Multi-functional groups decorated composite nanofiber separator with excellent chemical stability in ester-based electrolyte for enhancing the lithium-ion transport

As various heat-resistant polymer separators come out, although they possess better thermal stability and superior affinity to liquid electrolyte than commercial polyolefin separator, the porous structure and chemical stability of these novel separators should be paid more attention. In this work, we prepare a thin polyacrylonitrile/cellulose acetate (PAN/CA) composite nanofiber separator and discuss the importance of chemical stability in the ester-based electrolyte. The addition of CA decreases the PAN/CA fiber diameter from 310 nm to 210 nm. However, CA containing a lot of ester groups is easy to be dissolved by liquid electrolyte for the property of similarity and compatibility. Hence, the obtained PAN/CA composite nanofiber separator is treated via alkaline hydrolysis process, and some ester groups are transformed to be hydroxyl groups. Noteworthily, hydroxyl-rich PAN/CA composite nanofiber separator not only remains stable in electrolyte, but also possesses an improved lithium-ion transport property for reducing concentration polarization effect. As a result, the LiCoO2/Li half cells employing the hydroxyl-rich composite nanofiber separator exhibits better capacity retention (118.5 mAh g -1 after 300 cycles) and superior rate performance (143.1 mAh g -1 at 3C). Therefore, this multi-functional groups decorated composite nanofiber separator with excellent chemical stability is a candidate for next-generation lithium-based battery

Efficient gene editing in adult mouse livers via adenoviral delivery of CRISPR/Cas9

AbstractWe developed an adenovirus-based CRISPR/Cas9 system for gene editing in vivo. In the liver, we demonstrated that the system could reach the level of tissue-specific gene knockout, resulting in phenotypic changes. Given the wide spectrum of cell types susceptible to adenoviral infection, and the fact that adenoviral genome rarely integrates into its host cell genome, we believe the adenovirus-based CRISPR/Cas9 system will find applications in a variety of experimental settings

Probing the light harvesting and charge rectification of bismuth nanoparticles behind the promoted photoreactivity onto Bi/BiOCl catalyst by (in-situ) electron microscopy

State-of-the-art electron microscopy has enabled us to investigate microstructural details down to sub-subångström and milli-electron-volt resolution level. The enhanced photoreactivity over bismuth hybridized BiOCl catalyst (Bi/BiOCl) has been reported recently, however, the mechanistic understandings of this improved photoreactivity especially the optical behavior of bismuth nanoparticles (Bi NPs) are still obscured and in debate. The optical absorption features of Bi NPs and the charge transfer characteristic between bismuth and BiOCl have been considered as the major physicochemical origin for the promoted photoreactivity. Based on the advanced (in-situ) electron microscopy of monochromated electron energy loss spectroscopy in scanning transmission electron microscopy imaging mode (Mono-STEM-EELS) along with related theoretical investigations, in this work, we for the first time distinguished and explained the optical absorption originated from the localized surface plasmon resonances (LSPR) effect and direct band gap transition in an individual bismuth nanoparticle as well as transportation of photogenerated carriers at the interface of Bi/BiOCl. These findings could provide better understandings about the origin of the improved photoreactivity of various bismuth-hybridized photocatalysts

Age-related decline in hippocampal tyrosine phosphatase PTPRO is a mechanistic factor in chemotherapy-related cognitive impairment

Chemotherapy-related cognitive impairment (CRCI) or “chemo brain” is a devastating neurotoxic sequela of cancer-related treatments, especially for the elderly individuals. Here we show that PTPRO, a tyrosine phosphatase, is highly enriched in the hippocampus, and its level is tightly associated with neurocognitive function but declined significantly during aging. To understand the protective role of PTPRO in CRCI, a mouse model was generated by treating Ptpro–/– female mice with doxorubicin (DOX) because Ptpro–/– female mice are more vulnerable to DOX, showing cognitive impairments and neurodegeneration. By analyzing PTPRO substrates that are neurocognition-associated tyrosine kinases, we found that SRC and EPHA4 are highly phosphorylated/activated in the hippocampi of Ptpro–/– female mice, with increased sensitivity to DOX-induced CRCI. On the other hand, restoration of PTPRO in the hippocampal CA3 region significantly ameliorate CRCI in Ptpro–/– female mice. In addition, we found that the plant alkaloid berberine (BBR) is capable of ameliorating CRCI in aged female mice by upregulating hippocampal PTPRO. Mechanistically, BBR upregulates PTPRO by downregulating miR-25-3p, which directly targeted PTPRO. These findings collectively demonstrate the protective role of hippocampal PTPRO against CRCI.</p

Age-related decline in hippocampal tyrosine phosphatase PTPRO is a mechanistic factor in chemotherapy-related cognitive impairment

Chemotherapy-related cognitive impairment (CRCI) or “chemo brain” is a devastating neurotoxic sequela of cancer-related treatments, especially for the elderly individuals. Here we show that PTPRO, a tyrosine phosphatase, is highly enriched in the hippocampus, and its level is tightly associated with neurocognitive function but declined significantly during aging. To understand the protective role of PTPRO in CRCI, a mouse model was generated by treating Ptpro–/– female mice with doxorubicin (DOX) because Ptpro–/– female mice are more vulnerable to DOX, showing cognitive impairments and neurodegeneration. By analyzing PTPRO substrates that are neurocognition-associated tyrosine kinases, we found that SRC and EPHA4 are highly phosphorylated/activated in the hippocampi of Ptpro–/– female mice, with increased sensitivity to DOX-induced CRCI. On the other hand, restoration of PTPRO in the hippocampal CA3 region significantly ameliorate CRCI in Ptpro–/– female mice. In addition, we found that the plant alkaloid berberine (BBR) is capable of ameliorating CRCI in aged female mice by upregulating hippocampal PTPRO. Mechanistically, BBR upregulates PTPRO by downregulating miR-25-3p, which directly targeted PTPRO. These findings collectively demonstrate the protective role of hippocampal PTPRO against CRCI.</p

Age-related decline in hippocampal tyrosine phosphatase PTPRO is a mechanistic factor in chemotherapy-related cognitive impairment.

Chemotherapy-related cognitive impairment (CRCI) or chemo brain is a devastating neurotoxic sequela of cancer-related treatments, especially for the elderly individuals. Here we show that PTPRO, a tyrosine phosphatase, is highly enriched in the hippocampus, and its level is tightly associated with neurocognitive function but declined significantly during aging. To understand the protective role of PTPRO in CRCI, a mouse model was generated by treating Ptpro-/- female mice with doxorubicin (DOX) because Ptpro-/- female mice are more vulnerable to DOX, showing cognitive impairments and neurodegeneration. By analyzing PTPRO substrates that are neurocognition-associated tyrosine kinases, we found that SRC and EPHA4 are highly phosphorylated/activated in the hippocampi of Ptpro-/- female mice, with increased sensitivity to DOX-induced CRCI. On the other hand, restoration of PTPRO in the hippocampal CA3 region significantly ameliorate CRCI in Ptpro-/- female mice. In addition, we found that the plant alkaloid berberine (BBR) is capable of ameliorating CRCI in aged female mice by upregulating hippocampal PTPRO. Mechanistically, BBR upregulates PTPRO by downregulating miR-25-3p, which directly targeted PTPRO. These findings collectively demonstrate the protective role of hippocampal PTPRO against CRCI

Age-related decline in hippocampal tyrosine phosphatase PTPRO is a mechanistic factor in chemotherapy-related cognitive impairment

Chemotherapy-related cognitive impairment (CRCI) or “chemo brain” is a devastating neurotoxic sequela of cancer-related treatments, especially for the elderly individuals. Here we show that PTPRO, a tyrosine phosphatase, is highly enriched in the hippocampus, and its level is tightly associated with neurocognitive function but declined significantly during aging. To understand the protective role of PTPRO in CRCI, a mouse model was generated by treating Ptpro–/– female mice with doxorubicin (DOX) because Ptpro–/– female mice are more vulnerable to DOX, showing cognitive impairments and neurodegeneration. By analyzing PTPRO substrates that are neurocognition-associated tyrosine kinases, we found that SRC and EPHA4 are highly phosphorylated/activated in the hippocampi of Ptpro–/– female mice, with increased sensitivity to DOX-induced CRCI. On the other hand, restoration of PTPRO in the hippocampal CA3 region significantly ameliorate CRCI in Ptpro–/– female mice. In addition, we found that the plant alkaloid berberine (BBR) is capable of ameliorating CRCI in aged female mice by upregulating hippocampal PTPRO. Mechanistically, BBR upregulates PTPRO by downregulating miR-25-3p, which directly targeted PTPRO. These findings collectively demonstrate the protective role of hippocampal PTPRO against CRCI.</p

Trio-Based Deep Sequencing Reveals a Low Incidence of Off-Target Mutations in the Offspring of Genetically Edited Goats

Unintended off-target mutations induced by CRISPR/Cas9 nucleases may result in unwanted consequences, which will impede the efficient applicability of this technology for genetic improvement. We have recently edited the goat genome through CRISPR/Cas9 by targeting MSTN and FGF5, which increased muscle fiber diameter and hair fiber length, respectively. Using family trio-based sequencing that allow better discrimination of variant origins, we herein generated offspring from edited goats, and sequenced the members of four family trios (gene-edited goats and their offspring) to an average of ∼36.8× coverage. This data was to systematically examined for mutation profiles using a stringent pipeline that comprehensively analyzed the sequence data for de novo single nucleotide variants, indels, and structural variants from the genome. Our results revealed that the incidence of de novo mutations in the offspring was equivalent to normal populations. We further conducted RNA sequencing using muscle and skin tissues from the offspring and control animals, the differentially expressed genes (DEGs) were related to muscle fiber development in muscles, skin development, and immune responses in skin tissues. Furthermore, in contrast to recently reports of Cas9 triggered p53 expression alterations in cultured cells, we provide primary evidence to show that Cas9-mediated genetic modification does not induce apparent p53 expression changes in animal tissues. This work provides adequate molecular evidence to support the reliability of conducting Cas9-mediated genome editing in large animal models for biomedicine and agriculture

Separase Phosphosite Mutation Leads to Genome Instability and Primordial Germ Cell Depletion during Oogenesis

To ensure equal chromosome segregation and the stability of the genome during cell division, Separase is strictly regulated primarily by Securin binding and inhibitory phosphorylation. By generating a mouse model that contained a mutation to the inhibitory phosphosite of Separase, we demonstrated that mice of both sexes are infertile. We showed that Separase deregulation leads to chromosome mis-segregation, genome instability, and eventually apoptosis of primordial germ cells (PGCs) during embryonic oogenesis. Although the PGCs of mutant male mice were completely depleted, a population of PGCs from mutant females survived Separase deregulation. The surviving PGCs completed oogenesis but produced deficient initial follicles. These results indicate a sexual dimorphism effect on PGCs from Separase deregulation, which may be correlated with a gender-specific discrepancy of Securin. Our results reveal that Separase phospho-regulation is critical for genome stability in oogenesis. Furthermore, we provided the first evidence of a pre-zygotic mitotic chromosome segregation error resulting from Separase deregulation, whose sex-specific differences may be a reason for the sexual dimorphism of aneuploidy in gametogenesis