Evolutionary Diversity of Coxsackievirus A6 Causing Severe Hand,Foot,and Mouth Disease—China,2012-2023

Introduction:Coxsackievirus A6(CVA6)has emerged as a significant pathogen responsible for severe cases of hand,foot,and mouth disease(HFMD).This study aims to delineate the demographic characteristics and analyze the viral evolution of severe HFMD associated with CVA6,thereby assisting in its surveillance and management.Methods:In this investigation,74 strains of CVA6 were isolated from samples collected from severe HFMD cases between 2012 and 2023.The VP1 gene sequences of CVA6 were amplified and analyzed to assess population historical dynamics and evolutionary characteristics using BEAST,DnaSP6,and PopART.Results:A significant portion(94.4%)of severe CVA6-associated HFMD cases(51 out of 54,with 20 lacking age information)were children under 5 years old.Among the 74 CVA6 strains analyzed,72 belonged to the D3a sub-genotype,while only two strains were D2 sub-genotype.The average genetic distance between VP1 sequences prior to 2015 was 0.027,which increased to 0.051 when compared to sequences post-2015.Historical population dynamics analysis indicated three significant population expansions of severe CVA6-associated HFMD during 2012-2013,2013-2014,and 2019-2020,resulting in the formation of 65 distinct haplotypes.Consistent with the MCC tree findings,transitioning between regional haplotypes required multiple base substitutions,showcasing an increase in population diversity during the evolutionary process(from 14 haplotypes in 2013 to 55 haplotypes over the subsequent decade).Conclusions:CVA6,associated with severe HFMD,is evolving and presents a risk of outbreak occurrence.Thus,enhanced surveillance of severe HFMD is imperative.

Characterization of antennal sensilla of the wood-feeding cockroach Cryptocercus(Blattodea:Cryptocercidae):an exploration of taxonomy

Antennal sensilla are investigated in three xylophagous cockroaches： Cryptocercus meridianus, C. habaensis and C. changbaiensis, using scanning electron microscopy （SEM）. General morphology of the antenna is provided in detail, and no significant differences are found among the three species. Six primary types of sensilla are observed and measured： sensilla chaetica （Ch）, sensilla trichodea （Tr）, sensilla basiconica （Ba）, sensilla coeloconica （Co）, sensilla campaniformia （Ca） and sensilla capitula （Cp）. Sensilla trichodea 1 （Trl） is the most abundant sensillum in all three species. There are some statistical differences between sexes and among species. Comparing Cryptocercus with other cockroaches and termites, we briefly discuss the differences among them in terms of their habitat. According to the statistical analysis performed with the sensilla, these morphological characteristics are not enough to separate the three species and may not be suitable for a classification at species level.

Preparation and immunoprotective effects of a virus-like particle candidate vaccine of the dominant epidemic D3 genotype coxsackievirus A6 in China

Coxsackievirus A6 of the D3a genotype(CVA6 D3a)is a primary pathogen causingmainland of China's hand,foot,and mouth disease(HFMD).Viral‐like particle(VLP)vaccines represent a potential candidate vaccine to prevent HFMD.This study collected Anti‐CVA6 D3a VLPs serum from BALB/c female mice immunized using CVA6 D3a VLPs.The neutralizing antibody levels were compared against the representative 14‐JX2018(D3a)and N4‐YN2015(D3b)strains between the antisera of different immune pathways.The immunoprotective effect of anti‐CVA6 D3a VLPs against these strains was monitored using pathological sections and immuno-histochemical results of lung and skeletal muscle tissues in seven‐day‐old Institute of Cancer Research(ICR)mice.Immunological protection against different branches of viruses was evaluated in 7‐day‐old(serum passive immune protection)and 14‐day‐old(VLPs active immune protection)neonatal ICR mice models.Serum‐neutralizing antibody levels were positively correlated with the number of immunizations and higher against 14‐JX2018 than against N4‐YN2015.Furthermore,these levels were significantly higher with abdominal injection than intramuscular injection.The immunized serum of 7‐day‐old ICR mice inoculated three times was 100%protected against CVA6 D3a 14‐JX2018(lethal titer:106.25 TCID 50)and CVA6 D3b N4‐YN2015(lethal titer:105.25TCID 50)fatal attacks,respectively.For ICR mice that have completed two active immunizations for 14 days,both CVA6 D3a 14‐JX2015(challenge titer:108.25 TCID 50)and CVA6 D3b N4‐YN2015(challenge titer:107.25 TCID 50)were used for the challenge,and the mice were able to survive.Overall,the CVA6 D3a VLPs prepared in this study are a potential vaccine candidate for CVA6,as it has the optimal protective effect against both CVA6 D3a and D3b evolutionary branches viruses.

Generalized Isospectral-Nonisospectral Modified Korteweg-de Vries Integrable Hierarchies and Related Properties

In this article, a new technique for deriving integrable hierarchy is discussed, i.e., such that are derived by combining the Tu scheme with the vector product. Several classes of spectral problems are introduced by threedimensional loop algebra and six-dimensional loop algebra whose commutators are vector product, and the six-dimensional loop algebra is derived from the enlargement of the three-dimensional loop algebra. It is important that we make use of the variational method to create a new vector-product trace identity for which the Hamiltonian structure of the isospectral integrable hierarchy is worked out. The derived integrable hierarchies are reduced to the modified Korteweg-de Vries(mKdV) equation, generalized coupled mKdV integrable system and nonisospectral mKdV equation under specific parameter selection. Starting from a 3×3 matrix spectral problem, we subsequently construct an explicit N-fold Darboux transformation for integrable system(2.8) with the help of a gauge transformation of the corresponding spectral problem. At the same time, the determining equations of nonclassical symmetries associated with mKdV equation are presented in this paper. It follows that we investigate the coverings and the nonlocal symmetries of the nonisospectral mKdV equation by applying the classical Frobenius theorem and the coordinates of a infinitely-dimensional manifold in the form of Cartesian product.

A one-step reverse-transcription recombinase aided PCR assay for the rapid and sensitive detection of human enteroviruses

Human enteroviruses(HEVs)include many different types that cause a wide range of diseases,and an effective method of genus-level identification has therefore significant clinical implications.However,quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR),the gold-standard method,still has shortfalls in diagnostic sensitivity and timeliness.Here we established a one-step real-time reverse-transcription recombinase-aided PCR assay(RT-RAP)to detect HEV fragment within an hour.The RT-RAP assay showed a detection limit of 5 copies/μL using recombinant plasmids and was extensively verified using 15 HEV strains.Among 15 types of HEV(species A-C),the sensitivity of RT-RAP was approximately 2-8 folds lower than that of the qRT-PCR in 9 types,and no-cross reaction with other viruses was observed.RT-RAP was further applied to analyze CSF and fecal specimens;the clinical performance demonstrated that the RT-RAP and the commercial qRT-PCR kit provided consistent results.These results indicated that RT-RAP assay may be a promising approach for rapid and sensitive detection of HEV.

The Dynamic Mortise-and-Tenon Interlock Assists Hydrated Soft Robots Toward Off-Road Locomotion

Natural locomotion such as walking,crawling,and swimming relies on spatially controlled deformation of soft tissues,which could allow efficient interaction with the external environment.As one of the ideal candidates for biomimetic materials,hydrogels can exhibit versatile bionic morphings.However,it remains an enormous challenge to transfer these insitu deformations to locomotion,particularly above complex terrains.Herein,inspired by the crawling mode of inchworms,an isotropic hydrogel with thermoresponsiveness could evolve to an anisotropic hydrogel actuator via interfacial diffusion polymerization,further evolving to multisection structure and exhibiting adaptive deformation with diverse degrees of freedom.Therefore,a dynamic mortise-and-tenon interlock could be generated through the interaction between the self-deformation of the hydrogel actuator and rough terrains,inducing continual multidimensional locomotion on various artificial rough substrates and natural sandy terrain.Interestingly,benefiting from the powerful mechanical energy transfer capability,the crawlable hydrogel actuators could also be utilized as hydrogel motors to activate static cargos to overstep complex terrains,which exhibit the potential application of a biomimetic mechanical discoloration device.Therefore,we believe that this design principle and control strategy may be of potential interest to the field of deformable materials,soft robots,and biomimetic devices.

Interfacial Reinitiation of Free Radicals Enables the Regeneration of Broken Polymeric Hydrogel Actuators

Living organisms,from plants to animals,have inspired and guided the design and fabrication of polymeric hydrogels with biomimetic morphology,shape deformation,and actuation behavior.However,the existing polymeric hydrogels are fragile and vulnerable,which seriously hinders further application.Therefore,endowing hydrogels with a biomimetic self-growth property and regenerating the macroscopic shape of hydrogels after they suffer significant damage are highly desirable for the next generation of adaptive biomimetic hydrogels.Inspired by the tail regeneration of geckos,we herein report an efficient and universal strategy of interfacial diffusion polymerization(IDP),which can regenerate the polymeric layer at a solid–liquid interface,thereby growing new hydrogels on the existing hydrogel layers.Through changing the solvent viscosity and/or monomer type of the hydrogel precursor,diverse new hydrogels have been regenerated to endow the initial hydrogels with additional fluorescent functions and/or actuating properties.Due to the high efficiency and universality of IDP,an injured hydrogel actuator can be repaired,regenerated,and recovered to its initial condition,even after suffering severe damage such as cutting or piercing.We believe that the regeneration strategy of polymeric hydrogels will inspire the design of biomimetic materials and motivate the fabrication of the next generation of soft robots with adaptive and multifunctional properties.

可变剪接调控植物开花的作用机制进展

开花是植物生长发育的关键转折,与种子生产和作物产量密切相关。开花转变受到复杂的基因网络调控,许多开花相关基因通过可变剪接产生多种转录本,调控开花时间。文中从多个角度系统地综述了可变剪接调控植物开花的分子机制,并对将来的研究进行了展望。

RPD3家族成员调控植物发育及环境应答的分子机制

赖氨酸乙酰化是翻译后修饰的主要类型之一,在调节基因表达和蛋白质功能中起关键作用。组蛋白去乙酰化酶(Histone deacetylases,HDACs)负责从组蛋白和非组蛋白的赖氨酸中去除乙酰基。RPD3家族是研究最广的HDACs,文中对拟南芥RPD3家族在多个生长发育过程中的调控机制进行了综述,为深入研究RPD3家族成员调控植物发育的机制提供参考,也为探索HDACs其他家族成员的功能提供较为清晰的研究思路。

睡眠呼吸暂停患者呼吸环路增益的测定方法研究进展

睡眠呼吸暂停严重影响公众健康, 其发病机制涉及多个方面, 呼吸环路增益(LG)的异常是其重要的发病机制之一。因此, 准确测量评估LG, 筛选出LG异常的患者有助于实施个体化的治疗策略。目前, 已有多个LG测量方法用于临床实践。本文将总结LG测量的各种方法, 并对其优劣特点进行评价。

A new approach of using Lorentz force to study single-asperity friction inside TEM

Taking advantage of the magnetic field inside transmission electron microscope(TEM),a unique Lorentzforce-actuated method for quantitative friction tests was developed via a commercial electromechanical holder.With this approach,a submicron-sized silver asperity sliding on a tungsten flat punch was actuated by Lorentz force due to electrical current through the punch,with the normal force imposed by the built-in transducer of the holder.The friction force was determined by tracking the elastic deflection of the fabricated cantilever from in situ video.Through correlating the friction behavior with the microstructural evolution near the silver-tungsten interface,we revealed that even when the relative motion commenced with the plastic deformation of the silver asperity,the interface can still sustain the further increasing static friction force.Exactly following the arrival of the maximum static friction force,the sliding occurred at the interface,indicating the transition from static to dynamic friction.This work enriches our understanding of the underlying physics of the dynamic friction process for metallic friction behavior.

New Simian Enterovirus 19(EV-A122) Strains in China Reveal Large-Scale Inter-Serotype Recombination between Simian EV-As

Dear Editor,The genus Enterovirus(EV),belonging to the family Picornaviridae,order Picornavirales,comprises 15 species:Enterovirus A–L and rhinovirus A–C(Zell et al.2017).Enterovirus A(EV-A)has 25 serotypes,including several pathogens,such as EV-A71,coxsackievirus A16(CV-A16),and CV-A6 that infect humans,as well as four serotypes(EV-A122,123,124,and 125)isolated from simians(Zell et al.2017).EV genomes share a similar structure with a length of 7.5 kb,and two open reading frames(ORFs)flanked by 5′-and 3′-untranslated regions(UTRs)in some EVs(Oberste et al.2013b;Zell et al.2017;Guo et al.2019;Lulla et al.2019).