[Objective] To explore the relationship between neutrophil activation under cardiopulmonary bypass (CPB) and the incidence of cardiac surgery-associated acute kidney injury (CS-AKI). [Methods] This prospective cohort study enrolled adult patients who scheduled for cardiac surgery under CPB at West China Hospital between May 1, 2022 and March 31, 2023. The primary outcome was acute kidney injury (AKI). Blood samples (5 mL) were obtained from the central vein before surgery, at rewarming, at the end of CPB, and 24 hours after surgery. Neutrophils were labeled with CD11b, CD54 and other markers. To assess the effect of neutrophils activation on AKI, propensity score matching (PSM) was employed to equilibrate covariates between the groups. [Results] A total of 120 patients included into the study, and 17 (14.2%) developed AKI. Both CD11b⁺ and CD54⁺ neutrophils significantly increased during the rewarming phase and the increases were kept until 24 hours after surgery. During rewarming, the numbers of CD11b⁺ neutrophils were significantly higher in AKI compared to non-AKI (4.71×10⁹/L vs 3.31×10⁹/L, Z=-2.14, P<0.05). Similarly, the CD54⁺ neutrophils counts were also significantly higher in AKI than in non-AKI before surgery (2.75×10⁹/L vs 1.79×10⁹/L, Z=-2.99, P<0.05), during rewarming (3.12×10⁹/L vs 1.62×10⁹/L, Z=-4.34, P<0.05), and at the end of CPB (4.28×10⁹/L vs 2.14×10⁹/L, Z=-3.91, P<0.05). An analysis of 32 matched patients (16 in each group) revealed that CD11b⁺ and CD54⁺ neutrophil levels of AKI were 1.74 folds (4.83×10⁹/L vs 2.77×10⁹/L, Z=-2.72, P<0.05) and 2.34 folds (3.32×10⁹/L vs 1.42×10⁹/L, Z=-4.12, P<0.05), respectively, of non-AKI at rewarming phase. [Conclusion] Neutrophils are activated during CPB, and they can be identified by CD11b/CD54 markers. The activated neutrophils of AKI patients are approximately 2 folds of non-AKI during the rewarming phase, with disparity reached peak between groups during rewarming. These findings suggest the removal of 50% of activated neutrophils during the rewarming phase may be effective to reduce the risk of AKI.

Objective To introduce an innovative technique, the "balance-shaped sternal elevation device" and its application in the subxiphoid uniportal video-assisted thoracoscopic surgery (VATS) for anterior mediastinal masses resection. Methods Patients who underwent single-port thoracoscopic assisted anterior mediastinal tumor resection through the xiphoid process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from May to June 2024 were included, and their clinical data were analyzed. Results A total of 7 patients were included, with 3 males and 4 females, aged 28-72 years. The diameter of the tumor was 1.9-17.0 cm. The operation time was 62-308 min, intraoperative blood loss was 5-100 mL, postoperative chest drainage tube retention time was 0-9 days, pain score on the 7th day after surgery was 0-2 points, and postoperative hospital stay was 3-12 days. All patients underwent successful and complete resection of the masses and thymus, with favorable postoperative recovery. Conclusion The "balance-shaped sternal elevation device" effectively expands the retrosternal space, providing surgeons with satisfactory surgical views and operating space. This technique significantly enhances the efficacy and safety of minimally invasive surgery for anterior mediastinal masses, reduces trauma and postoperative pain, and accelerates patient recovery, demonstrating important clinical significance and application value.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Aluminum adjuvants are widely used in the field of vaccines due to their ability to induce efficient and long-lasting immune responses and good safety profile. With the development of immunology, the requirements for adjuvants have gradually increased, and traditional aluminum adjuvants can no longer meet all the needs of application. The development of novel aluminum adjuvants has become a hot research topic in order to achieve good immunity-enhancing effects and induce specific types and strengths of immune responses. This review briefly introduces the mechanism of action and safety of aluminum adjuvants, with focus on the research progress of novel aluminum adjuvants in recent years, mainly including nano-aluminum adjuvants and composite aluminum adjuvants (aluminum adjuvants compounded with immunity-stimulating molecules or delivery carriers), and a prospect of their future research direction, aiming to provide some reference for the further development and clinical application of aluminum adjuvants.

ObjectiveTransfer RNA-derived fragments (tRFs) are a recently characterized and rapidly expanding class of small non-coding RNAs, typically ranging from 13 to 50 nucleotides in length. They are derived from mature or precursor tRNA molecules through specific cleavage events and have been implicated in a wide range of cellular processes. Increasing evidence indicates that tRFs play important regulatory roles in gene expression, primarily by interacting with target messenger RNAs (mRNAs) to induce transcript degradation, in a manner partially analogous to microRNAs (miRNAs). However, despite their emerging biological relevance and potential roles in disease mechanisms, there remains a significant lack of computational tools capable of systematically predicting the interaction landscape between tRFs and their target mRNAs. Existing databases often rely on limited interaction features and lack the flexibility to accommodate novel or user-defined tRF sequences. The primary goal of this study was to develop a machine learning based prediction algorithm that enables high-throughput, accurate identification of tRF:mRNA binding events, thereby facilitating the functional analysis of tRF regulatory networks. MethodsWe began by assembling a manually curated dataset of 38 687 experimentally verified tRF:mRNA interaction pairs and extracting seven biologically informed features for each pair: (1) AU content of the binding site, (2) site pairing status, (3) binding region location, (4) number of binding sites per mRNA, (5) length of the longest consecutive complementary stretch, (6) total binding region length, and (7) seed sequence complementarity. Using this dataset and feature set, we trained 4 distinct machine learning classifiers—logistic regression, random forest, decision tree, and a multilayer perceptron (MLP)—to compare their ability to discriminate true interactions from non-interactions. Each model’s performance was evaluated using overall accuracy, receiver operating characteristic (ROC) curves, and the corresponding area under the ROC curve (AUC). The MLP consistently achieved the highest AUC among the four, and was therefore selected as the backbone of our prediction framework, which we named tRF Prospect. For biological validation, we retrieved 3 high-throughput RNA-seq datasets from the gene expression omnibus (GEO) in which individual tRFs were overexpressed: AS-tDR-007333 (GSE184690), tRF-3004b (GSE197091), and tRF-20-S998LO9D (GSE208381). Differential expression analysis of each dataset identified genes downregulated upon tRF overexpression, which we designated as putative targets. We then compared the predictions generated by tRF Prospect against those from three established tools—tRFTar, tRForest, and tRFTarget—by quantifying the number of predicted targets for each tRF and assessing concordance with the experimentally derived gene sets. ResultsThe proposed algorithm achieved high predictive accuracy, with an AUC of 0.934. Functional validation was conducted using transcriptome-wide RNA-seq datasets from cells overexpressing specific tRFs, confirming the model’s ability to accurately predict biologically relevant downregulation of mRNA targets. When benchmarked against established tools such as tRFTar, tRForest, and tRFTarget, tRF Prospect consistently demonstrated superior performance, both in terms of predictive precision and sensitivity, as well as in identifying a higher number of true-positive interactions. Moreover, unlike static databases that are limited to precomputed results, tRF Prospect supports real-time prediction for any user-defined tRF sequence, enhancing its applicability in exploratory and hypothesis-driven research. ConclusionThis study introduces tRF Prospect as a powerful and flexible computational tool for investigating tRF:mRNA interactions. By leveraging the predictive strength of deep learning and incorporating a broad spectrum of interaction-relevant features, it addresses key limitations of existing platforms. Specifically, tRF Prospect: (1) expands the range of detectable tRF and target types; (2) improves prediction accuracy through multilayer perceptron model; and (3) allows for dynamic, user-driven analysis beyond database constraints. Although the current version emphasizes miRNA-like repression mechanisms and faces challenges in accurately capturing 5'UTR-associated binding events, it nonetheless provides a critical foundation for future studies aiming to unravel the complex roles of tRFs in gene regulation, cellular function, and disease pathogenesis.

This study aimed to investigate halofuginone's inhibitory effect and mechanism on the activity of hepatocellular carcinoma cells. HepG2 cells were used to detect the effects of halofuginone. After treatment, cell activity, cell migration, cell cycle, and cell apoptosis were detected by CCK-8, transwell, and flow cytometry, respectively. The expression levels of growth and metabolism-related factors such as citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and isocitrate deoxygenase (IDH) were detected by real-time quantitative PCR and Western blot. Compared with the control group, the activity of HepG2 cells was significantly inhibited by halofuginone (P < 0.01), the migration rate of HepG2 cells was decreased (P < 0.01), the apoptosis of HepG2 cells was induced (P < 0.01), and the cell cycle was arrested in S phase (P < 0.01). The expression levels of tricarboxylic acid key enzymes CS, IDH3, and OGDH were up-regulated, the expression level of isocitrate dehydrogenase isoenzymes IDH1 and IDH2 were down-regulation. In conclusion, halofuginone can inhibit the proliferation and migration of HepG2 cells and promote apoptosis in a dose-dependent manner, which may be due to the promotion of the aerobic metabolism of cells.

Objective To explore the role and possible molecular mechanism of Isocitrate dehydrogenase 1(IDH1)gene in proliferation and migration of intrahepatic cholangiocarcinoma(iCCA)cell HuCCT1.Methods HuCCT1 cells with IDH1 gene knockout(HuCCT1IDH1-/-)were constructed by CRISPR/Cas9 gene editing technology.To investigate the capacities of proliferation,migration and invasion of HuCCT1WT(HuCCT1 cells with wild-type IDH1 gene)and HuCCT1IDH1-/-cells,assays of CCK-8,clone formation,scratch and transwell were performed.Western blotting was used to detect the expression levels of epithelial-mesenchymal transition(EMT)associated proteins E-cadherin,N-cadherin,Vimentin,MMP-9,Wnt3a and β-catenin in two groups of cells.The transcriptome sequencing data of HuCCT1WT and HuCCT1IDH1-/-cells were analyzed by bioinformatics methods,Western blotting was used to verify the expression of signaling pathway-related proteins.Results Compared with HuCCT1WT cells,HuCCT1IDH1-/-cells showed the number of proliferation and clone formation significantly reduced(P<0.05),the proportion of cells blocked in G2/M phase was significantly increased(P<0.01),the rate of scratch healing was significantly decreased(P<0.01),and the number of migrated cells(P<0.001)and invaded cells(P<0.05)was significantly reduced.qRT-PCR assay showed that the expression levels of IDH1,Vimentin,MMP-9 and genes related to the regulation of G2/M cycle proliferation,Cyclin A2,Cyclin B1 and CDK1 mRNA were down-regulated in HuCCT1IDH1-/-cells(P<0.05),and the expression of CDH1 mRNA encoding E-cadherin was up-regulated(P<0.01);Western blotting assay showed that the expression level of E-cadherin in HuCCT1IDH1-/-cells was significantly increased(P<0.05),and the expression level of N-cadherin,Vimentin and MMP-9 protein was significantly decreased(P<0.05)than that in HuCCT1WT cells.Data of transcriptome sequencing revealed 1476 differentially expressed genes(DEGs)between two groups of HuCCT1 cells.Go enrichment analysis showed the DEGs were significantly enriched in cell biological processes associated with inflammatory response,cell signaling and cell metabolism.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis suggested that the DEGs may be involved in some signaling pathways such as Wnt,MAPK,Rap1,Hippo and TNF,which are closely related to the regulation of proliferation and invasion of tumor cells.Western blotting verification results showed that compared with HuCCT1WT cells,the relative expression of Wnt3a and β-catenin proteins of HuCCT1IDH1-/-cells was significantly decreased(P<0.05).Conclusions IDH1 gene may participate in the control of biological functions of HuCCT1 cells,including cell proliferation,migration,invasion and epithelial mesenchymal transition.The mechanism may be related to the activation of the Wnt/β-catenin signaling pathway.

Objective:To evaluate the efficacy of cerebral-placental-uterine ratio(CPUR)in predicting late-on-set fetal growth restriction(FGR).Methods:From May 2020 to May 2021,1255 women with singleton pregnancy who underwent prenatal examinations at the University of Hong Kong Shenzhen Hospital were selected for fetal growth and Doppler measurements at 35-37 +6 weeks of gestation.Pregnant women with birth weight of newbo-rns＜the 10th percentile were the FGR group.The pulsatility index(PI)of uterine artery(UtA),umbilical artery(UA)and fetal middle cerebral artery(MCA)were analyzed separately and in combination.ROC curve was used to analyze the cerebral-placental-uterine ratio(CPUR),cerebral-placental ratio(CPR),cerebral-uterine ratio(C-UtA)for predicting late-onset FGR;and to evaluate the sensitivity,positive and negative predictive value and of CPUR in the prediction of late-onset FGR.Results:The area under the curve(AUC)of CPUR,CPR,C-UtA and mean UtA-PI for FGR grope were 0.88,0.86,0.84 and 0.72.Under certain cut-off values and 87% specificity,the specificity of CPUR,CPR,C-UtA and mean UtA-Pifor predicting FGR group was 43.2%,46.6%,39.8% and 23.9%,respectively.The positive predictive values of CPUR,CPR,C-UtA and mean UtA-PI,UA-PI for predicting FGR group were 90.5%,71.9%,83.3%,63.6%and 5.2%,respectively.Conclusions:CPUR is more effective in predicting late onset FGR than CPR,C-UtA and mean UtA-PI.It can effectively increase the detection rate of fetal growth restrictionand reduce the FGR risk.