Regulation of innate immune responses by rabies virus

Rabies virus(RABV)is an infectious and neurotropic pathogen that causes rabies and infects humans and almost all warm-blooded animals,posing a great threat to people and public safety.It is well known that innate immunity is the critical first line of host defense against viral infection.It monitors the invading pathogens by recognizing the pathogen-associated molecular patterns and danger-associated molecular patterns through pattern-recognition receptors,leading to the production of type I interferons(IFNα/β),inflammatory cytokines,and chemokines,or the activation of autophagy or apoptosis to inhibit virus replication.In the case of RABV,the innate immune response is usually triggered when the skin or muscle is bitten or scratched.However,RABV has evolved many ways to escape or even hijack innate immune response to complete its own replication and eventually invades the central nervous system(CNS).Once RABV reaches the CNS,it cannot be wiped out by the immune system or any drugs.Therefore,a better understanding of the interplay between RABV and innate immu-nity is necessary to develop effective strategies to combat its infection.Here,we review the innate immune responses induced by RABV and illustrate the antagonism mechanisms of RABV to provide new insights for the control of rabies.

Advanced Pt hollow nanospheres/rubrene nanoleaves coupled with M-shaped DNA walker for ultrasensitive electrochemiluminescence bioassay

Herein,an intense electrochemiluminescence(ECL)was achieved based on Pt hollow nanospheres/rubrene nanoleaves(Pt HNSs/Rub NLs)without the addition of any coreactant,which was employed for ultrasensitive detection of carcinoembryonic antigen(CEA)coupled with an M-shaped DNA walker(M-DNA walker)as signal switch.Specifically,in comparison with platinum nanoparticles(Pt NPs),Pt HNSs revealed excellent catalytic performance and pore confinement-enhanced ECL,which could significantly amplify ECL intensity of Rub NLs/dissolved O_(2)(DO)binary system.Then,the tracks and M-DNA walker were confined on the Pt HNSs simultaneously to promote the reaction efficiency,whose M-structure boosted the interaction sites between walking strands and tracks and reduced the rigidity of their recognition.Once the CEA approached the sensing interface,the M-DNA walker was activated based on highly specific aptamer recognition to recover ECL intensity with the assistance of exonucleaseⅢ(ExoⅢ).As proof of concept,the“on-off-on”switch aptasensor was constructed for CEA detection with a low detection limit of 0.20 fg/m L.The principle of the constructed ECL aptasensor also enables a universal platform for sensitive detection of other tumor markers.

An inactivated recombinant rabies virus chimerically expressed RBD induces humoral and cellular immunity against SARS-CoV-2 and RABV

Many studies suggest that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)can infect various animals and transmit among animals,and even to humans,posing a threat to humans and animals.There is an urgent need to develop inexpensive and efficient animal vaccines to prevent and control coronavirus disease 2019(COVID-19)in animals.Rabies virus(RABV)is another important zoonotic pathogen that infects almost all warmblooded animals and poses a great public health threat.The present study constructed two recombinant chimeric viruses expressing the S1 and RBD proteins of the SARS-CoV-2 Wuhan01 strain based on a reverse genetic system of the RABV SRV9 strain and evaluated their immunogenicity in mice,cats and dogs.The results showed that both inactivated recombinant viruses induced durable neutralizing antibodies against SARS-CoV-2 and RABV and a strong cellular immune response in mice.Notably,inactivated SRV-nCoV-RBD induced earlier antibody production than SRV-nCoV-S1,which was maintained at high levels for longer periods.Inactivated SRV-nCoV-RBD induced neutralizing antibodies against both SARS-CoV-2 and RABV in cats and dogs,with a relatively broadspectrum cross-neutralization capability against the SARS-CoV-2 pseudoviruses including Alpha,Beta,Gamma,Delta,and Omicron,showing potential to be used as a safe bivalent vaccine candidate against COVID-19 and rabies in animals.

Online optimization for optical readout of a single electron spin in diamond

The nitrogen-vacancy(NV)center in diamond has been developed as a promising platform for quantum sensing,especially for magnetic field measurements in the nano-tesla range with a nano-meter resolution.Optical spin readout performance has a direct effect on the signal-to-noise ratio(SNR)of experiments.In this work,we introduce an online optimization method to customize the laser waveform for readout.Both simulations and experiments reveal that our new scheme optimizes the optically detected magnetic resonance in NV center.The SNR of optical spin readout has been witnessed a 44.1%increase in experiments.In addition,we applied the scheme to the Rabi oscillation experiment,which shows an improvement of 46.0%in contrast and a reduction of 12.1%in mean deviation compared to traditional constant laser power SNR optimization.This scheme is promising to improve sensitivities for a wide range of NV-based applications in the future.

Pulse-width-induced polarization enhancement of optically pumped N-V electron spin in diamond

The nitrogen-vacancy(N-V)center in diamond is a widely used platform for quantum information processing and sensing.The electron-spin state of the N-V center could be initialized,read out optically,and manipulated by resonate microwave fields.In this work,we analyze the dependence of electron-spin initialization on widths of laser pulses.We build a numerical model to simulate this process and to verify the simulation results in experiments.Both simulations and experiments reveal that shorter laser pulses are helpful to the electron-spin polarization.We therefore propose to use extremely short laser pulses for electron-spin initialization.In this new scheme,the spin-state contrast could be improved about 10%in experiments by using laser pulses as short as 4 ns in width.Furthermore,we provide a mechanism to explain this effect,which is due to the occupation time in the meta-stable spin-singlet states of the N-V center.Our new scheme is applicable in a broad range of N-V-based applications in the future.

Effects of phosphate on the transport of graphene oxide nanoparticles in saturated clean and iron oxide-coated sand columns

In this study, transport behaviors of graphene oxide(GO) in saturated uncoated(i.e., clean sand) and goethite-coated sand porous media were examined as a function of the phosphate. We found that phosphate enhanced the transport of GO over a wide range of solution chemistry(i.e., pH 5.0–9.0 and the presence of 10 mmol/L Na^(+) or 0.5 mmol/L Ca^(2+)). The results were mainly ascribed to the increase of electrostatic repulsion between nanoparticles and porous media. Meanwhile, deposition site competition induced by the retained phosphate was another important mechanism leading to promote GO transport. Interestingly, when the phosphate concentration increased from 0.1 to 1.0 mmol/L, the transportenhancement effect of phosphate in goethite-coated sand was to a much larger extent than that in clean sand. The observations were primarily related to the difference in the total mass of retained phosphate between the iron oxide-coated sand and clean sand columns, which resulted in different degrees of the electrostatic repulsion and competitive effect of phosphate. When the background solution contained 0.5 mmol/L Ca^(2+), phosphate could be bind to sand/goethite-coated sand surface by cation bridging;and consequently, promoted competition between phosphate and nanoparticles for deposition sites, which was an important mechanism for the enhanced effect of phosphate. Moreover, the DLVO theory was applicable to describe GO transport behaviors in porous media in the absence or presence of phosphate. Taken together, these findings highlight the important status and role of phosphate on the transport and fate of colloidal graphene oxide in the subsurface environment.