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Alzheimer’s Disease (AD) is a multifaceted neurodegenerative disease predominantly defined by the extracellular accumulation of amyloid-β (Aβ) peptide. In light of this, in the past decade, several clinical approaches have been used aiming at developing peptides for therapeutic use in AD. The use of cationic arginine-rich peptides (CARPs) in targeting protein aggregations has been on the rise. Also, the process of peptide development employing computational approaches has attracted a lot of attention recently. Using a structure database containing pentapeptides made from 20 L-α amino acids, we employed molecular docking to sort pentapeptides that can bind to Aβ42, then performed molecular dynamics (MD) analyses, including analysis of the binding stability, interaction energy, and binding free energy to screen ligands. Transmission electron microscopy (TEM), circular dichroism (CD), thioflavin T (ThT) fluorescence detection of Aβ42 polymerization, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and the flow cytometry of reactive oxygen species (ROS) were carried out to evaluate the influence of pentapeptides on the aggregation and cell toxicity of Aβ42. Two pentapeptides (TRRRR and ARRGR) were found to have strong effects on inhibiting the aggregation of Aβ42 and reducing the toxicity of Aβ42 secreted by SH-SY5Y cells, including cell death, reactive oxygen species (ROS) production, and apoptosis.

Let $(X, d)$ be a metric space and $\mathcal{H}(X)$ represent all non-empty, compact subsets of $X$. The expansivity of the multivalued map sequence $\bar{f}_{1, \infty}: \mathcal{H}(X) \to \mathcal{H}(X)$, including expansivity, positive $\aleph_0$-expansivity, were investigated. Also, stronger forms of sensitivities, such as multi-sensitivity and syndetical sensitivity, were explored. This research demonstrated that some chaotic properties can be mutually derived between $(f_{1, \infty}, X)$ and $(\bar{f}_{1, \infty}, \mathcal{H}(X))$, showing fundamental similarities between these systems. Conversely, the inability to derive other properties underlined essential differences between them. These insights are crucial for simplifying theoretical models and enhancing independent research. Lastly, the relationship between expansivity and sensitivity was discussed and the concept of topological conjugacy to the system $ (\bar{f}_{1, \infty}, \mathcal{H}(X)) $ was extended.

Alzheimer’s disease (AD) is an intractable and progressive neurodegenerative disease. Amyloid beta (Aβ) aggregation is the hallmark of AD. Aβ induces neurotoxicity through a variety of mechanisms, including interacting with membrane receptors to alter downstream signaling, damaging cellular or organelle membranes, interfering with protein degradation and synthesis, and inducing an excessive immune-inflammatory response, all of which lead to neuronal death and other pathological changes associated with AD. In this study, we extracted gene expression profiles from the GSE5281 and GSE97760 microarray datasets in the GEO (Gene Expression Omnibus) database, as well as from the Human Gene Database. We identified differentially expressed genes in the brain tissues of AD patients and healthy persons. Through GO, KEGG, and ROC analyses, annexin A2 (AnxA2) was identified as a putative target gene. Notably, accumulating evidence suggests that intracellular AnxA2 is a key regulator in various biological processes, including endocytosis, transmembrane transport, neuroinflammation, and apoptosis. Thus, we conducted a series of cell biology experiments to explore the biological function of AnxA2 in AD. The results indicate that AnxA2 gene knockdown primarily affects oxidative phosphorylation, cell cycle, AD, protein processing in the endoplasmic reticulum, SNARE interactions in vesicular transport, and autophagy. In SH-SY5Y cells secreting Aβ42, AnxA2 gene knockdown exacerbated Aβ42-induced cytotoxicity, including cell death, intracellular ROS levels, and neuronal senescence, altered cell cycle, and reduced ATP levels, suggesting its critical role in mitochondrial function maintenance. AnxA2 gene knockdown also exacerbated the inhibitory effect of Aβ42 on cell migration. AnxA2 overexpression reduced the inflammatory response induced by Aβ42, while its absence increased pro-inflammatory and decreased anti-inflammatory responses. Furthermore, AnxA2 gene knockdown facilitated apoptosis and decreased autophagy. These results indicated potential pathophysiological roles of AnxA2 in AD.

Abstract Removal of introns from transfer RNA precursors (pre-tRNAs) occurs in all living organisms. This is a vital phase in the maturation and functionality of tRNA. Here we present a 3.2 Å-resolution cryo-EM structure of an active human tRNA splicing endonuclease complex bound to an intron-containing pre-tRNA. TSEN54, along with the unique regions of TSEN34 and TSEN2, cooperatively recognizes the mature body of pre-tRNA and guides the anticodon-intron stem to the correct position for splicing. We capture the moment when the endonucleases are poised for cleavage, illuminating the molecular mechanism for both 3′ and 5′ cleavage reactions. Two insertion loops from TSEN54 and TSEN2 cover the 3′ and 5′ splice sites, respectively, trapping the scissile phosphate in the center of the catalytic triad of residues. Our findings reveal the molecular mechanism for eukaryotic pre-tRNA recognition and cleavage, as well as the evolutionary relationship between archaeal and eukaryotic TSENs.

Abstract In conjunction with previous studies, we have noted that ferroptosis, as an emerging mode of regulated cell death (RCD), is intimately related to anthracycline pharmacotherapy. Not only does ferroptosis significantly modulate tumour resistance and drug toxicity, which are core links of the relevant chemotherapeutic process, but it also appears to play a conflicting role that has yet to be appreciated. By targeting the dual role of ferroptosis in anthracycline-based chemotherapy, this review aims to focus on the latest findings at this stage, identify the potential associations and provide novel perspectives for subsequent research directions and therapeutic strategies.

Assume that (Y,ρ) is a nontrivial complete metric space, and that (Y,g1,∞) is a time-varying discrete dynamical system (T-VDDS), which is given by sequences (gl)l=1∞ of continuous selfmaps gl:Y→Y. In this paper, for a given Furstenberg family G and a given T-VDDS (Y,g1,∞), G-scrambled pairs of points of the system (Y,g1,∞) (which contains the well-known scrambled pairs) are provided. Some properties of the set of G-scrambled pairs of a given T-VDDS (Y,g1,∞) are studied. Moreover, the generically G-chaotic T-VDDS and the generically strongly G-chaotic T-VDDS are defined. A sufficient condition for a given T-VDDS to be generically strongly G-chaotic is also presented.

The steel plate shear wall (SPSW) coupled with steel side columns (SSCs) through steel coupling beams, or the SPSW–SSC coupled structural system, is a novel lateral force resisting system that introduces coupling mechanism to the isolated SPSW pier. To simplify the complex iteration of the conventional seismic design procedure and obtain the favorable plasticity development and distribution pattern determined by the coupling mechanism, the energy-balance concept and the plastic design method are combined to develop the energy-balance-based plastic design (EBPD) method for the SPSW–SSC coupled system with the consideration of the degradation of hysteretic behavior. Twelve SPSW–SSC coupled system prototype cases with different story numbers and coupling ratios (CRs) were designed and numerically modeled to simulate the main seismic behavior. The pushover analyses and the incremental dynamic analyses were further carried out to examine the lateral load capacity and deformation relationships and the seismic fragility curves with respect to the performance levels quantified by the maximum interstory drift ratios. The analysis results prove that the coupling mechanism can be realized in the SPSW–SSC coupled system with preferred yielding sequence and plasticity distribution mode. The influences of story number and CR on the lateral load capacity curves are revealed. The seismic fragility analysis results indicate the exceeding probability of the limit states corresponding to different performance levels with the consideration of the influences of story number and CR, which further proves the effectiveness of the proposed EBPD methods in terms of the realization of the coupling mechanism and the earthquake collapse safety of the SPSW–SSC coupled structural system.

Abstract Osteosarcoma (OS) is the most common primary solid malignant tumour of bone, with rapid progression and a very poor prognosis. Iron is an essential nutrient that makes it an important player in cellular activities due to its inherent ability to exchange electrons, and its metabolic abnormalities are associated with a variety of diseases. The body tightly regulates iron content at the systemic and cellular levels through various mechanisms to prevent iron deficiency and overload from damaging the body. OS cells regulate various mechanisms to increase the intracellular iron concentration to accelerate proliferation, and some studies have revealed the hidden link between iron metabolism and the occurrence and development of OS. This article briefly describes the process of normal iron metabolism, and focuses on the research progress of abnormal iron metabolism in OS from the systemic and cellular levels.

Abstract Ferroptosis is a neoteric model of regulated cell death that shows great potential for the understanding of tumor immunology and as a target for therapy. The present study aimed to identify ferroptosis-related differentially expressed genes (DEGs) in glioma and to explore their value through systematic analysis. Ferroptosis-related DEGs were identified through the Gene Expression Omnibus database in combination with the FerrDb database and analyzed in the Genotype-Tissue Expression database and The Cancer Genome Atlas database. Possible signaling pathways involved were explored by construction of enrichment analysis and protein–protein interaction of these DEGs. Potential regulation of the immune microenvironment, immune checkpoint and chemokine was postulated by immune analysis. A prognosis model for glioma was developed using survival analysis, exhibited by the nomogram and evaluated by the calibration curve. The prognostic value of the model was validated by using an independent cohort. A total of 15 ferroptosis-related DEGs were identified, including 7 down-regulated and 8 up-regulated, with ATP6V1G2, GABARAPL1 and GOT1 as hub genes. The expression of all 3 hub genes was positively correlated with T follicular helper cells and natural killer CD56bright cells. These hub genes were negatively correlated with the macrophage cell type as well as B7H3, PDCD1, LAG3 and CXCL16, CXCR4, CCR5. Low expression of all 3 hub genes was associated with poor prognosis in glioma cases. ATP6V1G2 might be an independent prognostic factor and, as such, a high-precision prognostic model of glioma was constructed. We identified novel ferroptosis-related genes with clinical value in glioma and revealed their possible tumor immune relevance. Furthermore, in glioma, we pinpointed underlying critical elements of the chemokine, immune microenvironment and immune checkpoint, and were able to develop a predictive model of prognosis.

This paper focuses on the relationship between a non-autonomous discrete dynamical system (NDDS) (H,f1,∞) and its induced set-valued discrete dynamical systems (K(H),f¯1,∞). Specifically, it explores the chaotic properties of these systems. The main finding is that f1,∞ is Devaney chaotic if and only if f¯1,∞ is Devaney chaotic in we-topology. The paper also provides similar conclusions for weak mixing, mixing, mild mixing, chain-transitivity, and chain-mixing in non-autonomous set-valued discrete dynamical systems (NSDDSs). Additionally, the paper proves that weak mixing implies sensitivity in NSDDSs.

Abstract Osteosarcoma (OS) is the most common bone-derived tumor, and chemoresistance is a pivotal factor in the poor prognosis of patients with OS. Ferroptosis, as an emerging modality of regulated cell death, has demonstrated potential value in tumor chemoresistance studies. Through the gene expression omnibus database in conjunction with the FerrDb database, we identified novel ferroptosis-related differentially expressed genes (DEGs) involving chemoresistance in OS patients. Subsequently, enrichment analysis, protein–protein interaction network analysis and survival analysis were performed sequentially to recognize the hub genes and ultimately to construct a predictive model. The model constructed from the TARGET database was exhibited in a nomogram and assessed by calibration curves. The prognostic value of the model and hub genes was validated separately by an independent cohort. Twenty-two ferroptosis-related DEGs were identified, including 16 up-regulated and 6 down-regulated. Among them, expressions of CBS, COCS1, EGFR, as hub genes, were significantly associated with the prognosis of OS patients and were evidenced as independent prognostic factors. An efficient prognostic model covering hub gene expressions and clinical variables was developed and validated. Combining the results of hub genes in differential analysis, the actions of hub genes in ferroptosis, and the prognostic relevance of hub genes in patients, we revealed that CBS, SOCS1 and EGFR might play essential roles in OS and its chemoresistance with potential research and clinical value.

Purpose: Proximal femoral replacement (PFR) for oncology patients is gaining interest as a limb salvage operation due to its obvious advantages. However, almost all hip replacement surgeries including PFR, are faced with the challenge of how to reconstruct the functional musculature in an optimal way. To address the challenge, we have developed an innovative eggshell procedure and through this study we aim to investigate the specific efficacy of the procedure. Methods: A total of 44 tumor patients with PFR surgery were incorporated into the study, including 12 who underwent the eggshell procedure and 32 who did not. General characteristics, short-term indicators, long-term indicators and complication outcomes were compared successively between the two groups of patients. Results: No significant differences were identified in general characteristics between the two groups. Overall, in terms of both short-term and long-term indicators, the patients with eggshell procedure performed significantly superior to the patients without it. Moreover, the eggshell procedure significantly reduced the incidence of associated complications, including prosthesis dislocation and hip pain. Conclusions: Our eggshell procedure is convenient and accessible. On the one hand, it can reduce surgical side injuries without adding additional complications, and on the other it allows to improve joint mobility and life quality while diminishing the incidence of prosthesis dislocation and hip pain. Despite it may still remain limitations, we have reasons to believe that this procedure can be further promoted and applied.

Objective • Papillary thyroid carcinoma (PTC) metastasis to the retropharyngeal lymph node (RPLN) is rare but clinically significant due to its implications for patient prognosis and treatment strategies. This study aims to investigate the risk factors and prognosis associated with this uncommon metastasis. Methods • We conducted a retrospective case-control study involving 34 PTC patients with RPLN metastasis treated between January 2007 and December 2017. These patients were compared with a control group of 68 PTC patients with lateral lymph node metastasis but no RPLN involvement, selected randomly from those treated between January 2010 and December 2012. Inclusion criteria included confirmed PTC diagnosis, documented RPLN metastasis, and comprehensive follow-up data. Data collection encompassed preoperative examinations, surgical treatments, and follow-up outcomes. Statistical analyses were performed using SPSS 19, with survival analysis conducted via the Kaplan-Meier method and the Log-rank test for single-factor analysis. Results • Among the research group, only 7 patients were initially treated, while 27 had a history of thyroidectomy. The average time from initial thyroidectomy to RPLN metastasis was 93.1 months. Imaging methods such as CT scan, MRI, and 131I-SPECT/CT demonstrated high sensitivity in detecting RPLN metastasis. The 5-year survival rate was 77.5%. Patients with RPLN metastasis exhibited higher rates of tumor dedifferentiation, distant metastasis, and higher central lymph node density compared to the control group. Conclusions • RPLN metastasis in PTC, though rare, should be considered during follow-up, particularly for patients with tumor dedifferentiation, glandular dissemination, and distant metastasis. Routine ultrasonography may miss these metastases; hence, periodic CT scans, MRI, or 131I-SPECT/CT are recommended. Despite the advanced disease stage at diagnosis, active treatment, including surgical resection via the transcervical approach, can result in a favorable prognosis. Metastasis to lymph nodes below the hyoid plane indicates a poorer prognosis. [ABSTRACT FROM AUTHOR]