Biology subjects

Hang, H.

Publications and source records attributed to Hang, H..

10 recordsLinked to original sources

bioRxiv2026

Selective Elimination of TP53 Mutant Cells by Transcript-Activated Chromatin Shredding

Genetic mutations that drive cancer often occur in tumor suppressor proteins, including the p53 transcription factor which is altered in [~]40-50% of cases1,2. However, current therapies fail to target most such mutations because the mutant proteins typically lack defined drug-binding pockets, and restoring the endogenous function has proven challenging. Here, we programmed CRISPR-Cas12a2, an RNA-guided nuclease with trans-nucleolytic cleavage activities3,4, to selectively kill cancer cells by targeting cancer-specific transcripts. This approach eliminates cells by inducing trans chromatin cleavage, triggering DNA damage and cell death. Unlike existing methods, RNA-guided Cas12a2 senses cellular RNA signatures to shred chromatin, enabling precise targeting of undruggable mutations. Transcript-activated chromatin shredding provides an innovative paradigm to develop precision disease treatments for undruggable targets.

cell biology↗

bioRxiv2026

T-bet Expressing B cells are Key Determinants of Protective Immunity Against Norovirus Infection

The gastrointestinal tract (GI) is the largest environmental mucosal interface and is exposed to diverse commensal and pathogenic microbes. B cells are a prevalent immune component of the GI tract and its associated secondary lymphoid organs, yet we know little about the diversity and stability of distinct transcriptional programs that modulate B cell responses against different classes of pathogens or environmental perturbations. A subset of B cells defined by expression of the transcription factor T-bet, has been canonically associated with antiviral immunity through IgG production. However, the role of T-bet expressing B cells in mucosal tissues, where IgA responses predominate, is poorly understood. Here, we identify a population of intestinal T-bet+ B cells that, in the absence of overt perturbation, constitutes a minor fraction of intestinal associated B cells and undergoes continuous turnover. In contrast, during enteric viral infection with murine norovirus (MNV), T-bet B cells undergo a marked expansion, with T-bet expression stably maintained in the majority of virus-specific B cells, including IgG2c and IgA switched B cells. Moreover, virus-reactive IgG2c and IgA B cells arise independently rather than through sequential switching, and B cell intrinsic T-bet expression is required for effective germinal center responses but dispensable for IgA class switching. Moreover, T-bet expressing B cells are required for the generation of all MNV-specific circulating IgG and mucosal IgA, and for protection upon re-encounter with the virus. Together, these findings establish T-bet expressing B cells as a specialized B cell subset essential for mucosal immunity and protection against norovirus infection.

immunology↗

bioRxiv2025

Study on physiological and ecological responses of alfalfa during the germination stage under drought, bicarbonate, and combined stress conditions

Alfalfa (Medicago sativa L.) is frequently constrained by drought and salinity during cultivation and production. This study aimed to investigate the differential response characteristics and underlying physiological and ecological mechanisms of alfalfa during the germination stage under drought stress, bicarbonate stress, and their combined effects. Twelve alfalfa varieties were subjected to germination tests using PEG-6000 to simulate drought stress (0-20%) and NaHCO{square} to simulate bicarbonate stress (0-30 mM). Based on the semi-inhibitory concentrations and phenotypic indices observed under single-stress conditions, a combined stress treatment was designed. The subordinate function method was employed to comprehensively evaluate the variations in stress responses among the twelve alfalfa varieties during the germination stage. Additionally, this study explored the physiological and ecological response mechanisms of drought-tolerant, salt-tolerant, and drought-salt-sensitive varieties. Among the 12 alfalfa varieties, WL363HQ has the strongest drought and salt tolerance, while WL319HQ is the most sensitive to drought and salt stress. Based on this, the varieties can be classified into drought-tolerant, salt-tolerant, and sensitive categories. At low concentrations, the drought-salt combination shows antagonism (salt alleviates drought inhibition); at high concentrations, it turns into synergy, and the inhibitory effect is amplified.WL363HQ adapts to the combined stress by maintaining stable SOD activity and gradually accumulating soluble sugar; WL319HQ shows sensitivity due to fluctuating SOD, membrane lipid peroxidation, and uncontrolled soluble sugar.

plant biology↗

bioRxiv2025

Microbiota-derived secondary bile acids promote STING activation and antitumor activity

Microbiota metabolism generates diverse bile acids that are associated with health and disease, but the molecular targets and mechanisms of action for these metabolites have not been fully elucidated. Using deoxycholic acid (DCA) photoaffinity probes, with cholic acid (CA) probe as a comparator, we found many protein targets of microbiota-derived DCA in mammalian cells. Of note, we discovered that DCA binds the transmembrane domain of stimulator of interferon genes (STING), and enhances agonist-induced accumulation of higher-order STING species, type I interferon signaling and antitumor immunity. Moreover, DCA-producing microbiota species enhanced STING agonist-induced antitumor immunity primarily through the activation of natural killer (NK) cells. This reverse chemical microbiology approach revealed an unpredicted mechanism of action for DCA on STING activation and suggests that specific secondary bile acids and their associated microbiota species may promote NK activation and impact the efficacy of STING-targeted therapeutics.

immunology↗

bioRxiv2024

Mapping Spatial Patterns to Energetic Benefits in Groups of Flow-coupled Swimmers

The coordinated motion of animal groups through fluids is thought to reduce the cost of locomotion to individuals in the group. However, the connection between the spatial patterns observed in collectively moving animals and the energetic benefits at each position within the group remains unclear. To address this knowledge gap, we study the spontaneous emergence of cohesive formations in groups of fish, modeled as flapping foils, all heading in the same direction. We show in pairwise formations and with increasing group size that (1) in side-by-side arrangements, the reciprocal nature of flow coupling results in an equal distribution of energy re-quirements among all members, with reduction in cost of locomotion for swimmers flapping inphase but an increase in cost for swimmers flapping antiphase, and (2) in inline arrangements, flow coupling is non-reciprocal for all flapping phase, with energetic savings in favor of trailing swimmers, but only up to a finite number of swimmers, beyond which school cohesion and energetic benefits are lost at once. We explain these findings mechanistically and we provide efficient diagnostic tools for identifying locations in the wake of single and multiple swimmers that offer op-portunities for hydrodynamic benefits to aspiring followers. Our results imply a connection between the resources generated by flow physics and social traits that influence greedy and cooperative group behavior.

biophysics↗

bioRxiv2023

Interpretable and Generalizable Strategies for Stably Following Hydrodynamic Trails

Aquatic animals offer compelling evidence that flow sensing alone, without vision, is sufficient to guide a swimming organism to the source of an unsteady hydrodynamic trail. However, the sensory feedback strategies that allow these remarkable trail tracking abilities remain opaque. Here, by integrating mechanistic flow simulations with reinforcement learning techniques, we discovered two simple and equally effective strategies for hydrodynamic trail following. Though not a priori obvious, these strategies possess parsimonious interpretations, analogous to Braitenbergs simplest vehicles, where the agent senses local flow signals and turns away from or toward the direction of stronger signals. A rigorous stability analysis shows that the effectiveness of these strategies in robustly tracking flow currents is independent of the type of sensor but depends on sensor placement and the traveling nature of the flow signal. Importantly, these results inform a suite of versatile strategies for hydrodynamic trail following applicable to both vortical and turbulent flows. These insights support the future design and implementation of adaptive real-time sensory feedback strategies for autonomous robots in dynamic flow environments.

biophysics↗

bioRxiv2022

Study of the anti-inflammatory and anti-apoptosis effect of the traditional Mongolian Hohgardi-9 in acute lung injury

ObjectiveTo explore the main active components of Hohgardi-9 and its mechanism treating in ALI. MethodsThrough searching the TCMSP database, we obtained the main components and action targets of Hohgardi-9, and the targets related to ALI were analyzed as the possible targets of Hohgardi-9. Then, the compound target network was constructed using Cytoscape software and obtained the key compounds of Hohgardi-9 acting on ALI. The blood entering components of Hohgardi-9 were analyzed by metabonomics. Using a string database to investigate the interaction between proteins of possible targets of Hohgardi-9, Gene Ontology (GO) function annotation and Tokyo Encyclopedia of the genome (KEGG) pathway enrichment analysis were carried out at the same time to predict its mechanism. Finally, the ALI rat model verified the pharmacodynamic effects and key targets of Huhgridi-9. ResultsThe network pharmacology and blood component analysis results showed that 27 potentially active components such as quercetin, herbacetin, izoteolin, and columbinetin acetate were the major functional components in Hohgardi-9. Those might act on NF kappa B signalling pathway, toll-like receptor signalling pathway, and TNF signalling pathway through key targets such as RELA (p65), TLR4, etc. In vivo experiments showed that Hohgardi-9 significantly improved lung tissue injury and pulmonary edema in ALI rats. At the same time, the Hohgardi-9 intervention could significantly reduce the mRNA expression levels of TRL4, TNFa, IL-1 {beta}, and ICAM1 in ALI rats. ConclusionHohgardi-9 revealed ALI through the inhibiting inflammatory factor apoptosis-related gene expression.

pharmacology and toxicology↗

bioRxiv2021

A survey of optimal strategy for signature-based drug repositioning and an application to liver cancer

Pharmacologic perturbation projects, such as Connectivity Map (CMap) and Library of Integrated Network-based Cellular Signatures (LINCS), have produced many perturbed expression data, providing enormous opportunities for computational therapeutic discovery. However, currently there is no consensus on which methodologies and parameters are the most optimal to conduct such analysis. Aiming to fill this gap, we developed new benchmarking standards for quantitatively estimating drug retrieval performance. Investigations of potential factors influencing drug retrieval were conducted based on these standards. As a result, we determined an optimal strategy for LINCS data-based therapeutic discovery. With this approach, we further identified new therapeutics for liver cancer of which the current treatment modalities remain imperfect. Both computational and experimental results demonstrated homoharringtonine (HHT) could be a promising anti-liver cancer agent. In summary, our findings will not only impact the future applications of LINCS data but also offer new opportunities for therapeutic intervention for liver cancer.

bioinformatics↗

bioRxiv2021

Loss of STAT5 in adipocytes increases subcutaneous fat mass via sex-dependent and depot-specific pathways

The STAT (Signal Transducers and Activators of Transcription) family of transcription factors contributes to adipocyte development and function. STAT5A and STAT5B are induced during adipocyte differentiation and are primarily activated by growth hormone (GH). Studies in mice lacking adipocyte GH receptor or STAT5 support their roles in lipolysis-mediated reduction of adipose tissue mass. We have generated a mouse model lacking both STAT5 genes specifically in adipocytes (STAT5AKO). Notably, both sexes of STAT5AKO mice have increased inguinal adipose tissue without any changes in gonadal fat mass. However, both depots exhibit substantial differences in fat cell size. Study of STAT5AKO mice also have revealed that GHs ability to induce insulin resistance is dependent upon STAT5 in adipocytes, but its ability to reduce adipose tissue mass is STAT5 independent. Additional observations, which were not predicted, indicate that the causes and regulation of increased fat mass in STAT5AKO mice are sex- and depot-dependent.

cell biology↗

bioRxiv2020

Geometric and Topological Approaches to Shape Variation in Ginkgo Leaves

Leaf shape is a key plant trait that varies enormously. The diversity of leaf shape, and the range of applications for data on this trait, requires frequent methodological developments so that researchers have an up-to-date toolkit with which to quantify leaf shape. We generated a dataset of 468 leaves produced by Ginkgo biloba, and 24 fossil leaves produced by evolutionary relatives of extant Ginkgo. We quantified the shape of each leaf by developing a geometric method based on elastic curves and a topological method based on persistent homology. Our geometric method indicates that shape variation in our modern sample is dominated by leaf size, furrow depth, and the angle of the two lobes at the base of the leaf that is also related to leaf width. Our topological method indicates that shape variation in our modern sample is dominated by leaf size and furrow depth. We have applied both methods to modern and fossil material: the methods are complementary, identifying similar primary patterns of variation, but also revealing some different aspects of morphological variation. Our topological approach distinguishes long-shoot leaves from short-shoot leaves and both methods indicate that leaf shape influences or is at least related to leaf area.

plant biology↗