Biology subjects

Niu, H.

Publications and source records attributed to Niu, H..

At least 19 recordsLinked to original sources

bioRxiv2026

Information processing-like phenotype of human brain organoids

Human brain organoids recapitulate key physiological features and functions of the human brain and hold remarkable potential for studying neurological diseases. Despite clinical evidence suggesting that neurodegenerative diseases impair the information-processing ability of the human brain, the capacity of brain organoids for information processing and its relationship to neural network function remain largely unexplored. Here, we test and quantify information-processing-like properties of human cortical organoids using a task-based functional phenotyping framework (Brainopheno). We demonstrate the pattern-processing-like phenotype of cortical organoids through the representation and classification of evoked neural activities in response to distinct spatial input stimulation patterns via a microelectrode array (MEA) system. Moreover, this functional phenotype emerges with network maturation and is disrupted by pharmacological perturbations, linking classification performance to the functional integrity of organoid neural networks (ONNs). Importantly, this functional phenotype also reveals functional deficits in ONNs altered by a familial Alzheimer's disease (AD)-associated gene mutation (APP) and by monocytes from patients with sporadic AD. This work may establish a new quantifiable functional phenotype of neural organoids and provide a framework to bridge molecular and cellular profiles with neural circuit function for basic neurology, disease phenotyping, and therapeutic development.

bioengineering↗

bioRxiv2026

An engineered IdeS variant with enhanced activity and performance for IgG degradation

IgG-degrading enzymes have emerged as innovative therapeutic agents for treating conditions driven by pathogenic antibodies. Here, we used structure-guided rational design to engineer IdeSM33, a double mutant (K167R/D226E) of the IgG-specific bacterial protease IdeS from Streptococcus pyogenes, with improved catalytic efficiency. Biolayer interferometry revealed a fourfold increase in binding affinity relative to wild-type IdeS (IdeSWT). This enhancement is likely attributable to mutations that strengthen hydrogen bonding at the enzyme-IgG Fc interface. In vitro, IdeSM33 has higher performance than IdeSWT in cleaving serum IgG. In vivo studies in rabbits demonstrated that IdeSM33 effectively depleted circulating IgG and showed better performance at a dose of 0.005 mg/kg than the IdeSWT. Although doses greater than 0.2 mg/kg demonstrated higher plasma concentrations of IdeS and a larger AUClast, they did not show a significant enhancement in the pharmacodynamics of IgG degradation. Importantly, a single dose of IdeSM33 (0.2 mg/kg) potently degraded binding and neutralizing antibodies against AAV9 within 1-2 days and restored hepatic AAV9 transduction in pre-immunized animals. Together, these findings highlight IdeSM33 as a potent and safe engineered enzyme with therapeutic potential for autoimmune disorders, transplant rejection, and overcoming pre-existing humoral immunity in gene therapy.

bioengineering↗

bioRxiv2026

Spatial Transcriptomics Reveals Region-Specific Remodeling in Vein Grafts After Peripheral Arterial Bypass

BackgroundVein graft failure due to intimal hyperplasia and maladaptive remodeling remains a major limitation of peripheral bypass surgery. Although vascular remodeling is recognized as a multilayered process, layer-specific molecular mechanisms that distinguish adaptive from negative remodeling remain incompletely understood. We aimed to investigate the vascular microenvironment of patent and stenotic grafts using spatial transcriptomics. MethodsVein specimens were obtained from three patients undergoing revision surgery. For each patient, a matched set of three samples was collected: unused saphenous vein (Denovo), normally healed vein graft (Non-stenosed), and stenosed vein graft (Stenosed) (n = 3 patients). GeoMx Digital Spatial Profiling with the Human Whole Transcriptome Atlas was used to map gene expression across intima, medial, and adventitial layers. Differential expression, gene ontology, spatial deconvolution, and immunohistochemistry were integrated for analysis. ResultsNon-stenosed and Stenosed grafts shared transcriptional features distinct from Denovo veins, particularly in pathways related to cell proliferation. Non-stenosed grafts showed increased expression of CDKN1A across all vascular layers, whereas Stenosed grafts exhibited enhanced mitogen-activated protein kinase (MAPK) pathway activity, reduced DUSP1-mediated regulation, and increased macrophage accumulation. ECM remodeling showed layer-specific organization, with VCAN and ACAN enriched in the intima and DCN in the adventitia, while Stenosed grafts demonstrated a trend toward collagen-dominant remodeling. Cell deconvolution suggested a shift toward vascular smooth muscle cell (VSMC)-dominant architecture after arterialization, with modest enrichment of synthetic VSMC signatures in stenotic regions. ConclusionsVein graft stenosis appears to be associated with layer-specific alterations in cell cycle regulation, inflammatory signaling, extracellular matrix remodeling, and VSMC phenotype. Spatial transcriptomic analysis reveals molecular heterogeneity not captured by bulk approaches and provides preliminary insight into graft remodeling. These findings may inform future studies to improve long-term graft patency.

pathology↗

bioRxiv2026

Stromal Gasdermin D-mediated Pyroptosis Drives Maladaptive CD4⁺ T-cell Remodeling in Tet2-Deficient Hematopoiesis

An inflammatory bone marrow microenvironment is increasingly recognized as critical in myeloid disease evolution, yet how stromal inflammation interfaces with adaptive immunity remains poorly defined. Here, we show that stromal pyroptosis drives mutation-specific myeloid expansion by coordinating monocytic remodeling and CD4 T-cell activation. Genetic ablation of gasdermin D in the bone marrow stroma suppressed stromal pyroptosis and attenuated Tet2-deficient myeloid expansion. Tet2 deficiency skewed monocyte and macrophage differentiation toward an activated, antigen-presenting state that interacted with pyroptotic stromal cells to promote expansion of a distinct CD4 T-cell population. These cells expressed canonical T follicular helper markers (Bcl6, Cxcr5, Il21, and Cd40l) together with interferon-responsive and tissue-interaction programs, consistent with an inflammation-adapted TFH-like state. CD40L produced by these cells reinforced the expansion of Tet2-deficient monocytes and macrophages, establishing a feed-forward stromal-immune circuit. Disruption of this axis through stromal gasdermin D deficiency or CD40L blockade attenuated myeloid expansion in vivo. Consistent with these findings, patients with isolated TET2 loss-of-function mutations exhibited CD4 T-cell skewing and CD40L+ T-cell-rich tertiary lymphoid structures in the bone marrow. Together, these data identify a pyroptosis-dependent stromal-immune axis that links early myeloid inflammation to maladaptive remodeling of adaptive immunity and reveals a context-dependent therapeutic vulnerability in Tet2-deficient hematopoiesis.

cancer biology↗

bioRxiv2026

PARP1 regulates the genomic ribonucleotide processing activity of TOP1 to prevent the formation of toxic TOP1-DNA adducts and the associated mutations.

Ribonucleotides are frequently incorporated into our genome during replication. Canonically, RNase H2 is responsible for the removal of these embedded ribonucleotides. Alternatively, DNA topoisomerase 1 (TOP1) has also been shown to have genomic ribonucleotide processing activity. When this process occurs at short tandem repeat (STR) sequences, it can lead to 2-5 bp deletions. These deletions are the result of two sequential cuts by TOP1 at sites of ribonucleotide incorporation. In this study, we have determined that PARP1 regulates the TOP1-mediated excision of ribonucleotides by preventing the formation of TOP1-DNA adducts that occur through a second cleavage following the initial ribonucleotide cut by TOP1. We biochemically defined the mechanism by which this regulatory inhibition of TOP1 occurs, which involves both PARP1 physically restricting TOP1 from the cleavage site followed by the inhibitory PARylation of TOP1. We also show that this activity means that PARP1 prevents the TOP1-dependent deletions at STRs in cells. In the absence of both a functional RNase H2 complex and PARP1, we demonstrated that cells appear to be in a senescent state provoked by the accumulation of TOP1-DNA adducts, which are a result of TOP1 being unimpeded to remove genomic ribonucleotides. Our work has elucidated the role of PARP1 in preventing the deleterious consequences of the processing of genomic ribonucleotides by TOP1. Understanding this mechanism could help us develop therapies that better sensitize tumors to PARP inhibitors, especially in cancers that present loss-of-function RNase H2 mutations (seen in certain chronic lymphocytic leukemia and prostate cancers).

biochemistry↗

bioRxiv2026

MTB-KB: A Curated Knowledgebase of Mycobacterium tuberculosis Related Studies

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), has regained its position as the worlds leading killer among infectious diseases. Despite extensive research progress across epidemiology, diagnosis, drug development, treatment regimens, vaccines, drug resistance, virulence factors, and immune mechanisms, MTB-related knowledge remains fragmented across thousands of publications, limiting its effective use. To address this gap, we present MTB-KB, a literature-curated knowledgebase that systematically integrates high-impact findings from eight major sections of TB research. The current release contains 75,170 associations from 1,246 publications, covering 18,439 entities standardized using authoritative databases and WHO-endorsed classifications. A central feature is the interactive knowledge graph, which links cross-section associations to reveal and infer MTB-host interactions, treatment strategies, and vaccine development opportunities. MTB-KB also provides a user-friendly interface with browsing, advanced search, and statistical visualization. Overall, by consolidating dispersed MTB knowledge into a structured and accessible platform, MTB-KB provides a valuable resource for researchers, clinicians, and policymakers, supporting both basic and clinical TB research, enabling evidence-based TB prevention, diagnosis, and treatment, and contributing to global elimination efforts. MTB-KB is accessible at https://ngdc.cncb.ac.cn/mtbkb/.

bioinformatics↗

bioRxiv2025

MindSight: A Bio-Inspired Neural Architecture for Visual Restoration via Cortical Electrical Stimulation

Visual impairment is a common condition worldwide, and cortical electrical stimulation is one of the approaches to aid in visual restoration. However, existing methods suffer from limited precision, flexibility, and generalization in generating the desired visual perception. In this paper, we propose a novel deep learning-based algorithm for cortical electrical stimulation, named "MindSight," aimed at enhancing the clarity and accuracy of induced visual perceptions. Our framework introduces three key innovations: (1) A differentiable biophysical model simulating cortical state transitions under electrical stimulation, enabling end-to-end training; (2) A dual-path training architecture combining neural decoding fidelity with phosphene simulation constraints; (3) An attention-guided background gated network for input filtration and, a multi-channel activation constraint to ensure the effectiveness of electrical stimulation. We validated our approach through novel experiments with macaque monkeys, demonstrating superior performance in visual perception tasks. These results highlight the potential of our approach in assisting individuals with visual impairments. Codehttps://github.com/zyj9902/MindSight

bioengineering↗

bioRxiv2025

Divergent Macrophage-Regulated T cell States Determine Response to Bacillus Calmette-Guerin (BCG) in High-Risk Bladder Cancer

The primary therapy for high-risk bladder cancer (BCa) is repeated instillations of the tuberculosis vaccine, Bacillus Calmette-Guerin (BCG). While BCG decreases the risk of recurrence by more than half, the concerted mechanisms of immune activation from BCG are unknown. Our objective was to investigate how the immune response differs between responders and non-responders to BCG therapy. We performed single-cell RNA-sequencing of isolated immune cells adjacent to high-risk bladders before and after BCG in BCG responders and non-responders. We identify an increase in Th17-like Th1 cells in BCG responders, characterized by greater expression of pro-inflammatory cytokines. Alternatively, non-responders had increased CD8+ T-cell exhaustion and T-regulatory cells. We identify that the primary mechanism of divergent T cell activity is driven by altered polarization and immunosuppressive signaling with myeloid cells. Through a machine-learning-based approach, we identified a Th17-like Th1 cytokines, such as IL17, IL21, and IL26, were predictive of a response, which were then validated in a separate BCG-treated BCa cohort. Together, this suggests that dynamic regulation of myeloid-T cell interactions can be targeted to improve BCG activity.

immunology↗

bioRxiv2025

Dual DNA-binding capability of Cdc13 coordinates with Ku to safeguard telomere integrity

In eukaryotes, telomeres, nucleoprotein complexes assembled on telomeric 3-overhang DNA, protect linear chromosome ends from degradation and inappropriate DNA repair. In budding yeast, Saccharomyces cerevisiae, telomere assembly involves the Cdc13-Stn1-Ten1 (CST) complex, the Ku70-Ku80 (Ku) complex, and the Rap1-Rif1-Rif2 complex. Among these, the CST complex, centered on the binding of the G-rich single-stranded region by the Cdc13 subunit, is essential for telomere maintenance and protection. Here, we show that Cdc13 also interacts with the duplex DNA adjoining its bound single strand. This junction binding enables Cdc13 to reposition the Ku complex, potentially suppressing Ku-mediated end joining, while allowing the Cdc13 and Ku complexes to synergize in protecting telomeric DNA ends, a function that can be disrupted by mutation of a conserved residue (K504E). cdc13-K504E cells remain viable but are hypersensitive to Exo1 overexpression, particularly when combined with ku80{Delta}. Surprisingly, cdc13-K504E and other telomere protection mutants are prone to adaptive metabolic reprogramming during stationary-phase growth, leading to increased fitness. This reprogramming is inheritable and centers on elevated expression of thiamine biosynthesis, salvage, and intake pathways. Our findings reveal a stress-induced adaptive response associated with telomere erosion, indicating that telomere erosion may serve as a timer for its activation.

biochemistry↗

bioRxiv2025

NTM-DB: A Comprehensive Non-Tuberculosis Mycobacteria Genomic Database

Non-tuberculous mycobacteria (NTM) are a major group of environmental bacteria, with approximately one-third of them causing serious human infections, particularly respiratory diseases. The global rise in the prevalence and severity of NTM infections has posed a major public health challenge. While high-throughput sequencing has generated vast genomic data on NTM, there remains a lack of comprehensive resources for cross-species genomic analysis. To address these limitations, we have developed a specialized database called NTM-DB (https://ngdc.cncb.ac.cn/ntmdb) tailored for NTM researchers and clinicians. NTM-DB offers the most comprehensive collection of NTM genomic and bioinformatic resources, including 16,469 genome assemblies (13,134 newly assembled genomes), 189 type/standard strain genomes representing 177 species and 12 subspecies, 705 MLST types, 33,240 resistance genes, and 74,315 virulence genes. A user-friendly interactive website has been constructed to enable efficient browsing, MLST profiling, searching, online analysis, and downloading of the aforementioned data. Notably, with online analysis tools, users can perform customized genotyping, cross-species phylogeny, pan-genome, and virulence and drug resistance gene annotation analyses using our data and/or their uploaded data. Overall, with its comprehensive data, intuitive interface, and powerful analysis tools, NTM-DB serves as an important resource and reference for NTM researchers and clinicians, improving diagnosis and treatment for various NTM-related diseases, and supporting both scientific discovery and clinical practice.

microbiology↗

bioRxiv2025

Metabolic and transcriptomic insights into a GalNAc/Man-Specific lectin in yeast fermentation

Brewers yeast (Saccharomyces cerevisiae) plays a central role in fermentation, and improving its performance is crucial in the brewing industry. This study explored how Cyclina sinensis lectin (CSL), a bioactive peptide from shellfish, influences yeast metabolism using proteomics and metabolomics. CSL bound to yeast peptidoglycan in a concentration-dependent manner and altered cell surface structure. Proteomic analysis revealed 117 differentially expressed proteins after 24 h of CSL treatment, with upregulation of key glycolytic enzymes (e.g., hexokinase, GAPDH) and downregulation of TCA cycle enzymes, suggesting enhanced ethanol production via glycolysis activation and TCA suppression. Metabolomic profiling further confirmed this, showing increased -D-glucose, glucose-6-phosphate, NAD+, and glutathione, alongside reduced TCA intermediates like malic acid. These results indicate CSL promotes ethanol accumulation by reprogramming central carbon metabolism. This study provides novel insight into the metabolic modulation of yeast by marine lectins and suggests potential applications of CSL in improving fermentation

microbiology↗

bioRxiv2025

Incorporating LLM-Derived Information into Hypothesis Testing for Genomics Applications

We propose strategies for incorporating the information in large language models (LLMs) into statistical hypothesis tests in genomics studies. Using gene embeddings derived from text inputs to OpenAIs GPT-3.5 model, we show that biological signals in a variety of genomics datasets reside near the principal subspace spanned by the embeddings. We then use a frequentist and Bayesian (FAB) framework to propose several hypothesis tests that are either optimal or approximately optimal with respect to prior information based on the gene embedding subspace. In four real-world genomics examples, the FAB tests guided by the LLM-derived information achieve more power than classical counterparts.

bioinformatics↗

bioRxiv2025

Understanding monocyte-driven neuroinflammation in Alzheimers disease using human brain organoid microphysiological systems

Increasing evidence suggests that Alzheimers disease (AD) pathogenesis strongly correlates with neuroinflammation. Peripheral monocytes are crucial components of the human immune system that may play a role in neuroinflammation, but their contribution to AD pathogenesis is largely understudied partially due to the lack of appropriate human models. Here, we present human cortical organoid microphysiological systems (hCO-MPSs) for modeling dynamic AD neuroinflammation mediated by monocytes. By incorporating 3D printed devices into an existing cortical organoid protocol, 96 hCO-MPSs can be established with significantly reduced necrosis and hypoxia as well as enhanced viability within a commonly used 96 well plate, and each hCO-MPS consists of a doughnut-shaped hCO and a 3D printed device per well. Using this approach, monocytes from AD patients exhibit higher infiltration, decreased amyloid-beta (A{beta}) clearance, and stronger inflammatory responses compared to monocytes from age-matched control donors. Moreover, pro-inflammatory effects such as elevated astrocyte activation and neuronal apoptosis were observed to be induced by AD monocytes. Furthermore, the significant increase in the expression of IL1B and CCL3, both at the transcriptional and protein levels, indicated the pivotal role of these cytokine and chemokine in monocyte-mediated AD neuroinflammation. Our findings provide insight for understanding monocytes role in AD pathogenesis, and the user-friendly MPS models we present are compatible with existing laboratory settings, highlighting their potential for modeling neuroinflammation and developing new therapeutics for various neuroinflammatory diseases.

bioengineering↗

bioRxiv2025

Yeast DNA Polymerase δ Proofreading Nuclease Suppresses Translesion Synthesis and Facilitates Recombination in DNA Lesion Bypass.

Translesion synthesis (TLS) employs specialized polymerases to incorporate nucleotides opposite DNA lesions, allowing replication to continue temporarily without repairing the lesions, while sacrificing replication fidelity (1). TLS depends on a ubiquitin molecule attached to the clamp PCNA at residue Lys164 (2, 3); the precise biochemical and molecular basis how PCNA modification stimulates TLS is still elusive (4-10). In this study, we discovered that DNA polymerase {delta} (Pol {delta}) 3 to 5 "proofreading" exonuclease degrades nascent TLS synthesis opposite pyrimidine dimers and inhibits TLS on both leading and lagging strands. Rad18 E3 ligase and PCNA ubiquitylation become dispensable for TLS when Pol {delta} exonuclease is inactive. Biochemical reconstitution showed that the major UV lesion bypass polymerase Rad30 is intrinsically inefficient at bypassing thymidine dimers and requires multiple turnovers. Pol {delta} exonuclease impedes Rad30 activity both catalytically and non-catalytically during and post-lesion bypass. Importantly, PCNA and PCNA ubiquitylation enhance processivity of Rad30 after thymidine dimer bypass, a critical step for further DNA synthesis extension and overcoming Pol {delta} inhibition. Our study reveals a new paradigm how PCNA ubiquitylation facilitates TLS and the new role of Pol {delta} nuclease in lesion bypass pathway choice and replication fidelity at fork-blocking DNA lesions.

genetics↗

bioRxiv2024

Germinated brown rice research: bibliometric analysis of progress, hotspots and trends

To gain a deeper understanding of global research trends and focal points in germinated brown rice, this article takes the relevant literature on germinated brown rice in the core database of Web of Science as the research object. By using bibliometric analysis, the literature on germinated brown rice published from 2003 to 2023 is deeply analyzed, and the global research progress, hotspots and future development trend of germinated brown rice are summarized. Since 2018, research on germinated brown rice has been rapidly developing, with a significant surge in interest since 2020. China leads in the number of publications, institutions, and core authors in this research area. The primary research topics include the nutritional value, physiological active components, and industrial applications of germinated brown rice. Current research frontiers involve identifying, evaluating, and enhancing bioactive substances in germinated brown rice for food applications. Research in this field remains active, and application scenarios are becoming increasingly diverse. Future studies may explore new directions in related equipment and ingredients.

bioinformatics↗

bioRxiv2024

Cost-effective DNA storage with DNA movable type

In the face of exponential data growth, DNA-based storage offers a promising solution for preserving big-data. However, most existing DNA storage methods, akin to traditional block printing, require costly chemical synthesis for each individual data file, adopting a sequential, one-time-use synthesis approach. To overcome these limitations, we introduce a novel, cost-effective "DNA-Movable-Type Storage" system, inspired by movable type printing. This system utilizes pre-fabricated DNA movable types-short, double-stranded DNA oligonucleotides encoding specific payload, address, and checksum data. These DNA-MTs are enzymatically ligated/assembled into cohesive sequences, termed "DNA movable type blocks", streamlining the assembly process with the automated BISHENG-1 DNA-MT inkjet printer. Using BISHENG-1, we successfully printed, assembled, stored and accurately retrieved 43.7 KB of data files in diverse formats (text, image, audio, and video) in vitro and in vivo, using only 350 DNA-MTs. Notably, each DNA-MT, synthesized once (2 OD), can be used up to 10,000 times, reducing costs to 122 $/MB-outperforming existing DNA storage methods. This innovation circumvents the need to synthesize entire DNA sequences encoding files from scratch, offering significant cost and efficiency advantages. Furthermore, it has considerable untapped potential to advance a robust DNA storage system, better meeting the extensive data storage demands of the big-data era.

bioinformatics↗

bioRxiv2024

Single-Cell and Spatial Transcriptomic Analyses Deciphering the Three-Layer Architecture of Human Tuberculosis Granulomas

BackgroundGranulomas (defining tuberculosis histopathological feature) are central to the hosts defense against Mycobacterium tuberculosis, critically influencing patient outcomes. However, knowledge of human granulomas structure and function are incomplete. This study employs single-cell and spatial transcriptomics to dissect human granulomas cellular composition, structure, communication and function from 19 pulmonary, lymphatic and skeletal samples. ResultsOur study identified nine key immune-activated/signaling-active cell clusters. Notably, we delineated a three-layered granuloma structure: a core with macrophages (Macro-c09, Macro-c10) and occasional fibroblasts (Fib-c03); a fibroblast-rich (Fib-c01) periphery; and an immune-infiltrated intermediate layer comprising diverse immune-cells recruited by strong signaling-molecules (SPP1/MIF) from core/periphery cells. This study also shows granuloma heterogeneity across individuals and tissues. ConclusionsBy merging scRNA-seq with ST-seq, we offer an intricate single-cell perspective of granulomas spatial-structure and formation mechanisms, identify signaling-molecules and significantly changed genes as potential targets for host-directed tuberculosis immunotherapy, highlight fibroblasts crucial role in granuloma formation, and provide an important reference/improved understanding of TB.

microbiology↗

bioRxiv2023

Camel milk affects serum metabolites by modulating the intestinal microflora

Gut microbes play a vital role in human health and are influenced by numerous factors including diet, genetics, and environment. (Fermented) Camel milk, which is abundant in nutrients and lacks allergenic proteins, has been consumed for its edible and medicinal properties for centuries. Research on camel milks impact on gut microbiota and host metabolism is still limited. The results found that sour camel milk contained various beneficial bacteria such as Lactobacillus helveticus, Acinetobacter lwoffii, Eubacterium coprostanoligenes group, Lachnospiraceae, which could be transported to the recipients intestines by diet. This study specified that the transportation of microbiome happened both intra- and inter-species and played a principal role in the formation of progeny gut microflora. An investigation on type 2 diabetic rats revealed that the composition of gut microflora and serum metabolites of those fed with high-dose camel whey was closer to that of the normal. Eubacterium limnetica, which can reduce the risk of diseases by producing MtcB protein, was found in the gut microflora of the ones taking camel milk. These results evidenced the high potential of camel milk as a functional food.

microbiology↗