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2 years of median follow-up. Taken together, these findings show that de novo lipogenesis contributes to the aggressive phenotype induced by Pten loss in murine prostate and targeting Fasn may reduce the invasive potential of prostate cancer driven by Pten loss. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.Osteosarcoma is the most primary type of bone tumor occurring in the pediatric and adolescent age groups. In order to obtain the most appropriate prognosis, both tumor recurrence inhibition and bone repair promotion are required. In this study, a ternary nanoscale biomaterial/antitumor drug complex including hydroxyapatite (HA), bovine serum albumin (BSA) and paclitaxel (PTX) is prepared for post-surgical cancer treatment of osteosarcoma in situ. The HA-BSA-PTX nanoparticles, about 55 nm in diameter with drug loading efficiency (32.17 wt%), have sustained release properties of PTX and calcium ions (Ca2+ ) and low cytotoxicity to human fetal osteoblastic (hFOB 1.19) cells in vitro. However, for osteosarcoma (143B) cells, the proliferation, migration, and invasion ability are significantly inhibited. The in situ osteosarcoma model studies demonstrate that HA-BSA-PTX nanoparticles have significant anticancer effects and can effectively inhibit tumor metastasis. Meanwhile, the detection of alkaline phosphatase activity, calcium deposition, and reverse transcription-polymerase chain reaction proves that the HA-BSA-PTX nanoparticles can promote the osteogenic differentiation. Therefore, the HA-BSA-PTX nanodrug delivery system combined with sustained drug release, antitumor, and osteogenesis effects is a promising agent for osteosarcoma adjuvant therapy.

Osteogenesis imperfecta (OI) is a phenotypically and genetically heterogeneous bone disease characterized by bone fragility and recurrent fractures. X-linked inherited OI with mutation in PLS3 is so rare that its genotype-phenotype characteristics are not available.

We designed a novel targeted next-generation sequencing (NGS) panel with the candidate genes of OI to detect pathogenic mutations and confirmed them by Sanger sequencing. The phenotypes of the patients were also investigated.

The proband, a 12-year-old boy from a nonconsanguineous family, experienced multiple fractures of long bones and vertebrae and had low bone mineral density (BMD Z-score of -3.2 to -2.0). His younger brother also had extremity fractures. A novel frameshift mutation (c.1106_1107insGAAA; p.Phe369Leufs*5) in exon 10 of PLS3 was identified in the two patients, which was inherited from their mother who had normal BMD. Blue sclerae were the only extraskeletal symptom in all affected individuals. Zoledronic acid was beneficial for increasing BMD and reshaping the compressed vertebral bodies of the proband.

We first identify a novel mutation in PLS3 that led to rare X-linked OI and provide practical information for the diagnosis and treatment of this disease.

We first identify a novel mutation in PLS3 that led to rare X-linked OI and provide practical information for the diagnosis and treatment of this disease.The extent to which biologic payloads can be effectively delivered to cells is a limiting factor in the development of new therapies. Limitations arise from the lack of pharmacokinetic stability of biologics in vivo. Encapsulating biologics in a protective delivery vector has the potential to improve delivery profile and enhance performance. Coacervate microdroplets are developed as cell-mimetic materials with established potential for the stabilization of biological molecules, such as proteins and nucleic acids. Here, the development of biodegradable coacervate microvectors (comprising synthetically modified amylose polymers) is presented, for the delivery of biologic payloads to cells. Amylose-based coacervate microdroplets are stable under physiological conditions (e.g., temperature and ionic strength), are noncytotoxic owing to their biopolymeric structure, spontaneously interacted with the cell membrane, and are able to deliver and release proteinaceous payloads beyond the plasma membrane. In particular, myoglobin, an oxygen storage and antioxidant protein, is successfully delivered into human mesenchymal stem cells (hMSCs) within 24 h. Furthermore, coacervate microvectors are implemented for the delivery of human bone morphogenetic protein 2 growth factor, inducing differentiation of hMSCs into osteoprogenitor cells. This study demonstrates the potential of coacervate microdroplets as delivery microvectors for biomedical research and the development of new therapies.For a searchable version of these abstracts, please visit www.acrabstracts.org.Recent studies on recombinant adeno-associated viral (rAAV) vector production demonstrated the generation of infectious viral particles in Saccharomyces cerevisiae. Proof-of-concept results showed low vector yields that correlated with low AAV DNA encapsidation rates. In an attempt to understand the host cell response to rAAV production, we profiled proteomic changes throughout the fermentation process by mass spectrometry. By comparing an rAAV-producing yeast strain with a respective non-producer control, we identified a subset of yeast host proteins with significantly different expression patterns during the rAAV induction period. Gene ontology enrichment and network interaction analyses identified changes in expression patterns associated mainly with protein folding, as well as amino acid metabolism, gluconeogenesis, and stress response. Specific fold change patterns of heat shock proteins and other stress protein markers suggested the occurrence of a cytosolic unfolded protein response during rAAV protein expression. Also, a correlative increase in proteins involved in response to oxidative stress suggested cellular activities to ameliorate the effects of reactive oxygen species or other oxidants. We tested the functional relevance of the identified host proteins by overexpressing selected protein leads using low- and high-copy number plasmids. Increased vector yields up to threefold were observed in clones where proteins SSA1, SSE1, SSE2, CCP1, GTT1, and RVB2 were overexpressed. Recombinant expression of SSA1 and YDJ insect homologues (HSP40 and HSC70, respectively) in Sf9 cells led to a volumetric vector yield increase of 50% relative to control, which validated the importance of chaperone proteins in rAAV-producing systems. Overall, these results highlight the utility of proteomic-based tools for the understanding and optimization of rAAV-producing recombinant strains.Conservation tillage in conjunction with straw mulching is a sustainable agricultural approach. However, straw mulching reduces the soil temperature, inhibits early maize growth and reduces grain yield in cold regions. Guanosine 5'-monophosphate mw To address this problem, we investigated the effects of inoculation of plant growth-promoting rhizobacteria (PGPR) on maize growth and rhizosphere microbial communities under conservation tillage in Northeast China. The PGPR strains Sinorhizobium sp. A15, Bacillus sp. A28, Sphingomonas sp. A55 and Enterobacter sp. P24 were isolated from the maize rhizosphere in the same area and inoculated separately. Inoculation of these strains significantly enhanced maize growth, and the strains A15, A28 and A55 significantly increased grain yield by as much as 22%-29%. Real-time quantitative PCR and high-throughput sequencing showed that separate inoculation with the four strains increased the abundance and species richness of bacteria in the maize rhizosphere. Notably, the relative abundance of Acidobacteria_Subgroup_6, Chloroflexi_KD4-96, and Verrucomicrobiae at the class level and Mucilaginibacter at the genus level were positively correlated with maize biomass and yield. Inoculation with PGPR shows potential for improvement of maize production under conservation tillage in cold regions by regulating the rhizosphere bacterial community structure and by direct stimulation of plant growth.'Omics' studies have by now deposited massive amounts of data into the databases, and it is now time to return to the question as to what can we actually learn from them. Increased application of the deductive approach in synthetic microbial ecology and synthetic microbiome research will undoubtedly provide exciting new opportunities for advancing our understanding of microbial ecology.Although bioinks with both high printability and shape fidelity while maintaining high cell viability are developed, the biofunctionality of the resulting bioprinted construct is often overlooked. To address this, a methacrylated gelatin (GelMA)-based bioink biofunctionalized with bone particles (BPs) is developed as a personalized treatment strategy for bone regeneration. The bioink consists of incorporating BPs of various sizes (0-500 µm) in GelMA at various concentrations (ranging from 5 to 15% w/v). The printability of the bioink is systematically investigated and it is demonstrated that a 15% w/v BP-loading results in high print quality for 10% and 12.5% GelMA concentrations. Rheological evaluation reveals a strong shear thinning behavior essential for printing and a high gel strength in bioink with 15% w/v 0-500 µm BPs for both GelMA concentrations. In addition, the printability of the bioink and the metabolic activity of the resulting scaffolds are dependent on both the concentration of hydrogel and size of the BPs. Importantly, the cells initially contained in the BPs are able to migrate and colonize the bioprinted scaffold while maintaining their capacity to express early osteogenic markers. This study demonstrates the feasibility of bioprinted viable BPs and may have some potential for chairside clinical translation.The effects of cashew nut shell liquid (CNSL) feeding on the methane (CH4 ) emission and the ruminal microbiome of Lai Sind beef cattle were investigated. Changes in the methane production and rumen microbiome by CNSL feeding were monitored by a respiration chamber and 16S rRNA gene amplicon sequencing respectively. The results demonstrated that CNSL feeding mitigated 20.2%-23.4% of the CH4 emission in vivo without apparent adverse effects on feed intake and feed digestibility. The rumen fluid analysis revealed a significant increase in the proportion of propionate in the total short-chain fatty acids. The relative abundance of methanogen (order Methanobacteriales) decreased significantly, indicating the direct inhibitory effect of CNSL on methanogens. The predicted function of the rumen microbiome indicated that carbohydrate and lipid metabolisms including propionate production were upregulated by CNSL feeding, whereas CH4 metabolism was downregulated. A network analysis revealed that methanogen changed its partner bacteria after CNSL feeding. The δ13 C of CH4 ranged from -74.2‰ to -66.6‰ with significant fluctuation by CNSL feeding, in agreement with the shift of the rumen microbiome. Our findings demonstrate that CNSL feeding can mitigate the CH4 emission from local cattle production systems in South-East Asia by modifying the rumen microbiome and its function.Tissue regeneration driven by immunomodulatory agents has emerged as a potential solution for repairing bone defects. However, the therapeutic benefits are compromised by disturbances in the pro- and anti-inflammatory balance. Here, using magnesium nanoparticles (MgNPs) as a template, magnesium-enriched graphene oxide nanoscrolls (MgNPs@GNSs) designed for combinational modulation of the inflammatory response are reported. First, the different effects of graphene oxide (GO) and magnesium ions (Mg2+ ) on Raw264.7 macrophage phenotype transformation are screened. The results reveal that GO activates inflammatory M1 macrophages, and that Mg2+ facilitates repolarization of M1 macrophages to the pro-healing M2 phenotype. With sustained release of Mg2+ , the MgNPs@GNS nanoplatform can orchestrate harmonious type 1 and type 2 inflammatory responses. Mg2+ decrease the internalization of GO and downregulate the nuclear factor kappa-B pathway, which is profoundly involved in the inflammatory process. A series of experiments show that the ordered inflammatory response induced by MgNPs@GNSs stimulates in vitro angiogenesis and osteogenesis through chemotactic, mitogenic, and morphogenic actions.