Development and Characterization of West Nile Virus Replicon Expressing Secreted Gaussia Luciferase

We developed a Gaussia luciferase (Gluc) reporter replicon of West Nile virus (WNV) and used it to quantify viral translation and RNA replication. The advantage of the Gluc replicon is that Gaussia luciferase is secreted into the culture medium from cells transfected with Gluc replicon RNA, and the medium can be assayed directly for luciferase activity. Using a known Flavivirus inhibitor (NITD008), we demonstrated that the Gluc-WNV replicon could be used for antiviral screening. The Gluc-WNV-Rep will be useful for research in antiviral drug development programs, as well as for studying viral replication and pathogenesis of WNV.

Guiding magnetic liquid metal for flexible circuit

Liquid metal(LM) has potential applications in flexible electronics due to its high electrical conductivity and high flexibility. However, common methods of printing LM circuits on soft substrates lack controllability, precision, and the ability to repair a damaged circuit. In this paper, we propose a method that uses a magnetic field to guide a magnetic LM(MLM) droplet to print and repair a flexible LM circuit on a femtosecond(fs) laser-patterned silicone surface.After mixing magnetic iron(Fe) particles into LM, the movement of the resultant MLM droplet could be controlled by a magnetic field. A patterned structure composed of the untreated flat domain and the LM-repellent rough microstructure produced by fs laser ablation was prepared on the silicone substrate. As an MLM droplet was guided onto the designed pattern, a soft LM circuit with smooth, uniform, and high-precision LM lines was obtained. Interestingly, the MLM droplet could also be guided to repair the circuit broken LM lines, and the repaired circuit maintained its original electrical properties. A flexible tensile sensor was prepared based on the printed LM circuit, which detected the bending degree of a finger.

抗SARS-CoV-2变异株的广谱mRNA疫苗RQ3013的临床前研究

全球SARS-CoV-2病毒的不同变异株导致已接种疫苗的人群中突破性感染的比例上升,迫切需要研发更为有效和广谱的COVID-19疫苗.本研究报告了一项mRNA疫苗RQ3013的临床前研究结果,旨在提供对SARS-CoV-2各种变异株(VOCs)的广谱保护.RQ3013疫苗包含经过假尿苷修饰的mRNA,制备成脂质纳米颗粒的形式.该mRNA编码了SARS-CoV-2的刺突(S)蛋白嵌合体,包含与免疫逃逸有关的重要突变位点.我们在多种动物模型中对RQ3013的免疫原性、保护效果和安全性进行了评估.RQ3013在小鼠、仓鼠和非人灵长类动物(NHP)中引发了显著的免疫反应.它能够诱导高滴度的抗体产生,具备对野生型、B.1.1.7、B.1.351、B.1.617.2和奥密克戎系列变异株的广泛中和能力.在小鼠和NHP中,两剂RQ3013疫苗能够有效保护上呼吸道和下呼吸道免受SARS-CoV-2及其变异株的感染.此外,在NHP中对RQ3013的安全性进行了评估,未观察到不良反应.这些结果为在临床试验中评估RQ3013提供了有力的支持,表明它可能成为对抗COVID-19及其变种的广泛保护的有希望的候选疫苗.

Single-dose AAV-based vaccine induces a high level of neutralizing antibodies against SARS-CoV-2 in rhesus macaques

Dear Editor,Coronavirus disease 2019(COVID-19)is a highly infectious respiratory disease that continues to pose a serious global public health emergency.The disease shows a high infection rate,long incubation period,and rapidly emerging variants,which have led to its rapid spread worldwide(Krammer 2020).Many vaccines have been developed for the control of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for COVID-19,including vaccines based on messenger RNA(mRNA)(Polack et al.2020),viral vectors(Zhu et al.2020),recombinant proteins(Yang et al.2020),and inactivated SARS-CoV-2(Zhang et al.2021).

凝胶型树脂载纳米水合氧化铁复合材料的制备与除As(V)特性

以凝胶型离子交换树脂(201×4)为基体制备出负载水合氧化铁的纳米复合材料HFO-201×4,发现出现了明显的物理孔结构,机械强度显著提升;且纳米颗粒主要为针状,可利用活性位点密度相比大孔型复合材料提高了约67%;对低浓度As(V)的吸附容量与吸附速率均显著高于大孔型复合材料,对模拟As(V)污染水的处理容量显著提高至大孔型复合材料的2倍左右,并可实现稳定循环再生.

Protective Efficacy of Inactivated Vaccine against SARS-CoV-2 Infection in Mice and Non-Human Primates

The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the disease causative agent.Vaccine is the most effective approach to eradicate a pathogen.The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations.Here we evaluated the safety,immunogenicity,and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates.Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates,and subsequently provided partial(in low dose)or full(in high dose)protection of challenge in the tested animals.In addition,passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice.These results warranted positive outcomes in future clinical trials in humans.

Molecular and Isotopic Characteristics of Mature Condensates from the East China Sea Shelf Basin Using GC×GC-TOFMS and GC-IRMS

In this study, biomarkers, together with stable carbon(δ13 C) and hydrogen(δD) isotopic compositions of n-alkanes have been examined in a suite of condensates collected from the East China Sea Shelf Basin(ECSSB) in order to delineate their source organic matter input, depositional conditions and evaluate their thermal maturity. Previously, GC-MS analyses have shown that all the condensates are formed in oxidizing environment with terrestrial plants as their main source input. No significant differences were apparent for biomarker parameters, likely due to the low biomarker content and high maturity of these condensates. Conventional GC-MS analysis however, may provides limited information on the sources and thermal maturity of complex mixtures due to insufficient component resolution. In the current study, we used comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry(GC×GC-TOFMS) to increase the chromatographic resolution. Compounds such as alkyl cyclohexanes, alkyl cyclopentanes and diamondoids, which can be difficult to identify using conventional GC-MS analysis, were successfully identified using GC×GC-TOFMS. From our analyses we propose two possibly unreported indicators, including one maturity indicator(C5--cyclohexane/C5+-cyclohexane) and one oxidation-reduction environment indicator(alkyl-cyclohexane/alkyl-cyclopentane). Multiple petroleum charging events were proposed as an explanation for the maturity indicators indexes discrepancy between methyl-phenanthrene index(MPI) and methyl-adamantane index(MDI). In addition, the stable isotopic results show that condensates from the Paleogene have significantly higher positive δ13 C values of individual n-alkanes than the Neogene samples. Based on δD values, the samples can be divided into two groups, the differences between which are likely to be attributed to different biosynthetic precursors. Variation within each group can likely be attributed to vaporization.

Remote,selective,and in situ manipulation of liquid droplets on a femtosecond laser-structured superhydrophobic shape-memory polymer by near-infrared light

Droplet manipulation plays a significant role in the fields of biomedical detection,microfluidics,and chemical engineering.However,it still remains a great challenge to simultaneously achieve remote,selective,and in situ droplet manipulation on the same surface.Here,Fe_(3)O_(4)nanoparticles were doped in a shape-memory polymer(SMP)to prepare a photothermal-responsive Fe_(3)O_(4)-SMP composite which showed remarkable near-infrared(NIR)light-triggered shape-memory property.Superhydrophobic micropillar array was constructed on such Fe_(3)O_(4)-SMP composite through femtosecond laser microfabrication and fluoroalkylsilane modification.The surface wettability of the as-prepared surface can transform from a low-adhesive sliding state to a high-adhesive pinning state as the micropillars are deformed by pressing.Interestingly,the deformed micropillars can stand up and restore to their original morphology under remote NIR light irradiation,resulting in the reversible and repeatable recovery of the ultralow-adhesive superhydrophobicity.With such light-triggered wettability switching,the droplets pinning on the sample surface can be remotely,selectively,and in situ released.Furthermore,the superhydrophobic Fe_(3)O_(4)-SMP surface is successfully applied in lossless liquid transfer,selective droplet release,and droplet-based microreactor.The as-fabricated superhydrophobic surfaces with NIR light-controlled reversible wettability will hold great promise in the fields of liquid manipulation,lab-on-a-chip,and microfluidics.

Comparison of viral propagation and drug response among SARS-CoV-2 VOCs using replicons capable of recapitulating virion assembly and release

Several variants of concern(VOCs)have emerged since the WIV04 strain of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was first isolated in January 2020.Due to mutations in the spike(S)protein,these VOCs have evolved to enhance viral infectivity and immune evasion.However,whether mutations of the other viral proteins lead to altered viral propagation and drug resistance remains obscure.The replicon is a noninfectious viral surrogate capable of recapitulating certain steps of the viral life cycle.Although several SARS-CoV-2 replicons have been developed,none of them were derived from emerging VOCs and could only recapitulate viral genome replication and subgenomic RNA(sgRNA)transcription.In this study,SARS-CoV-2 replicons derived from the WIV04 strain and two VOCs(the Beta and Delta variants)were prepared by removing the S gene from their genomes,while other structural genes remained untouched.These replicons not only recapitulate viral genome replication and sgRNA transcription but also support the assembly and release of viral-like particles,as manifested by electron microscopic assays.Thus,the S-deletion replicon could recapitulate virtually all the post-entry steps of the viral life cycle and provides a versatile tool for measuring viral intracellular propagation and screening novel antiviral drugs,including inhibitors of virion assembly and release.Through the quantification of replicon RNA released into the supernatant,we demonstrate that viral intracellular propagation and drug response to remdesivir have not yet substantially changed during the evolution of SARS-CoV-2 from the WIV04 strain to the Beta and Delta VOCs.

Recombinant chimpanzee adenovirus vector vaccine expressing the spike protein provides effective and lasting protection against SARS-CoV-2 infection in mice

SARS-CoV-2 infection is a global public health threat.Vaccines are considered amongst the most important tools to control the SARS-CoV-2 pandemic.As expected,deaths from SARS-CoV-2 infection have dropped dramatically with widespread vaccination.However,there are concerns over the duration of vaccine-induced protection,as well as their effectiveness against emerging variants of concern.Here,we constructed a recombinant chimpanzee adenovirus vectored vaccine expressing the full-length spike of SARS-CoV-2(Ad C68-S).Rapid and high levels of humoral and cellular immune responses were observed after immunization of C57BL/6J mice with one or two doses of Ad C68-S.Notably,neutralizing antibodies were observed up to at least six months after vaccination,without substantial decline.Single or double doses Ad C68-S immunization resulted in lower viral loads in lungs of mice against SARS-CoV-2 challenge both in the short term(21 days)and long-term(6 months).Histopathological examination of Ad C68-S immunized mice lungs showed mild histological abnormalities after SARS-CoV-2 infection.Taken together,this study demonstrates the efficacy and durability of the Ad C68-S vaccine and constitutes a promising candidate for clinical evaluation.

SARS-CoV-2 infection induces testicular injury in Rhesus macaque

Dear Editor,COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which is the seventh coronavirus known to infect humans.The COVID-19 pandemic has spread to more than 200countries,with more than 600 million confirmed cases and over 6.5million deaths as of September 2022,posing a huge challenge to global public health.

Infection and pathogenesis of the Delta variant of SARS-CoV-2 in Rhesus macaque

Dear Editor,COVID-19 caused by SARS-Co V-2,is still a big threat to human populations around the world.As of Jan 2022,over 292 million cases were reported worldwide with more than 5.4 million deaths.After it was first reported in China in December 2019,the virus kept circulating and evolving and several variants with different transmissibility emerged in different countries and regions(WHO,2021a).