate that nanoparticles play an important role in DNA methylation of imprinted genes.

Urinary trypsin inhibitor attenuates LPS-induced endothelial barrier dysfunction by upregulation of vascular endothelial-cadherin expression.

INTRODUCTION: Urinary trypsin inhibitor (UTI) decreases inflammatory cytokine levels and mortality in experimental animal models of inflammation. Here, we observed the effect of UTI on lipopolysaccharide (LPS)-induced hyperpermeability in human umbilical vein endothelial cells (HUVECs) and explored the role of vascular endothelial-cadherin (VE-cadherin) in its effect. METHODS: The effect of UTI on endothelial barrier hyperpermeability was detected by an electrical cell-substrate impedance sensing (ECIS) system and a transwell chamber system. The expression of VE-cadherin in HUVECs was examined by real-time PCR and western blot. RESULTS: We demonstrated that the alleviation of LPS-induced barrier dysfunction could be achieved by pretreatment with 3000 U/mL of UTI. VE-cadherin monoclonal antibody (mAb) could inhibit the protective effects. UTI maintained VE-cadherin expression by increasing protein stability at both the transcriptional and post-transcriptional levels. Meanwhile, VE-cadherin expression on the cell surface increased when the cells were pretreated with UTI. Furthermore, pretreatment with UTI decreased the phosphorylation of VE-cadherin at Tyr658 but not Tyr731. CONCLUSIONS: Our data show that prophylactic UTI maintains the endothelial barrier function, increases VE-cadherin expression, and inhibits the phosphorylation of VE-cadherin at Tyr658 under inflammatory conditions. It suggests a scientific and potential clinical therapeutic importance of UTI in treatment of inflammatory disorders.

Epithelial sodium channel is involved in H2S-induced acute pulmonary edema.

Acute pulmonary edema is one of the major outcomes of exposure to high levels of hydrogen sulfide (H2S). However, the mechanisms involved in H2S-induced acute pulmonary edema are still poorly understood. Therefore, the present study is designed to evaluate the role of epithelial sodium channel (ENaC) in H2S-induced acute pulmonary edema. The Sprague-Dawley rats were exposed to sublethal concentrations of inhaled H2S, then the pulmonary histological and lung epithelial cell injury were evaluated by hematoxylin-eosin staining and electron microscopy, respectively. In addition to morphological investigation, our results also revealed that H2S exposure significantly decreased the alveolar fluid clearance and increased the lung tissue wet-dry ratio. These changes were demonstrated to be associated with decreased ENaC expression. Furthermore, the extracellular-regulated protein kinases 1/2 pathway was demonstrated to be implicated in H2S-mediated ENaC expression, because PD98059, an ERK1/2 antagonist, significantly mitigated H2S-mediated ENaC down-regulation. Therefore, our results show that ENaC might represent a novel pharmacological target for the treatment of acute pulmonary edema induced by H2S and other hazardous gases.