The maize ZmCPK39-ZmKnox2 module regulates plant height.

Plant height is an important agronomic trait that affects high-density tolerance and lodging resistance. However, the regulators and their underlying molecular mechanisms controlling plant height in maize remain understudied. Here, we report that knockout mutants of the calcium-dependent protein kinase gene ZmCPK39 (ZmCPK39-KO) exhibit dramatically reduced plant height, characterized by shorter internodes and a slight decrease in node numbers. Furthermore, we identified a ZmCPK39-interacting protein, the knotted-related homeobox (ZmKnox2), and observed that plant height was also significantly reduced in a mutator transposon-inserted mutant of ZmKnox2 (ZmKnox2-Mu). Combined analysis of transcriptomic and metabonomic data indicates that multiple phytohormone signaling and photosynthesis pathways are disrupted in both ZmCPK39-KO and ZmKnox2-Mu mutants. Taken together, these results provide new insights into the function of ZmCPK39 and identify potential targets for breeding lodging-resistant and high-density tolerant maize cultivars. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00150-y.

Application of linaclotide in bowel preparation for colonoscopy in patients with constipation: A prospective randomized controlled study.

BACKGROUND AND AIM: Colonoscopy plays a crucial role in the early diagnosis and treatment of colorectal cancer. Adequate bowel preparation is essential for clear visualization of the colonic mucosa and lesion detection. However, inadequate bowel preparation is common in patients with constipation, and there is no standardized preparation protocol for these patients. This study aimed to explore the effectiveness and tolerability of a pre-colonoscopy combination regimen of linaclotide and polyethylene glycol (PEG). METHODS: In this prospective, single-center, randomized controlled trial, 322 participants were divided into two groups: a 3-L PEG + 870-µg linaclotide group (administered as a single dose for 3 days) and a 4-L PEG group. The primary endpoints were the Boston Bowel Preparation Scale (BBPS) score and the rate of adequate and excellent bowel preparation. Secondary endpoints were the rates of detection of colonic adenomas and polyps, cecal intubation rates, colonoscopy time, adverse reactions, patient satisfaction, and physician satisfaction. RESULTS: The study included 319 patients. The 3-L PEG + linaclotide group showed significantly higher rates of adequate and excellent bowel preparation than the 4-L PEG group (89.4% vs 73.6% and 37.5% vs 25.3%, respectively; P < 0.05). The mean BBPS score for the right colon in the 3-L PEG + linaclotide group was significantly higher than that in the 4-L PEG group. There were no significant between-group differences regarding the detection rates of colonic polyps and adenomas (44.4% vs 37.7% and 23.1% vs 20.1%, respectively; P > 0.05). There were no significant between-group differences regarding cecal intubation rates, colonoscopy operation, and withdrawal times. However, patient tolerance and sleep quality were better in the 3-L PEG + linaclotide group. CONCLUSION: The combination of 3-L PEG and 870-µg linaclotide, because of its lower volume of intake, can be considered as an alternative bowel preparation regimen for constipated patients undergoing colonoscopy, especially for the elderly.

A portable lateral flow distance-based paper sensor for drinking water hardness test.

Hardness is one of the basic parameters of water, and a high-level hardness of drinking water may be harmful to human health. Thus, it is very important to monitor drinking water hardness. In this work, a portable lateral flow distance-based paper sensor for the semi-quantitative detection of drinking water hardness is demonstrated. In the presence of Ca2+/Mg2+, the hydrogel can be formed via the chelation between sodium alginate and Ca2+/Mg2+, inducing a phase separation process. The viscosity change of the sodium alginate solution is directly related to the Ca2+/Mg2+ concentration and can be determined by the water lateral flow distance on test strips. The sensor successfully realizes the quantification of Ca2+ and Mg2+ in the range of 0-10 mmol L-1 and 4-20 mmol L-1, respectively. The recoveries are found varied from 95% to 108.9%. The water hardness is acceptable for drinking if the Cr values lies in the range of 0.259 to 0.419, and it is high with the Cr value above 0.595. Remarkably, the performance of the sensor is comparable with the commercial kit for real water samples, which avoids the subjective judgment. Overall, this method provides a portable approach for semi-quantitative detection of drinking water hardness with the merits of convenience and low cost, which shows great potential for the potential application.

[Analysis of clinical characteristics and variant of NKX2-1 gene in a Chinese boy with Brain-Lung-Thyroid syndrome].

OBJECTIVE: To carry out clinical and genetic analysis for a child featuring Brain-Lung-Thyroid syndrome (BLTS). METHODS: A child who had presented at the Children's Hospital Affiliated to Shandong University on May 27, 2022 was selected as the study subject. Clinical data was collected. Trio-whole exome sequencing (Trio-WES) was carried out for the child and his parents, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The child was given individualized treatment following the diagnosis. RESULTS: The child, a two-year-and-seven-month-old boy, had presented with global developmental delay, ataxia and hypothyroidism. WES revealed that he has harbored a heterozygous c.674C>T variant of the NKX2-1 gene, based on which he was diagnosed with BLTS. CT scan revealed interstitial and parenchymal inflammation in his lungs, which was reduced by budesonide aerosol inhalation. CONCLUSION: Discovery of the novel c.674C>T variant has enriched the mutational spectrum of the NKX2-1 gene. Budesonide aerosol may be used to treat lung inflammation associated with BLTS.

Effects of jujube (Ziziphus jujuba mill.) fruit extracts on oxidative stress: A systematic review and meta-analysis of rodent studies.

This study aimed to evaluate the effects of jujube (Ziziphus jujuba Mill.) fruit extracts on oxidative stress levels in rodent models. Animal studies meeting the inclusion criteria were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP Periodical Service Platform. The Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tool was used to evaluate the risk of bias in the included studies. A meta-analysis was performed based on the guidelines provided in the Cochrane Handbook for Systematic Reviews of Interventions (CHSRI) by using Stata 17.0 software. Nineteen studies were included in the meta-analysis. Jujube fruit extracts significantly decreased the level of malonaldehyde (MDA) and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Meanwhile, there was no significant improvement in the catalase (CAT) levels. In addition, there was considerable heterogeneity in the results of the meta-analysis. The results of the subgroup analysis indicated that the animal model, type of extracts, and source of target parameters may have contributed to the heterogeneity. Jujube fruit extracts are healthy and effective antioxidant dietary supplements that may be an effective adjunctive therapy for diseases in which oxidative stress is a major pathological factor. However, the overall methodological quality of the included studies was low, and additional research is warranted.

Metformin enhances the therapeutic effects of extracellular vesicles derived from human periodontal ligament stem cells on periodontitis.

Metformin has shown outstanding anti-inflammatory and osteogenic abilities. Mesenchymal stem cell-derived extracellular vesicles (EVs) reveal promising therapeutic potency by carrying various biomolecules. This study explored the effects of metformin on the therapeutic potential of EVs derived from human periodontal ligament stem cells (PDLSCs) for periodontitis. PDLSCs were cultured in osteogenic medium with or without metformin, and the supernatant was then collected separately to extract EVs and metformin-treated EVs (M-EVs). After identifying the characteristics, we evaluated the anti-inflammatory and osteogenic effects of EVs and M-EVs in vivo and in vitro. Osteogenic differentiation of PDLSCs was markedly enhanced after metformin treatment, and the effect was dramatically inhibited by GW4896, an inhibitor of EVs' secretion. Metformin significantly increased EVs' yields and improved their effects on cell proliferation, migration, and osteogenic differentiation. Moreover, metformin significantly enhanced the osteogenic ability of EVs on inflammatory PDLSCs. Animal experiments revealed that alveolar bone resorption was dramatically reduced in the EVs and M-EVs groups when compared to the periodontitis group, while the M-EVs group showed the lowest levels of alveolar bone loss. Metformin promoted the osteogenic differentiation of PDLSCs partly through EVs pathway and significantly enhanced the secretion of PDLSCs-EVs with superior pro-osteogenic and anti-inflammatory potential, thus improving EVs' therapeutic potential on periodontitis.

Recent contributions of pyridazine as a privileged scaffold of anticancer agents in medicinal chemistry: An updated review.

Pyridazine, as a privileged scaffold, has been extensively utilized in drug development due to its multiple biological activities. Especially around its distinctive anticancer property, a massive number of pyridazine-containing compounds have been synthesized and evaluated that target a diverse array of biological processes involved in cancer onset and progression. These include glutaminase 1 (GLS1) inhibitors, tropomyosin receptor kinase (TRK) inhibitors, and bromodomain containing protein (BRD) inhibitors, targeting aberrant tumor metabolism, cell signal transduction and epigenetic modifications, respectively. Pyridazine moieties functioned as either core frameworks or warheads in the above agents, exhibiting promising potential in cancer treatment. Therefore, the review aims to summarize the recent contributions of pyridazine derivatives as potent anticancer agents between 2020 and 2024, focusing mainly on their structure-activity relationships (SARs) and development strategies, with a view to show that the application of the pyridazine scaffold by different medicinal chemists provides new insights into the rational design of anticancer drugs.

Role and mechanisms of autophagy, ferroptosis, and pyroptosis in sepsis-induced acute lung injury.

Sepsis-induced acute lung injury (ALI) is a major cause of death among patients with sepsis in intensive care units. By analyzing a model of sepsis-induced ALI using lipopolysaccharide (LPS) and cecal ligation and puncture (CLP), treatment methods and strategies to protect against ALI were discussed, which could provide an experimental basis for the clinical treatment of sepsis-induced ALI. Recent studies have found that an imbalance in autophagy, ferroptosis, and pyroptosis is a key mechanism that triggers sepsis-induced ALI, and regulating these death mechanisms can improve lung injuries caused by LPS or CLP. This article summarized and reviewed the mechanisms and regulatory networks of autophagy, ferroptosis, and pyroptosis and their important roles in the process of LPS/CLP-induced ALI in sepsis, discusses the possible targeted drugs of the above mechanisms and their effects, describes their dilemma and prospects, and provides new perspectives for the future treatment of sepsis-induced ALI.

Expression pattern of Stlhcb gene family in potato and effects of overexpression of Stcp24 gene on potato photosynthesis.

Potato is one of the four staple food crops in the world. It has a wide range of cultivation, high yield, and high nutritional value. Enhancing the photosynthesis of potato is particularly important as it leads to an increase in the potato yield. The light-harvesting pigment-binding protein complex is very important for plant photosynthesis. We identified 12 Stlhcb gene family members from the potato variety "Atlantic" using transcriptome sequencing and bioinformatics. The proteins encoded by the Stlhcb gene family have between 3358 and 4852 atomic number, a relative molecular weight between 24060.16 and 34624.54 Da, and an isoelectric point between 4.99 and 8.65. The RT-qPCR results showed that the 12 Stlhcb genes were expressed in a tissue-specific and time-dependent fashion under low light. The relative expression of the Stlhcb genes in the leaves was significantly higher than that in the stems and roots, and the relative expression of these genes first increased and then decreased with the prolongation of light exposure time. The Stcp24 gene with the highest expression was cloned, and an expression vector was constructed. A subcellular localization analysis was performed in tobacco and an overexpression experiment was performed in potato using an Agrobacterium-mediated method. The subcellular localization analysis showed that the protein encoded by Stcp24 was located in chloroplasts as expected. Overexpression of Stcp24 in transgenic potato increased the yield of potatoes and the content of chlorophyll a and b; increased the net photosynthetic rate, transpiration rate, stomatal conductance, electron transport efficiency, and semi-saturated light intensity; and promoted photosynthesis and plant growth. This study provides a reference for the study of the function of the potato light-harvesting pigment-binding protein gene family. It lays a foundation for further study of the mechanism of the photosynthesis of potato, improvement of the light energy utilization of potato, and molecular breeding of potato.

Mechanism of Lian Hua Qing Wen capsules regulates the inflammatory response caused by M1 macrophage based on cellular experiments and computer simulations.

PURPOSE: The polarization of macrophages with the resulting inflammatory response play a crucial part in tissue and organ damage due to inflammatory. Study has proved Lian Hua Qing Wen capsules (LHQW) can reduce activation of inflammatory response and damage of tissue derived from the inflammatory reactions. However, the mechanism of LHQW regulates the macrophage-induced inflammatory response is unclear. Therefore, we investigated the mechanism of LHQW regulated the inflammatory response of M1 macrophages by cellular experiments and computer simulations. METHODS: This study has analysed the targets and mechanisms of macrophage regulating inflammatory response at gene and protein levels through bioinformatics. The monomeric components of LHQW were analyzed by High Performance Liquid Chromatography (HPLC). We established the in vitro cell model by M1 macrophages (Induction of THP-1 cells into M1 macrophages). RT-qPCR and immunofluorescence were used to detect changes in gene and protein levels of key targets after LHQW treatment. Computer simulations were utilized to verify the binding stability of monomeric components and protein targets. RESULTS: Macrophages had 140,690 gene targets, inflammatory response had 12,192 gene targets, intersection gene targets were 11,772. Key monomeric components (including: Pinocembrin, Fargesone-A, Nodakenin and Bowdichione) of LHQW were screened by HPLC. The results of cellular experiments indicated that LHQW could significantly reduce the mRNA expression of CCR5, CSF2, IFNG and TNF, thereby alleviating the inflammatory response caused by M1 macrophage. The computer simulations further validated the binding stability and conformation of key monomeric components and key protein targets, and IFNG/Nodakenin was able to form the most stable binding conformation for its action. CONCLUSION: In this study, the mechanism of LHQW inhibits the polarization of macrophages and the resulting inflammatory response was investigated by computer simulations and cellular experiments. We found that LHQW may not only reduce cell damage and death by acting on TNF and CCR5, but also inhibit the immune recognition process and inflammatory response by regulating CSF2 and IFNG to prevent polarization of macrophages. Therefore, these results suggested that LHQW may act through multiple targets to inhibit the polarization of macrophages and the resulting inflammatory response.

Histone deacetylase 6 as a novel promising target to treat cardiovascular disease.

Histone deacetylase 6 (HDAC6) belongs to a class of epigenetic targets that have been found to be a key protein in the association between tumors and cardiovascular disease. Recent studies have focused on the crucial role of HDAC6 in regulating cardiovascular diseases such as atherosclerosis, myocardial infarction, myocardial hypertrophy, myocardial fibrosis, hypertension, pulmonary hypertension, and arrhythmia. Here, we review the association between HDAC6 and cardiovascular disease, the research progress of HDAC6 inhibitors in the treatment of cardiovascular disease, and discuss the feasibility of combining HDAC6 inhibitors with other therapeutic agents to treat cardiovascular disease.

Development of Dry and Liquid Duplex Reagent Mix-Based Polymerase Chain Reaction Assays as Novel Tools for the Rapid and Easy Quantification of Bovine Leukemia Virus (BLV) Proviral Loads.

Bovine leukemia virus (BLV) is prevalent worldwide, causing serious problems in the cattle industry. The BLV proviral load (PVL) is a useful index for estimating disease progression and transmission risk. We previously developed a quantitative real-time PCR (qPCR) assay to measure the PVL using the coordination of common motif (CoCoMo) degenerate primers. Here, we constructed a novel duplex BLV-CoCoMo qPCR assay that can amplify two genes simultaneously using a FAM-labeled MGB probe for the BLV LTR gene and a VIC-labeled MGB probe for the BoLA-DRA gene. This liquid duplex assay maintained its original sensitivity and reproducibility in field samples. Furthermore, we developed a dry duplex assay composed of PCR reagents necessary for the optimized liquid duplex assay. We observed a strong positive correlation between the PVLs measured using the dry and liquid duplex assays. Validation analyses showed that the sensitivity of the dry duplex assay was slightly lower than that of the other methods for the detection of a BLV molecular clone, but it showed similar sensitivity to the singleplex assay and slightly higher sensitivity than the liquid duplex assay for the PVL quantification of 82 field samples. Thus, our liquid and dry duplex assays are useful for measuring the BLV PVL in field samples, similar to the original singleplex assay.

Concurrent combined methylmalonic acidemia and homocystinuria with down syndrome in a Chinese preschool Child: An in-depth case report and literature review.

Background: Dual occurrence of distinct genetic diseases is exceptionally rare, complicating both diagnosis and management when the conditions share overlapping symptoms. Case presentation: We describe a preschooler girl diagnosed with Down syndrome at 27 months who developed unexplained motor regression with age. Extensive investigations were carried out to elucidate the etiology, encompassing comprehensive neuromuscular and skeletal assessments, radiographic evaluations of the joints, electrophysiological studies, cerebral-spinal magnetic resonance imaging (MRI), hematological biochemical assays, plasma ammonia and lactate levels, full blood count analyses, echocardiography, and chromatography-mass spectrometry-based testing of amino acids, fatty acids, and organic acid metabolites in both blood and urine. Notably, significantly elevated levels of homocysteine and propionylcarnitine were detected in her blood, while urinary methylmalonic acid was also found to be abnormally high. Trio-whole exome sequencing confirmed the diagnosis as Combined methylmalonic acidemia and homocystinuria (Combined MMA and HCU), specifically due to a cblC defect, resulting from two compound heterozygous pathogenic mutations (c.217C > T and c.482G > A) in the MMACHC gene. Upon a two-month course of treatment with hydroxocobalamin and l-carnitine, the patient demonstrated moderate improvement in her motor abilities. Conclusion: Our study highlights the special and intriguing aspects of managing Combined MMA and HCU, emphasizing the value of a comprehensive diagnostic approach that integrates clinical acumen, metabolic screening, and sophisticated molecular analyses for achieving precise diagnoses in such intricate cases.

Molecular mechanisms of gut microbiota in diabetic nephropathy.

Diabetic nephropathy is a common complication of diabetes and a considerable contributor to end-stage renal disease. Evidence indicates that glucose dysregulation and lipid metabolism comprise a pivotal pathogenic mechanism in diabetic nephropathy. However, current treatment outcomes are limited, as they only provide symptomatic relief without preventing disease progression. The gut microbiota is a group of microorganisms that inhabit the human intestinal tract and play a crucial role in maintaining host energy balance, metabolism, and immune activity. Patients with diabetic nephropathy exhibit altered gut microbiota, suggesting its potential involvement in the onset and progression of the disease. However, how a perturbed microbiota induces and promotes diabetic nephropathy remains unelucidated. This article summarizes the evidence of the impact of gut microbiota on the progression of diabetic nephropathy, with a particular focus on the molecular mechanisms involved, aiming to provide new insights into the treatment of diabetic nephropathy.

APOA5 alleviates reactive oxygen species to promote oxaliplatin resistance in PIK3CA-mutated colorectal cancer.

Although platinum-based chemotherapy is the frontline regimen for colorectal cancer (CRC), drug resistance remains a major challenge affecting its therapeutic efficiency. However, there is limited research on the correlation between chemotherapy resistance and lipid metabolism, including PIK3CA mutant tumors. In this present study, we found that PIK3CA-E545K mutation attenuated cell apoptosis and increased the cell viability of CRC with L-OHP treatment in vitro and in vivo. Mechanistically, PIK3CA-E545K mutation promoted the nuclear accumulation of SREBP1, which promoted the transcription of Apolipoprotein A5 (APOA5). APOA5 activated the PPARγ signaling pathway to alleviate reactive oxygen species (ROS) production following L-OHP treatment, which contributed to cell survival of CRC cells. Moreover, APOA5 overexpression enhanced the stemness-related traits of CRC cells. Increased APOA5 expression was associated with PIK3CA mutation in tumor specimens and poor response to first-line chemotherapy, which was an independent detrimental factor for chemotherapy sensitivity in CRC patients. Taken together, this study indicated that PIK3CA-E545K mutation promoted L-OHP resistance by upregulating APOA5 transcription in CRC, which could be a potent target for improving L-OHP chemotherapeutic efficiency. Our study shed light to improve chemotherapy sensitivity through nutrient management in CRC.

irGSEA: the integration of single-cell rank-based gene set enrichment analysis.

irGSEA is an R package designed to assess the outcomes of various gene set scoring methods when applied to single-cell RNA sequencing data. This package incorporates six distinct scoring methods that rely on the expression ranks of genes, emphasizing relative expression levels over absolute values. The implemented methods include AUCell, UCell, singscore, ssGSEA, JASMINE and Viper. Previous studies have demonstrated the robustness of these methods to variations in dataset size and composition, generating enrichment scores based solely on the relative gene expression of individual cells. By employing the robust rank aggregation algorithm, irGSEA amalgamates results from all six methods to ascertain the statistical significance of target gene sets across diverse scoring methods. The package prioritizes user-friendliness, allowing direct input of expression matrices or seamless interaction with Seurat objects. Furthermore, it facilitates a comprehensive visualization of results. The irGSEA package and its accompanying documentation are accessible on GitHub (https://github.com/chuiqin/irGSEA).

Association Analysis Between Intratumoral and Peritumoral MRI Radiomics Features and Overall Survival of Neoadjuvant Therapy in Rectal Cancer.

BACKGROUND: The use of peritumoral features to determine the survival time of patients with rectal cancer (RC) is still imprecise. PURPOSE: To explore the correlation between intratumoral, peritumoral and combined features, and overall survival (OS). STUDY TYPE: Retrospective. POPULATION: One hundred sixty-six RC patients (53 women, 113 men; average age: 55 ± 12 years) who underwent radical resection after neoadjuvant therapy. FIELD STRENGTH/SEQUENCE: 3 T; T2WI sagittal, T1WI axial, T2WI axial with fat suppression, and high-resolution T2WI axial sequences, enhanced T1WI axial and sagittal sequences with fat suppression. ASSESSMENT: Radiologist A segmented 166 patients, and radiologist B randomly segmented 30 patients. Intratumoral and peritumoral features were extracted, and features with good stability (ICC ≥0.75) were retained through intra-observer analysis. Seven classifiers, including Logistic Regression (LR), Support Vector Machine (SVM), K-Nearest Neighbors (KNN), Random Forest (RF), Extremely randomized trees (ET), eXtreme Gradient Boosting (XGBoost), and LightGBM (LGBM), were applied to select the classifier with the best performance. Next, the Rad-score of best classifier and the clinical features were selected to establish the models, thus, nomogram was built to identify the association with 1-, 3-, and 5-year OS. STATISTICAL TESTS: LASSO, regression analysis, ROC, DeLong method, Kaplan-Meier curve. P < 0.05 indicated a significant difference. RESULTS: Only Node (irregular tumor nodules in the surrounding mesentery) and ExtraMRF (lymph nodes outside the perirectal mesentery) were significantly different in 20 clinical features. Twelve intratumoral, 3 peritumoral, and 14 combined features related to OS were selected. LR, SVM, and RF classier showed the best efficacy in the intratumoral, peritumoral, and combined model, respectively. The combined model (AUC = 0.954 and 0.821) had better survival association than the intratumoral model (AUC = 0.833 and 0.813) and the peritumoral model (AUC = 0.824 and 0.687). DATA CONCLUSION: The proposed peritumoral model with radiomics features may serve as a tool to improve estimated survival time. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 4.

Enhancing the Uniformity of a Memristor Using a Bilayer Dielectric Structure.

Resistive random access memory (RRAM) holds great promise for in-memory computing, which is considered the most promising strategy for solving the von Neumann bottleneck. However, there are still significant problems in its application due to the non-uniform performance of RRAM devices. In this work, a bilayer dielectric layer memristor was designed based on the difference in the Gibbs free energy of the oxide. We fabricated Au/Ta2O5/HfO2/Ta/Pt (S3) devices with excellent uniformity. Compared with Au/HfO2/Pt (S1) and Au/Ta2O5/Pt (S2) devices, the S3 device has a low reset voltage fluctuation of 2.44%, and the resistive coefficients of variation are 13.12% and 3.84% in HRS and LRS, respectively, over 200 cycles. Otherwise, the bilayer device has better linearity and more conductance states in multi-state regulation. At the same time, we analyze the physical mechanism of the bilayer device and provide a physical model of ion migration. This work provides a new idea for designing and fabricating resistive devices with stable performance.

Neratinib impairs function of m6A recognition on AML1-ETO pre-mRNA and induces differentiation of t (8;21) AML cells by targeting HNRNPA3.

Acute myeloid leukemia (AML) is frequently linked to genetic abnormalities, with the t (8; 21) translocation, resulting in the production of a fusion oncoprotein AML1-ETO (AE), being a prevalent occurrence. This protein plays a pivotal role in t (8; 21) AML's onset, advancement, and recurrence, making it a therapeutic target. However, the development of drug molecules targeting AML1-ETO are markedly insufficient, especially used in clinical treatment. In this study, it was uncovered that Neratinib could significantly downregulate AML1-ETO protein level, subsequently promoting differentiation of t (8; 21) AML cells. Based on "differentiated active" probes, Neratinib was identified as a functional inhibitor against HNRNPA3 through covalent binding. The further studies demonstrated that HNRNPA3 function as a putative m6A reader responsible for recognizing and regulating the alternative splicing of AML-ETO pre-mRNA. These findings not only contribute to a novel insight to the mechanism governing post-transcriptional modification of AML1-ETO transcript, but also suggest that Neratinib would be promising therapeutic potential for t (8; 21) AML treatment.

The regulatory process and practical significance of non-coding RNA in the dissemination of prostate cancer to the skeletal system.

Prostate cancer is a major contributor to male cancer-related mortality globally. It has a particular affinity for the skeletal system with metastasis to bones seriously impacting prognosis. The identification of prostate cancer biomarkers can significantly enhance diagnosis and patient monitoring. Research has found that cancer and metastases exhibit abnormal expression of numerous non-coding RNA. Some of these RNA facilitate prostate cancer bone metastasis by activating downstream signaling pathways, while others inhibit this process. Elucidating the functional processes of non-coding RNA in prostate cancer bone metastasis will likely lead to innovative treatment strategies for this malignant condition. In this review, the mechanistic role of the various RNA in prostate cancer is examined. Our goal is to provide a new avenue of approach to the diagnosis and treatment of bone metastasis in this cancer.