Biology subjects

Miao, M.

Publications and source records attributed to Miao, M..

9 recordsLinked to original sources

bioRxiv2026

Dual-view Guided Context-aware Network for Automated Bone Lesion Segmentation and Quantification in Whole-body SPECT

Whole-body SPECT bone scintigraphy reflects skeletal metabolic activity throughout the body and plays an indispensable role in the screening, treatment evaluation, and prognostic assessment of bone metastases in tumors. However, the automatic detection and segmentation of hypermetabolic bone lesions remain challenging due to low contrast, limited spatial resolution, and complex lesion distributions. In this study, we proposed Bone-Segnet, a dual-view guided automatic segmentation network for hypermetabolic bone lesions that integrated multi-scale feature modeling, global context modeling, and view-conditioned modulation. Pixel-level annotated anterior and posterior whole-body bone scintigraphy images were used for model training and prediction. The proposed network enhanced the recognition of low-contrast and small-scale lesions through small-lesion enhancement and multi-scale contextual modeling. A Transformer module was further introduced to strengthen global feature representation, while cross-view collaborative modeling was achieved by incorporating the complementary characteristics of anterior and posterior imaging. Experimental results demonstrated that the proposed method outperformed existing approaches across multiple evaluation metrics, with the Dice score improving from 0.7440 to 0.8750, indicating a substantial improvement in segmentation performance. Further quantitative analysis based on the segmentation results revealed significant differences among disease types in lesion count, pixel burden, and spatial distribution patterns, reflecting the heterogeneity of disease-related skeletal metabolic activity. Overall, the proposed method improved automatic lesion segmentation performance and enabled quantitative analysis of lesion burden and spatial distribution patterns, providing objective data support for the assessment of related diseases. Index Terms--Whole-body SPECT, bone lesion segmentation, dual-view modeling, quantitative analysis.

bioinformatics↗

bioRxiv2025

Clonal lineage tracing of innate immune cells in human cancer

Innate immune cells constitute the majority of the tumor microenvironment (TME), where they mediate both natural anti-tumor immunity and immunotherapy responses. While single-cell T- and B-cell receptor sequencing has provided fundamental insights into the clonal dynamics of human adaptive immunity, the lack of appropriate tools has precluded similar analysis of innate immune cells. Here, we describe a method that leverages somatic mitochondrial DNA (mtDNA) mutations to reconstruct clonal lineage relationships between single cells across cell types in native human tissues. We jointly sequenced single-cell transposase-accessible chromatin and mtDNA to profile n=124,958 cells from matched tumor, non-involved lung tissue (NILT), and peripheral blood of early-stage non-small cell lung cancer (NSCLC) patients, as well as n=93,757 cells from matched tumor and peripheral blood of ovarian cancer patients. Single-cell concomitant profiling of lineage and cell states of thousands of immune cells resolved clonality across cell types, tissue sites, and malignancies. Clonal tracing of innate immune cells demonstrates that TME-resident myeloid subsets, including macrophages and type 3 dendritic cells (DC3), are clonally linked to both circulating and tissue-infiltrating monocytes. Further, we identify distinct DC-biased and macrophage-biased myeloid clones, enriched in the tumor and NILT, respectively, and find that their circulating monocyte precursors exhibit distinct epigenetic profiles, suggesting that myeloid differentiation fate may be predetermined before TME infiltration. These results delineate the clonal pathways of intratumoral myeloid cell recruitment and differentiation in human cancer and suggest that remodeling of the tumor myeloid compartment may be peripherally programmed.

genomics↗

bioRxiv2024

Screening of potential biomarkers using activity-based protein profiling in a rat model of chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition affecting cancer patients, often resulting from the use of neurotoxic agents, such as paclitaxel. This study aimed to establish a rat model of CIPN through systemic administration of paclitaxel and to identify potential biomarkers using activity-based protein profiling (ABPP) with a desthiobiotin iodoacetamide (DBIA) probe. Male Sprague-Dawley rats received paclitaxel injections at a dosage of 2 mg/kg on Days 0, 2, 4, and 6. Behavioral assessments revealed significant mechanical and thermal pain hypersensitivity in paclitaxel-treated rats compared to control groups. ABPP analysis identified a total of 2,445 proteins and 6,765 peptides, resulting in the identification of 7 candidate proteins as potential biomarkers for CIPN. Notably, 5 proteins were significantly upregulated, while 2 protein including Q63425 (Prx) demonstrated downregulation in response to paclitaxel. These findings suggest that alterations in candidate protein levels may compromise alterations in the spinal cord in the context of CIPN. This study underscores the utility of ABPP in elucidating the proteomic changes associated with CIPN and highlights the potential of identified biomarkers like Prx for enhancing our understanding of chemotherapy-induced neuropathic pain mechanisms.

molecular biology↗

bioRxiv2024

Tesorai Search: Large pretrained model boosts identifications in mass spectrometry proteomics without the need for Percolator.

The original mass spectrometry search engines used simple algorithms for peptide identification. Recent tools improved accuracy by adding several extra components such as fragment ion intensities or retention times prediction and training target-decoy classifiers on-the-fly, leading to sometimes inconsistent results. Our study explores the impact of replacing those extra components with a deep-learning pretrained model that directly learns the complex relationship between the full spectra and associated peptide sequence, without using decoys. This simplified workflow has fewer parameters to tweak, making it easier to use and perform robustly on data from instruments and use-cases never seen during training. Surprisingly, our approach consistently identifies more peptides than FragPipe, PEAKS, and Proteome Discoverer (12%, 9%, and 21% more, respectively, across a range of datasets). Tesorai Search is also fast - 250 immunopeptidomics searches in 45 minutes - and free for academics, available as a webserver at console.tesorai.com.

bioinformatics↗

bioRxiv2024

Adaptive optical third-harmonic generation microscopy for in vivo imaging of tissues

Third-harmonic generation microscopy is a powerful label-free nonlinear imaging technique, providing essential information about structural characteristics of cells and tissues without requiring external labelling agents. In this work, we integrated a recently developed compact adaptive optics module into a third-harmonic generation microscope, to measure and correct for optical aberrations in complex tissues. Taking advantage of the high sensitivity of the third-harmonic generation process to material interfaces and thin membranes, along with the 1,300-nm excitation wavelength used here, our adaptive optical third-harmonic generation microscope enabled high-resolution in vivo imaging within highly scattering biological model systems. Examples include imaging of myelinated axons and vascular structures within the mouse spinal cord and deep cortical layers of the mouse brain, along with imaging of key anatomical features in the roots of the model plant Brachypodium distachyon. In all instances, aberration correction led to significant enhancements in image quality.

biophysics↗

bioRxiv2024

Label-free structural imaging of plant roots and microbes using third- harmonic generation microscopy

Root biology is pivotal in addressing global challenges including sustainable agriculture and climate change. However, roots have been relatively understudied among plant organs, partly due to the difficulties in imaging root structures in their natural environment. Here we used microfabricated ecosystems (EcoFABs) to establish growing environments with optical access and employed nonlinear multimodal microscopy of third-harmonic generation (THG) and three-photon fluorescence (3PF) to achieve label-free, in situ imaging of live roots and microbes at high spatiotemporal resolution. THG enabled us to observe key plant root structures including the vasculature, Casparian strips, dividing meristematic cells, and root cap cells, as well as subcellular features including nuclear envelopes, nucleoli, starch granules, and putative stress granules. THG from the cell walls of bacteria and fungi also provides label-free contrast for visualizing these microbes in the root rhizosphere. With simultaneously recorded 3PF fluorescence signal, we demonstrated our ability to investigate root-microbe interactions by achieving single-bacterium tracking and subcellular imaging of fungal spores and hyphae in the rhizosphere.

plant biology↗

bioRxiv2020

SARS-CoV-2 infecting the inner ear results in potential hearing damage at the early stage or prognosis of COVID-19 in rodents

ObjectivesIn order to find out the association between the sensorineural hearing loss and COVID-19, we detected the expression ACE2 and TMPRSS2 in the mouse the hamster. DesignUsing the public data from NCBI and GISAID, we assessed the expression of ACE2 and TMPRSS2 at the transcriptomic, DNA, and protein levels of ACE2 in the brain, inner ear, and muscle from the golden Syrian hamster (Mesocricetus auratus) and mouse (Mus musculus). ResultsWe identified ACE2 and TMPRSS2 expressed at different level in the inner ear and brain at DNA and transcriptomic levels of both mouse and the hamster. The protein expression shows a similar pattern of the brain and inner ear, while the expression of ACE2 from the inner ear was relatively higher than it from the muscle. ConclusionSARS-CoV-2 could infect the hearing system potentially and SSNHL could be a characteristic to detect asymptomatic patients of COVID-19.

bioinformatics↗

bioRxiv2018

SlARF10, an auxin response factor, is required for chlorophyll and sugar accumulation during tomato fruit development

Tomato green fruits photosynthesis contributes to fruit growth and carbon economy. Tomato auxin response factor 10 (SlARF10) is one of the members of ARF family. Our results showed that SlARF10 locates in the nucleus and has no transcriptional activity. SlARF10 was expressed in various tomato tissues, but highly expressed in green fruit. Up-regulation of SlARF10 produced dark green phenotype of fruits, whereas down-regulation of SlARF10 had light green phenotype. Autofluorescence and chlorophyll content analysis confirmed the phenotypes, which indicated that SlARF10 plays an important role in chlorophyll accumulation in tomato fruits. Up-regulation of SlARF10 increased the photochemical potential in tomato leaves and fruits. Furthermore, the SlARF10 up-regulating lines displayed improved accumulation of starch in fruits, whereas SlARF10 suppressed lines had inhibited starch accumulation. Up-regulation of SlARF10 increased the expression of AGPases, the starch biosynthesis genes. SlARF10 up-regulating lines had increased accumulation of SlGLK1 and SlGLK2 transcripts in fruits. The promoter sequence of SlGLK1 gene had two conserved ARF binding sites. SlARF10 may regulate the expression of SlGLK1, thus controlling chlorophyll accumulation, photosynthesis rates and sugars synthesis in fruits. Our study provided more insight on the link between auxin signaling, chloroplastic activity and sugar metabolism during the development of tomato fruits.\n\nAbbreviations\n\nHighlightSlARF10 played an important role in the chlorophyll accumulation and photosynthesis in tomato fruits. SlARF10 was involved in starch accumulation by controlling the expression of starch synthesis related enzyme genes. SlARF10 may regulate the expression of SlGLK1, thus controlling chlorophyll accumulation, photosynthesis rates and sugars synthesis in tomato fruits.

plant biology↗

bioRxiv2017

Metabolic process of raffinose family oligosacharrides during cold stress and recovery in cucumber leaves

Raffinose family oligosacharrides (RFOs) accumulate under stress conditions in many plants and have been suggested to act as stress protectants. To elucidate the metabolic process of RFOs under cold stress, levels of RFOs and relative carbohydrates, the expression and activities of main metabolic enzymes and their subcellular compartments were investigated during low temperature treatment and recovery period in cucumber leaves. Cold stress induced the accumulation of stachyose in vacuoles, galactinol in vacuoles and cytosols, and sucrose and raffinose in vacuoles, cytosols and chloroplasts. After cold stress removal, levels of these sugars decreased gradually in respective compartments. Among 4 galactinol synthase genes (CsGS), CsGS1 was not affected by the cold stress, while other three CsGSs were up-regulated by the low temperature. RNA levels of acid--galactosidase (GAL) 3, alkaline--galactosidase (AGA) 2 and 3, and the activities of GAL and AGA were up-regulated after cold stress removal. The GAL3 protein and GAL activity were exclusively located in the vacuole, whereas the protein of AGA2 and AGA 3 were found in the cytosol and chloroplast respectively. The results indicate that RFOs accumulated during the cold stress in different subcellular compartments in cucumber leaves could be catabolized in situ by different galactosidases after stress removal.

plant biology↗