Biology subjects

Ni, C.

Publications and source records attributed to Ni, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Dynamic merging of enhancer- and promoter-associated assemblies is coupled to transcriptional bursting

Classical models attribute distal enhancer function to chromatin looping, whereas emerging models propose that spatially organized assemblies of transcriptional regulators also facilitate enhancer-promoter communication. To investigate how these processes relate to transcription, we developed an endogenous-tagging-based four-color live-cell imaging platform and an integrated quantitative analysis pipeline in mouse embryonic stem cells (mESCs), enabling simultaneous visualization of regulatory assembly dynamics, chromatin organization and transcriptional bursting at the endogenous Sox2 locus. We find that the pluripotency transcription factor OCT4 and the coactivator BRD4 form numerous spatially distinct but dynamically interacting assemblies. At non-bursting Sox2 alleles, the promoter and the distal Sox2 enhancer SCR occupy distinct assembly environments, with stronger BRD4 association at the SCR than at the promoter. At bursting Sox2 alleles, transcription is coupled to transient merging and partial overlap of enhancer- and promoter-associated assemblies, with the SCR, promoter and nascent RNA frequently sharing OCT4/BRD4-enriched assembly environments across a broad range of SCR-promoter distances. Pharmacological perturbation of bromodomain-dependent BRD4 function preferentially suppresses long-duration, high-amplitude bursts. Together, our findings support a model in which transcriptional bursting is coupled to the dynamic reorganization and merging of enhancer- and promoter-associated regulatory assemblies, linking chromatin-looping and assembly-based views of enhancer-promoter communication.

molecular biology↗

bioRxiv2026

Enhancer Tuning by Sequence-Specific Repressors

Enhancers integrate combinatorial inputs from sequence-specific transcription factors (TFs) and their activity must be calibrated to achieve precise spatiotemporal control of transcript dosage. Here we demonstrate that the sequence-specific repressors SNAI1 and SNAI2 (i.e. SNAIL and SLUG) quantitatively tune enhancer activity. In human neural crest cells, SNAI1/2 occupy a subset of active enhancers, where their depletion increases H3K27ac, chromatin accessibility, and enhancer regulatory potential. Changes in SNAI1/2 binding motifs contribute to enhancer divergence between human and chimpanzee, suggesting an evolutionary role for the repressor-mediated tuning. Single-molecule chromatin profiling using Deaminase-Assisted Fiber-seq (DAF-seq) reveals that individual enhancers toggle between an ensemble of open and nucleosome-dense chromatin states. While transcriptional activators increase the fraction of the open states, SNAI1/2 shift the equilibrium toward nucleosome-occupied states. This impedes binding of activator TFs, without fully repressing the enhancer. We propose that SNAI1/2 function as a molecular dimmer switch, modulating nucleosome dynamics to calibrate enhancer output.

molecular biology↗

bioRxiv2026

Enhancer buffering protects dosage-sensitive housekeeping genes during vulnerable developmental transitions

Housekeeping genes maintain robust expression across cell types despite dynamic transcription factor fluctuations, yet their haploinsufficiency is associated with many tissue-specific developmental disorders. To understand this paradox, we focus on TCOF1, a broadly expressed regulator of rRNA synthesis, whose haploinsufficiency causes Treacher Collins syndrome (TCS). We show that transitional cranial neural crest cells (tCNCC) undergoing mesenchymal specification exhibit extreme dosage-sensitivity to TCOF1, but not to RNA polymerase I, explaining both cellular origins of TCS and prevalence of TCOF1 mutations in the disease. To maintain robust expression, TCOF1 deploys CNCC-specific enhancers that buffer against fluctuations in promoter-regulating factors, converting sensitive expression responses into threshold-protected outputs. Systematic promoter-enhancer coupling experiments demonstrate this principle generalizes across many dosage-sensitive housekeeping genes, whose promoters operate near saturation and only reveal their enhancer-dependency under suboptimal conditions. Thus, enhancers play a unique role at housekeeping promoters: rather than amplifying expression, they ensure its robustness during vulnerable developmental transitions.

genetics↗

bioRxiv2026

Faster science, penalties in evaluation, and concerns on quality and impact: Researchers' use and perceptions of preprints

The preprint ecosystem has expanded rapidly over the past decade, fundamentally altering science communication. Yet, the scholarly community's attitudes toward this shift remain underexplored. Through a large-scale survey of US and Canadian biomedical scholars, we provide a comprehensive analysis of preprint utilization, perceived impact, and integration into academic credit systems. We find robust engagement across reading, citing, and submitting preprints; however, this activity is driven primarily by a desire for rapid dissemination rather than a foundational commitment to open science. Furthermore, while preprints are valued as networking assets, perceived career penalties during formal academic evaluations stifle broader cultural adoption. Crucially, to navigate the absence of formal peer review, scholars report a heavy reliance on author reputation as a primary heuristic for evaluating a preprint's credibility and guiding their reading and citation decisions. Notably, despite acknowledging preprints' role in accelerating knowledge sharing, scholars express significant concerns regarding fraud and misinformation, particularly amid declining public trust in science and emerging threats to scientific integrity from artificial intelligence. To resolve these tensions, the preprint ecosystem must evolve beyond prioritizing speed to foster genuine academic dialogue. Simultaneously, evaluation frameworks must adapt to the realities of preprinting, and innovative quality-control mechanisms are urgently needed to balance rapid dissemination with rigorous scientific integrity.

scientific communication and education↗

bioRxiv2025

Association of handgrip strength asymmetry and weakness with successful aging among older adults in China

BackgroundSuccessful aging (SA) is important for the increasing population aging. The role of handgrip strength(HGS) asymmetry and weakness in successful aging remains unclear. This study aimed to elucidate the association of HGS asymmetry and weakness with successful aging in older adults. MethodsWe included participants aged [≥] 60 years from the 2015 China Health and Retirement Longitudinal Study (CHARLS).SA absence of major diseases, absence of major chronic diseases, no impairment in physical function, high cognitive functioning, good mental health, and active participation in life. HGS asymmetry and weakness were measured using the maximum value of the HGS. Logistic regression modeling was used to examine the association of individuals with HGS asymmetry and weakness with SA. Restricted cubic spline (RCS) modeling was used to explore potential nonlinear relationships. ResultsOf the 5,031 individuals included, the median age of the study population was 67 years IQR: 63-73 years, 45.6% female. Only 6.3% met the criteria for successful aging. HGS asymmetry (OR = 0.597,95 % CI: 0.472-0.754) and weakness (OR = 0.643,95 % CI: 0.417-0.964) were both independent influences on SA. Participants were less likely to have SA when both HGD asymmetry and frailty were present (OR = 0.426,95 % CI: 0.240-0.757). Further subgroup analyses revealed significant associations between HGS status and each of the components of SA, particularly with regard to physical functioning. There was an n-shaped relationship between HGS asymmetry and SA. ConclusionHGS asymmetry is associated with a reduced likelihood of weak SA. Improving or maintaining HGS symmetry and frailty may contribute to SA in older adults.

physiology↗

bioRxiv2025

Impact of infusion conditions and anesthesia on CSF tracer dynamics in mouse brain

Tracer imaging has been instrumental in mapping the brains solute transport pathways facilitated by cerebrospinal fluid (CSF) flow. However, the impact of tracer infusion parameters on CSF flow remains incompletely understood. This study evaluated the influence of infusion location, rate, and anesthetic regimens on tracer transport using dynamic contrast-enhanced MRI with Gd-DTPA as a CSF tracer. Infusion rate effects were assessed by administering Gd-DTPA into the cisterna magna (ICM) at two rates under isoflurane anesthesia. Anesthetic effects were evaluated by comparing transport patterns between isoflurane and ketamine/xylazine (K/X) anesthesia at the slower rate. Gd-DTPA transport was also examined after lateral ventricle (ICV) infusion, the primary site of CSF production. The results demonstrate that, besides anesthesia, both the location and rate of infusion substantially affected solute transport within the brain. ICV infusion led to rapid, extensive transport into deep brain regions, while slower ICM infusion resulted in more pronounced transport to dorsal brain regions. Cross-correlation and hierarchical clustering analyses of region-specific Gd-DTPA signal time courses revealed that ICM infusion facilitated transport along periarterial spaces, while ICV infusion favored transport across the ventricular-parenchymal interface. These findings underscore the importance of experimental conditions in influencing tracer kinetics and spatial distribution in the brain.

physiology↗

bioRxiv2024

Framework for assessing the risk to a field from fraudulent research

Concerns over research integrity are rising, with increasing attention to potential threats from untrustworthy authors. We established a framework to gauge the potential negative influence of researchers potentially engaged in misconduct. The field of Alzheimers Disease (AD) research has been a focal point of these worries. This study aims to assess the risk posed by questionable studies or individuals potentially engaging in fraudulent science in research by examining citation relationships among papers, taking AD research as an illustrative example. Analysis of citation network structure can elucidate the potential propagation of misinformation arising at the author level. Our analysis revealed that there arent any single authors or papers whose citation connections jeopardize a major portion of the fields literature. This indicates a low probability of single entities undermining the majority of works in this area. However, our findings suggest that attention to research integrity of the most influential scientists is warranted. Some scientists can reach a sizable minority of the literature through citations to their work. Emphasizing oversight of the integrity of these authors is crucial, given their influence on the field. Our study introduces an analytical framework adaptable across various fields and disciplines to evaluate potential risks from fraudulence.

scientific communication and education↗

bioRxiv2024

Pandemic Vibrio parahaemolyticus wave succession by gene loss

While spontaneous mutation and gene acquisition are well-established drivers of pathogen adaptation, the role of gene loss remains underexplored. Here, we investigated the emergence and diversification of the pandemic clone (PC) of Vibrio parahaemolyticus through large-scale phylogenomic analysis of 8,684 global isolates. The PC rapidly acquired multiple marker genes and genomic islands, subsequently diverging into successive sublineages mediating independent waves of cross-country transmission, as also observed in V. cholerae. Wave succession in the last two decades was driven by loss of putrescine utilization (Puu) genes, conferring phenotypic advantages for environmental adaptation (enhanced biofilm formation) and human transmission (increased cell adhesion/intestinal colonization, reduced virulence), consistent with the virulence trade-off hypothesis. We identified Puu-gene loss in multiple bacterial genera, with effects on biofilm and adhesion replicated in V. cholerae and Escherichia coli, suggesting convergent evolution and universal phenotypic effects. Our results highlight the indispensable role of gene loss in bacterial pathogen adaptation.

microbiology↗

bioRxiv2024

A cryopreservation strategy for myoblast storage in paper-based scaffolds for inter-laboratory studies of skeletal muscle health

Three-dimensional tissue-engineered models are poised to facilitate understanding of skeletal muscle pathophysiology and identify novel therapeutic agents to improve muscle health. Adopting these culture models within the broader biology community is a challenge as many models involve complex methodologies and significant investments of time and resources to optimize manufacturing protocols. To alleviate this barrier, we developed a protocol with commercially available reagents to cryopreserve myoblasts in a 96-well compatible format that allows tissues to be transferred to users without expertise in 2D or 3D skeletal muscle cell culture. We validate that myoblasts encapsulated in a hydrogel and cryopreserved in paper-based scaffolds maintain cell viability, differentiation, and function via acetylcholine-induced transient calcium responses. Furthermore, we demonstrate successful shipping of myoblasts cryopreserved in paper-based scaffolds to intra-provincial and international collaborators who successfully thawed, cultured, and used the 3D muscle tissues. Finally, we confirm the application of our method to study muscle endogenous repair by seeding freshly isolated skeletal muscle stem cells to cryopreserved then differentiated and injured tissues, demonstrating expected responses to a known stimulator of muscle stem cell self-renewal, p38/{beta} MAPKi. Altogether, our 3D myoblast cryopreservation protocol offers broadened access of a complex skeletal muscle tissue model to the research community.

bioengineering↗

bioRxiv2024

An inappropriate decline in ribosome levels drives a diverse set of neurodevelopmental disorders

Many neurodevelopmental defects are linked to perturbations in genes involved in housekeeping functions, such as those encoding ribosome biogenesis factors. However, how reductions in ribosome biogenesis can result in tissue and developmental specific defects remains a mystery. Here we describe new allelic variants in the ribosome biogenesis factor AIRIM primarily associated with neurodevelopmental disorders. Using human cerebral organoids in combination with proteomic analysis, single-cell transcriptome analysis across multiple developmental stages, and single organoid translatome analysis, we identify a previously unappreciated mechanism linking changes in ribosome levels and the timing of cell fate specification during early brain development. We find ribosome levels decrease during neuroepithelial differentiation, making differentiating cells particularly vulnerable to perturbations in ribosome biogenesis during this time. Reduced ribosome availability more profoundly impacts the translation of specific transcripts, disrupting both survival and cell fate commitment of transitioning neuroepithelia. Enhancing mTOR activity by both genetic and pharmacologic approaches ameliorates the growth and developmental defects associated with intellectual disability linked variants, identifying potential treatment options for specific brain ribosomopathies. This work reveals the cellular and molecular origins of protein synthesis defect-related disorders of human brain development. HighlightsO_LIAIRIM variants reduce ribosome levels specifically in neural progenitor cells. C_LIO_LIInappropriately low ribosome levels cause a transient delay in radial glia fate commitment. C_LIO_LIReduced ribosome levels impair translation of a selected subset of mRNAs. C_LIO_LIGenetic and pharmacologic activation of mTORC1 suppresses AIRIM-linked phenotypes. C_LI

developmental biology↗

bioRxiv2023

Activating SRC/MAPK signaling via 5-HT1A receptor contributes to the effect of vilazodone on improving thrombocytopenia

Thrombocytopenia caused by long-term radiotherapy and chemotherapy exists in cancer treatment. Previous research demonstrates that 5-Hydroxtrayptamine (5-HT) and its receptors induces the formation of megakaryocytes (MKs) and platelets. However, the relationships between 5-HT1A receptor (5-HTR1A) and MKs is unclear so far. We screened and investigated the mechanism of vilazodone as a 5-HTR1A partial agonist in promoting MK differentiation and evaluated its therapeutic effect in thrombocytopenia. We employed a drug screening model based on machine learning (ML) to screen the megakaryocytopoiesis activity of VLZ. The effects of Vilazodone (VLZ) on megakaryocytopoiesis were verified in HEL and Meg-01 cells. Tg (itga2b: eGFP) zebrafish was performed to analyze the alterations in thrombopoiesis. Moreover, we established a thrombocytopenia mice model to investigate VLZ administration accelerates platelet recovery and function. We carried out network pharmacology, Western blot and immunofluorescence to demonstrate the potential targets and pathway of VLZ. VLZ has been predicted to have a potential biological action. Meanwhile, VLZ administration promotes MK differentiation and thrombopoiesis in cells and zebrafish models. Progressive experiments showed that VLZ has a potential therapeutic effect on radiation-induced thrombocytopenia in vivo. The network pharmacology and associated mechanism study indicated that SRC and MAPK signaling are both involved in the processes of megakaryopoiesis facilitated by VLZ. Furthermore, the expression of 5-HTR1A during megakaryocyte differentiation is closely related to the activation of SRC and MAPK. Our findings demonstrated that the expression of 5-HTR1A on MK, VLZ could bind to the 5-HTR1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production, which provides new insights into the alternative therapeutic options for thrombocytopenia.

pharmacology and toxicology↗

bioRxiv2023

Analysis of the comparative strengths of intramural and extramural grant funding mechanisms

Funding agencies use a variety of mechanisms to fund research. The National Institutes of Health in the United States, for example, employs scientists to perform research at its own laboratories (intramural research), and it also awards grants to pay for research at external institutions such as universities (extramural research). Here, using data from 1594 intramural grants and 97054 extramural grants funded between 2009 and 2019, we compare the scholarly outputs from these two funding mechanisms in terms of number of publications, relative citation ratio and clinical metrics. We find that extramural awards are more cost-effective for producing outputs commonly used for academic evaluation, such as publications and citations (per dollar), while intramural awards are more cost-effective for generating research that influences future clinical work, more closely in line with the agencys health goals. These findings provide evidence that institutional incentives associated with different funding mechanisms drive their comparative strengths.

scientific communication and education↗

bioRxiv2023

You do not receive enough recognition for your influential science

During career advancement and funding allocation decisions in biomedicine, reviewers have traditionally depended on journal-level measures of scientific influence like the impact factor. Prestigious journals reject large quantities of papers, many of which may be meritorious. It is possible that this process could create a system whereby some influential articles are prospectively identified and recognized by journal brands but most influential articles are overlooked. Here, we measure the degree to which journal prestige hierarchies capture or overlook influential science. We quantify the fraction of scientists articles that would receive recognition because (a) they are published in journals above a chosen impact factor threshold, or (b) they are at least as well-cited as articles appearing in such journals. We find that the number of papers cited at least as well as those appearing in high-impact factor journals vastly exceeds the number of papers published in such venues. At the investigator level, this phenomenon extends across gender, racial, and career stage groupings of scientists. We also find that approximately half of researchers never publish in a venue with an impact factor above 15, which under journal-level evaluation regimes may exclude them from consideration for opportunities. Many of these researchers publish equally influential work, however, raising the possibility that the traditionally chosen journal-level measures that are routinely considered under decision-making norms, policy, or law, may recognize as little as 10-20% of this influential work.

scientific communication and education↗

bioRxiv2023

Gender differences in submission behavior exacerbate publication disparities in elite journals

Women are particularly underrepresented as leading authors of papers in journals of the highest impact factor, with substantial consequences for their careers. While a large body of research has focused on the outcome and the process of peer review, fewer articles have explicitly focused on gendered submission behavior and the explanations for these differences. In our study of nearly five thousand active authors, we find that women are less likely to report having submitted papers to journals of the highest impact (e.g., Science, Nature, or PNAS) andto submit fewer manuscripts, on average, than men when they do submit. Women were more likely to indicate that they did not submit their papers (in general and their subsequently most cited papers) to high-impact journals because they were advised not to. In the aggregate, no statistically significant difference was observed between men and women in how they rated the quality of their work. Nevertheless, regardless of discipline, women were more likely than men to indicate that their "work was not ground-breaking or sufficiently novel" as a rationale for not submitting to one of the listed prestigious journals. Men were more likely than women to indicate that the "work would fit better in a more specialized journal." We discuss the implications of these findings and interventions that can serve to mitigate the disparities caused by gendered differences in submission behavior. SignificancePublishing in high-impact scholarly journals has a significant effect on researchers careers. Our findings identify factors that affect submission to Science, Nature, and the Proceedings of the National Academy of Sciences of the United States of America (PNAS) and explore whether there is a relationship between gender and desk rejections or submission rates. We found no relationship between gender and reported desk rejection and a relationship between gender and reported submissions, with men having a greater number of submissions. Women were more likely than men to indicate that their "work was not ground-breaking or sufficiently novel" for the listed prestigious journals and that they were advised against submitting to these venues. Men were more likely to indicate that the "work would fit better in a more specialized journal."

scientific communication and education↗

bioRxiv2023

Synthetic Frizzled agonist and LRP antagonist for high-efficiency Wnt/β-catenin signaling manipulation in organoid cultures and in vivo

Wnt/{beta}-catenin signaling and its dysregulation play critical roles in the fate determination of stem cells and the pathology of various diseases. However, the application of translated Wnt ligand in regenerative medicine is hampered by its hydrophobicity and cross-reactivity with Frizzled (FZD) receptors. Here, we generate an engineered water-soluble, FZD subtype-specific agonist, RRP-pbFn, for high-efficiency Wnt/{beta}-catenin signaling activation. In the absence of direct binding to LRP5/6, RRP-pbFn stimulates Wnt/{beta}-catenin signaling more potently than surrogate Wnt. RRP-pbFn supports the growth of a variety of mouse and human organoids, and induces the expansion of liver and intestine progenitors in vivo. Meanwhile, we develop a synthetic LRP antagonist, RRP-Dkk1c, which exhibits heightened effectiveness in attenuating Wnt/{beta}-catenin signaling activity compared to Dkk1, thereby abolishing the formation of CT26-derived colon cancer xenograft in vivo. Together, these two paired Wnt/{beta}-catenin signaling manipulators hold great promise for biomedical research and potential therapeutics.

synthetic biology↗

bioRxiv2023

The significant yet short-term influence of research covidization on journal citation metrics

COVID-19 has emerged as a major research hotspot in recent years, leading to increased publications and citations of related papers. While concerns exist about the potential citation boost in journals publishing these papers, the specifics are not fully understood. This study uses a generalized difference-in-differences approach to examine the impact of publishing COVID-19 papers on journal citation metrics in the Health Sciences fields. Findings indicate that journals publishing COVID-19 papers in 2020 received significantly higher citation premiums due to COVID-19 in 2020 and continued to benefit from the premium in 2021 in certain fields. In contrast, journals that began publishing COVID-19 papers in 2021 experienced weaker citation premiums. Although the publication volume of non-COVID-19 papers also surged, these papers experienced insignificant or negative citation gains, even when published in the same journals as COVID-19 papers. COVID-19 papers published in high-impact journals brought more significant citation premiums to journals in most fields. These citation premiums can affect various citation-based journal metrics, such as our simulated impact factor, to different degrees. The results highlight a "gold rush" pattern in which early entrants establish their citation advantage in research hotspots and caution against using citation-based metrics for research assessment.

scientific communication and education↗

bioRxiv2022

Genome-scale CRISPR screening reveals host factors required for ribosome formation and viral replication

Viruses are known to co-opt host machinery for translation initiation, but less is known about which host factors are required for the formation of ribosomes used to synthesize viral proteins. Using a loss of function CRISPR screen, we show that synthesis of a flavivirus encoded reporter depends on multiple host factors, including several 60S ribosome biogenesis proteins. Viral phenotyping revealed that two of these factors, SBDS, a known ribosome biogenesis factor, and the relatively uncharacterized protein SPATA5, were broadly required for replication of flaviviruses, coronaviruses, alphaviruses, paramyxoviruses, an enterovirus, and a poxvirus. Mechanistic studies revealed that loss of SPATA5 caused defects in ribosomal RNA processing and ribosome assembly, suggesting that this human protein may be a functional ortholog of yeast Drg1. These studies implicate specific ribosome biogenesis proteins as viral host dependency factors that are required for synthesis of virally encoded protein and accordingly, optimal viral replication.

microbiology↗

bioRxiv2022

The gender gap in academic career achievements and the mediation effect of work-family conflict and partner support

Parenthood has long been associated with gender disparities in academia. Yet, the underlying mechanism of how parenting is associated with career achievement gaps of academics remains unclear. Using data from a large-scale survey distributed to 7,764 scholars and their publication profiles from the Web of Science database, we analyze the gender differences in parenthood, academic achievements, and the mediation effect of work-family conflict and partner support in these gender gaps. Our results suggest that gender gaps in academic achievements are in fact "parenthood gaps". Specifically, we found significant gender gaps exist in all measures of objective and subjective career achievements of academics in the parent group but not in the non-parent group. Additionally, mothers are more likely than fathers to experience higher levels of work-family conflict, and receive lower levels of partner support, contributing significantly to the gender gaps in objective and subjective career achievements for the parent group. Findings from this study identify the forms and the impact of parenthood on gender disparities in career achievements of academics and shed light on possible interventions and actions for mitigating gender inequalities in academia.

scientific communication and education↗