Biology subjects

Ma, C.

Publications and source records attributed to Ma, C..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Looking backward for the future: long-term population recovery, habitat associations, and future climatic vulnerability of the critically endangered Sino-Mongolian beaver (Castor fiber birulai) in China

Despite the successful population recovery of the Eurasian beaver (Castor fiber) across much of Eurasia, its subspecies, the Sino-Mongolian beaver (C. f. birulai), remains critically endangered, with an estimated population of approximately 1,500 individuals confined to a small number of isolated and fragmented refugia along the China-Mongolia border. Effective conservation of this highly threatened subspecies requires a holistic perspective that integrates constraints on population dynamics, habitat associations, and future climatic vulnerability. Here, we combined systematic annual field surveys conducted between 2003 and 2023 with historical survey records from 1975 to 1989 in northern Xinjiang, China, to synthesize long-term spatiotemporal population dynamics, evaluate habitat preferences based on nine local environmental variables, and assess future climatic vulnerability using ensemble species distribution models (SDMs) under projected climate change scenarios. We detected a significant and phased population recovery, with beaver colony numbers increasing from 27 (approximately 100 individuals) in 1975 to 227 (681-908 individuals) in 2023. This recovery closely corresponded with major conservation milestones, including the establishment and upgrading of nature reserves, strengthened legislative protection, and enhanced multi-stakeholder collaboration. Habitat analyses further indicated that the Sino-Mongolian beaver preferentially occupied areas characterized by minimal anthropogenic disturbance and stable hydro-geomorphic conditions. Critically, SDM projections revealed that only 14% of the current study area presently exhibits high climatic suitability, and these highly suitable habitats are expected to disappear entirely by the 2050s. Together, our findings provide a comprehensive overview of the historical population recovery and conservation trajectory of the Sino-Mongolian beaver in China, and offer robust scientific support for developing adaptive management strategies in the face of ongoing climate change and increasing human pressures.

ecology↗

bioRxiv2026

Discovery of potent oligopeptides for various metabolic diseases using deep learning

Artificial intelligence (AI)-based methods are increasingly critical in peptide drug discovery, but their applications are limited in a narrow scope such as antimicrobial peptides. For indications where peptide therapy inherently excels, such as metabolism, endocrinology, and tissue regeneration, AI-based pipeline for therapeutic peptide discovery is long awaited but still unmet. Here, we propose a deep learning-based pipeline, Deepeptide, capable of identifying therapeutic oligopeptides for various metabolism-related indications. Leveraging the intrinsical relationship of disease indication -- biological processes -- molecular functions, Deepeptide discovers oligopeptides with indication-ameliorating-related molecular functions as lead candidates for indication of interest. Deepeptide was applied in five representative indications of metabolism, endocrinology, and tissue regeneration: angiogenesis, lipid metabolism, osteogenesis, glucose metabolism, and anti-angiogenesis. Overall, 62% of the identified oligopeptide candidates demonstrated significant bioactivity in vitro, with most of them showing comparable potency to the first-line drugs. Notably, the heptapeptide AP7 exhibited angiogenic potency comparable to VEGF in excisional wound splinting mouse model by promoting cell migration rather than proliferation, and hexapeptide TP6 showed significant dual-efficacy against hyperlipidemia and obesity in high-fat diet mice by inhibiting lipid synthesis and regulating gut microbiota. These findings highlight the potential and generalizability of Deepeptide in therapeutic oligopeptide discovery for metabolic diseases.

bioinformatics↗

bioRxiv2025

A Comprehensive Treatment-Induced Resistance Atlas of Glioblastoma Reveals a Fibrotic Niche Shielding the Tumor from Immunotherapy

Therapeutic resistance in IDH-wildtype glioblastoma (GBM) is driven by an intricate interplay between cellular plasticity and protective microenvironmental niches. By constructing the GRIT-Atlas--a massive transcriptomic compendium encompassing nearly one million high-quality single cells across 17 cohorts--and cross-analyzing it with 48 independent Visium spatial transcriptomics sections, we discover a recurrent "Spatial Resistance Triad" comprising mesenchymal-like (MES-like) malignant cells, myeloid-derived suppressor cells (MDSCs), and collagen-secreting cancer-associated fibroblasts (CAFs). This large-scale spatial integration reveals that the triad physically fortifies microvascular proliferation (MVP) and pseudopalisading necrosis (PAN) niches. To substantiate these findings at true single-cell resolution, we deploy high-plex spatial molecular imaging (CosMx SMI) to map over 400,000 single cells across a clinical validation cohort. This high-resolution architecture firmly validates the triads geography and, critically, provides structural gradient evidence unmasking a spatiotemporal continuum wherein PAN emerges as a direct functional consequence of MVP advancement and subsequent vascular collapse. Mechanistically, stromal CAF-derived COL6A1 engages CD44 receptors on MES-like cells to accelerate a potent neural stemness cascade within these protective domains. Utilizing a blood-brain barrier (BBB)-penetrant multi-library compound screen, we identify Lacidipine as a multi-modal stromal disruptor that successfully silences CAF activation and halts matrix secretion. Incorporating Lacidipine into the standard chemo-immunotherapy backbone (TMZ + anti-CSF1R) completely dismantles the protective desmoplastic matrix niche, forcing a profound collapse of intracranial tumor burden and dramatically extending overall survival in orthotopic models. Collectively, our study leverages unprecedented single-cell and spatial scale to provide a definitive blueprint of GBM therapeutic evasion, establishing matrix-targeted intervention as a mandatory prerequisite for successful glioblastoma eradication.

cancer biology↗

bioRxiv2025

Multimodal Data Fusion Reveals Morpho-Genetic Variations in Human Cortical Neurons Associated with Tumor Infiltration

We introduce LetsACT (Light-Electron-Transcriptome synergistic ACTomography), a multimodal integration platform that overcomes the limitations of single-modality data acquisition and analysis of human brain cells while synergistically leveraging the strengths of each modality. Our approach enables the rapid sample preparation, cell injection, imaging, and multimodal integration of large-scale human neuronal datasets at single-cell resolution. By generating initial laser-scanning-microscopy based optical reconstruction of neuron morphologies followed by refining them using electron-microscopy derived morphological priors, we have assembled one of the largest human cortical morphology datasets to date: 8,398 neurons from 58 donors, with high cortical coverage. This platform is then applied to studying morphological impact of tumor infiltration. Pyramidal neurons in glioma-infiltrated tissues display clear volume shrinkage in somas and branches, tapering from the soma to nearby dendritic compartments. By integrating these morphological variations with spatial and bulk transcriptomic profiles, we find that glioblastoma tissues exhibit dysregulation of 15.29% of genes, including overexpression of TERT, whereas infiltrated tissues show 7.74% gene dysregulation, characterized by overexpression of tumor suppressors such as CDKN2A and TP53. Our analysis implies that pyramidal neurons observed in these infiltrated tissues may involve an active defense instead of undergoing passive apoptosis. Our finding also indicates that LetsACT establishes a valuable resource for the large-scale, comprehensive morpho-genetic analysis of human tissues.

neuroscience↗

bioRxiv2025

Bio-synthesis of 15N-Labeled G-Quadruplexes to Investigate the Structure and Interactions in the Cell Lysate using Nuclear Magnetic Resonance

G-quadruplexes (G4) play key roles in biology, making it critical to understand their structure and ligand-binding behavior in cellular environments for advancing G4-targeted therapeutics. While in-cell nuclear magnetic resonance (NMR) is a powerful technique for studying G4 in situ, its application is limited by the challenge of producing isotope-labeled single-stranded DNA (ssDNA). Here, we introduce Restriction Endonuclease Digestion (RED), a simple and cost-effective method to generate 15N-labeled ssDNA. This approach combines molecular cloning and enzymatic design processing by propagating plasmids in E. coli cultured with 15NH4Cl, followed by double restriction digestion and isolation target 15N-ssDNA. Using RED, we produced milligram-scale quantities of 96%-enriched 15N-labeled human telomeric G4 ssDNA (wtTel23c, CTAGGG(TTAGGG)3), ideal for NMR analysis. The NMR spectra revealed that wtTel23c adopts G4 topology and undergoes multiple conformations of wtTel23c in potassium-containing solutions and in Xenopus laevis cell lysate. Interaction studies with the ligand TMPyP4 showed distinct binding profiles in cellular and dilute environments. In dilute solution, TMPyP4 binds to the top tetrad of wtTel23c, while it binds to the loop in cellular environments. The RED method offers an efficient strategy for producing stable isotope-labeled ssDNA, opening new avenues for studying G4 structures and their ligand interactions in complex biological contexts.

biochemistry↗

bioRxiv2025

Acetylation of Axonal G3BP1 through ELP3 Accelerates Axon Regeneration

Nerve injury triggers localized translation of axonal mRNAs to respond to injury and nerve regeneration. The core stress granule protein G3BP1 sequesters axonal mRNAs in granules before and after axotomy. G3BP1 granule disassembly can be regulated by post-translational modifications, including phosphorylation of S149 phosphorylation and acetylation of human K376 (mouse K374). Axonal G3BP1 undergoes phosphorylation after axotomy, but acetylation of G3BP1 in axons was unknown. Here we show that rodent G3BP1 undergoes K374 acetylation after axotomy is ELP3-dependent, which enhances axonal protein synthesis, accelerates nerve regeneration, and supports functional recovery. ELP3-depleted neurons exhibit reduced axon growth and increased axonal G3BP1 granules. The proximal axons degenerate rapidly despite maintaining soma connectivity, an effect prevented by expression of acetylmimetic G3BP1.Together, these findings identify G3BP1 acetylation via ELP3 as a critical regulator of both axonal regeneration and neuronal resilience, revealing a post-translational mechanism that links stress granule regulation to neuronal repair and protection.

neuroscience↗

bioRxiv2025

Genomic and genetic insights into speciation and pigment pattern diversification in Danio fishes

The Danioninae subfamily of teleost fishes boasts up to four hundred distinct species that have evolved to display a stunning diversity of morphological forms. Here we use newly assembled genome sequences of four laboratory and wild zebrafish strains as well as eleven species of the Danio and Danionella genera to explore their phylogenetic history and the genetic basis of pigment pattern diversification. Phylogenomic analyses uncover extensive introgression and incomplete lineage sorting that have obscured phylogenetic relationships within Danio and corroborate an ancient hybrid origin of zebrafish. Whereas D. rerio inherited ancestral horizontal stripes, relatives repeatedly evolved spots and vertical bars. Interspecific complementation tests reveal functional divergence of the adhesion molecule gene igsf11 and the gap junction gene gja5b between the striped zebrafish and Danio species with divergent patterns. Comparative genomic and transcriptomic analyses suggest that protein and regulatory evolution have accompanied pigment pattern diversification. Our analyses elucidate complex genetic changes underlying the phylogenetic history and morphological diversification in the Danio genus. Resolved phylogenetic relationships, available genome assemblies, transcriptomes, and genetic tractability establish Danio fish species as excellent models for biomedical research in vertebrates.

genomics↗

bioRxiv2025

Convergent utilization of APN receptor by hedgehog merbecoviruses

Dipeptidyl peptidase-4 (DPP4) and angiotensin-converting enzyme 2 (ACE2) are well-established receptors for merbecoviruses, yet the receptor usage of merbecoviruses of European and Asian hedgehogs (EriCoVs) remains unknown. Here, by testing hedgehog orthologs of known coronavirus receptors, we identify hedgehog aminopeptidase N (APN) as a functional receptor for EriCoVs. Analysis of 94 APN orthologs indicates that EriCoVs have a limited host range, primarily utilizing hedgehog APN and, to a lesser extent, APN from certain felids, shaped by specific determinants at the virus-receptor interface. Cryo-EM reveals an APN-binding mode distinct from those used by alpha- and deltacoronaviruses. Functional assays indicate that hedgehog transmembrane serine protease 2 (TMPRSS2) enhances spike activation and promotes pseudovirus entry. Neutralizing antibodies targeting RBD and APN were developed and could effectively block EriCoV pseudovirus entry and propagation. These findings reveal an unexpected convergent evolution of APN utilization among merbecovirus, establishing a foundation for risk assessment and countermeasure development. Graphic abstractConvergent utilization of hedgehog APN by EriCoVs O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/676546v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@1ea334aorg.highwire.dtl.DTLVardef@cd53bforg.highwire.dtl.DTLVardef@352102org.highwire.dtl.DTLVardef@a1eed_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

Unveiling the Chain Mediation Model of Sleep Quality and Fatigue in Linking Subjective Exercise Experience to Depression in Adolescent

While the positive correlation between physical exercise and depression has been widely replicated in cross-sectional research, the prognostic value of subjective exercise experience for depression continues to be disputed, and the mediating processes are not well understood. This study aims to elucidate the predictive role of subjective exercise experience in depression and examine the chain mediating effects of sleep quality and fatigue. We administered validated self-report questionnaires to assess these constructs in a sample of 538 Chinese high school students. The results demonstrated that adolescents depressive symptoms are influenced by subjective exercise experience, and this effect mediated through two independent pathways: sleep quality and fatigue. Moreover, subjective exercise experience can predict adolescent depression via either the sleep quality pathway or the fatigue pathway. The identification of mediating dual pathways provides empirical support for developing targeted exercise interventions that specifically address sleep disturbances and fatigue management in depressed adolescents.

physiology↗

bioRxiv2025

The growth and pathogenesis of Citrobacter rodentium is compromised by disrupted mucin sugar pathways that accumulate N-acetylglucosamine 6-phosphate

Many enteric bacterial pathogens, including the attaching/effacing (A/E) Escherichia coli strains, cause acute gastroenteritis in humans. Considering the highly competitive nature of the mammalian gastrointestinal (GI) tract, these pathogens must rely on specific metabolic adaptations to establish successful infections. We hypothesized that A/E pathogens exploit host-derived nutrients within GI mucus, including the monosaccharides N-acetylglucosamine (GlcNAc) and N-acetylneuraminic acid (NeuNAc) to fuel their pathogenesis. Using Citrobacter rodentium, a murine-specific A/E pathogen, we disrupted both GlcNAc and NeuNAc catabolism by deleting nagA, which encodes the GlcNAc-6-phosphate (GlcNAc-6P) deacetylase that converts GlcNAc-6P into glucosamine-6-phosphate (GlcN-6P). The {Delta}nagA mutant displayed dramatically impaired colonization in C57BL/6J mice and accumulated significant levels of GlcNAc-6P, unlike the {Delta}mana strain, a mutant lacking all GlcNAc and NeuNAc transporters, suggesting that the attenuation was due to sugar-phosphate stress rather than nutrient deprivation alone. Supplementation with glucosamine (GlcN) restored growth, indicating that dysregulated GlcN-6P synthesis, rather than GlcNAc-6P toxicity, underlies the defect. Furthermore, {Delta}nagA exhibited increased susceptibility to several cell wall-dependent stress conditions, in concert with compromised peptidoglycan biosynthesis due to reduced UDP-GlcNAc synthesis. These findings reveal a previously unrecognized metabolic vulnerability in C. rodentium and suggest that targeting sugar-phosphate stress responses may provide a new therapeutic strategy against GI bacterial pathogens. ImportanceEnteric pathogens like Citrobacter rodentium can exploit sugars, including N-acetylglucosamine and N-acetylneuraminic acid, derived from intestinal mucus to grow and infect their hosts. This study shows that disruption of mucin-derived sugar catabolism impairs the fitness of C. rodentium in infecting the murine intestine by causing the accumulation of a toxic intermediate of mucin sugar metabolism. Rather than impaired nutrient acquisition, the bacteria are impaired due to the buildup of N-acetylglucosamine-6-phosphate, which depletes substrates for peptidoglycan synthesis. This metabolic bottleneck weakens the bacterial cell wall, making the pathogen more sensitive to environmental stress. These findings identify a conserved metabolic stress response that could be targeted to combat enteric pathogen infections.

microbiology↗

bioRxiv2025

Light-Activated Nucleic Acid Amplification Systems Using Photo-caged DNA Polymerase or Primers

Precise control over nucleic acid amplification is essential for achieving reliable, quantitative, high-throughput, and multiplexed molecular diagnostics, particularly in point-of-care and field settings. However, conventional isothermal amplification methods, especially rapid assays at ambient temperature such as recombinase-aided amplification (RAA), suffer from spontaneous initiation and lack of synchronization across parallel reactions. Here, we report light-activatable RAA systems employing two distinct photocaging strategies to achieve spatiotemporal control. In the first, a photocaged DNA polymerase was engineered via site-specific incorporation of p-azido-L-phenylalanine and conjugation with a 2-nitrobenzyl-modified ssDNA blocker through click chemistry. This approach offers high stability, making it advantageous for long-term storage and lyophilized formats. In the second, 5'-nitrobenzyl-modified primers were synthesized to block hybridization or extension until UV activation, offering operational simplicity and rapid integration into existing workflows. Both strategies independently suppressed background activity in the dark and restored full amplification efficiency upon 365 nm UV exposure. The systems exhibited high sensitivity, low background, and compatibility with portable diagnostics. A custom-built device integrating UV activation and real-time fluorescence detection enabled seamless, on-demand operation. This modular platform provides flexible light-gated amplification solutions, allowing the selection of polymerase- or primer-based caging according to storage stability or workflow requirements, thereby advancing precise and field-ready molecular diagnostics.

molecular biology↗

bioRxiv2025

Single-cell transcriptome sequencing for opening the blood-brain barrier through specific mode electroacupuncture stimulation

BackgroundThe blood-brain barrier (BBB) interferes with the treatment of central nervous system disorders owing to the complexity of its structure and restrictive function. Thus, it is challenging to develop central nervous system drug delivery strategies. Specific mode electroacupuncture (EA) stimulation can effectively open the BBB in rats. MethodsHere, we used single-cell RNA sequencing (scRNA-seq) to comprehensively map the cell population in the Sprague-Dawley rat cerebral cortex. ResultsWe identified 23 cell subsets and eight types of cells in the brain by cell annotation. scRNA-seq revealed transcriptional changes in the cerebral cortex under EA. ConclusionsOur findings offer valuable insights into the molecular and cellular modifications in the brain resulting from EA intervention and serve as a resource for drug delivery across healthy and diseased states. Innovative approaches to enhance BBB opening will lead to more effective therapeutic plans and enhanced drug delivery.

neuroscience↗

bioRxiv2025

Exploring polycyclic scaffolds as adamantane replacements in M2 channel inhibitors of Influenza A virus

The increasing resistance of influenza A viruses to adamantane-based antivirals underscores the need for new inhibitors targeting both wild-type (WT) and mutant M2 ion channels. Here, we report the synthesis and biological evaluation of polycyclic cage amines designed to replace the adamantane scaffold as M2 inhibitors. These include ring-contracted and ring-expanded analogues, evaluated both as primary amines and as aryl-/heteroaryl-substituted derivatives. Most of the polycyclic amines inhibited the WT M2 channel as demonstrated by electrophysiological assays. Among them, compound 10, a 3,4,8,9-tetramethyltetracyclo[4.4.0.03..0.]decan-1-amine, emerged as a triple blocker active against M2 WT, M2 L27F, and M2 V27A channels. In contrast, compound 6c, a noradamantane-isoxazole derivative, showed selective inhibition of the S31N mutant. Although no antiviral activity was observed against influenza A virus in infected cell assays, both compounds 6c and 10 displayed significant antiviral activity against human coronavirus 229E. Furthermore, compound 10 demonstrated favourable pharmacokinetic properties. MD simulations show that noradamantane 6c binds inside the M2 S31N pore, with its ammonium forming H-bonds to Asn31 and the isoxazole positioned near Val27, restricting water entry. In contrast, larger polycyclic amines likely cannot access the pore due to steric hindrance.

pharmacology and toxicology↗

bioRxiv2025

Bidirectional regulation of glycoprotein nonmetastatic melanoma protein B by β-glucocerebrosidase deficiency in GBA1 isogenic dopaminergic neurons from a patient with Gaucher disease and parkinsonism

Variants in GBA1 are common genetic risk factors for several synucleinopathies. The increased risk has been attributed to the toxic effects of misfolded glucocerebrosidase (GCase) (gain-of-function), and the accumulation of lipid substrates due to reduced enzyme activity (loss-of-function). To delineate GBA1 pathogenicity, an iPSC line was generated from a patient with both type 1 Gaucher disease (GBA1: N370S/N370S; p.N409S/p.N409S) and Parkinson disease (PD). From this line, we created a reverted wild-type (WT) line and a GBA1 knockout (KO) line to eliminate misfolded GCase and intensify lipid accumulation. N370S/N370S and KO dopaminergic neurons (DANs) exhibited decreasing GCase levels and progressive accumulation of lipid substrates compared to WT DANs. Notably, the expression of GPNMB, whose levels correlate with PD risk, was upregulated by the mild lipid accumulation in N370S/N370S DANs but disrupted in KO DANs. These findings refine the loss-of-function mechanism by associating PD risk levels of GPNMB with lipid levels specific to GBA1 risk variants.

neuroscience↗

bioRxiv2025

Cryo-EM Structure of the Erlin1/2 Complex Reveals a Dynamic Scaffold for Membrane Protein Sequestration and Microdomain Assembly

The SPFH (Stomatin, Prohibitin, Flotillin, and HflK/C) family of proteins are key scaffolding components involved in the organization of functional membrane microdomains (FMMs) across various subcellular membranes, including those of the endoplasmic reticulum (ER) and mitochondria, which are characterized by a low content of saturated lipids. Among this protein family, the erlin1/2 complex is specifically located on the ER membrane. Previous studies have shown that the erlin1/2 complex plays an essential role in the ER-associated degradation (ERAD) pathway, mediating the ubiquitin-dependent degradation of various proteins such as inositol 1,4,5-trisphosphate receptors (InsP3Rs), which are important calcium ion transporters on the ER membrane. However, the molecular mechanisms underlying erlin-mediated FMMs organization and its role in ERAD remain poorly understood. In this study, we determined the single-particle cryo-electron microscopy (cryo-EM) structure of the erlin1/2 complex under different detergent conditions. Our findings reveal that the erlin1/2 complex forms a 26-mer cage-like structure, composed of alternating erlin1 and erlin2 subunits. The erlin1/2 complex defines a nanodomain on the ER membrane, which could recruit various types of proteins to both the interior and exterior membrane regions of the cage. By caging cargo proteins, the erlin1/2 complex physically secludes them from their binding partners, leading to a potential halt in their function. Moreover, individual cages can further interact with one another, facilitating the organization of FMMs of different sizes on the ER membrane. These dynamic properties may play a general and critical role in various processes occurring on the ER, including viral replication, positioning the erlin1/2 complex as a promising new target for antiviral drug development.

biophysics↗

bioRxiv2025

Spatial metabolic gradients in the liver and small intestine

Mammalian organs are composed of cells, whose properties differ depending upon their spatial location. Gene expression in liver varies between periportal and pericentral hepatocytes1-3, and in intestine from crypts to villus tips4,5. A key element of tissue spatial organization is likely metabolic, but direct assessments of spatial metabolism remain limited. Here we map spatial metabolic gradients in murine liver and intestine. We developed an integrated experimental-computational workflow using MALDI imaging mass spectrometry, isotope tracing, and deep-learning artificial intelligence. Most measured metabolites (> 95%) showed significant spatial concentration gradients in liver lobules and intestinal villi. In the liver, tricarboxylic acid (TCA)-cycle metabolites and their labeling from both glutamine and lactate localized periportally. Energy-stress metabolites including adenosine monophosphate (AMP) also localized periportally, consistent with high periportal energy demand. In intestine, the TCA intermediates malate (tip) and citrate (crypt) showed opposite spatial patterns, which aligned with higher glutamine catabolism in tips and lactate oxidation in crypts based on isotope tracing. Finally, we mapped the fate of the obesogenic dietary sugar fructose. In the intestine, oral fructose was catabolized faster in the villus bottom than the tips. In the liver, fructose-derived carbon accumulated pericentrally as fructose-1-phosphate and triggered pericentral adenosine triphosphate (ATP) depletion. Thus, we both provide foundational knowledge regarding intestine and liver metabolic organization and identify fructose-induced focal derangements in liver metabolism.

biochemistry↗

bioRxiv2025

TIP-seq: A Single-cell Multiomics Approach for Simultaneous Transcriptome and Intracellular Protein Profiling

Single-cell multiomics technologies have significantly advanced our understanding of cellular heterogeneity; however, the concurrent profiling of mRNA transcripts and target proteins continues to pose a substantial challenge. To bridge the gap between single-cell sequencing and proteomic methods, we developed an innovative single-cell multiomics methodology, termed TIP-seq, which facilitates the simultaneous profiling of the transcriptome and intracellular proteins without prior cell manipulation. In TIP-seq, microfluidic technology is leveraged to integrate oligonucleotide-labeled antibodies with hydrogel beads, allowing for the capture of mRNAs and proteins from individual cells within droplets, thereby enabling high-throughput and precise dual-omics data acquisition. When applied to lung cell lines and non-small cell lung cancer (NSCLC) tissues, TIP-seq analysis revealed notable cellular heterogeneity and molecular dynamics, emphasizing the distinct immune cell interactions within NSCLC tissues. Key immune checkpoint interactions in NSCLC, such as SPP1-CD44, NECTIN2-TIGIT, and NECTIN2-CTLA4, along with functional alterations in tumor-associated dendritic cells (DCs) and T cells, were identified via TIP-seq, underscoring their pivotal roles in mediating immune suppression within the tumor microenvironment. Collectively, TIP-seq represents a powerful methodology for identifying novel therapeutic targets and biomarkers, thereby holding significant potential for the advancement of precision medicine in the treatment of lung cancer and other complex diseases.

biochemistry↗

bioRxiv2025

The China Brain Multi-omics Atlas Project (CBMAP)

The China Brain Multi-omics Atlas Project (CBMAP) aims to generate a comprehensive molecular reference map of over 1,000 human brains (Phase I), spanning a broad age range and multiple regions in China, to address the underrepresentation of East Asian populations in brain research. By integrating genome, epigenome, transcriptome, proteome (including multiple post-translational modifications), and metabolome data, CBMAP is set to provide a rich and invaluable resource for investigating the molecular underpinnings of aging-related brain phenotypes and neuropsychiatric disorders. Leveraging high-throughput omics data and advanced technologies, such as spatial transcriptomics, proteomics, and single-nucleus 3D chromatin structure analysis, this atlas will serve as a crucial resource for the brain science community, illuminating disease mechanisms and enhancing the utility of data from genome-wide association studies (GWAS). CBMAP is also poised to accelerate drug discovery and precision medicine for brain disorders.

neuroscience↗