Bisphosphoglycerate mutase predicts myocardial dysfunction and adverse outcome in sepsis: an observational cohort study.

BACKGROUND: Sepsis not only causes inflammation, but also damages the heart and increases the risk of death. The glycolytic pathway plays a crucial role in the pathogenesis of sepsis-induced cardiac injury. This study aims to investigate the value of bisphosphoglycerate mutase (BPGM), an intermediate in the glycolytic pathway, in evaluating cardiac injury in septic patients and predicting poor prognosis in sepsis. METHODS: This prospective study included 85 patients with sepsis. Serum BPGM was measured at the time of enrollment, and the patients were divided into a BPGM-positive group (n = 35) and a BPGM-negative group (n = 50) according to their serum BPGM levels. Baseline clinical and echocardiographic parameters, and clinical outcomes were analyzed and compared between the two groups. Kaplan-Meier analysis was used to compare the 28-day survival rate between BPGM-negative and BPGM-positive patients. Multivariate logistic regression analysis was conducted to explore the independent risk factors for 28-day mortality in septic patients. The predictive value of serum BPGM for sepsis-induced myocardial injury and poor prognosis in sepsis was evaluated using receiver operating characteristic (ROC)curve analysis. RESULT: The serum level of BPGM was significantly higher in patients who died within 28 days compared to survivors (p < 0.001). Kaplan-Meier analysis showed that serum BPGM-positive sepsis patients had a significantly shorter 28-day survival time (p < 0.001). Multivariate logistic regression analysis showed that serum BPGM (OR = 9.853, 95%CI 1.844-52.655, p = 0.007) and left ventricular ejection fraction-simpson(LVEF-S) (OR = 0.032, 95% CI 0.002-0.43, p = 0.009) were independent risk factors for 28-day mortality in sepsis patients. Furthermore, BPGM levels was negatively correlated with LVEF-S (p = 0.005) and positively correlated with the myocardial performance (Tei) index (p < 0.001) in sepsis patients. ROC curve analysis showed that serum BPGM was a good predictor of septic myocardial injury and 28-day mortality in sepsis patients. CONCLUSION: The level of BPGM in the serum of sepsis patients can serve as a monitoring indicator for myocardial injury, with its high level indicating the occurrence of secondary myocardial injury events and adverse outcomes in sepsis patients.

Evaluate prognostic accuracy of SOFA component score for mortality among adults with sepsis by machine learning method.

INTRODUCTION: Sepsis has the characteristics of high incidence, high mortality of ICU patients. Early assessment of disease severity and risk stratification of death in patients with sepsis, and further targeted intervention are very important. The purpose of this study was to develop machine learning models based on sequential organ failure assessment (SOFA) components to early predict in-hospital mortality in ICU patients with sepsis and evaluate model performance. METHODS: Patients admitted to ICU with sepsis diagnosis were extracted from MIMIC-IV database for retrospective analysis, and were randomly divided into training set and test set in accordance with 2:1. Six variables were included in this study, all of which were from the scores of 6 organ systems in SOFA score. The machine learning model was trained in the training set and evaluated in the validation set. Six machine learning methods including linear regression analysis, least absolute shrinkage and selection operator (LASSO), Logistic regression analysis (LR), Gaussian Naive Bayes (GNB) and support vector machines (SVM) were used to construct the death risk prediction models, and the accuracy, area under the receiver operating characteristic curve (AUROC), Decision Curve Analysis (DCA) and K-fold cross-validation were used to evaluate the prediction performance of developed models. RESULT: A total of 23,889 patients with sepsis were enrolled, of whom 3659 died in hospital. Three feature variables including renal system score, central nervous system score and cardio vascular system score were used to establish prediction models. The accuracy of the LR, GNB, SVM were 0.851, 0.844 and 0.862, respectively, which were better than linear regression analysis (0.123) and LASSO (0.130). The AUROCs of LR, GNB and SVM were 0.76, 0.76 and 0.67, respectively. K-fold cross validation showed that the average AUROCs of LR, GNB and SVM were 0.757 ± 0.005, 0.762 ± 0.006, 0.630 ± 0.013, respectively. For the probability threshold of 5-50%, LY and GNB models both showed positive net benefits. CONCLUSION: The two machine learning-based models (LR and GNB models) based on SOFA components can be used to predict in-hospital mortality of septic patients admitted to ICU.

Gestational chronic intermittent hypoxia induces hypertension, proteinuria, and fetal growth restriction in mice.

PURPOSE: Pregnant women are predisposed to obstructive sleep apnea (OSA). Based on the fact that OSA is an independent risk factor for hypertension among the general population, we hypothesized that chronic intermittent hypoxia (CIH), as a feature of OSA, may lead to preeclampsia. METHODS: Pregnant and non-pregnant C57BL/6 J mice were exposed to two conditions of chronic intermittent hypoxia: CIH1 (21-5% O2 alternations), CIH2 (21-10% O2 alternations), and room air until day 19. RESULTS: In non-pregnant mice, compared with their respective baseline values, systolic blood pressure (SBP) started to rise from day 14 in the CIH1 group, and SBP rose until day 19 in the CIH2 group. Compared with the pregnant mice exposed to room air, pregnant mice exposed to CIH1 maintained elevated SBP from day 14, accompanied by proteinuria, fetal and placental growth restriction, and a reduction in the number of fetuses. An imbalance between proangiogenic and antiangiogenic factors and impairment of vascular remodeling existed in the placenta of pregnant mice exposed to CIH1. Maternal serum levels of the soluble form of vascular endothelial growth factor receptor-1 were also significantly increased. Pregnant mice exposed to CIH2 seemed to have milder changes than pregnant mice exposed to CIH1. CONCLUSION: Our results demonstrated that gestational CIH may induce gestational hypertension, proteinuria, fetal and placental growth restriction as well as impairments in placental angiogenesis and vascular remodeling.

Identification of early biomarkers of transcriptomics in alveolar macrophage for the prognosis of intubated ARDS patients.

BACKGROUND: Currently, the rate of morbidity and mortality in acute respiratory distress syndrome (ARDS) remains high. One of the potential reasons for the poor and ineffective therapies is the lack of early and credible indicator of risk prediction that would help specific treatment of severely affected ARDS patients. Nevertheless, assessment of the clinical outcomes with transcriptomics of ARDS by alveolar macrophage has not been performed. METHODS: The expression data GSE116560 was obtained from the Gene Expression Omnibus databases (GEO) in NCBI. This dataset consists of 68 BAL samples from 35 subjects that were collected within 48 h of ARDS. Differentially expressed genes (DEGs) of different outcomes were analyzed using R software. The top 10 DEGs that were up- or down-regulated were analyzed using receiver operating characteristic (ROC) analysis. Kaplan-Meier survival analysis within two categories according to cut-off and the value of prediction of the clinical outcomes via DEGs was verified. GO enrichment, KEGG pathway analysis, and protein-protein interaction were also used for functional annotation of key genes. RESULTS: 24,526 genes were obtained, including 235 up-regulated and 292 down-regulated DEGs. The gene ADORA3 was chosen as the most obvious value to predict the outcome according to the ROC and survival analysis. For functional annotation, ADORA3 was significantly augmented in sphingolipid signaling pathway, cGMP-PKG signaling pathway, and neuroactive ligand-receptor interaction. Four genes (ADORA3, GNB1, NTS, and RHO), with 4 nodes and 6 edges, had the highest score in these clusters in the protein-protein interaction network. CONCLUSIONS: Our results show that the prognostic prediction of early biomarkers of transcriptomics as identified in alveolar macrophage in ARDS can be extended for mechanically ventilated critically ill patients. In the long term, generalizing the concept of biomarkers of transcriptomics in alveolar macrophage could add to improving precision-based strategies in the ICU patients and may also lead to identifying improved strategy for critically ill patients.

Optical absorption enhancement in a Si nanohole structure with hexagonal unit cell for solar cell application.

Periodic hexagonal unit cell silicon nanohole (SiNH) structures with different structural dimensions have been fabricated using polystyrene spheres and investigated in terms of their microstructures and optical reflectance. Compared with a planar Si wafer, such structures exhibit much lower reflectance due to the enhanced scattering introduced by the SiNHs. Optical simulation using the finite element method has also been carried out in order to optimize the structural periodicity and hole diameter for maximum light absorption. The optimum structure is found to have a periodicity of 693 nm and hole diameter of 560 nm, and it yields the highest ultimate efficiency of 28.8%.

Design guideline of Si nanohole/PEDOT:PSS hybrid structure for solar cell application.

The finite element method is used to simulate light absorption in periodic hybrid Si nanohole (SiNH)/PEDOT:PSS arrays. The structural periodicity (P) and hole diameter (D) of the hybrid SiNH structure are varied to maximize light absorption. In terms of the solar cell performance under the AM1.5G spectrum, the highest ultimate efficiency achieved is 30.5%, when the D/P ratio is 0.8 and P is 600 nm. We have successfully fabricated the SiNH structure based on a low cost electroless chemical etching approach using a silver catalyst. The SiNH diameters formed vary from ∼200 to 300 nm, with periodicities from ∼300 to 1000 nm. The SiNH structure reveals a low average reflectance of 4% for incident light in the range 300 to 1100 nm.

Predictive factors for cerebrocardiac syndrome in patients with severe traumatic brain injury: a retrospective cohort study.

Background and objective: Cerebrocardiac syndrome (CCS) is a severe complication of severe traumatic brain injury (sTBI) that carries high mortality and disability rates. Early identification of CCS poses a significant clinical challenge. The main objective of this study was to investigate potential risk factors associated with the development of secondary CCS in patients with sTBI. It was hypothesized that elevated right heart Tei index (TI), lower Glasgow Coma Scale (GCS) scores, and elevated cardiac troponin-I (cTnI) levels would independently contribute to the occurrence of CCS in sTBI patients. Methods: A retrospective cohort study was conducted to identify risk factors for CCS secondary to sTBI. One hundred and fifty-five patients were enrolled with sTBI admitted to the hospital between January 2016 and December 2020 and divided them into a CCS group (n = 75) and a non-CCS group (n = 80) based on the presence of CCS. This study involved the analysis and comparison of clinical data from two patient groups, encompassing demographic characteristics, peripheral oxygen saturation (SPO2), neuron-specific enolase (NSE), cardiac troponin-I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), optic nerve sheath diameter (ONSD), cardiac ultrasound, acute physiology and chronic health evaluation (APACHE II) scores, and GCS scores and so on. Multivariate logistic regression was employed to identify independent risk factors for CCS, and receiver operating characteristic (ROC) curves were used to assess their predictive value for CCS secondary to sTBI. Results: The study revealed that 48.4% of sTBI patients developed secondary CCS. In the multivariate analysis model 1 that does not include NT-proBNP and cTnI, ONSD (OR = 2.582, 95% CI: 1.054-6.327, P = 0.038), right heart Tei index (OR = 2.81, 95% CI: 1.288-6.129, P = 0.009), and GCS (OR = 0.212, 95% CI: 0.086-0.521, P = 0.001) were independent risk factors for secondary CCS in sTBI patients. In multivariate analysis model 2 that includes NT-proBNP and cTnI, cTnI (OR = 27.711, 95%CI: 3.086-248.795, P = 0.003), right heart Tei index (OR = 2.736, 95% CI: 1.056-7.091, P = 0.038), and GCS (OR = 0.147, 95% CI: 0.045-0.481, P = 0.002) were independent risk factors for secondary CCS in sTBI patients. The area under the ROC curve for ONSD, Tei index, GCS, and cTnI were 0.596, 0.613, 0.635, and 0.881, respectively. ONSD exhibited a positive predictive value (PPV) of 0.704 and a negative predictive value (NPV) of 0.634. The Tei index demonstrated a PPV of 0.624 and an NPV of 0.726, while GCS had a PPV of 0.644 and an NPV of 0.815. On the other hand, cTnI exhibited a significantly higher PPV of 0.936 and an NPV of 0.817. These findings indicate that the Tei index, GCS score, and cTnI possess certain predictive value for secondary CCS in patients with sTBI. Conclusions: The study provides valuable insights into the identification of independent risk factors for CCS secondary to sTBI. The findings highlight the significance of right heart Tei index, GCS score, and cTnI as potential predictive factors for CCS in sTBI patients. Further larger-scale studies are warranted to corroborate these findings and to provide robust evidence for the development of early intervention strategies aimed at reducing the incidence of CCS in this patient population.

USP5 promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein.

BACKGROUND: The role of thioredoxin-interacting protein (TXNIP) in lipopolysaccharide-induced liver injury in mice has been reported, but the underlying mechanisms are poorly understood. METHODS: We overexpressed deubiquitinase in cells overexpressing TXNIP and then detected the level of TXNIP to screen out the deubiquitinase regulating TXNIP; the interaction between TXNIP and deubiquitinase was verified by coimmunoprecipitation. After knockdown of a deubiquitinase and overexpression of TXNIP in Huh7 and HepG2 cells, lipopolysaccharide was used to establish a cellular inflammatory model to explore the role of deubiquitinase and TXNIP in hepatocyte inflammation. RESULTS: In this study, we discovered that ubiquitin-specific protease 5 (USP5) interacts with TXNIP and stabilizes it through deubiquitylation in Huh-7 and HepG2 cells after treatment with lipopolysaccharide. In lipopolysaccharide-treated Huh-7 and HepG2 cells, USP5 knockdown increased cell viability, reduced apoptosis, and decreased the expression of inflammatory factors, including NLRP3, IL-1ß, IL-18, ASC, and procaspase-1. Overexpression of TXNIP reversed the phenotype induced by knockdown USP5. CONCLUSIONS: In summary, USP5 promotes lipopolysaccharide-induced apoptosis and inflammatory response by stabilizing the TXNIP protein.

An application based on bioinformatics and machine learning for risk prediction of sepsis at first clinical presentation using transcriptomic data.

Background: Linking genotypic changes to phenotypic traits based on machine learning methods has various challenges. In this study, we developed a workflow based on bioinformatics and machine learning methods using transcriptomic data for sepsis obtained at the first clinical presentation for predicting the risk of sepsis. By combining bioinformatics with machine learning methods, we have attempted to overcome current challenges in predicting disease risk using transcriptomic data. Methods: High-throughput sequencing transcriptomic data processing and gene annotation were performed using R software. Machine learning models were constructed, and model performance was evaluated by machine learning methods in Python. The models were visualized and interpreted using the Shapley Additive explanation (SHAP) method. Results: Based on the preset parameters and using recursive feature elimination implemented via machine learning, the top 10 optimal genes were screened for the establishment of the machine learning models. In a comparison of model performance, CatBoost was selected as the optimal model. We explored the significance of each gene in the model and the interaction between each gene through SHAP analysis. Conclusion: The combination of CatBoost and SHAP may serve as the best-performing machine learning model for predicting transcriptomic and sepsis risks. The workflow outlined may provide a new approach and direction in exploring the mechanisms associated with genes and sepsis risk.

Low-dose urokinase thrombolytic therapy for patients with acute intermediate-high-risk pulmonary embolism: A retrospective cohort study.

INTRODUCTION: Patients at intermediate-high risk of developing a pulmonary embolism (PE) are very likely to experience adverse outcomes, such as cardiovascular instability and death. The role of thrombolytic therapy in intermediate-high-risk PE remains controversial. OBJECTIVES: This study aimed to determine the efficacy and safety of low-dose urokinase (UK) thrombolytic therapy for intermediate-high-risk PE. PATIENTS AND METHODS: This retrospective study included 81 consecutive patients with intermediate-high-risk PE from two centers. Patients received low-dose UK or low-molecular-weight heparin (anticoagulant therapy group). The efficacy outcomes were mortality, computed tomography pulmonary angiography (CTPA)-confirmed absorption, and dyspnea. Safety was assessed as the incidence of bleedings. RESULTS: The in-hospital mortality, 9-month mortality, and long-term mortality at the last follow-up were comparable for the low-dose UK group and the anticoagulant therapy group (6.45% vs. 0%, p = 0.144, 9.68% vs. 8.16%, p = 0.815, and 12.90% vs. 12.24%, p = 0.931, respectively). CTPA-confirmed absorption at one month after admission was higher in the low-dose UK group than in the anticoagulant therapy group (p = 0.016). The incidences of short-term dyspnea at discharge and long-term dyspnea at the last follow-up were lower in the low-dose UK group than in the anticoagulant therapy group (27.59% vs. 52%, p = 0.035, 33.33% vs. 58.14%, p = 0.043, respectively). No major bleeding occurred. The incidence of minor bleeding was not significantly different between the two groups (3.23% vs. 6%, p = 0.974). CONCLUSION: In intermediate-high-risk PE, a low-dose UK might increase CTPA-confirmed absorption and improve short-term and long-term dyspnea without affecting mortality or increasing the bleeding risk.

Optical absorption enhancement in nanopore textured-silicon thin film for photovoltaic application.

Silicon thin film with a nanopore textured surface is systematically studied via simulation for photovoltaic application, where the optical characteristics are closely correlated with the nanopore structural parameters. It is found that the solar energy absorption could be optimized when the nanopore array structure dimensions are set as follows: periodicity of 700 nm, depth of 2000 nm, and pore diameter versus periodicity ratio of 87.5%. The result provides an additional guideline for the nanostructure surface texturing-process design for photovoltaic applications.

Role of RhoA/Rho kinase signaling pathway in microgroove induced stem cell myogenic differentiation.

In our previous report, the authors have demonstrated that direct laser machined microchannels would trigger upregulation of myogenic markers in human mesenchymal stem cells (hMSCs) through promotion of cell elongation. However, the molecular basis signaling pathways behind this observation remains unclear. In this work, three types of microchannels generated by femtosecond laser were utilized to investigate possible mechanisms behind the induction of hMSCs myogenesis by microchannels. The authors hypothesized that small G-proteins RhoA and Rac1 play a vital role on myogenesis of hMSCs through regulating cytoskeleton rearrangement, via cell tension signaling cascades. The RhoA and Rac1 activities were evaluated for cells cultured on the micropatterned substrates, using a flat unpatterned substrate as control. It was found that significant activation of RhoA GTPase was exhibited for cells cultured on narrow microchannels (20-20-20 and 30-30-20), while no obvious differences were obtained on wide ones (80-30-20). Meanwhile, no significant difference was found for Rac1 activities on all tested groups. To further deduce the role of RhoA signaling pathway in microchannel directed stem cell myogenesis, the effectors of Rho, Rho kinase (ROCK) was chosen to explore how cell shape regulate myogenesis of hMSCs cultured on laser micropatterned substrate. A pharmacological ROCK inhibitor, Y-27632, was used to treat the cells and the effect on RhoA activation was investigated. Our data on the role of RhoA/ROCK in regulating cell myogenic differentiation on lasered microchannels substrates may provide a mechanistic insight on hMSCs fate directed by substrate topography.

Surface Wettability Modification of Cyclic Olefin Polymer by Direct Femtosecond Laser Irradiation.

The effect of laser irradiation on surface wettability of cyclic olefin polymer (COP) was investigated. Under different laser parameters, a superhydrophilic or a superhydrophobic COP surface with a water contact angle (WCA) of almost 0° or 163°, respectively, could be achieved by direct femtosecond laser irradiation. The laser power deposition rate (PDR) was found to be a key factor on the wettability of the laser-treated COP surface. The surface roughness and surface chemistry of the laser-irradiated samples were characterized by surface profilometer and X-ray photoelectron spectroscopy, respectively; they were found to be responsible for the changes of the laser-induced surface wettability. The mechanisms involved in the laser surface wettability modification process were discussed.

Multifunctional wettability patterns prepared by laser processing on superhydrophobic TiO2 nanostructured surfaces.

A novel femtosecond laser patterning technique is reported to construct a three-dimensional (3D) wettability pattern on a superhydrophobic TiO2 nanotube array (TNA) surface in one-step. A 3D binary TNA pattern with extremely high contrast for microfluidic manipulators and biomedical scaffolds is used to guide droplet transportation and human mesenchymal stem cell site-selective growth, respectively.