Comprehensive insight on protein modification by V-type agent: A chemical proteomic approach employing bioorthogonal reaction.

Organophosphorus compounds (OPs) such as chemical agents and pesticides are posing critical threats to civilians due to their irreversible phosphonylation of diverse amino acids residues forming different protein adducts. However, traditional analytical approaches are quite limited in capturing the myriad of post-translational events that affect protein functions, especially in identifying the low-abundance OP adducts. Herein a systematic proteomic strategy based on a typical click-enrich-release-identify bioorthogonal operation was firstly developed by employing an alkynyl-tagged V-type agent probe (AVP) and a biotin-based azido-enrichment linker (BTP-N3 ). AVP targeting peptides from human serum albumin (HSA) or plasma were captured by BTP-N3 via CuAAC click reaction, enriched by streptavidin beads, released by selective alkaline hydrolysis of phenacyl ester bond, and subsequently sequenced by LC-MS/MS. This strategy has helped identifying 1115 unique OP adduction sites on 163 proteins in human plasma, and covers lots of OP adducts that cannot be achieved by traditional detection methods. The comprehensive coverage of novel OP substrates provided a general and sensitive approach to retrospective verification and/or dose assessment of toxic OPs.

Elevated serum IL-6 and total IgEAb are associated with poor survival in natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is an aggressive and malignant condition with a high mortality rate. Prognostic factors may assist to evaluate the outcome of the disease and may also be useful in selecting appropriate therapeutic strategies for patients. The study aims to describe NKTCL in terms of its clinical features, laboratory examinations, and immunophenotypes and to analyze relevance affecting patient survival outcomes. The patients diagnosed as NKTCL in Jinling Hospital from Jan. 2012 to Dec. 2022 were reviewed retrospectively in this study basing on histopathology. The analysis was performed to evaluate overall survival (OS). A total of 125 NKTCL patients were included, which mainly affected male more than female with the onset median age of 51.00 years old (range, 14 ~ 85 y). NKTCL commonly affects the nasopharynx and upper aerodigestive tract, intestines, and skin. The median overall survival was 13.00 months (range, 2-156 m), and the 5-year survival rate was 9.8%. Under univariable analysis revealed the following factors at diagnosis age: serum total IgEAb ≥ 54.6 IU/mL, IL-6 ≥ 32.445 ng/L, elevated PINK score, smoking, and extranasopharyngeal site were statistically significant predictors for OS. Compared to the patients who received radiotherapy alone or chemotherapy alone, the patients who received combined chemoradiotherapy had longer OS. We found that IL-6 and total IgEAb were significant prognostic factors in NKTCL patients. Also, extranasopharyngeal site was correlated with advanced disease.

Lung-PNet: An Automated Deep Learning Model for the Diagnosis of Invasive Adenocarcinoma in Pure Ground-Glass Nodules on Chest CT.

BACKGROUND. Pure ground-glass nodules (pGGNs) on chest CT representing invasive adenocarcinoma (IAC) warrant lobectomy with lymph node resection. For pGGNs representing other entities, close follow-up or sublobar resection without node dissection may be appropriate. OBJECTIVE. The purpose of this study was to develop and validate an automated deep learning model for differentiation of pGGNs on chest CT representing IAC from those representing atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA). METHODS. This retrospective study included 402 patients (283 women, 119 men; mean age, 53.2 years) with a total of 448 pGGNs on noncontrast chest CT that were resected from January 2019 to June 2022 and were histologically diagnosed as AAH (n = 29), AIS (n = 83), MIA (n = 235), or IAC (n = 101). Lung-PNet, a 3D deep learning model, was developed for automatic segmentation and classification (probability of IAC vs other entities) of pGGNs on CT. Nodules resected from January 2019 to December 2021 were randomly allocated to training (n = 327) and internal test (n = 82) sets. Nodules resected from January 2022 to June 2022 formed a holdout test set (n = 39). Segmentation performance was assessed with Dice coefficients with radiologists' manual segmentations as reference. Classification performance was assessed by ROC AUC and precision-recall AUC (PR AUC) and compared with that of four readers (three radiologists, one surgeon). The code used is publicly available (https://github.com/XiaodongZhang-PKUFH/Lung-PNet.git). RESULTS. In the holdout test set, Dice coefficients for segmentation of IACs and of other lesions were 0.860 and 0.838, and ROC AUC and PR AUC for classification as IAC were 0.911 and 0.842. At threshold probability of 50.0% or greater for prediction of IAC, Lung-PNet had sensitivity, specificity, accuracy, and F1 score of 50.0%, 92.0%, 76.9%, and 60.9% in the holdout test set. In the holdout test set, accuracy and F1 score (p values vs Lung-PNet) for individual readers were as follows: reader 1, 51.3% (p = .02) and 48.6% (p = .008); reader 2, 79.5% (p = .75) and 75.0% (p = .10); reader 3, 66.7% (p = .35) and 68.3% (p < .001); reader 4, 71.8% (p = .48) and 42.1% (p = .18). CONCLUSION. Lung-PNet had robust performance for segmenting and classifying (IAC vs other entities) pGGNs on chest CT. CLINICAL IMPACT. This automated deep learning tool may help guide selection of surgical strategies for pGGN management.

A novel lncRNA TCONS_00071187 upregulated by activated GSK3ß promotes high glucose-induced mesangial cell proliferation in the diabetic nephropathy.

Inhibiting mesangial cell proliferation is one of the strategies to control the early progression of diabetic nephropathy (DN). GSK3ß is closely related to cell apoptosis as well as the development of DN, but whether it acts on the proliferation of mesangial cells is unclear. This study aimed to elucidate the role and mechanism of GSK3ß-mediated lncRNA in high glucose-induced mesangial cell proliferation. HBZY-1 cells were used to establish the cell model of DN. The automatic cell counter was applied to assess cell proliferation. Flow cytometry was used to detect cell apoptosis and intracellular ROS levels. High-throughput transcriptomics sequencing was performed to detect the different expressions of long noncoding RNAs (lncRNAs) in the cell model of DN after knocking down the expression of GSK3ß by the transfection of siRNA. The expression of RNA was detected by real-time PCR. In the cell model of DN using HBZY-1 cells, cell proliferation was enhanced accompanied by GSK3ß activation and elevated apoptosis rate and reactive oxygen species (ROS) levels. A panel of novel lncRNAs, which were differentially expressed after GSK3ß knockdown in the cell model of DN, were identified by high-throughput transcriptomics sequencing. Among them, the expression of TCONS_00071187 was upregulated under high glucose conditions while the knockdown of the GSK3ß expression led to the downregulation of TCONS_00071187. The knockdown of TCONS_00071187 resulted in reduced mesangial cell proliferation, and decreased apoptosis rates and ROS levels. In conclusion, GSK3ß promoted mesangial cell proliferation by upregulating TCONS_00071187, which led to enhanced ROS production under high glucose conditions in the cell model of DN. This study revealed the role of GSK3ß medicated lncRNAs in the development of DN.

Coexistence of topological node surface and Dirac fermions in phonon-mediated superconductor YB2C2.

The interaction between nontrivial topology and superconductivity in condensed matter physics has attracted tremendous research interest as it could give rise to exotic phenomena. Herein, based on first-principles calculations, we investigate the electronic structures, mechanical properties, topological properties, dynamic stability, electron-phonon coupling (EPC), and superconducting properties of the synthesized real material YB2C2. It is a tetragonal structure with P4/mbm symmetry and exhibits excellent stability. The calculated electronic band structures reveal that a zero-dimension (0D) Dirac point and two-dimensional (2D) nodal surface coexist near the Fermi level. A spin-orbit coupling (SOC) Dirac point with the topological Fermi arc is observed on the (001) surface. These nodal surfaces are protected by a two-fold screw axis and time-reversal symmetry. Based on the Bardeen-Cooper-Schrieffer theory, the superconducting transition temperature (Tc) in the range 1.25-4.45 K with different Coulomb repulsion constant µ* for YB2C2 is estimated to be consistent with previous experimental results. In addition, the EPC is mainly from the coupling between the dx2-y2 and dz2 orbitals of the Y atom and low-energy phonon modes. The presence of superconductivity and nontrivial topological surface state in YB2C2 suggests that it may be a candidate material for topological superconductors.

A patient with acute myocardial infarction with electrocardiogram Aslanger's pattern.

BACKGROUND: Aslanger's pattern in electrocardiogram (ECG) indicates that patients may have acute inferior myocardial infarction(AMI) with concomitant critical stenoses on other coronary arteries, which needs to be evaluated the timing of revascularization as risk equivalents of ST elevation myocardial infarction(STEMI). CASE PRESENTATION: The patient was a 62-year-old male with chief complaint of intermittent exertional subxiphoid pain for 20 days from 30th June. One day after the last episode (19th July), the 18-lead electrocardiogram showed ST segment elevation of 0.05-0.1mV in lead III, ST segment depression in leads I, avL, and V2-V6, T wave inversion with positive terminal vector in lead V4-V5, and positive T wave in lead V6, which indicated Aslanger's pattern. With increased Troponin I (0.162ng/mL, 0-0.02), The patient was diagnosed as acute non-ST-segment elevation myocardial infarction (NSTEMI) and admitted to coronary ward on 20th July. The coronary angiography showed 95% stenosis in the distal left main coronary artery (LM) to the ostium of the left anterior descending artery (LAD), 90% stenosis in the proximal segment of the LAD, and 80% stenosis in the middle segment of the LAD, and TIMI blood flow was graded score 2. Three drug-eluting stents were implanted at the lesions. The patient's ECG returned close to normal one month after revascularization. CONCLUSION: We presented an acute coronary syndrome case whose ECG showed with Aslanger's pattern (i.e., isolated ST-segment elevation in lead III, associated ST-segment depression in lead V4-V6 with positive T wave/terminal vector, and greater ST-segment elevation in lead V1 than in lead V2), and was confirmed severe stenosis of the LM and the proximal segment of the LAD via coronary angiography. In clinical practice, especially in the emergency, patients with ECG presenting Aslanger's pattern should be urgently evaluated with prompt treatment, and the timing of emergency coronary angiography and revascularization should be evaluated to avoid adverse outcomes caused by delayed treatment.

Genotoxicity evaluation of food additive titanium dioxide using a battery of standard in vivo tests.

The increasing use of titanium dioxide (TiO2) nanoparticles (NPs) has raised concern about the safety of food additive TiO2. TiO2 has been considered no longer safe by EFSA due to concerns over genotoxicity, however, there are conflicting opinions upon the safety of TiO2 as a food additive, and the number of in vivo genotoxicity studies conducted on food additive TiO2 was limited. In order to investigate the potential genotoxicity of food additive TiO2, we evaluated the genotoxicity of a commercial food additive TiO2 (average size of 135.54 ± 41.01 nm, range from 60.83 to 230.16 nm, NPs account for 30% by number) using a battery of standard in vivo tests, including mammalian erythrocyte micronucleus test, mammalian bone marrow chromosomal aberration test and in vivo mammalian alkaline comet test. After 15 days of consecutive intragastric administration at doses of 250, 500, and 1000 mg/kgBW, food additive TiO2 neither increased the frequencies of bone marrow micronuclei or chromosomal aberration in mice, nor induced DNA strand breakage in rat liver cells. These results indicate that under the condition of this study, food additive TiO2 does not have genotoxic potential although it contains a fraction of NPs.

Genetic mutation and immune infiltration in embryonal tumor with multilayered rosettes.

PURPOSE: Genetic mutations stand as pivotal factors leading to the occurrence of embryonal tumor with multilayered rosettes (ETMR). This study aims to identify improved treatment approaches by unraveling the genetic drivers and immune infiltration in ETMR. METHODS: Two siblings with ETMR, treated at the General Hospital of Ningxia Medical University, were enrolled. Diagnosis involved MRI, Hematoxylin and Eosin (HE), and immunohistochemical (IHC) staining. Differentially expressed genes (DEGs) in ETMR were identified using GSE122077 and GSE14296 datasets. GO and KEGG analyses were used to determine ETMR-related pathways. Whole exome sequencing (WES) was utilized to annotate genetic variations in ETMR. Core genes, identified by protein-protein interaction (PPI), formed a diagnostic model evaluated by Logistic Regression. Single-sample Gene Set Enrichment Analysis (ssGSEA) assessed immune infiltration in ETMR, examining correlations between immune cells and core genes. RESULTS: Two siblings were diagnosed with ETMR. In ETMR, 135 DEGs were identified, of which 25 genes were annotated with 28 mutation sites. Moreover, ETMR-related pathways included cell cycle, synaptic functions, and neurodegeneration. Three ETMR-related core genes (ALB, PSMD1, and PAK2) were screened by protein-protein interaction (PPI). The diagnostic model constructed using these genes demonstrated an AUC value of 0.901 (95% CI: 0.811-0.991) in the training set, indicating accurate predictions in ETMR. Enhanced ssGSEA scores for 16 immune cells in ETMR tissues suggested a strong immune response. CONCLUSION: This study identifies diagnostic models associated with three core variant genes (ALB, PSMD1, PAK2) and enhanced immune cell activity in ETMR. It reveals crucial genetic features and significant immune responses in ETMR.

Prognostic nutritional index during hospitalization correlates with adverse outcomes in elderly patients with acute myocardial infarction: a single-center retrospective cohort study.

BACKGROUND AND AIMS: Acute myocardial infarction (AMI) is one of the most prevalent illnesses endangering the elderly's health. The predictive nutritional index (PNI) has been shown in several studies to be a good predictor of nutritional prognosis. In this study, we explored the correlation between PNI during hospitalization and the outcome of elderly AMI patients. METHODS: Elderly AMI patients in the Cardiac Intensive Care Unit of Huadong Hospital from September 2017 to April 2020 were recruited for analysis. The clinical and laboratory examination data of subjects were retrieved. All enrolled patients were monitored following discharge. The primary clinical endpoints encompass major adverse cardiovascular events (MACEs) and Composite endpoint (MACEs and all-cause mortality). Survival analyses were conducted via the Kaplan-Meier and the log-rank analyses, and the Cox, proportional hazards model, was employed for hazard rate (HR) calculation. RESULTS: 307 subjects were recruited for analysis. The optimal PNI threshold is 40.923. Based on the Kaplan-Meier analysis, the elevated PNI group experienced better prognosis (P < 0.001). Cox analysis demonstrated that the PNI group was a stand-alone predictor for elderly AMI patient prognosis (HR = 1.674, 95% CI 1.076-2.604, P = 0.022). Subgroup analysis showed that the HR of the PNI group was the highest in the ST-segment elevation myocardial infarction (STEMI) subgroup (HR = 3.345, 95% CI 1.889-5.923, P = 0.05), but no discernible difference was observed in the non-ST-segment elevation myocardial infarction (NSTEMI) subgroup. CONCLUSION: Based on our analyses, the PNI during hospitalization can accurately predict the prognosis of elderly STEMI patients but not that of elderly NSTEMI patients.

Retrospective evaluation of three types of expanded polytetrafluoroethylene grafts for upper limb vascular access.

Currently, three expanded polytetrafluoroethylene (ePTFE) prosthetic graft types are most commonly used for patients with end-stage kidney disease (ESKD) who require long-term vascular access for hemodialysis. However, studies comparing the three ePTFE grafts are limited. This study compared the clinical efficacy and postoperative complications of three ePTFE prosthetic graft types used for upper limb arteriovenous graft (AVG) surgery among patients with ESKD. Patients with ESKD requiring upper limb AVG surgery admitted to our center between January 2016 and September 2019 were enrolled. Overall, 282 patients who completed the 2-year follow-up were included and classified into the following three groups according to the ePTFE graft type: the GPVG group with the PROPATEN® graft, the GAVG group with the straight-type GORE® ACUSEAL, and the BVVG group with the VENAFLO® II. The patency rate and incidence of access-related complications were analyzed and compared between groups. The patients were followed up postoperatively, and data were collected at 6, 12, 18, and 24 months postoperatively. Respective to these follow-up time points, in the GPVG group, the primary patency rates were 74.29%, 65.71%, 51.43%, and 42.86%; the assisted primary patency rates were 85.71%, 74.29%, 60.00%, and 48.57%; and the secondary patency rates were 85.71%, 80.00%, 71.43%, and 60.00%. In the GAVG group, the primary patency rates were 73.03%, 53.93%, 59.42%, and 38.20%; the assisted primary patency rates were 83.15%, 68.54%, 59.55%, and 53.93%; and the secondary patency rates were 85.39%, 77.53%, 68.54%, and 62.92%, respectively. In the BVVG group, the primary patency rates were 67.24%, 53.45%, 41.38%, and 29.31%; the assisted primary patency rates were 84.48%, 67.24%, 55.17%, and 44.83%; and the secondary patency rates were 86.21%, 81.03%, 68.97%, and 60.34%, respectively. The differences in patency rates across the three grafts were not statistically significant. Overall, 18, 4, and 12 patients in the GPVG, GAVG, and BVVG groups, respectively, experienced seroma. Among the three grafts, GORE® ACUSEAL had the shortest anastomosis hemostatic time. The first cannulation times for the three grafts were GPVG at 16 (±8.2), GAVG at 4 (±4.9), and BVVG at 18 (±12.7) days. No significant difference was found in the postoperative swelling rate between the GPVG group and the other two groups. Furthermore, no statistically significant differences were found across the three graft types regarding postoperative vascular access stenosis and thrombosis, ischemic steal syndrome, pseudoaneurysm, or infection. In conclusion, no statistically significant differences in the postoperative primary, assisted primary, or secondary graft patency rates were observed among the three groups. A shorter anastomosis hemostatic time, first cannulation time, and seroma occurrence were observed with the ACUSEAL® graft than with its counterparts. The incidence of upper extremity swelling postoperatively was greater with the PROPATEN® graft than with the other grafts. No statistically significant differences were observed among the three grafts regarding the remaining complications.

Circ-MBOAT2 Regulates Angiogenesis via the miR-495/NOTCH1 Axis and Associates with Myocardial Perfusion in Patients with Coronary Chronic Total Occlusion.

Revascularization of coronary chronic total occlusion (CTO) still remains controversial. The factors that impact collateral circulation and myocardial perfusion are of interest. Circular RNA (circRNA) has been shown to regulate the process of angiogenesis. However, the effects of circ-membrane-bound O-acyltransferase domain containing 2 (circ-MBOAT2) on angiogenesis in patients with CTO were unclear. In this study, we evaluated circulating circRNAs and miRNAs in patients with CTO and stable coronary artery disease using high-throughput sequencing. Another cohort of patients were selected to verify the expressions of circ-MBOAT2 and miR-495. The role and mechanism of circ-MBOAT2 in the process of angiogenesis were explored through in vitro and vivo studies. Finally, we came back to a clinical perspective and investigated whether circ-MBOAT2 and miR-495 were associated with the improvement of myocardial perfusion evaluated by single-photon emission computed tomography (SPECT). We found that the expression of circ-MBOAT2 was significantly up-regulated while miR-495 was significantly down-regulated in patients with CTO. The expression of circ-MBOAT2 was negatively correlated with miR-495 in patients with CTO. In an in vitro study, we found that circ-MBOAT2 promoted tube formation and cell migration via the miR-495/NOTCH1 axis in endothelial cells. In an in vivo study, we showed that the inhibition of miR-495 caused the increase in collateral formation in mice after hindlimb ischemia. In a human study, we showed the expressions of circ-MBOAT2 and miR-495 were associated with myocardial perfusion improvement after revascularization of CTO. In conclusion, circ-MBOAT2 regulates angiogenesis via the miR-495/NOTCH1 axis and associates with myocardial perfusion in patients with CTO. Our findings suggest that circ-MBOAT2 and miR-495 may be potential therapeutic targets and prognostic factors for patients with CTO.

Iron-Catalyzed Sulfonylmethylation of Imidazo[1,2-α]pyridines with N,N-Dimethylacetamide and Sodium Sulfinates.

Functionalized imidazo[1,2-α]pyridines are important scaffolds in pharmaceuticals. Herein, we present an efficient 3-sulfonylmethylation protocol for imidazo[1,2-α]pyridines by sodium sulfinates in DMA and H2O (2:1) via an FeCl3-catalyzed three-component coupling reaction. Various sulfonylmethyl imidazo[1,2-α]pyridines were thus afforded in high yields with excellent functional group tolerance. A plausible oxidation-addition mechanism was proposed.

Measurement sensitivity analysis and on-orbit calibration of systematic errors for a narrow field-of-view camera.

Narrow field-of-view (FOV) cameras enable long-range observations and have been often used in deep space exploration missions. To solve the problem of systematic error calibration for a narrow FOV camera, the sensitivity of the camera systematic errors to the angle between the stars is analyzed theoretically, based on a measurement system for observing the angle between stars. In addition, the systematic errors for a narrow FOV camera are classified into "Non-attitude Errors" and "Attitude Errors". Furthermore, the on-orbit calibration methods for the two types of errors are researched. Simulations show that the proposed method is more effective in the on-orbit calibration of systematic errors for a narrow FOV camera than the traditional calibration methods.

Assessment of Lymphovascular Invasion in Breast Cancer Using a Combined MRI Morphological Features, Radiomics, and Deep Learning Approach Based on Dynamic Contrast-Enhanced MRI.

BACKGROUND: Assessment of lymphovascular invasion (LVI) in breast cancer (BC) primarily relies on preoperative needle biopsy. There is an urgent need to develop a non-invasive assessment method. PURPOSE: To develop an effective model to assess the LVI status in patients with BC using magnetic resonance imaging morphological features (MRI-MF), Radiomics, and deep learning (DL) approaches based on dynamic contrast-enhanced MRI (DCE-MRI). STUDY TYPE: Cross-sectional retrospective cohort study. POPULATION: The study included 206 BC patients, with 136 in the training set [97 LVI(-) and 39 LVI(+) cases; median age: 51.5 years] and 70 in the test set [52 LVI(-) and 18 LVI(+) cases; median age: 48 years]. FIELD STRENGTH/SEQUENCE: 1.5 T/T1-weighted images, fat-suppressed T2-weighted images, diffusion-weighted imaging (DWI), and DCE-MRI. ASSESSMENT: The MRI-MF model was developed with conventional MR features using logistic analyses. The Radiomic feature extraction process involved collecting data from categorized DCE-MRI datasets, specifically the first and second post-contrast images (A1 and A2). Next, a DL model was implemented to determine LVI. Finally, we established a joint diagnosis model by combining the MRI-MF, Radiomics, and DL approaches. STATISTICAL TESTS: Diagnostic performance was compared using receiver operating characteristic curve analysis, confusion matrix, and decision curve analysis. RESULTS: Rim sign and peritumoral edema features were used to develop the MRI-MF model, while six Radiomics signature from the A1 and A2 images were used for the Radiomics model. The joint model (MRI-MF + Radiomics + DL models) achieved the highest accuracy (area under the curve [AUC] = 0.857), being significantly superior to the MRI-MF (AUC = 0.724), Radiomics (AUC = 0.736), or DL (AUC = 0.740) model. Furthermore, it also outperformed the pairwise combination models: Radiomics + MRI-MF (AUC = 0.796), DL + MRI-MF (AUC = 0.796), or DL + Radiomics (AUC = 0.826). DATA CONCLUSION: The joint model incorporating MRI-MF, Radiomics, and DL approaches can effectively determine the LVI status in patients with BC before surgery. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Visible-light-driven Oxygen Vacancy and Carbon Doping of C@TiO2-x Photocatalyst for Enhanced Pollutants Degradation Performance.

Oxygen Vacancy (OVs) and carbon doping of the photocatalyst body will significantly enhance the photocatalytic efficiency. However, synchronous regulation of these two aspects is challenging. In this paper, a novel C@TiO2-x photocatalyst was designed by coupling the surface defect and doping engineering of titania, which can effectively remove rhodamine B (RhB) and has a relatively high performance with wide pH range, high photocatalytic activity and good stability. Within 90 minutes, the photocatalytic degradation rate of RhB by C@TiO2-x (94.1 % at 20 mg/L) is 28 times higher than that of pure TiO2 . Free radical trapping experiments and electron spin resonance techniques reveal that superoxide radicals (⋅O2- ) and photogenerated holes (h+ ) play key roles in the photocatalytic degradation of RhB. This study demonstrates the possibility of regulating photocatalysts to degrade pollutants in wastewater based on an integrated strategy.

Atorvastatin-induced tolerogenic dendritic cells improve cardiac remodeling by suppressing TLR-4/NF-κB activation after myocardial infarction.

OBJECTIVE: Myocardial infarction (MI) caused by ischemic cardiomyocyte necrosis induces inflammatory responses that strongly affect ventricular remodeling. Tolerogenic dendritic cells (tDCs) can suppress this effect on inflammatory responses. However, the precise role of atorvastatin-induced tDCs in ventricular remodeling after MI remains unclear. METHODS: To explore the effect of necrotic cardiomyocytes (SNC) and/or atorvastatin on DC function, the expression of CD40, CD80, CD86, and MHC-II was determined using flow cytometry. The protein levels of TLR-4/NF-κB-related molecules were evaluated using western blotting. The infarct area after MI was determined via 2,3,5-triphenyltetrazolium chloride staining. The TUNEL assay was employed to evaluate the apoptosis of cardiomyocytes in heart sections. Masson's trichrome method was used to determine the extent of fibrosis. RESULTS: Compared to the DCs co-cultured with PBS (control), cells co-cultured with Supernatant-IM or Supernatant-NH produced higher levels of inflammatory cytokines, including TNF-α, IL-1, IL-6, IL-12P40, and IL-8. This cytokine production was impaired by atorvastatin treatment. SNC treatment induced DC maturation and enhanced inflammatory cytokine secretion and oxidative stress through TLR-4/NF-κB pathway activation. Compared to that in the PBS-treated group, the left ventricular ejection fraction was significantly improved after tDC treatment. Additionally, compared to that in the PBS-treated group, tDC treatment reduced the left ventricular end-diastolic and end-systolic diameters in mice. Furthermore, treatment with tDCs improved the left ventricular systolic function, attenuated inflammatory cell infiltration, and reduced cardiomyocyte apoptosis, myocardial fibrosis, and infarct size compared to those in the control group. CONCLUSIONS: Adoptive transfer of atorvastatin-induced tDCs alleviated post-infarction cardiomyocyte apoptosis and myocardial fibrosis in association with decreased inflammatory cell infiltration and inhibited oxidative stress, likely by suppressing TLR-4/NF-κB activation after myocardial infarction.

Synthesis of Asymmetric Diaryl Sulfides via HI-Mediated C(sp2)-H Sulfenylation of Arenes with Sodium Sulfinates.

A novel hydroiodic acid-promoted metal-free C(sp2)-H sulfenylation of electron-rich arenes was developed using stable and easy-to-handle sodium sulfinates as sulfur sources. Diverse kinds of asymmetric aryl sulfides were afforded in good yields from various commercially available aromatic substrates under mild conditions. Comprehensive mechanistic experiments demonstrate that RSO2SR and RSSR are the key intermediates responsible for the redox process.

A time variant uncertainty propagation method for high-dimensional dynamic structural system via K-L expansion and Bayesian deep neural network.

In this paper, a time variant uncertainty propagation (TUP) method for dynamic structural system with high-dimensional input variables is proposed. Firstly, an arbitrary stochastic process simulation (ASPS) method based on Karhunen-Loève (K-L) expansion and numerical integration is developed, expressing the stochastic process as the combination of its marginal distributions and eigen functions at several discrete time points. Secondly, the iterative sorting method is implemented to the statistic samples of marginal distributions for matching the constraints of covariance function. Since marginal distributions are directly used to express the stochastic process, the proposed ASPS is suitable for stationary or non-stationary stochastic processes with arbitrary marginal distributions. Thirdly, the high-dimensional TUP problem is converted into several high-dimensional static uncertainty propagation (UP) problems after implementing ASPS. Then, the Bayesian deep neural network based UP method is used to compute the marginal distributions as well as the eigen functions of dynamic system response, the high-dimensional TUP problem can thus be solved. Finally, several numerical examples are used to validate the effectiveness of the proposed method. This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 1)'.

A first-principles study of the structural, electronic and elastic properties of the FeO2-FeO2He system under high pressure.

The origin of the wave velocity anomalies at the core-mantle boundary (CMB) has been controversial. The primordial helium reservoir in the deep lower mantle remains elusive even with geochemical evidence for its existence. Here, we calculated the density and wave velocity of the FeO2-FeO2He system under the CMB conditions using first principles. The FeO2 and FeO2He of pyrite-type can exist stably under the CMB conditions without melting, and the incorporated helium increases the stability of the system. The electrical properties of FeO2 and FeO2He are not related to pressure. Doped helium reduces the density of the system but increases the elastic modulus. Our results suggest that FeO2 can be used as a viable material composition of ultra-low velocity zones (ULVZs), and FeO2He can explain the D'' seismic discontinuity instead of ULVZs. The primordial helium reservoir possibly formed by the accumulation of FeO2He, the only stable solid helium-bearing compound under the CMB conditions, may coincide with the location of the D'' layer.

Relationship between the Ratio of Red Cell Distribution Width to Albumin and 28-Day Mortality among Chinese Patients over 80 Years with Atrial Fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is a prevalent heart arrhythmia in elderly adults aged 80 years or older. The red cell distribution width (RDW) to albumin ratio has been acknowledged as a reliable prognostic marker for poor outcomes in a variety of disorders. However, there exists limited scientific evidence on the association of RDW to albumin (RAR) with mortality in geriatric individuals with AF. METHODS: From January 2015 to June 2020, a retrospective study was conducted in a tertiary academic institution that diagnosed 1,141 elderly adults with AF. The RAR value was calculated as the ratio of RDW (%) to albumin (g/dL). The potential association between RAR and cardiovascular mortality and the risk of all-cause mortality within 28 days was evaluated by means of multivariable Cox regression analysis. RESULTS: The 28-day all-cause and cardiovascular mortality rates were 8.7% and 3.3%, respectively. Increased RAR tertiles were found to be significantly associated with greater all-cause mortality (T1: 1.6%; T2: 6.2%; T3: 18.1%, p < 0.001) and cardiovascular mortality (T1: 0.8%; T2: 2.9%; T3: 6.3%, p < 0.001) using Kaplan-Meier analysis. Continuous RAR had a positive association with all-cause mortality (hazard ratios [HR] = 1.42, 95% confidence interval [CI] 1.23-1.65) and cardiovascular mortality (HR = 1.31, 95% CI: 1.05-1.64), even after accounting for numerous confounding variables. In comparison to the T1 group, individuals with the highest RAR levels displayed a greater risk of all-cause mortality (HR = 2.73, 95% CI: 1.11-6.74) and cardiovascular mortality (HR = 2.59, 95% CI: 0.69-9.78). Increased RAR levels were related to higher rates of cardiovascular and all-cause mortality across almost all subgroups. CONCLUSION: RAR is independently correlated with 28-day all-cause mortality and cardiovascular mortality in AF-affected individuals aged ≥80.