Enhanced virulence of genetically engineered Autographa californica nucleopolyhedrovirus owing to accelerated viral DNA replication aided by inserted ascovirus genes.

Genetic engineering technology is an ideal method to improve insecticidal efficiency by combining the advantages of different pathogenic microorganisms. Thus, six ascovirus genes were introduced into the genomic DNA of Autographa californica nucleopolyhedrovirus (AcMNPV) to possibly transfer the intrinsically valuable insecticidal properties from ascovirus to baculovirus. The viral budded virus (BV) production and viral DNA replication ability of AcMNPV-111 and AcMNPV-165 were significantly stronger than that of AcMNPV-Egfp (used as the wild-type virus in this study), whereas AcMNPV-33 had reduced ones. AcMNPV-111 and AcMNPV-165 also exhibited excellent insecticidal efficiency in the in vivo bioassays: AcMNPV-111 showed a 24.1% decrease in the LT50 value and AcMNPV-165 exhibited a 56.3% decrease in the LD50 value compared with AcMNPV-Egfp against the 3rd instar of Spodoptera exigua larvae, respectively. Furthermore, the size of the occlusion bodies (OBs) of AcMNPV-33, AcMNPV-111, and AcMNPV-165 were significantly increased compared to that of AcMNPV-Egfp. AcMNPV-111 and AcMNPV-165 had stable virulence against the 2nd to 4th instars tested larvae and higher OB yield than AcMNPV-Egfp in the 3rd and 4th instar larvae. Correlation and regression analyses indicated that it is better to use 5 OBs/larva virus to infect the 2nd instar larvae to produce AcMNPV-111 and 50 OBs/larva virus to infect the 3rd instar larvae to produce AcMNPV-165. The results of this study obtained recombinant viruses with enhanced virulence and exhibited a diversity of ascovirus gene function based on the baculovirus platform, which provided a novel strategy for the improvement of baculovirus as a biological insecticide.

Photoactive Nanomaterials for Wireless Neural Biomimetics, Stimulation, and Regeneration.

Nanomaterials at the neural interface can provide the bridge between bioelectronic devices and native neural tissues and achieve bidirectional transmission of signals with our brain. Photoactive nanomaterials, such as inorganic and polymeric nanoparticles, nanotubes, nanowires, nanorods, nanosheets or related, are being explored to mimic, modulate, control, or even substitute the functions of neural cells or tissues. They show great promise in next generation technologies for the neural interface with excellent spatial and temporal accuracy. In this review, we highlight the discovery and understanding of these nanomaterials in precise control of an individual neuron, biomimetic retinal prosthetics for vision restoration, repair or regeneration of central or peripheral neural tissues, and wireless deep brain stimulation for treatment of movement or mental disorders. The most intriguing feature is that the photoactive materials fit within a minimally invasive and wireless strategy to trigger the flux of neurologically active molecules and thus influences the cell membrane potential or key signaling molecule related to gene expression. In particular, we focus on worthy pathways of photosignal transduction at the nanomaterial-neural interface and the behavior of the biological system. Finally, we describe the challenges on how to design photoactive nanomaterials specific to neurological disorders. There are also some open issues such as long-term interface stability and signal transduction efficiency to further explore for clinical practice.

Conductive Hydrogel for a Photothermal-Responsive Stretchable Artificial Nerve and Coalescing with a Damaged Peripheral Nerve.

Modern development of flexible electronics has made use of bioelectronic materials as artificial tissue in vivo. As hydrogels are more similar to nerve tissue, functional hydrogels have become a promising candidate for bioelectronics. Meanwhile, interfacing functional hydrogels and living tissues is at the forefront of bioelectronics. The peripheral nerve injury often leads to paralysis, chronic pain, neurologic disorders, and even disability, because it has affected the bioelectrical signal transmission between the brain and the rest of body. Here, a kind of light-stimuli-responsive and stretchable conducting polymer hydrogel (CPH) is developed to explore artificial nerve. The conductivity of CPH can be enhanced when illuminated by near-infrared light, which can promote the conduction of the bioelectrical signal. When CPH is mechanically elongated, it still has high durability of conductivity and, thus, can accommodate unexpected strain of nerve tissues in motion. Thereby, CPH can better serve as an implant of the serious peripheral nerve injury in vivo, especially in the case that the length of the missing nerve exceeds 10 mm.

Profile of the Paraoxonase 1 (PON1) Gene 192Q/R Polymorphism and Clinical Associations among Older Singaporean Chinese with Alzheimer's and Mixed Dementia.

BACKGROUND: To examine the prevalence of the Paraoxonase1 (PON1) gene 192Q/R polymorphism amongst Singaporean Chinese with Alzheimer's disease (AD) and mixed dementia and possible clinical associations. METHODS: We examined the presence of the PON1 192Q/R polymorphism together with cognitive status, functional status and neuropsychiatric symptoms among 186 older Singaporean Chinese with AD (n = 109) and mixed dementia (n = 77). RESULTS: The R allele predominated in 67% of the AD patients and 63.1% of the patients with mixed dementia. Within the mixed dementia subgroup, the R allele was significantly associated with a higher BADLS score, NPI-Q scores and CDR scores. CONCLUSION: Among older Singaporean Chinese with AD and mixed dementia, the R allele was predominant. In particular, within the mixed dementia subgroup, the R allele carrier status was associated with poorer functional status, greater presence of neuropsychiatric symptoms and a more severe stage of dementia. Further studies should be conducted.

Bosutinib inhibits migration and invasion via ACK1 in KRAS mutant non-small cell lung cancer.

The advent of effective targeted therapeutics has led to increasing emphasis on precise biomarkers for accurate patient stratification. Here, we describe the role of ACK1, a non-receptor tyrosine kinase in abrogating migration and invasion in KRAS mutant lung adenocarcinoma. Bosutinib, which inhibits ACK1 at 2.7 nM IC50, was found to inhibit cell migration and invasion but not viability in a panel of non-small cell lung cancer (NSCLC) cell lines. Knockdown of ACK1 abrogated bosutinib-induced inhibition of cell migration and invasion specifically in KRAS mutant cells. This finding was further confirmed in an in vivo zebrafish metastatic model. Tissue microarray data on 210 Singaporean lung adenocarcinomas indicate that cytoplasmic ACK1 was significantly over-expressed relative to paired adjacent non-tumor tissue. Interestingly, ACK1 expression in "normal" tissue adjacent to tumour, but not tumour, was independently associated with poor overall and relapse-free survival. In conclusion, inhibition of ACK1 with bosutinib attenuates migration and invasion in the context of KRAS mutant NSCLC and may fulfil a therapeutic niche through combinatorial treatment approaches.