Expression of SIRT6 and VNN1 in children with primary nephrotic syndrome and their correlation with acute kidney injury.

OBJECTIVE: To explore the diagnostic and prognostic values of Sirtuin 6 (SIRT6) and Vanin-1 (VNN1) in peripheral blood monocytes of children with primary nephrotic syndrome (PNS) and their correlation with acute kidney injury (AKI). METHODS: A retrospective analysis was conducted on 101 children (observation group) diagnosed with PNS and treated at the Shanxi University of Traditional Chinese Medicine Affiliated Hospital from December 2021 to December 2023. These children were categorized into two groups: the AKI group (n=35) and the non-AKI group (n=66), based on the presence of AKI. Additionally, 101 healthy children who underwent physical examinations during the same period served as the control group. Western blotting and RT-PCR were employed to measure the protein and mRNA levels of SIRT6 and VNN1 in monocytes across the three groups. The correlation between SIRT6 and VNN1 mRNA levels and clinical data, as well as kidney function indicators, was analyzed. The diagnostic value of SIRT6 and VNN1 mRNA levels for AKI in PNS was assessed using ROC curves. Multivariate logistic regression identified independent factors influencing AKI in PNS. The mRNA levels of SIRT6 and VNN1 were also compared before and after treatment in children with PNS. RESULTS: The AKI group exhibited lower SIRT6 protein and mRNA levels, and higher VNN1 protein and mRNA levels in monocytes compared to the other groups (all P<0.05). Correlation analysis revealed that SIRT6 mRNA levels were positively correlated with serum creatinine (Scr), uric acid (UA), blood urea nitrogen (BUN), 24-hour urine protein (24h UP), cystatin C (Cys-C), and ß2-microglobulin (ß2-MG), but negatively correlated with albumin (ALB) and estimated glomerular filtration rate (eGFR) (all P<0.05). In contrast, VNN1 levels showed the opposite correlations (P<0.05). ROC curve analysis showed that the AUC for SIRT6 or VNN1 mRNA alone in diagnosing AKI was above 0.8, with a combined diagnostic AUC exceeding 0.9. Logistic regression indicated that eGFR, ß2-MG, Cys-C, and the mRNA levels of SIRT6 and VNN1 were independent risk factors for AKI in PNS (all P<0.05). After treatment, SIRT6 mRNA levels significantly decreased, while VNN1 mRNA levels increased in children with PNS (both P<0.05). CONCLUSION: SIRT6 and VNN1 are closely associated with AKI in children with PNS and may serve as valuable biomarkers for the diagnosis of AKI.

Functional Characterization of the Gibberellin (GA) Receptor ScGID1 in Sugarcane.

Sugarcane smut caused by Sporisorium scitamineum represents the most destructive disease in the sugarcane industry, causing host hormone disruption and producing a black whip-like sorus in the apex of the stalk. In this study, the gibberellin metabolic pathway was found to respond to S. scitamineum infection, and the contents of bioactive gibberellins were significantly reduced in the leaves of diseased plants. The gibberellin receptor gene ScGID1 was identified and significantly downregulated. ScGID1 localized in both the nucleus and cytoplasm and had the highest expression level in the leaves. Eight proteins that interact with ScGID1 were screened out using a yeast two-hybrid assay. Novel DELLA proteins named ScGAI1a and ScGA20ox2, key enzymes in GA biosynthesis, were both found to interact with ScGID1 in a gibberellin-independent manner. Transcription factor trapping with a yeast one-hybrid system identified 50 proteins that interacted with the promoter of ScGID1, among which ScS1FA and ScPLATZ inhibited ScGID1 transcription, while ScGDSL promoted transcription. Overexpression of ScGID1 in transgenic Nicotiana benthamiana plants could increase plant height and promote flowering. These results not only contribute to improving our understanding of the metabolic regulatory network of sugarcane gibberellin but also expand our knowledge of the interaction between sugarcane and pathogens.

Multi-site DNA methylation alterations of peripheral blood mononuclear cells serve as novel biomarkers for the diagnosis of AIS/stage I lung adenocarcinoma: A multi-center cohort study.

BACKGROUND: Early diagnosis remains an obstacle for improving the outcome of lung adenocarcinoma (LUAD). DNA methylation changes in peripheral blood mononuclear cells (PBMCs) could reflect immune response to tumorigenesis, providing the theoretical basis for early cancer diagnosis based on immune cell profiling. METHODS: This multi-center study evaluated the DNA methylation patterns based on PBMCs samples from 1115 individuals at nine medical centers. Genome-wide DNA methylation profiling of PBMCs in a discovery cohort (35 LUAD patients and 50 healthy controls) was performed using Illumina 850K microarray. Candidate differentially methylated CpG positions (DMPs) were selected and validated in a two-step DMPs screening cohort (65 LUAD patients and 80 healthy controls) by pyrosequencing and multiple target region methylation enrichment sequencing (MTRMES). Then, an early LUAD Diagnostic Panel (LDP score) based on multi-site methylation-specific chip-based digital PCR was constructed in a training set and then confirmed in a validation set from the LDP score development cohort (389 AIS/stage I LUAD patients and 293 healthy controls). Besides, we included 157 other cancer patients, including 52 gastric cancer (GC) patients, 50 breast cancer (BC) patients, and 55 colorectal cancer (CRC) patients to assess the specificity of LDP score. In addition, we also evaluated the early warning ability of LDP score for LUAD in a prospective cohort (46 people who were at high-risk of developing LC). RESULTS: A total of 1415 LUAD-specific DMPs were identified. Then, six DMPs were selected for validation and three DMPs were finally verified. The LDP score was constructed by combining the three DMPs, age, and gender, and showed an AUC of 0.916, sensitivity of 88.17%, and specificity of 80.20% in combined set, outperforming traditional methods, such as CEA and CT (detection rate: 87.79% vs. 4.69%; 87.79% vs. 35.21%). This diagnostic performance was confirmed in sub-types of LUAD with clinical challenges, such as 6-20 mm LUAD (AUC: 0.914, 95%CI: 0.889-0.934) and ground-glass nodules (AUC: 0.916, 95%CI: 0.889-0.938). Importantly, our LDP score had significant improvement in terms of selecting high-risk individuals who should receive low-dose computed tomography (87.80% vs. 9.28%). Remarkably, LDP score could predict LUAD around two years before clinical diagnosis in our prospective cohort. CONCLUSIONS: The novel developed LDP score represented a convenient and effective assay for the detection of AIS/stage I LUAD with high sensitivity and specificity, and had demonstrated unique advantages over traditional detection methods.

A review of current developments in RNA modifications in lung cancer.

Lung cancer has the highest incidence and mortality rates worldwide and is the primary cause of cancer-related death. Despite the rapid development of diagnostic methods and targeted drugs in recent years, many lung cancer patients do not benefit from effective therapies. The emergence of drug resistance has led to a reduction in the therapeutic effectiveness of targeted drugs, highlighting a crucial need to explore novel therapeutic targets. Many studies have found that epigenetic plays an important role in the occurrence of lung cancer. This review describes the biological function of epigenetic RNA modifications, such as m6A, m5C, m7G, and m1A, and recent advancements in their role in the development, progression, and prognosis of lung cancer. This review aims to provide new guidance for the treatment of lung cancer.

ß-Ionone enhances the inhibitory effects of 5-fluorouracil on the proliferation of gastric adenocarcinoma cells by the GSK-3ß signaling pathway.

5-Fluorouracil (5-FU) is widely used in the treatment of gastric cancer, and the emergence of drug resistance and toxic effects has limited its application. Therefore, there is an urgent need for safe and effective novel drugs or new therapies. ß-Ionone (BI) is found in vegetables and fruits and possesses an inhibitory proliferation of tumor cells in vitro and in vivo. In this study, we investigated whether BI could enhance the inhibitory effects of 5-FU on the proliferation of gastric adenocarcinoma cells and the growth of gastric cancer cell xenografts in a mouse model. The effects of BI and 5-FU alone or their combination on the cell viability, apoptosis, and mitochondrial membrane potential, the cell cycle, and its related proteins-Cyclin D1, and CDK4 as well as PCNA and GSK-3ß were evaluated in SGC-7901 cells and MKN45 cells by MTT, MB, flow cytometry and Western blot. In addition, the effects of BI and 5-FU alone or their combination on the growth of SGC-7901 cell xenografts in nude mice were investigated. The results showed that BI significantly enhanced the sensitivity of gastric adenocarcinoma cells to 5-FU in vitro and in vivo, i.e. proliferation inhibited, apoptosis induced and GSK-3ß protein activated. Therefore, our results suggest that BI increases the antitumor effect of 5-FU on gastric adenocarcinoma cells, at least partly from an activated GSK-3ß signaling pathway.

CAISeg: A Clustering-Aided Interactive Network for Lesion Segmentation in 3D Medical Imaging.

Accurate lesion segmentation in medical imaging is critical for medical diagnosis and treatment. Lesions' diverse and heterogeneous characteristics often present a distinct long-tail distribution, posing difficulties for automatic methods. Currently, interactive segmentation approaches have shown promise in improving accuracy, but still struggle to deal with tail features. This triggers a demand of effective utilizing strategies of user interaction. To this end, we propose a novel point-based interactive segmentation model called Clustering-Aided Interactive Segmentation Network (CAISeg) in 3D medical imaging. A customized Interaction-Guided Module (IGM) adopts the concept of clustering to capture features that are semantically similar to interaction points. These clustered features are then mapped to the head regions of the prompted category to facilitate more precise classification. Meanwhile, we put forward a Focus Guided Loss function to grant the network an inductive bias towards user interaction through assigning higher weights to voxels closer to the prompted points, thereby improving the responsiveness efficiency to user guidance. Evaluation across brain tumor, colon cancer, lung cancer, and pancreas cancer segmentation tasks show CAISeg's superiority over the state-of-the-art methods. It outperforms the fully automated segmentation models in accuracy, and achieves results comparable to or better than those of the leading point-based interactive methods while requiring fewer prompt points. Furthermore, we discover that CAISeg possesses good interpretability at various stages, which endows CAISeg with potential clinical application value.

A novel role of ETV6 as a pro-viral factor in host response by inhibiting TBK1 phosphorylation.

E26-transforming specific (ETS) variant 6 (ETV6) is a transcription factor regulating the expression of interferon stimulating genes (ISGs) and involved in the embryonic development and hematopoietic regulation, but the role of ETV6 in host response to virus infection is not clear. In this study, we show that ETV6 was upregulated in DF-1 cells with poly(I:C) stimulation or IBDV, AIV and ARV infection via engagement of dsRNA by MDA5. Overexpression of ETV6 in DF-1 cells markedly inhibited IBDV-induced type I interferon (IFN-I) and ISGs expressions. In contrast, knockdown, or knockout of ETV6 remarkably inhibited IBDV replication via promoting IFN-I response. Furthermore, our data show that ETV6 negatively regulated host antiviral response to IBDV infection by interaction with TANK binding kinase 1 (TBK1) and subsequently inhibited its phosphorylation. These results uncovered a novel role of ETV6 as a pro-viral factor in host response by inhibiting TBK1 phosphorylation, furthering our understandings of RNA virus immunosuppression and providing a valuable clue to the development of antiviral reagents for the control of avian RNA virus infection.

Unilateral biportal endoscopic decompression versus anterior cervical decompression and fusion for unilateral cervical radiculopathy or coexisting cervical myelopathy: a prospective, randomized, controlled, noninferiority trial.

BACKGROUND: Cervical spondylosis (CS), including myelopathy and radiculopathy, is the most common degenerative cervical spine disease. This study aims to evaluate the clinical outcomes of unilateral biportal endoscopy (UBE) compared to those of conventional anterior cervical decompression and fusion (ACDF) for treating unilateral cervical radiculopathy or coexisting cervical myelopathy induced by unilateral cervical herniated discs. METHODS: A prospective, randomized, controlled, noninferiority trial was conducted. The sample consisted of 131 patients who underwent UBE or ACDF was conducted between September 2021 and September 2022. Patients with cervical nerve roots or coexisting spinal cord compression symptoms and imaging-defined unilateral cervical radiculopathy or coexisting cervical myelopathy induced by unilateral cervical herniated discs were randomized into two groups: a UBE group (n = 63) and an ACDF group (n = 68). The operative time, blood loss, length of hospital stay after surgery, and perioperative complications were recorded. Preoperative and postoperative modified Japanese Orthopaedic Association (mJOA) scale scores, visual analog scale (VAS) scores, neck disability index (NDI) scores, and recovery rate (RR) of the mJOA were utilized to evaluate clinical outcomes. RESULTS: The hospital stay after surgery was significantly shorter in patients treated with UBE than in those treated with ACDF (p < 0.05). There were no significant differences in the neck or arm VAS score, NDI score, mJOA score, or mean RR of the mJOA between the two groups (p < 0.05). Only mild complications were observed in both groups, with no significant difference (p = 0.30). CONCLUSION: UBE can significantly relieve pain and disability without severe complications, and most patients are satisfied with this technique. Consequently, this procedure can be used safely and effectively as an alternative to ACDF for treating unilateral cervical radiculopathy or coexisting cervical myelopathy induced by unilateral cervical herniated discs. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry on 02/08/2023 ( http://www.chictr.org.cn , #ChiCTR2300074273).

Generation of a novel attenuated IBDV vaccine strain by mutation of critical amino acids in IBDV VP5.

Infectious bursal disease virus (IBDV) is an acute and highly infectious RNA virus known for its immunosuppressive capabilities, chiefly inflicting rapid damage to the bursa of Fabricius (BF) of chickens. Current clinical control of IBDV infection relies on vaccination. However, the emergence of novel variant IBDV (nVarIBDV) has posed a threat to the poultry industry across the globe, underscoring the great demand for innovative and effective vaccines. Our previous studies have highlighted the critical role of IBDV VP5 as an apoptosis-inducer in host cells. In this study, we engineered IBDV mutants via a reverse genetic system to introduce amino acid mutations in VP5. We found that the mutant IBDV-VP5/3m strain caused reduced host cell mortality, and that strategic mutations in VP5 reduced IBDV replication early after infection, thereby delaying cell death. Furthermore, inoculation of chickens with IBDV-VP5/3m effectively reduced damage to BF and induced neutralizing antibody production comparable to that of parental IBDV WT strain. Importantly, vaccination with IBDV-VP5/3m protected chickens against challenges with nVarIBDV, an emerging IBDV variant strain in China, reducing nVarIBDV loads in BF while alleviating bursal atrophy and splenomegaly, suggesting that IBDV-VP5/3m might serve as a novel vaccine candidate that could be further developed as an effective vaccine for clinical control of IBD. This study provides a new clue to the development of novel and effective vaccines.

Exploring the Key Amino Acid Residues Surrounding the Active Center of Lactate Dehydrogenase A for the Development of Ideal Inhibitors.

Lactate dehydrogenase A (LDHA) primarily catalyzes the conversion between lactic acid and pyruvate, serving as a key enzyme in the aerobic glycolysis pathway of sugar in tumor cells. LDHA plays a crucial role in the occurrence, development, progression, invasion, metastasis, angiogenesis, and immune escape of tumors. Consequently, LDHA not only serves as a biomarker for tumor diagnosis and prognosis but also represents an ideal target for tumor therapy. Although LDHA inhibitors show great therapeutic potential, their development has proven to be challenging. In the development of LDHA inhibitors, the key active sites of LDHA are emphasized. Nevertheless, there is a relative lack of research on the amino acid residues around the active center of LDHA. Therefore, in this study, we investigated the amino acid residues around the active center of LDHA. Through structure comparison analysis, five key amino acid residues (Ala30, Met41, Lys131, Gln233, and Ala259) were identified. Subsequently, the effects of these five residues on the enzymatic properties of LDHA were investigated using site-directed mutagenesis. The results revealed that the catalytic activities of the five mutants varied to different degrees in both the reaction from lactic acid to pyruvate and pyruvate to lactic acid. Notably, the catalytic activities of LDHAM41G and LDHAK131I were improved, particularly in the case of LDHAK131I. The results of the molecular dynamics analysis of LDHAK131I explained the reasons for this phenomenon. Additionally, the optimum temperature of LDHAM41G and LDHAQ233M increased from 35 °C to 40 °C, whereas in the reverse reaction, the optimum temperature of LDHAM41G and LDHAK131I decreased from 70 °C to 60 °C. These findings indicate that Ala30, Met41, Lys131, Gln233, and Ala259 exert diverse effects on the catalytic activity and optimum temperature of LHDA. Therefore, these amino acid residues, in addition to the key catalytic site of the active center, play a crucial role. Considering these residues in the design and screening of LDHA inhibitors may lead to the development of more effective inhibitors.

Hypoxia-inducible factor in breast cancer: role and target for breast cancer treatment.

Globally, breast cancer stands as the most prevalent form of cancer among women. The tumor microenvironment of breast cancer often exhibits hypoxia. Hypoxia-inducible factor 1-alpha, a transcription factor, is found to be overexpressed and activated in breast cancer, playing a pivotal role in the anoxic microenvironment by mediating a series of reactions. Hypoxia-inducible factor 1-alpha is involved in regulating downstream pathways and target genes, which are crucial in hypoxic conditions, including glycolysis, angiogenesis, and metastasis. These processes significantly contribute to breast cancer progression by managing cancer-related activities linked to tumor invasion, metastasis, immune evasion, and drug resistance, resulting in poor prognosis for patients. Consequently, there is a significant interest in Hypoxia-inducible factor 1-alpha as a potential target for cancer therapy. Presently, research on drugs targeting Hypoxia-inducible factor 1-alpha is predominantly in the preclinical phase, highlighting the need for an in-depth understanding of HIF-1α and its regulatory pathway. It is anticipated that the future will see the introduction of effective HIF-1α inhibitors into clinical trials, offering new hope for breast cancer patients. Therefore, this review focuses on the structure and function of HIF-1α, its role in advancing breast cancer, and strategies to combat HIF-1α-dependent drug resistance, underlining its therapeutic potential.

The Difference of Milk-Derived Extracellular Vesicles from Cow Colostrum and Mature Milk on miRNAs Expression and Protecting Intestinal Epithelial Cells against Lipopolysaccharide Damage.

Intestinal epithelial cells (IECs) play crucial roles in forming an essential barrier, providing host defense against pathogens and regulating nutrients absorption. Milk-derived extracellular vesicles (EVs) within its miRNAs are capable of modulating the recipient cell function. However, the differences between colostrum and mature milk EVs and their biological function in attenuating intestinal epithelial cell injury remain poorly understood. Thus, we carried out the present study to characterize the difference between colostrum and mature milk-derived miRNA of EVs and the effect of colostrum and mature milk EVs on the proliferation, apoptosis, proinflammatory cytokines and intestinal epithelial barrier related genes in IEC-6 induced by LPS. Differential expression of 329 miRNAs was identified between colostrum and mature milk EVs, with 185 miRNAs being downregulated and 144 upregulated. In addition, colostrum contains a greater number and protein concentration of EVs than mature milk. Furthermore, compared to control, EVs derived from colostrum significantly inhibited the expression of apoptosis- (Bax, p53, and caspase-3) and proinflammatory-related genes (TNFα, IL6, and IL1ß). EVs derived from mature milk did not affect expression of apoptosis-related genes (Bax, p53, bcl2, and caspase-3). The EVs derived from mature milk significantly inhibited the expression of proinflammatory-related genes (TNFα and IL6). Western blot analysis also indicated that colostrum and mature milk EVs significantly decreased the apoptosis of IEC-6 cells. The EdU assay results showed that colostrum and mature milk EVs significantly increased the proliferation of IEC-6 cells. The expression of intestinal barrier-related genes (TJP1, CLDN1, OCLN, CDX2, MUC2, and IGF1R) was significantly promoted in IEC-6 cells after colostrum and mature milk EVs addition. Importantly, colostrum and mature milk EVs significantly relieved the LPS-induced inhibition of proliferation and intestinal barrier-related genes expression and attenuated apoptosis and proinflammatory responses induced by LPS in IEC-6 cells. Flow cytometry and Western blot analysis also indicated that colostrum and mature milk EVs significantly affect the apoptosis of IEC-6 cells induced by LPS. The results also indicated that EVs derived from colostrum had better effects on inhibiting the apoptosis- and proinflammatory cytokines-related genes expression. However, the EVs derived from mature milk exhibited beneficial effects on intestinal epithelial barrier protection. The present study will provide a better understanding of the role of EVs derived from colostrum and milk in dairy cows with different responses in the regulation of intestinal cells function, and also presents new evidence for the change of EVs cargos during various stages of lactation.

Unilateral Biportal Endoscopy for the Resection of Thoracic Intradural Extramedullary Tumors: Technique Case Report and Literature Review.

This study describes a patient with an intradural extramedullary (IDEM) tumor removed entirely using the unilateral biportal endoscopic technique (UBE), achieving satisfactory clinical outcomes. A 60-year-old woman had a diagnosis of meningioma with sensations and motor dysfunction in the lower extremities and perineum and gait disturbances for three years, which has worsened over the last month. Preoperative imaging data showed a sizeable IDEM tumor at the T10 level, significantly compressing the thoracic spinal cord to the right side, with 80% intraspinal encroachment. The IDEM tumor was removed entirely by UBE surgery. To the best of our knowledge, this study may be the first to report the application of UBE techniques for IDEM tumor treatment. In this case, UBE provides a magnified and clear surgical field, greater maneuverability, and a less invasive surgical procedure. The procedure objectives were pathological confirmation, spinal cord decompression, and complete tumor removal; all were met. The patient was satisfied with her dramatically improved clinical symptoms. UBE may be an alternative surgical treatment option for benign IDEM tumors presenting with symptomatic, especially the non-giant lateral and posterior tumors.

Therapy effect of cochleural alternating acoustic beam therapy versus traditional sound therapy for managing chronic idiopathic tinnitus patients.

Idiopathic tinnitus is a common and complex disorder with no established cure. The CAABT (Cochleural Alternating Acoustic Beam Therapy CAABT), is a personalized sound therapy designed to target specific tinnitus frequencies and effectively intervene in tinnitus according to clinical tinnitus assessment. This study aimed to compare the effectiveness of the CAABT and Traditional Sound Therapy (TST) in managing chronic idiopathic tinnitus. This was a randomized, double-blind, parallel-group, single-center prospective study. Sixty adult patients with tinnitus were recruited and randomly assigned to the CAABT or TST group in a 1:1 ratio using a computer-generated randomization. The treatment lasted for 12 weeks, and participants underwent assessments using the tinnitus handicap inventory (THI), visual analog scale (VAS), tinnitus loudness measurements, and resting-state functional magnetic resonance imaging (rs-fMRI). Both groups showed significant reductions in THI scores, VAS scores, and tinnitus loudness after treatment. However, CAABT showed superiority to TST in THI Functional (p = 0.018), THI Emotional (p = 0.015), THI Catastrophic (p = 0.022), THI total score (p = 0.005) as well as VAS score (p = 0.022). More interesting, CAABT showed superiority to TST in the changes of THI scores, and VAS scores from baseline. The rs-fMRI results showed significant changes in the precuneus before and after treatment in both groups. Moreover, the CAABT group showed more changes in brain regions compared to the TST. No side effects were observed. These findings suggest that CAABT may be a promising treatment option for chronic idiopathic tinnitus, providing significant improvements in tinnitus-related symptoms and brain activity.Trial registration: ClinicalTrials.gov:NCT02774122.

NH2-MIL-101(Fe)-mediated photo-Fenton reaction enhanced simultaneous removal of nitrogen and refractory organics in anammox process through interfacial electron transfer.

In this study, H2O2 (0.1 ‰) and NH2-MIL-101(Fe)-driven (150 mg/L) photo-Fenton-coupled anammox were proposed to simultaneously improve the removal efficiency of nitrogen and humic acid. Long-term experiments showed that the total nitrogen removal efficiency was increased by the photo-Fenton reaction to 91.9 ± 1.5 % by altering the bioavailability of refractory organics. Correspondingly, the total organic carbon removal efficiency was significantly increased. Microbial community analyses indicated that Candidatus_Brocadia maintained high activity during photo-Fenton reaction and was the most abundant genus in the reactor. Dissimilatory nitrate reduction to ammonium process and denitrification process were enhanced, resulting in reduced NO3--N production. The establishment of electron transfer between microorganisms and NH2-MIL-101 (Fe) improved the charge separation efficiency of the quantum dots and increased the intracellular adenosine triphosphate content of anammox bacteria. These results indicated that photo-Fenton-anammox process promoted the removal of nitrogen and refractory organics in one reactor which had good economic value and application prospects.

RNA 5-methylcytosine writer NSUN5 promotes hepatocellular carcinoma cell proliferation via a ZBED3-dependent mechanism.

Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer-related mortality worldwide. Nop2/Sun domain family member 5 (NSUN5), a conserved RNA 5-methylcytosine methyltransferase, is conventionally recognized as oncogenic. However, its role in HCC development remains unknown. In this study, we observed a remarkable upregulation of NSUN5 expression in both tumor tissues from patients with HCC, establishing a correlation with unfavorable clinical outcomes. NSUN5 knockdown and overexpression significantly inhibited and promoted HCC cell proliferation, respectively. Additionally, employing a combination of methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RIP-seq techniques, we identified zinc finger BED domain-containing protein 3 (ZBED3) as a novel downstream target of NSUN5. Additionally, we found that the overexpression of ZBED3 counteracted the tumor-suppressing effect of NSUN5 knockdown and simultaneously reversed the inhibition of the Wnt/ß-catenin signaling pathway. In summary, we elucidated the oncogenic role of NSUN5 in HCC development and identified the ZBED3/Wnt/ß-catenin signaling pathway as its downstream target. This study provides a novel therapeutic target for further development in HCC treatment.

Recent advances in the potential role of RNA N4-acetylcytidine in cancer progression.

N4-acetylcytidine (ac4C) is a highly conserved chemical modification widely found in eukaryotic and prokaryotic RNA, such as tRNA, rRNA, and mRNA. This modification is significantly associated with various human diseases, especially cancer, and its formation depends on the catalytic activity of N-acetyltransferase 10 (NAT10), the only known protein that produces ac4C. This review discusses the detection techniques and regulatory mechanisms of ac4C and summarizes ac4C correlation with tumor occurrence, development, prognosis, and drug therapy. It also comments on a new biomarker for early tumor diagnosis and prognosis prediction and a new target for tumor therapy. Video Abstract.

Research progress of N1-methyladenosine RNA modification in cancer.

N1-methyladenosine (m1A) is a post-transcriptionally modified RNA molecule that plays a pivotal role in the regulation of various biological functions and activities. Especially in cancer cell invasion, proliferation and cell cycle regulation. Over recent years, there has been a burgeoning interest in investigating the m1A modification of RNA. Most studies have focused on the regulation of m1A in cancer enrichment areas and different regions. This review provides a comprehensive overview of the methodologies employed for the detection of m1A modification. Furthermore, this review delves into the key players in m1A modification, known as the "writers," "erasers," and "readers." m1A modification is modified by the m1A methyltransferases, or writers, such as TRMT6, TRMT61A, TRMT61B, TRMT10C, NML, and, removed by the demethylases, or erasers, including FTO and ALKBH1, ALKBH3. It is recognized by m1A-binding proteins YTHDF1, TYHDF2, TYHDF3, and TYHDC1, also known as "readers". Additionally, we explore the intricate relationship between m1A modification and its regulators and their implications for the development and progression of specific types of cancer, we discuss how m1A modification can potentially facilitate the discovery of novel approaches for cancer diagnosis, treatment, and prognosis. Our summary of m1A methylated adenosine modification detection methods and regulatory mechanisms in various cancers provides useful insights for cancer diagnosis, treatment, and prognosis. Video Abstract.

Clinical study of classification and regression tree assisted endometrial biopsy in the diagnosis of endometrial carcinoma.

The early diagnosis of endometrial carcinoma is critical for improving patient survival and prognosis. However, the diagnostic efficiency of a single examination is often insufficient, because it is easy to cause misdiagnosis and missed diagnoses. Therefore, this study used the classification and regression tree (CART) algorithm to establish and validate a CART model to distinguish endometrial carcinoma from other endometrial lesions. The clinical data of 297 patients treated at Changde Hospital, Xiangya School of Medicine, Central South University between April 2021 and April 2023 for postmenopausal uterine effusion, postmenopausal vaginal bleeding, abnormal uterine bleeding and endometrial thickening were retrospectively analyzed. Among them, there were 203 cases of endometrial carcinoma and 94 cases of endometrial lesions. The pathological results from endometrial biopsy and hysteroscopic curettage were compared. The coincidence rate of endometrial biopsy was 90.34% (187/207) and the AUC, sensitivity, and specificity of the diagnosis of endometrial carcinoma were 0.920, 0.914, and 0.925, respectively. Six serological indicators with diagnostic significance were screened out: carbohydrate antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), human epididymis secretory protein 4 (HE4), vascular endothelial growth factor (VEGF), D-dimer, and absolute neutrophil count (N). The AUC, sensitivity and specificity of the CART model based on the above indicators were 0.949, 0.979, and 0.896, respectively. The CART model is an intuitive and simple tool for the clinical diagnosis of endometrial carcinoma and endometrial lesions.

Superficial vessel-based near infrared-assisted patient position recognition and real-time monitoring system (VIPS) for radiotherapy: A proof-of-concept study.

BACKGROUND: The accuracy and precision of patient position in radiotherapy process have dramatic impacts on the tumor local control and therapy-related side effects, and there exist demands to explore effective positioning solutions, particularly in the era with great progress in imaging recognition and matching. PURPOSE: Superficial vessel-based near infrared-assisted patient position recognition and real-time monitoring system (VIPS) was proposed to develop an automated, operator-independent and skin marker-free imaging system to improve patient setup and intrafractional motion monitoring. METHODS: VIPS includes two components, the imaging module and the image alignment software. Using a simulated blood vessel model, multiple NIR sources with various wavelength and bolus (pseudo-skin) were evaluated in terms of imaging quality to determine the optimal light source and the upper limit of superficial fatty tissue thickness. Then the performance of VIPS with reference to either CBCT or laser setup system was conducted using 3D phantom and clinical cases enrolled into the registered clinical trial. The position displacement from VIPS and laser system was compared, as well as the systematic and random errors of VIPS setup procedure. RESULTS: The NIR light source with the combined wavelengths of 760 nm + 940 nm (S760+940 nm ) provided the best performance among multiple tested light sources. The bolus (superficial fatty layer) thickness over 5 mm could dramatically compromise the NIR detection of vessels beneath. In the phantom study, the translational positional displacements according to VIPS guidance were within the submillimeter level with reference to CBCT, indicative of high setup accuracy. The clinical trial showed the prototype VIPS could effectively detect and control position displacement of patients in translational and rotational directions within an acceptable range, which was non-inferior to conventional laser/skin marker system. CONCLUSION: This proof-of-concept study validated the feasibility and reliability of VIPS in guiding radiotherapy setup. However, limitations and technical challenges should be resolved prior to further clinical evaluation, including isocenter alignment, potential NIR image distortion and the impact of the superficial tissues on the recognition of vessels.