Biology subjects

Zheng, A.

Publications and source records attributed to Zheng, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Rod pathway blockade improves visual function in a mouse model of photoreceptor degeneration

Retinitis pigmentosa (RP) refers to a group of inherited photoreceptor degenerations characterized by the initial death of rods and secondary loss of cones. In animal models of RP, the ganglion cells (GCs) exhibit increased spontaneous activity that can mask residual photoreceptor signals and reduce the efficacy of treatments for vision restoration. The A2 amacrine cells (ACs) are inhibitory interneurons that propagate aberrant activity to GCs, but it remains unclear whether rod or cone pathways drive altered A2-AC signaling or whether the relative contributions of these pathways change with disease progression. We examined the circuit mechanisms underlying aberrant activity in the rd10 mouse model and found that blocking rod pathway input to A2-ACs suppressed aberrant activity and improved the signal-to-noise ratio of residual cone-driven responses in On- GCs. The results also indicate that the On- but not the Off-pathway exhibits circuit-level compensation during the loss of photoreceptor input. The results suggest that pharmacological blockade of the rod pathway may improve residual cone-mediated function and improve the efficacy of vision restoration in rod-cone photoreceptor degenerations.

systems biology↗

bioRxiv2026

LizardLens: A Two-Stage Deep Learning Pipeline for Detecting and Classifying Similar Species in Visually Complex Environments

Community science platforms like iNaturalist generate unprecedented volumes of biodiversity data, but their scientific utility depends critically on accurate species identification--a persistent challenge when contributors often lack taxonomic expertise. We developed "LizardLens", a two-stage machine learning pipeline that decouples object detection from species classification to enable fine-grained identification of morphologically similar organisms in visually complex field photographs. Using 10,000 verified iNaturalist images of five Anolis lizard species in Florida, we trained specialized YOLO-based detection and Swin Transformer classification models and compared performance against state-of-the-art single-stage architectures. Our two-stage pipeline achieved 83.0% Top-1 accuracy and a macro-averaged F1-score of 89.0%, indicating strong precision-recall performance across species and outperforming single-stage YOLOv8 and YOLOv12 models across all evaluation metrics for all species, with relative improvements ranging from 10.5% to 13.2%. Gradient-weighted Class Activation Mapping (Grad-CAM) indicated that the models predictions were consistently associated with regions corresponding to diagnostic morphological (e.g., head shape, feet, and limb lengths) and pattern features (e.g., ocular rings and body patterning), providing evidence that LizardLens leverages biologically relevant visual cues consistent with those used by expert taxonomists. Error analysis identified partial occlusion and multiple proximate individuals as primary sources of missed detections, while spurious detections of lizard-like environmental features (e.g., sticks, bark) represented the dominant false positive error mode. We deployed LizardLens as an accessible web application featuring interactive bounding box correction, ranked species predictions with confidence scores, directly supporting the "Lizards on the Loose" middle school community science initiative. By combining technical advances in fine-grained visual classification with user-centered design, LizardLens demonstrates how machine learning can simultaneously enhance data quality for biodiversity monitoring and provide authentic scientific experiences for student participants. Our approach is generalizable to other small-bodied organisms in complex habitats and provides a framework for translating computer vision advances into practical tools for community science and conservation.

ecology↗

bioRxiv2026

STIMscope: centimeter-scale all-optical imaging and patterned optogenetic manipulation at single-cell resolution

Linking observation to intervention at cellular resolution makes it possible to move from measuring network activity to testing the contribution of defined neurons or ensembles within the same preparation. All-optical probing provides this capability by combining fluorescence-based readout with targeted optogenetic manipulation. Yet the platforms that deliver this capability remain complex, expensive, and difficult to maintain, requiring specialized expertise that has confined them to a small number of laboratories. They also typically provide fields of view too limited for studies of large, distributed neuronal populations. We address these constraints with the Spatiotemporal Illumination Microscope (STIMscope), a one-photon benchtop platform that integrates large-aperture tandem optics with a small-pixel back-illuminated CMOS sensor, a digital micromirror device for patterned illumination, and a GPU-based processing unit coordinated by a microcontroller for hardware-level synchronization. Ray-tracing simulations and point-spread-function measurements confirm cellular-scale resolution, with imaging lateral FWHM of 5.6 {micro}m at the field center and 5.8 {micro}m at the edge, and excitation lateral FWHM of 5.8 {micro}m at the center and 6.2 {micro}m at the edge, supporting fields of view as large as 14 mm x 11 mm in the demagnified configuration. The accompanying Closed-loop ready Real-time Imaging and Stimulation Pipeline (CRISPI) provides GPU-accelerated calibrated mask projection (26.3 ms latency), online ROI trace extraction, and modular ZeroMQ-based control, with a measured imaging-to-stimulation loop benchmark of 91.6 ms. We validate STIMscope in fixed mouse brain tissue, live iPSC-derived human neuronal cultures, and ex vivo organotypic slices of mouse auditory cortex. In organotypic slices, we show that both static and spatiotemporal stimulus identity can be decoded from population activity, revealing reservoir-like population dynamics, and that this decodability remains stable in the same neuronal population over hours. We further show that post-stimulus activity retains information about recent stimuli for several seconds, consistent with short-term memory dynamics. With a bill of materials under $5,000 USD and all mechanical designs, firmware, and software released open-source, STIMscope makes all-optical neuroscience experiments a routine capability accessible to laboratories without specialized optical engineering expertise.

bioengineering↗

bioRxiv2026

Integrative multi-omics and multi-trait analysis prioritizes regulatory mechanisms and genes for metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition that progresses from simple steatosis to advanced fibrosis, significantly affecting liver function and systemic health. Despite its widespread impact, therapeutic options are limited, highlighting the urgent need for comprehensive exploration to identify potential therapeutic targets. In this study, we created an analysis pipeline anchored on liver gene expression, integrating differential meta-analysis of transcriptomic data across three MASLD stages, transcriptome-wide Mendelian randomization (MR), and transcriptome-wide association studies (TWAS), to identify 39 candidate genes potentially involved in MASLD progression. Furthermore, we prioritized these genes using a scoring system that incorporated gene expression-clinical phenotype correlation meta-analysis, proteome-wide association studies (PWAS), and external genetic data from the GWAS Catalog and ExPheWAS. Single-nucleus RNA sequencing (snRNA-seq) analysis of liver cells from healthy to cirrhotic stages revealed stage- and cell-type-specific expression patterns of these prioritized genes. Through experimental validation in a lipid overload hepatocyte model, we confirmed the role of MLIP in lipid metabolism. These findings, available through an interactive web portal (masldportal.net), provide valuable insights into MASLD mechanisms and offer an easy-accessible resource for the research community. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/706502v2_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@184c03eorg.highwire.dtl.DTLVardef@6965ccorg.highwire.dtl.DTLVardef@19a5937org.highwire.dtl.DTLVardef@576b53_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2026

Kinetics of local C3 production orchestrates neutrophil recruitment in lung injury

Complement component 3 (C3) is crucial for host defense against bacteria. While the liver is the primary source of circulating C3, local C3 production at barrier surfaces such as the lung is key in early responses. Yet, how local complement-mediated responses are initiated at mucosal barriers is unknown. This study investigates the kinetics and necessity of lung-derived C3 during the initial hours of an infection. Using models of bacterial pneumonia in ex vivo-perfused human lungs and mice deficient in liver-derived C3, we demonstrate that intrapulmonary C3 production and activation precedes the accumulation of circulating C3 into the bronchoalveolar space. Utilizing mice deficient in lung-derived C3, we demonstrate that epithelial cell-derived C3 is required for early neutrophil recruitment in pneumonia. Transcriptomic and proteomic analyses reveal that neutrophil chemotactic pathways such as C5a and CXCL2 depend on lung epithelial cell-derived C3. These findings demonstrate how lung epithelial-derived C3 influences early mucosal responses to infection via both canonical (direct) and non-canonical (indirect) pathways. SUMMARYAlburquerque et al show an initial, entirely local phase of complement-mediated mucosal protection before a subsequent, systemic response occurs in the setting of barrier disruption. Their work suggests that complement component C3 derived locally at a barrier from the epithelium influences early responses to infection by recruiting neutrophils via multiple pathways independent of circulating C3.

immunology↗

bioRxiv2026

Anterior cingulate cortex projections to the amygdala in primates: topographic and layer-specific organization underlying emotion and mood regulation

Emotion and mood regulation critically depends on interactions between the anterior cingulate cortex (ACC) and the amygdala. However, the detailed architecture of ACC projections to their major targets, the basal (BA) and accessory (AcBA) basal nuclei of the amygdala, remains unclear. To address this issue, a combined retrograde and anterograde tracing with viral vectors were performed in macaques to map the projection patterns from pregenual (pgACC), subgenual (sgACC), and dorsal (dACC) subareas. Data revealed that ACC neurons projecting to the BA arose predominantly from the superficial layers (II/III) of all subareas and the deep layers (V/VI) of the sgACC, whereas ACC neurons projecting to the AcBA originated mainly in the deep layers of the sgACC and dACC. The present study defines the topographic and layer-specific organization of ACC-amygdala connectivity in primates and subserves to provide an anatomical basis for future causal and translational approaches, such as targeted interventions against ACC-related mood disorders. TeaserPrimate anterior cingulate cortex has topographic and layer-specific projections to amygdala that are involved in emotion and mood regulation.

neuroscience↗

bioRxiv2026

Functional organization underlying superior performance in a memory champion

Memory athletes can achieve superior performance (e.g., memorizing 339 digits in 5 minutes) with extensive daily training, by converting abstract information into vivid scenes, and placing them along a mental path, that is later retraced (Method of Loci). Understanding the brain mechanisms underlying such training-derived mastery would increase our understanding of the brains memory systems and could suggest novel approaches to improving cognition in other domains. As memory athletes use personalized training techniques, it has been challenging to study them with standard group paradigms. Fortunately, precision functional mapping (PFM) enables detailed investigation of individual brains through repeated sampling of resting-state functional connectivity and task fMRI. Here, we precisely mapped the brain organization of a 6-time U.S. Memory Champion (>13 hours fMRI). Relative to controls, the Memory Champions network functional connectivity (FC) was strengthened with the retrosplenial, extrastriate visual, and dorsal frontal cortex (area 55b), as well as with the caudate nucleus. The Memory Champion had modules related to scene and semantic processing not seen in controls, alongside stronger connectivity between the caudate and classical memory networks. During rote memorization, the Champions task fMRI patterns were typical, with the hippocampus active during encoding. This pattern was reversed when he used his Method of Loci technique, with greater hippocampal activity during recall than encoding. Hence, intense practice at converting abstract information into more memorable formats can develop a procedural memory skill that utilizes brain regions typically reserved for navigation, language, social cognition, and associative learning.

neuroscience↗

bioRxiv2025

TMPO promotes cellular dissemination and metastasis in circulating tumor cells

Metastasis--the process by which cancer cells spread beyond the primary tumor to distant organs--accounts for the vast majority of cancer-related deaths. To elucidate mechanisms underlying dissemination and metastasis in prostate cancer, we have investigated circulating tumor cells (CTCs) obtained from genetically engineered mouse models (GEMMs). The phenotypic and molecular properties of the CTCs, and organoids derived from these CTCs, closely model the tumor and metastatic phenotypes of their parental GEMMs. Moreover, organoids derived from individual CTCs exhibit molecular and morphological heterogeneity that is associated with distinct metabolic states as well as differences in human prostate cancer outcome. Using computational systems analyses, we have identified TMPO, encoding the nuclear membrane protein lamina-associated polypeptide 2 (Lap2), as a key driver of this heterogeneity. TMPO activity is upregulated in advanced human prostate tumors, metastases, and CTCs, and is associated with adverse clinical outcome. Our findings indicate that TMPO promotes dissemination and metastasis in vivo by enhancing survival in conditions of metabolic stress, and reveal a novel mechanistic link between CTC heterogeneity, stress adaptation, and metastatic potential.

cell biology↗

bioRxiv2025

Carbon bias from grassy tree misclassification: revealing forest structural heterogeneity by integrating GEDI and Sentinel-2

Tropical forests store roughly half of terrestrial carbon, yet carbon estimates in regenerating and disturbed forests remain highly uncertain. A major source of bias is the prevalence of fast-growing, canopy-forming monocots--such as bamboo, palms, and bananas--that are often misclassified as trees. These "grassy trees" achieve canopy dominance but lack secondary growth, violating woody allometries used in most biomass models. Although NASAs GEDI mission has transformed large-scale biomass mapping with spaceborne LiDAR, its products rely on coarse plant functional types (PFTs), causing grassy-tree-dominated canopies to be absorbed into evergreen broadleaf tree (EBT) classes. Using a texture-based Sentinel-2 classifier, we isolated bamboo-dominated forests within GEDI EBT products in Xishuangbanna, China. GEDI observations show that bamboo canopies are structurally distinct from tree-dominated forests and lead to systematic carbon overestimation of 20-44 Mg C ha-{superscript 1} relative to empirical benchmarks. Our framework improves carbon accounting in structurally heterogeneous forests while remaining adaptable for place-based management.

ecology↗

bioRxiv2025

Genome-wide analysis reveals the genetic basis of key agronomic traits and modern wheat breeding in Henan Province

Despite the continuous improvement of wheat cultivars in Henan Province, the largest Chinese wheat-producing area, there have been no reports of studies on their breeding advances in the past decades. This study aims to elucidate their genetic basis and breeding advances. A total of 351 landraces and 265 cultivars in Henan Province were employed in selective sweep studies and genome-wide association studies. All the wheat accessions were planted in five locations in Henan Province in 2016-2017, 2017-2018 and 2018-2019. Candidate genes were identified through differential expression, GO annotation, gene homology, and haplotype analyses. Breeding advances were summarized based on four breeding periods (1950s, 1960s-1970s, 1980s-1990s, and post-2000s) of all 265 cultivars. The results demonstrated that 263 known genes with selection signals were found to be associated with important traits. Around the detected quantitative trait loci, 51 genes had been previously reported, while 252 genes were identified as candidate genes. Of the 303 genes and loci identified, 80 genes and 50 loci contributed to the improvement of 12 traits like plant height, and 12 key candidate genes was verified by qRT-PCR, while superior haplotypes of 24 genes explained cultivar climate adaptation. The superior haplotypes of 164 genes are available for future breeding. Transmission of superior haplotypes in four varietal pedigrees revealed pyramiding of superior haplotypes in elite cultivars. The analysis of post-2000 cultivars suggests a broader range of germplasm resources should be considered in parental selection than only recent accessions. This study provides a genetic basis and guide for wheat improvement.

genetics↗

bioRxiv2025

Targeting anemia-induced CD71+ reticulocytes protects mice from Plasmodium infection

Malaria, caused by Plasmodium spp., is a global health concern linked to anemia and increased mortality. Compensatory erythropoiesis seen during acute anemia results in an increased circulating reticulocyte count (i.e., immature RBC) a key factor in understanding the relationship between pre-existing anemia and Plasmodium burden. Reticulocytes in mice are marked by transferrin receptor (CD71+) and glycophorin A-associated protein (Ter119+). To model acute anemia with increased reticulocytes, C57BL/6 mice were either bled (i.e. phlebotomized) or administered phenylhydrazine, before being infected with Plasmodium yoelii (P. yoelii), a mouse-specific strain with a preference for reticulocytes. In P. yoelii-infected anemic mice, we observed heightened parasitemia and significant body weight loss compared with non-anemic P. yoelii-infected mice. Additionally, serum inflammatory cytokines, erythropoietin, and liver injury markers, along with hemozoin deposition significantly increased in anemic P. yoelii-infected mice. RBC transfusion from healthy normal donors to P. yoelii-infected anemic recipient mice ameliorated anemia by reducing overall reticulocyte count and increasing mature RBC count. RBC transfusion rescued body weight loss, decreased parasitemia, and reduced serum erythropoietin levels. Finally, to confirm the role of reticulocytes in P. yoelii infection, reticulocytes were depleted using anti-CD71 monoclonal antibody in P. yoelii-infected mice. We observed improvement in hematologic parameters and stark reduction in parasitemia in both pre-existing anemic and non-anemic P. yoelii-infected mice. Collectively, our results suggest that pre-existing anemia may increase the risk of Plasmodium infection due to the greater reticulocytes population. Anti-CD71 treatment in Plasmodium infection may offer a novel therapeutic strategy to combat Plasmodium infection and malaria. Grant supportThis work was supported by grants from the Crohns and Colitis Foundation (CCF) and American Heart Association (AHA) Career Development Award (854385 and 855256 respectively) to Piu Saha; grant from the National Institutes of Health (NIH) to Matam Vijay-Kumar (DK134053) and Liver Scholar Award from American liver Foundation to Beng San Yeoh.

pathology↗

bioRxiv2025

Fast and flexible minimizer digestion with digest

Minimizer digestion is an increasingly common component of bioinformatics tools, including tools for De Bruijn-Graph assembly and sequence classification. We describe a new open source tool and library to facilitate efficient digestion of genomic sequences. It can produce digests based on the related ideas of minimizers, modimizers or syncmers. Digest uses efficient data structures, scales well to many threads, and produces digests with expected spacings between digested elements. Digest is implemented in C++17 with a Python API, and is available open-source at https://github.com/VeryAmazed/digest.

bioinformatics↗

bioRxiv2025

Colorectal tumor-induced orexigenic imbalance lowers protein appetite and drives early organ wasting symptoms

Cancer cachexia (CC) is characterized by organ wasting and ensuing involuntary weight loss. Despite advances, underlying mechanisms initiating CC remain unclear, including early symptoms like anorexia. Here, we use a fly gut-tumor model with a precise time-window before organ wasting starts. We show that tumor-induced factors involved in inflammation (unpaired 3/ Interleukin-6-like) and reduced insulin signaling (ImpL2/ Insulin Growth Factor Binding Protein) decrease NPF (Neuropeptide F/ Neuropeptide Y) in the brain prior to organ wasting. This early NPF decrease triggers low protein-specific food appetite and anorexia. We find that ImpL2 reduces NPF signaling while upd3 helps by concurrently disrupting the blood brain barrier. Tumor-induced NPF decrease, and early reduction of protein appetite drive the onset of weight loss and exacerbate the risk of death during organ wasting. Altogether, we provide evidence for an early orexigenic brain imbalance causing low protein appetite that regulates the onset and outcome of organ wasting.

genetics↗

bioRxiv2024

Evolutionary conserved cis-trans regulation machinery for diterpenoid phytoalexin production in Poaceae

O_LIMomilactones and phytocassanes are diterpenoid phytoalexins involved in plant chemical defense. These metabolites, along with biosynthetic gene clusters (BGCs), are conserved in wild rice. However, the mechanisms by which phytoalexins are regulated in wild rice are unclear. Thus, we aimed to investigate the regulatory mechanisms for biosynthetic genes within the BGCs of diterpenoid phytoalexins. C_LIO_LIWe conducted a transcriptome analysis of five wild rice species, Oryza rufipogon, Oryza punctata, Oryza officinalis, Oryza brachyantha, and Leersia perrieri, after CuCl2 treatment. C_LIO_LIAmong the CuCl2-responsive transcription factors, diterpenoid phytoalexin factor (DPF), which regulates phytoalexin production in cultivated rice (Oryza sativa), was broadly conserved in wild rice and showed phytoalexin-inducing activity when introduced into cultivated rice. Highly conserved genomic regions containing N-boxes (5'-CACGAG-3'), the potential binding motif of DPF, were found. CRISPR/Cas9 genome editing to remove these regions showed that biosynthetic gene expression and phytoalexin production were significantly attenuated after CuCl2 treatment in the leaves of the edited plants. Thus, the cis-trans factor combination of DPF and N-boxes is a key determinant of regulation. C_LIO_LIDPF has evolved as a strong cis-trans regulatory system for diterpenoid phytoalexin production, with N-boxes generated within the cluster region during the evolution from wild rice to cultivated rice. C_LI

plant biology↗

bioRxiv2024

EAP: a versatile cloud-based platform for comprehensive and interactive analysis of large-scale ChIP/ATAC-seq data sets

Epigenome profiling techniques such as ChIP-seq and ATAC-seq have revolutionized our understanding of gene expression regulation in tissue development and disease progression. However, increasing amount of ChIP/ATAC-seq data poses challenges in computational resources, and the absence of systematic tools for epigenomic analysis underscores the necessity for an efficient analysis platform. To address these issues, we developed the Epigenomic Analysis Platform (EAP, https://www.biosino.org/epigenetics), a scalable cloud-based tool that efficiently analyzes large-scale ChIP/ATAC-seq data sets. EAP employs advanced computational algorithms to derive biologically meaningful insights from heterogeneous datasets and automatically generates publication-ready figures and tabular results, enabling comprehensive epigenomic analysis and data mining in areas like cancer subtyping and therapeutic target discovery.

bioinformatics↗

bioRxiv2024

The first discovery of SFTSV in the Centre of Metropolitan Beijing, China

Severe fever with thrombocytopenia virus (SFTSV), an emerging tick-borne bandavirus, poses a significant public health threat in rural China. Since 2021, an increase in local cases has been noted in the rural-urban fringe surrounding Beijing. This study aimed to assess the formation of natural foci in urban areas by conducting a field survey of ticks and hedgehogs from Beijings second to fifth ring roads. Our survey revealed a diverse tick population in city parks, including the major SFTSV vector, H. longicornis. Parthenogenetic H. longicornis, known for its role in rapid SFTSV spread, was identified in key locations like Beihai Park and Taoranting Park, near the Forbidden City. Notably, high SFTSV seroprevalence and RNA prevalence were found in hedgehogs and parasitic ticks in the center of Beijing. These findings highlight the circulation of SFTSV in central Beijing, underscoring the need for urgent attention and enhanced surveillance measures.

microbiology↗

bioRxiv2023

Hidden rAAV Breakpoints Detected Using Single-Molecule, Modified Base Sequencing

The AAV genome is a single stranded DNA molecule packaged in an icosahedral protein capsid. Vector genomes of plus and minus polarities are packaged and complementary genomic strands hybridize when lysed in vitro. Standard sequencing library methods cause loss of information from individual genomes when mismatches and gaps are repaired. To retain original molecular information, modified bases are used during the repair step which allows pre-existing DNA to be distinguished from DNA added during library preparation. Modified bases introduced during repair are identified using the Sequel II system and used to detect HIDdEN DNA breakpoints (HIDEN-Seq). The most frequent breakpoints in an AAV vector subject to high strand breakage during packaging were linked to adjacent secondary structure, prompting changes in nearby sequences to reduce breakage. This use of modified bases for localizing DNA breaks enables better vector design, resulting in higher quality gene therapy vectors. The same approach can be used in other systems where knowledge of pre-existing sequence and structure is important.

genomics↗

bioRxiv2023

Establishing an AI-based evaluation system that quantifies social/pathophysiological behaviors of common marmosets

Nonhuman primates (NHPs) are indispensable animal models by virtue of the continuity of behavioral repertoires across primates, including humans. However, behavioral assessment at the laboratory level has so far been limited. By applying multiple deep neural networks trained with large-scale datasets, we established an evaluation system that could reconstruct and estimate three-dimensional (3D) poses of common marmosets, a small NHP that is suitable for analyzing complex natural behaviors in laboratory setups. We further developed downstream analytic methodologies to quantify a variety of behavioral parameters beyond simple motion kinematics, such as social interactions and the internal state behind actions, obtained solely from 3D pose data. Moreover, a fully unsupervised approach enabled us to detect progressively-appearing symptomatic behaviors over a year in a Parkinsons disease model. The high-throughput and versatile nature of our analytic pipeline will open a new avenue for neuroscience research dealing with big-data analyses of social/pathophysiological behaviors in NHPs.

neuroscience↗