Zhoupeele5481

No in-hospital/30-day death nor permanent paraplegia/paresis was observed. The mean follow-up time was 13±5months. Two type Ia endoleaks were found, but no late occlusion and migration of the supra-aortic branch arteries stents during the follow-up were observed.

The in situ laser fenestration of aortic arch stent grafts during TEVAR of RTAD is a potential total endovascular therapy of RTAD for patients unsuitable for direct surgical repair.

The in situ laser fenestration of aortic arch stent grafts during TEVAR of RTAD is a potential total endovascular therapy of RTAD for patients unsuitable for direct surgical repair.

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare lethal autosomal recessive liver disorder caused by loss-of-function variations of the ABCB4 gene, encoding a phosphatidylcholine transporter (ABCB4/MDR3). Currently, no effective treatment exists for PFIC3 outside of liver transplantation.

We have produced and screened chemically and genetically modified mRNA variants encoding human ABCB4 (hABCB4 mRNA) encapsulated in lipid nanoparticles (LNPs). We examined their pharmacological effects in a cell-based model and in a new invivo mouse model resembling human PFIC3 as a result of homozygous disruption of the Abcb4 gene in fibrosis-susceptible BALB/c.Abcb4

mice.

We show that treatment with liver-targeted hABCB4 mRNA resulted in de novo expression of functional hABCB4 protein and restored phospholipid transport in cultured cells and in PFIC3 mouse livers. Importantly, repeated injections of the hABCB4 mRNA effectively rescued the severe disease phenotype in young Abcb4

mice, with rapation of our mRNA construct completely rescues severe liver disease in a genetic model of PFIC3 in mice.Pregnancy demands major cardiovascular, renal and endocrine changes to provide an adequate blood supply for the growing fetus. The renin-angiotensin-aldosterone system plays a key role in this adaptation process. One of its components, prorenin, is released in significant amounts from the ovary and uteroplacental unit. This review describes the sources of prorenin in the periconception period and in pregnancy, including its modulation by in-vitro fertilization protocols, and discusses its potential effects, among others focusing on preeclampsia. It ends with discussing the long-term consequences, even in later life, of inappropriate renin-angiotensin-aldosterone system activity in pregnancy and offers directions for future research. Ultimately, a full understanding of the role of prorenin periconceptionally and during pregnancy will help to develop tools to diagnose and/or prevent reproductive complications.Immunotherapy has recently garnered plenty of attention to improve the clinical outcomes in the treatment of various diseases. However, owing to the dynamic nature of the immune system, this approach has often been challenged by concerns regarding the lack of adequate long-term responses in patients. The development of microneedles (MNs) has resulted in the improvement and expansion of immuno-reprogramming strategies due to the housing of high accumulation of dendritic cells, macrophages, lymphocytes, and mast cells in the dermis layer of the skin. In addition, MNs possess many outstanding properties, such as the ability for the painless traverse of the stratum corneum, minimal invasiveness, facile fabrication, excellent biocompatibility, convenient administration, and bypassing the first pass metabolism that allows direct translocation of therapeutics into the systematic circulation. These advantages make MNs excellent candidates for the delivery of immunological biomolecules to the dermal antigen-presenting cells in the skin with the aim of vaccinating or treating different diseases, such as cancer and autoimmune disorders, with minimal invasiveness and side effects. This review discusses the recent advances in engineered MNs and tackles limitations relevant to traditional immunotherapy of various hard-to-treat diseases.The excipients present in an amorphous solid dispersion (ASD) are essential functional additives that ultimately influence the drug release performance and absorption. Herein, the effect of a polymer, hypromellose (HPMC), and three chemically diverse surfactants, sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and polyoxyethylene sorbitan monooleate (Tween 80, Tween), on the size and stability of the colloidal ketoprofen (KTP)-rich phase generated by liquid-liquid phase separation was evaluated. In addition, the impact of the excipients on the thermodynamic activity of KTP at concentrations in excess of the amorphous solubility was evaluated. Dynamic light scattering measurements showed that using surfactant alone did not effectively suppress coarsening of the KTP-rich phase. In contrast, the combined use of surfactant and HPMC maintained the KTP-rich droplet size at around 200 nm, which was smaller than in HPMC solutions without surfactant. Solution nuclear magnetic resonance spectroscop when optimizing ASD formulations to maximize oral drug absorption. Ideally, excipients that do not substantially impact drug thermodynamic activity should be selected, in particular for drugs where achieving high supersaturation is critical to drive their absorption.Carbon dots (CDs) are the most promising candidates of the carbon family with superior properties like ultra-small size, high aqueous solubility, low cytotoxicity, and inherent photoluminescence which makes them suitable for diverse biomedical applications. Methods have been developed to enhance their applications. Doping/surface passivation of CDs improves their physicochemical properties, visible light absorption probability, and quantum yield by controlling their size, morphology, structure, and band-gap energy. Recently, metal-doped CDs have emerged as an important class of nanomaterials with numerous biomedical applications. Additionally, the conjugation of CDs with semiconductor metal-oxide nanoparticles (NPs) enhances their free radical production rates under visible light irradiation. Conjugation of fluorescent CDs with magnetic NPs leads to the development of multimodal imaging platforms. Similarly, ternary conjugates composed of fluorescent CDs, near-infrared (NIR) responsive, and magnetic NPs are useful for multi-modal imaging-guided, and NIR-responsive synergistic chemo-phototherapy. However, no comprehensive review is published yet which covers metal-doped and hybrid CDs. Therefore, herein we provide detailed information about their synthesis and important biomedical applications. Firstly, we have covered various synthesis methods for CD conjugation including the critical analysis of the effects of the reaction conditions and doping/conjugation on the structure and properties of the CDs. Then we have extensively reviewed their biomedical applications as antimicrobial, antioxidant, and bioimaging agents, and in the field of cancer phototherapy with special emphasis on their mechanisms of actions. Finally, the future directions of research and the applications of the metal-doped and hybrid CDs have been discussed. We believe that this review article will enrich the understanding of different synthetic routes of CD-nanocomposites and their biomedical applications.A new vehicle is designed for the intracellular delivery of antibodies at nanomolar concentrations by combination of domain Z, a small affibody with strong binding affinity to Fc regions of immunoglobulin G (IgG), and the multimers of LK sequences, α-helical cell penetrating peptides (CPP) with powerful cell penetrating activities. Domain Z and multimeric LK are fused together to form LK-domain Z proteins. The LK-domain Z can bind with IgG at a specific ratio at nanomolar concentrations by simple mixing. The IgG/LK-domain Z complexes can successfully penetrate live cells at nanomolar concentration and the delivery efficiency is strongly dependent upon the concentrations of IgG/LK-domain Z complex as well as the species and subclasses of IgGs. The IgG/LK-domain Z complexes penetrate cells via ATP-dependent endocytosis pathway and the majority of delivered IgG seems to escape endosome to cytosol. Remarkably, the delivered IgGs are able to control the targeted intracellular signaling pathway as shown in the down-regulation of pro-survival genes by the delivery of anti-NF-κB using an LK-domain Z vehicle with a cathepsin B-cleavable linker between the LK sequence and domain Z. The simple but very efficient intracellular delivery method of antibodies at nanomolar concentrations is expected to facilitate profound understanding of cell mechanisms and development of new future therapeutics on the basis of intracellular antibodies.Microbubbles (MBs) have been extensively investigated in the field of biomedicine for the past few decades. Ultrasound and laser are the most frequently used sources of energy to produce MBs. Traditional acoustic methods induce MBs with poor localized areas of action. A high energy level is required to generate MBs through the focused continuous laser, which can be harmful to healthy tissues. As an alternative, plasmonic light-responsive nanoparticles, such as gold nanoparticles (AuNPs), are preferably used with continuous laser to decrease the energy threshold and reduce the bubbles area of action. It is also well-known that the utilization of the pulsed lasers instead of the continuous lasers decreases the needed AuNPs doses as well as laser power threshold. When well-confined bubbles are generated in biological environments, they play their own unique mechanical and optical roles. The collapse of a bubble can mechanically affect its surrounding area. Such a capability can be used for cargo delivery to cancer cells and cell surgery, destruction, and transfection. Moreover, the excellent ability of light scattering makes the bubbles suitable for cancer imaging. This review firstly provides an overview of the fundamental aspects of AuNPs-mediated bubbles and then their emerging applications in the field of cancer nanotechnology will be reviewed. Although the pre-clinical studies on the AuNP-mediated bubbles have shown promising data, it seems that this technique would not be applicable to every kind of cancer. The clinical application of this technique may basically be limited to the good accessible lesions like the superficial, intracavity and intraluminal tumors. The other essential challenges against the clinical translation of AuNP-mediated bubbles are also discussed.Calanthe tsoongiana is a rare orchid species native to China. Asymbiotic seed germination is of great importance in the ex situ conservation of this species. Based on morphological characteristics and anatomical structures, the C. tsoongiana developmental process from seeds to seedlings was divided into four stages (SA, PB, PC and PD), and subsequently, changes in endogenous hormone contents and gene expression were assessed using RNA-seq analysis. K-means analysis divided the DEGs into eight clusters. buy CA77.1 The gene expression decreased markedly between the imbibed seed and globular protocorm stages, with this being the most notably enriched cluster. During the seed germination period, DEGs were dominated by ATP metabolic processes, respiration and photosynthesis. A small change in gene expression was found in the globular protocorm versus the finger-like protocorm stages. During the last developmental stage, DEGs were significantly enriched in lignin catabolic processes and plant-type secondary cell wall biogenesis.