Biology subjects

Meng, K.

Publications and source records attributed to Meng, K..

17 recordsLinked to original sources

bioRxiv2026

Optically addressable and programmable spins in DNA

Optically addressable spins, traditionally studied in semiconductors and, more recently, in (bio)chemical systems, are central to quantum technologies, yet existing platforms lack scalable and accessible site-specific programmability. Here, we show that DNA can serve as a functional nanoscale scaffold for optically addressable spin systems. By incorporating flavin chromophores into synthetic oligonucleotides, we generate spin-correlated radical pairs (SCRPs) that can be manipulated by radiofrequency (RF) fields and read out using optically detected magnetic resonance (ODMR). Pulsed ODMR resolves spin dynamics on sub-microsecond timescales under ambient conditions, while DNA sequence design enables atomically precise tuning of both the ODMR response and the associated spin chemistry with single-base resolution. DNA secondary structure provides an additional layer of functionality: duplex formation inverts the pulsed ODMR contrast, indicating a switch in the spin multiplicity of the SCRP precursor. The synthetic accessibility and chemical programmability of oligo-nucleotides as hosts for optically addressable spins are demonstrated through a series of proof-of-concept applications, including sensing, programmable SCRP positioning, and spin-enhanced molecular beacons. Our results establish DNA as a versatile scaffold for engineered spin systems, providing a platform for future applications ranging from quantum sensing and programmable spin arrays to bioimaging and RF-controlled molecular switches for gene regulation.

biophysics↗

bioRxiv2026

Salicylic acid mediates graft incompatibility by repressing auxin-dependent vascular reconnection in tomato

Graft incompatibility limits the combination of scions and rootstocks, yet the signals that block vascular reconnection remain poorly understood. Using incompatible tomato-pepper (Solanum lycopersicum-Capsicum annuum) grafts, we found that salicylic acid (SA) overaccumulates at the graft junction, predominantly in the rootstock, while incompatible scions exhibit enhanced pattern-triggered immunity. SA-deficient nahG-expressing tomato failed to rescue incompatibility and instead showed severely impaired self-graft healing, indicating that successful tissue reunion requires an optimal, rather than minimal, SA response. Defense-associated genes remained activated in failed grafts regardless of SA accumulation, placing SA downstream of incompatibility determination. Exogenous SA application phenocopied incompatibility, blocking xylem reconnection, inducing cell death, and suppressing auxin signaling. Incompatible grafts similarly displayed reduced auxin accumulation and response at the graft junction. Exogenous auxin partially rescued xylem reconnection in incompatible grafts but failed to activate cambial regulator genes or fully restore compatibility. We propose that graft compatibility depends on SA-auxin homeostasis, where moderate SA supports wound-associated defense and regeneration, whereas excessive SA suppresses the auxin-dependent program required for xylem differentiation. These findings identify SA as a dose-dependent regulator of graft healing in tomato and link excessive immune activation to failed vascular regeneration.

plant biology↗

bioRxiv2025

Oncogenic PTPN11/SHP2 drives immune escape in juvenile myelomonocytic leukemia (JMML) through activation of ectonucleotidase/adenosine signaling

Juvenile myelomonocytic leukemia (JMML) is a myelodysplastic/myeloproliferative neoplasm of early childhood driven by RAS pathway mutations. Allogeneic hematopoietic stem cell transplantation (HSCT) is the therapy of choice for most patients. However, relapse rate is high, in patients with adverse features, frequently noted in PTPN11-mutated JMML, or in patients without evidence of graft-versus-host disease (GvHD). Here we set out to understand the mechanisms associated with oncogenic PTPN11 immune escape. Analyzing primary PTPN11-mutated JMML samples and MxCre;Ptpn11D61Y/+ mice, we observed elevated expression of immune checkpoint molecules, including ectonucleotidases CD39 and CD73 - key mediators of the adenosine pathway - on monocytic and granulocytic leukemic cells. Stimulation with GM-CSF, a central mediator of JMML pathogenesis, induced ectonucleotidases expression on granulocytes and monocytes. In contrast, MEK inhibition downstream of Ptpn11D61Y/+ reduced ectonucleotidases expression. Functionally, Ptpn11D61Y/+-mutated myeloid cells suppressed activation and proliferation of wild-type (WT) T lymphocytes, an effect recapitulated by adenosine and reversed by pharmacological CD39 inhibition with POM-1. In vivo, POM-1 treatment of MxCre;Ptpn11D61Y/+mice presenting with myeloproliferation reduced spleen size and partially restored immune responsiveness. Moreover, POM-1 induced apoptosis in murine Ptpn11D61Y/+ myeloid cells, highlighting a dual therapeutic benefit of CD39 inhibition in JMML. Together, these findings suggest that targeting the adenosine pathway may represent an immunomodulatory approach to enhance T cell-mediated control of JMML, particularly in the context of HSCT and relapse prevention.

cancer biology↗

bioRxiv2025

Salmonella hijacks a host glucose transporter for intravacuolar proliferation

AbstractsSalmonella is an intracellular pathogen that resides within a vacuole, which protects it from cytosolic host defenses at the expense of limited nutrient access. Glucose serves as a critical carbon source supporting Salmonellas intracellular replication. However, the molecular mechanisms driving glucose enhancement and the pathways by which cytosolic glucose becomes accessible to intravacuolar Salmonella remain poorly understood. Here, we elucidate a sophisticated three-pronged strategy through which Salmonella hijacks GLUT1 to co-opt host glucose metabolism for pathogenic advantage. Firstly, Salmonella infection upregulates the glucose transporter GLUT1 by activating the MAPK signaling cascade, enhancing host glucose uptake, and accelerating glycolytic flux. Secondly, Salmonella redirects GLUT1 to the bacterial vacuolar membrane to establish a glucose-import conduit that facilitates bacterial acquisition of cytosolic glucose. Thirdly, K29-linked ubiquitination modifications on bacterial vacuolar membranes are a previously unrecognized regulatory mechanism that potentiates GLUT1 transporter activity. Inhibition of GLUT1 potentiates Salmonella-triggered innate immune responses and attenuates bacterial virulence in vitro (RAW264.7 macrophages) and in vivo (murine infection model). Collectively, these findings delineate a novel paradigm of metabolic hijacking, wherein Salmonella systematically rewires host glucose metabolic networks to support intracellular proliferation, providing new insights into host-directed antimicrobial interventions.

microbiology↗

bioRxiv2025

Optically detected and radio wave-controlled spin chemistry in cryptochrome

Optically addressable spin systems, such as nitrogen-vacancy centers in diamond, have been widely studied for quantum sensing applications. In this work, we demonstrate that certain flavoproteins -- specifically cryptochrome and iLOV -- which generate spin correlated radical pairs upon optical excitation, also exhibit optically detected magnetic resonance (ODMR). Remarkably, the iLOV protein, commonly used in cellular imaging, displays ODMR contrast approaching 50%. We present initial applications including widefield magnetic field sensing and spatial modulation of photoluminescence using radiofrequency pulses and magnetic field gradients. Our results establish radical pairs in proteins as a novel platform for optically addressable spin systems, offering the key advantages of molecular designability and genetic encodability. Moreover, due to the spin-selective nature of radical pair chemistry, the results lay the groundwork for future radiofrequency-based manipulation of biological systems.

biophysics↗

bioRxiv2024

Deciphering the Cell Specific Transcript Heterogeneity and Alternative Splicing during the Early Embryonic Development of Zebrafish

Cell fate determination during early embryonic development is a complex process modulated by gene expression. The intricate interplay of transcriptional and post-transcriptional regulation is integral to the developmental trajectory of embryogenesis, yet how RNA processing may contribute to early development programming is largely elusive. Leveraging recent technological advances in single-molecule nanopore sequencing, we developed a single-cell long-read transcriptome sequencing technology, allowing a clear view of transcript diversity during zebrafish embryogenesis during pre- and post-zygotic genome activation (ZGA). A closer examination of the dynamic transcript usage and potential alternative splicing revealed that abundant stage-specific transcripts with differential coding potentials are involved in distinct biological functions. Specifically, we identified two cell populations at the onset of ZGA based on isoform diversity instead of gene profiling, which followed divergent developmental trajectories toward the ectoderm and the presumptive ectoderm. These two populations of cells were characterized by divergent splicing regulations linked to differential RNA-binding proteins, including SNRPA and SFPQ. Altogether, using the single-cell long-read transcriptome sequencing strategy, we work has revealed the cell-specific transcriptome dynamics contributing to the cell fate determination during embryogenesis.

developmental biology↗

bioRxiv2023

African Swine Fever Virus major capsid p72 Trimers function as a pH sensor during uncoating process of virus endocytosis

African swine fever virus (ASFV) belongs to nucleocytoplasmic large DNA viruses (NCLDVs), the only member of Asfarviridae. So far, it is revealed that the ASFV uncoating is a pH-dependent process undergone in late endosomes. But, the research on how pH affects capsid stability is limited, and which protein plays an essential role in pH sensing remains unknown. In this study, we identified the main component of the ASFV capsid -- major capsid protein p72, as a pH sensitive residue abundance protein, and it is speculated that the conformational change of the p72 trimer is possibly responsible for the ASFV uncoating process. To test this speculation, we obtained recombinant p72 trimers, treated with the acidic environment that simulated endosomes and displayed structural analysis. The results showed that the p72 trimer depolymerized at low pH. The depolymerization of trimers rationally explains the disassembly mechanism of the ASFV icosahedral capsid in endosomes.

microbiology↗

bioRxiv2022

A host E3 ubiquitin ligase regulates Salmonella virulence by targeting an SPI-2 effector involved in SIF biogenesis

Salmonella Typhimurium creates an intracellular niche for its replication by utilizing a large cohort of effectors, including several that function to interfere with host ubiquitin signaling. Although the mechanism of action of many such effectors has been elucidated, how the interplay between the host ubiquitin network and bacterial virulence factors dictates the outcome of infection largely remains undefined. Here we found that the SPI-2 effector SseK3 inhibits SNARE pairing to promote the formation of Salmonella-induced filament by Arg-GlcNAcylation of SNARE proteins, including SNAP25, VAMP8, and Syntaxin. Further study reveals that host cells counteract the activity of SseK3 by inducing the expression of the ubiquitin E3 ligase TRIM32, which catalyzes K48-linked ubiquitination on SseK3 and targets its membrane-associated portion for degradation. Hence, TRIM32 antagonizes SNAP25 Arg-GlcNAcylation induced by SseK3 to restrict SIF biogenesis and Salmonella replication. Our study reveals a mechanism by which host cells inhibit bacterial replication by eliminating specific virulence factor.

cell biology↗

bioRxiv2021

Nucleocapsid 203 mutations enhance SARS-CoV-2 immune evasion

Previous work indicated that the nucleocapsid 203 mutation increase the virulence and transmission of the SARS-CoV-2 Alpha variant. However, Delta later outcompeted Alpha and other lineages, promoting a new wave of infections. Delta also possesses a nucleocapsid 203 mutation, R203M. Large-scale epidemiological analyses suggest a synergistic effect of the 203 mutation and the spike L452R mutation, associated with Delta expansion. Viral competition experiments demonstrate the synergistic effect in fitness and infectivity. More importantly, we found that the combination of R203M and L452R brings in a 3.2-fold decrease in neutralizing titers to the neutralizing serum relative to L452R-only virus. R203M/L452R show an increased fitness after the initiation of global vaccination programmes, possibly associated with the enhanced immune evasion. Another rapidly emerging variant Omicron also bears the 203 mutation. Thus, we proposed that nucleocapsid mutations play an essential role for the rise and predominance of variants in concern.

microbiology↗

bioRxiv2021

Nucleocapsid mutation R203K/G204R increases the infectivity, fitness and virulence of SARS-CoV-2

In addition to the mutations on the spike protein (S), co-occurring mutations on nucleocapsid (N) protein are also emerging in SARS-CoV-2 world widely. Mutations R203K/G204R on N, carried by high transmissibility SARS-CoV-2 lineages including B.1.1.7 and P.1, has a rapid spread in the pandemic during the past year. In this study, we performed comprehensive population genomic analyses and virology experiment concerning on the evolution, causation and virology consequence of R203K/G204R mutations. The global incidence frequency (IF) of 203K/204R has rose up from nearly zero to 76% to date with a shrinking from August to November in 2020 but bounced later. Our results show that the emergence of B.1.1.7 is associated with the second growth of R203K/G204R mutants. We identified positive selection evidences that support the adaptiveness of 203K/204R variants. The R203K/G204R mutant virus was created and compared with the native virus. The virus competition experiments show that 203K/204R variants possess a replication advantage over the preceding R203/G204 variants, possibly in relation to the ribonucleocapsid (RNP) assemble during the virus replication. Moreover, the 203K/204R virus increased the infectivity in a human lung cell line and induced an enhanced damage to blood vessel of infected hamsters lungs. In consistence, we observed a positive association between the increased severity of COVID-19 and the IF of 203K/204R from in silicon analysis of global clinical and epidemic data. In combination with the informatics and virology experiment, our work suggested the contribution of 203K/204R to the increased transmission and virulence of the SARS-CoV-2. In addition to mutations on the S protein, the mutations on the N protein are also important to virus spread during the pandemic.

evolutionary biology↗

bioRxiv2021

Impact of Prior Infection on Protection and Transmission of SARS-CoV-2 in Golden Hamsters

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 100 million confirmed human infections, and 2 million more deaths globally since its emergence in the end of 2019. Several studies have shown that prior infection provided protective immunity against SARS-CoV-2 in non-human primate models. However, the effect of prior infection on blocking SARS-CoV-2 transmission is not clear. Here, we evaluated the impact of prior infection on protection and transmission of the SARS-CoV-2 virus in golden hamsters. Our results showed that prior infection provided protective immunity against SARS-CoV-2 re-challenge, but it was not sterizing immunity. The transmission experiment results showed that SARS-CoV-2 was efficiently transmitted from naive hamsters to prior infected hamsters by direct contact and airborne route, but not by indirect contact. Further, the virus was efficiently transmitted from prior infected hamsters to naive hamsters by direct contact, but not by airborne route and indirect contact. Surprisingly, the virus can be transmitted between prior infected hamsters by direct contact during a short period of early infection. Taken together, our study demonstrated that prior infected hamsters with good immunity can still be naturally re-infected, and the virus can be transmitted between prior infected hamsters and the naive through different transmission routes, implying the potential possibility of human re-infection and the risk of virus transmission between prior infected population and the healthy. Our study will help to calculate the herd immunity threshold more accurately, make more reasonable public health decisions, formulate an optimized population vaccination program, as well as aid the implementation of appropriate public health and social measures to control COVID-19.

microbiology↗

bioRxiv2020

Prevailing role of mucosal immunoglobulions and B cells in teleost skin immune responses to bacterial infection

The skin of vertebrates is the outermost organ of the body and serves as the first line of defense against external aggressions. In contrast to mammalian skin, that of teleost fish lacks keratinization and has evolved to operate as a mucosal surface containing a skin-associated lymphoid tissue (SALT). Thus far, IgT representing the prevalent immunoglobulin (Ig) in SALT have only been reported upon infection with a parasite. However, very little is known about the types of B cells and Igs responding to bacterial infection in the teleost skin mucosa, as well as the inductive or effector role of the SALT in such responses. To address these questions, here we analyzed the immune response of trout skin upon infection with one of the most widespread fish skin bacterial pathogens, Flavobacterium columnare. This pathogen induced strong skin innate immune and inflammatory responses at the initial phases of infection. More critically, we found that the skin mucus of fish having survived the infection contained significant IgT-but not IgM- or IgD-specific titers against the bacteria. Moreover, we demonstrate the local proliferation and production of IgT+ B-cells and specific IgT titers respectively within the SALT upon bacterial infection. Thus, our findings represent the first demonstration that IgT is the main Ig isotype induced by the skin mucosa upon bacterial infection, and that because of the large surface of the skin, its SALT probably represents a prominent IgT inductive site in fish.

immunology↗

bioRxiv2020

Crystal structure of Senecavirus A 3C protease

Senecavirus A (SVA), an emerging picornavirus in porcine population, could infect porcines of all age group and cause FMD-like symptoms. Picornaviridae, a group of RNA viruses do harm to both human and stocks; however, most of picornaviruses are lack of effective vaccines and drugs. Picornaviral 3C protease (3Cpro), as an important role in virus maturation, they basically take charge of poly-protein cleavaging, RNA replication, and multiple interventions on host cells. In this study, we successfully solved the crystal structure of 3Cpro at 1.9 [A] resolution. The results showed several differences of the binding groove within picornaviral 3Cpro, and prompted that the accommodate ability of the pocket may associate with the cleavage efficiency. The further research on 3Cpro cleavage efficiency based on structural biology, will prospectively provide an instruction on designing of efficient 3Cpro for universally proteolysis in picornaviral VLP production.

microbiology↗

bioRxiv2020

A database resource for Genome-wide dynamics analysis of Coronaviruses on a historical and global scale

The recent outbreak of a new zoonotic origin Coronavirus has ring the bell for the potential spread of epidemic Coronavirus crossing the species. With the urgent needs to assist the control of the Coronavirus spread and to provide valuable scientific information, we developed a coronavirus database (CoVdb), an online genomics and proteomics analysis platform. Based on public available coronavirus genomic information, the database annotates the genome of every strain and identifies 780 possible ORFs of all strains available in Genebank. In addition, the comprehensive evaluation of all the published genomes of Coronavirus strains, including population genetics analysis, functional analysis and structural analysis on a historical and global scale were presented in the CoVdb. In the database, the researcher can easily obtain the basic information of a Coronavirus gene with the distribution of the gene among strains, conserved or high mutation regions, possible subcellular location and topology of the gene. Moreover, sliding windows for population genetics analysis results is provided, thereby facilitating genetics and evolutional analysis at the genomic level. CoVdb can be accessed freely at http://covdb.popgenetics.net.

bioinformatics↗

bioRxiv2020

A common problem in the purification of calicivirus raised by molecular sieving: balance between purification and loss of viral particles

Caliciviridae is a group of RNA viruses could lead to gastrointestinal disease in humans and acute oral or upper respiratory tract disease in felines, no efficient vaccine so far. The preparation of immunogen is a challenge to obtain a safe and efficient vaccine candidate. Molecular sieving, due to the advantage of simple and fast purifying, is considered as a very powerful tool in calicivirus purification; however, also introduce mechanical damage to the viron. In this study, we took Feline Calicivirus (FCV), a common natural pathogen in cats as well as a classic model for caliciviruses studies, as a research object. Here, with the help of the cryo-electron microscope (cryo-EM), we collected particle images in both conditions of with and without molecular sieving post-processing, the impact of molecular sieving on FCV particles was evaluated by building a flexibility evaluation system after 3D classification. The results indicated that the molecular sieving will impact the stability of P domains through increasing flexibility. In addition, we successfully built up a scoring system to describe this flexibility of FCV P-domains, which can be extended to assess the purification effect to the entire calicivirus.

microbiology↗

bioRxiv2020

Expression and purification of p72 trimers as subunit vaccine candidate

The authors have withdrawn this manuscript because the result is invalid. We intend to revise it on our technical approach and interpretation of the results. The authors do not wish for this manuscript to be cited as a reference for this project. Please contact the corresponding author if you have any questions.

microbiology↗

bioRxiv2019

Tissue mechanics controls T-cell activation and metabolism

Upon immunogenic challenge, lymph nodes become mechanically stiff as immune cells proliferate within their encapsulated environments, and with resolution, they reestablish a soft, baseline state. We found that these mechanical changes in the microenvironment promote and then restrict T-cell activation and metabolic reprogramming. Sensing of tissue mechanics by T cells requires the mechanosensor YAP. Unlike in other cells where YAP promotes proliferation, YAP in T cells suppresses proliferation in a stiffness-dependent manner by directly restricting the translocation of NFAT into the nucleus. YAP regulates T-cell responses against viral infections and in autoimmune diabetes. Our work reveals a new paradigm whereby tissue mechanics fine-tunes adaptive immune responses in health and disease.\n\nOne Sentence SummaryTissue mechanics regulates T cells.

immunology↗