Biology subjects

Huang, Z.

Publications and source records attributed to Huang, Z..

At least 145 records · Page 8Linked to original sources

bioRxiv2025

Comprehensive profiling of N6-methyladnosine (m6A) readouts reveals novel m6A readers that regulate human embryonic stem cell differentiation

N6-methyladenosine (m6A) methylation has emerged as a prevalent RNA modification that extensively impacts various physiological and pathological processes via various post-transcriptional readout effects in mammals. High-throughput methylome profiling has outlined the landscape of m6A modification sites, but their downstream readouts require comprehensive investigation. To this end, we systematically assessed the effects of m6A on mRNA half-life, translation efficiency, and alternative splicing across five cell lines (A549, HEK293T, HUVEC, JURKAT, and human embryonic stem cells (hESCs)) using actinomycin D-disrupted temporal transcriptome sequencing, ribosome sequencing, and ultra-high-depth transcriptome sequencing, respectively. Our analysis, coupled with the integration of public and re-profiled m6A methylome data, revealed high cell type specificity in m6A readouts where m6A level alone is insufficient to predict m6A readouts. Machine learning models focused on the RNA binding protein (RBP) binding context of m6A sites demonstrated substantial predictive ability of m6A readouts while prioritizing putative m6A readers from their informative RBP features. Four novel m6A readers (DDX6, FUBP3, FXR2, and L1TD1) were identified and validated through m6A RNA pull-down assays and transcriptome-wide RBP binding site mapping. Notably, FUBP3, FXR2 and L1TD1 were found to regulate hESC differentiation without impairing self-renewal, underscoring their critical roles in stem cell biology. Together, this study bridges the gap in understanding m6A functional readouts and lays the groundwork for future research on m6A-mediated stem cell fate decisions.

genomics↗

bioRxiv2025

RNA Architecture Underlies Discontinuous Transcription and Evolution of Coronavirus

Coronaviruses employ discontinuous transcription to produce canonical subgenomic RNAs (sgRNAs) essential for gene expression, as well as non-canonical sgRNAs with unclear function. Nevertheless, the mechanisms regulating the balance between canonical and non-canonical sgRNAs throughout the viral replication cycle remain unknown. We conducted an integrated analysis on 234 transcriptome and 12 RNA-RNA interactome samples across various coronavirus genera. RNA-RNA interactions were identified between TRS-B and TRS-L flanking regions in the same genomic direction, correlating with the formation of canonical junctions. Non-canonical junctions frequently span short or long genomic distance, with short-range junctions generally mediated by reverse complementary stem-loops and coinciding with genomic deletion regions. Conserved long-range non-canonical sgRNAs were identified across different coronaviruses, and these sgRNAs harbor ORF10 or an evolving gene to suppress antiviral innate immune responses. This work establishes a structural framework that enables an understanding of the regulatory mechanism behind discontinuous transcription and the evolutionary pathway of coronaviruses. TeaserDeciphering coronavirus transcription and evolution: an integration analysis of transcriptome and RNA-RNA interactome. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=165 HEIGHT=200 SRC="FIGDIR/small/642953v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1c58502org.highwire.dtl.DTLVardef@9f87d7org.highwire.dtl.DTLVardef@18f3492org.highwire.dtl.DTLVardef@c49362_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

D-LMBmapX: Generalized Deep-Learning Pipeline for Automated Whole-brain Neural Circuitry Profiling Across Any Developmental Stages

Understanding whole-brain circuitry development is essential for uncovering the origins of disorders linked to abnormal neural wiring, yet progress has been limited by the lack of tools for accurate, comprehensive analysis. Brain development is highly dynamic and region-specific, with pronounced inter-individual variability during early stages, and no existing method achieves whole-brain profiling at arbitrary stages. The rapidly changing morphology of developing axons further complicates segmentation. Here, we present D-LMBmapX, a deep learning pipeline for automated whole-brain circuitry profiling across postnatal development. D-LMBmapX constructs sample-inferred atlases from flanking anchor stages, enabling accurate registration at any time point. By developing a foundation model for generalised axon and soma segmentation, it supports quantitative mesoscale developmental connectomics, demonstrated through spatial-temporal profiling of catecholaminergic projections. D-LMBmapX also enables robust cross-modality and cross-dimensional registration, including precise alignment of single 2D slices to 3D references, and offers generalizable strategies for 5D analysis of diverse biomedical spatial datasets.

neuroscience↗

bioRxiv2025

CellFateExplorer: An integrated platform for exploring cell fate

Cell fate prediction from single-cell omics data is a central task for reconstructing developmental dynamics and inferring lineage relationships, but existing tools remain fragmented and often tailored to specific trajectory structures. Here we present Cafe (CelluAr Fate Explorer), an integrated platform for cell fate analysis that unifies trajectory-aware data storage, heterogeneous inference methods, benchmarking, visualization, and downstream interpretation. Cafe standardizes diverse inputs into a common milestone-network representation, supports both native and Dynverse-compatible methods, and evaluates performance across representative benchmark criteria. Applied to representative case studies across atlas-scale and lineage-resolved datasets, Cafe recovers coherent developmental trajectories and provides benchmark-guided method selection across data types and biological contexts. A browser-based interface built on cellxgene enables interactive trajectory inspection. Cafe also supports downstream analyses, including driver-gene prioritization and gene-regulatory-network inference. As an open, community-driven platform, Cafe is designed to evolve continuously with contributions from developers and users, expanding method coverage and functionality for cell fate prediction.

cell biology↗

bioRxiv2025

From imaging to computational domains for physics-driven molecular biology simulations: Hindered diffusion in platelet masses

When formed in vivo, murine hemostatic thrombi exhibit a heterogeneous architecture comprised of distinct regions of densely and sparsely packed platelets. In this study, we utilize high-resolution electron microscopy alongside machine learning and physics-based simulations to investigate how such clot microstructure impacts molecular diffusivity. We used Serial Block Face - Scanning Electron Microscopy (SBF-SEM) to image select volumes of hemostatic masses formed in a mouse jugular vein, producing large stacks of high-resolution 2D images. Images were segmented using machine learning software (Cellpose), whose training was augmented by manually segmented images. The segmented images were then utilized as a computational domain for Lattice Kinetic Monte-Carlo (LKMC) simulations. This process constitutes a computational pipeline that combines purely data-derived biological domains with physics-driven simulations to estimate how molecular movement is hindered in a hemostatic platelet mass. Using our pipeline, we estimated that the hindered diffusion rates of a globular protein range from 2% to 40% of the unhindered rate, with denser packing regions lending to lower molecular diffusivity. These data suggest that coagulation reactions rates, thrombin generation and activity, as well as platelet releasate activity may be drastically impacted by the internal geometry of a hemostatic thrombus. Author SummaryHemostasis and coagulation are two exquisitely complex, intertwined, and tightly regulated biological processes. Dysregulation of either process may lead to severe health consequences or death. Coagulation reactions have been extensively studied under static laboratory conditions, which are different from in vivo conditions. It is therefore imperative to understand if and how the chemical reactions underlying coagulation are regulated by the environment where they occur. In vivo experimentation enables us to image hemostasis, but not chemical reactions. Physics-driven molecular simulations of chemical reactions can bridge the gap, provided the physical environment is correctly represented computationally. The present work serves as a much-needed foundation for image-to-computation for physics based molecular simulations in biological domains.

systems biology↗

bioRxiv2025

Single-Cell Genomics Elucidates Molecular Variations and Regulatory Mechanisms in Circulating Immune Cells

The human peripheral blood displays diverse molecular characteristics across populations, understanding the drivers and underlying mechanisms of which remains challenging. Here, we introduce the Chinese Immune Multi-Omics Atlas (CIMA), elucidating sex-, age-, and genetic-related molecular variations by analyzing multi-omics data from 428 adults with over 10 million immune cells. CIMA generated an enhancer-driven gene regulatory network, identifying 237 high-quality regulons and revealing cell type-specific regulatory mechanisms. Additionally, 11,521 lead cis-expression quantitative trait loci (eQTLs) and 46,339 chromatin accessibility QTLs (caQTLs) were identified at cell type level. CIMA also uncovered pleiotropic associations among immune-related disease risk loci, eQTLs, and caQTLs in a cell type-specific manner. Lastly, a novel cell language model, CIMA-CLM, was developed to predict chromatin accessibility and noncoding variant effects using chromatin sequences and gene expressions. This work represents a population-scale multi-omics resource of human immune cells, providing a valuable reference for future investigation of immune-related diseases.

immunology↗

bioRxiv2025

Sequencing-based Spatial Transcriptomics with scRNA-seq Sensitivity

The advent of spatial transcriptomics has dramatically expanded our ability to study the vast network of cell-cell interactions at the molecular level in tissue. Among current methods, sequencing-based approaches have great potential in discovering because of its unbiased capture. In the last couple of years, the spatial resolution for the capture addresses has been significantly improved from 100 m to <1 m, well below the size of a mammalian cell. However, the capture efficiency has always been a pain point, [~]one order of magnitude lower than that of single cell RNA sequencing (scRNA-seq). The low capture efficiency limits the depth and breadth of its applications in the study of complex biological systems and diseases. Here, we introduce Salus Spatial transcriptomic system (Salus-STS), which provides [~]1 m capture resolution and a capture efficiency [~]1 order of magnitude higher than other current methods. Analysis with sub-cellular resolution becomes practical for sequencing-based spatial transcriptomics.

molecular biology↗

bioRxiv2025

Intracellular tension relaxation engineered through D-enantiomeric hydrogel maneuvers neurogenesis and immunomodulation to facilitate spinal cord repair

Microenvironmental mechanics regulate morphogenesis and post-injury inflammation, however, the fragile mechanical strength and oxidative physiological environment hinder precise and consistent mechanical management after spinal cord injury (SCI). Here, we engineered self-assembling hydrogels of enantiomeric peptides with neural tissue- matching mechanical properties to persistently manipulate mechanosensing and mechanotransduction through stereo conformational recognition and consequent protein affinity difference. While hindering proliferation and morphogenesis in non-neural cells, D-hydrogel-induced intracellular tension relaxation triggered neurogenesis and ECM remolding in astrocytes, while simultaneously suppressing pro-inflammation and promoting pro-regeneration in microglia, which together enable neuroprotection from degeneration and enhance functional recovery in severe SCI rat models. These effects are mediated through neurogenic morphology changes resulting from cytoskeletal tension relaxation, leading to the opening of mechanosensitive ion channels in the cellular membrane, chromatin unfolding, and YAP nuclear translocation. This exclusive D- hydrogel-dependent neurogenesis, triggered by intracellular tension relaxation, revealed a neural-specific response to mechanical cues and provided a targeted tissue repair strategy for nerve injury. TeaserIntracellular tension relaxion activates morphogenesis specifically in neural cells through reversing neurogenic cellular morphology.

neuroscience↗

bioRxiv2025

Synergizing Network Pharmacology and Pan-Cancer Analysis in TCM Repositioning for Tumor Therapy

BackgroundRepositioning Traditional Chinese Medicine (TCM) for cancer treatment, addressing heterogeneity through synergistic effects, aligns with the evolving trend of combination therapy. However, the complexity of TCM and the lack of methodology hinders the elucidation of TCM treatment mechanisms and potential indications. The research aims to construct develop a comprehensive method combining network pharmacology and pan-cancer analysis (NetPharm-PanCan) for TCM repositioning, exemplified by the Astragali Radix-Curcumae Rhizoma (ARCR) herb pair. MethodThe TCM-component-gene network was constructed using Cytoscape3.7.2 with gene screening based on components from TCMSP and targets predicted via the Swiss Target Prediction database. The core gene set of the ARCR (CGSARCR) was identified by analyzing network via the dual algorithm, namely Degree and MCODE followed by GO and KEGG enrichment analyses. The pan-cancer analysis encompassing Gene Set Variation Analysis (GSVA), immune infiltration correlation, cancer pathway analysis, and Gene Set Enrichment Analysis (GSEA) was unveiled to identify the potential indications. Multivariate cox regression analysis was employed for identifying prognostic genes, followed by the modeling for potential therapeutic indications using the R software. The Metescape database was harnessed to reveal similarities and differences in the mechanisms for prognostic genes associated with potential indications. The XGBoost algorithm was used to construct an indication prediction system according to the analysis results above. ResultThe CGSARCR comprises 28 genes targeting all ARCR components. The pan-cancer analysis revealed that the CGSARCR showed significantly higher tumor scores than normal tissue scores across nine different types of cancer, including THCA, KIRC, LUAD, COAD, BRCA, STAD, ESCA, and others. The CGSARCR correlated strongly with cancer-related pathways and the immune microenvironment. Prognostic models evaluate the potential of these indications as follows: THCA> KIRC> LUAD> COAD> BRCA> STAD> ESCA, with enrichment analysis suggesting KIRC and LUAD as the most potential indications of ARCR. The XGBoost-based system achieved high predictive accuracy (training AUC: 0.985, testing AUC: 0.96, training logloss: 0.21, testing logloss: 0.25). ConclusionThe NetPharm-PanCan method provides a robust, network-based pan-cancer analysis framework for TCM repositioning in cancer research. It provides theoretical foundations and practical tools for TCM-based drug development, with potential applicability to broader drug repurposing efforts.

bioinformatics↗

bioRxiv2025

Crosslinker-free in situ hydrogel induces self-aggregation of human dental pulp stem cells with enhanced antibacterial activity

Recently, injectable hydrogels have garnered significant attention in tissue engineering due to their controlled flowability, strong plasticity, adaptability, and good biocompatibility. However, research on readily injectable in situ-forming hydrogels capable of forming functional three-dimensional (3D) tissue condensations remains limited. This study explores the development and evaluation of a carboxymethyl chitosan (CMCTS) / oxidized hyaluronic acid (oHA) hydrogel incorporated with silver sulfadiazine (AgSD) for tissue engineering applications with inherent antibacterial activity. Through physicochemical analysis, the optimal formulation of CMCTS/oHA hydrogels was established. The hydrogel demonstrated excellent injectability, enabling minimally invasive in situ delivery. In vitro cytotoxicity assays identified 0.1% AgSD as the optimal concentration, supporting cell proliferation while exhibiting antimicrobial efficacy against S. mutans and E. faecalis. In vivo studies revealed complete hydrogel degradation and good biocompatibility, with no adverse tissue reactions. The hydrogels ability to form 3D cell aggregates and support tissue regeneration underscores its potential for future 3D tissue engineering applications. Consequently, the injectable CMCTS/oHA/AgSD hydrogel developed in this study holds significant potential for application in a wide range of bioengineering fields, including antibacterial substance delivery systems and 3D tissue engineering, indicating potential for future clinical application.

bioengineering↗

bioRxiv2024

The genetic diversity and populational specificity of the human gut virome at single nucleotide resolution

Large-scale characterization of gut viral genomes provides strain-resolved insights into host-microbe interactions. However, existing viral genomes are mainly derived from Western populations, limiting our understanding of global gut viral diversity and functional variations necessary for personalized medicine and addressing regional health disparities. Here, we introduce the Chinese Gut Viral Reference (CGVR) set, consisting of 120,568 viral genomes from 3,234 deeply sequenced fecal samples collected nationwide, covering 72,751 viral species-level clusters (VSCs), nearly 90% of which are absent from current databases. Analysis of single nucleotide variations (SNVs) in 233 globally prevalent VSCs revealed that 18.9% showed significant genetic stratification between Chinese and non-Chinese populations, potentially linked to bacterial infection susceptibility. The predicted bacterial hosts of population-stratified viruses exhibit distinct genetic components associated with health-related functions, including multidrug resistance. Additionally, viral strain diversity at the SNV level correlated with human phenotypic traits, such as age and gastrointestinal issues like constipation. Our analysis also indicates that the human gut bacteriome is specifically shaped by the virome, which mediates associations with human phenotypic traits. This foundational resource underscores the unique genetic makeup of the gut virome across populations and emphasizes the importance of recognizing gut viral genetic heterogeneity for deeper insights into regional health implications.

microbiology↗

bioRxiv2024

The Basal Ciliary but not Cytosol PKA Specifically Regulates HH Pathway Downstream of Smoothened

Effectors of the vertebrate Hedgehog (HH) signaling pathway are organized through primary cilia (PC) that grow and retract in lockstep with the cell cycle in response to extracellular signals. Protein kinase A (PKA), a kinase with ubiquitous distribution in most cells, functions as a specific negative regulator of the HH pathway. Its functional specificity in the HH pathway has been suggested to be controlled by cAMP in the PC. However, the regulation of PKA and its functions in PC remain unclear, in part due to the lack of observation of PKA localization in PC during HH resting state as well as conflicting reports of the dynamic changes of cAMP in cilia and HH pathway activity. To address this issue, we have developed a ciliary-localized FRET-based A-kinase activity probe (Nphp3N-AKAR2-CR) as an improved biosensor for monitoring real-time PKA activity in the PC of both cultured cells and living zebrafish embryos. Although the PKA catalytic subunit (PKA-C) was not observed in PC, basal PKA activity in cells could be detected with this probe. In addition, we have found that only ciliary-targeted PKA and not cytosolic PKA, can modulate the HH pathway, even when the integrity of the PC is disrupted. Notably, ciliary PKA activity was barely changed either by inhibition or activation of the HH pathway at the level of Smoothened (SMO), the obligate HH signal transducer. Moreover, we found that even low concentration of the adenylyl cyclase agonist forskolin (FSK) can efficiently inhibit the HH pathway in the presence of the constitutively active variant SMOA1, suggesting that the activation of the HH pathway by SMO may not be due solely to direct regulation of PKA activity in the PC.

cell biology↗

bioRxiv2024

AtKC1 inhibits AtAKT1 activation via its amino-terminal inhibitory domain

AKT1 is a plant Shaker-like, hyperpolarization-activated K+ channel which plays a crucial role in K+ absorption. Besides phosphorylation, AKT1 is subject to negative regulation by AtKC1, a silent channel of the same family. Previous structural studies unveiled that AKT1 and AtKC1 form 2:2 heterotetramer in purified samples. However, the structural analysis failed to offer more insight into the inhibition mechanism of AKT1 activation by AtKC1. Here, inspecting the complex structure of AKT1-AtKC1 reveals that a stable domain of AtKC1 (residues 53 to 80), named inhibitory domain or I-domain, may inhibit AKT1 activation by stabilizing its depolarized, closed conformation. We confirmed this hypothesis with electrophysiological experiments. Interestingly, a single-point mutation (G315D) in AtKC1 has been reported to abolish its ability to inhibit AKT1. We solved the structure of AKT1-AtKC1(G315D) at a resolution of 2.8 [A] which revealed an unexpected stoichiometry alteration between AKT1 and AtKC1 from 2:2 to 3:1. This stoichiometry change further supports the hypothesis as we reason that single I-domain of AtKC1 in the channel complex is insufficient to effectively inhibit channel activation. Our findings reveal the inhibition mechanism of AtKC1 on AKT1 and offer insight into the regulatory mechanisms of hyperpolarization-activated channels.

biochemistry↗

bioRxiv2024

G-quadruplexes catalyze protein folding by reshaping the energetic landscape

Many proteins have slow folding times in vitro that are physiologically untenable. To combat this challenge, ATP-dependent chaperonins are thought to possess the unique ability to catalyze protein folding. Performing quantitative model selection using protein folding and unfolding data, we here show that short nucleic acids containing G-quadruplex (G4) structure can also catalyze protein folding. Performing the experiments as a function of temperature demonstrates that the G4 reshapes the underlying driving forces of protein folding. As short nucleic acids can catalyze protein folding without the input of ATP, the ability of the cell to fold proteins is far higher than previously anticipated. Significance StatementHow folding of proteins occurs en masse in the cell is still a daunting unsolved problem. Many proteins have complicated and difficult folding trajectories, with in vitro folding times that are physiologically untenable. The acceleration of protein folding to physiologically relevant timescales is a biologically essential function thought to be accomplished by a small set of ATP-dependent chaperonins. In this work, we surprisingly show that small nucleic acid sequences containing G-quadruplexes can catalyze protein folding and reshape protein folding energy landscapes. As a result, the capacity for accelerating protein folding in the cells is far higher than previously suggested, potentially explaining the accommodation of large number of proteins with physiologically unreasonable folding times.

biophysics↗

bioRxiv2024

Homogeneously crosslinked in situ hydrogel enclosing high-density human-cancer cells promotes vascularized in vivo tumor modeling for immune cell therapy

Cancer models in animal studies play a central role in cancer research, particularly in investigating vascularized tumor tissues for the validation of immune cell therapies. However, xenografts relying solely on cancer cells are ineffective for optimal tumor tissue formation. Additionally, tumor modeling using hydrogels with cancer cells to promote vascularization often leaves behind residual biomaterials that inhibit integration with surrounding tissues. To address these issues, we utilized a straightforward in vivo vascularized tumor modeling method with a completely degradable, crosslinker-free carboxymethyl chitosan (CMCTS)/oxidized hyaluronic acid (OHA) hydrogel that encapsulates high-density human cancer cells for in situ injection. The CMCTS/oHA hydrogel was fully degraded within 3 weeks, enabling three-dimensional (3D) cell condensation in vitro. 2 weeks after subcutaneous injection in mice, solid tumors formed, with native host vasculature infiltrating the transplanted human cancer cells, confirming spontaneous hydrogel degradation. Following this, human macrophages were administered via tail vein injection, enhancing the accumulation of mouse immune cells in the humanized tumor twofold and showing murine macrophages adjacent to the vasculature. This study thus provides proof-of-concept for a facile and fully vascularized humanized tumor model in mice for validating immune cell therapies. HIGHLIGHTSO_LIThe oHA was prepared using sodium periodate treatment, which facilitated the formation of in situ CMCTS/oHA hydrogels C_LIO_LICMCTS/oHA hydrogels completely degraded within a short period, allowing for 3D cell condensation C_LIO_LIHigh-density cell-laden CMCTS/oHA hydrogels were injected subcutaneously in mice, resulting in the generation of a vascularized solid tumor C_LIO_LIThe transplanted therapeutic cell was observed to adhere to the tumor tissue through the bloodstream C_LI

bioengineering↗

bioRxiv2024

Human Hippocampal Theta Oscillations Organise Distance to Goal Coding

The rodent hippocampal local field potential is dominated by 6-12 Hz theta oscillations during active behaviour that are strongly implicated in spatial coding and memory function across species. Invasive electrophysiology in both rodents and humans has shown increases in hippocampal theta power immediately before the onset of translational movement that persists throughout subsequent motion, and the magnitude of this increase correlates with the distance subsequently travelled. Using non-invasive magnetoencephalography (MEG) and an abstract navigation task, we observed increased theta power during both spatial planning and subsequent navigation. Importantly, theta power in the right hippocampus covaried with subsequent path distance during planning, only when participants were aware of the distance to their goal. During subsequent navigation, hippocampal theta power decreased dynamically as participants approached the goal, only when they were aware of how far they still needed to travel. In addition, theta phase during navigation modulated 70-140 Hz fast gamma amplitude in the entorhinal cortex while traversing novel paths; and 30-70 Hz slow gamma amplitude in the right hippocampus while traversing previously experienced paths. In both cases, theta-gamma phase-amplitude coupling increased with proximity to the goal during navigation, consistent with the hypothesis that sequences of upcoming locations were represented by gamma bursts occurring at successive theta phases. In sum, these findings are consistent with the proposed role of hippocampal theta oscillation in flexible planning and goal-directed spatial navigation across mammalian species.

neuroscience↗

bioRxiv2024

Oncogenic RAS Induces a Distinctive Form of Non-Canonical Autophagy Mediated by the P38-ULK1-PI4KB Axis

Cancer cells with RAS mutations exhibit enhanced autophagy, essential for their proliferation and survival, making it a potential target for therapeutic intervention. However, the regulatory differences between RAS-induced autophagy and physiological autophagy remain poorly understood, complicating the development of cancer-specific anti-autophagy treatments. In this study, we identified a form of non-canonical autophagy induced by oncogenic KRAS expression, termed RAS-induced non-canonical autophagy via ATG8ylation (RINCAA). RINCAA involves distinct autophagic factors compared to those in starvation-induced autophagy and incorporates non-autophagic components, resulting in the formation of non-canonical autophagosomes with multivesicular/multilaminar structures labeled by ATG8 family proteins (e.g., LC3 and GABARAP). We have designated these structures as RAS-induced multivesicular/multilaminar bodies of ATG8ylation (RIMMBA). A notable feature of RINCAA is the substitution of the class III PI3K in canonical autophagy for PI4KB. We identified a regulatory P38-ULK1-PI4KB-WIPI2 signaling cascade governing this process, where ULK1 phosphorylation at S317, S479, S556, and S758 activates PI4KB. This activation involves PI4KB phosphorylation at S256 and T263, initiating PI4P production, ATG8ylation, and non-canonical autophagy. Importantly, elevated PI4KB phosphorylation at S256 and T263 was observed in RAS-mutated cancer cells and colorectal cancer specimens. Inhibition of PI4KB S256 and T263 phosphorylation led to a reduction in RINCAA activity and tumor growth in both xenograft and KPC models of pancreatic cancer, suggesting that ULK1-mediated PI4KB-Peptide-1 phosphorylation could represent a promising therapeutic target for RAS-mutated cancers.

cell biology↗

bioRxiv2024

Employing Microsoft Sway as a Repository for Data Generated in Pharmaceutics Experimental Courses: A Case study on Topical Formulation Characterization

Microsoft Sway is an easy-to-use online creative software developed by Microsoft. It has many advantages as follows: easy to operate and does not require long-term practice and learning; network links can be created and accessed by devices such as Personal Computer (PC) and mobile terminals; Educators and Learners are allowed to browse this repository at anytime to facilitate the application prospects of mining relevant data. Therefore, the author proposes that Microsoft Sway may be a very promising data repository for pharmaceutical experimental teaching courses, and is expected to be extended to undergraduate experimental teaching in other natural science fields.

scientific communication and education↗