Thin film nanocomposite membranes of PIM-1 and graphene oxide/ZIF-8 nanohybrids for organophilic pervaporation

In this work, thin film nanocomposite (TFN) membranes of super-glassy polymer PIM-1 containing zeolitic imidazolate framework-8 (ZIF-8)/graphene oxide (GO) composites (ZG) have been prepared by dip-coating onto water pre-impregnated polyvinylidene fluoride (PVDF) substrates. Higher flux and improved separation factors as compared to bare PIM-1 thin film composite (TFC) membranes have been achieved in organophilic pervaporation; for an aqueous feed solution with 5 wt% of butanol at 65 °C, a total permeate flux of 7.9 ± 0.69 kg m−2h−1 and a separation factor (βBtOH/H2O) of 29.9 ± 1.99 have been obtained with a TFC membrane containing 0.5 wt% of ZG filler. The pervaporation separation index (PSI) of this membrane (228 kg m−2h−1) is amongst the highest values reported in the literature. This excellent performance is attributed to the formation of a defect-free PIM-1 active layer (<1 μm) and the hydrophobic nature of the ZG fillers.Patricia Gorgojo is grateful to the Spanish Ministerio de Economía y Competitividad and the European Social Fund for her Ramon y Cajal Fellowship (RYC2019-027060-I/AEI/10.13039/501100011033). Boya Qiu would like to acknowledge the China Scholarship Council (CSC, file no. 202006240076)and the University of Manchester for the joint PhD studentship to support her research.Peer reviewe

Transplantation of Pro-Oligodendroblasts, Preconditioned by LPS-Stimulated Microglia, Promotes Recovery After Acute Contusive Spinal Cord Injury

Spinal cord injury (SCI) is a significant clinical challenge, and to date no effective treatment is available. Oligodendrocyte progenitor cell (OPC) transplantation has been a promising strategy for SCI repair. However, the poor posttransplantation survival and deficiency in differentiation into myelinating oligodendrocytes (OLs) are two major challenges that limit the use of OPCs as donor cells. Here we report the generation of an OL lineage population [i.e., pro-oligodendroblasts (proOLs)] that is relatively more mature than OPCs for transplantation after SCI. We found that proOLs responded to lipopolysaccharide (LPS)-stimulated microglia conditioned medium (L+M) by preserving toll-like receptor 4 (TLR4) expression, improving cell viability, and enhancing the expression of a myelinating OL marker myelin basic protein (MBP), compared to other OL lineage cells exposed to either LPS-stimulated (L+M) or nonstimulated microglia conditioned medium (L−M). When L+M-stimulated proOLs were intrathecally delivered through a lumbar puncture after a T10 thoracic contusive SCI, they promoted behavioral recovery, as assessed by the Basso‐Beattie‐Bresnahan (BBB) locomotor rating scale, stride length, and slips on the grid tests. Histologically, transplantation of L+M proOLs caused a considerable increase in intralesional axon numbers and myelination, and less accumulation of invading macrophages when compared with the vehicle control or OPC transplantation. Thus, transplantation of proOLs, preconditioned by L+M, may offer a better therapeutic potential for SCI than OPCs since the former may have initiated the differentiation process toward OLs prior to transplantation

Zn⁺-O⁻ dual-spin surface states formation by modification of ZnO nanoparticles with diboron compounds

ZnO semiconductor oxides are versatile functional materials that are used in photoelectronics, catalysis, sensing, etc. The Zn⁺–O⁻ surface electronic states of semiconductor oxides were formed on the ZnO surface by Zn 4s and O 2p orbital coupling with the diboron compound’s B 2p orbitals. The formation of spin-coupled surface states was based on the spin–orbit interaction on the interface, which has not been reported before. This shows that the semiconductor oxide’s spin surface states can be modulated by regulating surface orbital energy. The Zn⁺–O⁻ surface electronic states were confirmed by electron spin resonance results, which may help in expanding the fundamental research on spintronics modulation and quantum transport

Antifungal Activity and Action Mechanism of Ginger Oleoresin Against Pestalotiopsis microspora Isolated From Chinese Olive Fruits

Pestalotiopsis microspora (P. microspora) is one of dominant pathogenic fungi causing rotten disease in harvested Chinese olive (Canarium album Lour.) fruits. The purposes of this study were to evaluate the antifungal activities of ginger oleoresin (GO) against P. microspora and to illuminate the underlying action mechanisms. The in vitro assays indicate that GO exhibited strong antifungal activity against mycelial growth of P. microspore, and with 50%-inhibition concentration (EC50) and 90%-inhibition concentration (EC90) at 2.04 μL GO and 8.87 μL GO per mL propylene glycol, respectively, while the minimal inhibitory concentration (MIC) and minimal fungicidal concentration were at 10 μL GO and 30 μL GO per mL propylene glycol, respectively. Spore germination of P. microspora was inhibited by GO in a dose-dependent manner, and with 100% inhibition rate at the concentration of 8 μL GO per mL propylene glycol. Compared to the control, the cellular membrane permeability of P. microspora increased due to severe leakage of intercellular electrolytes, soluble proteins, and total sugars with the treatments (EC50, EC90) by GO during incubation. In addition, analysis of fatty acid contents and compositions in cellular membrane by GC-MS indicated that GO could significantly promote the degradation or peroxidation of unsaturated fatty acids in P. microspore, resulting in the enhancement of membrane fluidity. Moreover, observations of microstructure further showed the damage to plasma membrane and morphology of P. microspora caused by GO, which resulted in distortion, sunken and shriveled spores and mycelia of the pathogen. Furthermore, in vivo assay confirmed that over 3 MIC GO treatments remarkably suppressed disease development in P. microspore inoculated-Chinese olive fruit. These results demonstrate that owing to its strong antifungal activity, GO can be used as a promising antifungal agent to inhibit the growth of pathogenic fungi in Chinese olives

Application of stimuli-responsive nanomedicines for the treatment of ischemic stroke

Ischemic stroke (IS) refers to local brain tissue necrosis which is caused by impaired blood supply to the carotid artery or vertebrobasilar artery system. As the second leading cause of death in the world, IS has a high incidence and brings a heavy economic burden to all countries and regions because of its high disability rate. In order to effectively treat IS, a large number of drugs have been designed and developed. However, most drugs with good therapeutic effects confirmed in preclinical experiments have not been successfully applied to clinical treatment due to the low accumulation efficiency of drugs in IS areas after systematic administration. As an emerging strategy for the treatment of IS, stimuli-responsive nanomedicines have made great progress by precisely delivering drugs to the local site of IS. By response to the specific signals, stimuli-responsive nanomedicines change their particle size, shape, surface charge or structural integrity, which enables the enhanced drug delivery and controlled drug release within the IS tissue. This breakthrough approach not only enhances therapeutic efficiency but also mitigates the side effects commonly associated with thrombolytic and neuroprotective drugs. This review aims to comprehensively summarize the recent progress of stimuli-responsive nanomedicines for the treatment of IS. Furthermore, prospect is provided to look forward for the better development of this field

The Toxoplasma monocarboxylate transporters are involved in the metabolism within the apicoplast and are linked to parasite survival

The apicoplast is a four-membrane plastid found in the apicomplexans, which harbors biosynthesis and organelle housekeeping activities in the matrix. However, the mechanism driving the flux of metabolites, in and out, remains unknown. Here we used TurboID and genome engineering to identify apicoplast transporters in Toxoplasma gondii. Among the many novel transporters, we show that one pair of apicomplexan monocarboxylate transporters (AMTs) appears to be evolved from the putative host cell that engulfed a red alga. Protein depletion showed that AMT1 and AMT2 are critical for parasite growth. Metabolite analyses supported the notion that AMT1 and AMT2 are associated with biosynthesis of isoprenoids and fatty acids. However, stronger phenotypic defects were observed for AMT2, including in the inability to establish T. gondii parasite virulence in mice. This study clarifies, significantly, the mystery of apicoplast transporter composition and reveals the importance of the pair of AMTs in maintaining the apicoplast activity in apicomplexan

Functional screening reveals Toxoplasma prenylated proteins required for endocytic trafficking and rhoptry protein sorting

In the apicomplexans, endocytosed cargos (e.g., hemoglobin) are trafficked to a specialized organelle for digestion. This follows a unique endocytotic process at the micropore/cytostome in these parasites. However, the mechanism underlying endocytic trafficking remains elusive, due to the repurposing of classical endocytic proteins for the biogenesis of apical organelles. To resolve this issue, we have exploited the genetic tractability of the model apicomplexan Toxoplasma gondii, which ingests host cytosolic materials (e.g., green fluorescent protein[GFP]). We determined an association between protein prenylation and endocytic trafficking, and using an alkyne-labeled click chemistry approach, the prenylated proteome was characterized. Genome editing, using clustered regularly interspaced short palindromic repaet/CRISPR-associated nuclease 9 (CRISPR/Cas9), was efficiently utilized to generate genetically modified lines for the functional screening of 23 prenylated candidates. This identified four of these proteins that regulate the trafficking of endocytosed GFP vesicles. Among these proteins, Rab1B and YKT6.1 are highly conserved but are non-classical endocytic proteins in eukaryotes. Confocal imaging analysis showed that Rab1B and Ras are substantially localized to both the trans-Golgi network and the endosome-like compartments in the parasite. Conditional knockdown of Rab1B caused a rapid defect in secretory trafficking to the rhoptry bulb, suggesting a trafficking intersection role for the key regulator Rab1B. Further experiments confirmed a critical role for protein prenylation in regulating the stability/activity of these proteins (i.e., Rab1B and YKT6.1) in the parasite. Our findings define the molecular basis of endocytic trafficking and reveal a potential intersection function of Rab1B on membrane trafficking in T. gondii. This might extend to other related protists, including the malarial parasites

Fast character modeling with sketch-based PDE surfaces

© 2020, The Author(s). Virtual characters are 3D geometric models of characters. They have a lot of applications in multimedia. In this paper, we propose a new physics-based deformation method and efficient character modelling framework for creation of detailed 3D virtual character models. Our proposed physics-based deformation method uses PDE surfaces. Here PDE is the abbreviation of Partial Differential Equation, and PDE surfaces are defined as sculpting force-driven shape representations of interpolation surfaces. Interpolation surfaces are obtained by interpolating key cross-section profile curves and the sculpting force-driven shape representation uses an analytical solution to a vector-valued partial differential equation involving sculpting forces to quickly obtain deformed shapes. Our proposed character modelling framework consists of global modeling and local modeling. The global modeling is also called model building, which is a process of creating a whole character model quickly with sketch-guided and template-based modeling techniques. The local modeling produces local details efficiently to improve the realism of the created character model with four shape manipulation techniques. The sketch-guided global modeling generates a character model from three different levels of sketched profile curves called primary, secondary and key cross-section curves in three orthographic views. The template-based global modeling obtains a new character model by deforming a template model to match the three different levels of profile curves. Four shape manipulation techniques for local modeling are investigated and integrated into the new modelling framework. They include: partial differential equation-based shape manipulation, generalized elliptic curve-driven shape manipulation, sketch assisted shape manipulation, and template-based shape manipulation. These new local modeling techniques have both global and local shape control functions and are efficient in local shape manipulation. The final character models are represented with a collection of surfaces, which are modeled with two types of geometric entities: generalized elliptic curves (GECs) and partial differential equation-based surfaces. Our experiments indicate that the proposed modeling approach can build detailed and realistic character models easily and quickly

Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas.

DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in ∼20% of samples. Homologous recombination deficiency (HRD) was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein structure-based analyses allowed us to predict functional consequences of rare, recurrent DDR mutations. A new machine-learning-based classifier developed from gene expression data allowed us to identify alterations that phenocopy deleterious TP53 mutations. These frequent DDR gene alterations in many human cancers have functional consequences that may determine cancer progression and guide therapy