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The thin walled metal plates (TWMP) on top of a commercial vehicle body are easy to produce vibration and booming noise under the action of high-speed airflow, which reduces the sound quality inside the vehicle. Therefore, the effective control of the noise of TWMP is very important for vehicle comfort performance. Based on experimental, finite element, dynamic and fluid techniques, a method for identification, analysis and optimization of TWMP booming noise under high-speed airflow is proposed in this paper. The problem frequency, the noise source and the cause of booming noise inside the vehicle are identified by amplitude-frequency characteristics analysis and modal analysis. By establishing the dynamic model of damping patch, the matching method of damping patch is proposed. The simulation results are in good agreement with the experimental results, which shows that the method is correct. And the damping coefficient, attachment position and attachment area of the damping plate can be analyzed quickly and accurately by using the method, and the vibration and noise of TWMP can be reduced obviously.

Interferon-γ (IFN-γ) is essential for the innate immune response to intracellular bacteria. Noncoding RNAs and RNA-binding proteins (RBPs) need to be further considered in studies of regulation of the IFN-γ-activated signaling pathway in macrophages. In the present study, we found that the microRNA miR-1 promoted IFN-γ-mediated clearance of Listeria monocytogenes in macrophages by indirectly stabilizing the Stat1 messenger RNA through the degradation of the cytoplasmic long noncoding RNA Sros1. Inducible degradation or genetic loss of Sros1 led to enhanced IFN-γ-dependent activation of the innate immune response. Mechanistically, Sros1 blocked the binding of Stat1 mRNA to the RBP CAPRIN1, which stabilized the Stat1 mRNA and, consequently, promoted IFN-γ–STAT1-mediated innate immunity. These observations shed light on the complex RNA–RNA regulatory networks involved in cytokine-initiated innate responses in host–pathogen interactions. Cao and colleagues found that the microRNA miR-1 promotes IFN-γ-mediated clearance of Listeria monocytogenes in macrophages by stabilizing the Stat1 mRNA through the degradation of the cytoplasmic long noncoding RNA Sros1.

Deep eutectic solvents (DES)/reduced graphene oxide (rGO) composite materials can remove dibenzothiophene (DBT) from fuel oil by adsorption desulfurization. However, the whole synthesis process is complicated, and the DES/rGO is high-cost and not strong enough, which limits its application in industry. Therefore, a one-step method to produce DES/rGO composite materials is proposed. The performance of desulfurization was studied and the feasibility of industrial application was analyzed. First, the proposed method can improve the single extraction efficiency to 94.8% without a complicated process. Secondly, the DES/rGO can also be reused and recycled. Third, the proposed method overcomes the inconvenient storage and transportation of liquid DES. Finally, the proposed method could effectively reduce the cost of desulphurization in the industry.

Background Clinically, prophylactic anti-recurrence treatments for hepatocellular carcinoma (HCC) patients after radical surgery are extremely limited. Neoantigen based vaccine can generate robust anti-tumor immune response in several solid tumors but whether it could induce anti-tumor immune response in HCC and serve as a safe and effective prophylactic strategy for preventing postoperative HCC recurrence still remain largely unclear. Methods Personalized neoantigen vaccine was designed and immunized for 10 HCC patients with high risk of postoperative recurrence in a prime-boost schedule. The safety and immune response were assessed through adverse events, tissue sequencing, ELISpot, TCR sequencing. The clinical response was evaluated by recurrence-free survival (RFS) and personalized circulating tumor DNA (ctDNA) sequencing. Results In the 10 enrolled patients, no obvious adverse events were observed during neoantigen vaccinations. Until the deadline of clinical trial, 8 of 10 patients were confirmed with clinical relapse by imaging, the other 2 patients remained relapse-free. From receiving first neoantigen vaccination, the median RFS of 10 patients were 7.4 months. Among 7 patients received all planned neoantigen vaccinations, 5 of them demonstrated neoantigen-induced T cell responses and have significantly longer RFS after radical surgery than other 5 patients without responsive neoantigens or only with prime vaccination and propensity scores matching control patients ( p  = 0.035). Moreover, tracking personalized neoantigen mutations in ctDNA could provide real-time evaluation of clinical response in HCC patients during neoantigen vaccination and follow up. Conclusion Personalized neoantigen vaccine is proved as a safe, feasible and effective strategy for HCC anti-recurrence, and its progression could be sensitively monitored by corresponding neoantigen mutations in ctDNA, and thus provided solid information for individualized medicine in HCC. Trial registration This study was registered at Chinese Clinical Trial Registry; Registration number: ChiCTR1900020990 .

Treatment with Menin inhibitor (MI) disrupts the interaction between Menin and MLL1 or MLL1-fusion protein (FP), inhibits HOXA9/MEIS1, induces differentiation and loss of survival of AML harboring MLL1 re-arrangement (r) and FP, or expressing mutant (mt)-NPM1. Following MI treatment, although clinical responses are common, the majority of patients with AML with MLL1-r or mt-NPM1 succumb to their disease. Pre-clinical studies presented here demonstrate that genetic knockout or degradation of Menin or treatment with the MI SNDX-50469 reduces MLL1/MLL1-FP targets, associated with MI-induced differentiation and loss of viability. MI treatment also attenuates BCL2 and CDK6 levels. Co-treatment with SNDX-50469 and BCL2 inhibitor (venetoclax), or CDK6 inhibitor (abemaciclib) induces synergistic lethality in cell lines and patient-derived AML cells harboring MLL1-r or mtNPM1. Combined therapy with SNDX-5613 and venetoclax exerts superior in vivo efficacy in a cell line or PD AML cell xenografts harboring MLL1-r or mt-NPM1. Synergy with the MI-based combinations is preserved against MLL1-r AML cells expressing FLT3 mutation, also CRISPR-edited to introduce mtTP53. These findings highlight the promise of clinically testing these MI-based combinations against AML harboring MLL1-r or mtNPM1.

Objective Identifying precise biomarkers for colorectal cancer (CRC) detection and management remains challenging. Here, we developed an innovative prognostic model for CRC using cuproptosis-related long non-coding RNAs (lncRNAs). Methods In this retrospective study, CRC patient transcriptomic and clinical data were sourced from The Cancer Genome Atlas database. Cuproptosis-related lncRNAs were identified and used to develop a prognostic model, which helped categorize patients into high- and low-risk groups. The model was validated through survival analysis, risk curves, independent prognostic analysis, receiver operating characteristic curve analysis, decision curves, and nomograms. In addition, we performed various immune-related analyses. LncRNA expression levels were examined in normal human colorectal epithelial cells (FHC) and CRC cells (HCT-116) using quantitative polymerase chain reaction (qPCR). Results Six cuproptosis-related lncRNAs were identified: ZKSCAN2-DT, AL161729.4, AC016394.1, AC007128.2, AL137782.1, and AC099850.3. The prognostic model distinguished between high-/low-risk populations, demonstrating excellent predictive ability for survival outcomes. Immunocorrelation analysis showed significant differences in immune cell infiltration and functions, immune checkpoint expression, and m6A methylation-related genes. The qPCR results showed significant upregulation of ZKSCAN2-DT, AL161729.4, AC016394.1, AC007128.2 in HCT-116 cells, while AL137782.1 and AC099850.3 expression patterns were significantly downregulated. Conclusion Cuproptosis-related lncRNAs can potentially serve as reliable diagnostic and prognostic biomarkers for CRC.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with poor outcomes with conventional therapy. Nearly 100% of BPDCNs overexpress interleukin 3 receptor subunit alpha (CD123). Given that CD123 is differentially expressed on the surface of BPDCN cells, it has emerged as an attractive therapeutic target. UCART123 is an investigational product consisting of allogeneic T cells expressing an anti-CD123 chimeric antigen receptor (CAR), edited with TALEN ® nucleases. In this study, we examine the antitumor activity of UCART123 in preclinical models of BPDCN. We report that UCART123 have selective antitumor activity against CD123-positive primary BPDCN samples (while sparing normal hematopoietic progenitor cells) in the in vitro cytotoxicity and T cell degranulation assays; supported by the increased secretion of IFNγ by UCART123 cells when cultured in the presence of BPDCN cells. UCART123 eradicate BPDCN and result in long-term disease-free survival in a subset of primary patient-derived BPDCN xenograft mouse models. One potential challenge of CD123 targeting therapies is the loss of CD123 antigen through diverse genetic mechanisms, an event observed in one of three BPDCN PDX studied. In summary, these results provide a preclinical proof-of-principle that allogeneic UCART123 cells have potent anti-BPDCN activity. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematologic malignancy derived from the precursors of plasmacytoid dendritic cells. Here the authors characterize the anti-tumor activity of allogeneic anti-CD123 CAR-T cells in preclinical models of BPDCN.

The transverse leaf spring (TLS) suspension has simple structure, convenient installation and low cost. And the suspension stiffness is optimized by changing the TLS fixing bracket position without changing TLS size, which makes the TLS suspension have higher application prospect. The dynamic modeling method is proposed for analysis of elastic characteristics of the TLS suspension. The trend of the TLS stiffness is theoretically expounded. And the stiffness, natural frequency, damping characteristic and vibration of the suspension are simulated and tested. The comparative analysis shows that the precision of numerical results is high, which also shows that the TLS suspension modeling method is correct. The results provide a basis for grasping the TLS stiffness trend and the suspension dynamic characteristics.

Many complex social systems can be modeled as directed signed networks whose edges are marked with a positive/negative sign or direction. Network embedding representation is aimed at mapping rich structural and semantic information into low-dimensional vectors, and extensive research has demonstrated that Graph Neural Networks (GNNs) are an effective way. However, existing GNNs are primarily designed for undirected signed networks and usually used to capture the semantics of the complex structure by social structural balance theory, thus omitting the directional information of the links. In this research, we introduce a reciprocity relationship and status theory to enhance the modeling of the directed positive/negative relationship between two nodes, which has been widely applied in complex network research, and design SR-GNN, a GNN model for signed directed networks, to enable a more accurate vector representation of the nodes and convolution operations on edges with different directions and signs. Experiments demonstrate a reciprocity relationship, and status theory can allow the model to extract the most essential comprehensive information in signed directed graphs. Furthermore, SR-GNN can obtain effective status scores of nodes for link sign predictions and node ranking tasks, both of which yield state-of-the-art performance in most cases.

Fatigue failure of concrete under action of freeze-thaw cycles and repeated loading posess a critical challenge seasonally frozen soil regions, and concrete reinforcement technology offers a viable solution to this issue. However, based on current research results, BFRP, as a relatively young member of FRP materials, has not been fully studied in the field of interfacial bonding. This study emphasizes the importance of concrete fatigue resistance in seasonally frozen regions and aims to provide a theoretical basis for the practical application of BFRP-reinforced concrete therein. In this work, BFRP was employed in concrete reinforcement technology, and the fatigue characteristics of BFRP-concrete under freeze-thaw cycles were evaluated through double shear tests and finite element analysis. The test results demonstrated that freeze-thaw damage gradually propagated from the concrete surface to the interior, and the thickness of concrete layer peeled off by the adhesive layer decreased progressively with freeze-thaw cycles increasing. Double shear test results showed that the interfacial shear strength of BFRP-concrete decreased by approximately 46.86% after 200 freeze-thaw cycles. Then, finite element analysis further revealed that freeze-thaw cycles exerted the larger adverse impact on the fatigue life of BFRP-concrete than stress amplitude.