Hoylebondesen9540

X-chromosome inactivation (XCI) is the form of dosage compensation in mammalian female cells to balance X-linked gene expression levels of the two sexes. Many diseases are related to XCI due to inactivation escape and skewing, and the symptoms and severity of these diseases also largely depend on the status of XCI. They can be divided into 3 types X-linked diseases, diseases that are affected by XCI escape, and X-chromosome aneuploidy. Here, we review representative diseases in terms of their definition, symptoms, and XCI's role in the pathogenesis of these diseases.The red flour beetle, Tribolium castaneum (T. castaneum), generates great financial losses to the grain storage and food processing industries. Previous studies have shown that essential oil (EO) from Artemisia vulgaris (A. vulgaris) has strong contact toxicity to larvae of the beetle, and odorant-binding proteins (OBPs) contribute to the defense of larvae against A. vulgaris. However, the functions of OBPs in insects defending against plant oil is still not clear. Here, expression of one OBP gene, TcOBPC17, was significantly induced 12-72 h after EO exposure. Furthermore, compared to the control group, RNA interference (RNAi) against TcOBPC17 resulted in a higher mortality rate after EO treatment, which suggests that TcOBPC17 involves in the defense against EO and induces a declining sensitivity to EO. In addition, the tissue expression profile analysis revealed that the expression of TcOBPC17 was more abundant in the metabolic detoxification organs of the head, fat body, epidermis, and hemolymph than in other larval tissue. The expression profile of developmental stages showed that TcOBPC17 had a higher level in early and late adult stages than in other developmental stages. Taken together, these results suggest that TcOBPC17 could participate in the sequestration process of exogenous toxicants in T. castaneum larvae.

Cardiac radioablation has evolved as a potential treatment modality for therapy-refractory ventricular tachycardia. To standardize cardiac radioablation treatments, promote accurate communication and target identification, and to assess toxicity, robust, and reproducible methods for angulation and cardiac segmentation are paramount. In this study, we developed and evaluated a tool for semiautomated angulation and segmentation according to the American Heart Association 17-segment model.

The semiautomated angulation and segmentation of the planning-computed tomography (CT) was based on an in-house developed tool requiring placement of only 4 point-markers and a rotation matrix. For angulation, 2 markers defining the cardiac long-axis were placed at the cardiac apex and at the center of the mitral valve. A rotation matrix was derived that angulates the CT volume, resulting in the cardiac short axis. Segmentation was subsequently performed based on marking the 2 left ventricular hinge points. To evaluate rep oncology and cardiology, enables cardiology-oriented targeting and permits focused toxicity evaluations.

In this study a method for semiautomatic angulation and segmentation of the heart for cardiac radioablation according to the American Heart Association Segmented Model is presented and evaluated. Based on our results we believe that the segmentation is reproducible and that it can be used to promote communication between radiation oncology and cardiology, enables cardiology-oriented targeting and permits focused toxicity evaluations.The clinical application of bone morphogenetic protein-2 (BMP-2) is limited by several factors, including ineffectiveness at low doses and severe adverse effects at high doses. To address these efficacy and safety limitations, we explored whether orchestration of energy metabolism and osteogenesis by magnesium ion (Mg2+) could reduce the dose and thereby improve the safety of BMP-2. Our results demonstrated that rapid metabolic activation triggered by BMP-2 was indispensable for subsequent osteogenesis. Moreover, inadequate metabolic stimulation was shown to be responsible for the ineffectiveness of low-dose BMP-2. Next, we identified that Mg2+, as an energy propellant", substantially increased cellular bioenergetic levels to support the osteogenesis via the Akt-glycolysis-Mrs2-mitochondrial axis, and consequently enhanced the osteoinductivity of BMP-2. Based on the mechanistic discovery, microgel composite hydrogels were fabricated as low-dose BMP-2/Mg2+ codelivery system through microfluidic and 3D printing technologies. An in vivo study further confirmed that rapid and robust bone regeneration was induced by the codelivery system. Collectively, these results suggest that this bioenergetic-driven, cost-effective, low-dose BMP-2-based strategy has substantial potential for bone repair.Sonodynamic therapy (SDT) is one of the promising strategies for tumor therapy, but its application is usually hindered by fast clearance in blood-circulation, abnormal tumor microenvironment, and inefficient generation of reactive oxygen species. To solve these problems, we proposed an on-demand assembly-disassembly strategy, where the assembly is favorable for longer-blood-circulation and then the disassembly in tumor is favorable for boosting SDT. Selleck Fluorofurimazine Hematoporphyrin monomethyl ether (HMME) as the model of organic sonosensitizers were conjugated with hyaluronic acid (HA). Then HA-HMME was mixed with catalase (CAT) and assembled into polymeric nanoparticles (CAT@HA-HMME NPs) with size of ∼80 nm. CAT@HA-HMME NPs exhibit good biocompatibility and a longer blood half-time (t1/2 = 4.17 h) which is obviously longer than that (∼0.82 h) of HMME molecules. After HA receptor-mediated endocytosis of cancer cells, CAT@HA-HMME NPs can be cleaved by endogenous hyaluronidase, resulting in the on-demand disassembly in tumor to release HA-HMME molecules and CAT. The CAT catalyzes the endogenous H2O2 into O2 to relieve the hypoxic microenvironment, and the released HA-HMME exhibits a higher ROS generation ability, greatly boosting SDT for the inhibition of tumor growth. Therefore, the on-demand assembly-disassembly strategy may provide some insight in the design and development of nanoagents for tumor therapy.During the postoperative management of urinary diseases, oral or intravenous administration of drugs and implanting ureteral stents are usually required, making localized drug delivery by ureteral stent a precise and effective medication strategy. In the traditional drug loading method, the drug was premixed in the implants in production lines and the versatility of drugs was restricted. However, the complex situation in the urinary system fails the possibility of finding a "one fits all" medication plan, and the intraoperative drug-loading of implants is highly desired to support customized therapy. Here, we designed an ultrathin (8 μm), elastic, and self-adhesive nanofiber bio-tape (NFBT) that can easily encapsulate drugs on the stent surface for controllable localized drug delivery. The NFBT exhibited high binding strength to a ureteral stent, a sustained release over 7 d in PBS for hydrophilic drug, and a zero-order release curve over 28 days for the hydrophobic drug nitrofurantoin (NFT). Further in vivo experiments using a porcine ureteral tract infection model demonstrated that NFBT loaded with NFT could significantly reduce the bacterial concentration in urine. The total amount of NFT delivered by the NFBT was about 2.68 wt% of the recommended dose for the systemic administration.Thromboembolism is the leading cause of cardiovascular mortality. Currently, for the lack of targeting, short half-life, low bioavailability and high bleeding risk of the classical thrombolytic drugs, pharmacological thrombolysis is usually a slow process based on micro-pumping. In addition, frequently monitoring and regulating coagulation functions are also required during (and after) the process of thrombolysis. To address these issues, a targeted thrombolytic and anticoagulation nanoplatform (UCATS-UK) is developed based on upconversion nanoparticles (UCNPs) that can convert 808 or 980 nm near-infrared (NIR) light into UV/blue light. This nanoplatform can target and enrich in the thrombus site. Synergistic thrombolysis and anticoagulation therapy thus could be realized through the controlled release of urokinase (UK) and nitric oxide (NO). Both in vitro and in vivo experiments have confirmed the excellent thrombolytic and anticoagulative capabilities of this multifunctional nanoplatform. Combined with the unique fluorescent imaging capability of UCNPs, this work is expected to contribute to the development of clinical thrombolysis therapy towards an integrated system of imaging, diagnosis and treatment.Compared to conventional artificial nerve guide conduits (NGCs) prepared using natural polymers or synthetic polymers, acellular nerve grafts (ACNGs) derived from natural nerves with eliminated immune components have natural bionic advantages in composition and structure that polymer materials do not have. To further optimize the repair effect of ACNGs, in this study, we used a composite technology based on supercritical carbon dioxide (scCO2) extraction to process the peripheral nerve of a large mammal, the Yorkshire pig, and obtained an innovative Acellular nerve xenografts (ANXs, namely, CD + scCO2 NG). After scCO2 extraction, the fat and DNA content in CD + scCO2 NG has been removed to the greatest extent, which can better supported cell adhesion and proliferation, inducing an extremely weak inflammatory response. Interestingly, the protein in the CD + scCO2 NG was primarily involved in signaling pathways related to axon guidance. Moreover, compared with the pure chemical decellularized nerve graft (CD NG), the DRG axons grew naturally on the CD + scCO2 NG membrane and extended long distances. In vivo studies further revealed that the regenerated nerve axons had basically crossed the CD + scCO2 NG 3 weeks after surgery. 12 weeks after surgery, CD + scCO2 NG was similar to autologous nerves in improving the quality of nerve regeneration, target muscle morphology and motor function recovery and was significantly better than hollow NGCs and CD NG. Therefore, we believe that the fully decellularized and fat-free porcine ACNGs may be the most promising "bridge" for repairing human nerve defects at this stage and for some time to come.Insufficient osseointegration and biofilm-associated bacterial infection are important challenges for clinical application of titanium (Ti)-based implants. Here, we constructed mesoporous polydopamine (MPDA) nanoparticles (NPs) loaded with luteolin (LUT, a quorum sensing inhibitor), which were further coated with the shell of calcium phosphate (CaP) to construct MPDA-LUT@CaP nanosystem. Then, MPDA-LUT@CaP NPs were immobilized on the surface of Ti implants. Under acidic environment of bacterial biofilm-infection, the CaP shell of MPDA-LUT@CaP NPs was rapidly degraded and released LUT, Ca2+ and PO4 3- from the surface of Ti implant. LUT could effectively inhibit and disperse biofilm. Furthermore, under near-infrared irradiation (NIR), the thermotherapy induced by the photothermal conversion effect of MPDA destroyed the integrity of the bacterial membrane, and synergistically led to protein leakage and a decrease in ATP levels. Combined with photothermal therapy (PTT) and quorum-sensing-inhibition strategy, the surface-functionalized Ti substrate had an antibacterial rate of over 95.