Biology subjects

Gu, Z.

Publications and source records attributed to Gu, Z..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Biomimetic Neoadjuvant Platform: Controlled Nanotoxicology as a Novel Approach to Preoperative Immunomodulation

The persistent immunosuppression and spatial heterogeneity of advanced solid tumors necessitate next-generation neoadjuvant platforms capable of reprogramming tumor microenvironments while overcoming resistance to immune checkpoint blockade. Addressing this unmet clinical challenge, we report a {beta}-glucan-empowered nano-neoadjuvant agents (NNAs) engineered through topology-guided supramolecular assembly of pathogen-mimetic {beta}-glucan motifs onto photoresponsive single-wall carbon nanotubes. This biomimetic architecture capitalizes on three synergistic mechanisms: (1) Dectin-1-mediated pathogen-associated molecular pattern recognition to rewire myeloid cell functionality, (2) endogenous leukocyte-hitchhiking delivery paradigm, and (3) spatiotemporally controlled photothermal ablation via near-infrared transducing SWNT cores. NNAs also orchestrates a proinflammatory cascade involving IL-12-dependent Th1 polarization and activation, effectively converting "cold" tumors into immunogenic niches. This strategy redefines preoperative therapeutic paradigms, offering a multimodal platform to harness the proinflammatory adjuvant effect of SWNTs for preoperative immunomodulation in advanced-stage malignancies. By bridging innate immune recognition with nanotechnology-enabled precision, this paradigm establishes a new roadmap for preoperative conditioning of advanced malignancies, offering a theranostic framework to transform surgical outcomes through immunologically informed nanomedicine design.

bioengineering↗

bioRxiv2025

Supramolecular Biomimetic Topology: Macrophage-Engaged Neoadjuvant Platform for Preoperative Immunotherapy

immunology↗

bioRxiv2025

The Binary Cellular Biology of Human Growth I Quantifying the Creation and Growth of the Body and its Parts

Assessing and understanding the Growth and Development of animals generally, and of human fetuses specifically, provides essential information for the management of the health of the newborn and its mother. Here we show that a consideration of the formation of the body, in units of numbers of cells, N, and the change in these numbers by the binary either/or decisions of cells to divide or not, an approach we call Binary Cellular Analysis, provides new insights and new equations for quantifying the growth and development of the body and its parts. These equations include: 1) The Binary Cellular Universal Growth Equation, which captures growth from conception to adulthood, and provides a method for biologically-based, data-driven, Growth Curves; 2) The Binary Cellular Universal Mitotic Fraction Equation, which lies within the Binary Cellular Universal Growth Equation, and captures the mechanism of growth to adult size, control of cell division; 3) The Binary Cellular Allometric Growth Equation, which captures the creation and growth of the Tissues, Organs, and Anatomical Structures of the body, and how the embryo creates each Body Part from a Single Founder Cell; and, 4) Binary Cellular Estimated Fetal Weight Equations, derived from the Binary Cellular Allometric Growth Equation, which captures the relationship between Ultrasound Measurement and the Size of the body as a whole. These equations capture the developmental process of Cellular Selection, resulting from Differential Cellular Proliferation, which molds the formation of the body from a single fertilized ovum into a multicellular animal. The parameters of these equations both capture the differences in Size and Growth between animals across the taxonomic spectrum, and between human fetuses, as well as identify the individual mechanisms of mitosis that drive Growth and Development. From the Binary Cellular Universal Growth Equation, the Growth of human fetuses can be measured, thus providing a much-needed tool for understanding the biological forces that cause a fetus to grow to Small, Average, or Large Size at birth, for providing the basis of biologically-based, data-driven, Growth Curves, and for assisting the management of the obstetric care of the fetus and its mother.

developmental biology↗

bioRxiv2025

The Binary Cellular Biology of Human Growth II Calculating the Size of the Human Fetus from the Size of its Parts

Assessing and understanding the Size of the human fetus provides essential information for the management of the health of the newborn and its mother, a quality that is commonly measured by Fetal Ultrasound. Many equations for making such calculations have been considered, none of which have been entirely satisfactory. As we have shown in the previous paper in this series, a consideration of the formation of the body, in units of numbers of cells, N, an approach we call Binary Cellular Analysis, provides new quantitative tools for estimating the Size and Age of the fetus. These tools include a new mathematical basis for creating useful expressions, Binary Cellular Estimated Fetal Weight Equations, for calculating human Fetal Weight from Ultrasound Measurements. As we show here, the most promising of these expressions, the Abdominal Circumference Binary Cellular Estimated Fetal Weight Equation, performs better than other currently used Fetal Weight Equations, while also yielding up new methods for improving ultrasound size assessment. Web-based calculators (https://kidzgrowth.com) make these mathematical manipulations available for obstetric care.

developmental biology↗

bioRxiv2024

Birds migrate longitudinally in response to the resultant Asian monsoons of the Qinghai-Tibet Plateau uplift

The uplift of the Qinghai-Tibet Plateau is one of the greatest geological events on Earth, pivotally shaping biogeographic patterns across continents, especially for migratory species that need to overcome topographical barriers to fulfil their annual circle. However, how the uplift influences animal migration strategies remains largely unclear. We compare the current flyways of 50 avian species migrating across the plateau with those reconstructed before the uplift as a counterfactual. We find that the major effect of the plateau uplift is changing avian migratory directions from the latitudinal to the longitudinal. The monsoon system generated by the uplift rather than the high elevation per se shapes those changes. These findings unveil how an important global geological event has influenced biogeographic patterns of migratory birds, yielding testable hypotheses for how observed avian distributions emerge.

ecology↗

bioRxiv2024

eProbe: a capture probe design toolkit for genetic diversity reconstructions from ancient environmental DNA

Ancient environmental DNA (aeDNA) is now commonly used in paleoecology and evolutionary ecology, yet due to difficulties in gaining sufficient genome coverage on individual species from metagenome data, its genetic perspectives remain largely uninvestigated. Hybridization capture has proven as an effective approach for enriching the DNA of target species, thus increasing the genome coverage of sequencing data and enabling population and evolutionary genetics analysis. However, to date there is no tool available for designing capture probe sets tailored for aeDNA based population genetics. Here we present eProbe, an efficient, flexible and easy-to-use program toolkit that provides a complete workflow for capture probe design, assessment and validation. By benchmarking a probe set for foxtail millet, an annual grass, made by the eProbe workflow, we demonstrate a remarkable increase of capturing efficiency, with the target taxa recovery rate improved by 577-fold, and the genome coverage achieved by soil capture-sequencing data even higher than data directly shotgun sequenced from the plant tissues. Probes that underwent our filtering panels show notably higher efficiency. The capture sequencing data enabled accurate population and evolutionary genetic analysis, by effectively inferring the fine-scale genetic structures and patterns, as well as the genotypes on functional genes.

bioinformatics↗

bioRxiv2024

The Ptch methylase installs an m3U modification on 28S rRNA for efficient protein synthesis in flies and men

The ribosomal RNA (rRNA) is one of the most heavily modified RNA species in nature. Although we have advanced knowledge of the sites, functions and the enzymology of many of the rRNA modifications from all kingdoms, we lack basic understanding on many of those that are not universally present. A single N3 modified Uridine base (m3U) was identified on the 28S rRNA from human and frog over thirty years ago, which is absent in bacteria or yeast. Here we show that the equivalent m3U is present in Drosophila, and that the Ptch enzyme and its human homolog are both necessary and sufficient for carrying out the modification. The Ptch-modified U is at a functional center of the large ribosome, and consistently ptch-mutant cells suffer loss of ribosomal functions. Ptch, proposed to be the most druggable RNA methyltransferases in human, represents a unique target where ribosomal functions could be specifically compromised in cancer cells.

genetics↗

bioRxiv2024

Two separated worlds - on the international influence of life science and biomedical research

We introduced a new metric, "citation enrichment", to measure country-to-country influence using citation data. This metric evaluates the degree to which a country prefers to cite another country compared to a random citation process. We applied the citation enrichment method to over 12 million publications in the life science and biomedical fields and we have the following key findings: 1) The global scientific landscape is divided into two separated worlds where developed Western countries exhibit an overall mutual under-influence with the rest of the world; 2) Within each world, countries form clusters based on their mutual citation preferences, with these groupings strongly associated with their geographical and cultural proximity; 3) The two worlds exhibit distinct patterns of the influence balance among countries, revealing underlying mechanisms that drive influence dynamics. We have constructed a comprehensive world map of scientific influence which greatly enhances the deep understanding of the international exchange of scientific knowledge. The citation enrichment metric is developed under a well-defined statistical framework and has the potential to be extended into a versatile and powerful tool for bibliometrics and related research fields.

scientific communication and education↗

bioRxiv2024

Optimizing ex vivo CAR-T cell-mediated cytotoxicity assay through multimodality imaging

CAR-T cell-based therapies have demonstrated remarkable efficacy in treating malignant cancers, especially liquid tumors, and are increasingly being evaluated in clinical trials for solid tumors. With the FDAs initiative for advancing alternative methods for drug discovery and development, full human ex vivo assays are increasingly essential for precision CAR-T development. However, prevailing ex vivo CAR-T cell-mediated cytotoxicity assays are limited by their use of radioactive materials, lack of real-time measurement, low throughput, and inability to automate, among others. To address these limitations, we optimized the assay using multimodality imaging methods, including bioluminescence, impedance tracking, phase contrast, and fluorescence, to track CAR-T cells co-cultured with CD19, CD20, and HER2 luciferase reporter cancer cells in real-time. Additionally, we varied the ratio of CAR-T cells to cancer cells to determine optimal cytotoxicity readouts. Our findings demonstrated that the CAR-T cell group effectively attacked cancer cells, and the optimized assay provided superior temporal and spatial precision measurements of ex vivo CAR-T killing of cancer cells, confirming the reliability, consistency, and high throughput of the optimized assay.

immunology↗

bioRxiv2024

Detection of High-Frequency Oscillations from Intracranial EEG Data with Switching State Space Model

High Frequency Oscillations (HFOs) is an important biomarker that can potentially pinpoint the epileptogenic zones (EZs). However, the duration of HFO is short with around 4 cycles, which might be hard to recognize when embedded within signals of lower frequency oscillatory background. In addition, annotating HFOs manually can be time-consuming given long-time recordings and up to hundreds of intracranial electrodes. We propose to leverage a Switching State Space Model (SSSM) to identify the HFOs events automatically and instantaneously without relying on extracting features from sliding windows. The effectiveness of the SSSM for HFOs detection is fully validated in the intracranial EEG recording from human subjects undergoing the presurgical evaluations and showed improved accuracy when capturing the HFOs occurrence and their duration.

bioengineering↗

bioRxiv2024

Viscoelastic Extracellular Matrix Enhances Epigenetic Remodeling and Cellular Plasticity

Extracellular matrices of living tissues exhibit viscoelastic properties, yet how these properties regulate chromatin and the epigenome remains unclear. Here, we show that viscoelastic substrates induce changes in nuclear architecture and epigenome, with more pronounced effects on softer surfaces. Fibroblasts on viscoelastic substrates display larger nuclei, lower chromatin compaction, and differential expression of distinct sets of genes related to the cytoskeleton and nuclear function compared to those on purely elastic surfaces. Slow-relaxing viscoelastic substrates reduce lamin A/C expression and enhance nuclear remodeling. These structural changes are accompanied by a global increase in euchromatin marks and local increase in chromatin accessibility at cis-regulatory elements associated with neuronal and pluripotent genes. Consequently, viscoelastic substrates improve the reprogramming efficiency from fibroblasts into neurons and induced pluripotent stem cells. Collectively, our findings unravel the roles of matrix viscoelasticity in epigenetic regulation and cell reprogramming, with implications for designing smart materials for cell fate engineering.

cell biology↗

bioRxiv2024

Release the Krakencoder: A unified brain connectome translation and fusion tool

Brain connectivity can be estimated in many ways, depending on modality and processing strategy. Here we present the Krakencoder, a joint connectome mapping tool that simultaneously, bidirectionally translates between structural (SC) and functional connectivity (FC), and across different atlases and processing choices via a common latent representation. These mappings demonstrate unprecedented accuracy and individual-level identifiability; the mapping between SC and FC has identifiability 42-54% higher than existing models. The Krakencoder combines all connectome flavors via a shared low-dimensional latent space. This "fusion" representation i) better reflects familial relatedness, ii) preserves age- and sex-relevant information and iii) enhances cognition-relevant information. The Krakencoder can be applied without retraining to new, out-of-age-distribution data while still preserving inter-individual differences in the connectome predictions and familial relationships in the latent representations. The Krakencoder is a significant leap forward in capturing the relationship between multi-modal brain connectomes in an individualized, behaviorally- and demographically-relevant way.

neuroscience↗

bioRxiv2023

simona: a Comprehensive R package for Semantic Similarity Analysis on Bio-Ontologies

BackgroundBio-ontologies are keys in structuring complex biological information for effective data integration and knowledge representation. Semantic similarity analysis on bio-ontologies quantitatively assesses the degree of similarity between biological concepts based on the semantics encoded in ontologies. It plays an important role in structured and meaningful interpretations and integration of complex data from multiple biological domains. ResultsWe present simona, a novel R package for semantic similarity analysis on general bioontologies. Simona implements infrastructures for ontology analysis by offering efficient data structures, fast ontology traversal methods, and elegant visualizations. Moreover, it provides a robust toolbox supporting over 70 methods for semantic similarity analysis. With simona, we conducted a benchmark against current semantic similarity methods. The results demonstrate methods are clustered based on their mathematical methodologies, thus guiding researchers in the selection of appropriate methods. Additionally, we explored annotation-based versus topology-based methods, revealing that semantic similarities solely based on ontology topology can efficiently reveal semantic similarity structures, facilitating analysis on less-studied organisms and other ontologies. ConclusionsSimona offers a versatile interface and efficient implementation for processing, visualization, and semantic similarity analysis on bio-ontologies. We believe that simona will serve as a robust tool for uncovering relationships and enhancing the interoperability of biological knowledge systems.

bioinformatics↗

bioRxiv2023

An Artificial Intelligence-Assisted Digital Microfluidic System for Multistate Droplet Control

AbstractDigital microfluidics (DMF) is a versatile technique for parallel and field-programmable control of individual droplets. Given the high freedom in droplet manipulation, it is essential to establish self-adaptive and intelligent control methods for DMF systems with informed of the transient state of droplets and their interactions. However, most related studies focus on the localization and shape recognition of droplets. Here, we develop an AI-assisted DMF framework named "DropAI" for multistate droplet control based on droplet morphology. Semantic segmentation model is integrated into our custom-designed DMF system to recognize the droplet states and their interactions for feedback control with a state machine. The proposed model has a strong generalization ability and can recognize droplets of different colors and shapes with an error rate of less than 0.63%. It enables control of droplets without user intervene. The proposed system will inspire the development of semantic-driven DMF systems which can interface with artificial general intelligence (AGl) models for fully automatic control.

bioengineering↗

bioRxiv2023

Present: flexible neuroscience- and technology-driven frameworks for the study of classroom engagement

Classroom engagements impact on academic success is crucial. However, the contributions of affective, cognitive, and behavioral components of engagement remain uncertain. We conducted two studies using non-invasive, research-based approaches to clarify these contributions. Study 1 employed portable EEG headsets to measure cognitive engagement, in-class quizzes assessed content retention, and post-class subjective questionnaires indexed affective engagement by measuring feelings of learning and engagement. Content retention predicted subjective measures, while the EEG theta/beta ratio was negatively related to content retention but positively related to subjective measures. Study 2 featured embedded measures of content retention, confidence, engagement, background knowledge, and indexed behavioral engagement looking at nonverbal behavior quantified via video camera recordings. Confidence and engagement were significantly correlated with each other and with particular facial muscle, gaze direction, and head pose movements. We discuss how these approaches enable real-time studies of classroom engagement and can be integrated to develop neurofeedback interventions.

neuroscience↗

bioRxiv2023

Artificially cultivated duckweed: a high-efficiency starch producer

The increasing demand for starch has been a social struggle. We report a new technology that efficiently produces starch from duckweed. Although Landoltia punctata has a dramatic contraction of gene families, its starch content and productivity reached 72.2% (dry basis) and 10.4 g m-2 d-1 in 10 days, equivalent to a yield of 38.0 t ha-1 y-1 under nutrient limitation and CO2 elevation treatment. Meanwhile, we also examined the mechanism of duckweeds high starch accumulation. This is exhibited in the regulation of DNA methylation and transcription factors as well as the significantly up-regulated transcription levels and the increased enzyme activities of key genes in starch biosynthesis. Meantime, while nitrogen redistribution was enhanced, sucrose biosynthesis and transportation, and lignocellulose biosynthesis were all reduced. These alterations led to a reduction in lignocellulose and protein content and ultimately an increase in an accumulation of starch in the chloroplast. This work demonstrates duckweeds potential of being a highly efficient starch producer.

plant biology↗

bioRxiv2022

PXN/Paxillin Phase Separation Promotes Focal Adhesion Assembly and Integrin Signaling

Focal adhesions (FAs) are transmembrane protein assemblies mediating cell-matrix connection. Tools to manipulate the compositionally intricate and dynamic FAs are currently limited, rendering many fundamental hypotheses untestable. Although protein liquid-liquid phase separation (LLPS) has been tied to the organization and dynamics of FAs, the underlying mechanisms remain unclear. Here, we experimentally tune the LLPS of PXN/Paxillin, an essential scaffold protein of FAs, by utilizing light-inducible Cry2 system. In addition to nucleating FA components, light-triggered PXN LLPS potently activates integrin signaling and subsequently accelerates cell spreading. PXN favors homotypic interaction-driven LLPS in vitro. In cells, PXN condensates are associated with plasma membrane, and modulated by actomyosin contraction and client proteins of FAs. Interestingly, non-specific weak inter-molecular interactions, together with specific molecular interactions, underlie the multicomponent condensation of PXN, and are efficient to promote FA assembly and integrin signaling. Thus, our data establish an active role of PXN phase transition into a condensed membrane-associated compartment in promoting assembly/maturation of FAs.

cell biology↗

bioRxiv2022

A SI3-sigma; arch stabilizes cyanobacteria transcription initiation complex

Multi-subunit RNA polymerases (RNAPs) associate with initiation factors ({sigma} in bacteria) to start transcription. The {sigma} factors are responsible for recognizing and unwinding promoter DNA in all bacterial RNAPs. Here, we report two cryo-EM structures of cyanobacterial transcription initiation complexes at near-atomic resolutions. The structures show that cyanobacterial RNAP forms an SI3-{sigma} arch interaction between domain 2 of {sigma}A ({sigma}2) and the sequence insertion 3 (SI3) in the mobile catalytic domain Trigger Loop (TL). The SI3-{sigma} arch facilitates transcription initiation from promoters of different classes through sealing the main cleft and thereby stabilizing RNAP-promoter DNA open complex. Disruption of the SI3-{sigma} arch disturbs cyanobacteria growth and stress response. Our study reports the structure of cyanobacterial RNAP and unique mechanism for its transcription initiation. Our data suggest functional plasticity of SI3 and provide foundation for further research into cyanobacteria and chloroplasts transcription.

biochemistry↗