Alleviation of cadmium toxicity in cucumber (Cucumis sativus) seedlings by the application of selenium

In the present study, the role of selenium in cadmium toxicity was investigated in cucumber seedlings by hydroponic experiments. The application of Se for cucumber exposed to Cd significantly reduced Cd accumulation in all tissues, elevated Cd-depressed chlorophyll content, and improved photosynthetic performance. External Se significantly reduced ·OH, H2O2 and malondialdehyde content. Exogenous Se balanced Cd-depressed elements (e.g., Se enhanced Cd-induced decreases in root Zn, leaf/stem/root Mn concentrations) and carbohydrate contents. External Se also significantly decreased the Cd-induced increases in Na+K+-, Ca2+Mg2+- and total ATPase activities, which recovered almost to control level. Results indicate that application of Se can alleviate Cd toxicity in cucumber seedlings by reducing Cd uptake and reactive oxygen species (ROS) accumulation, moreover protecting photosynthetic machinery from damaging, balancing elements and carbohydrate contents, and improving ATPase activities in cucumber

Polycaprolactone/multi-walled carbon nanotube nerve guidance conduits with tunable channels fabricated via novel extrusion-stretching method for peripheral nerve repair

Multi-channeled nerve guidance conduit is a prospective way to repair peripheral nerve injury, which is still difficult to be fabricated. A novel extrusion-stretching method was utilized in this study to produce multi-walled carbon nanotubes (MWCNTs) loaded multi-channeled nerve conduits with improved flexibility and versatility. The channels and geography of the conduits were tunable. The results showed that the mechanical properties of the multi-channeled nerve conduits were suitable for peripheral nerve restoration. MWCNTs increased the biocompatibility of the multi-channeled nerve conduits. This study proved that the MWCNTs loaded multi-channeled produced by extrusion-stretching method have great potential to repair peripheral nerve injury

Multifunctional-high resolution imaging plate based on hydrophilic graphene for digital pathology

In the present study, we showed that hydrophilic graphene can serve as an ideal imaging plate for biological specimens. Graphene being a single-atom-thick semi-metal with low secondary electron emission, array tomography analysis of serial sections of biological specimens on a graphene substrate showed excellent image quality with improved z-axis resolution, without including any conductive surface coatings. However, the hydrophobic nature of graphene makes the placement of biological specimens difficult; graphene functionalized with polydimethylsiloxane oligomer was fabricated using a simple soft lithography technique and then processed with oxygen plasma to provide hydrophilic graphene with minimal damage to graphene. High-quality scanning electron microscopy images of biological specimens free from charging effects or distortion were obtained, and the optical transparency of graphene enabled fluorescence imaging of the specimen; high-resolution correlated electron and light microscopy analysis of the specimen became possible with the hydrophilic graphene plate

VCP suppresses proteopathic seeding in neurons

Background: Neuronal uptake and subsequent spread of proteopathic seeds, such as alphaS (alpha-synuclein), Tau, and TDP-43, contribute to neurodegeneration. The cellular machinery participating in this process is poorly understood. One proteinopathy called multisystem proteinopathy (MSP) is associated with dominant mutations in Valosin Containing Protein (VCP). MSP patients have muscle and neuronal degeneration characterized by aggregate pathology that can include alphaS, Tau and TDP-43. Methods: We performed a fluorescent cell sorting based genome-wide CRISPR-Cas9 screen in alphaS biosensors. alphaS and TDP-43 seeding activity under varied conditions was assessed using FRET/Flow biosensor cells or immuno fluorescence for phosphorylated alphaS or TDP-43 in primary cultured neurons. We analyzed in vivo seeding activity by immunostaining for phosphorylated alphaS following intrastriatal injection of alphaS seeds in control or VCP disease mutation carrying mice. Results: One hundred fifty-four genes were identified as suppressors of alphaS seeding. One suppressor, VCP when chemically or genetically inhibited increased alphaS seeding in cells and neurons. This was not due to an increase in alphaS uptake or alphaS protein levels. MSP-VCP mutation expression increased alphaS seeding in cells and neurons. Intrastriatal injection of alphaS preformed fibrils (PFF) into VCP-MSP mutation carrying mice increased phospho alphaS expression as compared to control mice. Cells stably expressing fluorescently tagged TDP-43 C-terminal fragment FRET pairs (TDP-43 biosensors) generate FRET when seeded with TDP-43 PFF but not monomeric TDP-43. VCP inhibition or MSP-VCP mutant expression increases TDP-43 seeding in TDP-43 biosensors. Similarly, treatment of neurons with TDP-43 PFFs generates high molecular weight insoluble phosphorylated TDP-43 after 5days. This TDP-43 seed dependent increase in phosphorylated TDP-43 is further augmented in MSP-VCP mutant expressing neurons. Conclusion: Using an unbiased screen, we identified the multifunctional AAA ATPase VCP as a suppressor of alphaS and TDP-43 aggregate seeding in cells and neurons. VCP facilitates the clearance of damaged lysosomes via lysophagy. We propose that VCPs surveillance of permeabilized endosomes may protect against the proteopathic spread of pathogenic protein aggregates. The spread of distinct aggregate species may dictate the pleiotropic phenotypes and pathologies in VCP associated MSP

Systemic chemotherapy with doxorubicin, cisplatin and capecitabine for metastatic hepatocellular carcinoma

BACKGROUND: Although numerous chemotherapeutic agents have been tested, the role of systemic chemotherapy for hepatocellular carcinoma (HCC) has not been clarified. New therapeutic strategies are thus needed to improve outcomes, and we designed this study with new effective drug combination. METHODS: Twenty-nine patients with histologically-confirmed, metastatic HCC received a combination chemotherapy with doxorubicin 60 mg/m(2 )and cisplatin 60 mg/m(2 )on day 1, plus capecitabine 2000 mg/m(2)/day as an intermittent regimen of 2 weeks of treatment followed by a 1-week rest. RESULTS: The median age was 49 years (range, 32–64) and 19 patients were hepatitis B virus seropositive. Child-Pugh class was A in all patients and 4 had Zubrod performance status of 2. The objective response rate was 24% (95% CI 9–40) with 6 stable diseases. The chemotherapy was generally well tolerated despite one treatment-related death. CONCLUSION: Combination chemotherapy with doxorubicin, cisplatin and capecitabine produced modest antitumor activity with tolerable adverse effects in patients with metastatic HCC

Structural Basis of Enzymatic Activity for the Ferulic Acid Decarboxylase (FADase) from Enterobacter sp. Px6-4

Microbial ferulic acid decarboxylase (FADase) catalyzes the transformation of ferulic acid to 4-hydroxy-3-methoxystyrene (4-vinylguaiacol) via non-oxidative decarboxylation. Here we report the crystal structures of the Enterobacter sp. Px6-4 FADase and the enzyme in complex with substrate analogues. Our analyses revealed that FADase possessed a half-opened bottom β-barrel with the catalytic pocket located between the middle of the core β-barrel and the helical bottom. Its structure shared a high degree of similarity with members of the phenolic acid decarboxylase (PAD) superfamily. Structural analysis revealed that FADase catalyzed reactions by an “open-closed” mechanism involving a pocket of 8×8×15 Å dimension on the surface of the enzyme. The active pocket could directly contact the solvent and allow the substrate to enter when induced by substrate analogues. Site-directed mutagenesis showed that the E134A mutation decreased the enzyme activity by more than 60%, and Y21A and Y27A mutations abolished the enzyme activity completely. The combined structural and mutagenesis results suggest that during decarboxylation of ferulic acid by FADase, Trp25 and Tyr27 are required for the entering and proper orientation of the substrate while Glu134 and Asn23 participate in proton transfer

Recent Progress in Electrospun Nanofibres: Reinforcement Effect and Mechanical Performance

Composite materials are becoming increasingly important as structural materials for aeronautical and space engineering, naval, automotive, and civil engineering, sporting goods, and other consumer products. Fiber-based reinforcement represents one of the most effective manufacturing strategies for enhancing the mechanical strength and other properties of composite materials. Electrospinning has gained widespread interest in the last two decades because of its ability to fabricate continuous ultrafine nanofibers with unique characteristics. The impact of electrospinning on fiber synthesis and processing, characterization, and applications in drug delivery, nanofiltration, tissue scaffolding, and electronics has been extensively studied in the past. In this article, the authors have focused on a comprehensive review of the mechanical performance and properties of electrospun nanofibers as potential reinforcements as well as their advanced nanocomposites

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data