Functional Mechanisms Research Articles

Stomatal penetration: the cornerstone of plant resistance to the fungal pathogen Zymoseptoria tritici

BackgroundSeptoria tritici blotch (STB), caused by the foliar fungus Zymoseptoria tritici, is one of the most damaging disease of wheat in Europe. Genetic resistance against this fungus relies on different types of resistance from non-host resistance (NHR) and host species specific resistance (HSSR) to host resistance mediated by quantitative trait loci (QTLs) or major resistance genes (Stb). Characterizing the diversity of theses resistances is of great importance for breeding wheat cultivars with efficient and durable resistance. While the functional mechanisms underlying these resistance types are not well understood, increasing piece of evidence suggest that fungus stomatal penetration and early establishment in the apoplast are both crucial for the outcome of some interactions between Z. tritici and plants. To validate and extend these previous observations, we conducted quantitative comparative phenotypical and cytological analyses of the infection process corresponding to 22 different interactions between plant species and Z. tritici isolates. These interactions included four major bread wheat Stb genes, four bread wheat accessions with contrasting quantitative resistance, two species resistant to Z. tritici isolates from bread wheat (HSSR) and four plant species resistant to all Z. tritici isolates (NHR).ResultsInfiltration of Z. tritici spores into plant leaves allowed the partial bypass of all bread wheat resistances and durum wheat resistance, but not resistances from other plants species. Quantitative comparative cytological analysis showed that in the non-grass plant Nicotiana benthamiana, Z. tritici was stopped before stomatal penetration. By contrast, in all resistant grass plants, Z. tritici was stopped, at least partly, during stomatal penetration. The intensity of this early plant control process varied depending on resistance types, quantitative resistances being the least effective. These analyses also demonstrated that Stb-mediated resistances, HSSR and NHR, but not quantitative resistances, relied on the strong growth inhibition of the few Z. tritici penetrating hyphae at their entry point in the sub-stomatal cavity.ConclusionsIn addition to furnishing a robust quantitative cytological assessment system, our study uncovered three stopping patterns of Z. tritici by plant resistances. Stomatal resistance was found important for most resistances to Z. tritici, independently of its type (Stb, HSSR, NHR). These results provided a basis for the functional analysis of wheat resistance to Z. tritici and its improvement.

Study on the Expression of GAB/GBAP1 Gene in Hepatocellular Carcinoma and Its Functional Mechanism of Interaction with miRNAs

This study aims to investigate the expression of the GAB/GBAP1 gene in hepatocellular carcinoma (HCC) and explore its interaction with microRNAs (miRNAs) and functional mechanisms. By employing bioinformatics analysis on publicly available databases of HCC tissue samples and normal tissues, we determined the expression level of the GAB/GBAP1 gene in HCC. Moreover, we predicted potential miRNAs that interact with the GAB/GBAP1 gene and further screened miRNAs associated with the occurrence and development of HCC. PCR analysis was utilized to verify the interaction between the GAB/GBAP1 gene and selected miRNAs, investigating their functional regulatory mechanisms in HCC cell lines. The results showed that the expression level of the GAB/GBAP1 gene was significantly upregulated in HCC tissue samples compared to normal tissues (P < 0.05). Bioinformatics prediction identified a group of miRNAs that potentially interact with the GAB/GBAP1 gene, among which miRNAs were found to be downregulated in HCC. Furthermore, we confirmed a direct binding interaction between miRNAs and the GAB/GBAP1 gene, and overexpression of miRNAs significantly inhibited the proliferation, invasion, and migration abilities of HCC cells. In summary, this study demonstrated the expression of the GAB/GBAP1 gene in HCC cell lines through PCR analysis and cell line culture, supporting its potential as a therapeutic target. Furthermore, this study revealed the overexpression of the GAB/GBAP1 gene in HCC and demonstrated that miRNAs exert inhibitory effects on HCC occurrence and development through their interaction with the GAB/GBAP1 gene.

A comprehensive prognostic and immune infiltration analysis of UBA1 in pan-cancer: A computational analysis and invitro experiments.

Ubiquitin like modifier activating enzyme 1 (UBA1) plays an important role in immune regulation and cellular function. However, the functional mechanism and role of UBA1 in pan-cancer have not been fully elucidated and its value in haematological tumours (diffuse large B cell lymphoma (DLBC/DLBCL) and acute myeloid leukaemia (AML/LAML)) has not been explored. We conducted a comprehensive analysis of the functional mechanism and role of UBA1 in pan-cancer using multiple databases, including differential expression analysis, clinical pathological staging analysis, prognosis analysis and immune analysis. Then, we confirmed the function of UBA1 in haematological tumours through cell experiments. The results showed that the expression of UBA1 was significantly increased in most cancers and the differential expression of UBA1 was mainly concentrated in digestive tumours, haematological tumours and brain tumours. Moreover, the high expression of UBA1 had poor prognosis in most tumours, which may be related to its involvement in various cancer-related pathways such as cell cycle, as well as its methylation level, protein phosphorylation level, immune cell infiltration and immune therapy response. Cell experiments have confirmed that UBA1 can significantly regulate the cycle progression and apoptosis of DLBCL cells and AML cells. Therefore, UBA1 may be a potential therapeutic target for haematological tumours. In summary, our study not only comprehensively analysed the functional mechanisms and clinical value of UBA1 in pan-cancer, but also validated for the first time the regulatory role of UBA1 in haematological tumours.

The functions of leg muscles, structures and mechanisms in running.

The actions of the major human leg muscles are well established; however, the functions of these muscle actions during steady running remain unclear. Here, leg structures and mechanisms are considered in terms of their functions in meeting the task of a vehicle acting as an effective machine, supporting body weight during translation with low mechanical work demand and in supplying mechanical work economically. Legs are modelled as a sequence of linkages that predict muscle actions and reveal the varying muscle functions within the integrated leg. Work avoidance is achieved with isometric muscles and linkages that promote a sliding of the hip over the ground contact, resulting in an approximately horizontal path of the centre of mass. Economical work supply requires, for muscle with constrained power, shortening over the entire stance duration; this function is achieved by the hamstrings without disrupting the linkages resulting in work avoidance. In late stance, the two functions occur through coactivation of antagonistic muscles, providing one answer to Lombard's paradox. Quadriceps and hamstring tensions result in opposing moments about both hip and knee joints, but by doing so perform the independent yet complementary roles of work avoidance during translating weight support and economical work supply.

Potential role of short-chain fatty acids in the pathogenesis and management of acute lymphocytic leukemia.

Acute lymphocytic leukemia (ALL) is an aggressive hematological malignancy of highly proliferative lymphoblasts. ALL is the most common cancer in children, and is typically treated with combination chemotherapy. The 5-year survival of ALL improved significantly in recent decades with this treatment approach. However, certain age groups (below 2 and over 10 years of age) have much worse prognosis, and over 50% of patients with ALL experience long-term side effects proportional to the dosage of anticancer drugs. Therefore, different treatment strategies are required to improve survival in ALL and to reduce side effects of chemotherapy. Since epigenetic modifications are dominantly reversible, "epidrugs" (drugs targeting epigenetic markers) are considered for feasibility in the treatment of ALL as epigenetic modifications, and acetylation of histones was demonstrated to play a critical role in the pathogenesis of ALL. Histone deacetylases (HDACs) have been shown to be differentially expressed in several hematological malignancies, including ALL. HDAC inhibitors (HDACis) have been shown to express selective toxicity for ALL cells, but they showed limited efficacy and higher than expected toxicity in mouse models or clinical trials in ALL. The aim of this review is to examine the role of the microbiota and microbial metabolites in the mechanisms of HDAC functions, and explore the utilization of the microbiota and microbial metabolites in improving the efficacy of HDACi in ALL. HDAC regulators and natural HDACi are depleted in ALL due to microbiota change leading to a decrease in butyrate and propionate, and HDACi treatment is not effective in ALL due to their short half-life. We propose that HDACi released by the microbiota may be necessary in HDAC regulation and this process is impaired in ALL. Furthermore, the review will also consider the role of restoration of the microbiota or supplementation of natural HDACi in potentially restoring HDAC and HDACi functions.

Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effects

Periodontitis is a critical risk factor for the occurrence and development of diabetes. Porphyromonas gingivalis may participate in insulin resistance (IR) caused by periodontal inflammation, but the functional role and specific mechanisms of P. gingivalis in IR remain unclear. In the present study, clinical samples were analysed to determine the statistical correlation between P. gingivalis and IR occurrence. Through culturing of hepatocytes, myocytes, and adipocytes, and feeding mice P. gingivalis orally, the functional correlation between P. gingivalis and IR occurrence was further studied both in vitro and in vivo. Clinical data suggested that the amount of P. gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score. In vitro studies suggested that coculture with P. gingivalis decreased glucose uptake and insulin receptor (INSR) protein expression in hepatocytes, myocytes, and adipocytes. Mice fed P. gingivalis tended to undergo IR. P. gingivalis was detectable in the liver, skeletal muscle, and adipose tissue of experimental mice. The distribution sites of gingipain coincided with the downregulation of INSR. Gingipain proteolysed the functional insulin-binding region of INSR. Coculture with P. gingivalis significantly decreased the INSR–insulin binding ability. Knocking out gingipain from P. gingivalis alleviated the negative effects of P. gingivalis on IR in vivo. Taken together, these findings indicate that distantly migrated P. gingivalis may directly proteolytically degrade INSR through gingipain, thereby leading to IR. The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.

YTHDF3 Regulates the Degradation and Stability of m6A-Enriched Transcripts to Facilitate the Progression of Castration-Resistant Prostate Cancer.

RNA N6-methyladenosine (m6A) readers mediate cancer progression. However, the functional role and potential mechanisms of the m6A readers in prostate cancer tumorigenicity remain to be elucidated. In this study, we demonstrate that YTHDF3 expression is elevated in castration-resistant prostate cancer (CRPC) and positively correlated to high grade, bone metastasis and poor survival. YTHDF3 expression promoted CRPC cell proliferation, epithelial to mesenchymal transition (EMT) and tumour progression. Mechanistically, YTHDF3 promoted the RNA degradation of SPOP and NXK3.1 but stabilized RNA expressions of TWIST1 and SNAI2 dependent on m6A to facilitate cell proliferation and EMT. Additionally, YTHDF3 expression enhanced AKT activity via degrading SPOP in an m6A-dependent manner. Importantly, we found that melatonin can compete with m6A to occupy the m6A-binding cage of YTHDF3, leading to inhibition of YTHFD3 and its target expressions as well as CRPC tumour growth. Our findings uncover an essential role of YTHDF3 in the progression of CRPC and highlight the role of melatonin in anti-CRPC activity.

Artificial intelligence in fusion protein three-dimensional structure prediction: Review and perspective.

Recent advancements in artificial intelligence (AI) have accelerated the prediction of unknown protein structures. However, accurately predicting the three-dimensional (3D) structures of fusion proteins remains a difficult task because the current AI-based protein structure predictions are focused on the WT proteins rather than on the newly fused proteins in nature. Following the central dogma of biology, fusion proteins are translated from fusion transcripts, which are made by transcribing the fusion genes between two different loci through the chromosomal rearrangements in cancer. Accurately predicting the 3D structures of fusion proteins is important for understanding the functional roles and mechanisms of action of new chimeric proteins. However, predicting their 3D structure using a template-based model is challenging because known template structures are often unavailable in databases. Deep learning (DL) models that utilize multi-level protein information have revolutionized the prediction of protein 3D structures. In this review paper, we highlighted the latest advancements and ongoing challenges in predicting the 3D structure of fusion proteins using DL models. We aim to explore both the advantages and challenges of employing AlphaFold2, RoseTTAFold, tr-Rosetta and D-I-TASSER for modelling the 3D structures. HIGHLIGHTS: This review provides the overall pipeline and landscape of the prediction of the 3D structure of fusion protein. This review provides the factors that should be considered in predicting the 3D structures of fusion proteins using AI approaches in each step. This review highlights the latest advancements and ongoing challenges in predicting the 3D structure of fusion proteins using deep learning models. This review explores the advantages and challenges of employing AlphaFold2, RoseTTAFold, tr-Rosetta, and D-I-TASSER to model 3D structures.

Maize ZmSRO1e promotes mesocotyl elongation and deep sowing tolerance by inhibiting the activity of ZmbZIP61.

Deep sowing is a traditional method for drought resistance in maize production, and mesocotyl elongation is strongly associated with the ability of maize to germinate from deep soil. However, little is known about the functional genes and mechanisms regulating maize mesocotyl elongation. In the present study, we identified a plant-specific SIMILAR TO RCD-ONE (SRO) protein family member, ZmSRO1e, involved in maize mesocotyl elongation. The expression of ZmSRO1e is strongly inhibited upon transfer from dark to white light. The loss-of-function zmsro1e mutant exhibited a dramatically shorter mesocotyl than the wild-type in both constant light and darkness, while overexpression of ZmSRO1e significantly promoted mesocotyl elongation, indicating that ZmSRO1e positively regulates mesocotyl elongation. We showed that ZmSRO1e physically interacted with ZmbZIP61, an ortholog of Arabidopsis ELONGATED HYPOCOTYL 5 (HY5) and showed a function similar to that of HY5 in regulating photomorphogenesis. We found that ZmSRO1e repressed the transcriptional activity of ZmbZIP61 toward target genes involved in the regulation of cell expansion, such as ZmEXPB4 and ZmEXPB6, by interfering with the binding of ZmbZIP61 to the promoters of target genes. Our results provide a new understanding of the mechanism by which SRO regulates photomorphogenesis and highlight its potential application in deep sowing-resistant breeding.

Medicinal perspectives, molecular docking and structure activity relationship of benzothiazole derived thiazole-based bis-benzohydrazide as potential anti-Alzheimer agents

A new series of benzothiazole derived thiazole-based bis-benzohydrazide hybrid (1–20) analogs were synthesized. Initially, the product confirmation was identified by employing TLC and the basic skeleton of the new hybrid synthesized compounds was further confirmed through spectroscopic techniques such as 13CNMR, 1HNMR and HREI-MS. Moreover, the synthesized analogs were tested for their inhibitory activities against acetylcholinesterase and butyrylcholinesterase. In the whole series, compounds 1, 2, 3 and 6 were found with potent activity against acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE). Molecular docking inveatigation of the potent compounds was performed within the active site of acetylcholinesterase and butyrylcholinesterase revealing compounds 1, 2, 3 and 6 showing promising binding orientations against both enzymes as compared to reference drug donepezil with their IC50 values 1(2.20 ± 1.40 and 3.18 ± 0.45 μM), 2 (2.89 ± 1.25 and 2.78 ± 1.49 μM), 3 (2.94 ± 1.10 and 3.07 ± 1.23 μM), 6 (5.83 ± 1.45 and 6.03 ± 3.08 μM), respectively, and reference drug (IC50 = 8.73 ± 2.68 and 9.30 ± 2.60 μM for acetylcholinesterase and butyrylchlinesterase, respectively. In addition, ADME studies were conducted to gain a deeper understanding of the functional mechanisms of a drug on a living organism. It is considered that benzothiazole derived thiazole based bis-benzohydrazide hybrid analogs (1, 2, 3, 6) might be better inhibitors of acetylcholinesterase and butyrylcholinesterase enzymes.

Introversion and Functionality of Defense Mechanisms: Basis for Personality Enhancement Program

Challenges in life enables an individual to exhibit different personalities as one of their defense mechanisms. The personality dimension of introversion is a well-established concept that deals with an individual’s tendency to turn their energy inward, opposing the primarily outward projection of extroversion. Discussions of this topic, while prominent, are outdated and limited in their scopes especially when relating to the functionality of these mechanisms to introverted individuals. With these, this study sought to find the level of introversion of the Grade 11 students, the functionality of their defense mechanisms, and the correlation between these variables. The survey solely included the published and pre-made questionnaires of specific authors cited in the review of related literature. The findings of the study revealed that approximately three-quarters of respondents showed moderate introversion. Meanwhile, it was also found out that signs of dysfunctionality were prominent within the usage of defense mechanisms of the respondents. On the other hand, statistical analysis of data through the Pearson Product-Moment Correlation Coefficient indicated that out of the 24 defense mechanisms determined using the research instrument, only three showed significant correlation with introversion. Based on these results, it was recommended to conduct a personality enhancement program educating the learners on proper utilization of their defense mechanisms.

Differences of endophytic microbial compositions and metabolites in roots between fusarium wilt resistant and susceptible melon varieties

BackgroundStudies have shown that plant endophytic microbial communities are ubiquitous and closely related to plant growth and health. To clarify the mechanism of the melon varieties with high resistant to wilt, the endophytic microbial compositions and metabolites in roots of melon varieties with high resistant ability to wilt were analyzed.ResultsThe results showed that the abundances of Firmicutes, Ascomycota, Bacillus, Bradyrhizobium, Amycolatopsis, Actinospica, and Catenulispora all increased in roots of wilt high resistant melon varieties (MT) which compared to wilt susceptible melon varieties (MS). Meanwhile, Ochrobactrum, Bordetella, Roseateles, Staphylococcus, Acidovorax, Amycolatopsis, Catenulispora, Promicromonospora, and Gymnopilus were the unique endophytic microbes in roots of MT. Moreover, in comparison with the MS varieties, the functions of Defense mechanisms, Secondary metabolites biosynthesis, transport and catabolism, Nucleotide transport and metabolism, Signal transduction mechanisms, Coenzyme transport and metabolism, Carbohydrate transport and metabolism and Amino acid transport and metabolism all increased in roots of MT varieties. Additionally, the nucleotide metabolism and biosynthesis of cofactors metabolic pathways were also significantly increased in roots of MT varieties. On the other hand, the untargeted metabolome results showed that Biosynthesis of various plant secondary metabolites, Nucleotide metabolism and Biosynthesis of cofactors metabolic pathways were significantly increased in the expression of MT varieties; and the content of metabolic compounds such as flavonoids, Cinnamic acid compounds, Organic acid compounds, and Nucleotides were increased. In addition, the correlation between microbiome and metabolome indicates a significant correlation between the two.ConclusionsAll above results suggested that higher abundant antagonistic microbes and metabolic functions of endophytes in roots of wilt high resistant melon varieties (MT) were the important mechanisms for their high resistance to wilt.Graphical

An Improved Vibration Multi Mode-Based Technique for the Characterization of Metallic Adhesion Impulses

Adhesion impulses generated at the separation of metallic surfaces significantly impact the functionality and performance of launch-lock and release space mechanisms. The testing concept adopted here consists of a suspended plate set into contact with an end-effector, which is retracted to simulate an in-flight release. At the retraction, the bonds are stretched up to failure, transferring an impulse to the plate. The proposed technique focuses on plate-free vibration: if at least two amplitudes of the excited vibration modes are measured, it is possible to estimate the impulse intensity and duration. This technique is developed by exploiting the plate multimode response with redundant outputs to the same dynamic input to characterize adhesion dynamics with improved measurement performance.

Functional Activities and Mechanisms of Aronia melanocarpa in Our Health.

Aronia melanocarpa, known as black chokeberry, is rich in polyphenols, comprising flavonoids, such as anthocyanins, flavanols, and flavonols, and phenolic acids, such as chlorogenic acid. These polyphenols endow Aronia melanocarpa with preventive and therapeutic properties against various human diseases. Aronia melanocarpa has beneficial effects against diseases such as diabetes, inflammation, and hypertension. Considering the diverse functional components of Aronia melanocarpa, its efficacy in disease prevention and treatment can operate through multiple pathways, offering a more robust approach to disease control. This review covers the latest research results on the functional components of Aronia melanocarpa and their effects on human diseases.

Design of Coatings for Sulfur-Based Cathode Materials in Lithium-Sulfur Batteries: A review.

Lithium-sulfur batteries (LSBs) are considered next-generation energy storage and conversion solutions owing to their high theoretical specific capacity and the high abundance/low-cost of sulfur-based cathode materials. However, LSBs still encounter significant challenges, including the low conductivities of sulfur-based materials, severe volumetric expansion of sulfur during the discharge process, and the persistent "shuttle effect" of polysulfides. In recent years, a tremendous amount of research has been conducted to address the above challenges by developing coating and compositing materials and corresponding fabrication strategies for sulfur-based cathode materials. In this study, the surface coating, compositing materials, and fabrication methodologies of LSB cathodes are comprehensively reviewed in terms of advanced materials, structure/component characterization, functional mechanisms, and performance validation. Some technical challenges are analyzed in detail, and possible future research directions are proposed to overcome the challenges toward practical applications of lithium-sulfur batteries.

Cortical and subcortical gray matter abnormalities in mild cognitive impairment

Gray matter changes are thought to be closely related to cognitive decline in mild cognitive impairment (MCI) patients. The study aimed to explore cortical and subcortical structural alterations in MCI and their association with cognitive assessment. 24 MCI patients and 22 normal controls (NCs) were included. Voxel-based morphometry (VBM), vertex-based shape analysis and surface-based morphometry (SBM) analysis were applied to explore subcortical nuclei volume, shape and cortical morphology. Correlations between structural changes and cognition were explored using spearman correlation analysis. Support vector machine (SVM) classification evaluated MCI identification accuracy. MCI patients showed significant atrophy in the left thalamus, left hippocampus, left amygdala, right pallidum, right hippocampus, along with inward deformation in the left amygdala. SBM analysis revealed that MCI group exhibited shallower sulci depth in the left hemisphere and increased cortical gyrification index (GI) in the right frontal gyrus. Correlation analysis showed the positive correlation between right hippocampus volume and episodic memory, while negative correlation between the altered GI and memory performance in MCI group. SVM analysis demonstrated superior performance of sulci depth and GI derived from SBM in MCI identification. When combined with cortical and subcortical metrics, SVM achieved a peak accuracy of 89 % in distinguishing MCI from NC. The study reveals significant gray matter structural changes in MCI, suggesting their potential role in underlying functional differences and neural mechanisms behind memory impairment in MCI.

Investigation of antigen-presenting cells in the intestinal mesentery in normal and adhesive processes

The morphology and topography of dendritic cells in the mesentery of the small intestine, their quantity, and their presence under normal conditions and during progressive adhesive processes have been insufficiently studied, presenting an important issue in immunomorphology. This study aimed to identify and determine the functional activity of antigen-presenting cells using lectin histochemistry with peanut and lentil lectins under normal conditions and during adhesive processes. The methods employed included morphometric analysis, lectin histochemistry, and statistical analysis. For the first time, using lectin histochemistry with lentil and soy lectins, functionally active and immunologically immature antigen-presenting cells were found in the structure of lymphoid clusters of the small intestine mesentery. A correlation was established between the progression of adhesion processes and the number of antigen-presenting cells. Correlation between dendritic cells and the quantity of immunologically immature lymphocytes and B-lymphocytes was identified, enhancing the understanding of the functional mechanisms of the local arm of innate immunity. An increasing trend in immunologically immature lymphocytes and B-lymphocytes was observed alongside an increase in antigen presenting cells. The results indicated that the activation of dendritic cells in mesenteric tissues induced an increase in immunologically immature lymphocytes, from which B-lymphocytes subsequently developed, initiating a local immune response. The increased frequency of PNA+- and LCA+- antigen-presenting cells pointed to an elevated immune reactivity of lymphoid clusters. This study on the distribution of antigen-presenting cells contributes to a deeper understanding of the structure of lymphoid tissue associated with serous membranes, as well as fat-associated lymphoid aggregates, and underscores the connection between innate and adaptive immunity in the abdominal cavity

Resuscitation Promotion Factor: A Pronounced Bacterial Cytokine in Propelling Bacterial Resuscitation.

While confronted with unfavorable growth conditions, bacteria may transform into the dormant state, such as viable but nonculturable (VBNC) state, which is a reversible state characterized by low metabolic activity and lack of division. These dormant cells can be reactivated through the influence of the resuscitation promoting factor (Rpf) family, which are classified as autocrine growth factors and possess peptidoglycan hydrolase activities. To date, with the significant resuscitation or growth promotion ability of Rpf, it has been extensively applied to increasing bacterial diversity and isolating functional microbial species. This review provides a comprehensive analysis of the distribution, mode of action, and functional mechanisms of Rpf proteins in various bacterial species. The aim is to create opportunities for decoding microbial communities and extracting microbial resources from real samples across different research fields.

Crosstalk among Alternative Polyadenylation, Genetic Variants and Ubiquitin Modification Contribute to Lung Adenocarcinoma Risk.

Ubiquitin modification and alternative polyadenylation play crucial roles in the onset and progression of cancer. Hence, this study aims to comprehensively and deeply understand gene regulation and associated biological processes in lung adenocarcinoma (LUAD) by integrating both mechanisms. Alternative polyadenylation (APA)-related E3 ubiquitin ligases in LUAD were identified through multiple databases, and the association between selected genetic loci influencing gene expression (apaQTL-SNPs) and LUAD risk were evaluated through the GWAS database of the Female Lung Cancer Consortium in Asia (FLCCA). Subsequently, the interaction between RNF213 and ZBTB20, as well as their functional mechanisms in LUAD, were investigated using bioinformatics analysis, Western blot, co-immunoprecipitation, and colony formation experiments. A total of five apaQTL-SNPs (rs41301932, rs4494603, rs9890400, rs56066320, and rs41301932), located on RNF213, were significantly associated with LUAD risk (p < 0.05), and they inhibit tumor growth through ubiquitin-mediated degradation of ZBTB20.

Characterization and stress-responsive regulation of CmPHT1 genes involved in phosphate uptake and transport in Melon (Cucumis melo L.)

BackgroundPhosphorus (P) deficiency, a major nutrient stress, greatly hinders plant growth. Phosphate (Pi) uptake in plant roots relies on PHT1 family transporters. However, melon (Cucumis melo L.) lacks comprehensive identification and characterization of PHT1 genes, particularly their response patterns under diverse stresses.ResultsThis study identified and analyzed seven putative CmPHT1 genes on chromosomes 3, 4, 5, 6, and 7 using the melon genome. Phylogenetic analysis revealed shared motifs, domain compositions, and evolutionary relationships among genes with close histories. Exon number varied from 1 to 3. Collinearity analysis suggested segmental and tandem duplications as the primary mechanisms for CmPHT1 gene family expansion. CmPHT1;4 and CmPHT1;5 emerged as a tandemly duplicated pair. Analysis of cis-elements in CmPHT1 promoters identified 14 functional categories, including putative PHR1-binding sites (P1BS) in CmPHT1;4, CmPHT1;6, and CmPHT1;7. We identified that three WRKY transcription factors regulated CmPHT1;5 expression by binding to its W-box element. Notably, CmPHT1 promoters harbored cis-elements responsive to hormones and abiotic factors. Different stresses regulated CmPHT1 expression differently, suggesting that the adjusted expression patterns might contribute to plant adaptation.ConclusionsThis study unveils the characteristics, evolutionary diversity, and stress responsiveness of CmPHT1 genes in melon. These findings lay the foundation for in-depth investigations into their functional mechanisms in Cucurbitaceae crops.