MYC2: A Master Switch for Plant Physiological Processes and Specialized Metabolite Synthesis.

The jasmonic acid (JA) signaling pathway plays important roles in plant defenses, development, and the synthesis of specialized metabolites synthesis. Transcription factor MYC2 is a major regulator of the JA signaling pathway and is involved in the regulation of plant physiological processes and specialized metabolite synthesis. Based on our understanding of the mechanism underlying the regulation of specialized metabolite synthesis in plants by the transcription factor MYC2, the use of synthetic biology approaches to design MYC2-driven chassis cells for the synthesis of specialized metabolites with high medicinal value, such as paclitaxel, vincristine, and artemisinin, seems to be a promising strategy. In this review, the regulatory role of MYC2 in JA signal transduction of plants to biotic and abiotic stresses, plant growth, development and specialized metabolite synthesis is described in detail, which will provide valuable reference for the use of MYC2 molecular switches to regulate plant specialized metabolite biosynthesis.

Comparisons between Plant and Animal Stem Cells Regarding Regeneration Potential and Application.

Regeneration refers to the process by which organisms repair and replace lost tissues and organs. Regeneration is widespread in plants and animals; however, the regeneration capabilities of different species vary greatly. Stem cells form the basis for animal and plant regeneration. The essential developmental processes of animals and plants involve totipotent stem cells (fertilized eggs), which develop into pluripotent stem cells and unipotent stem cells. Stem cells and their metabolites are widely used in agriculture, animal husbandry, environmental protection, and regenerative medicine. In this review, we discuss the similarities and differences in animal and plant tissue regeneration, as well as the signaling pathways and key genes involved in the regulation of regeneration, to provide ideas for practical applications in agriculture and human organ regeneration and to expand the application of regeneration technology in the future.

GhMYC2 activates cytochrome P450 gene CYP71BE79 to regulate gossypol biosynthesis in cotton.

MAIN CONCLUSION: GhMYC2 regulates the gossypol biosynthesis pathway in cotton through activation of the expression of gossypol synthesis gene CYP71BE79, CDNC, CYP706B1, DH1, and CYP82D113. Cotton is one of the main cash crops globally. Cottonseed contains fiber, fat, protein, and starch, and has important economic value. However, gossypol in cottonseed seriously affects the development and utilization of cottonseed. Nonetheless, gossypol has great application potential in agriculture, medicine, and industry. Therefore, it is very important to study gossypol biosynthesis and its upstream regulatory pathways. It has been reported that the content of gossypol in hairy roots of cotton is regulated through jasmonic acid signaling; however, the specific molecular mechanism has not been revealed yet. We found that the expression of basic helix-loop-helix family transcription factor GhMYC2 was significantly upregulated after exogenous administration of methyl jasmonate to cotton seedlings, and the content of gossypol changed significantly with the variation of GhMYC2 expression. Further studies revealed that GhMYC2 could specifically bind to the G-Box in the promoter region of CDNC, CYP706B1, DH1, CYP82D113, CYP71BE79 to activate its expression and regulate gossypol synthesis, and its activation of CYP71BE79 promoter was inhibited by GhJAZ2. Not only that GhMYC2 could also interact with GoPGF. In this work, the molecular mechanisms of gossypol biosynthesis regulated by GhMYC2 were analyzed. The results provide a theoretical basis for cultivating new varieties of low-gossypol or high-gossypol cotton and creating excellent germplasm resources.

Defense Mechanisms of Cotton Fusarium and Verticillium Wilt and Comparison of Pathogenic Response in Cotton and Humans.

Cotton is an important economic crop. Fusarium and Verticillium are the primary pathogenic fungi that threaten both the quality and sustainable production of cotton. As an opportunistic pathogen, Fusarium causes various human diseases, including fungal keratitis, which is the most common. Therefore, there is an urgent need to study and clarify the resistance mechanisms of cotton and humans toward Fusarium in order to mitigate, or eliminate, its harm. Herein, we first discuss the resistance and susceptibility mechanisms of cotton to Fusarium and Verticillium wilt and classify associated genes based on their functions. We then outline the characteristics and pathogenicity of Fusarium and describe the multiple roles of human neutrophils in limiting hyphal growth. Finally, we comprehensively compare the similarities and differences between animal and plant resistance to Fusarium and put forward new insights into novel strategies for cotton disease resistance breeding and treatment of Fusarium infection in humans.

Core concepts in pharmacoepidemiology: Violations of the positivity assumption in the causal analysis of observational data: Consequences and statistical approaches.

In the causal analysis of observational data, the positivity assumption requires that all treatments of interest be observed in every patient subgroup. Violations of this assumption are indicated by nonoverlap in the data in the sense that patients with certain covariate combinations are not observed to receive a treatment of interest, which may arise from contraindications to treatment or small sample size. In this paper, we emphasize the importance and implications of this often-overlooked assumption. Further, we elaborate on the challenges nonoverlap poses to estimation and inference and discuss previously proposed methods. We distinguish between structural and practical violations and provide insight into which methods are appropriate for each. To demonstrate alternative approaches and relevant considerations (including how overlap is defined and the target population to which results may be generalized) when addressing positivity violations, we employ an electronic health record-derived data set to assess the effects of metformin on colon cancer recurrence among diabetic patients.

Feedback regulation of antioxidant transcription factor NFE2L1 and immunostimulatory factor 41BBL mediates the crosstalk between oxidative stress and tumor immunity.

Targeting the immune checkpoint to inhibit tumor immune escape, which is one of the fundamental causes of cancer, has become an important strategy for cancer treatment. The molecular mechanism of tumor immune escape involved in the process of spontaneous hepatocellular carcinoma after specifically knocking out NFE2L1, the core regulator of redox homeostasis, in the mouse liver is still unclear. Transcriptome data showed that the immunostimulatory TNFSF9/41BBL was significantly reduced in NFE2L1 knockdown hepatocarcinoma HepG2 cells, and this suggests that 41BBL may be an oxidative stress-responsive immune checkpoint. The results of the promoter activity experiment showed that NFE2L1 can promote 41BBL gene transcription activation through the ARE element in the promoter region. In addition, cell biology experiments have found that overexpression of 41BBL can inhibit cell proliferation and promote senescence. Importantly, reactive oxygen species in cells significantly increased after overexpression of 41BBL, whereas NFE2L1 was inhibited, indicating that 41BBL has the effect of feedback regulating oxidative stress in cells. In conclusion, in this study, the transcriptional activation effect of NFE2L1 on 41BBL and the feedback inhibition relationship of 41BBL on NFE2L1 was clarified. The NFE2L1/41BBL axis might be an important pathway that mediates the crosstalk between oxidative stress and the tumor immune response.

Identification and Comprehensive Structural and Functional Analyses of the EXO70 Gene Family in Cotton.

The EXO70 gene is a vital component of the exocytosis complex and participates in biological processes ranging from plant cell division to polar growth. There are many EXO70 genes in plants and their functions are extensive, but little is known about the EXO70 gene family in cotton. Here, we analyzed four cotton sequence databases, identified 165 EXO70 genes, and divided them into eight subgroups (EXO70A-EXO70H) based on their phylogenetic relationships. EXO70A had the most exons (≥11), whereas the other seven each had only one or two exons. Hence, EXO70A may have many important functions. The 84 EXO70 genes in Asian and upland cotton were expressed in the roots, stems, leaves, flowers, fibers, and/or ovules. Full-length GhEXO70A1-A cDNA was homologously cloned from upland cotton (Gossypium hirsutum, G. hirsutum). Subcellular analysis revealed that GhEXO70A1-A protein was localized to the plasma membrane. A yeast two-hybrid assay revealed that GhEXO70A1-A interacted with GhEXO84A, GhEXO84B, and GhEXO84C. GhEXO70A1-A silencing significantly altered over 4000 genes and changed several signaling pathways related to metabolism. Thus, the EXO70 gene plays critical roles in the physiological functions of cotton.

[The clinical efficacy and cardiac safety of itraconazole injection in treatment of acute pulmonary invasive fungal infection in chronic pulmonary diseases in the elderly].

OBJECTIVE: To observe the clinical efficiency and cardiac safety of itraconazole injection in the treatment of the elderly patients with chronic pulmonary diseases suffered from acute pulmonary invasive fungal infection (IFI). METHODS: The research was single centre and open experimental designed trial. We selected patients (> 70 years old) who were admitted to our department of respiratory medicine because of chronic pulmonary diseases combined with pulmonary IFI. All patients received intravenous itraconazole injection. The clinical efficiency and cardiac safety was observed for 14 days. RESULTS: Thirty-five patients were included, 3 patients were proven, 32 patients were probable. There were 26 patients combined with coronary artery disease (74.28%), 20 patients combined with cor pulmonale (57.14%), and 17 patients simultaneously combined with both (48.57%). The temperature of 22 patients (62.86%) decreased to normal in 7 days, 31 patients (90.39%) in 11 days. After 14 days' therapy, the level of 1, 3-beta-D glucan decreased to normal in 26 patients (78.79%). The foci in sternum of 5 patients who were infected by candida albicans were completely absorbed in 14 days. Two patients were suffered from left heart insufficiency and arrhythmia ventricular on the 4th and 5th day respectively, and disappeared on the next day after given symptomatic treatment. There was a significant difference in B-type natriuretic peptide (BNP) between before and after treatment. CONCLUSION: The clinical efficiency of itraconazole injection in the elderly patients who suffered from chronic pulmonary diseases and then combined with acute pulmonary IFI were 78.79%. Even if combined with coronary artery disease and/or cor pulmonale, the elderly patients who have chronic pulmonary diseases were safe when using the itraconazole injection in 14 days.

Impact of severe-to-very severe chronic obstructive pulmonary disease on the prognosis of patients with non-small cell lung cancer who received chemotherapy.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is associated with poor prognosis in non-small cell lung cancer (NSCLC) patients. There are limited data about the impact of severe-to-very severe COPD on prognosis in patients with NSCLC receiving first-line chemotherapy. OBJECTIVES: To investigate whether severe-to-very severe COPD impacted survival of patients with NSCLC receiving first-line chemotherapy. METHODS: A retrospective review was performed on 513 consecutive NSCLC patients receiving first-line chemotherapy between February 2014 and May 2018. Prognostic impact of severe-to-very severe COPD was analysed using regression analyses. RESULTS: Totally 258 NSCLC patients (118 non-COPD, 96 mild-to-moderate COPD and 44 severe-to-very severe COPD) were evaluated retrospectively. Kaplan-Meier analysis showed that the median overall survival times in the severe-to-very severe COPD, mild-to-moderate COPD and non-COPD groups were 14.0 months [95% confidence interval (CI): 11.0-17.0], 18 months (95% CI: 14.8-21.2) and 19 months (95% CI: 15.3-22.7), respectively. The difference was significant between patients with severe-to-very severe COPD and those without COPD (χ2  = 6.8, P = 0.009) and between patients with severe-to-very severe COPD and those with mild-to-moderate COPD (χ2  = 4.0, P = 0.045). Multivariate analysis showed that survival time was significantly shorter in the severe-to-very severe COPD group than in the non-COPD group (adjusted hazard ratio: 1.876, 95% CI: 1.161-3.030, P = 0.01) and mild-to-moderate COPD group (adjusted hazard ratio: 1.782, 95% CI: 1.046-3.034, P = 0.033). CONCLUSION: Severe-to-very severe COPD may worsen the prognosis of NSCLC patients who received first-line chemotherapy.

Geographic Differences in Lung Cancer Incidence: A Study of a Major Metropolitan Area within Southeastern Pennsylvania.

This study investigated the geographic variation and the clustering of lung cancer incidence rates in Philadelphia and the surrounding areas using addresses at the time of diagnosis. Using 60,844 cases from Pennsylvania Cancer Registry, we calculated and mapped the age-adjusted incidence rates for five Pennsylvania (PA) counties near Philadelphia between 1998-2007 and 2008-2017. We identified ZIP codes with significantly higher incidence rates than the state rates and examined their demographic and exposure characteristics. Further, we tested for spatial autocorrelation and identified spatial clusters using Moran's I statistic. Our results showed that approximately one in four ZIP codes had an incidence rate that was significantly higher than the PA state rate in each period studied. Clusters of higher incidences were detected in the southeastern part of PA bordering New Jersey. These areas tended to be more populated, of lower socioeconomic status, and closer to manufacturing facilities and major highways. Possibly driven by the community and environmental factors, the observed differences in disease incidence suggest the importance of including residential location in risk assessment tools for lung cancer.

Evaluating the effects of design parameters on the performances of phase I trial designs.

Numerous designs have been proposed for phase I clinical trials. Although studies have compared their performances, few have considered the effects of changing design parameters. In this article, we review a few popular designs, including the 3 + 3, continuous reassessment method (CRM), Bayesian optimal interval (BOIN) design, and Keyboard design, and evaluate how varying design parameters (such as number of dose levels, target toxicity rate, maximum sample size, and cohort size) could impact the performances of each design through simulations. Excluded from our analysis is the mTPI-2 design, which operates in the same way as the Keyboard. Our results suggest that regardless of the choices of design parameters, the 3 + 3 design performs worse than the other ones, and BOIN and Keyboard have comparable performance to CRM. For any design, the performance varies with the choice of parameters. In particular, it improves as sample sizes increase, but the magnitude of benefit from increasing sample sizes varies substantially across scenarios. The impact of cohort size on design performances seems to have no clear direction. Therefore, BOIN and Keyboard designs are generally recommended due to their simplicity and good performance. With regard to choices of sample size and cohort size in designing a trial, it is recommend that simulations be performed for the particular clinical settings to aid decision making.

Association between features of COPD and risk of venous thromboembolism.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is associated with risk of venous thromboembolism (VTE) events. A detailed understanding of which clinical features of COPD increase risk of VTE events is needed. OBJECTIVES: To investigate the association between features of COPD and risk of venous thromboembolism. METHODS: A retrospective observational clinical study was conducted on 551 consecutive COPD patients visiting the Department of Respiratory and Critical Care Medicine of Tianjin Chest Hospital between February 2014 and April 2018. Finally, 151 patients were eligible for inclusion. Of these, 29 patients had COPD with VTE and 121 patients had COPD without VTE. Patient informations regarding age, gender, BMI, smoking history, smoking status (package/year), COPD-related symptoms, lung function, number of acute exacerbations and imaging visual emphysema were gathered. RESULTS: Among the 29 VTE patients, 18 patients had PE and five had DVT, while 6 patients had simultaneous PE and DVT. There were statistically significant differences in GOLD grade, Imaging visual emphysema, and frequent acute exacerbations between the two groups. Multivariate logistic regression analysis showed that after adjustment for gender, age, BMI and smoking history, there were statistically significant for visible emphysema (OR = 3.54, 95% CI: 1.13-11.08; P = 0.03) and GOLD grade (OR = 1.77, 95% CI: 1.04-3.01; P = 0.035), but not for frequent acute exacerbations (OR = 1.65, 95% CI: 0.62-4.38; P = 0.31). CONCLUSIONS: Visual emphysema is an independent risk factor for VTE events and the risk of VTE in COPD patients increases with the degree of airway obstruction. However, there is no evidence of an association between exacerbation frequency and VTE events.

Probiotics Biofilm-Integrated Electrospun Nanofiber Membranes: A New Starter Culture for Fermented Milk Production.

Electrospun nanofiber membranes are widely investigated in the past few decades as candidates for tissue engineering, which can mimic natural extracellular matrix (ECM) and improve cell adhesion, proliferation, and expression on nanofiber membranes. However, the formation of bacterial biofilms on nanofiber membranes and application of the biofilm-integrated nanofiber membranes remain largely unknown. Here, electrospun cellulose acetate nanofiber membranes are first utilized as scaffold materials for Lactobacillus plantarum ( L. plantarum) biofilm formation. Nanofiber membranes proved to be an excellent scaffold for bacteria biofilm with high stability, where biofilms were interlocked with nanofibers forming a cohesive structure. In comparison with planktonic bacteria, L. plantarum biofilms on nanofiber membranes show excellent gastrointestinal resistance. Instead of decreasing, the number of viable cells increased after 3 h digestion in vitro. The L. plantarum biofilm-integrated nanofiber membranes were used as reusable starter cultures for fermented milk production showing excellent fermentative ability and higher survival of L. plantarum during shelf life. The viable cells in fermented milk remained at 11 log CFU/g throughout the reusable batches, which is far above the required value of 7 log CFU/g in commercial products. In addition, the produced fermented milk possesses shorter fermentation time and higher survival of probiotics during shelf life. The results suggest electrospun nanofiber membranes are ideal scaffold materials for bacteria biofilms immobilization in biotechnology and fermentation engineering, which broaden the potential use of electrospun nanofiber membranes in microbiology and strengthen the application of biofilms in fermentation engineering.