Singleron Biotechnologies (china)

BackgroundSingle-cell multi-omics (SCMO) technologies simultaneously profile multiple molecular layers (e.g., DNA, RNA, proteins) within individual cells. Unlike traditional bulk analyses that average signals across thousands of cells, SCMO captures the unique molecular characteristics of each cell, potentially transforming our understanding of disease pathogenesis and clinical management. Despite its promise, SCMO methodologies remain complex and difficult for clinicians to interpret and utilize effectively.MethodsWe conducted a narrative review specifically tailored to clinicians, summarizing key SCMO methodologies, recent discoveries, and their translational relevance for cardiovascular and aging-related diseases. Our goal was to simplify complex SCMO concepts, highlight practical clinical insights, clarify methodological details in accessible terms, and openly discuss barriers currently preventing routine clinical implementation.ResultsSCMO techniques have identified clinically relevant cellular heterogeneity within diseases such as atherosclerosis and heart failure, uncovering subpopulations linked to disease severity and potential therapeutic targets. Notably, SCMO studies revealed specific inflammatory immune subsets in unstable plaques, pathogenic fibroblast populations driving cardiac fibrosis, and distinct immune profiles associated with aging and longevity. Early clinical trials integrating SCMO demonstrate feasibility in oncology and cardiology, and prototype clinical assays (e.g., single-cell “liquid biopsies”) are emerging. These advances are yielding predictive biomarkers and guiding personalized and preventive applications.ConclusionSCMO is rapidly evolving, offering unprecedented precision in diagnostics and personalized therapeutics by pinpointing disease-driving cells and molecular pathways. However, significant hurdles including high costs, technical complexity, and analytical challenges currently limit immediate clinical application. To the best of our knowledge, as of 2025, FDA authorization for single-cell diagnostics is limited to established technologies like flow cytometry, while next-generation multi-omic platforms remain confined to research use. This manuscript is explicitly designed to help clinicians navigate the complexity of SCMO, providing clear, digestible explanations of its methodologies and emphasizing how these tools might practically benefit patient care. Clinicians should remain cautiously optimistic, viewing SCMO as a complementary, specialized tool. Continued technological and methodological advances suggest SCMO will become increasingly integral to precision medicine.

BackgroundTransgender women (transfemales) often undergo gender-affirming hormone therapy (GAHT). However, the testicular impacts of feminising hormones present heterogeneity due to the complexity of testicular regulatory mechanisms.MethodIn this study, we analyzed approximately 49,385 single-cell transcriptomes from transfemale human testicular tissue, comparing cellular composition with that of cisgender male individuals across a range of ages. Our approach included clustering of cell types, identification of marker genes, pseudotime analysis of germ cells, and comprehensive cell-cell interaction analyses. We employed immunohistochemistry, quantitative real-time PCR, and immunostaining to validate the key molecular signatures identified in the pathways of interest.ResultsGAHT led to a significant reduction in spermatogenic cells, accompanied by an unexpected increase in Sertoli cell numbers per seminiferous tubule, suggesting disrupted germ cell-Sertoli cell interactions. Molecular analyses revealed upregulation of genes such as Decorin (DCN), Myoglobin (MB), and Beta-2-Microglobulin (B2M) in Sertoli cells, with enrichment in pathways related to cell adhesion, cytokine response, and wnt signaling. Notably, β-catenin was significantly elevated and translocated into the nucleus of Sertoli cells determined by immunostaining analysis. Additionally, collagen fiber infiltration disrupted the testicular microenvironment, further impairing germline-Sertoli cell communication.ConclusionThis study provides novel insights into the testicular alterations associated with GAHT in transfemales, particularly highlighting the role of germline-Sertoli cell interactions in testicular injury. Our findings contribute to a deeper understanding of the testicular response to feminizing hormones, offering a foundation for future therapeutic strategies.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13578-025-01445-3.

Single-cell sequencing provides transcriptomic profiling at single-cell resolution, uncovering cellular heterogeneity with unprecedented precision. Yet, current single cell data analysis suffers from the inherent data noises, batch effects, and sparsity, highlighting the requirement of a unified model to represent cellular states. To circumvent this problem, many recent efforts focus on training single-cell foundation models based on large datasets. However, current human foundation models are still limited by the sizes of training data and model parameters. Here, we have collected a diverse dataset of 100 million human cells, on which we train a single-cell foundation model (CellFM) containing 800 million parameters. To balance efficiency and performance, the model is trained through a modified RetNet framework on the MindSpore. Extensive experiments have shown that CellFM outperforms existing models in cell annotation, perturbation prediction, gene function prediction, and gene-gene relationship capturing.

BackgroundPeople living with HIV (PLWH) who experience low-level viremia (LLV) face unique challenges in disease management, particularly when diagnosed with concurrent malignancies. Albuvirtide (ABT), a long-acting HIV fusion inhibitor approved in China, has shown promise in clinical trials for treatment-experienced individuals. However, its efficacy in managing LLV in the context of concurrent malignancies remains under-explored.Case presentationWe report two cases of PLWH with LLV who developed non-AIDS-defining cancers(NADCs). The first individual developed lung squamous cell carcinoma, and the second was diagnosed with breast cancer. Both patients received ABT as part of their optimized antiretroviral therapy (ART) regimen during their cancer treatment course. After treatment optimization, both cases achieved viral suppression (HIV-1 RNA < 50 copies/mL) with improvements in CD4 + T cell counts. Both patients received appropriate cancer treatments according to clinical practice guidelines. The patient diagnosed with lung cancer required an adjustment to his PD-1 inhibitor monotherapy due to intolerance to chemotherapy, whereas the breast cancer patient successfully completed her planned multimodal treatment regimen.ConclusionsThese cases suggest potential benefits of ABT-containing ART regimens in PLWH who have LLV and concurrent NADCs. While two cases cannot establish definitive conclusions, they highlight the need for larger studies investigating the role of ABT in this complex clinical scenario.

Single-cell RNA sequencing (scRNA-seq) using metabolic RNA labeling enables detailed analysis of dynamic gene expression within single cells. However, most studies are limited to in vitro settings, restricting the exploration of in vivo transcriptomic dynamics. To address this, we developed scDyna-seq, a time-resolved scRNA-seq method for in vivo applications using 4-thiouridine (4sU) labeling. scDyna-seq efficiently captures nascent RNA, allowing for precise tracking of gene expression in both in vitro and in vivo contexts, including crossing the blood-brain and blood-fetal barriers. It is also compatible with other single-cell multiomics approaches. In a mouse bladder cancer model, scDyna-seq revealed that cisplatin (cis-diaminodichloroplatinum, CDDP) induced significant dynamic changes in tumor-infiltrating lymphocytes, particularly in genes related to costimulation, effector functions, and exhaustion, which were not detected by conventional methods. When coupled with scTCR-seq, scDyna-seq showed increased TCR clonal expansion linked to CDDP-induced immunogenic death and neoantigen production. In conclusion, scDyna-seq offers safe, precise in vivo RNA labeling as well as single-cell analysis, expanding our understanding of cellular dynamics and facilitating research in health and disease.

Albuvirtide (ABT) is the first long-acting HIV fusion inhibitor developed in China, blocking the invasion of HIV-1 virus into target cells. This study aimed to compare the pharmacokinetics (PK), tolerability, and safety of ABT following a single intravenous (IV) bolus injection or intravenous drip in healthy Chinese subjects. A single-center, randomized, open-label, single-period, parallel phase I clinical trial was conducted. Thirty subjects were randomly divided into three groups in a ratio of 1:1:1. After an overnight fast, all subjects received a single dose of 320mg ABT either by intravenous drip for 45min (group A) or bolus injection for 0.5min (group B), or bolus injection for 3min (group C). ABT plasma concentrations were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Non-compartmental analysis was used to evaluate PK parameters. The median time to reach maximum concentration was 0.75h in group A and 0.16h in both groups B and C. Elimination half-life, mean residence time, apparent clearance, and apparent volume of distribution were similar among the three groups. The 90% confidence intervals (CI) of geometric mean ratios of PK parameters for groups B and C relative to group C were within 85-120%. All adverse events (AEs) reported in this study were mild, according to the CTCAE guidelines and the study investigator's judgement. ABT bolus injections for 0.5min and 3min are expected to be well tolerated and to exhibit similar PK characteristics as IV drip for 45min, offering potential clinical benefits.

Plant mitochondrial genomes are a valuable source of genetic information for a better understanding of phylogenetic relationships. However, no mitochondrial genome of any species in Ebenaceae has been reported. In this study, we reported the first mitochondrial genome of an Ebenaceae model plant Diospyros oleifera. The mitogenome was 493,958 bp in length, contained 39 protein-coding genes, 27 transfer RNA genes, and 3 ribosomal RNA genes. The rps2 and rps11 genes were missing in the D. oleifera mt genome, while the rps10 gene was identified. The length of the repetitive sequence in the D. oleifera mt genome was 31 kb, accounting for 6.33%. A clear bias in RNA-editing sites were found in the D. oleifera mt genome. We also detected 28 chloroplast-derived fragments significantly associated with D. oleifera mt genes, indicating intracellular tRNA genes transferred frequently from chloroplasts to mitochondria in D. oleifera. Phylogenetic analysis based on the mt genomes of D. oleifera and 27 other taxa reflected the exact evolutionary and taxonomic status of D. oleifera. Ka/Ks analysis revealed that 95.16% of the protein-coding genes in the D. oleifera mt genome had undergone negative selections. But, the rearrangement of mitochondrial genes has been widely occur among D. oleifera and these observed species. These results will lay the foundation for identifying further evolutionary relationships within Ebenaceae.

To develop new anti-metastasis chemotherapeutic drugs, a series of flurbiprofen (FLP) and zaltoprofen (ZTP) platinum(IV) complexes targeting COX-2, PD-L1 and DNA was prepared and investigated. Complex 2 with dual FLP ligands displays promising antitumor activities in vitro and exhibits much potential in overcoming drug resistance. More importantly, the antitumor evaluation in vivo demonstrates that complex 2 possesses promising inhibition of cancer growth and metastasis simultaneously. Further investigation of the mechanism revealed the multi-specific antitumor function of complex 2. It exerts remarkable DNA damage after reduction to platinum(II) complex, and up-regulates the expression of p53 and γ-H2AX. Then, complex 2 promotes mitochondria-mediated apoptosis effectively by activating the Bcl-2/Bax/caspase3 pathway. Furthermore, inflammation in tumor tissues is restrained by the suppression of enzymes COX-2, MMP-9, NLRP3 and caspase1, which would favor the inhibition of tumor metastasis. Moreover, compound 2 boosts T-cell immunity by restraining PD-L1 expression, and further improving the density of CD3+ and CD8+ T cells in tumor tissues.

Breast cancer stem-like cells (BCSCs) play vital roles in tumorigenesis and progression. However, the origin and dynamic changes of BCSCs are still to be elucidated. Using the breast cancer mouse model MMTV-PyMT, we constructed a single-cell atlas of 31,778 cells from four distinct stages of tumor progression (hyperplasia, adenoma/MIN, early carcinoma and late carcinoma), during which malignant transition occurs. We identified that the precise cell type of ERlow epithelial cell lineage gave rise to the tumors, and the differentiation of ERhigh epithelial cell lineage was blocked. Furthermore, we discovered a specific signature with a continuum of gene expression profiles along the tumor progression and significantly correlated with clinical outcomes, and we also found a stem-like cell cluster existed among ERlow epithelial cells. Further clustering on this stem-like cluster showed several sub-clusters indicating heterogeneity of stem-like epithelial cells. Moreover, we distinguished normal and cancer stem-like cells in this stem-like epithelial cell cluster and profiled the molecular portraits from normal stem-like cell to cancer stem-like cells during the malignant transition. Finally, we found the diverse immune cell infiltration displayed immunosuppressive characteristics along tumor progression. We also found the specific expression pattern of cytokines and their corresponding cytokine receptors in BCSCs and immune cells, suggesting the possible cross-talk between BCSCs and the immune cells. These data provide a useful resource for illuminating BCSC heterogeneity and the immune cell remodeling during breast tumor progression, and shed new light on transcriptomic dynamics during the progression at the single-cell level.