Minghui Tan

Background: Pulmonary collapse is a common and serious respiratory condition, but there is no dedicated bedside tool to estimate prognosis. This study aimed to develop a nomogram to predict 28-day mortality in patients with pulmonary collapse. Methods: We extracted data for patients with pulmonary collapse from MIMIC-III, identified predictors using regression analyses, and used MIMIC-IV for temporal validation. We then built a nomogram based on the selected predictors. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), AUC comparisons using the DeLong test, reclassification (NRI and IDI), calibration (calibration curves, calibration slope, and Brier score), and decision curve analysis (DCA). Results: A total of 4,088 patients with pulmonary collapse were included in the study. Logistic regression analysis identified twelve independent predictive factors associated with 28-day mortality: age (OR = 1.01, P =0.040), married status (OR =0 .63, P =0 .040), Glasgow Coma Scale score (OR = 0.94, P = 0.02), creatinine (OR = 0.82, P = 0.03), chloride ions (OR = 0.85, P = 0.03), sodium ions (OR = 1.19, P = 0.02), blood urea nitrogen (OR = 1.02, P < 0.001), white blood cell count (OR = 1.04, P < 0.001), heart rate (OR = 1.02, P = 0.02), respiratory rate (OR = 1.05, P = 0.03), temperature (OR = 0.54, P < 0.001), and metastatic cancer (OR = 6.66, P < 0.001). The nomogram showed moderate discrimination and consistently higher AUC than Age+Gender, SOFA, and SAPSII across cohorts. Conclusion: This study identified factors associated with 28-day mortality in patients with pulmonary collapse and developed a nomogram for early risk stratification.

Objective: This study aimed to explore whether serum amyloid A (SAA) triggers an inflammatory response by activating the NOD-like receptor protein 3 (NLRP3) pathway, resulting in hippocampal neuron apoptosis and cognitive impairments in mice. Methods: SAA was applied to BV-2 and HT22 cells to determine the optimal concentration and duration for stimulation. Inflammation-related and differentially expressed genes were identified through mRNA transcriptome sequencing (RNA-seq). Furthermore, apoptosis in hippocampal neurons was detected following treatment with the SAA-pretreated BV-2 cell culture medium. Furthermore, a postoperative cognitive dysfunction (POCD) mouse model was established using internal fixation of tibial fractures, followed by intraperitoneal injection of SAA and MCC950 (a selective NLRP3 inhibitor). Behavioral tests were then conducted to evaluate cognitive dysfunction in mice. Results: mRNA transcriptome sequencing revealed that SAA led to the upregulation of inflammatory factors, including interleukin-1β (IL-1β). In cultured BV-2 cells, SAA treatment activated the NLRP3 signaling pathway. Additionally, the supernatants from SAA-treated BV-2 cells significantly increased the apoptotic rate in HT22 cells and primary hippocampal neurons. Pharmacological inhibition of NLRP3 using MCC950 reduced this apoptosis. The tibial fracture intramedullary nailing technique effectively established a mouse model of POCD, with SAA administration increasing inflammatory factor levels in the hippocampus of POCD mice and impairing their cognitive abilities. However, treatment with MCC950 significantly alleviated the cognitive dysfunction induced by SAA in the POCD mice. Conclusion: SAA treatment triggers an inflammatory response through the activation of NLRP3, which subsequently causes hippocampal neuron apoptosis and impairs cognitive function in POCD mice. This dysfunction can be reversed by inhibiting NLRP3 with the administration of MCC950.

Neurite outgrowth is critically controlled by calcium influx-mediated cytoskeleton dynamics. Spastin, a AAA ATPase microtubule-severing protein, also plays an important role in neurite outgrowth. However, the detailed mechanisms underlying posttranscriptional fine-tuning spastin activity, particularly in the context of calcium signaling, remain elusive. Here, we identified that the Ca ²⁺ /calmodulin-dependent protein kinase II beta (CaMKIIβ) isoform acted as an upstream kinase to mediate the phosphorylation of spastin. CaMKIIβ interacted with and phosphorylated spastin on Ser233 and Ser562 amino acids. Moreover, CaMKIIβ-mediated phosphorylation reduced the polyubiquitination level of spastin and suppressed its proteasomal degradation. This enhanced protein stability by CaMKIIβ increased the microtubule-severing activity of spastin and coordinately promoted the neurite outgrowth in hippocampal neurons. Inhibition of spastin or CaMKIIβ impaired synaptic activity, as evidenced by reduced frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs). Behaviorally, treatment with spastin or CaMKIIβ inhibitors led to deficits in short-term working memory and spatial learning, as assessed by Y-maze and Morris water maze tests in male mice, respectively. In general, this study unveils a novel mechanism whereby CaMKIIβ-mediated phosphorylation of spastin connects extracellular calcium signaling to the regulation of cytoskeleton dynamics and neurite outgrowth.

JOURNAL/nrgr/04.03/01300535-202604000-00044/figure1/v/2026-04-21T135625Z/r/image-tiff Post-translational modification of spastin enables precise spatiotemporal control of its microtubule severing activity. However, the detailed mechanism by which spastin turnover is regulated in the context of neurite outgrowth remains unknown. Here, we found that spastin interacted with ubiquitin and was significantly degraded by K48-mediated poly-ubiquitination. Cullin3 facilitated spastin degradation and ubiquitination. RING-box protein 1, but not RING-box protein 2, acted synergistically with Cullin3 protein to regulate spastin degradation. Overexpression of Culin3 or BRX1 markedly suppressed spastin expression, and inhibited spastin-mediated microtubule severing and promotion of neurite outgrowth. Moreover, USP14 interacted directly with spastin to mediate its de-ubiquitination. USP14 overexpression significantly increased spastin expression and suppressed its ubiquitination and degradation. Although co-expression of spastin and USP14 did not enhance microtubule severing, it did increase neurite length in hippocampal neurons. Taken together, these findings elucidate the intricate regulatory mechanisms of spastin turnover, highlighting the roles of the Cullin-3–Ring E3 ubiquitin ligase complex and USP14 in orchestrating its ubiquitination and degradation. The dynamic interplay between these factors governs spastin stability and function, ultimately influencing microtubule dynamics and neuronal morphology. These insights shed light on potential therapeutic targets for neurodegenerative disorders associated with spastin defects.

Background: Subendocardial myocardial infarction (SEMI) represents a more severe form of myocardial infarction. Currently, there lacks a comprehensive clinical index for predicting mortality in cases of subendocardial myocardial infarction. The objective of our study was to develop and evaluate a nomogram for predicting the 28-day risk of mortality among patients with SEMI.Methods: Patients diagnosed with subendocardial infarction were identified from the MIMIC-III database based on ICD-9 codes. Independent risk factors were screened utilizing the least absolute shrinkage and selection operator (LASSO) method alongside multivariate logistic regression. These identified risk factors were then employed to construct a nomogram aimed at predicting the 28-day mortality risk in patients with subendocardial infarction. The performance of the nomogram was evaluated by the Area Under the Curve (AUC), calibration curves, Hosmer-Lemeshow test, Integrated Discrimination Improvement (IDI), Net Reclassification Improvement (NRI), Decision Curve Analysis (DCA).Results: A total of 3046 patients with subendocardial infarction were included in the study. Logistic regression analysis revealed that age, GCS score, creatinine level, hematocrit, hemoglobin, international normalized ratio, blood urea nitrogen level, urine output, heart rate, respiratory rate, peripheral oxygen saturation, peripheral vascular disease, diabetes complications, and solid tumors were independent risk factors for 28-day mortality. The AUC values of the nomogram surpassed those of the Acute Physiology Score III (APSIII), Simplified Acute Physiology Score II (SAPSII), and Sequential Organ Failure Assessment (SOFA) scoring systems in both the training and validation cohorts. Calculation of the IDI and NRI, along with DCA analysis, indicated a greater net benefit of the nomogram model.Conclusion: This study successfully identified independent risk factors for 28-day mortality in patients with SEMI. A nomogram model was developed to predict mortality, offering potential assistance in improving the prognosis of SEMI patients.

As a key component of the cytoskeleton, microtubule dynamic provides structural support for neurite outgrowth. Spastin, a microtubule severing enzyme associated with hereditary spastic paraplegia (HSP), is crucial for the growth and branching of neuronal processes. Thus, the activity and function of spastin need to be strictly regulated. However, the mechanism by which spastin protein levels are regulated is still poorly understood. In the current study, we showed that UCHL1 interacted with spastin via mass spectrometry, GST-pulldown and immunoprecipitation assays. Overexpression of UCHL1 decreased the protein level of spastin, while the genetic knockdown of UCHL1 increased that of spastin. CHX chase assay showed that UCHL1 regulated the protein degradation of spastin. Application of proteasome inhibitor MG-132 suppressed UCHL1-mediated spastin degradation. Furthermore, overexpression or knockout of UCHL1 can inhibit or restore spastin-mediated microtubule severing, thereby regulating neuronal length and branch formation. These findings reveal the important regulatory mechanism of UCHL1 on spastin-mediated neurite outgrowth.