Normothermic Ex Vivo Heart Perfusion With Exosomes From Human Umbilical Cord Mesenchymal Stem Cells Improves Graft Function in Donation After Circulatory Death Hearts.

BACKGROUND: This study aimed to investigate the cardioprotective effect of exosomes derived from human umbilical cord mesenchymal stem cells on donation after circulatory death (DCD) hearts preserved with normothermic ex vivo heart perfusion (EVHP) in a rat heart transplantation model. METHODS: Thirty-two male Lewis rats were divided into 2 groups: the control group and the exosome group. The donor-heart rats were subjected to the DCD procedure by suffering a 15-min warm ischemia injury, subsequently preserved with EVHP for 90 min, and then transplanted into recipients via abdominal heterotopic heart transplantation. Vehicle or exosome was added into the perfusate of normothermic EVHP in the control or exosome group. We evaluated left ventricular graft function, myocardial inflammation, and myocardial apoptosis of the donor heart 1.5 h after heart transplantation. Furthermore, we investigate the alternation of myocardial gene expression in the donor hearts between both groups by transcriptome sequencing. RESULTS: The treatment with exosome significantly enhanced cardiac function through increasing left ventricular developed pressure, dp/dtmax, and dp/dtmin of DCD hearts at 90 min after heart transplantation compared with the control group. The myocardial cells in the exosome group exhibited an orderly arrangement without obvious edema. Furthermore, exosome added into perfusate in the exosome group significantly attenuated the level of inflammatory response and apoptosis. Transcriptome sequencing and RT-qPCR showed the phosphoinositide 3-kinase/protein kinase B pathway was activated after exosome treatment. CONCLUSIONS: Normothermic EVHP combined with exosome can be a promising and novel DCD heart preservation strategy, alleviating myocardial ischemia-reperfusion injury in the DCD heart.

Transesophageal echocardiography-guided percutaneous closure of the patent foramen ovale only uses the sheath.

Background: Percutaneous closure of the patent foramen ovale (PFO) is primarily guided by fluoroscopy in the catheter room, during which procedure both the guidewire and sheath need to pass through the PFO. We performed PFO closure using a transesophageal echocardiography (TEE)-guided approach and only the sheath was passed through the PFO during the procedure. This study aimed to evaluate the feasibility and safety of PFO closure using this technique. Methods: A retrospective observational study was performed. A total of 117 consecutive adult patients underwent percutaneous PFO closure without fluoroscopy, under the sole guidance of TEE in our hospital between December 2018 and December 2021. The data of each patient consisted of preoperative, operative, and postoperative variables collected. The primary outcome is that the occluder was successfully released. The secondary outcomes included perioperative and follow-up transthoracic echocardiography (TTE), Headache impact test-6 (HIT-6) score and clinical symptoms. Results: Transvenous PFO closure under TEE guidance was successful in all cases. The sample consisted of 93 females and 24 males with an average age of 42.3±7.8 years. There were 28 patients with preoperative cerebral infarction [Risk of Paradoxical Embolism (RoPE) score >6 points] and 89 patients with migraine. All patients underwent a preoperative TEE to confirm the presence of PFO, and contrast-enhanced transcranial Doppler (c-TCD) acoustic contrast suggested grades 3 to 4. The average time of surgery for patients (puncture to removal of the sheath) was 32 minutes. Three cases of vagus nerve reflex manifestations during surgery and two cases of transient ventricular arrhythmia all improved after symptomatic treatment. There were no instances of metal allergy, hemolysis, or other acute vascular procedural complications. For all 89 patients with migraine, significant relief or resolution was achieved during the first six-month follow-up (P<0.001). Conclusions: As a monotherapy, percutaneous closure of PFO guided by TEE where only the sheath passes through the PFO during the operation is an effective procedure with a high success rate and a low complication rate.

Synergetic EGCG and coenzyme Q10 DSPC liposome nanoparticles protect against myocardial infarction.

At the site of myocardial infarction (MI), various phenomena such as oxidative stress and myocardial apoptosis can be observed. Both epigallocatechin gallate (EGCG) and coenzyme Q10 (CoQ10) exhibit antioxidant and anti-inflammatory effects. Macrophages have demonstrated a higher internalization rate of cationic liposomes, thereby increasing their bioavailability. This study utilized EGCG in synergy with CoQ10 as an antioxidant agent and distearyl phosphatidylcholine (DSPC) as the carrier, to create liposome nanoparticles known as CE-LNPs. The CE-LNPs exhibited favorable biocompatibility and were effectively engulfed by macrophages in vitro. In addition, the CE-LNPs effectively eradicated reactive oxygen species (ROS) in hypoxic cardiomyocytes, mitigated myocardial cell apoptosis, and sustained the functionality and proliferation of myocardial cells. The anti-apoptotic effect of the CE-LNPs was further validated through TUNEL and Annexin V FITC/PI experiments. The therapeutic efficacy of CE-LNPs was evaluated in a murine model of MI. CE-LNPs demonstrated a significant reduction in scar area in vivo, facilitating cardiac repair and improving cardiac function. These findings provide evidence that EGCG synergistically combined with CoQ10 in DSPC liposome nanoparticles offers protection against MI.

Coaxially Conductive Organic Wires Through Self-Assembly.

Here, we describe the synthesis of the hexameric macrocyclic aniline (MA[6]), which spontaneously assembles into coaxially conductive organic wires in its oxidized and acidified emeraldine salt (ES) form. Electrical measurements reveal that ES-MA[6] exhibits high electrical conductivity (7.5 × 10-2 S·cm-1) and that this conductivity is acid-base responsive. Single-crystal X-ray crystallography reveals that ES-MA[6] assembles into well-defined trimeric units that then stack into nanotubes with regular channels, providing a potential route to synthetic nanotubes that are leveraged for ion or small molecule transport. Ultraviolet-visible-near-infrared absorbance spectroscopy and electron paramagnetic spectroscopy showcase the interconversion between acidic (conductive) and basic (insulating) forms of these macrocycles and how charge carriers are formed through protonation, giving rise to the experimentally observed high electrical conductivity.

Anti-Oxidative, Anti-Apoptotic, and M2 Polarized DSPC Liposome Nanoparticles for Selective Treatment of Atherosclerosis.

Purpose: Oxidative stress is one of the main pathogenic factors of atherosclerosis. However, no antioxidants have brought positive effects on the treatment of atherosclerosis. To selectively treat atherosclerosis, various means such as antioxidation, anti-apoptosis, and M2 polarization are used. The ultimate goal is that multiple regulatory pathways can help to treat atherosclerosis. Patients and Methods: In this study, Simvastatin (SIM) as a model drug, EGCG as an antioxidant agent, and distearyl phosphatidylcholine (DSPC) as major carriers were used to make liposome nanoparticles (SE-LNPs). The cytotoxicity, phagocytosis, antioxidant, and anti-apoptotic properties of nanoparticles were tested in vitro. ApoE-/- atherosclerotic mice were treated with nanoparticles. The changes of aortic Oil red staining, blood lipid, HE, and Masson sections of the aortic root were observed. Results: SE-LNPs exhibited a sustained release profile, potentially enabling the accumulation of the majority amount of drugs at the atherosclerotic plaque. The phagocytosis effect was stronger in RAW. The anti-oxidative and anti-apoptotic effects of the formulation were verified in vitro. SE-LNPs promoted the polarization of M2 macrophages. The therapeutic effect of SE-LNPs was assessed in the ApoE-/- mice model of atherosclerosis. SE-LNPs reduced reactive oxygen species and lipids in vivo. The results of Oil red staining, blood lipid, HE, and Masson sections of the aortic root showed the recovery of the focus. Conclusion: Studies have shown that SE-LNPs could resist oxidation, and apoptosis, promote M2 polarization, and reduce blood lipids and lesions, which is a reliable and selective treatment for atherosclerosis.

Imaging the Thermal Hysteresis of Single Spin-Crossover Nanoparticles.

The magnetic hysteresis property during the spin transition of spin-crossover (SCO) materials holds great promise for their applications in spin electronics, information storage, thermochromic, and nanophotonic devices. Existing studies often measured the averaged property of a bulk sample consisting of lots of individuals. When considering the significant heterogeneity among different individuals and the inevitable interparticle interactions, ensemble measurement not only blurred the structure-property relationship but also compromised the intrinsic hysteresis property and cyclability. Herein, we employed a recently developed surface plasmon resonance microscopy (SPRM) method to measure the thermal hysteresis curve of single isolated SCO nanoparticles. The thermal-induced spin transition was found to alter the optical contrast of single SCO nanoparticles, which was optically readout using SPRM in a quantitative, nonintrusive, and high-throughput manner. Single nanoparticle measurements revealed an intrinsic transition temperature that was independent of the temperature scan rate and superior stability after over 11 000 cycles of single SCO nanoparticles. Correlations between the hysteresis and the size and morphology of the same individuals further uncovered the significant nanoparticle-to-nanoparticle heterogeneity with implications for the size-property relationship and rational design of SCO materials with improved performance.

Characterization of Cu(II) and Cd(II) resistance mechanisms in Sphingobium sp. PHE-SPH and Ochrobactrum sp. PHE-OCH and their potential application in the bioremediation of heavy metal-phenanthrene co-contaminated sites.

Soil that is co-contaminated with heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) is difficult to bioremediate due to the ability of toxic metals to inhibit PAH degradation by bacteria. We demonstrated the resistance mechanisms to Cu(II) and Cd(II) of two newly isolated strains of Sphingobium sp. PHE-SPH and Ochrobactrum sp. PHE-OCH and further tested their potential application in the bioremediation of HM-phenanthrene (PhA) co-contaminated sites. The PHE-SPH and PHE-OCH strains tolerated 4.63 and 4.34 mM Cu(II) and also showed tolerance to 0.48 and 1.52 mM Cd(II), respectively. Diverse resistance patterns were detected between the two strains. In PHE-OCH cells, the maximum accumulation of Cu(II) occurred in the cell wall, while the maximum accumulation was in the cytoplasm of PHE-SPH cells. This resulted in a sudden suppression of growth in PHE-OCH and a gradual inhibition in PHE-SPH as the concentration of Cu(II) increased. Organic acid production was markedly higher in PHE-OCH than in PHE-SPH, which may also have a role in the resistance mechanisms, and contributes to the higher Cd(II) tolerance of PHE-OCH. The factors involved in the absorption of Cu(II) or Cd(II) in PHE-SPH and PHE-OCH were identified as proteins and carbohydrates by Fourier transform infrared (FT-IR) spectroscopy. Furthermore, both strains showed the ability to efficiently degrade PhA and maintained this high degradation efficiency under HM stress. The high tolerance to HMs and the PhA degradation capacity make Sphingobium sp. PHE-SPH and Ochrobactrum sp. PHE-OCH excellent candidate organisms for the bioremediation of HM-PhA co-contaminated sites.

Simultaneous enhanced removal of Cu, PCBs, and PBDEs by corn from e-waste-contaminated soil using the biodegradable chelant EDDS.

We evaluated the influence of the biodegradable chelant ethylenediamine disuccinic acid (EDDS) on plant uptake of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and Cu by corn from electronic waste (e-waste)-contaminated soil. The highest concentration and highest total uptake of Cu in corn were observed in the treatment with 5 mM EDDS, which resulted in a 4-fold increase of the Cu translocation factor (C(shoot)/C(root)) compared to the control. The concentrations of PCBs and PBDEs in shoots and roots increased with increasing application rates of EDDS, and 1.58- and 1.32-fold average increases in the concentrations of PCBs and PBDEs, respectively, were observed in shoots in the EDDS treatments. A significant positive correlation was observed between shoot Cu and shoot PCBs and PBDEs. We speculate that PCBs and PBDEs were activated by the EDDS-triggered dissolved organic carbon (DOC) and then indiscriminately taken up by roots and translocated to shoots following damage to the roots mainly by the increased extractable Cu resulting from the EDDS application.

Permeability of Plant Young Root Endodermis to Cu Ions and Cu-Citrate Complexes in Corn and Soybean.

The non-selective apoplastic passage of Cu and Cu-citrate complexes into the root stele of monocotyledonous corn and dicotyledonous soybean was investigated using an inorganic-salt-precipitation technique. Either Cu ions or Cu-citrate complexes were drawn into root through the apoplast from the root growth medium, and K4[Fe(CN)6] was subsequently perfused through xylem vessels or the entire root cross section. Based on microscopic identification of the reddish-brown precipitates of copper ferrocyanide in the cell walls of the xylem of corn and soybean roots, Cu(2+) passed through the endodermal barrier into the xylem of both species. When the solution containing 200 µM CuSO4 and 400 µM sodium citrate (containing 199.98 µM Cu-citrate, 0.02 µM Cu(2+)) was drawn via differential pressure gradients into the root xylem while being perfused with K4[Fe(CN)6] through the entire root cross-section, reddish-brown precipitates were observed in the walls of the stele of soybean, but not corn root. However, when a CuSO4 solution containing 0.02 or 0.2 µM free Cu(2+) was used, no reddish-brown precipitates were detected in the stele of either of the two plants. Results indicated that endodermis was permeable to Cu-citrate complexes in primary roots of soybean, but not corn. The permeability of the endodermal barrier to the Cu-citrate complex may vary between dicotyledonous and monocotyledonous plants, which has considerable implications for chelant-enhanced phytoextraction.