A cypovirus VP5 displays the RNA chaperone-like activity that destabilizes RNA helices and accelerates strand annealing.

For double-stranded RNA (dsRNA) viruses in the family Reoviridae, their inner capsids function as the machinery for viral RNA (vRNA) replication. Unlike other multishelled reoviruses, cypovirus has a single-layered capsid, thereby representing a simplified model for studying vRNA replication of reoviruses. VP5 is one of the three major cypovirus capsid proteins and functions as a clamp protein to stabilize cypovirus capsid. Here, we expressed VP5 from type 5 Helicoverpa armigera cypovirus (HaCPV-5) in a eukaryotic system and determined that this VP5 possesses RNA chaperone-like activity, which destabilizes RNA helices and accelerates strand annealing independent of ATP. Our further characterization of VP5 revealed that its helix-destabilizing activity is RNA specific, lacks directionality and could be inhibited by divalent ions, such as Mg(2+), Mn(2+), Ca(2+) or Zn(2+), to varying degrees. Furthermore, we found that HaCPV-5 VP5 facilitates the replication initiation of an alternative polymerase (i.e. reverse transcriptase) through a panhandle-structured RNA template, which mimics the 5'-3' cyclization of cypoviral positive-stranded RNA. Given that the replication of negative-stranded vRNA on the positive-stranded vRNA template necessitates the dissociation of the 5'-3' panhandle, the RNA chaperone activity of VP5 may play a direct role in the initiation of reoviral dsRNA synthesis.

Albumin-assembled copper-bismuth bimetallic sulfide bioactive nanosphere as an amplifier of oxidative stress for enhanced radio-chemodynamic combination therapy.

The tumor microenvironment with overexpressed hydrogen peroxide (H2O2) and reinforced antioxidative system (glutathione, GSH) becomes a double-edged sword for the accessibility of nano-therapy. Since reactive oxygen species (ROS) are easily quenched by the developed antioxidative network, ROS-based treatments such as chemodynamic therapy (CDT) and radiotherapy (RT) for killing cancer cells are severely attenuated. To overcome such limitations, a bioactive nanosphere system is developed to regulate intracellular oxidative stress for enhanced radio-chemodynamic combination therapy by using bovine serum albumin (BSA) based bioactive nanospheres that are BSA assembled with in situ generated copper-bismuth sulfide nanodots and diallyl trisulfide (DATS). The copper-bismuth sulfide nanodots react with H2O2 to produce •OH and release Cu2+. Then, the Cu2+ further depletes GSH to generate Cu+ for more •OH generation in the way of Fenton-like reaction. Such a cascade reaction can initiate •OH generation and GSH consumption to realize CDT. The elevation of ROS triggered by the DATS from BBCD nanospheres further augments the breaking of redox balance for the increased oxidative stress in 4T1 cells. With the sensitization of increased oxidative stress and high Z element Bi, an enhanced radio-chemodynamic combination therapy is achieved. The current work provides an enhanced radio-chemodynamic combination treatment for the majority of solid tumors by using the co-assembled bioactive nanospheres as an amplifier of oxidative stress.

Bioinspired membrane provides periosteum-mimetic microenvironment for accelerating vascularized bone regeneration.

Periosteum plays a pivotal role in vascularization, ossification and remodeling during the healing process of bone injury. However, there are few studies focused on the construction of artificial implants with periosteum-mimetic effect. To emulate the primary role of natural periosteum or endosteal tissues in bone regeneration, here we provide a functional biomimetic membrane with micropatterns of site-specific biomineralization. The micropattern is generated by using printed hydroxyapatite nanoparticles (HANPs), combined with selective growth of biomineralized apatite and in situ coprecipitation with growth factors. The biomimetic membrane can sustainably provide a periosteum-mimetic microenvironment, such as long-term topographical guidance for cell recruitment and induced cell differentiation, by releasing calcium phosphate and growth factors. We demonstrated that rat mesenchymal stem cells (rMSCs) on such biomimetic membrane exhibited highly aligned organization, leading to enhanced angiogenesis and osteogenesis. In the rat calvarial defect model, our biomimetic membranes with biomineralized micropatterns could significantly enhance vascularized ossification and accelerate new bone formation. The current work suggests that the functionally biomimetic membranes with specific biomineralized micropatterns can be a promising alternative to periosteal autografts, with great potential for bench-to-bedside translation in orthopedics.

Enhanced effect of nano-monetite hydrosol on dentin remineralization and tubule occlusion.

OBJECTIVES: We aim to investigate the dentin tubule occlusion and remineralization potential of a novel nano-monetite hydrosol (nMH). METHODS: First, nano-monetite hydrosol (nMH) was fabricated by homogeneous precipitation method. Then, the effectiveness of toothpaste with nMH on improving remineralization was evaluated by the measurement of tubule occluding ratio and acid-resistant stability compared with dentifrices comprising nano-hydroxyapatite hydrosol (nHH) and bioactive glass (BG). To explain this result, we studied the ions releasing and remineralization based on gelatin scaffold among nMH, nHH and BG. Finally, the cytotoxicity of these three minerals on Human dental pulp stem cells (HDPSCs) was evaluated. RESULTS: Processing for more than 7 days, the toothpaste containing nMH exhibited the significant remineralization potential and acid-resistant compared with two commercial de-sensitive dentifrices comprising nHH and BG. In addition, cytotoxicity test resulted that nMH has good cell compatibility to HDPSCs below extracts concentration of 3.12mg/mL. SIGNIFICANCE: Small size, the release of Ca2+ and PO43- with high concentration, strongly binding on dental surface, and fast transformation to HAp, were all needed in the preparation of effective dentin tubule occluding biomaterials.