SreC-dependent adaption to host iron environments regulates the transition of trophic stages and developmental processes of Curvularia lunata.

Plant pathogens are challenged by host-derived iron starvation or excess during infection, but the mechanism of plant pathogens rapidly adapting to the dynamic host iron environments to assimilate iron for invasion and colonization remains largely unexplored. Here, we found that the GATA transcription factor SreC in Curvularia lunata is required for virulence and adaption to the host iron excess environment. SreC directly binds to the ATGWGATAW element in an iron-dependent manner to regulate the switch between different iron assimilation pathways, conferring adaption to host iron environments in different trophic stages of C. lunata. SreC also regulates the transition of trophic stages and developmental processes in C. lunata. SreC-dependent adaption to host iron environments is essential to the infectious growth and survival of C. lunata. We also demonstrate that CgSreA (a SreC orthologue) plays a similar role in Colletotrichum graminicola. We conclude that Sre mediates adaption to the host iron environment during infection, and the function is conserved in hemibiotrophic fungi.

Clinicopathological correlations of peritoneal endometriosis and deep infiltrating endometriosis.

OBJECTIVE: The present study aims to investigate the clinical and histopathological features of peritoneal endometriosis (PEM) and deep infiltrating endometriosis (DIE). METHODS: A total of 100 patients with PEM and DIE admitted to Dalian Women and Children's Hospital/Dalian Women and Children's Medical Center between October 2018 and December 2021 were selected as the study subjects. One hundred and thirty-one PEM specimens and 37 DIE were collected, 22 cases of these patients' eutopic endometrium were used as control (15 in PEM, seven in DIE). The present study mainly analysed the pelvic distribution, the histopathological and immunohistochemical features and peritoneal invasion of PEM and DIE. RESULTS: The main distribution of PEM and DIE was located in the posterior pelvic cavity (p < .001). The histopathological characteristics of different PEM forms were different: the contents of endometrioid glands, endometrioid stroma, smooth muscle, fibrous tissue and blood vessels in different lesions were statistically significant (all p < .050). Estrogen receptor (ER) of PEM and DIE was highly expressed in endometrioid glandular epithelium and endometrioid stroma, without statistical significance (p = .330/.113). Progesterone receptor (PR) was also highly expressed in endometrioid glandular epithelium and endometrioid stroma without statistical significance (p = .757/.798). Ki-67 expression of DIE in endometrioid glandular epithelium was significantly higher than that in brown and white lesions (p < .001), while its expression in the endometrioid stroma was not statistically significant in red lesions (p = .070), but higher than that in other PEM lesions (p < .001). Different morphological lesions had different invasiveness rates and depths of invasion to the peritoneum. White lesions had a deeper subperitoneal invasion level than transparent and vesicular lesions. CONCLUSIONS: Although different morphological appearance of PEM is a degenerative process, some active brown lesions of PEM have invasive effects during the process and may further develop into DIE. PEM and DIE may be different developmental stages of the same disease.

In summary, PEM is a progressive disease, and its different morphological appearance reflects different stages of lesion development.Ectopic endometrial cells have a destructive effect on the peritoneal structures; as the lesion progresses, it continuously infiltrates the subperitoneum.PEM and DIE are different development stages of the same disease. The homology of the two lesions has yet to be explored in terms of pathogenesis.

Circ_0000231 promotes paclitaxel resistance in ovarian cancer by regulating miR-140/RAP1B.

Circular RNAs (circRNAs) are identified as vital regulators in a variety of cancers. However, the involvement of circ_0000231 in paclitaxel (PTX) resistant ovarian cancer (OC) remains unclear. In this study, we examined the levels of circ_0000231, microRNA-140 (miR-140) and RAP1B in PTX-resistant OC tissues and cells and found that circ_0000231 and RAP1B levels were increased, while miR-140 level was decreased in these cells. Depletion of circ_0000231 could inhibit the resistance, proliferation, invasion, migration and EMT and promoted the apoptosis of PTX-resistant OC cells. The opposite effects were observed by overexpression of circ_0000231. Furthermore, the effect of circ_0000231 on the PTX sensitivity of OC cells was investigated by using xenograft tumor models, and circ_0000231 knockdown increased PTX sensitivity of OC in vivo. Mechanistically, we demonstrated that circ_0000231 acted as a sponge for miR-140, and RAP1B was the target gene of miR-140. Taken together, these data indicated that circ_0000231 was a key molecule required for the growth, migration, and PTX-resistance of OC cells and was involved in EMT. Knockdown of circ_000231 suppressed PTX-resistant OC progression via regulating miR-140/RAP1B signaling pathway. circ_0000231 might play vital roles in the tumorigenesis and chemoresistance of OC.

Iron redistribution induces oxidative burst and resistance in maize against Curvularia lunata.

MAIN CONCLUSION: ΔClnps6 induced iron redistribution in maize B73 leaf cells and resulted in reactive oxygen species (ROS) burst to enhance plant resistance against Curvularia lunata. Iron is an indispensable co-factor of various crucial enzymes that are involved in cellular metabolic processes and energy metabolism in eukaryotes. For this reason, plants and pathogens compete for iron to maintain their iron homeostasis, respectively. In our previous study, ΔClnps6, the extracellular siderophore biosynthesis deletion mutant of Curvularia lunata, was sensitive to exogenous hydrogen peroxide and virulence reduction. However, the mechanism was not studied. Here, we report that maize B73 displayed highly resistance to ΔClnps6. The plants recruited more iron at cell wall appositions (CWAs) to cause ROS bursts. Intracellular iron deficiency induced by iron redistribution originated form up-regulated expression of genes involved in intracellular iron consumption in leaves and absorption in roots. The RNA-sequencing data also showed that the expression of respiratory burst oxidase homologue (ZmRBOH4) and NADP-dependent malic enzyme 4 (ZmNADP-ME4) involved in ROS production was up-regulated in maize B73 after ΔClnps6 infection. Simultaneously, jasmonic acid (JA) biosynthesis genes lipoxygenase (ZmLOX), allene oxide synthase (ZmAOS), GA degradation gene gibberellin 2-beta-dioxygenase (ZmGA2OX6) and ABA degradation genes abscisic acid hydroxylase (ZmABH1, ZmABH2) involved in iron homeostasis were up-regulated expression. Ferritin1 (ZmFER1) positive regulated maize resistance against C. lunata via ROS burst under Fe-limiting conditions. Overall, our results showed that iron played vital roles in activating maize resistance in B73-C. lunata interaction.

Physician-Nurse Communication Surrounding Computerized Physician Order Entry Systems From Social and Technical Perspective: An Ethnographic Study.

Although computerized physician order entry systems improve order transmission and patient safety, overdependence on these systems can impede users' communication. This ethnographic study explored physician-nurse communication surrounding computerized physician order entry systems using a sociotechnical framework. Fieldwork conducted in a tertiary teaching hospital comprised 89 hours of participant observation, and individual semistructured interviews were held with seven nurses and five physicians. In addition, documents and artifacts were collected. Three core themes emerged. First, computerized physician order entry quality-related issues undermined the work efficiency of physicians and nurses. Specifically, usability was error prone because of cognitive overload, and the system was unable to perform relevant traces and raise alerts, demonstrating poor interoperability. Second, social factors, including insufficient training, unclear responsibilities, and a lack of awareness concerning interdisciplinary communication, compounded communication problems. Last, environmental factors, including noncoterminous spaces and times and insufficient technical support, impeded the resolution of communication problems. Technical and social contextual factors relating to computerized physician order entry systems jointly affected physician-nurse communication. Cognitive issues and insufficient alerts impacted work efficiency the most and were compounded by contextual individual- and team-related factors and environmental factors. Therefore, improved functions of computerized physician order entry systems and interprofessional communication training are required to optimize technical and social aspects of physician-nurse communication.

The key iron assimilation genes ClFTR1, ClNPS6 were crucial for virulence of Curvularia lunata via initiating its appressorium formation and virulence factors.

Iron is virtually an essential nutrient for all organisms, to understand how iron contributes to virulence of plant pathogenic fungi, we identified ClFTR1 and ClNPS6 in maize pathogen Curvularia lunata (Cochliobolus lunatus) in this study. Disruption of ClNPS6 significantly impaired siderophore biosynthesis. ClFTR1 and ClNPS6 did mediate oxidative stress but had no significant impact on vegetative growth, conidiation, cell wall integrity and sexual reproduction. Conidial germination delayed and appressoria formation reduced in ΔClftr1 comparing with wild type (WT) CX-3. Genes responsible for conidial germination, appressoria formation, non-host selective toxin biosynthesis and cell wall degrading enzymes were also downregulated in the transcriptome of ΔClftr1 and ΔClnps6 compared with WT. The conidial development, toxin biosynthesis and polygalacturonase activity were impaired in the mutant strains with ClFTR1 and ClNPS6 deletion during their infection to maize. ClFTR1 and ClNPS6 were upregulated expression at 12-24 and 48-120 hpi in WT respectively. ClFTR1 positively regulated conidial germination, appressoria formation in the biotrophy-specific phase. ClNPS6 positively regulates non-host selective toxin biosynthesis and cell wall degrading enzyme activity in the necrotrophy-specific phase. Our results indicated that ClFTR1 and ClNPS6 were key genes of pathogen known to conidia development and virulence factors.

NADPH Oxidase ClNOX2 Regulates Melanin-Mediated Development and Virulence in Curvularia lunata.

The role of NADPH oxidases (NOXs) in pathogenesis and development in the Curvularia leaf spot agent Curvularia lunata remains poorly understood. In this study, we identified C. lunata ClNOX2, which localized to the plasma membrane and was responsible for reactive oxygen species (ROS) generation. Scavenging the ROS production inhibited the conidial germination and appressorial formation. The ClNOX2 and ClBRN1 deletion mutants were defective in 1,8-dihydroxynaphthalene (DHN) melanin accumulation, appressorial formation, and cellulase synthesis and exhibited lower virulence. However, disruption of the ClNOX2 and ClBRN1 genes facilitated hyphal growth, enhanced stress adaptation to cell-wall-disrupting agents, and promoted developmental processes such as conidiation, conidial germination, and pseudothecium and ascus formation. Interestingly, loss of ClM1, the cell wall integrity (CWI) mitogen-activated protein kinase gene in C. lunata, led to morphology and pathogenicity phenotypes similar to ClNOX2 and ClBRN1 deletion mutants such as abnormal conidia, fewer appressoria, less melanin, increased hyphal growth, and enhanced tolerance to Congo red (CR). These results indicated that the ClNOX2 gene plays an important role in C. lunata development and virulence via regulating intracellular DHN melanin biosynthesis. Quantitative reverse-transcription PCR revealed that the ClNOX2-related ROS signaling pathway and ClM1-mediated CWI signaling pathway are cross-linked in regulating DHN melanin biosynthesis. Our findings provide new insights into how ClNOX2 participates in pathogenesis and development in hemibiotrophic plant fungal pathogens.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Breast Cancer Survivors Report Similar Concerns Related to Return to Work in Developed and Developing Nations.

Aim To determine whether breast cancer survivors (BCS) at work following the diagnosis and/or treatment of breast cancer, in a rapidly developing country such as China experience similar to return to work challenges as reported in nations with established return to work (RTW) policy and procedures for employees with cancer. Methods Semi-structured interviews were conducted with 16 BCS who returned to work following diagnosis and/or primary cancer treatment. An Interpretative Phenomenological Analysis was used to investigate responses. Results Three recurring themes emerged: (1) challenges at work related to residual effects of diagnosis and/or primary treatment; (2) positive and negative responses from employers and/or supervisors; and (3) positive and negative responses from co-workers/colleagues. Although several participants experienced a high level of workplace support, there was a subgroup that did report challenges related to symptom burden, cognitive limitations, and both positive and negative responses by employers and co-workers were reported. Conclusions Findings indicate similar challenges in BCS who RTW during and/or following cancer treatment in both rapidly developing and developed nations. Results suggest that regardless of the existence of workplace policies and practices related to RTW for workers with a history of cancer, a subgroup of BCS experience similar challenges when returning to work. These findings highlight the international nature of RTW challenges and suggest the need for more global efforts to develop and evaluate workplace interventions to assist with these similarities.