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Cancer immunotherapy has shown to be a promising method in treating hepatocellular carcinoma (HCC), but suboptimal responses in patients are attributed to cellular and molecular heterogeneity. Iron metabolism-related genes (IRGs) are important in maintaining immune system homeostasis and have the potential to help develop new strategies for HCC treatment. Herein, we constructed and validated the iron-metabolism gene prognostic index (IPX) using univariate Cox proportional hazards regression and LASSO Cox regression analysis, successfully categorizing HCC patients into two groups with distinct survival risks. Then, we performed single-sample gene set enrichment analysis, weighted correlation network analysis, gene ontology enrichment analysis, cellular lineage analysis, and SCENIC analysis to reveal the key determinants underlying the ability of this model based on bulk and single-cell transcriptomic data. We identified several driver transcription factors specifically activated in specific malignant cell sub-populations to contribute to the adverse survival outcomes in the IPX-high subgroup. Within the tumor microenvironment (TME), T cells displayed significant diversity in their cellular characteristics and experienced changes in their developmental paths within distinct clusters identified by IPX. Interestingly, the proportion of Treg cells was increased in the high-risk group compared with the low-risk group. These results suggest that iron-metabolism could be involved in reshaping the TME, thereby disrupting the cell cycle of immune cells. This study utilized IRGs to construct a novel and reliable model, which can be used to assess the prognosis of patients with HCC and further clarify the molecular mechanisms of IRGs in HCC at single-cell resolution.

【Objective】 The aim of this study is to improve the accuracy of water level control, minimize water level oscillations, and improve the convergence efficiency of control algorithms for multi-stage gate-controlled canals operating under significant water level variations. 【Method】 We propose an adaptive predictive control algorithm (APC) which dynamically adjusts the parameters of the identification (ID) model based on real-time canal water level data and modifies the activation frequency of sluices. The performance of the APC algorithm is comprehensively evaluated and compared with other control algorithms under six distinct operational conditions. 【Result】 In comparison to the linear quadratic controller (LQR) and the model predictive controller (MPC) based on the ID model, the APC algorithm shows significant improvements in accuracy and reliability, reducing the regulation duration by 19% to 32% and 8% to 40% respectively, damping the cumulative fluctuation of the canal water level by 47% to 97% and 14% to 93% respectively, lowering the mean absolute deviation of canal water level by 24% to 77% and 5% to 59%, respectively. 【Conclusion】 The APC method can substantially improve the precision of water level control and the convergence for multi-stage gate-controlled canals. It is robust for various canal water level amplitudes, thereby providing a crucial technical support for advancing intelligent management of water conservancy infrastructures.

The pre-release operation has the potential to enhance the ability of a reservoir to manage exceedance floods. However, the mechanisms for the initiation and termination of such operations are unclear, and a clear method for calculating the pre-release water amount at each time step of the scheduling phase is lacking. To address this, the framework and mathematical expression for a pre-release index are proposed herein, and a refined pre-release scheduling model is developed based on the pre-release indices and their thresholds. Then, the proposed pre-release operation model is applied to the Shuifumiao Reservoir in the Lianshui River Basin in Hunan Province, China. The simulation results demonstrate that the refined pre-release scheduling model can effectively prevent exceedance floods, ensuring the safety of flood control without compromising the effectiveness of water supply safety. The proposed model provides a valuable framework and tool for enhancing the ability of reservoir operators to manage flood events and improve overall flood control safety. [ABSTRACT FROM AUTHOR]

Abstract The secondary structures of hepatitis C virus (HCV) RNA and the cellular proteins that bind to them are important for modulating both translation and RNA replication. However, the sets of RNA-binding proteins involved in the regulation of HCV translation, replication and encapsidation remain unknown. Here, we identified RNA binding motif protein 24 (RBM24) as a host factor participated in HCV translation and replication. Knockdown of RBM24 reduced HCV propagation in Huh7.5.1 cells. An enhanced translation and delayed RNA synthesis during the early phase of infection was observed in RBM24 silencing cells. However, both overexpression of RBM24 and recombinant human RBM24 protein suppressed HCV IRES-mediated translation. Further analysis revealed that the assembly of the 80S ribosome on the HCV IRES was interrupted by RBM24 protein through binding to the 5′-UTR. RBM24 could also interact with HCV Core and enhance the interaction of Core and 5′-UTR, which suppresses the expression of HCV. Moreover, RBM24 enhanced the interaction between the 5′- and 3′-UTRs in the HCV genome, which probably explained its requirement in HCV genome replication. Therefore, RBM24 is a novel host factor involved in HCV replication and may function at the switch from translation to replication.

The effect of tooth surface friction from mesh- in to mesh- out on bending strength is researched,including the normal and friction force of the driving gear. Based on the variation of tooth surface friction,the engaging region is divided into the upper and lower regions bounded by pitch circle,and then the calculation equations of root stress in different meshing regions are derived. The case shows that the root bending stress with friction is 3% bigger than the one without friction in the upper region,but that the stress with friction is 4% smaller than the one without friction in the lower region. The mutation of the root bending stress is in line with the direction reverse of friction force at pitch point. The experimental and calculating results show that the curves of root bending stress are basically consistent and that the deviation is within 10% when the dynamic load factor is considered in the calculation equations. The calculation model preliminarily is verified by the experimental results,and the calculation equation of tooth root bending stress including friction is more reliable.

Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration, which ultimately leads to paralysis and death. Mutation of TAR DNA binding protein 43 (TDP-43) has been linked to the development of an inherited form of ALS. Existing TDP-43 transgenic animals develop a limited loss of motor neurons and therefore do not faithfully reproduce the core phenotype of ALS. Here, we report the creation of multiple lines of transgenic rats in which expression of ALS-associated mutant human TDP-43 is restricted to either motor neurons or other types of neurons and skeletal muscle and can be switched on and off. All of these rats developed progressive paralysis reminiscent of ALS when the transgene was switched on. Rats expressing mutant TDP-43 in motor neurons alone lost more spinal motor neurons than rats expressing the disease gene in varying neurons and muscle cells, although these rats all developed remarkable denervation atrophy of skeletal muscles. Intriguingly, progression of the disease was halted after transgene expression was switched off; in rats with limited loss of motor neurons, we observed a dramatic recovery of motor function, but in rats with profound loss of motor neurons, we only observed a moderate recovery of motor function. Our finding suggests that mutant TDP-43 in motor neurons is sufficient to promote the onset and progression of ALS and that motor neuron degeneration is partially reversible, at least in mutant TDP-43 transgenic rats., Introduction Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motor neurons and denervation atrophy of skeletal muscles. The disease inexorably progresses to paralysis and to death, often within [...]