Effectively Sieving Alkali Metal Ions Using Functionalized Graphene Oxide Membranes by Exploiting Water-Repellent Interactions.

Sieving membranes capable of discerning different alkali metal ions are important for many technologies, such as energy, environment, and life science. Recently, two-dimensional (2D) materials have been extensively explored for the creation of sieving membranes with angstrom-scale channels. However, because of the same charge and similar hydrated sizes, mostly laminated membranes typically show low selectivity (<10). Herein, we report a facile and scalable method for functionalizing graphene oxide (GO) laminates by dually grafting cations and water-repellent dimethylsiloxane (DMDMS) molecules to achieve high selectivities of ∼50 and ∼20 toward the transport of Cs+/Li+ and K+/Li+ ion pairs, surpassing many of the state-of-the-art laminated membranes. The enhanced selectivity for alkali metal ions can be credited to a dual impact: (i) strong hydrophobic interactions between the incident cations' hydration shells and the water-repellent DMDMS; (ii) the efficient screening of electrostatic interactions that hamper selectivity.

Cocatalyst Embedded Ce-BDC-CeO2 S-Scheme Heterojunction Hollowed-Out Octahedrons With Rich Defects for Efficient CO2 Photoreduction.

Constructing heterojunction photocatalysts with optimized architecture and components is an effective strategy for enhancing CO2 photoreduction by promoting photogenerated carrier separation, visible light absorption, and CO2 adsorption. Herein, defect-rich photocatalysts (Ni2P@Ce-BDC-CeO2 HOOs) with S-scheme heterojunction and hollowed-out octahedral architecture are prepared by decomposing Ce-BDC octahedrons embedded with Ni2P nanoparticles and subsequent lactic acid etching for CO2 photoreduction. The hollowed-out octahedral architecture with multistage pores (micropores, mesopores, and macropores) and oxygen vacancy defects are simultaneously produced during the preparation process. The S-scheme heterojunction boosts the quick transfer and separation of photoinduced charges. The formed hollowed-out multi-stage pore structure is favorable for the adsorption and diffusion of CO2 molecules and gaseous products. As expected, the optimized photocatalyst exhibits excellent performance, producing CO with a yield of 61.6 µmol h-1 g-1, which is four times higher than that of the original Ce-BDC octahedrons. The X-ray photoelectron spectroscopy, scanning Kelvin probe, and electron spin resonance spectroscopy characterizations confirm the S-schematic charge-transfer route. The key intermediate species during the CO2 photoreduction process are detected by in situ Fourier transform infrared spectroscopy to support the proposed mechanism for CO2 photoreduction. This work presents a synthetic strategy for excellent catalysts with potential prospects in photocatalytic applications.

Engineering of Ultra-Thin Layer of MIL-125(Ti) Nanosheet\Zn-Tetracarboxy-Phthalocyanine S-Scheme Heterojunction as Photocatalytic CO2 Reduction Catalyst.

Metal-organic frameworks (MOFs) with ultrathin 2D structure have attracted remarkable attention in photocatalytic application owing to the accessibility of abundant active sites on the surface. But high charge recombination results in poor photocatalytic activity. Herein, the synthesis of ultrathin MIL-125(Ti) nanosheets is reported with a thickness of 1.3 nm through a simple chemical reaction route of precursor solution aging and subsequent solvothermal process for photocatalytic CO2 production. The maximal CO evolution rate achieves 200.8 µmol g-1 h-1, which is prominently higher than that (78.6 µmol g-1 h-1) of the bulk MIL-125(Ti) counterpart. Furthermore, the structurally stable Zn (II) tetracarboxy phthalocyanine (ZnTcPc) molecules assembly on ultrathin MIL-125(Ti) nanosheet (NS) to form MIL-125(Ti) NS\ZnTcPc S-scheme heterojunction through the strong interaction between the Ti3+ in MIL-125(Ti) and the COOH in ZnTcPc. The introduction of ZnTcPc greatly extends light absorption range and increases charge separation rate. The experimental and density functional theory calculation results validate that the MIL-125(Ti) NS\ZnTcPc S-scheme heterojunction can favor CO2 adsorption and effectively depress the formation energy of the intermediates, achieving a high CO evolution rate of 450.8 µmol g-1 h-1. This work provides a strategy of engineering 2D MOF-based heterostructure systems for photocatalytic application.

Inactivation of the tumor suppressor p53 by long noncoding RNA RMRP.

p53 inactivation is highly associated with tumorigenesis and drug resistance. Here, we identify a long noncoding RNA, the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP), as an inhibitor of p53. RMRP is overexpressed and associated with an unfavorable prognosis in colorectal cancer. Ectopic RMRP suppresses p53 activity by promoting MDM2-induced p53 ubiquitination and degradation, while depletion of RMRP activates the p53 pathway. RMRP also promotes colorectal cancer growth and proliferation in a p53-dependent fashion in vitro and in vivo. This anti-p53 action of RMRP is executed through an identified partner protein, SNRPA1. RMRP can interact with SNRPA1 and sequester it in the nucleus, consequently blocking its lysosomal proteolysis via chaperone-mediated autophagy. The nuclear SNRPA1 then interacts with p53 and enhances MDM2-induced proteasomal degradation of p53. Remarkably, ablation of SNRPA1 completely abrogates RMRP regulation of p53 and tumor cell growth, indicating that SNRPA1 is indispensable for the anti-p53 function of RMRP. Interestingly and significantly, poly (ADP-ribose) polymerase (PARP) inhibitors induce RMRP expression through the transcription factor C/EBPß, and RMRP confers tumor resistance to PARP inhibition by preventing p53 activation. Altogether, our study demonstrates that RMRP plays an oncogenic role by inactivating p53 via SNRPA1 in colorectal cancer.

Development of a highly specific LAMP assay for detection of Sarcocystis tenella and Sarcocystis gigantea in sheep.

Sarcocystis infection in sheep has caused significant economic losses in the livestock industry, and the genetic similarity among Sarcocystis species highlights the need for precise diagnostic methods in sheep. This study developed a loop-mediated isothermal amplification (LAMP) method targeting COX-1 and 28S rRNA genes to detect Sarcocystis tenella and Sarcocystis gigantea, respectively. The LAMP method exhibited high specificity, selectively amplifying target DNA sequences without cross-reactivity with closely related protozoa, such as Toxoplasma gondii and Neospora caninum. Detection limits were determined as 3 × 105 copies/L for S. tenella and 6 × 104 copies/L for S. gigantea, enabling sensitive identification of low-level infections. Comparative analysis with conventional PCR on sheep cardiac tissues demonstrated a higher LAMP detection rate (80.0% vs 66.7%). In conclusion, the LAMP method offers superior sensitivity to conventional PCR, allows visual confirmation of results, and provides a rapid diagnostic tool for identifying S. tenella and S. gigantea infection in sheep. However, due to the limitation of sample availability, we were unable to assess all Sarcocystis species that use sheep as intermediate hosts, which warrants further research.

Long-term SARS-CoV-2 neutralizing antibody level prediction using multimodal deep learning: A prospective cohort study on longitudinal data in Wuhan, China.

The ongoing epidemic of SARS-CoV-2 is taking a substantial financial and health toll on people worldwide. Assessing the level and duration of SARS-CoV-2 neutralizing antibody (Nab) would provide key information for government to make sound healthcare policies. Assessed at 3-, 6-, 12-, and 18-month postdischarge, we described the temporal change of IgG levels in 450 individuals with moderate to critical COVID-19 infection. Moreover, a data imputation framework combined with a novel deep learning model was implemented to predict the long-term Nab and IgG levels in these patients. Demographic characteristics, inspection reports, and CT scans during hospitalization were used in this model. Interpretability of the model was further validated with Shapely Additive exPlanation (SHAP) and Gradient-weighted Class Activation Mapping (GradCAM). IgG levels peaked at 3 months and remained stable in 12 months postdischarge, followed by a significant decline in 18 months postdischarge. However, the Nab levels declined from 6 months postdischarge. By training on the cohort of 450 patients, our long-term antibody prediction (LTAP) model could predict long-term IgG levels with relatively high area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1-score, which far exceeds the performance achievable by commonly used models. Several prognostic factors including FDP levels, the percentages of T cells, B cells and natural killer cells, older age, sex, underlying diseases, and so forth, served as important indicators for IgG prediction. Based on these top 15 prognostic factors identified in IgG prediction, a simplified LTAP model for Nab level prediction was established and achieved an AUC of 0.828, which was 8.9% higher than MLP and 6.6% higher than LSTM. The close correlation between IgG and Nab levels making it possible to predict long-term Nab levels based on the factors selected by our LTAP model. Furthermore, our model identified that coagulation disorders and excessive immune response, which indicate disease severity, are closely related to the production of IgG and Nab. This universal model can be used as routine discharge tests to identify virus-infected individuals at risk for recurrent infection and determine the optimal timing of vaccination for general populations.

Experiences Shape Hippocampal Neuron Morphology and the Local Levels of CRHR1 and OTR.

The dorsal hippocampus is involved in behavioral avoidance regulation. It is unclear how experiences such as the neonatal stress of maternal deprivation (MD) and post-weaning environmental enrichment (EE) affect avoidance behavior and the dorsal hippocampal parameters, including neuronal morphology, corticotrophin-releasing hormone (CRH) signaling, and oxytocin receptor (OTR) level. In male BALB/c mice, we found that MD impaired avoidance behavior in the step-on test compared to non-MD and EE rearing conditions could alleviate that partially. MD increased neuronal branches in the CA1 but decreased synaptic connection levels in the CA2, CA3, and DG. Meanwhile, MD increased the CA1's OTR levels, which negatively correlated with nucleus densities. MD also increased the CA1's and CA2's CRH levels, which positively correlated with CRHR1 levels. However, MD statistically elevated the CA3's CRH receptor 1 (CRHR1) levels, which negatively correlated with nucleus densities and, probably, synaptic connection levels in the CA3. The additive effects of MD and EE maintained similar CRH levels and CRHR1 levels as well as OTR levels in the hippocampal areas as the additive of non-MD and non-EE. However, the presence of MD and EE still decreased the CA1's neuronal branches and the CA2's and DG's synaptic connection levels. The study illustrates how MD and EE affect avoidance behaviors, hippocampal neuron morphology, and CRH and OTR levels. The results indicate that the late-life environmental improvement partially restores the alterations in dorsal hippocampal areas induced by early life stress.

Combination of Backbone Rigidity and Richness in Aryl Structures Enables Direct Membrane Translocation of Polymer Scaffolds for Efficient Gene Delivery.

The development of cell-penetrating polymers with endocytosis-independent cell uptake pathways has emerged as a prominent strategy to enhance the transfection efficiency. Inspired by the rigid α-helical structure that endows polypeptides with cell-penetrating ability, we propose that a rigid backbone can facilitate the corresponding polymer vector's performance in gene delivery by bypassing the difficult endosomal escape process. Meanwhile, the installation of aromatic domains, as a way to promote gene transfection efficiency, is employed through the construction of a poly(benzyl ether) (PBE)-based scaffold in this work. We demonstrate that the direct membrane translocation capability of the synthesized PBE contributes to its enhanced transfection performance and excellent biocompatibility profile, rendering the imidazolium-functionalized PBE scaffold with higher activity and biocompatibility. Molecular details of the PBE-lipid interaction are also revealed in molecular dynamics simulations, indicating the important roles of individual structural elements on the polymeric scaffold in the membrane penetration process.

Thermal preconditioning can reduce the incidence of intraoperatively acquired pressure injuries.

Intraoperatively acquired pressure injuries (IAPIs) occur frequently among patients who undergo surgical procedures that last longer than 3 h. Several studies indicated that heat shock proteins (HSPs) play an important role in the protection of stress-induced damages in skin tissues. Hence, the aim of this study was to investigate the potential preventive effect of thermal preconditioning (TPC) on IAPIs in surgical patients and rats and to identify the differentially expressed HSP genes in response to the above treatment. TPC was performed on one group of hairless rats before the model of pressure injuries was established. Subsequently, the size of skin lesions was measured and the expression levels of mRNA and protein of HSPs of the pressured skin were detected by real-time polymerase chain reaction (RT-PCR), western blot, and immunohistochemical staining. For human studies, 118 surgical patients were randomly divided into the TPC group (n = 59) and the control group (n = 59), respectively. The temperature and pressure of sacral skin, as well as the incidence of pressure injury (PI) were detected and compared. In animal studies, TPC significantly reduced both the size and incidence of PI in rats on the second, third and fourth days post treatment. In addition, the expression levels of both mRNA and protein of HSP27 were increased in the TPC group, compared with the control group. Immunohistochemical staining showed that HSP27 was distributed in various types of dermal cells and increased in basal cells. In human studies, a significant reduction (75%) of IAPIs was observed among the patients in the TPC group. TPC can reduce the incidence of PI in rats and humans, and the upregulation of HSP27 may play an important role in this biological progress. Further studies are warranted to explore the molecular mechanism of the preventive effect in PI mediated by HSP27.

Effects of Follicular Fluid on Physiological Characteristics and Differentiation of Fallopian Tube Epithelial Cells Implicating for Ovarian Cancer Pathogenesis.

The fallopian tube (FT) is an important reproductive organ in females. Ample evidence suggests that the distal end of FT is the original site of high-grade serous ovarian carcinoma (HGSC). FT may suffer from repeated injury and repair stimulated by follicular fluid (FF); however, this hypothesis has not been examined. In fact, the molecular mechanism of homeostasis, differentiation, and the transformation of fallopian tube epithelial cells (FTECs) resulting from the stimulation of FF are still enigmatic. In this study, we examined the effects of FF along with factors present in the FF on a variety of FTEC models, including primary cell culture, ALI (air-liquid interface) culture, and 3D organ spheroid culture. We found that FF plays a similar role to estrogen in promoting cell differentiation and organoid formation. Moreover, FF significantly promotes cell proliferation and induces cell injury and apoptosis in high concentrations. These observations may help us to investigate the mechanisms of the initiation of HGSC.

CircASPH promotes KGN cells proliferation through miR-375/MAP2K6 axis in Polycystic Ovary Syndrome.

Polycystic Ovary Syndrome (PCOS) is a kind of endocrine disorder which is prevalent in adult women, so exploring more biomarkers for PCOS is imperative. Recently, circular RNA and microRNA are confirmed to be related with PCOS development. Whether circular RNA ASPH (circASPH) is involved in PCOS need to be studied further. We utilized RT-qPCR to measure the expression levels of circASPH, miR-375 and MAP2K6 in PCOS patients and normal group. The effects of circASPH and miR-375 on KGN cells proliferation and apoptosis were observed by CCK-8 assay, EdU incorporation assay and apoptosis assay, separately. Then Dual-luciferase reporter assay was carried out to verify the circASPH/miR375 axis and miR375/MAP2K6 axis. The interaction between circASPH and MAP2K6 were detected with the support of RT-qPCR and Western blot. We found circASPH and MAP2K6 were both over-expressed in PCOS patients, while miR-375 was in the opposite direction. Moreover, miR-375 was negatively regulated by circASPH, while MAP2K6 was positively regulated by circASPH. In addition, circASPH directly targeted miR-375, which targeted MAP2K6. More than that, the knockdown of circASPH repressed KGN cells proliferation and enhanced apoptosis, while the silence of miR-375 reversed the above effects. In conclusion, circASPH promotes KGN cells proliferation through miR-375/MAP2K6 axis in PCOS, and they are thought-provoking biomarkers for PCOS diagnosis and therapy.

Universal and Stable Slippery Coatings: Chemical Combination Induced Adhesive-Lubricant Cooperation.

Liquid lubricant of low affinity makes slippery coatings widely used in lubricating, anti-biofouling, anti-icing, fluid guiding, and drag reduction. Two critical challenges, however, remain in the practical application of slippery coatings consisting of liquid lubricants: (1) universality regardless of roughness and chemical composition of substrates, (2) stability of surface lubricity against evaporation. Herein, a chemical method is reported to create a universal and stable slippery lubricant-adhesive cooperated coating (SLACC) through acid catalyzed dehydration reaction between the phenolic hydroxyl of polydopamine (PDA), with universal (for challenge-1) and strong (for challenge-2) adhesion properties, and liquid-like polydimethylsiloxane (PDMS), with lubricant properties. Through overlying PDMS on PDA, a spatial gradient interpenetration of chemical combined PDA and PDMS leaving lubricant PDMS at the outermost of coating is achieved. This structure contributes to the following performances of SLACC: nearly universality suitable for 100 different abiotic or biotic substrates and stability sustainable for long-term usages, UV radiating, refrigerating, hot air drying, freeze drying, knife scratch and abrasion. This proposed strategy is envisioned anti-fouling from plane to tube and exhibits drag reduction in confined space.

Copper Azide Nanoparticle-Encapsulating MOF-Derived Porous Carbon: Electrochemical Preparation for High-Performance Primary Explosive Film.

It is highly desired but still remains challenging to design a primary explosive-based nanoparticle-encapsulated conductive skeleton for the development of powerful yet safe energetic films employed in miniaturized explosive systems. Herein, a proof-of-concept electrochemical preparation of metal-organic frameworks (MOFs) derived porous carbon embedding copper-based azide (Cu(N3 )2 or CuN3 , CA) nanoparticles on copper substrate is described. A Cu-based MOF, i.e., Cu-BTC is fabricated based on anodized Cu(OH)2 nanorods, as a template, to achieve CA/C film through pyrolysis and electrochemical azidation. Such a CA/C film, which is woven by numerous ultrafine nanofibers, favorably demonstrates excellent energy release (945-2090 J g-1 ), tunable electrostatic sensitivity (0.22-1.39 mJ), and considerable initiation ability. The performance is superior to most reported primary explosives, since the CA nanoparticles contribute to high brisance and the protection of the porous carbon network. Notably, the growth mechanism of the CA/C film is further disclosed by detailed experimental investigation and density functional theory (DFT) calculation. This work will offer new insight to design and develop a CA-based primary explosive film for applications in advanced explosive systems.

Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression.

BACKGROUND: Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury. RESULTS: By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurological damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode. CONCLUSION: MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD.

Effect of Heat Shock Preconditioning on Pressure Injury Prevention via Hsp27 Upregulation in Rat Models.

Pressure injury (PI) prevention is a huge industry and involves various interventions. Temperature and moisture are important factors for wound healing; however, the active mechanism by which "moist heat" affects PI prevention has not yet been clarified. Thus, we explored the protective and therapeutic effects of hydrotherapy on PI based on the preconditioning (PC) principle, which might be useful for clinical practice. This study aimed to investigate the preventive mechanisms of heat shock preconditioning on PIs in rat models. The experiment was performed in the basic medical laboratory of Nagano College of Nursing in Japan. Ten rats were divided into two groups, with five rats in each group. Rats in the control group were not bathed. Rats in the preconditioning group (PC group) were bathed with hot tap-water. Bathing was conducted thrice a week. After bathing for 4 weeks, the PI model was constructed on the rats' dorsal skin. The skin temperature, skin moisture, and area of ulcers were compared between the two groups. In vitro, we investigated the expression of heat shock protein 27 (Hsp27) in 6, 12, and 24 h after the PI model was constructed through Western blot analysis. Ulcers occurred in the control group 24 h after the PI model constructed, wheras the PC group exhibited ulcers after 36 h. The ulcer area was larger in the control group than that in the PC group after 24 h (all p < 0.05). The temperatures of PI wounds in the control group decreased and were lower than those in the PC group after 1, 6, 12, 36, and 48 h (all p < 0.05). However, the skin moisture levels of PI wounds increased in the control group and were higher than those in the PC group at the same time (all p < 0.05). Using Western blot analysis, hydrotherapy preconditioning showed the potential to increase Hsp27 expression after pressure was released (p < 0.05). We determine that heat shock preconditioning had a preventive effect on PIs in rat models, a result that may be associated with their actions in the upregulation of Hsp27.

Exponential Increase in an Ionic Signal: A Dominant Role of the Space Charge Effect on the Outer Surface of Nanochannels.

Nanochannels have advantage in sensitive analyses due to the confinement effects on ionic signal in nano- or sub-nanometric confines but could realize further gains by optimizing signal mechanism. Making target recognitions on the outer surface of nanochannels has been verified to improve target recognitions and signal conversions by maximizing surfaces accessible to targets and ions, but until recently, the signal mechanism has been still unclear. Using electroneutral peptide nucleic acid (PNA) and negative-charged DNA, we verified a dominant space charge effect on an ionic signal on the outer surface of nanochannels. A typical exponential increase of the ionic signal with the charge density on the outer surface has been demonstrated through the PNA-PNA, PNA-DNA, DNA-DNA hybrid, DNA cleavage, and hybridization chain reaction. These results challenge the essential role of steric hindrance on the ionic signal and describe a new ion passageway surrounded and accelerated by the stern layer of charged species on the nanochannel outer surface.

Hierarchical Co0.85 Se-CdSe/MoSe2 /CdSe Sandwich-Like Heterostructured Cages for Efficient Photocatalytic CO2 Reduction.

Fabricating efficient photocatalysts with rapid charge carrier separation and high visible light harvesting is an advisable strategy to improve CO2 reduction performance. Herein, hierarchical Co0.85 Se-CdSe/MoSe2 /CdSe cages with sandwich-like heterostructure are prepared to act as efficient photocatalysts for CO2 reduction. In this study, the structure and composition of the final products can be regulated through the cation-exchange reaction in the presence of ascorbic acid. In the Co0.85 Se-CdSe/MoSe2 /CdSe cages, MoSe2 nanosheets function as a bridge to integrate Co0.85 Se-CdSe and CdSe on both sides of the MoSe2 nanosheet shell into a sandwich-like heterostructured catalyst system, which possesses multiple positive merits for photocatalysis, including accelerated transport and separation of photogenerated carriers, improved visible light utilization, and increased catalytic active sites. Thus, the optimized Co0.85 Se-CdSe/MoSe2 /CdSe cages exhibit remarkable visible-light photocatalytic performance and outstanding stability for CO2 reduction with a high CO average yield of 15.04 µmol g-1 h-1 and 90.14% selectivity, which are much higher than those of other control samples including single-component catalysts and binary hybrid catalysts. This study provides a promising way for the design and fabrication of high-efficiency photocatalysts.

Apolipoprotein CIII Deficiency Protects Against Atherosclerosis in Knockout Rabbits.

OBJECTIVE: Apo (apolipoprotein) CIII mediates the metabolism of triglyceride (TG)-rich lipoproteins. High levels of plasma apoCIII are positively correlated with the plasma TG levels and increase the cardiovascular risk. However, whether apoCIII is directly involved in the development of atherosclerosis has not been fully elucidated. Approach and Results: To examine the possible roles of apoCIII in lipoprotein metabolism and atherosclerosis, we generated apoCIII KO (knockout) rabbits using ZFN (zinc finger nuclease) technique. On a normal standard diet, apoCIII KO rabbits exhibited significantly lower plasma levels of TG than those of WT (wild type) rabbits while total cholesterol and HDL (high-density lipoprotein) cholesterol levels were unchanged. Analysis of lipoproteins isolated by sequential ultracentrifugation revealed that reduced plasma TG levels in KO rabbits were accompanied by prominent reduction of VLDLs (very-low-density lipoproteins) and IDLs (intermediate-density lipoproteins). In addition, KO rabbits showed faster TG clearance rate after intravenous fat load than WT rabbits. On a cholesterol-rich diet, KO rabbits exhibited constantly and significantly lower levels of plasma total cholesterol and TG than WT rabbits, which was caused by a remarkable reduction of ß-VLDLs-the major atherogenic lipoproteins. ß-VLDLs of KO rabbits showed higher uptake by cultured hepatocytes and were cleared faster from the circulation than ß-VLDLs isolated from WT rabbits. Both aortic and coronary atherosclerosis was significantly reduced in KO rabbits compared with WT rabbits. CONCLUSIONS: These results indicate that apoCIII deficiency facilitates TG-rich lipoprotein catabolism, and therapeutic inhibition of apoCIII expression may become a novel means not only for the treatment of hyperlipidemia but also for atherosclerosis.

Integrated endotoxin-adsorption and antibacterial properties of platelet-membrane-coated copper silicate hollow microspheres for wound healing.

Serious infection caused by drug-resistant gram-negative bacteria and their secreted toxins (e.g., lipopolysaccharide) is a serious threat to human health. Thus, treatment strategies that efficiently kill bacteria and reducing the impact of their toxins simultaneously are urgently required. Herein, a novel antibacterial platform composed of a mesoporous copper silicate microsphere (CSO) core and a platelet membrane (PM) shell was prepared (CSO@PM). CSO@PM specifically targets bacteria owing to formyl peptide receptors on the PM and, combined with photothermal therapy (PTT), exhibits highly effective bacter icidal activity. Importantly, CSO@PM can adsorb lipopolysaccharide secreted by gram-negative bacteria, resulting in inflammation reduction. Thus, CSO@PM stimulates re-epithelialization and granulation-tissue formation, promoting wound healing. Moreover, this antibacterial platform exhibits no obvious toxicity at all the test concentrations in vitro and in vivo. Thus, CSO@PM exhibits a robust antibacterial effect and a strong toxin-adsorption capacity, facilitating the clinical treatment of many bacterial infections and the development of next-generation antibacterial nanoagents.

Macrophage-derived MMP-9 enhances the progression of atherosclerotic lesions and vascular calcification in transgenic rabbits.

Matrix metalloproteinase-9 (MMP-9), or gelatinase B, has been hypothesized to be involved in the progression of atherosclerosis. In the arterial wall, accumulated macrophages secrete considerable amounts of MMP-9 but its pathophysiological functions in atherosclerosis have not been fully elucidated. To examine the hypothesis that macrophage-derived MMP-9 may affect atherosclerosis, we created MMP-9 transgenic (Tg) rabbits to overexpress the rabbit MMP-9 gene under the control of the scavenger receptor A enhancer/promoter and examined their susceptibility to cholesterol diet-induced atherosclerosis. Tg rabbits along with non-Tg rabbits were fed a cholesterol diet for 16 and 28 weeks, and their aortic and coronary atherosclerosis was compared. Gross aortic lesion areas were significantly increased in female Tg rabbits at 28 weeks; however, pathological examination revealed that all the lesions of Tg rabbits fed a cholesterol diet for either 16 or 28 weeks were characterized by increased monocyte/macrophage accumulation and prominent lipid core formation compared with those of non-Tg rabbits. Macrophages isolated from Tg rabbits exhibited higher infiltrative activity towards a chemoattractant, MCP-1 in vitro and augmented capability of hydrolysing extracellular matrix in granulomatous tissue. Surprisingly, the lesions of Tg rabbits showed more advanced lesions with remarkable calcification in both aortas and coronary arteries. In conclusion, macrophage-derived MMP-9 facilitates the infiltration of monocyte/macrophages into the lesions thereby enhancing the progression of atherosclerosis. Increased accumulation of lesional macrophages may promote vascular calcification.