Review on strategies for improving the added value and expanding the scope of CO2 electroreduction products.

The electrochemical reduction of CO2 into value-added chemicals has been explored as a promising solution to realize carbon neutrality and inhibit global warming. This involves utilizing the electrochemical CO2 reduction reaction (CO2RR) to produce a variety of single-carbon (C1) and multi-carbon (C2+) products. Additionally, the electrolyte solution in the CO2RR system can be enriched with nitrogen sources (such as NO3-, NO2-, N2, or NO) to enable the synthesis of organonitrogen compounds via C-N coupling reactions. However, the electrochemical conversion of CO2 into valuable chemicals still faces challenges in terms of low product yield, poor faradaic efficiency (FE), and unclear understanding of the reaction mechanism. This review summarizes the promising strategies aimed at achieving selective production of diverse carbon-containing products, including CO, formate, hydrocarbons, alcohols, and organonitrogen compounds. These approaches involve the rational design of electrocatalysts and the construction of coupled electrocatalytic reaction systems. Moreover, this review presents the underlying reaction mechanisms, identifies the existing challenges, and highlights the prospects of the electrosynthesis processes. The aim is to offer valuable insights and guidance for future research on the electrocatalytic conversion of CO2 into carbon-containing products of enhanced value-added potential.

The effects of tranexamic acid in patients treated with extracorporeal membrane oxygenation after cardiac surgery.

BACKGROUND: The lysine analog tranexamic acid (TXA) is used as a blood protective drug in cardiac surgery, but efficacy and safety outcomes in patients treated with extracorporeal membrane oxygenation (ECMO) after surgery remain poorly understood. METHODS: From January 1, 2017 to December 31, 2022, we retrospectively analyzed patients assisted by ECMO after cardiac surgery and divided them into TXA and control groups depending on whether TXA was used or not. The primary study outcome was red blood cell (RBC) transfusion during ECMO. RESULTS: In total, 321 patients treated with ECMO after cardiac surgery were assessed; 185 patients were eligible for inclusion into to the TXA-intervention group and 136 into to the control group. RBC transfusion during ECMO was 8.0 IU (4.0 IU-14.0 IU) in the TXA group versus 10.0 IU (6.0 IU-16.0 IU) in the control group (p = .034). Median total chest drainage volume after surgery was 1460.0 mL (650.0-2910.0 mL) and 1680.0 mL (900.0-3340.0 mL) in TXA and control groups, respectively (p = .021). Postoperative serum D-dimer levels were significantly lower in the TXA group when compared with the control group; 1.125 µg/mL (0.515-2.176 µg/mL) versus 3.000 µg/mL (1.269-5.862 µg/mL), p < .001. Serious adverse events, including vascular occlusive events, did not differ meaningfully between groups. CONCLUSIONS: In patients treated with ECMO after cardiac surgery, TXA infusion modestly but significantly reduced RBC transfusions and chest tube output when compared with the control group.

One-Step Prepared Multifunctional Polyacrylonitrile/MIL-100(Fe) Membrane with High-Density Porous Fibers for Efficient Dye/Oil Wastewater Remediation.

With environmental pollution becoming more serious, developing efficient treatment technologies for all kinds of organic wastewater has become the focus of current research. In this work, the coaxial electrospinning technology was used to one-step fabricate a porous and underwater superoleophobic polyacrylonitrile nanofibrous membrane with an Fe-based metal-organic framework (MIL-100(Fe)). Benefiting from the synergistic effect of two jets, the nanofibers are smaller and denser, which prompt the exposure of more nanomaterial additives (MIL-100(Fe)). The BET surface area increased to 202.888 m2/g, and the membranes demonstrated outstanding underwater superoleophobicity. Moreover, compared with traditional blended matrix membranes by the single-axis method, separation of the modifier and membrane matrix material by coaxial methods also maintained excellent mechanical properties, which enhanced Young's modulus 3.4 times (∼1.34 MPa). As a result, facing soluble dyes, the porous C-PAN/MIL-100(Fe) membrane can demonstrate outstanding and fast adsorptive property (the Qm of MB and CR reached 44.71 and 88.74 mg g-1, respectively). For oily emulsion, the hydrophilic and oleophobic nanofibrous reticular surface provided excellent separation performance (flux: 1124.0-1549.3 L m-2 h-1, R > 98%). Moreover, the porous and underwater superoleophobic C-PAN/MIL-100(Fe)-0.5 membrane can synchronously purify the dye/oil mixture emulsions by one-step filtration. Based on the above performance, we believe that the modified nanofibrous membrane prepared by one-step coaxial electrospinning technology can promote more studies of the development of membrane preparation technology in the field of oily wastewater treatment.

Photoaged microplastics enhanced the antibiotic resistance dissemination in WWTPs by altering the adsorption behavior of antibiotic resistance plasmids.

Growing concerns have raised about the microplastic eco-coronas in the ultraviolet (UV) disinfection wastewater, which accelerated the pollution of antibiotic resistance genes (ARGs) in the aquatic environment. As the hotspot of gene exchange, microplastics (MPs), especially for the UV-aged MPs, could alter the spread of ARGs in the eco-coronas and affect the resistance of the environment through adsorbing antibiotic resistant plasmids (ARPs). However, the relationship between the MP adsorption for ARPs and ARG spreading characteristics in MP eco-corona remain unclear. Herein, this study explored the distribution of ARGs in the MP eco-corona through in situ investigations of the discharged wastewater, and the adsorption behaviors of MPs for ARPs by in vitro adsorption experiments and in silico calculations. Results showed that the adsorption capacity of MPs for ARPs was enhanced by 42.7-48.0 % and the adsorption behavior changed from monolayer to multilayer adsorption after UV-aging. It was related to the increased surface roughness and oxygen-containing functional groups of MPs under UV treatment. Moreover, the abundance of ARGs in MP eco-corona of UV-treated wastewater was 1.33-1.55 folds higher than that without UV treatment, promoting the proliferation of drug resistance. DFT and DLVO theoretical calculations indicated that the MP-ARP interactions were dominated by electrostatic physical adsorption, endowing the aged MPs with low potential oxygen-containing groups to increase the electrostatic interaction with ARPs. Besides, due to the desorption of ARPs on MPs driven by the electrostatic repulsion, the bioavailability of ARGs in the MP eco-coronas was increased with pH and decreased with salinity after the wastewater discharge. Overall, this study advanced the understanding of the adsorption behavior of MPs for ARPs and provided inspirations for the evaluation of the resistance spread in the aquatic environment mediated by MP eco-coronas.

SERS Immunoassay Based on an Enzyme-Catalyzed Cascade Reaction and Metal-Organic Framework/Alkaline Phosphatase for Ultrasensitive Detection of Adenosine Triphosphate.

Herein, an adenosine triphosphate (ATP)-induced enzyme-catalyzed cascade reaction system based on metal-organic framework/alkaline phosphatase (MOF/ALP) nanocomposites was designed to establish a surface-enhanced Raman spectroscopy (SERS) biosensor for use in rapid, sensitive ATP detection. Numerous ALP molecules were first encapsulated using ZIF-90 to temporarily deactivate the enzyme activity, similar to a lock. Au nanostars (AuNSs), as SERS-enhancing substrates, were combined with o-phenylenediamine (OPD) to form AuNSs@OPD, which could significantly improve the Raman signal of OPD. When the target ATP interacted with the MOF/ALP nanocomposites, ATP could act as a key to open the MOF structure, releasing ALP, which should further catalyze the conversion of OPD to oxOPD with the aid of ascorbic acid 2-phosphate. Therefore, with the increasing concentrations of ATP, more ALP was released to catalyze the conversion of OPD, resulting in the reduced intensity of the Raman peak at 1262 cm-1, corresponding to the level of OPD. Based on this principle, the ATP-induced enzyme-catalyzed cascade reaction SERS biosensor enabled the ultrasensitive detection of ATP, with a low detection limit of 0.075 pM. Consequently, this study provides a novel strategy for use in the ultrasensitive, rapid detection of ATP, which displays considerable potential for application in the fields of biomedicine and disease diagnosis.

Novel venous balloon for compliance measurement and stent sizing in a post-thrombotic swine model.

Objective: Real-time accurate venous lesion characterization is needed during endovenous interventions for stent deployment. The goal of this study is to validate a novel device for venoplasty sizing and compliance measurements. Methods: A compliance measuring sizing balloon (CMSB) uses real-time electrical conductance measurements based on Ohm's Law to measure the venous size and compliance in conjunction with pressure measurement. The sizing accuracy and repeatability of the CMSB system were performed with phantoms on the bench and in a swine model with an induced post thrombotic (PT) stenosis in the common femoral vein of swine. Results: The accuracy and repeatability of the CMSB system were validated with phantom bench studies of known dimensions in the range of venous diameters. In 9 swine (6 experimental and 3 control animals), the luminal cross-sectional areas (CSA) increased heterogeneously along the PT stenosis when the CMSB system was inflated by stepwise pressures. The PT stenosis showed lower compliance compared to the non-PT vein segments (5 mm2 vs. 10 mm2 and 13 mm2 at a pressure change of 40 cm H2O). Compliance had no statistical difference between venous hypertension (VHT) and Control. Compliance at PT stenosis, however, was significantly smaller than that at Control and VHT (p < 0.05, ANOVA). Conclusion: The CMSB system provides accurate, repeatable, real-time measurements of CSA and compliance for assessment of venous lesions to guide interventions. These findings provide the impetus for future first-in-human studies.

Bufalin targeting CAMKK2 inhibits the occurrence and development of intrahepatic cholangiocarcinoma through Wnt/ß-catenin signal pathway.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) accounts for about 15% of primary liver cancer, and the incidence rate has been rising in recent years. Surgical resection is the best treatment for ICC, but the 5-year survival rate is less than 30%. ICC signature genes are crucial for the early diagnosis of ICC, so it is especially important to find its signature genes and therapeutic drug. Here, we studied that bufalin targeting CAMKK2 promotes mitochondrial dysfunction and inhibits the occurrence and metastasis of intrahepatic cholangiocarcinoma through Wnt/ß-catenin signal pathway. METHODS: IC50 of bufalin in ICC cells was determined by CCK8 and invasive and migratory abilities were verified by wound healing, cell cloning, transwell and Western blot. IF and IHC verified the expression of CAMKK2 between ICC patients and normal subjects. BLI and pull-down demonstrated the binding ability of bufalin and CAMKK2. Bioinformatics predicted whether CAMKK2 was related to the Wnt/ß-catenin pathway. SKL2001, an activator of ß-catenin, verified whether bufalin acted through this pathway. In vitro and in vivo experiments verified whether overexpression of CAMKK2 affects the proliferative and migratory effects of ICC. Transmission electron microscopy verified mitochondrial integrity. Associated Ca2+ levels verified the biological effects of ANXA2 on ICC. RESULTS: It was found that bufalin inhibited the proliferation and migration of ICC, and CAMKK2 was highly expressed in ICC, and its high expression was positively correlated with poor prognosis.CAMKK2 is a direct target of bufalin, and is associated with the Wnt/ß-catenin signaling pathway, which was dose-dependently decreased after bufalin treatment. In vitro and in vivo experiments verified that CAMKK2 overexpression promoted ICC proliferation and migration, and bufalin reversed this effect. CAMKK2 was associated with Ca2+, and changes in Ca2+ content induced changes in the protein content of ANXA2, which was dose-dependently decreasing in cytoplasmic ANXA2 and dose-dependently increasing in mitochondrial ANXA2 after bufalin treatment. In CAMKK2 overexpressing cells, ANXA2 was knocked down, and we found that reversal of CAMKK2 overexpression-induced enhancement of ICC proliferation and migration after siANXA2. CONCLUSIONS: Our results suggest that bufalin targeting CAMKK2 promotes mitochondrial dysfunction and inhibits the proliferation and migration of intrahepatic cholangiocarcinoma through Wnt/ß-catenin signal pathway. Thus, bufalin, as a drug, may also be used for cancer therapy in ICC in the future.

Experimental study and numerical analysis on axial compression of round-ended concrete filled CFRP-aluminum tube columns.

To enhance the concrete confinement ability of circular-ended aluminum alloy tubes, carbon fiber reinforced polymer (CFRP) was bonded onto the tube surface to form CFRP confined concrete columns with circular ends (RCFCAT). Eight specimens were designed with number of CFRP layers and section aspect ratio as variables. Axial loading test and finite element analysis were carried out. Results showed CFRP delayed buckling of the aluminum alloy tube flat surfaces, transforming inclined shear buckling failure into CFRP fracture failure. Specimens with aspect ratio above 4 experienced instability failures. Under same cross-section, CFRP increased axial compression bearing capacity and ductility by up to 30.8% and 43.4% respectively. As aspect ratio increased, enhancement coefficients of bearing capacity and ductility gradually decreased, the aspect ratio is restrictive when it is less than 2.5. CFRP strengthening increased initial axial compression stiffness of specimens by up to 117.9%. The stiffness decreased gradually with increasing aspect ratio, with most significant increase at aspect ratio of 4. Strain analysis showed CFRP bonding remarkably reduced circumferential and longitudinal strains. Confinement effect was optimal at aspect ratio around 2.0. The rationality of the refined FE model established has been verified in terms of load displacement curves, capturing circular aluminum tube oblique shear buckling, concrete "V" shaped crushing, and CFRP tearing during specimen failure. The parameter analysis showed that increasing the number of CFRP layers is one of the most effective methods for improving the ultimate bearing capacity of RCFCAT.

Camouflaged Nanoreactors Mediated Radiotherapy-Adjuvant Chemodynamic Synergistic Therapy.

Chemodynamic therapy based on the Fenton-like catalysis ability of Fe3O4 has the advantages of no involvement of chemical drugs and minimal adverse effects as well as the limitation of depletable efficacy. Radiotherapy based on high-energy radiation offers the convenience of treatment and cost-effectiveness but lacks precision and cellular adaptation of tumor cells. Approaching such dilemmas from a nanoscale materials perspective, we aim to bridge the weaknesses of both treatment methods by combining the principles of two therapeutics reciprocally. We have designed a camouflaged Fe3O4@HfO2 composite nanoreactor (FHCM), which combines a chemodynamic therapeutic agent Fe3O4 and a radiosensitizer HfO2 that both has passed clinical trials and was inspired by a cell membrane biomimetic technique. FHCM is employed as conceived radiotherapy-adjuvant chemodynamic synergistic therapy of malignant tumors, which has undergone dual scrutiny from both the physical and biological aspects. Experimental results obtained at different levels, including theory, material characterizations, and in vitro and in vivo verifications, suggest that FHCM effectively impaired tumor cells through physical and molecular biological mechanisms involving a HfO2-Fe3O4 photoelectron-electron transfer chain and DNA damage-ferroptosis-immunity chain. It is worth noting that compared to single therapies such as only chemodynamic therapy or radiotherapy, FHCM-mediated radiotherapy-adjuvant chemodynamic synergistic therapy exhibits stronger tumor inhibition efficacy. It significantly addresses the inherent limitations of chemodynamic therapy and radiotherapy and underscores the feasibility and importance of using existing clinical weapons, such as radiotherapy, as auxiliary strategies to overcome certain flaws of emerging antitumor therapeutics like chemodynamic therapy.

Combustion Behavior of Ethanol/Ether Molecules-Coated Al Nanoparticles with H2O Vapor by Non-equilibrium Molecular Dynamics Simulations.

Al nanoparticles (ANPs) have high reactivity and can improve the system's combustion performance. However, ANPs are susceptible to inactivation by external oxidants. Here, we use ethanol and ether molecules to coat ANPs and then compare and discuss the combustion process between coated ANPs and bare ANPs. Our results show that the ethanol/ether coating can adsorb more H2O molecules and increase the active Al atom number and the Al core area in the ignition stage. The combustion phase can be divided into four stages according to the rate of the combustion temperature. The ethanol/ether coating can enable ANPs to deliver a better combustion performance, reducing the ignition delay time of particles, greatly increasing the combustion temperature, and making the whole system enter the gas phase combustion stage. These will enable the ethanol/ether-ANPs systems to release more energy and improve the combustion efficiency of the system.

USP32 deubiquitinase: cellular functions, regulatory mechanisms, and potential as a cancer therapy target.

An essential protein regulatory system in cells is the ubiquitin-proteasome pathway. The substrate is modified by the ubiquitin ligase system (E1-E2-E3) in this pathway, which is a dynamic protein bidirectional modification regulation system. Deubiquitinating enzymes (DUBs) are tasked with specifically hydrolyzing ubiquitin molecules from ubiquitin-linked proteins or precursor proteins and inversely regulating protein degradation, which in turn affects protein function. The ubiquitin-specific peptidase 32 (USP32) protein level is associated with cell cycle progression, proliferation, migration, invasion, and other cellular biological processes. It is an important member of the ubiquitin-specific protease family. It is thought that USP32, a unique enzyme that controls the ubiquitin process, is closely linked to the onset and progression of many cancers, including small cell lung cancer, gastric cancer, breast cancer, epithelial ovarian cancer, glioblastoma, gastrointestinal stromal tumor, acute myeloid leukemia, and pancreatic adenocarcinoma. In this review, we focus on the multiple mechanisms of USP32 in various tumor types and show that USP32 controls the stability of many distinct proteins. Therefore, USP32 is a key and promising therapeutic target for tumor therapy, which could provide important new insights and avenues for antitumor drug development. The therapeutic importance of USP32 in cancer treatment remains to be further proven. In conclusion, there are many options for the future direction of USP32 research.

Performance of xenogeneic pulmonary visceral pleura as bioprosthetic heart valve cusps in swine.

Objective: Bovine pericardium is common biological material for bioprosthetic heart valve. There remains a significant need, however, to improve bioprosthetic valves for longer-term outcomes. This study aims to evaluate the chronic performance of bovine pulmonary visceral pleura (PVP) as bioprosthetic valve cusps. Methods: The PVP was extracted from the bovine lung and fixed in 0.625% glutaraldehyde overnight at room temperature. The PVP valve cusps for the bioprosthetic valve were tailored using a laser cutter. Three leaflets were sewn onto a nitinol stent. Six PVP bioprosthetic valves were loaded into the test chamber of the heart valve tester to complete 100 million cycles. Six other PVP bioprosthetic valves were transcardially implanted to replace pulmonary artery valve of six pigs. Fluoroscopy and intracardiac echocardiography were used for in vivo assessments. Thrombosis, calcification, inflammation, and fibrosis were evaluated in the terminal study. Histologic analyses were used for evaluations of any degradation or calcification. Results: All PVP bioprosthetic valves completed 100 million cycles without significant damage or tears. In vivo assessments showed bioprosthetic valve cusps open and coaptation at four months post-implant. No calcification and thrombotic deposits, inflammation, and fibrosis were observed in the heart or pulmonary artery. The histologic analyses showed complete and compact elastin and collagen fibers in the PVP valve cusps. Calcification-specific stains showed no calcific deposit in the PVP valve cusps. Conclusions: The accelerated wear test demonstrates suitable mechanical strength of PVP cusps for heart valve. The swine model demonstrates that the PVP valve cusps are promising for valve replacement.

Effective Absorption of Dichloromethane Using Carboxyl-Functionalized Ionic Liquids.

Dichloromethane (DCM) is recognized as a very harmful air pollutant because of its strong volatility and difficulty to degrade. Ionic liquids (ILs) are considered as potential solvents for absorbing DCM, while it is still a challenge to develop ILs with high absorption performances. In this study, four carboxyl-functionalized ILs-trioctylmethylammonium acetate [N1888][Ac], trioctylmethylammonium formate [N1888][FA], trioctylmethylammonium glycinate [N1888][Gly], and trihexyl(tetradecyl)phosphonium glycinate [P66614][Gly]-were synthesized for DCM capture. The absorption capacity follows the order of [P66614][Gly] > [N1888][Gly] > [N1888][FA] > [N1888][Ac], and [P66614][Gly] showed the best absorption capacity, 130 mg DCM/g IL at 313.15 K and a DCM concentration of 6.1%, which was two times higher than the reported ILs [Beim][EtSO4] and [Emim][Ac]. Moreover, the vapor-liquid equilibrium (VLE) of the DCM + IL binary system was experimentally measured. The NRTL (non-random two-liquid) model was developed to predict the VLE data, and a relative root mean square deviation (rRMSD) of 0.8467 was obtained. The absorption mechanism was explored via FT-IR spectra, 1H-NMR, and quantum chemistry calculations. It showed a nonpolar affinity between the cation and the DCM, while the interaction between the anion and the DCM was a hydrogen bond. Based on the results of the study of the interaction energy, it was found that the hydrogen bond between the anion and the DCM had the greatest influence on the absorption process.

Identification of a Conserved, Linear Epitope on VP3 of Enterovirus A Species Recognized by a Broad-Spectrum Monoclonal Antibody.

Outbreaks of hand, foot and mouth disease (HFMD) have occurred frequently in the Asian-Pacific region over the last two decades, caused mainly by the serotypes in Enterovirus A species. High-quality monoclonal antibodies (mAbs) are needed to improve the accuracy and efficiency of the diagnosis of enteroviruses associated HFMD. In this study, a mAb 1A11 was generated using full particles of CV-A5 as an immunogen. In indirect immunofluorescence and Western blotting assays, 1A11 bound to the viral proteins of CV-A2, CV-A4, CV-A5, CV-A6, CV-A10, CV-A16, and EV-A71 of the Enterovirus A and targeted VP3. It has no cross-reactivity to strains of Enterovirus B and C. By mapping with over-lapped and truncated peptides, a minimal and linear epitope 23PILPGF28 was identified, located at the N-terminus of the VP3. A BLAST sequence search of the epitope in the NCBI genus Enterovirus (taxid: 12059) protein database indicates that the epitope sequence is highly conserved among the Enterovirus A species, but not among the other enterovirus species, first reported by us. By mutagenesis analysis, critical residues for 1A11 binding were identified for most serotypes of Enterovirus A. It may be useful for the development of a cost-effective and pan-Enterovirus A antigen detection for surveillance, early diagnosis and differentiation of infections caused by the Enterovirus A species.

Annexin A protein family: Focusing on the occurrence, progression and treatment of cancer.

The annexin A (ANXA) protein family is a well-known tissue-specific multigene family that encodes Ca2+ phospholipid-binding proteins. A considerable amount of literature is available on the abnormal expression of ANXA proteins in various malignant diseases, including cancer, atherosclerosis and diabetes. As critical regulatory molecules in cancer, ANXA proteins play an essential role in cancer progression, proliferation, invasion and metastasis. Recent studies about their structure, biological properties and functions in different types of cancers are briefly summarised in this review. We further discuss the use of ANXA as new class of targets in the clinical diagnosis and treatment of cancer.

Adipose-derived mesenchymal stem cell-loaded ß-chitin nanofiber hydrogel activates the AldoA/HIF-1α pathway to promote diabetic wound healing.

OBJECTIVES: To identify the effect of adipose-derived mesenchymal stem cell-loaded ß-chitin nanofiber (ADSC-loaded ß-ChNF) hydrogel on diabetic wound healing and clarify its mechanism of action. METHODS: We prepared the ADSC-loaded ß-ChNF hydrogel to repair wounds of db/db diabetic mice. Wound healing rate, histopathology, enzyme-linked immunosorbent assay, and western blot were used to confirm its role and mechanism in promoting diabetic wound healing. RESULTS: The ADSC-loaded ß-ChNF hydrogel accelerated wound healing in db/db diabetic mice, as indicated by increased cell proliferation, epithelization, and tissue granulation in the skin. Moreover, expression of vascular endothelial growth factor (VEGF) and its receptor (VEGFR), matrix metalloproteinase 9 (MMP9), and TIMP metallopeptidase inhibitor 1 (TIMP1) were upregulated. These results demonstrate the beneficial effects of this ADSC-loaded ß-ChNF hydrogel on diabetic wound healing. Furthermore, we show that the ADSC-loaded ß-ChNF hydrogel activated aldolase A (AldoA)/hypoxia-inducible factor 1α (HIF-1α) signaling. An inhibitor of HIF-1α markedly decreased the promotive effects of the ADSC-loaded ß-ChNF hydrogel on wound healing and reduced expression of VEGF, VEGFR, MMP9, and TIMP1. CONCLUSIONS: Our findings suggest that the ADSC-loaded ß-ChNF hydrogel activated the HIF-1α/MMP9 axis through AldoA feedback to promote diabetic wound healing.

Safety and feasibility of left atrial appendage inversion in swine: A proof-of-concept study for potential therapy to prevent embolic stroke.

Objective: Left atrial appendage (LAA) occlusion or exclusion has been used in patients with atrial fibrillation to prevent stroke, but the techniques and devices have shortcomings. This study aims to validate the safety and feasibility of a novel LAA inversion procedure. Methods: LAA inversion procedures were done in six pigs. Before the procedure and at 8 weeks postoperatively, heart rate, blood pressure, and electrocardiogram (ECG) were recorded. The serum concentration of atrial natriuretic peptide (ANP) was measured. The LAA was observed and measured by transesophageal echocardiogram (TEE) and intracardiac echocardiogram (ICE). At 8 weeks after LAA inversion, the animal was euthanized. The heart was collected for morphology and histology, including hematoxylin-eosin, Masson trichrome, and immunofluorescence staining. Results: TEE and ICE showed that LAA was inverted, and the inversion was maintained during the 8-week study duration. Food intake, body weight gain, heart rate, blood pressure, ECG, and serum ANP level were comparable before and after the procedure. Morphology and histological staining showed that there was no obvious inflammation or thrombus. Tissue remodeling and fibrosis were observed at the LAA inverted site. Conclusion: The inversion of LAA effectively eliminates the dead space of LAA and thus may reduce the risk of embolic stroke. The novel procedure is safe and feasible, but the efficacy in reducing embolization remains to be demonstrated in future studies.

Development and validation of risk prediction models for large for gestational age infants using logistic regression and two machine learning algorithms.

BACKGROUND: Large for gestational age (LGA) is one of the adverse outcomes during pregnancy that endangers the life and health of mothers and offspring. We aimed to establish prediction models for LGA at late pregnancy. METHODS: Data were obtained from an established Chinese pregnant women cohort of 1285 pregnant women. LGA was diagnosed as >90th percentile of birth weight distribution of Chinese corresponding to gestational age of the same-sex newborns. Women with gestational diabetes mellitus (GDM) were classified into three subtypes according to the indexes of insulin sensitivity and insulin secretion. Models were established by logistic regression and decision tree/random forest algorithms, and validated by the data. RESULTS: A total of 139 newborns were diagnosed as LGA after birth. The area under the curve (AUC) for the training set is 0.760 (95% confidence interval [CI] 0.706-0.815), and 0.748 (95% CI 0.659-0.837) for the internal validation set of the logistic regression model, which consisted of eight commonly used clinical indicators (including lipid profile) and GDM subtypes. For the prediction models established by the two machine learning algorithms, which included all the variables, the training set and the internal validation set had AUCs of 0.813 (95% CI 0.786-0.839) and 0.779 (95% CI 0.735-0.824) for the decision tree model, and 0.854 (95% CI 0.831-0.877) and 0.808 (95% CI 0.766-0.850) for the random forest model. CONCLUSION: We established and validated three LGA risk prediction models to screen out the pregnant women with high risk of LGA at the early stage of the third trimester, which showed good prediction power and could guide early prevention strategies.

Analysis of N-linked Glycan Alterations in Tissue and Serum Reveals Promising Biomarkers for Intrahepatic Cholangiocarcinoma.

There is an urgent need for the identification of reliable prognostic biomarkers for patients with intrahepatic cholangiocarcinoma (iCCA) and alterations in N-glycosylation have demonstrated an immense potential to be used as diagnostic strategies for many cancers, including hepatocellular carcinoma (HCC). N-glycosylation is one of the most common post-translational modifications known to be altered based on the status of the cell. N-glycan structures on glycoproteins can be modified based on the addition or removal of specific N-glycan residues, some of which have been linked to liver diseases. However, little is known concerning the N-glycan alterations that are associated with iCCA. We characterized the N-glycan modifications quantitatively and qualitatively in three cohorts, consisting of two tissue cohorts: a discovery cohort (n = 104 cases) and a validation cohort (n = 75), and one independent serum cohort consisting of patients with iCCA, HCC, or benign chronic liver disease (n = 67). N-glycan analysis in situ was correlated to tumor regions annotated on histopathology and revealed that bisected fucosylated N-glycan structures were specific to iCCA tumor regions. These same N-glycan modifications were significantly upregulated in iCCA tissue and serum relative to HCC and bile duct disease, including primary sclerosing cholangitis (PSC) (P < 0.0001). N-glycan modifications identified in iCCA tissue and serum were used to generate an algorithm that could be used as a biomarker of iCCA. We demonstrate that this biomarker algorithm quadrupled the sensitivity (at 90% specificity) of iCCA detection as compared with carbohydrate antigen 19-9, the current "gold standard" biomarker of CCA. Significance: This work elucidates the N-glycan alterations that occur directly in iCCA tissue and utilizes this information to discover serum biomarkers that can be used for the noninvasive detection of iCCA.

Identification of specific and shared epitopes at the extreme N-terminal VP1 of Coxsackievirus A4, A2 and A5 by monoclonal antibodies.

Hand, foot and mouth disease (HFMD) is caused by a variety of serotypes in species A of the Enterovirus genus, including recently re-emerged Coxsackievirus A2 (CV-A2), CV-A4 and CV-A5. For development of diagnostic reagents, for surveillance, and the development of multivalent vaccines against HFMD, the antigenicity of HFMD-associated enteroviruses warrants investigation. The purified virions of CV-A4 were inoculated into Balb/c mice and hybridomas were obtained secreting monoclonal antibodies (mAbs) directed against CV-A4 and cross-reacting with other closely related species A enteroviruses. The mAbs were characterized by ELISA, Western blotting and in vitro neutralizing assays. The majority of mAbs was non-neutralizing, with only 2% of the mAbs neutralizing CV-A4 specifically. Most of mAbs bound to linear VP1 epitopes of CV-A4. Interestingly, four types of mAbs were obtained which bound specifically to CV-A4 or were broadly to CV-A4/-A2, CV-A4/-A5 and CV-A4/-A2/-A5, respectively. Mapping with overlapping or single-amino-acid mutant peptides revealed that the four types of mAbs all bound to the first 15 amino acids at the N-terminus of the VP1. This region of picornaviruses is functionally important as it is involved in uncoating and releasing of viral RNA into the cytosol. The binding footprints of four type mAbs are composed of conserved and variable residues and are different from each other. The newly discovered broadly cross-reactive mAbs reflect the high homology of CV-A4/ CV-A2/CV-A5. The results also demonstrate that it is possible and beneficial to develop the diagnostic reagents to detect rapidly the main pathogens of enteroviruses associated with HFMD cause by CV-A4/CV-A2/CV-A5.