Biology subjects

Zong, S.

Publications and source records attributed to Zong, S..

11 recordsLinked to original sources

bioRxiv2026

Biophysical properties of IgD determine thresholds for self-tolerance and selection into germinal centers

Immunoglobulin D (IgD) is among the most conserved antibody isotypes, found in virtually all jawed vertebrates1. Unlike other isotypes, IgD contains an unusually long hinge region of up to 160 amino acids that connects the constant and variable regions. Its expression pattern is also conserved; IgD is co-expressed with IgM on transitional and mature naive B cells. However, the function of IgD has remained enigmatic since its discovery in 19652,3. Here we present and test a biophysical model positing that IgD increases the entropic cost of bivalent antigen binding. Single-molecule measurements revealed that the antigen-binding arms of IgD are substantially more dynamic than those of IgM, suggesting that cell surface IgD would be energetically penalized in bivalent antigen binding. Consistent with the model and biophysical data, we find that the long hinge compromises antigen capture by IgD B cell receptors (BCRs) compared to IgM BCRs. To determine how the difference in antigen binding impacts immunity, we produced mice that express only IgM and IgD, exclusively IgM or IgD, or IgD with a truncated hinge region. The data indicate that the increased entropic cost of antigen binding imposed by the IgD hinge attenuates negative selection by self-antigen while increasing the affinity-based threshold for positive selection into the germinal center (GC). Together the results indicate that IgD functions physiologically to desensitize B cells to antigen, thereby expanding the B cell repertoire while optimizing affinity-based selection into the GC.

immunology↗

bioRxiv2026

Large river eDNA sampling designs with remote-sensing-based clustering stratification

Environmental DNA (eDNA) provides a powerful tool for biodiversity monitoring in large river ecosystems. However, current studies often rely on subjective site selection and lack systematic sampling designs. This can limit the ability to capture the full spectrum of environmental conditions that species depend on, thereby compromising sampling efficiency. To address this challenge, we propose utilizing remote sensing-based clustering for environmental stratification of sampling designs, thereby enhancing detection capabilities and increasing the objectivity of eDNA sampling. Using GBIF-based fish species distribution models and simulated distributions along the Danube, we demonstrate that this approach enhances detection efficiency compared to conventional random and regular sampling methods. To facilitate practical implementation, we developed a tool to help fieldwork planners of river sampling campaigns automatically apply this method and select stratified sampling sites without the need for extensive data processing. Finally, we demonstrate that eDNA detection occurred most frequently within the range of 0-20km downstream of the expected modeled distribution of species, suggesting that the diffusion of the signal should be further considered in the sampling design process. Our findings highlight the potential of remote sensing-based stratification to create more efficient and objective sampling designs but suggest that sampling design should be further combined with hydrological information to optimize cost-efficient sampling. The development of standard and robust sampling protocols will help advance more cost-effective eDNA-based biodiversity monitoring in riverine ecosystems.

ecology↗

bioRxiv2025

Integrating host plants and a natural enemy into MaxEnt improves global suitability predictions for Semanotus bifasciatus

BACKGROUNDSemanotus bifasciatus is a major conifer pest that causes severe wood damage. The parasitoid Sclerodermus guani is its important natural enemy. However few studies have jointly considered host plants and enemy effects when predicting pest ranges. We applied the optimized MaxEnt model and, on this basis, constructed two models: the "host-pest" model and the "host-pest-enemy" model, to predict the potential global distribution of S. bifasciatus under future scenarios and to explore the effects of climate change and the introduction of biotic interactions. RESULTSResults showed that the climate-only model projected 2.73 x 10{square} km{superscript 2} of suitable area under the historical climate condition, concentrated in Asia, North America and Europe, with expansion toward higher latitudes. The expansion of host plants further enhanced pest habitat suitability, nearly doubling the predicted range (5.46 x 10{square} km{superscript 2}) and increasing the mean suitability. Moreover, the potential distribution of S. guani overlapped extensively with S. bifasciatus, reducing the total suitable area of S. bifasciatus by up to 2.67 x 10{square} km{superscript 2}, and mean suitability declined by nearly 40%, indicating effective suppression of pest risk. Centroid shifts were consistently northward, though magnitude and fragmentation varied among models. CONCLUSIONIntegrating host availability and enemy suppression improves the realism of distribution forecasts for S. bifasciatus. The study highlights the roles of biotic factors in shaping pest suitability and identifies potential future high-risk regions of infestation. These insights provide a solid scientific foundation for targeted monitoring, and the strategic application of biological control in adaptive forest pest management.

ecology↗

bioRxiv2024

Darwin's Naturalization Conundrum explained by gradients of environmental stress and disturbance

Darwins Naturalization Conundrum (DNC) states that non-native species closely related to the native community are either more likely to succeed because shared adaptations help them overcome environmental filtering, or less likely to succeed because of strong competition with their native relatives. Despite extensive research, no general patterns have so far emerged. One reason may be that the relative importance of competition and environmental filtering depends on environmental conditions. To test this hypothesis, we conducted a global assessment of DNC examining patterns of phylogenetic relatedness of non-native plant species to the native community along gradients of elevation and anthropogenic disturbance in mountains. Phylogenetic distance of non-native to native species decreased with increasing elevation and in disturbed plant communities. Our results help resolve DNC by showing that the environmental context sets expectations for patterns of relatedness between non-native and native species and helps illuminate the ecological and evolutionary processes generating these patterns.

ecology↗

bioRxiv2023

Terrestrial land cover shapes fish diversity in major subtropical rivers

Freshwater biodiversity is critically affected by human modifications of terrestrial land use and land cover (LULC)1,2. Yet, knowledge of the spatial extent and magnitude of LULC-aquatic biodiversity linkages is still surprisingly limited, impeding the implementation of optimal management strategies3. Here, we compiled fish diversity data across a 160,000-km2 subtropical river catchment in Thailand characterized by exceptional biodiversity4 yet intense anthropogenic alterations5, and attributed fish species richness and community composition to contemporary terrestrial LULC across the catchment. We estimated a spatial range of LULC effects extending up to about 20 km upstream from sampling sites, and explained nearly 60 % of the variance in the observed species richness, associated with major LULC categories including croplands, forest, and urban areas. We find that integrating both spatial range and magnitudes of LULC effects is needed to accurately predict fish species richness. Further, projected LULC changes showcase future gains and losses of fish species richness across the river network and offer a scalable basis for riverine biodiversity conservation and land management, allowing for potential mitigation of biodiversity loss in highly diverse yet data-deficient tropical to sub-tropical riverine habitats.

ecology↗

bioRxiv2022

Memory B cell responses to Omicron subvariants after SARS-CoV-2 mRNA breakthrough infection

Individuals that receive a 3rd mRNA vaccine dose show enhanced protection against severe COVID19 but little is known about the impact of breakthrough infections on memory responses. Here, we examine the memory antibodies that develop after a 3rd or 4th antigenic exposure by Delta or Omicron BA.1 infection, respectively. A 3rd exposure to antigen by Delta breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a 3rd mRNA vaccine dose. A 4th antigenic exposure with Omicron BA.1 infection increased variant specific plasma antibody and memory B cell responses. However, the 4th exposure did not increase the overall frequency of memory B cells or their general potency or breadth compared to a 3rd mRNA vaccine dose. In conclusion, a 3rd antigenic exposure by Delta infection elicits strain-specific memory responses and increases in the overall potency and breadth of the memory B cells. In contrast, the effects of a 4th antigenic exposure with Omicron BA.1 is limited to increased strain specific memory with little effect on the potency or breadth of memory B cell antibodies. The results suggest that the effect of strain-specific boosting on memory B cell compartment may be limited.

immunology↗

bioRxiv2022

Anaerobic degradation of acid red 73 by obligately aerobic Aspergillus tabacinus LZ-M though a self-redox mechanism

Fungi are potential biological resources for refractory organics degradation, but their anaerobic degradation of azo dyes are rarely reported. In this study, a fungus Aspergillus tabacinus LZ-M was isolated grown aerobically and degraded acid red 73 (AR73) with a decolorization rate of 90.28% in 5 days at 400 mg/L of concentration anaerobically. Metabolic pathway showed that AR73 was reduced into 2-hydroxynaphthalene and aniline then mineralized into CO2. The anaerobic self-redox process revealed electrons generated in carbon oxidation and transferred to -C-N= and -N=N, resulting in complete mineralization of AR73 in strain LZ-M. Data of transcriptome analysis showed that the benzene compounds produced from AR73 by declorizing reductase entered the catechol pathway and glycolysis process to mineralize. Enzymes involved in aromatics degradation, glycolysis processes, cytochrome C and quinone oxidoreductases were up-regulate, but the key reductase responsible to cleave AR73 to phenylhydrazine was not found. A novel enzyme Ord95 containing a glutamate S-transferase domain was identified in the unknown genes as a reductase which cleaving -C-N= in AR73 using NADH as electron donor, and three arginines key active sites. These observations reveal a new degradation mechanism of AR73 in strain LZ-M which would be potential candidate for treatment of azo dyes wastewater. Graphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

microbiology↗

bioRxiv2022

Humoral immunity to SARS-CoV-2 elicited by combination COVID-19 vaccination regimens

The SARS-CoV-2 pandemic prompted a global vaccination effort and the development of numerous COVID-19 vaccines at an unprecedented scale and pace. As a result, current COVID- 19 vaccination regimens comprise diverse vaccine modalities, immunogen combinations and dosing intervals. Here, we compare vaccine-specific antibody and memory B cell responses following two-dose mRNA, single-dose Ad26.COV2.S and two-dose ChAdOx1 or combination ChAdOx1/mRNA vaccination. Plasma neutralizing activity as well as the magnitude, clonal composition and antibody maturation of the RBD-specific memory B cell compartment showed substantial differences between the vaccination regimens. While individual monoclonal antibodies derived from memory B cells exhibited similar binding affinities and neutralizing potency against Wuhan-Hu-1 SARS-CoV-2, there were significant differences in epitope specificity and neutralizing breadth against viral variants of concern. Although the ChAdOx1 vaccine was inferior to mRNA and Ad26.COV2.S in several respects, biochemical and structural analyses revealed enrichment in a subgroup of memory B cell neutralizing antibodies with distinct RBD-binding properties resulting in remarkable potency and breadth.

immunology↗

bioRxiv2022

Increased Potency and Breadth of SARS-CoV-2 Neutralizing Antibodies After a Third mRNA Vaccine Dose

The omicron variant of SARS-CoV-2 infected very large numbers of SARS-CoV-2 vaccinated and convalescent individuals1-3. The penetrance of this variant in the antigen experienced human population can be explained in part by the relatively low levels of plasma neutralizing activity against Omicron in people who were infected or vaccinated with the original Wuhan-Hu-1 strain4-7. The 3rd mRNA vaccine dose produces an initial increase in circulating anti-Omicron neutralizing antibodies, but titers remain 10-20-fold lower than against Wuhan-Hu-1 and are, in many cases, insufficient to prevent infection7. Despite the reduced protection from infection, individuals that received 3 doses of an mRNA vaccine were highly protected from the more serious consequences of infection8. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving 3 mRNA vaccine doses9,10. We find that the 3rd dose is accompanied by an increase in, and evolution of, anti-receptor binding domain specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the 2nd vaccine dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared to antibodies obtained after the 2nd vaccine dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells that differed from the persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analyzed neutralizing antibodies in the memory compartment obtained from individuals receiving a 3rd mRNA vaccine dose neutralized Omicron. Thus, individuals receiving 3 doses of an mRNA vaccine encoding Wuhan-Hu-1, have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help explain why a 3rd dose of an mRNA vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.

immunology↗

bioRxiv2022

Conserved Neutralizing Epitopes on the N-Terminal Domain of Variant SARS-CoV-2 Spike Proteins

SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for the antibody system. Neutralizing antibodies targeting the RBD bind to several different sites on this domain. In contrast, most neutralizing antibodies to NTD characterized to date bind to a single supersite, however these antibodies were obtained by methods that were not NTD specific. Here we use NTD specific probes to focus on anti-NTD memory B cells in a cohort of pre-omicron infected individuals some of which were also vaccinated. Of 275 NTD binding antibodies tested 103 neutralized at least one of three tested strains: Wuhan-Hu-1, Gamma, or PMS20, a synthetic variant which is extensively mutated in the NTD supersite. Among the 43 neutralizing antibodies that were further characterized, we found 6 complementation groups based on competition binding experiments. 58% targeted epitopes outside the NTD supersite, and 58% neutralized either Gamma or Omicron, but only 14% were broad neutralizers. Three of the broad neutralizers were characterized structurally. C1520 and C1791 recognize epitopes on opposite faces of the NTD with a distinct binding pose relative to previously described antibodies allowing for greater potency and cross-reactivity with 7 different variants including Beta, Delta, Gamma and Omicron. Antibody C1717 represents a previously uncharacterized class of NTD-directed antibodies that recognizes the viral membrane proximal side of the NTD and SD2 domain, leading to cross-neutralization of Beta, Gamma and Omicron. We conclude SARS-CoV-2 infection and/or Wuhan-Hu-1 mRNA vaccination produces a diverse collection of memory B cells that produce anti-NTD antibodies some of which can neutralize variants of concern. Rapid recruitment of these cells into the antibody secreting plasma cell compartment upon re-infection likely contributes to the relatively benign course of subsequent infections with SARS-CoV-2 variants including omicron.

immunology↗

bioRxiv2018

TP promotes malignant progression in hepatocellular carcinoma through pentose Warburg effect

Tumor progression is dependent on metabolic reprogramming. Metastasis and vasculogenic mimicry (VM) are typical tumor progression. The relationship of metastasis, VM and metabolic reprogramming is not clear. In this study, we identified the novel role of Twist1, a VM regulator, in the transcriptional regulation of the expression of thymidine phosphorylase (TP). We demonstrated that TP promoted extracellular thymidine metabolization into ATP and amino acids through pentose Warburg effect by coupling the pentose phosphate pathway and glycolysis. Moreover, Twist1 relied on TP-induced metabolic reprogramming to promote hepatocellular carcinoma (HCC) metastasis and VM formation mediated by VE-Cad, VEGFR1, and VEGFR2 in vitro and in vivo. TP inhibitor tipiracil reduced promotion effect of TP enzyme activity on HCC VM formation and metastasis. Our findings demonstrate that TP, transcriptionally activated by Twist1, promotes HCC VM formation and metastasis through pentose Warburg effect, contributing to tumor progression.

cell biology↗