Cep57 regulates human centrosomes through multivalent interactions.

Human Cep57 is a coiled-coil scaffold at the pericentriolar matrix (PCM), controlling centriole duplication and centrosome maturation for faithful cell division. Genetic truncation mutations of Cep57 are associated with the mosaic-variegated aneuploidy (MVA) syndrome. During interphase, Cep57 forms a complex with Cep63 and Cep152, serving as regulators for centrosome maturation. However, the molecular interplay of Cep57 with these essential scaffolding proteins remains unclear. Here, we demonstrate that Cep57 undergoes liquid-liquid phase separation (LLPS) driven by three critical domains (NTD, CTD, and polybasic LMN). In vitro Cep57 condensates catalyze microtubule nucleation via the LMN motif-mediated tubulin concentration. In cells, the LMN motif is required for centrosomal microtubule aster formation. Moreover, Cep63 restricts Cep57 assembly, expansion, and microtubule polymerization activity. Overexpression of competitive constructs for multivalent interactions, including an MVA mutation, leads to excessive centrosome duplication. In Cep57-depleted cells, self-assembly mutants failed to rescue centriole disengagement and PCM disorganization. Thus, Cep57's multivalent interactions are pivotal for maintaining the accurate structural and functional integrity of human centrosomes.

HyperTMO: a trusted multi-omics integration framework based on hypergraph convolutional network for patient classification.

MOTIVATION: The rapid development of high-throughput biomedical technologies can provide researchers with detailed multi-omics data. The multi-omics integrated analysis approach based on machine learning contributes a more comprehensive perspective to human disease research. However, there are still significant challenges in representing single-omics data and integrating multi-omics information. RESULTS: This article presents HyperTMO, a Trusted Multi-Omics integration framework based on Hypergraph convolutional network for patient classification. HyperTMO constructs hypergraph structures to represent the association between samples in single-omics data, then evidence extraction is performed by hypergraph convolutional network, and multi-omics information is integrated at an evidence level. Last, we experimentally demonstrate that HyperTMO outperforms other state-of-the-art methods in breast cancer subtype classification and Alzheimer's disease classification tasks using multi-omics data from TCGA (BRCA) and ROSMAP datasets. Importantly, HyperTMO is the first attempt to integrate hypergraph structure, evidence theory, and multi-omics integration for patient classification. Its accurate and robust properties bring great potential for applications in clinical diagnosis. AVAILABILITY AND IMPLEMENTATION: HyperTMO and datasets are publicly available at https://github.com/ippousyuga/HyperTMO.

Reversible and bidirectional signaling of notch ligands.

The Notch signaling pathway is a direct cell-cell communication system involved in a wide variety of biological processes, and its disruption is observed in several pathologies. The pathway is comprised of a ligand-expressing (sender) cell and a receptor-expressing (receiver) cell. The canonical ligands are members of the Delta/Serrate/Lag-1 (DSL) family of proteins. Their binding to a Notch receptor in a neighboring cell induces a conformational change in the receptor, which will undergo regulated intramembrane proteolysis (RIP), liberating the Notch intracellular domain (NICD). The NICD is translocated to the nucleus and promotes gene transcription. It has been demonstrated that the ligands can also undergo RIP and nuclear translocation, suggesting a function for the ligands in the sender cell and possible bidirectionality of the Notch pathway. Although the complete mechanism of ligand processing is not entirely understood, and its dependence on Notch receptors has not been ruled out. Also, ligands have autonomous functions beyond Notch activation. Here we review the concepts of reverse and bidirectional signalization of DSL proteins and discuss the characteristics that make them more than just ligands of the Notch pathway.

Advances in the Application of Microneedles in the Treatment of Local Organ Diseases.

In recent years, microneedles (MNs) have attracted a lot of attention due to their microscale sizes and high surface area (500-1000 µm in length), allowing pain-free and efficient drug delivery through the skin. In addition to the great success of MNs based transdermal drug delivery, especially for skin diseases, increasing studies have indicated the expansion of MNs to diverse nontransdermal applications, including the delivery of therapeutics for hair loss, ocular diseases, and oral mucosal. Here, the current treatment of hair loss, eye diseases, and oral disease is discussed and an overview of recent advances in the application of MNs is provided for these three noncutaneous localized organ diseases. Particular emphasis is laid on the future trend of MNs technology development and future challenges of expanding the generalizability of MNs.

Upregulation of IQGAP2 by EBV transactivator Rta and its influence on EBV life cycle.

Epstein-Barr virus (EBV) is a human oncogenic γ-herpesvirus that establishes persistent infection in more than 90% of the world's population. EBV has two life cycles, latency and lytic replication. Reactivation of EBV from latency to the lytic cycle is initiated and controlled by two viral immediate-early transcription factors, Zta and Rta, encoded by BZLF1 and BRLF1, respectively. In this study, we found that IQGAP2 expression was elevated in EBV-infected B cells and identified Rta as a viral gene responsible for the IQGAP2 upregulation in both B cells and nasopharyngeal carcinoma cell lines. Mechanistically, we showed that Rta increases IQGAP2 expression through direct binding to the Rta-responsive element in the IQGAP2 promoter. We also demonstrated the direct interaction between Rta and IQGAP2 as well as their colocalization in the nucleus. Functionally, we showed that the induced IQGAP2 is required for the Rta-mediated Rta promoter activation in the EBV lytic cycle progression and may influence lymphoblastoid cell line clumping morphology through regulating E-cadherin expression. IMPORTANCE Elevated levels of antibodies against EBV lytic proteins and increased EBV DNA copy numbers in the sera have been reported in patients suffering from Burkitt's lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma, indicating that EBV lytic cycle progression may play an important role in the pathogenesis of EBV-associated diseases and highlighting the need for a more complete mechanistic understanding of the EBV lytic cycle. Rta acts as an essential transcriptional activator to induce lytic gene expression and thus trigger EBV reactivation. In this study, scaffolding protein IQGAP2 was found to be upregulated prominently following EBV infection via the direct binding of Rta to the RRE in the IQGAP2 promoter but not in response to other biological stimuli. Importantly, IQGAP2 was demonstrated to interact with Rta and promote the EBV lytic cycle progression. Suppression of IQGAP2 was also found to decrease E-cadherin expression and affect the clumping morphology of lymphoblastoid cell lines.

Type I Interferon Orchestrates Demand-Adapted Monopoiesis during Influenza A Virus Infection via STAT1-Mediated Upregulation of Macrophage Colony-Stimulating Factor Receptor Expression.

Whether and how a local virus infection affects the hematopoietic system in the bone marrow is largely unknown, unlike with systemic infection. In this study, we showed that influenza A virus (IAV) infection leads to demand-adapted monopoiesis in the bone marrow. The beta interferon (IFN-ß) promoter stimulator 1 (IPS-1)-type I IFN-IFN-α receptor 1 (IFNAR1) axis-mediated signaling was found to induce the emergency expansion of the granulocyte-monocyte progenitor (GMP) population and upregulate the expression of the macrophage colony-stimulating factor receptor (M-CSFR) on bipotent GMPs and monocyte progenitors via the signal transducer and activator of transcription 1 (STAT1), leading to a scaled-back proportion of granulocyte progenitors. To further address the influence of demand-adapted monopoiesis on IAV-induced secondary bacterial infection, IAV-infected wild-type (WT) and Stat1-/- mice were challenged with Streptococcus pneumoniae. Compared with WT mice, Stat1-/- mice did not demonstrate demand-adapted monopoiesis, had more infiltrating granulocytes, and were able to effectively eliminate the bacterial infection. IMPORTANCE Our findings show that influenza A virus infection induces type I interferon (IFN)-mediated emergency hematopoiesis to expand the GMP population in the bone marrow. The type I IFN-STAT1 axis was identified as being involved in mediating the viral-infection-driven demand-adapted monopoiesis by upregulating M-CSFR expression in the GMP population. As secondary bacterial infections often manifest during a viral infection and can lead to severe or even fatal clinical complications, we further assessed the impact of the observed monopoiesis on bacterial clearance. Our results suggest that the resulting decrease in the proportion of granulocytes may play a role in diminishing the IAV-infected host's ability to effectively clear secondary bacterial infection. Our findings not only provide a more complete picture of the modulatory functions of type I IFN but also highlight the need for a more comprehensive understanding of potential changes in hematopoiesis during local infections to better inform clinical interventions.

A new species of Populus and the extensive hybrid speciation arising from it on the Qinghai-Tibet Plateau.

While the diversity of species formation is broadly acknowledged, significant debate exists regarding the universal nature of hybrid species formation. Through an 18-year comprehensive study of all Populus species on the Qinghai-Tibet Plateau, 23 previously recorded species and 8 new species were identified. Based on morphological characteristics, these can be classified into three groups: species in section Leucoides, species with large leaves, and species with small leaves in section Tacamahaca. By conducting whole-genome re-sequencing of 150 genotypes from these 31 species, 2.28 million single nucleotide polymorphisms (SNPs) were identified. Phylogenetic analysis utilizing these SNPs not only revealed a highly intricate evolutionary network within the large-leaf species of section Tacamahaca but also confirmed that a new species, P. curviserrata, naturally hybridized with P. cathayana, P. szechuanica, and P. ciliata, resulting in 11 hybrid species. These findings indicate the widespread occurrence of hybrid species formation within this genus, with hybridization serving as a key evolutionary mechanism for Populus on the plateau. A novel hypothesis, "Hybrid Species Exterminating Their Ancestral Species (HSEAS)," is introduced to explain the mechanisms of hybrid species formation at three different scales: the entire plateau, the southeastern mountain region, and individual river valleys.

Nonlinear dynamics of an interband cascade laser with optical injection.

This work reports the nonlinear dynamics of a mid-infrared interband cascade laser (ICL) subject to optical injection. It is shown that the stable locking regime is asymmetric and broadens with increasing injection strength. Outside the locking regime, the ICL mostly produces period-one oscillations. However, three categories of periodic pulse oscillations are observed in the vicinity of the Hopf bifurcation and the saddle-node bifurcation. In particular, it is found that the ICL generates broadband chaos at a near-threshold pump current, and the chaos bandwidth is over 300 MHz.

The SMAC mimetic GDC-0152 is a direct ABCB1-ATPase activity modulator and BIRC5 expression suppressor in cancer cells.

Upregulation of the multidrug efflux pump ABCB1/MDR1 (P-gp) and the anti-apoptotic protein BIRC5/Survivin promotes multidrug resistance in various human cancers. GDC-0152 is a DIABLO/SMAC mimetic currently being tested in patients with solid tumors. However, it is still unclear whether GDC-0152 is therapeutically applicable for patients with ABCB1-overexpressing multidrug-resistant tumors, and the molecular mechanism of action of GDC-0152 in cancer cells is still incompletely understood. In this study, we found that the potency of GDC-0152 is unaffected by the expression of ABCB1 in cancer cells. Interestingly, through in silico and in vitro analysis, we discovered that GDC-0152 directly modulates the ABCB1-ATPase activity and inhibits ABCB1 multidrug efflux activity at sub-cytotoxic concentrations (i.e., 0.25×IC50 or less). Further investigation revealed that GDC-0152 also decreases BIRC5 expression, induces mitophagy, and lowers intracellular ATP levels in cancer cells at low cytotoxic concentrations (i.e., 0.5×IC50). Co-treatment with GDC-0152 restored the sensitivity to the known ABCB1 substrates, including paclitaxel, vincristine, and YM155 in ABCB1-expressing multidrug-resistant cancer cells, and it also restored the sensitivity to tamoxifen in BIRC5-overexpressing tamoxifen-resistant breast cancer cells in vitro. Moreover, co-treatment with GDC-0152 restored and potentiated the anticancer effects of paclitaxel in ABCB1 and BIRC5 co-expressing xenograft tumors in vivo. In conclusion, GDC-0152 has the potential for use in the management of cancer patients with ABCB1 and BIRC5-related drug resistance. The findings of our study provide essential information to physicians for designing a more patient-specific GDC-0152 clinical trial program in the future.

Broadband chaos of an interband cascade laser with a 6-GHz bandwidth.

Near-infrared semiconductor lasers subject to optical feedback usually produce chaos with a broad bandwidth of a few GHz. However, the reported mid-infrared interband cascade lasers (ICLs) only show chaos with a limited bandwidth below 1 GHz. Here we show that an ICL with optical feedback is able to generate broadband chaos as well. The mid-infrared chaos exhibits a remarkable bandwidth of about 6 GHz, which is comparable to that of the near-infrared counterpart. In addition, the spectral coverage in the electrical domain reaches as high as 17.7 GHz. It is found that the chaos bandwidth generally broadens with increasing feedback ratio and/or increasing pump current of the laser, while it is insensitive to the feedback length.

Biallelic COQ4 Variants in Hereditary Spastic Paraplegia: Clinical and Molecular Characterization.

BACKGROUND: Hereditary spastic paraplegias (HSP) are neurologic disorders characterized by progressive lower-extremity spasticity. Despite the identification of several HSP-related genes, many patients lack a genetic diagnosis. OBJECTIVES: The aims were to confirm the pathogenic role of biallelic COQ4 mutations in HSP and elucidate the clinical, genetic, and functional molecular features of COQ4-associated HSP. METHODS: Whole exome sequences of 310 index patients with HSP of unknown cause from three distinct populations were analyzed to identify potential HSP causal genes. Clinical data obtained from patients harboring candidate causal mutations were examined. Functional characterization of COQ4 variants was performed using bioinformatic tools, single-cell RNA sequencing, biochemical assays in cell lines, primary fibroblasts, induced pluripotent stem cell-derived pyramidal neurons, and zebrafish. RESULTS: Compound heterozygous variants in COQ4, which cosegregated with HSP in pedigrees, were identified in 7 patients from six unrelated families. Patients from four of the six families presented with pure HSP, whereas probands of the other two families exhibited complicated HSP with epilepsy or with cerebellar ataxia. In patient-derived fibroblasts and COQ4 knockout complementation lines, stable expression of these missense variants exerted loss-of-function effects, including mitochondrial reactive oxygen species accumulation, decreased mitochondrial membrane potential, and lower ubiquinone biosynthesis. Whereas differentiated pyramidal neurons expressed high COQ4 levels, coq4 knockdown zebrafish displayed severe motor dysfunction, reflecting motor neuron dysregulation. CONCLUSIONS: Our study confirms that loss-of-function, compound heterozygous, pathogenic COQ4 variants are causal for autosomal recessive pure and complicated HSP. Moreover, reduced COQ4 levels attributable to variants correspond with decreased ubiquinone biosynthesis, impaired mitochondrial function, and higher phenotypic disease severity. © 2023 International Parkinson and Movement Disorder Society.

The biocontrol potentials of rhizospheric bacterium Bacillus velezensis K0T24 against mulberry bacterial wilt disease.

Mulberry bacterial wilt disease, caused by Ralstonia pseudosolanacearum, is a devastating soil-borne disease in the silk-mulberry-related industry. In this study, through high-throughput sequencing, we compared the rhizosphere bacterial composition of the mulberry-resistant cultivar (K10) and susceptible cultivar (G12), confirming Bacillus as a genus-level biomarker for K10. Next, twelve Bacillus spp. isolates, derived from the rhizosphere of K10, were screened for their antagonistic activity against R. pseudosolanacearum. The isolate showing strong antagonism was identified as B. velezensis K0T24 and selected for further analysis. The fermentation supernatant of B. velezensis K0T24 significantly inhibited the growth of R. pseudosolanacearum (82.47%) and the expression of its pathogenic genes. Using B. velezensis K0T24 in mulberry seedlings also increased defense enzyme activities and achieved a control efficacy of up to 55.17% against mulberry bacterial wilt disease. Collectively, our findings demonstrate the potential of B. velezensis K0T24 in suppressing mulberry bacterial wilt disease.

Mitofilin in cardiovascular diseases: Insights into the pathogenesis and potential pharmacological interventions.

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.

Higher tumor mutational burden is associated with inferior outcomes among pediatric patients with neuroblastoma.

INTRODUCTION: Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. Our aim was to identify prognostic genetic markers for patients with neuroblastoma, who were treated with the Taiwan Pediatric Oncology Group (TPOG) neuroblastoma N2002 protocol, to improve risk stratification and inform treatment. METHODS: Our analysis was based on 53 primary neuroblastoma specimens, diagnosed pre-chemotherapy, and 11 paired tumor relapse specimens. Deep sequencing of 113 target genes was performed using a custom panel. Multiplex ligation-dependent probe amplification was performed to identify clinical outcomes related to copy-number variations. RESULTS: We identified 128 variations associated with survival, with the number of variations being higher in the relapse than that in the diagnostic specimen (p = .03). The risk of event and mortality was higher among patients with a tumor mutational burden ≥10 than that in patients with a lower burden (p < .0001). Multivariate analysis identified tumor mutational burden, MYCN amplification, and chromosome 3p deletion as significant prognostic factors, independent of age at diagnosis, sex, and tumor stage. The 5-year event-free survival and overall survival rate was lower among patients with high tumor burden than in patients with low tumor burden. Furthermore, there was no survival of patients with an ALK F1147L variation at 5 years after diagnosis. CONCLUSIONS: Genome sequencing to determine the tumor mutational burden and ALK variations can improve the risk classification of neuroblastoma and inform treatment.

A xonotlite nanofiber bioactive 3D-printed hydrogel scaffold based on osteo-/angiogenesis and osteoimmune microenvironment remodeling accelerates vascularized bone regeneration.

BACKGROUND: Coordination between osteo-/angiogenesis and the osteoimmune microenvironment is essential for effective bone repair with biomaterials. As a highly personalized and precise biomaterial suitable for repairing complex bone defects in clinical practice, it is essential to endow 3D-printed scaffold the above key capabilities. RESULTS: Herein, by introducing xonotlite nanofiber (Ca6(Si6O17) (OH)2, CS) into the 3D-printed silk fibroin/gelatin basal scaffold, a novel bone repair system named SGC was fabricated. It was noted that the incorporation of CS could greatly enhance the chemical and mechanical properties of the scaffold to match the needs of bone regeneration. Besides, benefiting from the addition of CS, SGC scaffolds could accelerate osteo-/angiogenic differentiation of bone mesenchymal stem cells (BMSCs) and meanwhile reprogram macrophages to establish a favorable osteoimmune microenvironment. In vivo experiments further demonstrated that SGC scaffolds could efficiently stimulate bone repair and create a regeneration-friendly osteoimmune microenvironment. Mechanistically, we discovered that SGC scaffolds may achieve immune reprogramming in macrophages through a decrease in the expression of Smad6 and Smad7, both of which participate in the transforming growth factor-ß (TGF-ß) signaling pathway. CONCLUSION: Overall, this study demonstrated the clinical potential of the SGC scaffold due to its favorable pro-osteo-/angiogenic and osteoimmunomodulatory properties. In addition, it is a promising strategy to develop novel bone repair biomaterials by taking osteoinduction and osteoimmune microenvironment remodeling functions into account.

Quercetin-loaded mesoporous nano-delivery system remodels osteoimmune microenvironment to regenerate alveolar bone in periodontitis via the miR-21a-5p/PDCD4/NF-κB pathway.

BACKGROUND: Impaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in the pathogenesis of the alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack of ideal therapeutic strategies for periodontitis that can regenerate the alveolar bone while remodeling the osteoimmune microenvironment. Quercetin, as a monomeric flavonoid, has multiple pharmacological activities, such as pro-regenerative, anti-inflammatory, and immunomodulatory effects. Despite its vast spectrum of pharmacological activities, quercetin's clinical application is limited due to its poor water solubility and low bioavailability. RESULTS: In this study, we fabricated a quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with the function of continuously releasing quercetin, which could better promote the bone regeneration and regulate the immune microenvironment in the alveolar bone defect with periodontitis compared to pure MBG treatment. In particular, this nano-delivery system effectively decreased injection frequency of quercetin while yielding favorable therapeutic results. In view of the above excellent therapeutic effects achieved by the sustained release of quercetin, we further investigated its therapeutic mechanisms. Our findings indicated that under the periodontitis microenvironment, the intervention of quercetin could restore the osteo-/angiogenic capacity of periodontal ligament stem cells (PDLSCs), induce immune regulation of macrophages and exert an osteoimmunomodulatory effect. Furthermore, we also found that the above osteoimmunomodulatory effects of quercetin via macrophages could be partially blocked by the overexpression of a key microRNA--miR-21a-5p, which worked through inhibiting the expression of PDCD4 and activating the NF-κB signaling pathway. CONCLUSION: In summary, our study shows that quercetin-loaded mesoporous nano-delivery system has the potential to be a therapeutic approach for reconstructing alveolar bone defects in periodontitis. Furthermore, it also offers a new perspective for treating alveolar bone defects in periodontitis by inhibiting the expression of miR-21a-5p in macrophages and thereby creating a favorable osteoimmune microenvironment.

Synthesis and in†vitro Anti-Inflammatory Activity of Novel Dendrobine Amide/Sulfonamide Derivatives.

A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti-inflammatory properties. However, due to its poor anti-inflammatory properties, its clinical use is limited. Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti-inflammatory activities in vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96 µM. Western blot research revealed that 14 decreased the concentration-dependent expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation-associated proteins COX-2 and INOS to compound 14.

Structurally Diverse Coumarins from Peucedanum praeruptorum and their Anti-Inflammatory Activities via NF-κB Signaling Pathway.

The phytochemical study of Peucedanum praeruptorum led to the isolation of twenty-five coumarins (1-25). Of which, (±) praeruptol A (±1), one pair of previous undescribed seco-coumarin enantiomers were obtained. Their structures were established according to HR-ESI-MS, NMR, X-ray single crystal diffraction analysis, as well as ECD calculation. All compounds were tested for anti-inflammatory activity in the RAW264.7 macrophage model, and eight compounds (7-10, and 13-16) exhibited significant inhibitory effects with IC50 values ranging from 9.48 to 34.66 µM. Among them, compound 7 showed the strongest inhibitory effect, which significantly suppressed the production of IL-6, IL-1ß, and TNF-α, as well as iNOS and COX-2 in a concentration-dependent manner. Further investigated results showed that compound 7 exerted an anti-inflammatory effect via the NF-κB signaling pathway.

The association between systemic inflammatory response index and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.

Quantitative comparison of 2D and 3D monitoring dimensions in fish behavior analysis.

To improve the accuracy and efficiency of fish behavior assessment, this paper focuses on quantitatively exploring the variations and relationships between different monitoring dimensions. A systematic comparison was conducted between 3D and 2D behavioral factors using an infrared tracing system, during both day and night. Significant differences in swimming distance were observed among the different monitoring methods, as determined by two-way ANOVA and Tukey's test. A correction was applied to account for the disparities observed in 2D swimming distance, ensuring accurate measurements. These findings present a cost-effective and efficient approach for obtaining precise 3D distance data. Additionally, a kinematic factor called the "number of U-turns" was proposed to provide a more intuitive characterization of directional changes in fish swimming. Significant differences were observed between 2D and 3D data, with higher percentages of false U-turn counts and missing U-turn counts compared to correct counts in the 2D view. These findings suggest that reducing the monitoring dimension may impact the accurate estimation of swimming motion, potentially resulting in inaccurate outcomes. Finally, the statistical analyses of the non-linear properties of fractal dimension revealed significant differences among the various monitoring methods. This conclusion has practical implications for biologists and physicists, enabling them to improve the accuracy of behavioral phenotyping for organisms exhibiting 3D motion.