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Background Transcription factors (TFs) are involved in many important biological processes, including cell stretching, histological differentiation, metabolic activity, seed storage, gene regulation, and response to abiotic and biotic stresses. Little is known about the functions, evolutionary history, and expression patterns of basic region-leucine zipper TF family genes in pear, despite the release of the genome of Chinese white pears (“Dangshansuli”). Results Overall, 92 bZIP genes were identified in the pear genome ( Pyrus breschneideri ). Of these, 83 were randomly distributed on all 17 chromosomes except chromosome 4, and the other 9 genes were located on loose scaffolding. The genes were divided into 14 subgroups. Whole-genome duplications, dispersed duplication, and purifying selection for whole-genome duplications are the main reasons for the expansion of the PbrbZIP gene family. The analysis of functional annotation enrichment indicated that most of the functions of PbrbZIP genes were enriched in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways involved in the abiotic stress response. Next, expression analysis and virus-induced gene silencing results indicated that PbrbZIP genes might play critical roles in response to drought and cold stresses, especially for the genes from subgroups A, C, G, I, and S. Conclusions Ninety-two PbrbZIP genes were identified from the pear genome and classified into 14 subgroups. PbrbZIP genes were mainly expanded from whole-genome duplications and dispersed duplications and retained by purifying selection. PbrbZIP genes were induced by cold and drought stresses and played important roles in drought and cold tolerance. These results provided useful information for further increasing the tolerance of pears to stresses and a foundation to study the cold and drought tolerance mechanism of PbrbZIP genes.

Background The basic helix-loop-helix (bHLH) transcription factors play important roles in many processes in plant growth, metabolism and responses to abiotic stresses. Although, the sequence of Chinese white pear genome (cv. ‘Dangshansuli’) has already been reported, there is still a lack of clarity regarding the bHLH family genes and their evolutionary history. Results In this work, a genome-wide identification of the bHLH genes in Chinese white pear was performed, and we characterized the functional roles of these PbrbHLH genes in response to abiotic stresses. Based on the phylogenetic analysis and structural characteristics, 197 identified bHLH genes could be well classified into 21 groups. Expansion of PbrbHLH gene family was mainly driven by WGD and dispersed duplication with the purifying selection from the recent WGD. The functional annotation enrichment showed that the majority of PbrbHLHs were enriched in the GO terms and KEGG pathways involved in responds to stress conditions as TFs. Transcriptomic profiles and qRT-PCR revealed that PbrbHLH7 , PbrbHLH8 , PbrbHLH128 , PbrbHLH160 , PbrbHLH161 and PbrbHLH195 were significantly up-regulated under cold and drought treatments. In addition, PbrbHLH195 -silenced pear seedlings display significant reduced cold tolerance, exhibiting reduced chlorophyll content, as well as increased electrolyte leakage and concentrations of malondialdehyde and H 2 O 2 . Conclusion For the first time, a comprehensive analysis identified the bHLH genes in Chinese white pear and demonstrated that PbrbHLH195 is involved in the production of ROS in response to cold stress, suggesting that members of the PbrbHLH family play an essential role in the stress tolerance of pear.

Ethnopharmacological relevance: Curcumin is a bright yellow chemical produced by plants of the Curcuma longa species. Chemically, curcumin is a diarylheptanoid, belonging to the group of curcuminoids. The therapeutic potential of curcumin has been widely investigated, including its utilization in various of cardiovascular diseases. However, its effect in cardiac remodeling post myocardial infarction and underlying mechanism remains to be uncover. Aim: To evaluate the therapeutic effect and underlying mechanism of curcumin on cardiac fibrosis after myocardial infarction via macrophage-fibroblast crosstalk. Methods: Male C57BL/6 (C57) mice were subjected to left anterior descending coronary artery ligation to establish myocardial infarction and intragastrically fed vehicle or curcumin (50 mg/kg or 100 mg/kg) for 4 weeks. In parallel, neonatal rat cardiac fibroblasts were isolated and co-cultured with liposaccharide (LPS − or LPS + ) curcumin-treated macrophages, followed by TGF-β stimulation for 24 h. Cardiac function was determined by 2-dimensional echocardiography, and cardiac fibrosis was measured by picrosirius red staining. Apoptosis of macrophages was investigated by flow cytometry; all pro-fibrotic protein expression (EDA-Fibronectin, Periostin, Vimentin, and α-SMA) as well as TGF-βR1 downstream signaling activation reflected by phosphorylated SMAD2/3 ( p -SMAD2 and p -SMAD3) were demonstrated by western blotting. Results: Curcumin significantly ameliorated the inflammation process subsequent to myocardial infarction, reflected by decreased expression of CD68 + and CD3 + cells, accompanied by dramatically improved cardiac function compared with the placebo group. In addition, cardiac fibrosis is inhibited by curcumin administration. Interestingly, no significant reduction in fibrotic gene expression was observed when isolated cardiac fibroblasts were directly treated with curcumin in vitro; however, pro-fibrotic protein expression was significantly attenuated in CF, which was co-cultured with LPS-stimulated macrophages under curcumin treatment compared with the placebo group. Mechanistically, we discovered that curcumin significantly downregulated pro-inflammatory cytokines in macrophages, which in turn inhibited IL18 expression in co-cultured cardiac fibroblasts using bulk RNA sequencing, and the TGF-β1- p -SMAD2/3 signaling network was also discovered as the eventual target downstream of IL18 in curcumin-mediated anti-fibrosis signaling. Conclusion: Curcumin improves cardiac function and reduces cardiac fibrosis after myocardial infarction. This effect is mediated by the inhibition of macrophage-fibroblast crosstalk in the acute phase post-MI and retrained activation of IL18-TGFβ1- p -SMAD2/3 signaling in cardiac fibroblasts.

In this study, we conceptualize the demands imposed on emergency supply chains during extraordinary emergency events as “stress” and develop a scenario-based stress evolution (SE) analytical approach in emergency mobilization decision-making. First, we characterize emergency supply chain stress by uncertainty, abruptness, urgency, massiveness of scale, and latency. Leveraging lifecycle theory and aligning it with the event’s natural lifecycle progression, we construct a dual-cycle model—the emergency event-stress dual-cycle curve model—to intuitively conceptualize the SE process. Second, taking China’s emergency medical supply chain as an illustrative example, we employ set theory to achieve a structured representation of emergency supply chain stress evolution (ESCSE). Third, we propose a novel ESCSE modeling methodology based on stochastic Petri nets and establish both an ESCSE model and a corresponding isomorphic Markov chain model. To address parameter uncertainties inherent in the modeling process, the fuzzy theory is integrated for parameter optimization, enabling realistic simulation of emergency supply chain stress evolution dynamics. Finally, the SE of the ibuprofen supply chain in Beijing during the COVID-19 pandemic is presented as a case study to demonstrate the working principle of the model. The results indicate that the ESCSE model effectively simulates the SE process, identifies critical states, and triggers actions. It also reveals the evolution trends of key scenario elements, thereby assisting decision-makers in deploying more targeted mobilization strategies in dynamic and changing environments.

Background Lysin motif-containing proteins (LYP), which act as pattern-recognition receptors, play central roles in growth, node formation, and responses to biotic stresses. The sequence of Chinese white pear genome (cv. ‘Dangshansuli’) along with the seven other species of Rosaceae has already been reported. Although, in these fruit crops, there is still a lack of clarity regarding the LYP family genes and their evolutionary history. Results In the existing study, eight Rosaceae species i.e. , Pyrus communis , Prunus persica , Fragaria vesca , Pyrus bretschneideri, Prunus avium, Prunus mume , Rubus occidentalis , and Malus × domestica were evaluated. Here, we determined a total of 124 LYP genes from the underlined Rosaceae species. While eighteen of the genes were from Chinese white pear, named as PbrLYPs . According to the LYPs structural characteristics and their phylogenetic analysis, those genes were classified into eight groups (group LYK1, LYK2, LYK3, LYK4/5, LYM1/3, LYM2, NFP, and WAKL). Dispersed duplication and whole-genome duplication (WGD) were found to be the most contributing factors of LYP family expansion in the Rosaceae species. More than half of the duplicated PbrLYP gene pairs were dated back to the ancient WGD (~ 140 million years ago (MYA)), and PbrLYP genes have experienced long-term purifying selection. The transcriptomic results indicated that the PbrLYP genes expression was tissue-specific. Most PbrLYP genes showed differential expression in leaves under fungal pathogen infection with two of them located in the plasmalemma. Conclusion A comprehensive analysis identified 124 LYP genes in eight Rosaceae species. Our findings have provided insights into the functions and characteristics of the Rosaceae LYP genes and a guide for the identification of other candidate LYPs for further genetic improvements for pathogen-resistance in higher plants.

Background Lysin motif (LysM)-containing proteins are involved in the recognition of fungal and bacterial pathogens. However, few studies have reported on their roles in the defense responses of woody plants against pathogens. A previous study reported that the apple MdCERK1 gene was induced by chitin and Rhizoctonia solani , and its protein can bind to chitin. However, its effect on defense responses has not been investigated. Results In this study, a new apple CERK gene, designated as MdCERK1–2 , was identified. It encodes a protein that shares high sequence identity with the previously reported MdCERK1 and AtCERK1. Its chitin binding ability and subcellular location are similar to MdCERK1 and AtCERK1, suggesting that MdCERK1–2 may play a role in apple immune defense responses as a pattern recognition receptor (PRR). MdCERK1–2 expression in apple was induced by 2 fungal pathogens, Botryosphaeria dothidea and Glomerella cingulate, but not by the bacterial pathogen, Erwinia amylovora , indicating that MdCERK1–2 is involved in apple anti-fungal defense responses. Further functional analysis by heterologous overexpression (OE) in Nicotiana benthamiana ( Nb ) demonstrated that MdCERK1–2 OE improved Nb resistance to the pathogenic fungus, Alternaria alternata . H 2 O 2 accumulation and callose deposition increased after A. alternata infection in MdCERK1–2 OE plants compared to wild type (WT) and empty vector (EV)-transformed plants. The induced expression of NbPAL4 by A. alternata significantly ( p  < 0.01, n  = 4) increased in MdCERK1–2 OE plants. Other tested genes, including NbNPR1 , NbPR1a , NbERF1 , and NbLOX1 , did not exhibit significant changes after A. alternata infection in OE plants compared to EV or WT plants. OE plants also accumulated more polyphenols after A. alternata infection. Conclusions Heterologous MdCERK1–2 OE affects multiple defense responses in Nb plants and increased their resistance to fungal pathogens. This result also suggests that MdCERK1–2 is involved in apple defense responses against pathogenic fungi.

The testosterone (TT)/androgen receptor axis plays a crucial role in the initiation and progression of prostate cancer (PCa). We aimed to investigate the predictive value of serum TT levels on metastatic PCa progression. A total of 219 patients with metastatic PCa were included in this study. Analyses performed included Pearson’s correlation test, Wilcoxon rank test, Chi-square test, Cox regression, and Kaplan-Meier analysis. High serum TT levels (> 405 ng/dL) before ADT treatment, deep testosterone reduction (DTR) within the first year of ADT, rapid DTR within 3 months of ADT, and sustained DTR in the first year of ADT are associated with longer CRPC progression-free time. Low serum TT levels before abiraterone treatment are a risk factor for early PSA progression. We constructed a nomogram model based on the DTR within the first year of ADT. Calibration curve and decision curve analyses suggest the model has a high predictive ability for 1-, 1.5-, and 2-year CRPC progression and well clinical utility. Serum TT levels before and during ADT, as well as before abiraterone treatment, can predict metastatic PCa progression. Monitoring serum TT levels throughout the entire course of treatment is crucial for patient follow-up and prognosis.

Metabolic modulation is a promising therapeutic approach to prevent adverse remodeling of the ischemic heart. Because little is known about the involvement of long non-coding RNAs (lncRNAs) in regulating cardiac metabolism, we used unbiased transcriptome profiling in a mouse model of myocardial infarction (MI). We identified a novel cardiomyocyte-enriched lncRNA, called LncHrt, which regulates metabolism and the pathophysiological processes that lead to heart failure. AAV-based LncHrt overexpression protects the heart from MI as demonstrated by improved contractile function, preserved metabolic homeostasis, and attenuated maladaptive remodeling responses. RNA-pull down followed by mass spectrometry and RNA immunoprecipitation (RIP) identified SIRT2 as a LncHrt-interacting protein involved in cardiac metabolic regulation. Mechanistically, we established that LncHrt interacts with SIRT2 to preserve SIRT2 deacetylase activity by interfering with the CDK5 and SIRT2 interaction. This increases downstream LKB1-AMPK kinase signaling, which ameliorates functional and metabolic deficits. Importantly, we found the expression of the human homolog of mouse LncHrt was decreased in patients with dilated cardiomyopathy. Together, these studies identify LncHrt as a cardiac metabolic regulator that plays an essential role in preserving heart function by regulating downstream metabolic signaling pathways. Consequently, LncHrt is a potentially novel RNA-based therapeutic target for ischemic heart disease.

Fibroblasts are the essential cell type of skin, highly involved in the wound regeneration process. In this study, we sought to screen out the novel genes which act important roles in diabetic fibroblasts through bioinformatic methods. A total of 811 and 490 differentially expressed genes (DEGs) between diabetic and normal fibroblasts were screened out in GSE49566 and GSE78891, respectively. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in type 2 diabetes were retrieved from miRWalk. Consequently, the integrated bioinformatic analyses revealed the shared KEGG pathways between DEG-identified and diabetes-related pathways were functionally enriched in the MAPK signaling pathway, and the MAPKAPK3, HSPA2, TGFBR1, and p53 signaling pathways were involved. Finally, ETV4 and NPE2 were identified as the targeted transcript factors of MAPKAPK3, HSPA2, and TGFBR1. Our findings may throw novel sight in elucidating the molecular mechanisms of fibroblast pathologies in patients with diabetic wounds and targeting new factors to advance diabetic wound treatment in clinic.

The Arabidopsis Tóxicos en Levadura (ATL) protein is a subfamily of the E3 ubiquitin ligases, which exists widely in plants and is extensively involved in plant growth and development. Although the ATL family has been identified in other species, such as Arabidopsis, Oryza sativa, and grapevine, few reports on pear ATL gene families have been reported. In this study, 92 PbrATL genes were identified and analyzed from the Pyrus breschneideri genome. Motif analysis and phylogenetic tree generation divided them into nine subgroups, and chromosome localization analysis showed that the 92 PbrATL genes were distributed in 16 of 17 pear chromosomes. Transcriptome data and quantitative real-time polymerase chain reaction (qRT-PCR) experiments demonstrated that PbrATL18, PbrATL41, and PbrATL88 were involved in both pear drought resistance and Colletotrichum fructicola infection. In addition, Arabidopsis thaliana overexpressing PbrATL18 showed greater resistance to drought stress than the wild type (WT), and PbrATL18-silenced pear seedlings showed greater sensitivity to drought and C. fructicola infection than the controls. PbrATL18 regulated plant resistance by regulating chitinase (CHI), phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) activities. This study provided a reference for further exploring the functions of the PbrATL gene in drought resistance and C. fructicola infection.