DHPS-Mediated Hypusination Regulates METTL3 Self-m6A-Methylation Modification to Promote Melanoma Proliferation and the Development of Novel Inhibitors.

Discovering new treatments for melanoma will benefit human health. The mechanism by which deoxyhypusine synthase (DHPS) promotes melanoma development remains elucidated. Multi-omics studies have revealed that DHPS regulates m6A modification and maintains mRNA stability in melanoma cells. Mechanistically, DHPS activates the hypusination of eukaryotic translation initiation factor 5A (eIF5A) to assist METTL3 localizing on its mRNA for m6A modification, then promoting METTL3 expression. Structure-based design, synthesis, and activity screening yielded the hit compound GL-1 as a DHPS inhibitor. Notably, GL-1 directly inhibits DHPS binding to eIF5A, whereas GC-7 cannot. Based on the clarification of the mode of action of GL-1 on DHPS, it is found that GL-1 can promote the accumulation of intracellular Cu2+ to induce apoptosis, and antibody microarray analysis shows that GL-1 inhibits the expression of several cytokines. GL-1 shows promising antitumor activity with good bioavailability in a xenograft tumor model. These findings clarify the molecular mechanisms by which DHPS regulates melanoma proliferation and demonstrate the potential of GL-1 for clinical melanoma therapy.

The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes: findings from a prospective, nationwide, and multicenter registry.

OBJECTIVES: To evaluate the predictive value of fasting plasma glucose (FPG) for in-hospital mortality in patients with acute myocardial infarction (AMI) with different glucose metabolism status. METHODS: We selected 5,308 participants with AMI from the prospective, nationwide, multicenter CAMI registry, of which 2,081 were diabetic and 3,227 were nondiabetic. Patients were divided into high FPG and low FPG groups according to the optimal cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts, respectively. The primary endpoint was in-hospital mortality. RESULTS: Overall, 94 diabetic patients (4.5%) and 131 nondiabetic patients (4.1%) died during hospitalization, and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L, respectively. Compared with individuals who had low FPG, those with high FPG were significantly associated with higher in-hospital mortality in diabetic cohort (10.1% vs. 2.8%; odds ratio [OR] = 3.862, 95% confidence interval [CI]: 2.542-5.869) and nondiabetic cohort (7.4% vs. 1.7%; HR = 4.542, 95%CI: 3.041-6.782). After adjusting the potential confounders, this significant association was not changed. Furthermore, FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic status. Adding FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic cohorts. CONCLUSIONS: This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mortality in AMI patients with and without diabetes. FPG might be useful to stratify patients with AMI.

Endoscopic ultrasound-guided biliary drainage vs percutaneous transhepatic bile duct drainage in the management of malignant obstructive jaundice.

BACKGROUND: Malignant obstructive jaundice (MOJ) is a condition characterized by varying degrees of bile duct stenosis and obstruction, accompanied by the progressive development of malignant tumors, leading to high morbidity and mortality rates. Currently, the two most commonly employed methods for its management are percutaneous transhepatic bile duct drainage (PTBD) and endoscopic ultrasound-guided biliary drainage (EUS-BD). While both methods have demonstrated favorable outcomes, additional research needs to be performed to determine their relative efficacy. AIM: To compare the therapeutic effectiveness of EUS-BD and PTBD in treating MOJ. METHODS: This retrospective analysis, conducted between September 2015 and April 2023 at The Third Affiliated Hospital of Soochow University (The First People's Hospital of Changzhou), involved 68 patients with MOJ. The patients were divided into two groups on the basis of surgical procedure received: EUS-BD subgroup (n = 33) and PTBD subgroup (n = 35). Variables such as general data, preoperative and postoperative indices, blood routine, liver function indices, myocardial function indices, operative success rate, clinical effectiveness, and complication rate were analyzed and compared between the subgroups. RESULTS: In the EUS-BD subgroup, hospital stay duration, bile drainage volume, effective catheter time, and clinical effectiveness rate were superior to those in the PTBD subgroup, although the differences were not statistically significant (P > 0.05). The puncture time for the EUS-BD subgroup was shorter than that for the PTBD subgroup (P < 0.05). Postoperative blood routine, liver function index, and myocardial function index in the EUS-BD subgroup were significantly lower than those in the PTBD subgroup (P < 0.05). Additionally, the complication rate in the EUS-BD subgroup was lower than in the PTBD subgroup (P < 0.05). CONCLUSION: EUS-BD may reduce the number of punctures, improve liver and myocardial functions, alleviate traumatic stress, and decrease complication rates in MOJ treatment.

Yinchenhao Decoction Protects Against Acute Liver Injury in Mice With Biliary Acute Pancreatitis by Regulating the Gut Microflora-Bile Acids-Liver Axis.

Background and Aims: Acute liver injury (ALI) often follows biliary acute pancreatitis (BAP), but the exact cause and effective treatment are unknown. The aim of this study was to investigate the role of the gut microflora-bile acids-liver axis in BAP-ALI in mice and to assess the potential therapeutic effects of Yinchenhao decoction (YCHD), a traditional Chinese herbal medicine formula, on BAP-ALI. Methods: Male C57BL/6 mice were allocated into three groups: negative control (NC), BAP model, and YCHD treatment groups. The severity of BAP-ALI, intrahepatic bile acid levels, and the gut microbiota were assessed 24 h after BAP-ALI induction in mice. Results: Our findings demonstrated that treatment with YCHD significantly ameliorated the severity of BAP-ALI, as evidenced by the mitigation of hepatic histopathological changes and a reduction in liver serum enzyme levels. Moreover, YCHD alleviated intrahepatic cholestasis and modified the composition of bile acids, as indicated by a notable increase in conjugated bile acids. Additionally, 16S rDNA sequencing analysis of the gut microbiome revealed distinct alterations in the richness and composition of the microbiome in BAP-ALI mice compared to those in control mice. YCHD treatment effectively improved the intestinal flora disorders induced by BAP-ALI. Spearman's correlation analysis revealed a significant association between the distinct compositional characteristics of the intestinal microbiota and the intrahepatic bile acid concentration. Conclusions: These findings imply a potential link between gut microbiota dysbiosis and intrahepatic cholestasis in BAP-ALI mice and suggest that YCHD treatment may confer protection against BAP-ALI via the gut microflora-bile acids-liver axis.

The ubiquitin-like protein UBTD1 promotes colorectal cancer progression by stabilizing c-Myc to upregulate glycolysis.

Dysfunction of the ubiquitin-proteasome system (UPS) is involved in the pathogenesis of various malignancies including colorectal cancer (CRC). Ubiquitin domain containing 1 (UBTD1), a ubiquitin-like protein, regulates UPS-mediated protein degradation and tumor progression in some cancer types. However, the biological function and mechanism of UBTD1 are far from being well elucidated, and its role in CRC has not been explored yet. In our study, we analyzed CRC patients' clinical information and UBTD1 expression data, and found that the expression of UBTD1 in cancer tissue was significantly higher than that in adjacent normal tissue. Higher UBTD1 expression was significantly associated with poorer survival and more lymph node metastasis. Overexpression of UBTD1 could facilitate, while knockdown could inhibit CRC cell proliferation and migration, respectively. RNA-seq and proteomics indicated that c-Myc is an important downstream target of UBTD1. Metabolomics showed the products of the glycolysis pathway were significantly increased in UBTD1 overexpression cells. In vitro, we verified UBTD1 upregulating c-Myc protein and promoting CRC cell proliferation and migration via regulating c-Myc. UBTD1 promoted CRC cells' glycolysis, evidenced by the increased lactate production and glucose uptake following UBTD1 overexpression. Mechanistically, UBTD1 prolonged the half-life of the c-Myc protein by binding to E3 ligase ß-transducin repeat-containing protein (ß-TrCP), thereby upregulated the expression of glycolysis rate-limiting enzyme hexokinase II (HK2), and enhanced glycolysis and promoted CRC progression. In conclusion, our study revealed that UBTD1 promotes CRC progression by upregulating glycolysis via the ß-TrCP/c-Myc/HK2 pathway, suggesting its potential as a prognostic biomarker and therapeutic target in CRC.

MB38(M=Be and Zn): A Quasi-Planar Structure Rather Than A Core-Shell Octahedral Borospherene Structure.

In a recent paper (ChemPhysChem, 2023, 24, e202200947), based on the results computed using DFT method, the perfect core-shell octahedral configuration Be@B38 and Zn@B38 was reported to be the global minima of the MB38(M=Be and Zn) clusters. However, this paper presents the lower energy structures of MB38(M=Be and Zn) clusters as a quasi-planar configuration, the Be atom is found to reside on the convex surface of the quasi-planar B38 isomer, while the Zn atom tends to be attached to the top three B atoms of the quasi-planar B38 isomer. Our results show that quasi-planar MB38(M=Be and Zn) at DFT method have lower energy than core-shell octahedral configuration M@B38(M=Be and Zn). Natural atomic charges, valence electron density, electron localization function (ELF) analyses identify the MB38(M=Be and Zn) to be charge transfer complexes (Be2+B382-and Be1+B381-) and suggest primarily the electrostatic interactions between doped atom and B38 fragment. The photoelectron spectra of the corresponding anionic structures were simulated, providing theoretical basis for future structural identification.

Alzheimer's Disease Knowledge Graph Enhances Knowledge Discovery and Disease Prediction.

Background: Alzheimer's disease (AD), a progressive neurodegenerative disorder, continues to increase in prevalence without any effective treatments to date. In this context, knowledge graphs (KGs) have emerged as a pivotal tool in biomedical research, offering new perspectives on drug repurposing and biomarker discovery by analyzing intricate network structures. Our study seeks to build an AD-specific knowledge graph, highlighting interactions among AD, genes, variants, chemicals, drugs, and other diseases. The goal is to shed light on existing treatments, potential targets, and diagnostic methods for AD, thereby aiding in drug repurposing and the identification of biomarkers. Results: We annotated 800 PubMed abstracts and leveraged GPT-4 for text augmentation to enrich our training data for named entity recognition (NER) and relation classification. A comprehensive data mining model, integrating NER and relationship classification, was trained on the annotated corpus. This model was subsequently applied to extract relation triplets from unannotated abstracts. To enhance entity linking, we utilized a suite of reference biomedical databases and refine the linking accuracy through abbreviation resolution. As a result, we successfully identified 3,199,276 entity mentions and 633,733 triplets, elucidating connections between 5,000 unique entities. These connections were pivotal in constructing a comprehensive Alzheimer's Disease Knowledge Graph (ADKG). We also integrated the ADKG constructed after entity linking with other biomedical databases. The ADKG served as a training ground for Knowledge Graph Embedding models with the high-ranking predicted triplets supported by evidence, underscoring the utility of ADKG in generating testable scientific hypotheses. Further application of ADKG in predictive modeling using the UK Biobank data revealed models based on ADKG outperforming others, as evidenced by higher values in the areas under the receiver operating characteristic (ROC) curves. Conclusion: The ADKG is a valuable resource for generating hypotheses and enhancing predictive models, highlighting its potential to advance AD's disease research and treatment strategies.

Lattice-Confined Single-Atom Catalyst: Preparation, Application and Electron Regulation Mechanism.

Lattice-confined single-atom catalyst (LC SAC), featuring exceptional activity, intriguing stability and prominent selectivity, has attracted extensive attention in the fields of various reactions (e.g., hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), etc.). To design a "smart" LC SAC for catalytic applications, one must systematically comprehend updated advances in the preparation, the application, and especially the peculiar electron regulation mechanism of LC SAC. In this review, the specific preparation methods of LC SAC based on general coordination strategy are updated, and its applications in HER, OER, ORR, N2 reduction reaction (NRR), advanced oxidation processes (AOPs) and so forth are summarized to display outstanding activity, stability and selectivity. Uniquely, the electron regulation mechanisms are first and deeply discussed and can be primarily categorized as electron transfer bridge with monometallic active sites, novel catalytic centers with polymetallic active sites, and positive influence by surrounding environments. In the end, the existing issues and future development directions are put forward with a view to further optimize the performance of LC SAC. This review is expected to contribute to the in-depth understanding and practical application of highly efficient LC SAC.

Glucocorticoid does not improve the renal prognosis of patients with diabetic nephropathy combined with acute tubulointerstitial nephritis: a retrospective analysis.

BACKGROUND AND OBJECTIVES: In clinical practice, some patients are diagnosed with diabetic nephropathy (DN) combined with acute tubulointerstitial nephritis (ATIN) through renal biopsy. There is relatively little research on the treatment and prognosis of such patients, and no consensus exists on the use of glucocorticoid for treatment. Therefore, our study explores the progression of DN combined with ATIN and the renal outcomes after treatment with glucocorticoid. METHODS: This study retrospectively analyzed patients diagnosed with DN combined with ATIN through renal biopsy at our center from January 1, 2015, to December 31, 2021. We collected general patient information, laboratory indicators, renal pathology indicators, and the glucocorticoid usage after kidney biopsy. Follow-up data were collected from medical records. Statistical analysis methods included t-tests, non-parametric tests, and chi-square tests. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for renal endpoint events in patients. Statistical significance was defined as p-values < 0.05. RESULTS: In this study, a total of 67 patients were included. The subjects were divided into two groups based on whether they received glucocorticoid treatment: 33 patients in the steroid group and 34 in the non-steroid group. In the steroid group, 19 patients reached the renal endpoint event, which was significantly higher than in the non-steroid group (57.58% vs. 29.41%, p = 0.038). Univariate Cox regression analysis showed that serum creatinine (HR = 1.008, p < 0.001), albumin (HR = 0.919, p < 0.001), 24-h urinary protein (HR = 1.093, p = 0.002), hemoglobin (HR = 0.964, p = 0.001), triglycerides (HR = 1.12, p = 0.04), and the use of glucocorticoid (HR = 2.507, p = 0.019) were influencing factors for renal endpoint events in patients with DN combined with ATIN. Multivariate Cox regression analysis showed that albumin (HR = 0.863, p = 0.003) was an independent risk factor for renal endpoint events in patients with DN combined with ATIN. CONCLUSIONS: The use of glucocorticoid in treatment does not improve renal prognosis in patients with DN combined with ATIN. Lower levels of albumin are associated with a worse renal prognosis.

Coopetition, exploration and exploitation capabilities, and growth performance in digital healthcare ventures.

Introduction: Studies focusing on coopetition and dynamic capabilities have expanded significantly over the past several decades. Coopetition strategy and dynamic capabilities are increasingly recognised as sources of sustained competitive advantage. The purpose of this paper is to provide a better understanding of the factors driving growth performance in digital healthcare ventures by examining the role of coopetition, exploration and exploitation capabilities, and environmental uncertainty. While numerous studies have examined the competitive advantage of coopetition, its specific contribution to the growth of ventures in the digital realm remains less explored. Clarifying the strategic role of coopetition in driving growth performance is critical for delineating the intricate relationship between coopetition and growth performance, particularly in the context of digital healthcare ventures. To fill in this research gap, this study uses coopetition theory and dynamic capabilities theory to look at how exploration and exploitation capabilities, as well as environmental uncertainty, affect the relationship between coopetition and growth performance in digital healthcare ventures. Methods: We collected a total of 338 questionnaires from Chinese digital healthcare ventures between March 2023 and August 2023. We conducted data analysis using SPSS 26.0 and its macro-program PROCESS. Results: Our results confirm that coopetition has a positive effect on growth performance in digital healthcare ventures. Furthermore, exploration and exploitation capabilities fully mediate the relationship between coopetition and growth performance. Moreover, environmental uncertainty significantly and distinctively moderates the impact of exploration and exploitation capabilities on growth performance. Discussion: This study contributes to the existing literature by providing deeper insight into the relationship between coopetition and growth performance in digital healthcare ventures. It also offers important practical implications for public health improvement and socio-economic development.

A Dual-Modal, Label-Free Raman Imaging Method for Rapid Virtual Staining of Large-Area Breast Cancer Tissue Sections.

As one of the most common cancers, accurate, rapid, and simple histopathological diagnosis is very important for breast cancer. Raman imaging is a powerful technique for label-free analysis of tissue composition and histopathology, but it suffers from slow speed when applied to large-area tissue sections. In this study, we propose a dual-modal Raman imaging method that combines Raman mapping data with microscopy bright-field images to achieve virtual staining of breast cancer tissue sections. We validate our method on various breast tissue sections with different morphologies and biomarker expressions and compare it with the golden standard of histopathological methods. The results demonstrate that our method can effectively distinguish various types and components of tissues, and provide staining images comparable to stained tissue sections. Moreover, our method can improve imaging speed by up to 65 times compared to general spontaneous Raman imaging methods. It is simple, fast, and suitable for clinical applications.

rTMS applied to the PFC relieves neuropathic pain and modulates neuroinflammation in CCI rats.

The study aimed to assess the analgesic effect of 10 Hz repetitive transcranial magnetic stimulation (rTMS) targeted to the prefrontal cortex (PFC) region on neuropathic pain (NPP) in rats with chronic constriction injury (CCI) of the sciatic nerve, and to investigate the possible underlying mechanism. Rats were randomly divided into three groups: sham operation, CCI, and rTMS. In the latter group, rTMS was applied to the left PFC. Von Frey fibres were used to measure the paw withdrawal mechanical threshold (PWMT). At the end of the treatment, immunofluorescence and western blotting were applied to detect the expression of M1 and M2 polarisation markers in microglia in the left PFC and sciatic nerve. ELISA was further used to detect the concentrations of inflammation-related cytokines. The results showed that CCI caused NPP in rats, reduced the pain threshold, promoted microglial polarisation to the M1 phenotype, and increased the secretion of pro-inflammatory and anti-inflammatory factors. Moreover, 10 Hz rTMS to the PFC was shown to improve NPP induced by CCI, induce microglial polarisation to M2, reduce the secretion of pro-inflammatory factors, and further increase the secretion of anti-inflammatory factors. Our data suggest that 10 Hz rTMS can alleviate CCI-induced neuropathic pain, while the underlying mechanism may potentially be related to the regulation of microglial M1-to-M2-type polarisation to regulate neuroinflammation.

Eye-brain connections revealed by multimodal retinal and brain imaging genetics.

The retina, an anatomical extension of the brain, forms physiological connections with the visual cortex of the brain. Although retinal structures offer a unique opportunity to assess brain disorders, their relationship to brain structure and function is not well understood. In this study, we conducted a systematic cross-organ genetic architecture analysis of eye-brain connections using retinal and brain imaging endophenotypes. We identified novel phenotypic and genetic links between retinal imaging biomarkers and brain structure and function measures from multimodal magnetic resonance imaging (MRI), with many associations involving the primary visual cortex and visual pathways. Retinal imaging biomarkers shared genetic influences with brain diseases and complex traits in 65 genomic regions, with 18 showing genetic overlap with brain MRI traits. Mendelian randomization suggests bidirectional genetic causal links between retinal structures and neurological and neuropsychiatric disorders, such as Alzheimer's disease. Overall, our findings reveal the genetic basis for eye-brain connections, suggesting that retinal images can help uncover genetic risk factors for brain disorders and disease-related changes in intracranial structure and function.

Quorum Quenching in Membrane Bioreactors for Fouling Retardation: Complexity Provides Opportunities.

The occurrence of biofouling restricts the widespread application of membrane bioreactors (MBRs) in wastewater treatment. Regulation of quorum sensing (QS) is a promising approach to control biofouling in MBRs, yet the underlying mechanisms are complex and remain to be illustrated. A fundamental understanding of the relationship between QS and membrane biofouling in MBRs is lacking, which hampers the development and application of quorum quenching (QQ) techniques in MBRs (QQMBRs). While many QQ microorganisms have been isolated thus far, critical criteria for selecting desirable QQ microorganisms are still missing. Furthermore, there are inconsistent results regarding the QQ lifecycle and the effects of QQ on the physicochemical characteristics and microbial communities of the mixed liquor and biofouling assemblages in QQMBRs, which might result in unreliable and inefficient QQ applications. This review aims to comprehensively summarize timely QQ research and highlight the important yet often ignored perspectives of QQ for biofouling control in MBRs. We consider what this "information" can and cannot tell us and explore its values in addressing specific and important questions in QQMBRs. Herein, we first examine current analytical methods of QS signals and discuss the critical roles of QS in fouling-forming microorganisms in MBRs, which are the cornerstones for the development of QQ technologies. To achieve targeting QQ strategies in MBRs, we propose the substrate specificity and degradation capability of isolated QQ microorganisms and the surface area and pore structures of QQ media as the critical criteria to select desirable functional microbes and media, respectively. To validate the biofouling retardation efficiency, we further specify the QQ effects on the physicochemical properties, microbial community composition, and succession of mixed liquor and biofouling assemblages in MBRs. Finally, we provide scale-up considerations of QQMBRs in terms of the debated QQ lifecycle, practical synergistic strategies, and the potential cost savings of MBRs. This review presents the limitations of classic QS/QQ hypotheses in MBRs, advances the understanding of the role of QS/QQ in biofouling development/retardation in MBRs, and builds a bridge between the fundamental understandings and practical applications of QQ technology.

[Diagnostic efficacy of serum 14-3-3ß protein combined with fractional exhaled nitric oxide and conventional ventilatory lung function parameters for bronchial asthma in children]. / è¡€æ¸ 14-3-3ß蛋白联合呼出气一氧化氮及常规通气肺功能参数对儿童支气管哮喘的诊断效能.

OBJECTIVES: To explore the diagnostic efficacy of serum 14-3-3ß protein combined with fractional exhaled nitric oxide (FeNO) and conventional ventilatory lung function parameters in diagnosing bronchial asthma (referred to as "asthma") in children. METHODS: A prospective study included 136 children initially diagnosed with asthma during an acute episode as the asthma group, and 85 healthy children undergoing routine health checks as the control group. The study compared the differences in serum 14-3-3ß protein concentrations between the two groups, analyzed the correlation of serum 14-3-3ß protein with clinical indices, and evaluated the diagnostic efficacy of combining 14-3-3ß protein, FeNO, and conventional ventilatory lung function parameters for asthma in children. RESULTS: The concentration of serum 14-3-3ß protein was higher in the asthma group than in the control group (P<0.001). Serum 14-3-3ß protein showed a positive correlation with the percentage of neutrophils and total serum immunoglobulin E, and a negative correlation with conventional ventilatory lung function parameters (P<0.05). Cross-validation of combined indices showed that the combination of 14-3-3ß protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume had an area under the curve of 0.948 for predicting asthma, with a sensitivity and specificity of 88.9% and 93.7%, respectively, demonstrating good diagnostic efficacy (P<0.001). The model had the best extrapolation. CONCLUSIONS: The combination of serum 14-3-3ß protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume can significantly improve the diagnostic efficacy for asthma in children. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 723-729.

Structural and functional neural patterns among sub-threshold bulimia nervosa: Abnormalities in dorsolateral prefrontal cortex and orbitofrontal cortex.

BACKGROUND: Disordered eating behaviors are prevalent among youngsters and highly associated with dysfunction in neurocognitive systems. We aimed to identify the potential changes in individuals with bulimia symptoms (sub-BN) to generate insights to understand developmental pathophysiology of bulimia nervosa. METHODS: We investigated group differences in terms of degree centrality (DC) and gray matter volume (GMV) among 145 undergraduates with bulimia symptoms and 140 matched control undergraduates, with the secondary analysis of the whole brain connectivity in these regions of interest showing differences in static functional connectivity (FC). RESULTS: The sub-BN group exhibited abnormalities of the right dorsolateral prefrontal cortex and right orbitofrontal cortex in both GMV and DC, and displayed decreased FC between these regions and the precuneus. We also observed that sub-BN presented with reduced FC between the calcarine and superior temporal gyrus, middle temporal gyrus and inferior parietal gyrus. Additionally, brain-behavioral associations suggest a distinct relationship between these FCs and psychopathological symptoms in sub-BN group. CONCLUSIONS: Our study demonstrated that individuals with bulimia symptoms present with aberrant neural patterns that mainly involved in cognitive control and reward processing, as well as attentional and self-referential processing, which could provide important insights into the pathology of BN.

Inhibition of FSP1: A new strategy for the treatment of tumors (Review).

Ferroptosis, a regulated form of cell death, is intricately linked to iron­dependent lipid peroxidation. Recent evidence strongly supports the induction of ferroptosis as a promising strategy for treating cancers resistant to conventional therapies. A key player in ferroptosis regulation is ferroptosis suppressor protein 1 (FSP1), which promotes cancer cell resistance by promoting the production of the antioxidant form of coenzyme Q10. Of note, FSP1 confers resistance to ferroptosis independently of the glutathione (GSH) and glutathione peroxidase­4 pathway. Therefore, targeting FSP1 to weaken its inhibition of ferroptosis may be a viable strategy for treating refractory cancer. This review aims to clarify the molecular mechanisms underlying ferroptosis, the specific pathway by which FSP1 suppresses ferroptosis and the effect of FSP1 inhibitors on cancer cells.

Pseudogene OCT4-pg5 upregulates OCT4B expression to promote bladder cancer progression by competing with miR-145-5p.

Bladder cancer (BC) is one of the most common malignant neoplasms worldwide. Competing endogenous RNA (ceRNA) networks may identify potential biomarkers associated with the progression and prognosis of BC. The OCT4-pg5/miR-145-5p/OCT4B ceRNA network was found to be related to the progression and prognosis of BC. OCT4-pg5 expression was significantly higher in BC cell lines than in normal bladder cells, with OCT4-pg5 expression correlating with OCT4B expression and advanced tumor grade. Overexpression of OCT4-pg5 and OCT4B promoted the proliferation and invasion of BC cells, whereas miR-145-5p suppressed these activities. The 3' untranslated region (3'UTR) of OCT4-pg5 competed for miR-145-5p, thereby increasing OCT4B expression. In addition, OCT4-pg5 promoted epithelial-mesenchymal transition (EMT) by activating the Wnt/ß-catenin pathway and upregulating the expression of matrix metalloproteinases (MMPs) 2 and 9 as well as the transcription factors zinc finger E-box binding homeobox (ZEB) 1 and 2. Elevated expression of OCT4-pg5 and OCT4B reduced the sensitivity of BC cells to cisplatin by reducing apoptosis and increasing the proportion of cells in G1. The OCT4-pg5/miR-145-5p/OCT4B axis promotes the progression of BC by inducing EMT via the Wnt/ß-catenin pathway and enhances cisplatin resistance. This axis may represent a therapeutic target in patients with BC.

Fucoidan alleviates high sucrose-induced metabolic disorders and enhances intestinal homeostasis through modulation of Notch signaling.

INTRODUCTION: The therapeutic potential of fucoidan (FUC), a natural polysaccharide, in metabolic disorders is recognized, yet its underlying mechanisms remain unclear. METHODS: We conducted investigations into the therapeutic mechanisms of FUC sourced from Sargassum fulvellum concerning metabolic disorders induced by a high-sucrose diet (HSD), employing Drosophila melanogaster and mice models. Drosophila larvae were subjected to HSD exposure to monitor growth inhibition, reduced pupation, and developmental delays. Additionally, we examined the impact of FUC on growth- and development-related hormones in Drosophila. Furthermore, we assessed the modulation of larval intestinal homeostasis by FUC, focusing on the regulation of Notch signaling. In mice, we evaluated the effects of FUC on HSD-induced impairments in intestinal epithelial barrier integrity and gut hormone secretion. RESULTS: FUC supplementation significantly enhanced pupal weight in Drosophila larvae and effectively countered HSD-induced elevation of glucose and triglyceride levels. It notably influenced the expression of growth- and development-related hormones, particularly augmenting insulin-like peptides production while mitigating larval growth retardation. FUC also modulated larval intestinal homeostasis by negatively regulating Notch signaling, thereby protecting against HSD-induced metabolic stress. In mice, FUC ameliorated HSD-induced impairments in ileum epithelial barrier integrity and gut hormone secretion. CONCLUSIONS: Our findings demonstrate the multifaceted therapeutic effects of FUC in mitigating metabolic disorders and maintaining intestinal health. FUC holds promise as a therapeutic agent, with its effects attributed partly to the sulfate group and its ability to regulate Notch signaling, emphasizing its potential for addressing metabolic disorders.

Screening of drug targets for tuberculosis on the basis of transcription factor regulatory network and mRNA sequencing technology.

Background: Tuberculosis is a worldwide epidemic disease, posing a serious threat to human health. To find effective drug action targets for Mycobacterium tuberculosis, differentially expressed genes in tuberculosis patients and healthy people were screened by mRNA sequencing in this study. A total of 556 differentially expressed genes in tuberculosis patients and healthy people were screened out by mRNA sequencing technology. 26 transcription factors and 66 corresponding target genes were screened out in the AnimalTFDB 3.0 database, and a transcription factor regulatory network was constructed. Results: Three key transcription factors (TP53, KLF5 and GATA2) and one key gene (AKT1) were screened as new potential drug targets and diagnostic targets for tuberculosis by MCODE cluster analysis, and the key genes and key transcription factors were verified by RT-PCR. Finally, we constructed the and a key factor and KEGG signaling pathway regulatory network to clarify the possible molecular pathogenesis of tuberculosis. Conclusion: This study suggested M. tuberculosis may activate the AKT1 gene expression by regulating transcription factors TP53, KLF5, and GATA2, thus activating the B cell receptor signaling pathway to induce the infection and invasion of M. tuberculosis. AKT1, TP53, KLF5, and GATA2 can be used as new potential drug targets for tuberculosis.