Two imprinted genes primed by DEMETER in the central cell and activated by WRKY10 in the endosperm.

The early development of the endosperm is crucial for balancing the allocation of maternal nutrients to offspring. This process is believed to be evolutionarily associated with genomic imprinting, resulting in parentally biased allelic gene expression. Beyond FertilizationIndependentSeed (FIS) genes, the number of imprinted genes involved in early endosperm development and seed size determination remains limited. This study introduces two early endosperm-expressed HAIKU (IKU) downstream Candidate F-box 1 (ICF1) and ICF2, as maternally expressed imprinted genes (MEGs). Although these genes are also demethylated by DEMETER (DME) in the central cell, their activation differs from the direct DME-mediated activation seen in classical MEGs such as the FIS genes. Instead, ICF maternal alleles carry pre-established hypomethylation in their promoters, priming them for activation by the WRKY10 transcription factor in the endosperm. On the contrary, paternal alleles are predominantly suppressed by CG methylation. Furthermore, we find that ICF genes partially contribute to the small seed size observed in iku mutants. Our discovery reveals a two-step regulatory mechanism that highlights the important role of conventional transcription factors in the activation of imprinted genes, which was previously not fully recognized. Therefore, the mechanism provides a new dimension to understand the transcriptional regulation of imprinting in plant reproduction and development.

Effect of decentration and tilt on the in vitro optical quality of monofocal and trifocal intraocular lenses.

PURPOSE: To evaluate and compare the effect of decentration and tilt on the optical quality of monofocal and trifocal intraocular lenses (IOL). METHODS: Optical quality of a monofocal IOL (AcrySof IQ SN60WF; Alcon Laboratories, Inc., USA) and a trifocal IOL (AcrySof IQ PanOptix; Alcon Laboratories, Inc., USA) was assessed using an in vitro optical bench (OptiSpheric IOL R&D; Trioptics GmbH, Germany). At apertures of 3.0 mm and 4.5 mm, modulation transfer function (MTF) at spatial frequency of 50 lp/mm, MTF curve and the United States Air Force (USAF) resolution test chart of the two IOLs were measured and compared at their focus with different degrees of decentration and tilt. Optical quality at infinity, 60 cm and 40 cm and the through-focus MTF curves were compared when the two IOLs were centered at apertures of 3.0 mm and 4.5 mm. Spectral transmittance of the two IOLs was measured by the UV-visible spectrophotometer (UV 3300 PC; MAPADA, China). RESULTS: The SN60WF and the PanOptix filtered blue light from 400 to 500 nm. Both IOLs at the far focus and the PanOptix at the intermediate focus showed a decrease in optical quality with increasing decentration and tilt. The PanOptix demonstrated enhanced optical quality compared to the previous gradient at the near focus at a decentration range of 0.3-0.7 mm with a 3.0 mm aperture, and 0.5 mm with a 4.5 mm aperture, whereas other conditions exhibited diminished optical quality with increasing decentration and tilt at the focus of both IOLs. When the two IOLs were centered, the SN60WF had better optical quality at infinity, while the PanOptix had better optical quality at 60 cm and 40 cm defocus. The optical quality of the SN60WF exceeded that of the PanOptix at far focus, with a 3 mm aperture decentration up to 0.7 mm and a 4.5 mm aperture decentration up to 0.3 mm; this observation held true for all tilts, irrespective of aperture size. As both decentration and tilt increased, the optical quality of the SN60WF deteriorated more rapidly than that of the PanOptix at the far focal point. CONCLUSIONS: The SN60WF showed a decrease in optical quality with increasing decentration and tilt. Optical quality of the PanOptix at the near focus increased in some decentration conditions and decreased in some conditions, while it showed a decrease at the other focuses with increasing decentration. While tilt only had a negative effect on optical quality. When both IOLs were centered, the PanOptix provided a wider range of vision, while the SN60WF provided better far distance vision. At the far focus, the SN60WF has better resistance to tilt than the PanOptix, but the optical quality degrades more quickly when decentered and tilted.

A Six-gene Prognostic Model Based on Neutrophil Extracellular Traps (NETs)-related Gene Signature for Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common malignant cancers. Neutrophil extracellular traps (NETs) have been discovered to play a crucial role in the pathogenesis of LUAD. We aimed to establish an innovative prognostic model for LUAD based on the distinct expression patterns of NETs-related genes. METHODS: The TCGA LUAD dataset was utilized as the training set, while GSE31210, GSE37745, and GSE50081 were undertaken as the verification sets. The patients were grouped into clusters based on the expression signature of NETs-related genes. Differentially expressed genes between clusters were identified through the utilization of the random forest and LASSO algorithms. The NETs score model for LUAD prognosis was developed by multiplying the expression levels of specific genes with their corresponding LASSO coefficients and then summing them. The validity of the model was confirmed by analysis of the survival curves and ROC curves. Additionally, immune infiltration, GSEA, mutation analysis, and drug analysis were conducted. Silencing ABCC2 in A549 cells was achieved to investigate its effect. RESULTS: We identified six novel NETs-related genes, namely UPK1B, SFTA3, GGTLC1, SCGB3A1, ABCC2, and NTS, and developed a NETs score signature, which exhibited a significant correlation with the clinicopathological and immune traits of the LUAD patients. High-risk patients showed inhibition of immune-related processes. Mutation patterns exhibited variability among the different groups. AZD3759, lapatinib, and dasatinib have been identified as potential candidates for LUAD treatment. Moreover, the downregulation of ABCC2 resulted in the induction of apoptosis and suppression of migration and invasion in A549 cells. CONCLUSION: Altogether, this study has identified a novel NET-score signature based on six novel NET-related genes to predict the prognosis of LUAD and ABCC2 and has also explored a new method for personalized chemo-/immuno-therapy of LUAD.

Cohort profile: the China surgery and anesthesia cohort (CSAC).

The China Surgery and Anaesthesia Cohort (CSAC) study was launched in July 2020 and is an ongoing prospective cohort study recruiting patients aged 40-65 years who underwent elective surgeries with general anaesthesia across four medical centres in China. The general objective of the CSAC study is to improve our understanding of the complex interaction between environmental and genetic components as well as to determine their effects on a wide range of interested surgery/anaesthesia-related outcomes. To achieve this goal, we collected enriched phenotypic data, e.g., sociodemographic characteristics, lifestyle factors, perioperative neuropsychological changes, anaesthesia- and surgery-related complications, and medical conditions, at recruitment, as well as through both active (at 1, 3, 7 days and 1, 3, 6, 12 months after surgery) and passive (for more than 1 year after surgery) follow-up assessments. We also obtained omics data from blood samples. In addition, COVID-19-related information was collected from all participants since January 2023, immediately after COVID-19 restrictions were eased in China. As of July 18, 2023, 12,766 participants (mean age = 52.40 years, 57.93% were female) completed baseline data collection (response rate = 94.68%), among which approximately 70% donated blood and hair samples. The follow-up rates within 12 months after surgery were > 92%. Our initial analyses have demonstrated the incidence of and risk factors for chronic postsurgical pain (CPSP) and postoperative cognitive dysfunction (POCD) among middle-aged Chinese individuals, which may prompt further mechanistic exploration and facilitate the development of effective interventions for preventing those conditions. Additional studies, such as genome-wide association analyses for identifying the genetic determinants of CPSP and POCD, are ongoing, and their findings will be released in the future.

Exploring the impact of pericentric inversion of chromosome 9 on fertility in sperm donors.

ABSTRACT: Pericentric inversion of chromosome 9 (inv[9]) is a common chromosomal structural variant, but its impact on clinical outcomes remains debated. The screening criteria of sperm banks are rarely mentioned to individuals with inv(9). In this study, we evaluated the fertility of sperm donors with inv(9) who met eligibility criteria for sperm banks (inv[9]-eligible donors). From March 2004 to May 2022, chromosomal analysis of 16 124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province (Changsha, China) found that 251 (1.6%) had chromosome variations, with inv(9) being the most prevalent at 1.1%. All 169 inv(9)-eligible donors were contacted to collect fertility outcome data, along with 206 eligible donors without inv(9) as controls. In addition, semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization (FISH), mitochondrial membrane potential, DNA fragmentation index, acrosome integrity, reactive oxygen species (ROS), and sperm morphology. Results showed that inv(9) did not significantly increase reproductive risks overall. Despite detecting ROS level differences, the clinical impact may be insignificant. This study provides new data on the inv(9) population that can serve as a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individuals carrying inv(9) variant.

Preoperative psychological symptoms and chronic postsurgical pain: analysis of the prospective China Surgery and Anaesthesia Cohort study.

BACKGROUND: Both preoperative psychological symptoms and chronic postsurgical pain (CPSP) are prevalent conditions and major concerns among surgery patients, with inconclusive associations. METHODS: Based on the China Surgery and Anaesthesia Cohort (CSAC), we recruited 8350 surgery patients (40-65 yr old) from two medical centres between July 2020 and March 2023. Patients with preoperative psychological symptoms (i.e. anxiety, depression, stress reaction, and poor sleep quality) were identified using corresponding well-established scales. We then examined the associations of individual preoperative psychological symptoms and major patterns of preoperative psychological symptoms (identified by k-means clustering analysis) with CPSP, and different pain trajectories within 3 months. Lastly, mediation analyses were conducted to elucidate the mediating role of surgery/anaesthesia-related factors and the presence of 1-month postoperative psychological symptoms on the studied associations. RESULTS: We included 1302 (1302/8350, 15.6%) CPSP patients. When analysed separately, all studied preoperative psychological symptoms were associated with increased CPSP risk, with the most pronounced odds ratio noted for anxiety (1.52, 95% confidence interval [CI] 1.23-1.86). Compared with patients clustered in the minor symptom group, excess risk of CPSP and experiencing an increasing pain trajectory was increased among patients with preoperative psychological symptoms featured by sleep disturbances (odds ratio=1.46, 95% CI 1.25-1.70 for CPSP and 1.58, 95% CI 1.20-2.08 for increasing pain trajectory) and multiple psychological symptoms (1.84 [95% CI 1.48-2.28] and 4.34 [95% CI 3.20-5.88]). Mediation analyses revealed acute/subacute postsurgical pain and psychological symptoms existing 1 month after surgery as notable mediators of the observed associations. CONCLUSIONS: The presence of preoperative psychological symptoms might individually or jointly increase the risk of chronic postsurgical pain or experiencing deterioration in pain trajectory. Interventions for managing acute/subacute postsurgical pain and psychological symptoms at 1 month after surgery might help reduce such risk. CLINICAL TRIAL REGISTRATION: ChiCTR2000034039.

Osimertinib versus comparator first-generation epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment in patients with advanced EGFR-mutated non-small cell lung cancer: a Chinese, multicenter, real-world cohort study.

Background: In the phase 3 FLAURA trial, osimertinib was compared with first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as a first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib showed longer progression-free survival (PFS), overall survival (OS), and a similar safety profile. However, more studies demonstrating the effectiveness and safety of osimertinib as a first-line strategy are needed in real-world populations. Methods: We enrolled 1,556 patients with EGFR-mutated stage IIIc-IV NSCLC from the CAPTRA-Lung database. All patients received either osimertinib (n=202) or a first-generation EGFR-TKI (n=1,354) as their initial treatment. To adjust for differences in baseline characteristics between two groups, 1:2 propensity score matching (PSM) was performed. Propensity scores included gender, age, Eastern Cooperative Oncology Group performance status score, smoking history, family history of tumor, pathology, EGFR mutations, and central nervous system (CNS) metastases. The standardized mean differences (SMD) before and after PSM were calculated to examine the balance of covariate distributions between two groups. Results: After PSM, 202 patients receiving osimertinib and 404 patients receiving first-generation EGFR-TKIs were finally identified. SMD of each matched variable is less than 0.10. The median PFS was 19.4 months [95% confidence interval (CI): 14.3-24.4] in the osimertinib arm and 10.9 months (95% CI: 9.3-12.5) in the comparator arm [hazard ratio (HR) for progression, 0.47; 95% CI: 0.38-0.59; P<0.001). The median OS was 40.5 months (95% CI: 27.1-54.0) vs. 34.3 months (95% CI: 30.6-38.0) in two groups, respectively (HR for death, 0.76; 95% CI: 0.58-1.00; P=0.045). The incidence of grade 3 adverse events (AEs) between the two groups was 1% and 4.2%, respectively. No grade 4 AEs and treatment-related deaths were reported in both groups. Conclusions: In real-world settings, osimertinib demonstrates longer PFS and OS, with a similar safety profile to that of comparator EGFR-TKIs when used as a first-line strategy in NSCLC patients.

Advances in the relationship between ferroptosis and epithelial-mesenchymal transition in cancer.

Epithelial-mesenchymal transition (EMT) is a cellular reprogramming process that converts epithelial cells into mesenchymal-like cells with migratory and invasive capabilities. The initiation and regulation of EMT is closely linked to a range of transcription factors, cell adhesion molecules and signaling pathways, which play a key role in cancer metastasis and drug resistance. The regulation of ferroptosis is intricately linked to various cell death pathways, intracellular iron homeostasis, and the protein network governing iron supply and storage. The ability of ferroptosis to disrupt cancer cells and overcome drug resistance lies in its control of intracellular iron ion levels. EMT process can promote the accumulation of iron ions, providing conditions for ferroptosis. Conversely, ferroptosis may impact the regulatory network of EMT by modulating transcription factors, signaling pathways, and cell adhesion molecules. Thus, ferroptosis related genes and signaling pathways and oxidative homeostasis play important roles in the regulation of EMT. In this paper, we review the role of ferroptosis related genes and their signaling pathways in regulating cancer EMT to better understand the crosstalk mechanism between ferroptosis and EMT, aiming to provide better therapeutic strategies for eradicating cancer cells and overcoming drug resistance.

Semi-supervised Counting of Grape Berries in the Field Based on Density Mutual Exclusion.

Automated counting of grape berries has become one of the most important tasks in grape yield prediction. However, dense distribution of berries and the severe occlusion between berries bring great challenges to counting algorithm based on deep learning. The collection of data required for model training is also a tedious and expensive work. To address these issues and cost-effectively count grape berries, a semi-supervised counting of grape berries in the field based on density mutual exclusion (CDMENet) is proposed. The algorithm uses VGG16 as the backbone to extract image features. Auxiliary tasks based on density mutual exclusion are introduced. The tasks exploit the spatial distribution pattern of grape berries in density levels to make full use of unlabeled data. In addition, a density difference loss is designed. The feature representation is enhanced by amplifying the difference of features between different density levels. The experimental results on the field grape berry dataset show that CDMENet achieves less counting errors. Compared with the state of the arts, coefficient of determination (R2) is improved by 6.10%, and mean absolute error and root mean square error are reduced by 49.36% and 54.08%, respectively. The code is available at https://github.com/youth-tang/CDMENet-main.

Postsurgery Subjective Cognitive and Short-Term Memory Impairment Among Middle-Aged Chinese Patients.

Importance: Perioperative neurocognitive disorder, particularly postoperative cognitive impairment, is common and associated with multiple medical and social adversities, although data from China are lacking. Objective: To examine the incidence, trajectory, and risk factors for subjective cognitive and short-term memory impairment after surgery in the Chinese population. Design, Setting, and Participants: This cohort study used data from the China Surgery and Anesthesia Cohort to assess surgical patients aged 40 to 65 years from 2 medical centers between July 15, 2020, and March 31, 2023, with active follow-up within 1 year after the surgery. Of 11 158 patients who were successfully recruited (response rate, 94.4%), 10 149 participants were eligible and available for analysis. From this population, separate cohorts were constructed for analyzing subjective cognitive impairment (8105 noncardiac and 678 cardiac surgery patients) and short-term memory impairment (5246 noncardiac and 454 cardiac surgery patients). Exposures: Twenty-four potential risk factors regarding comorbidities, preoperative psychological conditions, anesthesia- or surgery-related factors, and postsurgical events were included. Main Outcomes and Measures: Outcomes included subjective cognitive function measured by the 8-Item Informant Interview to Differentiate Aging and Dementia (AD8; scores range from 0 to 8, with higher scores indicating more severe cognitive impairment) and short-term memory measured by the 3-Word Recall Test (TRT; scores range from 0 to 3, with lower scores indicating more severe short-term memory impairment) at 1, 3, 6, and 12 months after noncardiac and cardiac surgery. Generalized linear mixed models were used to identify risk factors associated with the presence of AD8 (score ≥2) or TRT (score <3) abnormality as well as the aggressively deteriorative trajectories of those cognitive measurements. Results: For noncardiac surgery patients, the AD8 analysis included 8105 patients (mean [SD] age, 52.3 [7.1] years; 3378 [41.7%] male), and the TRT analysis included 5246 patients (mean [SD] age, 51.4 [7.0] years; 1969 [37.5%] male). The AD8 abnormality incidence rates after noncardiac surgery increased from 2.2% (175 of 8105) at 7 days to 17.1% (1059 of 6191) at 6 months after surgery, before appearing to decrease. In contrast, the TRT abnormality incidence rates followed a U-shaped pattern, with the most pronounced incidence rates seen at 7 days (38.9% [2040 of 5246]) and 12 months (49.0% [1394 of 2845]). Similar patterns were seen among cardiac surgery patients for the AD8 analysis (678 patients; mean [SD] age, 53.2 [6.3] years; 393 [58.0%] male) and TRT analysis (454 patients; mean [SD] age, 52.4 [6.4] years; 248 [54.6%] male). Among noncardiac surgery patients, the top risk factors for aggressively deteriorative AD8 trajectory and for AD8 abnormality, respectively, after surgery were preoperative sleep disturbances (Pittsburgh Sleep Quality Index ≥16 vs 0-5: odds ratios [ORs], 4.04 [95% CI, 2.20-7.40] and 4.54 [95% CI, 2.40-8.59]), intensive care unit stay of 2 days or longer (ORs, 2.43 [95% CI, 1.26-4.67] and 3.07 [95% CI, 1.67-5.65]), and preoperative depressive symptoms (ORs, 1.76 [95% CI, 1.38-2.24] and 2.23 [95% CI, 1.79-2.77]). Analyses for TRT abnormality and trajectory, as well as the analyses conducted among cardiac surgery patients, found fewer associated factors. Conclusions and Relevance: This cohort study of middle-aged Chinese surgery patients found subjective cognitive and short-term memory impairment within 12 months after both cardiac and noncardiac surgery, with multiple identified risk factors, underscoring the potential of preoperative psychological interventions and optimized perioperative management for postoperative cognitive impairment prevention.

Anoikis-related gene signatures can aid prognosis of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, and while advancements in diagnosis, surgery, radiotherapy, and molecular therapy have improved clinical prognosis, the long-term survival rate and quality of life of patients remain unsatisfactory. Therefore, identifying new prognostic biomarkers and potential therapeutic targets is crucial. OBJECTIVES: This study aimed to analyze the role of anoikis-related gene characteristics in LUAD. MATERIAL AND METHODS: The anoikis-related genes were obtained from the GeneCards database. Genetic expression data and clinical characteristic information were collected from The Cancer Genome Atlas (TCGA)-LUAD, and the Gene Expression Omnibus (GEO) GSE31210, GSE37745, and GSE68465 datasets. Random survival forest and least absolute shrinkage and selection operator (LASSO) models were applied to construct the risk model. An analysis of immune cell infiltration and function was performed with the scores. RESULTS: Four prognosis-related genes (TLE1, GLI2, PLK1, and BAK1) were obtained and used to construct the anoikis score. We found that the patient survival rate was higher in the low-anoikis score (LAS) group. Moreover, both the stromal and immune scores were negatively correlated with the anoikis score. With the increase of the anoikis score, the levels of natural killer cells, regulatory T cells, CD4+ T cells, CD8+ T cells, B cells, and macrophages decreased. The anoikis score had a negative regulatory relationship with the immune response, natural killer cell activation and T cell activation. The TP53 mutation was significant in LUAD patients and was present in 56% of the high-anoikis score (HAS) group and in 40% of the LAS group. CONCLUSIONS: The anoikis score was associated with poor prognosis in LUAD patients. Anoikis-related genes were associated with tumor immune dysregulation and TP53 mutation in LUAD. This study opens a new perspective for LUAD therapy.

Evaluation of safety and efficacy of inhaled ambroxol in hospitalized adult patients with mucopurulent sputum and expectoration difficulty.

Background: Ambroxol is a widely used mucoactive drug in sputum clearance of respiratory diseases taken orally and by injection. However, there is a paucity of evidence for inhaled ambroxol in sputum clearance. Methods: This study performed a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial at 19 centers in China. Hospitalized adult patients with mucopurulent sputum and expectoration difficulty were recruited. Patients were randomized by 1:1 to receive inhalation of either ambroxol hydrochloride solution 3 mL (22.5 mg) + 0.9% sodium chloride 3 mL or 0.9% sodium chloride 6 mL twice daily for 5 days, with an interval of more than 6 h. The primary efficacy endpoint was the absolute change in the sputum property score after treatment compared to the baseline in the intention-to-treat population. Results: Between 10 April 2018 and 23 November 2020, 316 patients were recruited and assessed for eligibility, of whom 138 who received inhaled ambroxol and 134 who received a placebo were included. Patients who received inhaled ambroxol had a significantly greater decrease in the sputum property score compared with patients who received inhalation of placebo (difference: -0.29; 95% CI: -0.53 to -0.05; p = 0.0215). Compared with the placebo, inhaled ambroxol also significantly reduced more expectoration volume in 24 h (difference: -0.18; 95% CI: -0.34 to -0.03; p = 0.0166). There was no significant difference in the proportion of adverse events between the two groups, and no deaths were reported. Discussion: In hospitalized adult patients with mucopurulent sputum and expectoration difficulty, inhaled ambroxol was safe and effective for sputum clearance compared with a placebo. Clinical trial registration: [https://www.chictr.org.cn/showproj.html?proj=184677], Chinese Clinical Trial Registry [ChiCTR2200066348].

Correlation Analysis of the Therapy Adherence to Long-Acting Inhalers Among Patients with Stable COPD.

Purpose: Long-acting inhalers are the mainstay maintenance therapy for stable chronic obstructive pulmonary disease (COPD) management. The aim of this study was to assess adherence to inhalers among adults with COPD in China and to develop strategies to improve adherence for the next step. Patients and Methods: A cross-sectional study was conducted among 246 adult patients with COPD using long-acting inhalers to explore different demographic characteristics, disease characteristics and medication regimens. Adherence to inhalers was assessed using the Medication Adherence Report Scale (MARS). Results: Among the 246 patients included in the present study, 93 (37.80%) had good adherence, while 153 (62.20%) had poor adherence. From the comparison of patients with good and poor adherence, we found that the course of disease and education background had a significant effect on adherence (p < 0.05). Among the LAMA therapy group, inhaled tiotropium bromide spray (Ingelheim am Rhein, Germany) with active release technology had better adherence than inhaled tiotropium bromide powder (Ingelheim am Rhein, Germany) (p < 0.05). Moreover, COPD patients with good adherence had better pulmonary function and fewer moderate or severe exacerbations in the past year (p < 0.05). Conclusion: The factors affecting the use of inhalers in patients with stable COPD are complicated. Medical staff should select appropriate inhalers according to the patient's disease status and duration and provide medication education to improve adherence.

Loosely Adsorbed Chains Expedite the Desorption of Flattened Polystyrene Chains on Flat Silicon Surface.

Herein, the desorption of the adsorbed chains (including two regions of flattened chains and loosely adsorbed chains) was examined by monitoring the chain exchange kinetics between the adsorbed chains and the top-free chains in a bilayer system by using fluorine-labeled polystyrene (PS). The results indicated that the exchange behavior of PS-flattened chains with the top-free chains is much slower than that of PS-loose chains and has a strong molecular weight (MW) dependence. Interestingly, in the presence of loosely adsorbed chains, the desorption of flattened chains was accelerated greatly and had weaker MW dependency. We attribute the MW-dependent desorption phenomena to the average number of contact sites between polymer adsorbed chains and the substrate, which rapidly increased with increasing MW. Likewise, the desorption of loosely adsorbed chains may provide extra conformational energy to accelerate the desorption of flattened chains.

Melatonin alleviates lung injury in H1N1-infected mice by mast cell inactivation and cytokine storm suppression.

Influenza A virus (IAV) H1N1 infection is a constant threat to human health and it remains so due to the lack of an effective treatment. Since melatonin is a potent antioxidant and anti-inflammatory molecule with anti-viral action, in the present study we used melatonin to protect against H1N1 infection under in vitro and in vivo conditions. The death rate of the H1N1-infected mice was negatively associated with the nose and lung tissue local melatonin levels but not with serum melatonin concentrations. The H1N1-infected AANAT-/- melatonin-deficient mice had a significantly higher death rate than that of the WT mice and melatonin administration significantly reduced the death rate. All evidence confirmed the protective effects of melatonin against H1N1 infection. Further study identified that the mast cells were the primary targets of melatonin action, i.e., melatonin suppresses the mast cell activation caused by H1N1 infection. The molecular mechanisms involved melatonin down-regulation of gene expression for the HIF-1 pathway and inhibition of proinflammatory cytokine release from mast cells; this resulted in a reduction in the migration and activation of the macrophages and neutrophils in the lung tissue. This pathway was mediated by melatonin receptor 2 (MT2) since the MT2 specific antagonist 4P-PDOT significantly blocked the effects of melatonin on mast cell activation. Via targeting mast cells, melatonin suppressed apoptosis of alveolar epithelial cells and the lung injury caused by H1N1 infection. The findings provide a novel mechanism to protect against the H1N1-induced pulmonary injury, which may better facilitate the progress of new strategies to fight H1N1 infection or other IAV viral infections.

Reductive transformation of Cr(VI) in contaminated soil by polyphenols: The role of gallic and tannic acid.

Polyphenols, as an important category of natural organics, are ubiquitous in plants and structurally diverse. Batch experiments were conducted to investigate the role of natural polyphenol, such as gallic acid (GA) and tannic acid (TA), in the biochemical behavior of Cr(VI) in soil media. GA and TA can effectively convert Cr(VI) to Cr(III) under neutral conditions (pH 7.0). However, there are significant differences in the transport, leaching toxicity, and bioavailability of reduced Cr(III) between the two systems. UV-vis spectra, chromium (Cr) mass balance, speciation distribution, and X-ray photoelectron spectroscopy were used to explore the intrinsic mechanisms of Cr(VI) reduction and (im)mobilization in the presence of GA or TA. Results showed that the reduction of Cr(VI) by GA was accompanied by poor immobilization of reduced Cr(III), especially at high GA concentrations (4-10 g/L), which was associated with the formation of soluble Cr(III) complexes. After treatment with 4 g/L GA, 51.49 ± 3.04% of the Cr in GA system was mobilized as complexes into aqueous phase. In contrast, the reduction of Cr(VI) and the subsequent precipitation of reduced Cr(III) was dominant in the TA system. After treatment with 4 g/L TA, 97.24 ± 0.31% of the total Cr in the TA system was immobilized into soil phase and transformed into more stable fractions. Our findings provide new insights into how natural organics shape the fate and transport of Cr in soils, which also have substantial implications for the development of Cr sequestration technology.

Chrome shaving-derived biochar as efficient persulfate activator: Ti-induced charge distribution modulation for 1O2 dominated nonradical process.

Efficient degradation of organic contaminants by oxidative radicals remains a challenge due to invalid consumption of radicals and easy generation of secondary halogenated pollutants. In this work, an efficient and recyclable bimetallic biochar (Cr-Ti/BC) was developed through peroxydisulfate (PDS) activation via nonradical pathway for sulfamethoxazole (SMX) degradation. The Cr-Ti/BC exhibited excellent catalytic activity for 99.9 % of SMX removal with a high kobs of 0.13 min-1, and negligible inhibitory effects were observed under various pH condition. The activation mechanisms were (i) metastable reactive intermediates (Cr-Ti/BC-PDS) formation via an interaction between Cr-Ti/BC and PDS on the active defective sites (e.g., OH/COC, COOH, CO, nitric oxides, graphitic N, and pyridinic N), and (ii) 1O2 generation through electron transfer between Cr-Ti/BC-PDS intermediates and dissolved oxygen. The high reusability and strong stability of Cr-Ti/BC also verified the outstanding advantage of the Cr-Ti/BC during practical application. This study not only is the first study the catalytic performance of Cr and Ti co-doped biochar for PDS activation, but also successfully provides a promising strategy to induce a nonradical pathway for PDS activation, which is of great significance for the subsequent method design, and thus paving the path for exploiting advanced oxidation systems in practical application for organic contaminant removal toward polluted site remediation.

PI3K/AKT-mediated autophagy inhibition facilitates mast cell activation to enhance severe inflammatory lung injury in influenza A virus- and secondary Staphylococcus aureus-infected mice.

Influenza A virus infection causes considerable morbidity and mortality each year globally, and secondary bacterial infection further exacerbates the severity and fatality of the initial viral infection. Mast cells have substantial roles in protecting the respiratory tract mucosa, while their role in viral and bacterial co-infection remains unclear. The present study revealed that secondary Staphylococcus aureus infection significantly aggravated the activation of mast cells during the initial H1N1 infection both in vivo and in vitro, which was closely related to the increased inflammatory lung injury and mortality. Meanwhile, the secondary S. aureus infection suppressed autophagy and promoted inflammatory mediators released by mast cells through activating the PI3K/Akt signaling pathway. Blocking PI3K/Akt pathway by LY294002, an inhibitor of Akt phosphorylation, could rescue autophagy and inhibit the release of inflammatory mediators. Furthermore, based on the influenza A viral and secondary bacterial infected mice model, we showed that the combination of LY294002 and antiviral drug oseltamivir could effectively reduce the inflammatory damage and pro-inflammatory cytokines releasing in lungs, recovering body weight loss and improving the survival rate from the co-infections. In conclusion, secondary bacterial infection can inhibit autophagy and stimulate mast cell activation through the PI3K/Akt pathway, which might explain why secondary bacterial infection would cause severe and fatal consequences following an initial influenza A viral infection.