Animal models of mpox virus infection and disease

Mpox(monkeypox)virus(MPXV),which causes a mild smallpox-like disease,has been endemic in Africa for several decades,with sporadic cases occurring in other parts of the world.However,the most recent outbreak of mpox mainly among men that have sex with men has affected several continents,posing serious global public health concerns.The infections exhibit a wide spectrum of clinical presentation,ranging from asymptomatic infection to mild,severe disease,especially in immunocompromised individuals,young children,and pregnant women.Some therapeutics and vaccines developed for smallpox have partial protective and therapeutic effects against MPXV historic isolates in animal models.However,the continued evolution of MPXV has produced multi-ple lineages,leading to significant gaps in the knowledge of their pathogenesis that constrain the development of targeted antiviral therapies and vaccines.MPXV infections in various animal models have provided a central plat-form for identification and comparison of diseased pathogenesis between the contemporary and historic isolates.In this review,we discuss the susceptibility of various animals to MPXV,and describe the key pathologic features of rodent,rabbit and nonhuman primate models.We also provide application examples of animal models in elu-cidating viral pathogenesis and evaluating effectiveness of vaccine and antiviral drugs.These animal models are essential to understand the biology of MPXV contemporary isolates and to rapidly test potential countermeasures.Finally,we list some remaining scientific questions of MPXV that can be resolved by animal models.

Early lethality of shRNA-transgenic pigs due to saturation of microRNA pathways

RNA interference （RNAi） is considered as a potential modality for clinical treatment and anti-virus animal breeding. Here, we investigate the feasibility of inhibiting classical swine fever virus （CSFV） replication by short hairpin RNA （shRNA） in vitro and in vivo. We generate four different shRNA-positive clonal cells and two types of shRNA-transgenic pigs. CSFV could be effectively inhibited in shRNA-positive clonal cells and tail tip fibroblasts of shRNA-transgenic pigs. Unexpectedly, an early lethality due to shRNA is observed in these shRNA-transgenic pigs. With further research on shRNA-positive clonal cells and transgenic pigs, we report a great induction of interferon （IFN）-responsive genes in shRNA-positive clonal cells, altered levels of endogenous microRNAs （miRNA）, and their processing enzymes in shRNA-positive cells. What is more, abnormal expressions of miRNAs and their processing enzymes are also observed in the livers of shRNA-transgenic pigs, indicating saturation of miRNNshRNA pathways induced by shRNA. In addition, we investigate the effects of shRNAs on the development of somatic cell nuclear transfer （SCNT） embryos. These results show that shRNA causes adverse effects in vitro and in vivo and shRNA- induced disruption of the endogenous miRNA pathway may lead to the early lethality of shRNA-transgenic pigs. We firstly report abnormalities of the miRNA pathway in shRNA-transgenic animals, which may explain the early lethality of shRNA-transgenic pigs and has important implications for shRNA-transgenic animal preparation.

Quantification of light-enhanced ionic transport in lead iodide perovskite thin films and its solar cell applications

Ionic transport in organometal halide perovskites is of vital importance because it dominates anomalous phenomena in perovskite solar cells,from hysteresis to switchable photovoltaic effects.However,excited state ionic transport under illumination has remained elusive,although it is essential for understanding the unusual light-induced effects(light-induced self-poling,photo-induced halide segregation and slow photoconductivity response)in organometal halide perovskites for optoelectronic applications.Here,we quantitatively demonstrate light-enhanced ionic transport in CH3NH3PbI3 over a wide temperature range of 17–295 K,which reveals a reduction in ionic transport activation energy by approximately a factor of five(from 0.82 to 0.15 eV)under illumination.The pure ionic conductance is obtained by separating it from the electronic contribution in cryogenic galvanostatic and voltage-current measurements.On the basis of these findings,we design a novel light-assisted method of catalyzing ionic interdiffusion between CH3NH3I and PbI2 stacking layers in sequential deposition perovskite synthesis.X-ray diffraction patterns indicate a significant reduction of PbI2 residue in the optimized CH3NH3PbI3 thin film produced via lightassisted sequential deposition,and the resulting solar cell efficiency is increased by over 100%(7.5%–15.7%)with little PbI2 residue.This new method enables fine control of the reaction depth in perovskite synthesis and,in turn,supports light-enhanced ionic transport.