Essential role of stem cell factor–c‐Kit signalling pathway in bleomycin‐induced pulmonary fibrosis

Stem cell factor ( SCF ) and its receptor c‐Kit have been implicated in tissue remodelling and fibrosis. Alveolar fibroblasts from patients with diffuse interstitial fibrosis secrete more SCF . However, its precise role remains unclear. In this study the potential role of the SCF –c‐Kit axis in pulmonary fibrosis was examined. Fibrosis was induced by intratracheal instillation of bleomycin ( BLM ), which caused increased SCF levels in plasma, bronchoalveolar lavage fluid ( BALF ) and lung tissue, as well as increased expression by lung fibroblasts. These changes were accompanied by increased numbers of bone marrow‐derived c‐Kit + cells in the lung, with corresponding depletion in bone marrow. Both recombinant SCF and lung extracts from BLM ‐treated animals induced bone‐marrow cell migration, which was blocked by c‐Kit inhibitor. The migrated cells promoted myofibroblast differentiation when co‐cultured with fibroblasts, suggesting a paracrine pathogenic role. Interestingly, lung fibroblast cultures contained a subpopulation of cells that expressed functionally active c‐Kit, which were significantly greater and more responsive to SCF induction when isolated from fibrotic lungs, including those from patients with idiopathic pulmonary fibrosis ( IPF ). This c‐Kit + subpopulation was α SMA ‐negative and expressed lower levels of collagen I but significantly higher levels of TGF β than c‐Kit‐negative cells. SCF deficiency achieved by intratracheal treatment with neutralizing anti‐ SCF antibody or by use of Kitl Sl / Kitl Sl ‐d mutant mice in vivo resulted in significant reduction in pulmonary fibrosis. Taken together, the SCF –c‐Kit pathway was activated in BLM ‐injured lung and might play a direct role in pulmonary fibrosis by the recruitment of bone marrow progenitor cells capable of promoting lung myofibroblast differentiation. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98368/1/path4177.pd

The LcKNAT1-LcEIL2/3 Regulatory Module Is Involved in Fruitlet Abscission in Litchi

Large and premature organ abscission may limit the industrial development of fruit crops by causing serious economic losses. It is well accepted that ethylene (ET) is a strong inducer of organ abscission in plants. However, the mechanisms underlying the control of organ abscission by ET are largely unknown. We previously revealed that LcKNAT1, a KNOTTED-LIKE FROM ARABIDOPSIS THALIANA1 (KNAT1)-like protein, acted as a negative regulator in control of fruitlet abscission through suppressing the expression of ET biosynthetic genes in litchi. In this study, we further reported that LcKNAT1 could also directly repress the transcription of LcEIL2 and LcEIL3, two ETHYLENE INSENSITIVE 3-like (EIL) homologs in litchi, which functioned as positive regulators in ET-activated fruitlet abscission by directly promoting the expression of genes responsible for ET biosynthesis and cell wall degradation. The expression level of LcKNAT1 was downregulated, while LcEIL2/3 was upregulated at the abscission zone (AZ) accompanying the fruitlet abscission in litchi. The results of electrophoretic mobility shift assays (EMSAs) and transient expression showed that LcKNAT1 could directly bind to the promoters of LcEIL2 and LcEIL3 and repress their expression. Furthermore, the genetic cross demonstrated that the β-glucuronidase (GUS) expression driven by the promoters of LcEIL2 or LcEIL3 at the floral AZ was obviously suppressed by LcKNAT1 under stable transformation in Arabidopsis. Taken together, our findings suggest that the LcKNAT1-LcEIL2/3 regulatory module is likely involved in the fruitlet abscission in litchi, and we propose that LcKNAT1 could suppress both ET biosynthesis and signaling to regulate litchi fruit abscission

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Smoking‐induced genetic and epigenetic alterations in infertile men

Male fertility rates have shown a progressive decrease in both developing and industrialised countries in the past 50 years. Clinical and epidemiological studies have demonstrated controversial results about the harmful effects of cigarette smoking on seminal parameters. Some studies could not establish a negative effect by tobacco smoking on sperm quality and function, whereas others have found a significant reduction in sperm quality and function. This study reviews the components in cigarette smoke and discusses the effects of smoking on male fertility by focusing extensively on smoking‐induced genetic and epigenetic alterations in infertile men. Chromosomal aneuploidies, sperm DNA fragmentation and gene mutations are discussed in the first section, while changes in DNA methylation, chromatin remodelling and noncoding RNAs are discussed in the second section as part of epigenetic alterations

Sperm DNA fragmentation: A new guideline for clinicians

Sperm DNA integrity is crucial for fertilization and development of healthy offspring. The spermatozoon undergoes extensive molecular remodeling of its nucleus during later phases of spermatogenesis, which imparts compaction and protects the genetic content. Testicular (defective maturation and abortive apoptosis) and post-testicular (oxidative stress) mechanisms are implicated in the etiology of sperm DNA fragmentation (SDF), which affects both natural and assisted reproduction. Several clinical and environmental factors are known to negatively impact sperm DNA integrity. An increasing number of reports emphasizes the direct relationship between sperm DNA damage and male infertility. Currently, several assays are available to assess sperm DNA damage, however, routine assessment of SDF in clinical practice is not recommended by professional organizations

The effect of DNA-V model intervention on learning behaviors and stress in Chinese adolescents: A randomized controlled trial

Objective: The Discoverer Noticer Advisor-Value (DNA-V) model is an adaption of Acceptance and Commitment Therapy, which focuses on adolescent development and value-led behavioral change. However, few studies have validated the effectiveness of this model in adolescents in learning environments. This study thus aimed to examine the effectiveness of a Chinese version of the DNA-V model in a Chinese middle school student population. Additionally, we sought to determine whether online or face-to-face versions of the model were more effective. Methods: One-hundred and thirty-six middle school students were randomly divided into a face-to-face DNA-V group (n = 40), an Internet DNA-V (iDNA-V) group (n = 50), and a traditional group (control, n = 46). The intervention was administered with a 45-min psychology course once a week for six weeks. The three groups were assessed on three core variables of academic learning motivation, strategies, and confidence, as well as stress at three time points (pre-intervention, post-intervention, and at a two-month follow-up). Results: Repeated-measures ANOVA showed that the Group x Time Point interaction was significant for learning motivation (F(4,266) = 2.746, p = 0.029, eta p2 = 0.04) and stress (F(4,266) = 3.681, p = 0.006,eta p2 = 0.05). Learning motivation scores showed no between-group differences at any of the three time points, but the iDNA-V group showed significant improvement at the two-month follow-up and the traditional group showed significant gains at post-intervention that were maintained until the follow-up test. The DNA-V group exhibited lower stress scores at follow-up than at the pre-intervention assessment (p = 0.002) and post-intervention assessment (p = 0.005), with significantly lower stress follow-up scores than those of the iDNA-V (p = 0.024) and control (p = 0.023) groups. Conclusion: These results suggest that different intervention formats of DNA-V can be used as an alternative to traditional adolescent school psychology programs. It is important to consider how to emotionally support students when designing and developing internet-based DNA-V intervention programs to increase the effectiveness of this program for stress intervention

Degradation of Phenol in Wastewater with Ozone Produced by Self-design Ozone Generator

The optimized tube’s structure of the self-design ozone generator was made with the double dielectric inner electrode and small metal cones were embedded in the outside electrode. This ozone generator was used for the degradation of phenol in wastewater. The research was studied from ozone gas flow rate, reaction time, the initial pH and concentration of the phenol in wastewater. In addition, the article also discusses the reaction mechanism of ozone degraded the phenol in wastewater. The results illustrate that the ozone concentration of self-design ozone generator under the pure oxygen flux (1.0 L/min) were 7.06 mg/L, compared with the unoptimized ozone, the optimized ozone generator’s efficiency was improved 56.89%; the phenol removal rate was increased as the initial pH increased in wastewater, when pH was 12, the phenol removal rate was 80.17%; GC-MS analysis was adopted to analyze and determine the phenol intermediates. The results illustrate that the major oxidation degradation products of phenol may be p-benzoquinone benzenequinone, 4-cyclopentene-1, 3-dione and diacetone alcohol

Data_Sheet_1_The LcKNAT1-LcEIL2/3 Regulatory Module Is Involved in Fruitlet Abscission in Litchi.doc

Large and premature organ abscission may limit the industrial development of fruit crops by causing serious economic losses. It is well accepted that ethylene (ET) is a strong inducer of organ abscission in plants. However, the mechanisms underlying the control of organ abscission by ET are largely unknown. We previously revealed that LcKNAT1, a KNOTTED-LIKE FROM ARABIDOPSIS THALIANA1 (KNAT1)-like protein, acted as a negative regulator in control of fruitlet abscission through suppressing the expression of ET biosynthetic genes in litchi. In this study, we further reported that LcKNAT1 could also directly repress the transcription of LcEIL2 and LcEIL3, two ETHYLENE INSENSITIVE 3-like (EIL) homologs in litchi, which functioned as positive regulators in ET-activated fruitlet abscission by directly promoting the expression of genes responsible for ET biosynthesis and cell wall degradation. The expression level of LcKNAT1 was downregulated, while LcEIL2/3 was upregulated at the abscission zone (AZ) accompanying the fruitlet abscission in litchi. The results of electrophoretic mobility shift assays (EMSAs) and transient expression showed that LcKNAT1 could directly bind to the promoters of LcEIL2 and LcEIL3 and repress their expression. Furthermore, the genetic cross demonstrated that the β-glucuronidase (GUS) expression driven by the promoters of LcEIL2 or LcEIL3 at the floral AZ was obviously suppressed by LcKNAT1 under stable transformation in Arabidopsis. Taken together, our findings suggest that the LcKNAT1-LcEIL2/3 regulatory module is likely involved in the fruitlet abscission in litchi, and we propose that LcKNAT1 could suppress both ET biosynthesis and signaling to regulate litchi fruit abscission.</p

Delayed PCI is not beneficial for STEMI patients with impaired renal function: a retrospective cohort study

Abstract Background Preexisting impaired renal function (IRF) and contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) are important prognostic parameters, but it is unknown whether delayed PCI is still beneficial for STEMI patients with IRF. Methods A retrospective single-center cohort study was performed in 164 patients who presented at least 12 h after symptom onset, and were diagnosed with STEMI and IRF. They were assigned to two groups to receive PCI plus optimal medical therapy (OMT) and OMT alone respectively. Clinical outcomes at 30 days and 1 year were compared between two groups, and hazard ratio for survival was analyzed using Cox regression model. A power analysis demanded 34 patients in each group to produce a power of 90% and a P value of 0.05. Results The 30-day mortality was significantly lower in PCI group (n = 126) than in non-PCI group (n = 38) (11.1% versus 28.9%, P = 0.018), while there was no significant difference in the 1-year mortality and incidence of cardiovascular comorbidities between the two groups. Cox regression analysis showed that patients with IRF didn’t benefit from receiving PCI on survival rate (P = 0.267). Conclusions Delayed PCI is not beneficial on one-year clinical outcomes for STEMI patients with IRF