The Potential Value of Mean Platelet Volume and Platelet Distribution Width as Inflammatory Indicators in Surgical Necrotizing Enterocolitis.

Background: This study aims to investigate the potential significance of mean platelet volume (MPV) and platelet distribution width (PDW) in predicting surgical neonatal necrotizing enterocolitis (NEC) and establish the correlation between MPV/PDW levels and the severity/prognosis of NEC. Methods: A retrospective study was conducted on a cohort of 372 patients diagnosed with NEC. The patients were categorized into two groups based on whether they underwent surgical therapy. Univariate /multivariate analysis were employed to compare the MPV and PDW between the two groups. Moreover, patients in surgical group were categorized into multiple subgroups based on intraoperative findings and postoperative prognosis, and the levels of MPV and PDW were compared among these subgroups. Results: Of the 372 patients, the operative group exhibited significantly higher levels of MPV and PDW than the nonoperative group (P < 0.05). Logistic regression analysis revealed that MPV (OR = 4.895, P < 0.001) and PDW (OR = 1.476, P < 0.001) independently associated with surgical NEC. The analysis of the receiver operating characteristic (ROC) curve revealed that the area under the curve (AUC) was 0.706 for MPV alone, with a cut-off value of 11.8 fL. Similarly, the AUC was 0.728 for PDW alone, with a cut-off value of 16%. However, when MPV and PDW were combined, the AUC increased to 0.906 for predicting surgical NEC. In accordance with the intraoperative findings, the levels of MPV and PDW were found to be higher in the large area necrosis group than in the partial or mild necrosis group (P < 0.01). Furthermore, the MPV and PDW values in the death group were significantly greater than those in the survival group (P =0.040, P =0.008). Conclusion: MPV and PDW may serve as potentially valuable indicators for determining the need for surgical intervention and predicting the prognosis of patients with NEC.

Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury.

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood-brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

Association study of FLT4 and HYDIN single nucleotide polymorphisms with atrial septal defect susceptibility in the Han Chinese population of Southwest China.

BACKGROUND: Atrial septal defect (ASD) is a common form of congenital heart disease. Although several genes related to ASD have been found, the genetic factors of ASD remain unclear. This study aimed to evaluate the correlation between 10 candidate single nucleotide polymorphisms (SNPs) and sporadic atrial septal defects. METHODS: Based on the results of 34 individual whole exome sequences, 10 candidate SNPs were selected. In total, 489 ASD samples and 420 normal samples were collected. The 10 SNPs in the case group and the control group were identified through Snapshot genotyping technology. The χ2-test and unconditional regression model were used to evaluate the relationship between ASD and each candidate SNP. Haploview software was used to perform linkage disequilibrium and haplotype analysis. RESULTS: The χ2 results showed that the FLT4 rs383985 (P = 0.003, OR = 1.115-1.773), HYDIN rs7198975 (P = 0.04621, OR = 1.003-1.461), and HYDIN rs1774266 (P = 0.04621, OR = 1.003-1.461) alleles were significantly different between the control group and the case group (P < 0.05). Only the association with the FLT4 polymorphism was statistically significant after adjustment for multiple comparisons. CONCLUSION: These findings suggest that a possible molecular pathogenesis associated with sporadic ASD is worth exploring in future studies.

18F-labeled somatostatin analogs for somatostatin receptors (SSTRs) targeted PET imaging of neuroendocrine tumors (NETs).

PURPOSE: A novel 18F-radiolabeled somatostatin analogue, [Al18F]NODA-MPAA-HTA, was synthesized and evaluated for positron emission tomography (PET) imaging of Neuroendocrine tumors (NETs). [Al18F]NODA-MPAA-HTA was designed and synthesized by conjugating 18F nuclide with a modified KE108 peptide, a somatostatin analog with high affinity for all five subtypes of somatostatin receptors (SSTR 1-5), through coupling a bifunctional chelator (NODA) to target somatostatin receptor (SSTR) positive tumors. METHODS: The amino group of KE108 peptide, a SSTRs-targeting pharmacophore, was conjugated with the carboxyl group of NODA by a condensation reaction to obtain the labeling precursor of [Al18F]NODA-MPAA-HTA, in which its precursor was obtained through Fmoc solid-phase methods. A novel methodology for Al18F labeling of chelating agent-biomolecule conjugates was used to synthesize [Al18F]NODA-MPAA-HTA. In vitro stabilities of [Al18F]NODA-MPAA-HTA were evaluated by incubating it in saline or bovine serum for 2 h. Ex vivo biodistribution and in vivo imaging of [Al18F]NODA-MPAA-HTA were further investigated to evaluate its SSTRs targeting ability and feasibility for the diagnosis of NETs using PET imaging. RESULTS: [Al18F]NODA-MPAA-HTA was synthesized using a one-step 18F-AlF labeling procedure resulting in moderate radiochemical yield (60-80 %, non-decay corrected) and high radiochemical purity (>95 %). It exhibited good hydrophilicity and excellent stability in vitro, with a molar activity of 122 GBq/µmol. At 30 min and 60 min, the uptake of [Al18F] NODA-MPAA-HTA by HEK293-SSTR2 cells was 5.47 ± 0.97 %/105 cells and 12.11 ± 0.32 %/105 cells, respectively. The affinity of [Al18F]NODA-MPAA-HTA for SSTR2 was determined to be 8.77 ± 1.14 nM. In micro-PET imaging of HEK293-SSTR2 tumor-bearing mice, [Al18F]NODA-MPAA-HTA showed high tumor uptake of radioactivity and a high tumor-to-muscle ratio. Biodistribution results confirmed that radioactivity uptake in the tumor was significantly higher than that in the muscle by more than five-fold (P<0.001). Furthermore, the relatively low bone uptake of [Al18F]NODA-MPAA-HTA suggested that defluorination did not occur in vivo. These preliminary results provide experimental evidence for further study of Al18F-labeled somatostatin analogues as tumor probes for PET imaging of NETs. CONCLUSION: Fluorine-18 is widely used as a radionuclide for the production of radiopharmaceuticals for positron emission tomography (PET). Due to its short half-life (T1/2,109.8 min), its ease of production will facilitate the widespread dissemination of this radiopharmaceutical. A high-quality [Al18F]NODA-MPAA-HTA was synthesized with satisfactory yield. This radiopharmaceutical demonstrated higher tumor uptake and better tumor-to-muscle contrast, resulting to excellent image quality. These findings suggest that the novel 18F-labeled somatostatin analogue, [Al18F]NODA-MPAA-HTA, is a promising tool for PET imaging of NETs.

[Effects of Mirror Therapy Combined With Task-Oriented Training on Limb Function Recovery in Stroke Patients With Hemiplegia].

Objective: To explore the effects of mirror therapy combined with task-oriented training on limb function recovery in stroke patients with hemiplegia. Methods: A total of 304 older patients with post-stroke hemiplegia who received treatment in Nanyang Third People's Hospital between March 2020 and March 2022 were enrolled as the subjects. They were assigned to the intervention group and the control group through a systematic randomization method, with 152 patients in each group. The control group was treated with conventional medication and task-oriented training, while the intervention group received a combined mirror therapy in addition to the treatment given to the control group. Both groups received continuous treatment for 3 months. The pre-treatment findings and those obtained after 3 month of treatment were compared between the two groups in the following areas, the neurological functions, including the levels of neuron-specific enolase (NSE) and S100ß, a central nervous system specific protein, upper and lower limb motor function as reflected by Fugl-Meyer Assessment (FMA) score, balance ability as measured by Berg Balance Scale (BBS), and the integrated electromyography (iEMG) values of quadriceps femoris, gastrocnemius, and tibialis anterior muscles, three-dimensional gait spatiotemporal parameters, and quality of life as reflected by the assessment results for the National Institute of Stroke Scale (NIHSS) and Stroke-Specific Quality of Life Scale (SS-QOL). The findings were compared to identify changes. Results: After 3 months of treatment, the FMA and BBS scores and three-dimensional gait spatio-temporal parameters in the intervention group were significantly better than those in the control group (all P<0.05). Conclusion: Mirror therapy combined with task-oriented training promotes the function recovery of the affected limbs in older patients with post-stroke hemiplegia, effectively improves their motor function and quality of life, and helps improve patient prognosis.

A deep learning-based drug repurposing screening and validation for anti-SARS-CoV-2 compounds by targeting the cell entry mechanism.

The recent outbreak of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a severe threat to the global public health and economy, however, effective drugs to treat COVID-19 are still lacking. Here, we employ a deep learning-based drug repositioning strategy to systematically screen potential anti-SARS-CoV-2 drug candidates that target the cell entry mechanism of SARS-CoV-2 virus from 2635 FDA-approved drugs and 1062 active ingredients from Traditional Chinese Medicine herbs. In silico molecular docking analysis validates the interactions between the top compounds and host receptors or viral spike proteins. Using a SARS-CoV-2 pseudovirus system, we further identify several drug candidates including Fostamatinib, Linagliptin, Lysergol and Sophoridine that can effectively block the cell entry of SARS-CoV-2 variants into human lung cells even at a nanomolar scale. These efforts not only illuminate the feasibility of applying deep learning-based drug repositioning for antiviral agents by targeting a specified mechanism, but also provide a valuable resource of promising drug candidates or lead compounds to treat COVID-19.

Shape-induced crystallization of binary DNA-functionalized nanocubes.

Leveraging the anisotropic shape of DNA-functionalized nanoparticles holds potential for shape-directed crystallization of a wide collection of superlattice structures. Using coarse-grained molecular dynamics simulations, we study the self-assembly of a binary mixture of cubic gold nanoparticles, which are functionalized by complementary DNA strands. We observe the spontaneous self-assembly of simple cubic (SC), plastic body-centered tetragonal (pBCT), and compositionally disordered plastic body-centered tetragonal (d-pBCT) phases due to hybridization of the DNA strands. We systematically investigate the effect of length, grafting density, as well as rigidity of the DNA strands on the self-assembly behavior of cubic nanoparticles. We measure the potential of mean force between DNA-functionalized nanocubes for varying rigidity of the DNA strands and DNA lengths. Using free-energy calculations, we find that longer and flexible DNA strands can lead to a phase transformation from SC to the pBCT phase due to a gain in entropy arising from the orientational degrees of freedom of the nanocubes in the pBCT phase. Our results may serve as a guide for self-assembly experiments on DNA-functionalized cubic nanoparticles.

Perspective of sodium reduction based on endogenous proteases via the strategy of sodium replacement in conjunction with mediated-curing.

NaCl is the main curing agent in dry-cured meat products, and a large amount of NaCl addition leads to high salt content of final products. Salt content and composition are important factors affecting the activity of endogenous proteases, which in turn could affect proteolysis as well as the quality of dry-cured meat products. With the increasing emphasis on the relationship between diet and health, reducing sodium content without sacrificing quality and safety of products is a great challenge for dry-cured meat industry. In this review, the change of endogenous proteases activity during processing, the potential relationship between sodium reduction strategy, endogenous proteases activity, and quality were summarized and discussed. The results showed that sodium replacement strategy and mediated-curing had a complementary advantage in influencing endogenous proteases activity. In addition, mediated-curing had the potential to salvage the negative effects of sodium substitution by affecting endogenous proteases. Based on the results, a sodium reduction strategy that sodium replacement in conjunction with mediated-curing based on endogenous proteases was proposed for the future perspective.

Catalytic-assembly of programmable atom equivalents.

Escape from metastable states in self-assembly of colloids is an intractable problem. Unlike the commonly adopted approach of thermal annealing, the recently developed enthalpy-mediated strategy provided a different option to address this dilemma in a dynamically controllable manner at room temperature. However, it required a complex catalytic-assembly DNA strand-displacement circuitry to mediate interaction between multiple components. In this work, we present a simple but effective way to achieve catalytic-assembly of DNA-functionalized colloidal nanoparticles, i.e., programmable atom equivalents, in a far-from-equilibrium system. A removable molecule named "catassembler" that acts as a catalyst was employed to rectify imperfect linkages and help the system escape from metastability without affecting the assembled framework. Notably, catalytic efficiency of the catassembler can be effectively improved by changing the seesaw catassembler in toehold length design or numbers of the repeat units. Leveraging this tractable catalytic-assembly approach, different ordered architectures were easily produced by directly mixing all reactants, as in chemical reactions. By switching bonding identities, solid-solid phase transformations between different colloidal crystals were achieved. This work opens up an avenue for programming colloid assembly in a far-from-equilibrium system.

Identification and In Silico Simulation on Inhibitory Platelet-Activating Factor Acetyl Hydrolase Peptides from Dry-Cured Pork Coppa.

The unique processing technology of dry-cured meat products leads to strong proteolysis, which produces numerous peptides. The purpose of this investigation was the systematic isolation, purification, and identification of potentially cardioprotective bioactive peptides from dry-cured pork coppa during processing. According to the results of anti-platelet-activating factor acetyl hydrolase activity and radical scavenging ability in vitro, the inhibitory effect of M1F2 in purified fractions on cardiovascular inflammation was higher than that of M2F2. The peptide of M1F2 was identified by nano-liquid chromatography-tandem mass spectrometry. A total of 30 peptides were identified. Based on bioinformatics methods, including in silico analysis and molecular docking, LTDKPFL, VEAPPAKVP, KVPVPAPK, IPVPKK, and PIKRSP were identified as the most promising potential platelet-activating factor acetyl hydrolase inhibitory peptides. Overall, bioactive peptides produced during dry-cured pork coppa processing demonstrate positive effects on human health.

Catalytic assembly of symmetric diblock copolymers in a thin film: a dissipative particle dynamics simulation study.

Obtaining a thin block copolymer film with a perfect structure by self-assembly is difficult because the system is, in general, trapped in a metastable state. We used dissipative particle dynamics (DPD) to investigate the self-assembly of AB symmetric diblock copolymers in a thin film. We discovered that addition of a small molecule (molecule C) as the third composition could help the system evade the metastable state. Therefore, imperfect structures could be corrected, and ordered structures formed. Analogous to the performance of a catalyst in catalytic chemistry, molecule C could promote assembly into an ordered structure, but was less involved within the polymer phase. Moreover, simulation results showed that the content of molecule C and its repulsive interactions with blocks A and B were quite important for promoting assembly into ordered structures effectively.

How Did the Built Environment Affect Urban Vibrancy? A Big Data Approach to Post-Disaster Revitalization Assessment.

Quantitative assessment of urban vibrancy is crucial to understanding urban development and promoting sustainability, especially for rapidly developing areas and regions that have experienced post-disaster reconstruction. Taking Dujiangyan City, the hardest-hit area of the earthquake, as an example, this paper quantifies the urban economic, social, and cultural vibrancy after reconstruction by the use of multi-source data, and conducts a geographic visualization analysis. The purpose is to establish an evaluation framework for the relationship between the urban built environment elements and vibrancy in different dimensions, to evaluate the benefits of post-disaster restoration and reconstruction. The results show that the urban vibrancy reflected by classified big data can not be completely matched due to the difference in the data generation and collection process. The Criteria Importance Though Inter-criteria Correlation and entropy (CRITIC-entropy) method is used to construct a comprehensive model is a better representation of the urban vibrancy spatial characteristics. On a global scale, comprehensive vibrancy demonstrates high continuity and a bi-center structure. In the old town, the distribution of various urban vibrancies show diffusion characteristics, while those in the new district demonstrated a high degree of aggregation, and the comprehensive vibrancy is less sensitive to land-use mixture and more sensitive to residential land.

Chrysanthemum MAF2 regulates flowering by repressing gibberellin biosynthesis in response to low temperature.

Chrysanthemum (Chrysanthemum morifolium) is well known as a photoperiod-sensitive flowering plant. However, it has also evolved into a temperature-sensitive ecotype. Low temperature can promote the floral transition of the temperature-sensitive ecotype, but little is known about the underlying molecular mechanisms. Here, we identified MADS AFFECTING FLOWERING 2 (CmMAF2), a putative MADS-box gene, which induces floral transition in response to low temperatures independent of day length conditions in this ecotype. CmMAF2 was shown to bind to the promoter of the GA biosynthesis gene CmGA20ox1 and to directly regulate the biosynthesis of bioactive GA1 and GA4 . The elevated bioactive GA levels activated LEAFY (CmLFY) expression, ultimately initiating floral transition. In addition, CmMAF2 expression in response to low temperatures was directly activated by CmC3H1, a CCCH-type zinc-finger protein upstream. In summary, our results reveal that the CmC3H1-CmMAF2 module regulates flowering time in response to low temperatures by regulating GA biosynthesis in the temperature-sensitive chrysanthemum ecotype.

Nanogels as Novel Nanocarrier Systems for Efficient Delivery of CNS Therapeutics.

Nanogels have come out as a great potential drug delivery platform due to its prominently high colloidal stability, high drug loading, core-shell structure, good permeation property and can be responsive to environmental stimuli. Such nanoscopic drug carriers have more excellent abilities over conventional nanomaterials for permeating to brain parenchyma in vitro and in vivo. Nanogel-based system can be nanoengineered to bypass physiological barriers via non-invasive treatment, rendering it a most suitable platform for the management of neurological conditions such as neurodegenerative disorders, brain tumors, epilepsy and ischemic stroke, etc. Therapeutics of central nervous system (CNS) diseases have shown marked limited site-specific delivery of CNS by the poor access of various drugs into the brain, due to the presences of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). Hence, the availability of therapeutics delivery strategies is considered as one of the most major challenges facing the treatment of CNS diseases. The primary objective of this review is to elaborate the newer advances of nanogel for CNS drugs delivery, discuss the early preclinical success in the field of nanogel technology and highlight different insights on its potential neurotoxicity.

How does the design of personal carbon trading system affect willingness to participate under carbon neutrality goal?-evidence from a choice experiment.

In order to achieve the emission peak and carbon neutrality ("30·60" goals), personal carbon trading may be included in China's carbon trading market in the future, based on the corporate-level carbon trading that is already in place. It will be an effective solution to reduce carbon emissions from the consumption side and can be used as a supplement to the corporate carbon trading mechanism and carbon tax. This study constructs a personal carbon trading system based on the fundamental realities of China, which includes four attributes: carbon quota acquisition, trading partner selection, low-carbon behavior offset mechanism, and value preservation mode. Through questionnaire survey and choice experiment, the logit model is used to analyze the influence of the four attributes upon the individual willingness to participate in personal carbon trading and the heterogeneity of the public on personal carbon trading in the context of carbon neutrality policy. The study found that the influence of the attributes on the willingness to participate was ranked as follows: carbon quota acquisition > value preservation mode > low-carbon behavior offset mechanism > trading partner selection. The level of knowledge about carbon neutrality and salary will have a significant positive impact on the attribute-level preference of personal carbon trading. Finally, suggestions are made for designing, applying, and promoting personal carbon trading mechanisms to improve the public's willingness to participate in personal carbon trading and perfect the construction of carbon trading systems at the consumption side. The take-home message of the study is that a well-established personal carbon trading mechanism is an effective solution for reducing greenhouse gas emissions.

Cadherin-dependent adhesion modulated 3D cell-assembly.

The emergence of synthetic biology has opened new avenues in constructing cell-assembly biosystems with specific gene expression and function. The phenomena of cell spreading and detachment during tissue development and cancer metastasis are caused by surface tension, which in turn results from differences in cell-cell adhesion mediated by the dimerization of cadherin expressed on the cell surface. In this study, E- and P-cadherin plasmids were first constructed based on the differential adhesion hypothesis, then they were electroporated into K562 cells and HEK293T cells, respectively, to explore the process of cell migration and assembly regulated by cadherins. Using this approach, some special 3D cell functional components with a phase separation structure were fabricated successfully. Our work will be of potential application in the construction of self-assembling synthetic tissues and organoids.

Curvature-Mediated Pair Interactions of Soft Nanoparticles Adhered to a Cell Membrane.

The curvature-mediated interactions by cell membranes are crucial in many biological processes. We systematically studied the curvature-mediated wrapping of soft nanoparticles (NPs) by a tensionless membrane and the underlying pair interactions between NPs in determining it. We found that there are three types of wrapping pathways, namely, independence, cooperation, and tubulation. The particle size, adhesion strength, and softness are found to be strongly related with the wrapping mechanism. Reducing the adhesion strength transforms the wrapping pathway from cooperation to independence, while enhancing the NP softness requires a stronger adhesion to achieve the cooperative wrapping. This transformation of the wrapping pathway is controlled by the curvature-mediated interactions between NPs. For either soft or rigid NPs, the pair interactions are repulsive at short-ranged distances between NPs, while at long-ranged distances, a larger adhesion between NPs and a membrane is needed to generate attraction between NPs. Moreover, an enhancement of NP softness weakens the repulsion between NPs. These distinct behaviors of soft NPs are ascribed to the gentler deformation of the membrane at the face-to-face region between NPs due to the flattening and spreading of soft NPs along the membrane, requiring a reduced energy cost for soft NPs to approach each other. Our results provide a mechanistic understanding in detail about the membrane-mediated interactions between NPs and their interactions with cell membranes, which is helpful to understand the curvature-mediated assemblies of adhesive proteins or NPs on membranes, and offer novel possibilities for designing an effective NP-based vehicle for controlled drug delivery.

Prevalence and prognostic significance of malnutrition in diabetic patients with coronary artery disease: a cohort study.

BACKGROUND: Malnutrition is associated with poor prognosis in cardiovascular disease patients or in diabetic patients. However, the relationship between malnutrition and clinical outcomes in diabetic patients with coronary artery disease (CAD) is not well known. The aim of this study is to report the prevalence and prognostic consequences of malnutrition in diabetic patients with CAD. METHODS: In this retrospective observational study, the Controlling Nutritional Status (CONUT) score applied to 12,898 consecutive diabetic patients with CAD. The association between malnutrition and long-term all-cause mortality was examined using Cox proportional hazards regression analysis. RESULTS: According to CONUT score, 60.5% patients suffered from malnutrition; 46.4%, 13.2%, and 0.9% patients had mild, moderate, and severe malnutrition, respectively. During a median follow-up of 4.88 (2.83-7.51) years, 1973 (15.3%) patients died. After adjustment for confounders, malnutrition was associated with significantly increased risk for long-term all-cause mortality (adjusted hazard ratio for mild malnutrition and moderate to severe malnutrition, respectively: 1.38 [95% confidence interval (CI) 1.07-1.77]; P value = 0.012 and 1.63 [95% CI 1.18-2.24]; P value = 0.003). A similar association was observed around subgroups. CONCLUSIONS: Malnutrition is common in diabetic patients with CAD and is strongly associated with increased mortality. It is necessary to adequately assess the nutritional status and take the effective nutritional guidance to improve the prognosis of diabetic patients with CAD.

Predictive value of creatine kinase MB for contrast-induced acute kidney injury among myocardial infarction patients.

BACKGROUND: Predictive value of creatine kinase MB (CK-MB) for contrast-induced acute kidney injury (CI-AKI) among myocardial infarction (MI) patients has rarely been reported. We aim to evaluate the predictive value of CK-MB for CI-AKI among MI patients. METHODS: Totally, 1131 MI patients were included from the REduction of rIsk for Contrast-Induced Nephropathy (REICIN) study. The peak CK-MB before coronary angiography (CAG) was chosen. The study population was divided into two groups by log-transformed CK-MB cut-off point. The association between CK-MB and CI-AKI was tested by multivariable logistic regression. CK-MB was integrated with Age, creatinine and ejection fraction (ACEF) score and Mehran risk score (MRS) to evaluate the additive value of CK-MB. The integrated models were validated internally by the bootstrap method and externally by the PREdictive Value of COntrast voluMe to creatinine Clearance Ratio (PRECOMIN) study data set. RESULTS: Overall, 62(5.48%) patients developed CI-AKI, patients with CK-MB point > 4.7 displayed a higher incidence of CI-AKI than those without (11.9% vs. 4.0%, p < 0.001). CK-MB point > 4.7 was independently associated with CI-AKI (adjusted OR: 3.40, 95% CI: 1.93-5.98, p < 0.001). The additions of CK-MB to ACEF score, Mehran score A and Mehran score B resulted in increases in C-statistics, which ranged from 0.680 to 0.733 (p = 0.046), 0.694 to 0.727 (p = 0.091), 0.704 to 0.734 (p = 0.102), respectively. Internal validation also showed increases in C-statistics, and external validation performed well in discrimination and calibration. CONCLUSIONS: Preprocedural peak CK-MB was a predictor of CI-AKI among MI patients.

p53 Promoted Ferroptosis in Ovarian Cancer Cells Treated with Human Serum Incubated-Superparamagnetic Iron Oxides.

METHODS: In this study, we used MTT assays to demonstrate that a combination of SPIO-Serum and wild-type p53 overexpression can reduce ovarian cancer cell viability in vitro. Prussian blue staining and iron assays were used to determine changes in intracellular iron concentration following SPIO-Serum treatment. TEM was used to evaluate any mitochondrial damage induced by SPIO-Serum treatment, and Western blot was used to evaluate the expression of the iron transporter and lipid peroxidation regulator proteins. JC-1 was used to measure mitochondrial membrane potential, and ROS levels were estimated by flow cytometry. Finally, xCT protein expression and mitochondrial ROS levels were confirmed using fluorescence microscopy. RESULTS: SPIO-Serum effectively induced lipid peroxidation and generated abundant toxic ROS. It also facilitated the downregulation of GPX4 and xCT, ultimately resulting in iron-dependent oxidative death. These effects could be reversed by iron chelator DFO and lipid peroxidation inhibitor Fer-1. SPIO-Serum treatment disrupted intracellular iron homeostasis by regulating iron uptake and the cells presented with missing mitochondrial cristae and ruptured outer mitochondrial membranes. Moreover, we were able to show that p53 contributed to SPIO-Serum-induced ferroptosis in ovarian cancer cells. CONCLUSION: SPIO-Serum induced ferroptosis and overexpressed p53 contributed to ferroptosis in ovarian cancer cells. Our data provide a theoretical basis for ferroptosis as a novel cell death phenotype induced by nanomaterials.