Oncolytic virus-based hepatocellular carcinoma treatment:Current status,intravenous delivery strategies,and emerging combination therapeutic solutions

Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies.Recently,there has been increased interest in oncolytic viruses(OVs)as a therapeutic modality for HCC.OVs undergo selective replication in cancerous tissues and kill tumor cells.Strikingly,pexastimogene devacirepvec(Pexa-Vec)was granted an orphan drug status in HCC by the U.S.Food and Drug Administration(FDA)in 2013.Meanwhile,dozens of OVs are being tested in HCC-directed clinical and preclinical trials.In this review,the pathogenesis and current therapies of HCC are outlined.Next,we summarize multiple OVs as single therapeutic agents for the treatment of HCC,which have demonstrated certain efficacy and lowtoxicity.Emerging carrier cell-,bioengineered cell mimetic-or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described.In addition,we highlight the combination treatments between oncolytic virotherapy and other modalities.Finally,the clinical challenges and prospects of OV-based biotherapy are discussed,with the aim of continuing to develop a fascinating approach in HCC patients.

A New Species of the Genus Tylototriton(Amphibia: Urodela: Salamandridae) from the Southern Dabie Mountains in Anhui Province

A new species of the genus Tylototriton is described,from Yuexi county,Anhui province,in the south of the Dabie Mountains.It is based on morphological and molecular analysis.The new species is identified as belonging to the Tylototriton asperrimus group and shares a number of similarities with T.wenxianensis,T.broadoridgus and T.dabienicus.The diagnostic characteristics of the new species are as follows： the head length is greater than the width of the head; bony ridges on the head are prominent and necked-in; the distal digit ends,ventral digits,peripheral area of the cloaca and the tail＇s lower edge are orange.The result from the molecular analysis of the genus Tylototriton（including the type specimen of the new species） based on three mitochondrial genes（ND1,ND2 and CYTB） indicated that the new species was close to T.wenxianensis,T.dabienicus,and T.broadoridgus,but formed an independent clade.This result was consistent with the morphological analysis above,which supports the theory that the population distributed in the south of the Dabie Mountains,namely in from Yuexi county,Anhui province,represented a distinct species,Tylototriton anhuiensis sp.nov.

Self-assembly 2D plasmonic nanorice film for surface-enhanced Raman spectroscopy

As an ultrasensitive sensing technology,the application of surface enhanced Raman spectroscopy(SERS)is one interesting topic of nano-optics,which has huge application prospectives in plenty of research fields.In recent years,the bottleneck in SERS application could be the fabrication of SERS substrate with excellent enhancement.In this work,a two-dimensional(2D)Ag nanorice film is fabricated by self-assembly method as a SERS substrate.The collected SERS spectra of various molecules on this 2D plasmonic film demonstrate quantitative detection could be performed on this SERS substrate.The experiment data also demonstrate this 2D plasmonic film consisted of anisotropic nanostructures has no obvious SERS polarization dependence.The simulated electric field distribution points out the SERS enhancement comes from the surface plasmon coupling between nanorices.And the SERS signals is dominated by molecules adsorbed at different regions of nanorice surface at various wavelengths,which could be a good near IR SERS substrate for bioanalysis.Our work not only enlarges the surface plasmon properties of metal nanostructure,but also exhibits the good application prospect in SERS related fields.

Stochastic Food Deprivation Increases Cellular Immunity in Kunming Mice

Animals’ immunity is an important factor to determine their survival and fitness. Unpredictable food shortage is common to small mammals due to fluctuation of food resources throughout a year. In general, acute food deprivation (FD) inhibited immune function in rodents. In the present study we tested the hypothesis that stochastic FD would also suppress T cell-mediated immunity in mice. Fifteen adult male Kunming mice were randomly assigned into the Fed (n = 7) and FD (n = 8) groups, in which the latter were subjected to stochastic FD regime. Unexpectedly, T cell-mediated immunity assessed by PHA response was increased in the FD mice compared with the fed controls. However, body fat mass, wet thymus and spleen mass, white blood cells, serum leptin and corticosterone concentrations did not differ between the Fed and FD groups. Taken together, stochastic food deprivation can enhance cellular immunity in Kunming mice.

A cell wall invertase modulates resistance to fusarium crown rot and sharp eyespot in common wheat

Fusarium crown rot(FCR) and sharp eyespot(SE)are serious soil-borne diseases in wheat and its relatives that have been reported to cause wheat yield losses in many areas. In this study, the expression of a cell wall invertase gene, TaCWI-B1,was identified to be associated with FCR resistance through a combination of bulk segregant RNA sequencing and genome resequencing in a recombinant inbred line population. Two biparental populations were developed to further verify TaCWI-B1 association with FCR resistance.Overexpression lines and ethyl methanesulfonate(EMS) mutants revealed TaCWI-B1 positively regulating FCR resistance. Determination of cell wall thickness and components showed that the TaCWI-B1-overexpression lines exhibited considerably increased thickness and pectin and cellulose contents. Furthermore, we found that TaCWI-B1 directly interacted with an alphagalactosidase(TaGAL). EMS mutants showed that TaGAL negatively modulated FCR resistance. The expression of TaGAL is negatively correlated with TaCWI-B1 levels, thus may reduce mannan degradation in the cell wall, consequently leading to thickening of the cell wall. Additionally, TaCWI-B1-overexpression lines and TaGAL mutants showed higher resistance to SE;however, TaCWI-B1 mutants were more susceptible to SE than controls.This study provides insights into a FCR and SE resistance gene to combat soil-borne diseases in common wheat.

Molecular rotaxane shuttle-relay accelerates K^(+)/Cl^(-) symport across a lipid membrane

Synthetic molecules that can mediate the coupled transport of Cl^(-) with K^(+) and/or Na+across the lipid bilayers have aroused great interest due to their potential as a novel therapeutic strategy by disrupting cellular ion homeostasis.Based on the structural advantages of molecular rotaxanes,we herein show that two rotaxane-based transporters[2]R and[3]R induce coupled K^(+)/Cl^(-) channel transport by introducing Cl^(-) recognition sites in the thread and K^(+) binding group in the wheel,respectively.The welldesigned molecular structures allow the insertion of unimolecular rotaxanes into the lipid bilayer,thus achieving effective ion transport by means of thermodynamically controlled movement and driven by the difference in ion concentration inside and outside the vesicles.In addition,the use of a three-component rotaxane can accelerate ion transport through a cooperative shuttlerelay mechanism in which two wheels move along the thread in the lipid membrane,thereby enabling[3]R to have higher ion transport capacity.This work represents a major advance in the use of rotaxane molecules to accomplish more complex and effective tasks.