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Anthocyanins, constituents of flavonoid compounds prevalent in plants, possess significant value in both plant development and human nutrition. The regulation of anthocyanin biosynthesis primarily involves the orchestration of MYB, bHLH, and WD40 transcription factors. Consequently, the bHLH family assumes a pivotal role in modulating plant developmental processes. In the present investigation, a transcription factor, denoted as LvbHLH13, was identified as a positive regulator of anthocyanin pigmentation in lily petals. LvbHLH13 is classified within the IIId subgroup of Arabidopsis bHLH proteins. Functional analyses involving the transient expression and gene silencing of LvbHLH13 revealed its capacity to enhance and diminish anthocyanin accumulation, respectively, by modulating the LvMYB5 expression, thereby influencing the downstream structural gene expression. The overexpression of LvbHLH13 resulted in an increase in the expression of the downstream structural genes related to anthocyanin synthesis, whereas silencing of LvbHLH13 correspondingly decreased the expression. Yeast one-hybrid and EMSA assays demonstrated the interaction between LvbHLH13 and the LvMYB5 promoter, leading to the activation of anthocyanin biosynthesis. A further luciferase (LUC) analysis corroborated the stimulatory effect of LvbHLH13 on the LvMYB5 promoter sequence. Consequently, LvbHLH13 assumed a crucial role in lily-petal pigmentation. A yeast two-hybrid analysis revealed that LvbHLH13 diverged from typical bHLH transcription factor behavior as it did not form a complex with MYB to regulate anthocyanin biosynthesis. This discrepancy could be attributed to the deletion of the N-terminal conserved sequence of LvbHLH13. This study provides a new bHLH candidate and bHLH-MYB partner to explore the anthocyanin regulatory network in further research and provides new opportunities for breeding lilies with various anthocyanin contents. These findings lay a theoretical foundation for subsequent investigations into lily flower coloring mechanisms. [ABSTRACT FROM AUTHOR]

Soybean (Glycine max (L.) Merr) is one of the most important crops worldwide, but its yield is vulnerable to abiotic stresses. In Arabidopsis, the AlkB homologue (ALKBH) family genes plays a crucial role in plant development and stress response. However, the identification and functions of its homologous genes in soybean remain obscured. Here, we identified a total of 22 ALKBH genes in soybean and classified them into seven subfamilies according to phylogenetic analysis. Gene duplication events among the family members and gene structure, conserved domains, and motifs of all candidate genes were analyzed. By comparing the changes in the m6A levels on mRNA from hair roots between soybean seedlings harboring the empty vector and those harboring the GmALKBH10B protein, we demonstrated that all four GmALKBH10B proteins are bona fide m6A RNA demethylases in vivo. Subcellular localization and expression patterns of the GmALKBH10B revealed that they might be functionally redundant. Furthermore, an analysis of cis-elements coupled with gene expression data demonstrated that GmALKBH10B subfamily genes, including GmALKBH10B1, GmALKBH10B2, GmALKBH10B3, and GmALKBH10B4, are likely involved in the cis-elements' response to various environmental stimuli. In summary, our study is the first to report the genome-wide identification of GmALKBH family genes in soybean and to determine the function of GmALKBH10B proteins as m6A RNA demethylases, providing insights into GmALKBH10B genes in response to abiotic stresses. [ABSTRACT FROM AUTHOR]

A study examined the use of a probiotic called Probio-M9 in treating mastitis and improving antibiotic treatment. The researchers found that Probio-M9 effectively reduced mastitis symptoms, decreased inflammation, and enhanced the response to antibiotics. It also had an impact on the gut microbiome and the immune system. The study suggests that Probio-M9 can move from the gut to the mammary tissue during bacterial mastitis and lactation. These findings provide insight into the connection between the gut and mammary glands and the potential benefits of probiotics. [Extracted from the article]

Simple Summary: Immune defense against bacterial infection involves a fierce struggle between bacteria and immune cells. Neutrophils, as the first line of defense, must cross the epithelial barrier to reach the infected site. During this process, communication between neutrophils and endothelial cells is crucial for regulating immune defense, cascade reactions, and inflammation. Therefore, we present the detailed steps of neutrophil–endothelial cell interactions and the principles of neutrophil biology. The overview of the research progress focuses on transendothelial neutrophil killing and how endothelial dysfunction affects inflammatory cascade reactions. These summaries of neutrophil activation and endothelial dysfunction provide potential therapeutic targets for discovering and developing antibacterial and anti-inflammatory drugs. The endothelial barrier plays a critical role in immune defense against bacterial infection. Efficient interactions between neutrophils and endothelial cells facilitate the activation of both cell types. However, neutrophil activation can have dual effects, promoting bacterial clearance on one hand while triggering inflammation on the other. In this review, we provide a detailed overview of the cellular defense progression when neutrophils encounter bacteria, focusing specifically on neutrophil–endothelial interactions and endothelial activation or dysfunction. By elucidating the underlying mechanisms of inflammatory pathways, potential therapeutic targets for inflammation caused by endothelial dysfunction may be identified. Overall, our comprehensive understanding of neutrophil–endothelial interactions in modulating innate immunity provides deeper insights into therapeutic strategies for infectious diseases and further promotes the development of antibacterial and anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Objective: With the improvement of medical level, the number of elderly patients is increasing, and the postoperative outcome of the patients cannot be ignored. However, there have been no studies on the relationship between preoperative heart rate variability (HRV) and Perioperative Neurocognitive Disorders (PND). The purpose of this study was to explore the correlation between (HRV) and (PND), postoperative intensive care unit (ICU), and hospital stay in patients undergoing non-cardiac surgery. Method: This retrospective analysis included 687 inpatients who underwent 24-hour dynamic electrocardiogram examination in our six departments from January 2021 to January 2022. Patients were divided into two groups based on heart rate variability (HRV): high and low. Possible risk factors of perioperative outcomes were screened using univariate analysis, and risk factors were included in multivariate logistic regression to screen for independent risk factors. The subgroup analysis was carried out to evaluate the robustness of the results. The nomogram of PND multi-factor logistic prediction model was constructed. The receiver operating characteristic (ROC) curve was drawn, and the calibration curve was drawn by bootstrap resampling 1000 times for internal verification to evaluate the prediction ability of nomogram. Result: A total of 687 eligible patients were included. The incidence of low HRV was 36.7% and the incidence of PND was 7.6%. The incidence of PND in the low HRV group was higher than that in the high HRV group (11.8% vs 5.2%), the postoperative ICU transfer rate was higher (15.9% than 9.3%P = 0.009), and the hospital stay was longer [15 (11, 19) vs (13), 0.015]. The multivariable logistic regression analysis showed that after adjusting for other factors, decreased low HRV was identified as an independent risk factor for the occurrence of PND (Adjusted Odds Ratio = 2.095; 95% Confidence Interval: 1.160–3.784; P = 0.014) and postoperative ICU admission (Adjusted Odds Ratio = 1.925; 95% Confidence Interval: 1.128–3.286; P = 0.016). This study drew a nomogram column chart for a multivariate logistic regression model, incorporating age and HRV. The calibration curve shows that the predicted value of the model for the occurrence of cardio-cerebrovascular events is in good agreement with the actual observed value, with C-index of 0.696 (95% CI: 0.626 ~ 0.766). Subgroup analysis showed that low HRV was an independent risk factor for PND in patients with gastrointestinal surgery and ASA Ⅲ, aged ≥ 65 years. Conclusion: In patients undergoing non-cardiac surgery, the low HRV was an independent risk factor for PND and postoperative transfer to the ICU, and the hospitalization time of patients with low HRV was prolonged. Through establishing a risk prediction model for the occurrence of PND, high-risk patients can be identified during the perioperative period for early intervention. [ABSTRACT FROM AUTHOR]

Although intravenous bevacizumab (IVBEV) is the most promising treatment for cerebral radiation necrosis (CRN), there is no conclusion on the optimal dosage. Our retrospective study aimed to compare the efficacy and safety of high‐dose with low‐dose IVBEV in treating CRN associated with radiotherapy for brain metastases (BMs). This paper describes 75 patients who were diagnosed with CRN secondary to radiotherapy for BMs, treated with low‐dose or high‐dose IVBEV and followed up for a minimum of 6 months. The clinical data collected for this study include changes in brain MRI, clinical symptoms, and corticosteroid usage before, during, and after IVBEV treatment. At the 3‐month mark following administration of IVBEV, a comparison of two groups revealed that the median percentage decreases in CRN volume on T2‐weighted fluid‐attenuated inversion recovery and T1‐weighted gadolinium contrast‐enhanced image (T1CE), as well as the signal ratio reduction on T1CE, were 65.8% versus 64.8% (p = 0.860), 41.2% versus 51.9% (p = 0.396), and 37.4% versus 35.1% (p = 0.271), respectively. Similarly, at 6 months post‐IVBEV, the median percentage reductions of the aforementioned parameters were 59.5% versus 62.0% (p = 0.757), 39.1% versus 31.3% (p = 0.851), and 35.4% versus 28.2% (p = 0.083), respectively. Notably, the incidence of grade ≥3 adverse events was higher in the high‐dose group (n = 4, 9.8%) than in the low‐dose group (n = 0). Among patients with CRN secondary to radiotherapy for BMs, the administration of high‐dose IVBEV did not demonstrate superiority over low‐dose IVBEV. Moreover, the use of high‐dose IVBEV was associated with a higher incidence of grade ≥3 adverse events compared with low‐dose IVBEV. [ABSTRACT FROM AUTHOR]

Leukemia-initiating cells (LICs) are responsible for the initiation, development, and relapse of leukemia. The identification of novel therapeutic LIC targets is critical to curing leukemia. In this report, we reveal that junctional adhesion molecule 3 (JAM3) is highly enriched in both mouse and human LICs. Leukemogenesis is almost completely abrogated upon Jam3 deletion during serial transplantations in an MLL-AF9-induced murine acute myeloid leukemia model. In contrast, Jam3 deletion does not affect the functions of mouse hematopoietic stem cells. Moreover, knockdown of JAM3 leads to a dramatic decrease in the proliferation of both human leukemia cell lines and primary LICs. JAM3 directly associates with LRP5 to activate the downstream PDK1/AKT pathway, followed by the downregulation of GSK3[beta] and activation of [beta]-catenin/CCND1 signaling, to maintain the self-renewal ability and cell cycle entry of LICs. Thus, JAM3 may serve as a functional LIC marker and play an important role in the maintenance of LIC stemness through unexpected LRP5/PDK1/AKT/GSK3[beta]/[beta]-catenin/CCND1 signaling pathways but not via its canonical role in cell junctions and migration. JAM3 may be an ideal therapeutic target for the eradication of LICs without influencing normal hematopoiesis., Introduction Acute myeloid leukemia (AML) is one of the most common malignant hematopoietic disorders in adults and may originate from hematopoietic stem cells (HSCs) or their downstream progenitors with the [...]

Objective: To investigate the genetic stability of Lacticaseibacillus rhamnosus Probio-M9 (L. rhamnosus Pro- bio-M9) during continuous passage. Methods: The morphological changes, carbohydrate utilization capacity, activity and metabolic characteristics of L. rhamnosus Probio-M9 were compared in the 0, 25, 50, 75 and 100 passages of the pro- biotic strain. At the same time, comparative genomics was used to analyze the changes of genome level during the con¬tinuous culture of 100 generations. Results: There were no significant changes (P >0.05) in phenotypic characteristics and metabolic characteristics of L. rhamnosus Probio-M9 during 100 generations of continuous culture, and the phenotyp- ic characteristics were stable, and the strain activity was maintained well. At the same time, using the genome of L. rhamnosus Probio-M9 as the reference sequence, 15 strains of different generations were sequenced, and the genome size and GC content showed no significant difference between the 15 strains cultured continuously and L. rhamnosus Probio- M9. Phylogenetic relationships showed that the 15 strains were closely related to the original genome. From the identified SNP loci, no mutation locus with stable inheritance was found in every two generations, and the collinear strain was good. The mutation level of the coding gene at the genome level confirmed that L. rhamnosus Probio-M9 had stable phe- notypic characteristics and metabolic characteristics during the continuous culture of 100 generations. Conclusion: L. rhamnosus Probio-M9 has good genetic stability during continuous passage, which provides a theoretical basis for further development, research and industrialization of L. rhamnosus Probio-M9. [ABSTRACT FROM AUTHOR]

Certain secretory proteins are known to be critical for maintaining the sternness of stem cells through autocrine signaling. However, the processes underlying the biogenesis, maturation, and secretion of these proteins remain largely unknown. Here we demonstrate that many secretory proteins produced by hematopoietic stem cells (HSCs) undergo exosomal maturation and release that is controlled by vacuolar protein sorting protein 33b (VPS33B). Deletion of VPS33B in either mouse or human HSCs resulted in impaired exosome maturation and secretion as well as loss of sternness. Additionally, VPS33B deficiency led to a dramatic delay in leukemogenesis. Exosomes purified from either conditioned medium or human plasma could partially rescue the defects of HSCs and leukemia-initiating cells (LICs). VPS33B co- existed in exosomes with GDI2, VPS16B, FLOT1, and other known exosome markers. Mechanistically, VPS33B interacted with the GDI2/RAB11A/RAB27A pathway to regulate the trafficking of secretory proteins as exosomes. These findings reveal an essential role for VPS33B in exosome pathways in HSCs and LICs. Moreover, they shed light on the understanding of vesicle trafficking in other stem cells and on the development of improved strategies for cancer treatment., Introduction Adult hematopoietic stem cells (HSCs) reside in a unique BM microenvironment (niche) and give rise to all circulating blood cells. The fates of HSCs are tightly orchestrated among quiescence, [...]