N-glycan signatures identified in the serum from biliary tract cancer patients: Association with clinical diagnosis and prognosis.

BACKGROUND: Changes in the expression of genes related to glycosyltransferases may lead to alterations in N-glycan structure abundance, potentially acting as markers for diagnosis and prognosis in biliary tract cancer (BTC). METHODS: This study was divided into cross-sectional and longitudinal approaches. The cross-sectional study included 316 BTC and 301 non-BTC. Propensity score matching was applied to adjust for sex and age differences between BTC and non-BTC. Univariate and multivariate logistic regression identified independent risk factors for BTC and constructed the BTC-G model. The ROC curve was used to validate the diagnostic performance of BTC-G. Longitudinal follow-up studies included postoperative (N = 50) and immunotherapy (N = 43) follow-up cohorts. Cox regression analysis identified N-glycan structures impacting BTC prognosis postoperative and immunotherapy, with further confirmation through Kaplan-Meier curves. RESULTS: Univariate and multivariate analyses identified Peak3 (OR: 0.790, 95% CI: 0.658-0.949), Peak9 (OR: 1.646, 95% CI: 1.409-1.922), and Peak9p (OR: 2.467, 95% CI: 1.267-4.804) as independent BTC risk factors, leading to the creation of the BTC-G. The ROC curve confirmed that BTC-G performed well in training (AUC: 0.753, 95% CI: 0.703-0.799), validation (AUC: 0.811, 95% CI: 0.740-0.870), and CA19-9 negative cohorts (AUC: 0.717, 95% CI: 0.664-0.767). Cox regression analysis and Kaplan-Meier curves established that Peak12 (HR: 5.578, 95% CI: 1.145-27.170) and Peak11 (HR: 1.104, 95% CI: 0.611-1.994) are independent risk factors for BTC prognosis following surgery and immunotherapy, respectively. CONCLUSIONS: Our NGFP technology supplements BTC diagnostics, distinguishing survival and recurrence subtypes for postoperative and immunotherapy, thereby supporting the development of treatment strategies.

Critical role of the gut microbiota in immune responses and cancer immunotherapy.

The gut microbiota plays a critical role in the progression of human diseases, especially cancer. In recent decades, there has been accumulating evidence of the connections between the gut microbiota and cancer immunotherapy. Therefore, understanding the functional role of the gut microbiota in regulating immune responses to cancer immunotherapy is crucial for developing precision medicine. In this review, we extract insights from state-of-the-art research to decipher the complicated crosstalk among the gut microbiota, the systemic immune system, and immunotherapy in the context of cancer. Additionally, as the gut microbiota can account for immune-related adverse events, we discuss potential interventions to minimize these adverse effects and discuss the clinical application of five microbiota-targeted strategies that precisely increase the efficacy of cancer immunotherapy. Finally, as the gut microbiota holds promising potential as a target for precision cancer immunotherapeutics, we summarize current challenges and provide a general outlook on future directions in this field.

Surviving a Double-Edged Sword: Response of Horticultural Crops to Multiple Abiotic Stressors.

Climate change-induced weather events, such as extreme temperatures, prolonged drought spells, or flooding, pose an enormous risk to crop productivity. Studies on the implications of multiple stresses may vary from those on a single stress. Usually, these stresses coincide, amplifying the extent of collateral damage and contributing to significant financial losses. The breadth of investigations focusing on the response of horticultural crops to a single abiotic stress is immense. However, the tolerance mechanisms of horticultural crops to multiple abiotic stresses remain poorly understood. In this review, we described the most prevalent types of abiotic stresses that occur simultaneously and discussed them in in-depth detail regarding the physiological and molecular responses of horticultural crops. In particular, we discussed the transcriptional, posttranscriptional, and metabolic responses of horticultural crops to multiple abiotic stresses. Strategies to breed multi-stress-resilient lines have been presented. Our manuscript presents an interesting amount of proposed knowledge that could be valuable in generating resilient genotypes for multiple stressors.

Therapeutic targeting of white adipose tissue metabolic dysfunction in obesity: mechanisms and opportunities.

White adipose tissue is not only a highly heterogeneous organ containing various cells, such as adipocytes, adipose stem and progenitor cells, and immune cells, but also an endocrine organ that is highly important for regulating metabolic and immune homeostasis. In individuals with obesity, dynamic cellular changes in adipose tissue result in phenotypic switching and adipose tissue dysfunction, including pathological expansion, WAT fibrosis, immune cell infiltration, endoplasmic reticulum stress, and ectopic lipid accumulation, ultimately leading to chronic low-grade inflammation and insulin resistance. Recently, many distinct subpopulations of adipose tissue have been identified, providing new insights into the potential mechanisms of adipose dysfunction in individuals with obesity. Therefore, targeting white adipose tissue as a therapeutic agent for treating obesity and obesity-related metabolic diseases is of great scientific interest. Here, we provide an overview of white adipose tissue remodeling in individuals with obesity including cellular changes and discuss the underlying regulatory mechanisms of white adipose tissue metabolic dysfunction. Currently, various studies have uncovered promising targets and strategies for obesity treatment. We also outline the potential therapeutic signaling pathways of targeting adipose tissue and summarize existing therapeutic strategies for antiobesity treatment including pharmacological approaches, lifestyle interventions, and novel therapies.

R2R3-MYB transcription factor CsMYB60 controls mature fruit skin color by regulating flavonoid accumulation in cucumber.

Skin color is an important trait that determines the cosmetic appearance and quality of fruits. In cucumber, the skin color ranges from white to brown in mature fruits. However, the genetic basis for this important trait remains unclear. We conducted a genome-wide association study of natural cucumber populations, along with map-based cloning techniques, on an F2 population resulting from a cross between Pepino (with yellow-brown fruit skin) and Zaoer-N (with creamy fruit skin). We identified CsMYB60 as a candidate gene responsible for skin coloration in mature cucumber fruits. In cucumber accessions with white to pale yellow skin color, a premature stop mutation (C to T) was found in the second exon region of CsMYB60, whereas light yellow cucumber accessions exhibited splicing premature termination caused by an intronic mutator-like element insertion in CsMYB60. Transgenic CsMYB60c cucumber plants displayed a yellow-brown skin color by promoting accumulation of flavonoids, especially hyperoside, a yellow-colored flavonol. CsMYB60c encodes a nuclear protein that primarily acts as a transcriptional activator through its C-terminal activation motif. RNA sequencing and DNA affinity purification sequencing assays revealed that CsMYB60c promotes skin coloration by directly binding to the YYTACCTAMYT motif in the promoter regions of flavonoid biosynthetic genes, including CsF3'H, which encodes flavonoid 3'-hydroxylase. The findings of our study not only offer insight into the function of CsMYB60 as dominantly controlling fruit coloration, but also highlight that intronic DNA mutations can have a similar phenotypic impact as exonic mutations, which may be valuable in future cucumber breeding programs.

RNA-seq-based comparative transcriptome analysis reveals the role of CsPrx73 in waterlogging-triggered adventitious root formation in cucumber.

Abiotic stressors like waterlogging are detrimental to cucumber development and growth. However, comprehension of the highly complex molecular mechanism underlying waterlogging can provide an opportunity to enhance cucumber tolerance under waterlogging stress. We examined the hypocotyl and stage-specific transcriptomes of the waterlogging-tolerant YZ026A and the waterlogging-sensitive YZ106A, which had different adventitious rooting ability under waterlogging. YZ026A performed better under waterlogging stress by altering its antioxidative machinery and demonstrated a greater superoxide ion (O 2-) scavenging ability. KEGG pathway enrichment analysis showed that a high number of differentially expressed genes (DEGs) were enriched in phenylpropanoid biosynthesis. By pairwise comparison and weighted gene co-expression network analysis analysis, 2616 DEGs were obtained which were categorized into 11 gene co-expression modules. Amongst the 11 modules, black was identified as the common module and yielded a novel key regulatory gene, CsPrx73. Transgenic cucumber plants overexpressing CsPrx73 enhance adventitious root (AR) formation under waterlogging conditions and increase reactive oxygen species (ROS) scavenging. Silencing of CsPrx73 expression by virus-induced gene silencing adversely affects AR formation under the waterlogging condition. Our results also indicated that CsERF7-3, a waterlogging-responsive ERF transcription factor, can directly bind to the ATCTA-box motif in the CsPrx73 promoter to initiate its expression. Overexpression of CsERF7-3 enhanced CsPrx73 expression and AR formation. On the contrary, CsERF7-3-silenced plants decreased CsPrx73 expression and rooting ability. In conclusion , our study demonstrates a novel CsERF7-3-CsPrx73 module that allows cucumbers to adapt more efficiently to waterlogging stress by promoting AR production and ROS scavenging.

Bibliometric analysis and visualization of quorum sensing research over the last two decade.

Background: Quorum sensing (QS) research stands as a pivotal and multifaceted domain within microbiology, holding profound implications across various scientific disciplines. This bibliometric analysis seeks to offer an extensive overview of QS research, covering the period from 2004 to 2023. It aims to elucidate the hotspots, trends, and the evolving dynamics within this research domain. Methods: We conducted an exhaustive review of the literature, employing meticulous data curation from the Science Citation Index Extension (SCI-E) within the Web of Science (WOS) database. Subsequently, our survey delves into evolving publication trends, the constellation of influential authors and institutions, key journals shaping the discourse, global collaborative networks, and thematic hotspots that define the QS research field. Results: The findings demonstrate a consistent and growing interest in QS research throughout the years, encompassing a substantial dataset of 4,849 analyzed articles. Journals such as Frontiers in Microbiology have emerged as significant contributor to the QS literature, highlighting the increasing recognition of QS's importance across various research fields. Influential research in the realm of QS often centers on microbial communication, biofilm formation, and the development of QS inhibitors. Notably, leading countries engaged in QS research include the United States, China, and India. Moreover, the analysis identifies research focal points spanning diverse domains, including pharmacological properties, genetics and metabolic pathways, as well as physiological and signal transduction mechanisms, reaffirming the multidisciplinary character of QS research. Conclusion: This bibliometric exploration provides a panoramic overview of the current state of QS research. The data portrays a consistent trend of expansion and advancement within this domain, signaling numerous prospects for forthcoming research and development. Scholars and stakeholders engaged in the QS field can harness these findings to navigate the evolving terrain with precision and speed, thereby enhancing our comprehension and utilization of QS in various scientific and clinical domains.

Serum N-glycomic profiling identifies candidate biomarker panels for assessing coronary artery stenosis severity.

Stenosis severity may escalate over the course of coronary artery disease (CAD), increasing the risk of death for the patient. Conventionally, the assessment of stenosis degree relies on invasive coronary angiography (ICA), an invasive examination unsuitable for patients in poor physical condition or those with contrast allergies and one that imposes a psychological burden on patients. Although abnormal serum N-glycan profiles have exhibited robust associations with various cardiovascular diseases, including CAD, their potential in diagnosing CAD stenosis remains to be determined. In this study, we performed a comprehensive analysis of serum N-glycome from 132 patients who underwent ICA and 27 healthy controls using MALDI-TOF-mass spectrometry. The patients who underwent ICA examination were categorized into four groups based on stenosis severity: no/mild/moderate/severe stenosis. Twenty-seven N-glycans were directly quantified, and 47 derived glycan traits were obtained. Notably, among these 74 glycan features, 18 exhibited variations across the study groups. Using a combination of least absolute shrinkage and selection operator and logistic regression analyses, we developed five diagnostic models for recognizing stenosis degree. Our results suggested that alterations in serum N-glycosylation modifications might be valuable for identifying stenosis degree and monitoring disease progression in individuals with CAD. It is expected to offer a noninvasive alternative for those who could not undergo ICA because of various reasons. However, the diagnostic potential of serum N-glycan panels as biomarkers requires multicenter, large cohort validation in the future.

Clinical features and surgical treatments of scoliosis in neurofibromatosis type 1: a systemic review and meta-analysis.

BACKGROUND: Neurofibromatosis type 1 (NF 1) is an autosomal-dominant tumor predisposition genetic disease affecting approximately 1 in 3000 live births. The condition could present various manifestations ranging from skin abnormalities to neurological tumors. The musculoskeletal system could also be frequently affected, and scoliosis is the most common orthopedic manifestation. Characterized by the early-onset and rapid progression tendency, NF 1-related dystrophic scoliosis presented discrepancies from idiopathic scoliosis in terms of natural history, clinical features, and management outcomes and thus required special attention. In the current study, the authors conducted a systemic review to outline the body of evidence of the natural history, clinical characteristics, surgical outcomes, and surgical complications of NF 1-induced scoliosis, aiming to provide an elucidative insight into this condition. METHOD: Systemic review and meta-analysis were conducted according to the latest Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) guidelines. The search was performed in Medline, Embase, and Web of Science Core Collection up to December 27, 2022, using related keywords. Clinical features such as frequencies, segmental involvement, and hereditary information were summarized and described qualitatively. Meta-analysis was conducted using R software and the 'meta' package to yield an overall outcome of efficacy and safety of surgical management, precisely, spinal fusion procedure and growing rods procedure. Corrective rate of Cobb angle, sagittal kyphosis angle, and T1-S1 length post-operative and at the last follow-up was used to evaluate the efficacy, and the occurrence of surgery-related complications was used to evaluate the safety. RESULT: A total of 37 articles involving 1023 patients were included. Approximately 26.6% of the NF 1 patients would present with scoliosis. Patients tend to develop scoliosis at an earlier age. The thoracic part turned out to be the most affected segment. No obvious correlation between scoliosis and genotype or hereditary type was observed. Both spinal fusion and growing rod surgery have shown acceptable treatment outcomes, with spinal fusion demonstrating better performance in terms of effectiveness and safety. The growing rods technique seemed to allow a better lengthening of the spine. The mainstay post-operative complications were implant-related complications but could be managed with limited revision surgery. Severe neurological deficits were rarely reported. CONCLUSION: Scoliosis, especially the subtype characterized by dystrophic bony changes, is a significant orthopedic manifestation of NF1. It has an early onset, a tendency to persistently and rapidly progress, and is challenging to deal with. The current review outlines the available evidence from the perspective of natural history, clinical features, and the treatment efficacy and safety of the mainstay surgical options. Patients with NF1 scoliosis will benefit from a better understanding of the disease and evidence based treatment strategies.

Optimizing lifestyle profiles is potential for preventing nonalcoholic fatty liver disease and enhancing its survival.

The aim of this study was to evaluate the association between lifestyle profile and disease incidence/mortality in patients with non-alcoholic fatty liver disease (NAFLD). Lifestyle profiles ascertainment was based on the latent profile analysis. The associations of lifestyle profile and outcomes were analyzed by multivariate logistic or Cox regressions. Four lifestyle profiles (profile 1 and 2 for male, profile 3 and 4 for female) were established for all participants. Compared to profile 1, profile 2 (P = 0.042) and profile 3 (P = 0.013) had lower incidence for NAFLD. In contrast, profile 4 showed similar NAFLD prevalence compared to profile 1 (P = 0.756). Individuals with NAFLD within profile 3 had the best long-term survival, and the HR was 0.55 (95% CI 0.40-0.76) for all-cause mortality (compared to profile 1). Profile 4 (P = 0.098) and profile 2 (P = 0.546) had similar all-cause survival compared to profile 1. We explored the associations of healthy lifestyle score with mortality and incidence of NAFLD stratified by lifestyle profiles. We observed that with the increase of healthy lifestyle score, participants within profile 2 did not display lower NAFLD incidence and better long-term survival in NAFLD cases. In this study, lifestyle profiles were constructed in NHANES participants. The distinct lifestyle profiles may help optimize decision-making regarding lifestyle management in preventing NAFLD development, as well as selection of a more personalized approach for improving NAFLD survival.

H3K27ac modification and transcription characteristics of adipose and muscle tissues in Chuxiang Black pig.

The establishment of high-quality pork breeds for improving meat quality in the pig industry is needed. The Chuxiang Black (CX) pig is a new breed developed from Chinese local pigs and Western lean pigs that has a high proportion of lean meat and excellent meat quality. However, the characteristics of cis-regulatory elements in CX pigs are still unknown. In this study, cis-regulatory elements of muscle and adipose tissues in CX pigs were investigated using ChIP-seq and RNA sequencing. Compared with the reported cis-regulatory elements of muscle and adipose tissues, 1768 and 1012 highly activated enhancers and 433 and 275 highly activated promoters in CX muscle and adipose tissues were identified, respectively. Motif analysis showed that transcription factors, such as MEF2A and MEF2C, were core regulators of highly activated enhancers and promoters in muscle. Similarly, the transcription factors JUNB and CUX1 were identified as essential for highly activated enhancers and promoters in CX adipose tissue. These results enrich the resources for the analysis of cis-regulatory elements in the pig genome and provide new basic data for further meat quality improvement through breeding in pigs.

Quercetin, a key active ingredient of Jianpi Zishen Xiehuo Formula, suppresses M1 macrophage polarization and platelet phagocytosis by inhibiting STAT3 activation based on network pharmacology.

Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease, and abnormal M1 macrophage polarization participates in the pathogenesis of ITP. Jianpi Zishen Xiehuo (JZX) Formula has a good therapeutic effect on ITP. However, its key active ingredients and molecular mechanisms remain unclear. In this study, we explored the key active ingredients and potential targets of JZX in treating ITP using network pharmacology combined with in vitro experimental verification. A total of 157 active ingredients of JZX were identified from public databases, and quercetin was the most important one. One hundred sixty-five intersection targets of active ingredients in JZX, ITP, and macrophage polarization were obtained by Venn diagram. The top three potential targets were signal transducer and activator of transcription 3 (STAT3), protein kinase B (PKB/AKT) 1, and c-JUN through protein-protein interaction analysis. Molecular docking showed that quercetin had strong binding affinities with them all. In vitro experiment, CD16+ monocytes increased in ITP patients compared with healthy controls, which indicated a M1/M2 polarization imbalance in ITP. The expression levels of M1 polarization markers, CD86, CD80, and inducible nitric oxide synthase (iNOS), M1 polarization-associated cytokines, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), and antibody-opsonized platelet phagocytosis significantly increased in THP-1 macrophages stimulated with lipopolysaccharide (LPS). Quercetin markedly inhibited the expressions of M1 markers, decreased the levels of TNF-α and IL-6, and down-regulated the phosphorylated STAT3 (p-STAT3) protein, which confirmed the prediction by network pharmacology and molecular docking. Importantly, quercetin significantly reduced the phagocytosis of antibody opsonised platelet. In conclusion, quercetin suppressed platelet phagocytosis in M1 macrophages via its anti-inflammatory effects and may serve as a potential drug for the treatment of ITP. Quercetin could be a key ingredient for JZX against ITP.

Bisphenol S induces brown adipose tissue whitening and aggravates diet-induced obesity in an estrogen-dependent manner.

Bisphenol S (BPS) exposure has been implied epidemiologically to increase obesity risk, but the underlying mechanism is unclear. Here, we propose that BPS exposure at an environmentally relevant dose aggravates diet-induced obesity in female mice by inducing brown adipose tissue (BAT) whitening. We explored the underlying mechanism by which KDM5A-associated demethylation of the trimethylation of lysine 4 on histone H3 (H3K4me3) in thermogenic genes is overactivated in BAT upon BPS exposure, leading to the reduced expression of thermogenic genes. Further studies have suggested that BPS activates KDM5A transcription in BAT by binding to glucocorticoid receptor (GR) in an estrogen-dependent manner. Estrogen-estrogen receptors facilitate the accessibility of the KDM5A gene promoter to BPS-activated GR by recruiting the activator protein 1 (AP-1) complex. These results indicate that BAT is another important target of BPS and that targeting KDM5A-related signals may serve as an approach to counteract the BPS-induced susceptivity to obesity.

Impact of apolipoprotein A1 on tumor immune microenvironment, clinical prognosis and genomic landscape in hepatocellular carcinoma.

Background: Current knowledge on apolipoprotein A1 (APOA1) in hepatocellular carcinoma (HCC) is fragmented and even contradictory. Multi-dimensional analyses are required to comprehensively elucidate its value and underlying mechanism. Methods: We collected 49 RNA-seq datasets, 40 cell line types data and 70 scRNA pan-cancer datasets public available, including 17 HCC datasets (1754 tumor samples), and enrolled 73 pairs of HCC tissue and 516 blood samples independently from our clinics. APOA1 impacting on the HCC tumor microenvironment (TME) was analyzed using intensive data mining. Methylation sequencing, flow cytometry, quantitative PCR, western blot, immunohistochemistry and clinical chemistry assays were conducted for wet experimental investigation. Results: The APOA1 ontology fingerprint indicated that it played various crucial biological roles in HCC, primarily involved in cholesterol efflux. Consistent findings at histology, serology, and clinical follow-up revealed that high APOA1 was a good prognosis indicator of HCC. Hypermethylation in the APOA1 promoter region was found in clinical samples which is in accordance with the reduction of APOA1 in HCC. The cell cycle, DNA replication, mismatch repair pathways, and tumor cell proliferation were less observed in the HCC APOA1high subgroup. The favorable immunoregulatory abilities of APOA1 showed interesting findings: a positive correlation between APOA1 and anti-tumor immune cells (NK, CD8+ T cells) and a negative association with immune cells exerting immunosuppressive effects, including M2 macrophages. Conclusion: This is an integrative multidimensional exploration of APOA1 using bioinformatics and experiments. Both the prognostic value and anti-tumor effects based on APOA1 panoramic exploration in the HCC TME demonstrate a new potential clinical target for HCC assessment and intervention in the future.

Research hotspot and trend of chronic wounds: A bibliometric analysis from 2013 to 2022.

Chronic wounds have been confirmed as a vital health problem facing people in the global population aging process. While significant progress has been achieved in the study of chronic wounds, the treatment effect should be further improved. The number of publications regarding chronic wounds has been rising rapidly. In this study, bibliometric analysis was conducted to explore the hotspots and trends in the research on chronic wounds. All relevant studies on chronic wounds between 2013 and 2022 were collected from the PubMed database of the Web of Science (WOS) and the National Center for Biotechnology Information (NCBI). The data were processed and visualised using a series of software. On that basis, more insights can be gained into hotspots and trends of this research field. Wound Repair and Regeneration has the highest academic achievement in the field of chronic wound research. The United States has been confirmed as the most productive country, and the University of California System ranks high among other institutions. Augustin, M. is the author of the most published study, and Frykberg, RG et al. published the most cited study. Furthermore, the hotspots of wound research over the last decade were identified (e.g., bandages, infection and biofilms, pathophysiology and therapy). This study will help researchers gain insights into chronic wound research's hotspots and trends accurately and quickly. Moreover, the exploration of bacterial biofilm and the pathophysiological mechanism of the chronic wound will lay a solid foundation and clear direction for treating chronic wounds.

Bibliometric analysis and visualization of transdermal drug delivery research in the last decade: global research trends and hotspots.

Background: Transdermal delivery has become a crucial field in pharmaceutical research. There has been a proliferation of innovative methods for transdermal drug delivery. In recent years, the number of publications regarding transdermal drug delivery has been rising rapidly. To investigate the current research trends and hotspots in transdermal drug delivery, a comprehensive bibliometric analysis was performed. Methods: An extensive literature review was conducted to gather information on transdermal drug delivery that had been published between 2003 and 2022. The articles were obtained from the Web of Science (WOS) and the National Center for Biotechnology Information (NCBI) databases. Subsequently, the collected data underwent analysis and visualization using a variety of software tools. This approach enables a deeper exploration of the hotspots and emerging trends within this particular research domain. Results: The results showed that the number of articles published on transdermal delivery has increased steadily over the years, with a total of 2,555 articles being analyzed. The most frequently cited articles were related to the optimization of drug delivery and the use of nanotechnology in transdermal drug delivery. The most active countries in the field of transdermal delivery research were the China, United States, and India. Furthermore, the hotspots over the past 2 decades were identified (e.g., drug therapy, drug delivery, and pharmaceutical preparations and drug design). The shift in research focus reflects an increasing emphasis on drug delivery and control release, rather than simply absorption and penetration, and suggests a growing interest in engineering approaches to transdermal drug delivery. Conclusion: This study provided a comprehensive overview of transdermal delivery research. The research indicated that transdermal delivery would be a rapidly evolving field with many opportunities for future research and development. Moreover, this bibliometric analysis will help researchers gain insights into transdermal drug delivery research's hotspots and trends accurately and quickly.

Nf1 in heart development: a potential causative gene for congenital heart disease: a narrative review.

Congenital heart disease is the most frequent congenital disorder, affecting a significant number of live births. Gaining insights into its genetic etiology could lead to a deeper understanding of this condition. Although the Nf1 gene has been identified as a potential causative gene, its role in congenital heart disease has not been thoroughly clarified. We searched and summarized evidence from cohort-based and experimental studies on the issue of Nf1 and heart development in congenital heart diseases from various databases. Available evidence demonstrates a correlation between Nf1 and congenital heart diseases, mainly pulmonary valvar stenosis. The mechanism underlying this correlation may involve dysregulation of epithelial-mesenchymal transition (EMT). The Nf1 gene affects the EMT process via multiple pathways, including directly regulating the expression of EMT-related transcription factors and indirectly regulating the EMT process by regulating the MAPK pathway. This narrative review provides a comprehensive account of the Nf1 involvement in heart development and congenital cardiovascular diseases in terms of epidemiology and potential mechanisms. RAS signaling may contribute to congenital heart disease independently or in cooperation with other signaling pathways. Efficient management of both NF1 and cardiovascular disease patients would benefit from further research into these issues.

Cucumber abscisic acid 8'-hydroxylase Csyf2 regulates yellow flesh by modulating carotenoid biosynthesis.

Cucumber (Cucumis sativus L.) flesh is typically colorless or pale green. Flesh with yellow or orange pigment, determined mainly by carotenoid content and composition, is mostly found in semi-wild Xishuangbanna cucumber, which has a very narrow genetic background. Here, we identified a spontaneous cucumber mutant with yellow flesh (yf-343), which accumulated more ß-cryptoxanthin and less lutein than regular cultivated European glasshouse-type cucumbers. Genetic analysis revealed that the yellow flesh phenotype was controlled by a single recessive gene. Through fine mapping and gene sequencing, we identified the candidate gene C. sativus yellow flesh 2 (Csyf2), encoding an abscisic acid (ABA) 8'-hydroxylase. Overexpression and RNAi-silencing of Csyf2 in cucumber hairy roots produced lower and higher ABA contents than in non-transgenic controls, respectively. Further, RNA-seq analysis suggested that genes related to ABA signal transduction were differentially expressed in fruit flesh between yf-343 and its wild type, BY, with white flesh. The carotenoid biosynthesis pathway was specifically enriched in fruit flesh at 30 days after pollination when yf-343 fruit flesh turns yellow. Our findings highlight a promising target for gene editing to increase carotenoid content, expanding our genetic resources for pigmented cucumber flesh breeding for improving the nutritional quality of cucumber.