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Rong Fan

Publications and source records attributed to Rong Fan.

At least 19 recordsLinked to original sources
PubMed2025

The new frontier in understanding human and mammalian brain development.

Neurodevelopmental disorders that cause cognitive, behavioural or motor impairments affect around 15% of children and adolescents worldwide1, with diagnoses of profound autism and attention deficit hyperactivity disorder increasing in the USA and contributing to a major economic burden2,3. Yet the origins and mechanisms of these conditions remain poorly understood, limiting progress in therapies. Comprehensive cell atlases of the developing human brain, alongside those of model organisms such as mice and non-human primates, are now providing high-resolution measures of gene expression, cell-type abundance and spatial distribution. In this Perspective, we highlight recent studies that have identified novel developmental cell populations, revealed conserved and divergent patterns of cell genesis, migration and maturation across species, and begun testing hypotheses that link them to processes ranging from transcriptional control of cell fate specification to the emergence of complex behaviours. We present remaining conceptual and technical challenges and provide an outlook on how further studies of human and mammalian brain development can empower a deeper understanding of neurodevelopmental and neuropsychiatric disorders. Future efforts expanding to additional developmental stages, including adolescence, as well as whole-brain, multimodal and cross-species integration, will yield new insights into how development shapes the brain. These atlases promise to serve as essential references for unravelling mechanisms of brain function and disease vulnerability, and for advancing precision medicine.

Humans↗
PubMed2025

Exploring endothelial cell environments across organs in spatially resolved omics data.

Endothelial cells are ubiquitously present in the human body and line the luminal surface of blood and lymphatic vessels. The oxygen-dependence of cells impacts their proximity to blood vessels, and consequently, to endothelial cells depending on their functional properties and priorities. This paper presents cell-to-nearest-endothelial-cell distance distributions for various cell types using 399 spatially resolved omics datasets from 14 studies comprising 12 tissue types with a total of 47,349,496 cells. Additionally, we developed an open-source web-based interactive tool, Cell Distance Explorer, that allows researchers to interactively visualize cell graphs and linkages in 2D and 3D datasets. Finally, we present a hierarchical neighborhood analysis focused on the endothelial cell neighborhoods in small and large intestine datasets. This paper provides an open-access resource (datasets, tools, and analyses) to characterize and compare cell distances and cell neighborhoods in spatially resolved omics data.

Journal Article↗
PubMed2024

Integration of Imaging-based and Sequencing-based Spatial Omics Mapping on the Same Tissue Section via DBiTplus.

Spatially mapping the transcriptome and proteome in the same tissue section can significantly advance our understanding of heterogeneous cellular processes and connect cell type to function. Here, we present Deterministic Barcoding in Tissue sequencing plus (DBiTplus), an integrative multi-modality spatial omics approach that combines sequencing-based spatial transcriptomics and image-based spatial protein profiling on the same tissue section to enable both single-cell resolution cell typing and genome-scale interrogation of biological pathways. DBiTplus begins with in situ reverse transcription for cDNA synthesis, microfluidic delivery of DNA oligos for spatial barcoding, retrieval of barcoded cDNA using RNaseH, an enzyme that selectively degrades RNA in an RNA-DNA hybrid, preserving the intact tissue section for high-plex protein imaging with CODEX. We developed computational pipelines to register data from two distinct modalities. Performing both DBiT-seq and CODEX on the same tissue slide enables accurate cell typing in each spatial transcriptome spot and subsequently image-guided decomposition to generate single-cell resolved spatial transcriptome atlases. DBiTplus was applied to mouse embryos with limited protein markers but still demonstrated excellent integration for single-cell transcriptome decomposition, to normal human lymph nodes with high-plex protein profiling to yield a single-cell spatial transcriptome map, and to human lymphoma FFPE tissue to explore the mechanisms of lymphomagenesis and progression. DBiTplusCODEX is a unified workflow including integrative experimental procedure and computational innovation for spatially resolved single-cell atlasing and exploration of biological pathways cell-by-cell at genome-scale.

Journal Article↗
PubMed2024

Integration of Imaging-based and Sequencing-based Spatial Omics Mapping on the Same Tissue Section via DBiTplus.

Spatially mapping the transcriptome and proteome in the same tissue section can significantly advance our understanding of heterogeneous cellular processes and connect cell type to function. Here, we present Deterministic Barcoding in Tissue sequencing plus (DBiTplus), an integrative multi-modality spatial omics approach that combines sequencing-based spatial transcriptomics and image-based spatial protein profiling on the same tissue section to enable both single-cell resolution cell typing and genome-scale interrogation of biological pathways. DBiTplus begins with in situ reverse transcription for cDNA synthesis, microfluidic delivery of DNA oligos for spatial barcoding, retrieval of barcoded cDNA using RNaseH, an enzyme that selectively degrades RNA in an RNA-DNA hybrid, preserving the intact tissue section for high-plex protein imaging with CODEX. We developed computational pipelines to register data from two distinct modalities. Performing both DBiT-seq and CODEX on the same tissue slide enables accurate cell typing in each spatial transcriptome spot and subsequently image-guided decomposition to generate single-cell resolved spatial transcriptome atlases. DBiTplus was applied to mouse embryos with limited protein markers but still demonstrated excellent integration for single-cell transcriptome decomposition, to normal human lymph nodes with high-plex protein profiling to yield a single-cell spatial transcriptome map, and to human lymphoma FFPE tissue to explore the mechanisms of lymphomagenesis and progression. DBiTplusCODEX is a unified workflow including integrative experimental procedure and computational innovation for spatially resolved single-cell atlasing and exploration of biological pathways cell-by-cell at genome-scale.

Journal Article↗
PubMed2006

In situ localization and substrate specificity of earthworm protease-II and protease-III-1 from Eisenia fetida.

Recently, the function in fibrinolysis of earthworm proteases has been studied. In our experiments, earthworm protease-II (EfP-II) and earthworm protease-III-1 (EfP-III-1) were isolated and purified from Eisenia fetida. As shown by the assay of sections of the earthworm on fibrin plates, the enzymic activity was mainly detected around the clitellum. In the presence of anti-EfP-II or anti-EfP-III-1 serum, the immunological signals of the two isozymes were clearly found in the anterior alimentary mucosa, suggesting that EfP-II and -III-1 are localized and expressed in intestinal epithelial cells. The Michaelis-Menten constant (K(m)) for EfP-III-1 reacting with BAEE is smaller (1.7x10(-5)M) in comparison with the K(m) values of other substrates such as Chromozym-Try and -TH (3.3-6.0x10(-5)M). This indicates that EfP-III-1 is a trypsin-like protein. EfP-II shows a strong trypsin-like, moderate elastase-like and weak chymotrypsin-like serine function. The relative broad substrate specificity of EfP-II and EfP-III-1 is consistent with their localization in the anterior alimentary canal where different micro-organisms and ingested proteins require to be digested.

Animals↗
PubMed2006

Inorganic nanotubes: a novel platform for nanofluidics.

Templating approaches are being developed for the synthesis of inorganic nanotubes, a novel platform for nanofluidics. Single crystalline semiconductor GaN nanotubes have been synthesized using an epitaxial casting method. The partial thermal oxidation of silicon nanowires leads to the synthesis of silica nanotubes. The dimension of these nanotubes can be precisely controlled during the templating process. These inorganic nanotubes can be integrated into metal-oxide solution field effect transistors (MOSolFETs), which exhibit rapid field effect modulation of ionic conductance. These nanofluidic devices have been further demonstrated to be useful for single-molecule sensing, as single DNA molecules can be readily detected either by charge effect or by geometry effect. These inorganic nanotubes will have great implications in subfemtoliter analytical technology and large-scale nanofluidic integration.

Chemistry, Inorganic↗
PubMed2005

Polarity switching and transient responses in single nanotube nanofluidic transistors.

We report the integration of inorganic nanotubes into metal-oxide-solution field effect transistors (FETs) which exhibit rapid field effect modulation of ionic conductance. Surface functionalization, analogous to doping in semiconductors, can switch the nanofluidic transistors from p-type to ambipolar and n-type field effect transistors. Transient study reveals the kinetics of field effect modulation is controlled by ion-exchange step. Nanofluidic FETs have potential implications in subfemtoliter analytical technology and large-scale nanofluidic integration.

Electric Conductivity↗
PubMed2005

Differential regulation of Abeta42-induced neuronal C1q synthesis and microglial activation.

Expression of C1q, an early component of the classical complement pathway, has been shown to be induced in neurons in hippocampal slices, following accumulation of exogenous Abeta42. Microglial activation was also detected by surface marker expression and cytokine production. To determine whether C1q induction was correlated with intraneuronal Abeta and/or microglial activation, D-(-)-2-amino-5-phosphonovaleric acid (APV, an NMDA receptor antagonist) and glycine-arginine-glycine-aspartic acid-serine-proline peptide (RGD, an integrin receptor antagonist), which blocks and enhances Abeta42 uptake, respectively, were assessed for their effect on neuronal C1q synthesis and microglial activation. APV inhibited, and RGD enhanced, microglial activation and neuronal C1q expression. However, addition of Abeta10-20 to slice cultures significantly reduced Abeta42 uptake and microglial activation, but did not alter the Abeta42-induced neuronal C1q expression. Furthermore, Abeta10-20 alone triggered C1q production in neurons, demonstrating that neither neuronal Abeta42 accumulation, nor microglial activation is required for neuronal C1q upregulation. These data are compatible with the hypothesis that multiple receptors are involved in Abeta injury and signaling in neurons. Some lead to neuronal C1q induction, whereas other(s) lead to intraneuronal accumulation of Abeta and/or stimulation of microglia.

Journal Article↗
PubMed2005

Controlled growth of Si nanowire arrays for device integration.

Silicon nanowires were synthesized, in a controlled manner, for their practical integration into devices. Gold colloids were used for nanowire synthesis by the vapor-liquid-solid growth mechanism. Using SiCl4 as the precursor gas in a chemical vapor deposition system, nanowire arrays were grown vertically aligned with respect to the substrate. By manipulating the colloid deposition on the substrate, highly controlled growth of aligned silicon nanowires was achieved. Nanowire arrays were synthesized with narrow size distributions dictated by the seeding colloids and with average diameters down to 39 nm. The density of wire growth was successfully varied from approximately 0.1-1.8 wires/microm2. Patterned deposition of the colloids led to confinement of the vertical nanowire growth to selected regions. In addition, Si nanowires were grown directly into microchannels to demonstrate the flexibility of the deposition technique. By controlling various aspects of nanowire growth, these methods will enable their efficient and economical incorporation into devices.

Colloids↗
PubMed2005

Electrostatic control of ions and molecules in nanofluidic transistors.

We report a nanofluidic transistor based on a metal-oxide-solution (MOSol) system that is similar to a metal-oxide-semiconductor field-effect transistor (MOSFET). Using a combination of fluorescence and electrical measurements, we demonstrate that gate voltage modulates the concentration of ions and molecules in the channel and controls the ionic conductance. Our results illustrate the efficacy of field-effect control in nanofluidics, which could have broad implications on integrated nanofluidic circuits for manipulation of ions and biomolecules in sub-femtoliter volumes.

Electrochemistry↗
PubMed2005

Effects of biological reactions and modifications on conductance of nanofluidic channels.

Conductance characteristics of nanofluidic channels (nanochannels) fall into two regimes: at low ionic concentrations, conductance is governed by surface charge while at high ionic concentrations it is determined by nanochannel geometry and bulk ionic concentration. We used aminosilane chemistry and streptavidin-biotin binding to study the effects of surface reactions on nanochannel conductance at different ionic concentrations. Immobilization of small molecules such as aminosilane or biotin mainly changes surface charge, affecting conductance only in the low concentration regime. However, streptavidin not only modifies surface charge but also occludes part of the channel, resulting in observable conductance changes in both regimes. Our observations reflect the interplay between the competing effects of charge and size of streptavidin on nanochannel conductance.

Biotin↗
PubMed2005

DNA translocation in inorganic nanotubes.

Inorganic nanotubes were successfully integrated with microfluidic systems to create nanofluidic devices for single DNA molecule sensing. Inorganic nanotubes are unique in their high aspect ratio and exhibit translocation characteristics in which the DNA is fully stretched. Transient changes of ionic current indicate DNA translocation events. A transition from current decrease to current enhancement during translocation was observed on changing the buffer concentration, suggesting interplay between electrostatic charge and geometric blockage effects. These inorganic nanotube nanofluidic devices represent a new platform for the study of single biomolecule translocation with the potential for integration into nanofluidic circuits.

DNA↗
PubMed2004

Defective DNA strand break repair after DNA damage in prostate cancer cells: implications for genetic instability and prostate cancer progression.

Together with cell cycle checkpoint control, DNA repair plays a pivotal role in protecting the genome from endogenous and exogenous DNA damage. Although increased genetic instability has been associated with prostate cancer progression, the relative role of DNA double-strand break repair in malignant versus normal prostate epithelial cells is not known. In this study, we determined the RNA and protein expression of a series of DNA double-strand break repair genes in both normal (PrEC-epithelial and PrSC-stromal) and malignant (LNCaP, DU-145, and PC-3) prostate cultures. Expression of genes downstream of ATM after ionizing radiation-induced DNA damage reflected the p53 status of the cell lines. In the malignant prostate cell lines, mRNA and protein levels of the Rad51, Xrcc3, Rad52, and Rad54 genes involved in homologous recombination were elevated approximately 2- to 5-fold in comparison to normal PrEC cells. The XRCC1, DNA polymerase-beta and -delta proteins were also elevated. There were no consistent differences in gene expression relating to the nonhomologous end-joining pathway. Despite increased expression of DNA repair genes, malignant prostate cancer cells had defective repair of DNA breaks, alkali-labile sites, and oxidative base damage. Furthermore, after ionizing radiation and mitomycin C treatment, chromosomal aberration assays confirmed that malignant prostate cells had defective DNA repair. This discordance between expression and function of DNA repair genes in malignant prostate cancer cells supports the hypothesis that prostate tumor progression may reflect aberrant DNA repair. Our findings support the development of novel treatment strategies designed to reinstate normal DNA repair in prostate cancer cells.

Animals↗
PubMed2004

Complement C1q expression induced by Abeta in rat hippocampal organotypic slice cultures.

Amyloid beta peptide (Abeta) is a major component of senile plaques, one of the principle pathological features in Alzheimer's disease (AD) brains. Fibrillar Abeta has been shown to bind C1 via C1q, the recognition component of the classical complement pathway, resulting in the activation of the complement pathway, thereby initiating an inflammatory cascade in the brain. C1q has also been shown to enhance phagocytic activities of microglia, which could benefit in clearance of apoptotic cells or cellular debris. To begin to define the role of C1q in tissue injury mediated by Abeta, we assessed the appearance of C1q in hippocampal slice cultures treated with freshly solubilized or fibrillar Abeta 1-42. Here we demonstrate a dose- and time-dependent uptake of exogenously applied Abeta by pyramidal neurons in organotypic slice cultures from rat hippocampus. Importantly, when slices were immunostained with antibody against rat C1q, a distinct reactivity for C1q in cells within the neuronal cell layer of cornu ammonis (CA) of hippocampus, primarily the CA1/CA2, was observed in the Abeta-treated slices. No such immunoreactivity was detected in untreated cultures or upon addition of control peptides. ELISA assays also showed an increase in C1q in tissue extracts from slices of the treated group. Similarly, the mRNA level of C1q in slices was increased within 24 h after Abeta treatment. These data demonstrate that upon exposure to Abeta, C1q is expressed in neurons in this organotypic system. The induction of C1q may be an early, perhaps beneficial, tissue or cellular response to injury triggered by particular pathogenic stimuli.

Amyloid beta-Peptides↗
PubMed2004

[The early warning signs of deterioration of severe acute respiratory syndrome].

OBJECTIVE: To explore the risk factors related to severe cases of severe acute respiratory syndrome (SARS) in order to find the early warning signs of deterioration of this disease. METHODS: Three hundred and fifty-five patients with severe SARS and 841 patients with regular SARS from Beijing were studied. RESULTS: Patients with elder age or with comorbid conditions were more likely to develop into severe cases. Data also showed the following characteristics in those severe cases: sustained fever, tachycardia (pulse rate being over 100 per minute), persistent decrease in lymphocytes (< 0.9 x 10(9)/L), increase in neutrophils (> 7.1 x 10(9)/L, 80%), and rapid changes in abnormal chest X-ray. The Cox proportional hazard multi-variable stepwise analysis showed the prediction model of severe SARS included age, comorbid disease, body temperature being still abnormal after 2 days of hospitalization, neutrophil percentage began to increase steadily to more than 80% after 3 days of hospitalization, counts of lymphocytes persisted < 0.9 x 10(9)/L after 4 days of hospitalization. CONCLUSIONS: According to patient's age, comorbid conditions, one can effectively predict the development of the severe SARS by closely monitoring temperature, pulse rate, the counts of lymphocytes and percent of neutrophils.

Adult↗
PubMed2004

[Promoter specificity of LE-ACS6 gene in LE-ACS6::GUS transgenic arabidopsis plants].

The LE-ACS6 gene encodes ACC synthase, the key enzyme of ethylene biosynthesis pathway. Accumulation of LE-ACS6 transcripts is concomitant with the system 1 ethylene production in the pre-climacteric tomato fruit, and both are down regulated by exogenous ethylene treatment. To elucidate the possible role of system 1 ethylene in plant development and investigate the promoter tissue specificity of LE-ACS6 gene, stable transformation of Arabidopsis with a LE-ACS6 promoter-GUS fusion construct by Agrobacterium method has been done. Histochemical localization of GUS activity and beta-glucuronidase enzyme assay in transgenic LE-ACS6::GUS plants showed strong expression of GUS in cotyledons and hypocotyls of 6 d seedlings, but no GUS activity was detected in roots. The GUS activity of 6 d seedling was increased significantly when treated with NAA 10(-4)mol/L. In 40 d rosette leaf LE-ACS6 promoter driven GUS gene was predominantly expressed in mature leaves. Lower level of GUS expression was detected in younger and older leaves. Wounding was found to increase GUS gene expression in transgenic leaves. Again, exogenous NAA was found to increase the GUS activity in wounded leaf tissue. Strong staining reaction was observed in the top part of rapidly growing stems. In different developmental stages of Arabidopsis seeds, "mature green" pods were strongly stained, but "ripening fruits" were not colored. These observations are concomitant with the system 1 ethylene production, suggesting a popular mechanism in regulating ethylene biosynthesis in different plants, at least in tomato and Arabidopsis.

Amino Acid Sequence↗
PubMed2003

[Epidemiologic features, clinical diagnosis and therapy of first cluster of patients with severe acute respiratory syndrome in Beijing area].

OBJECTIVE: Investigate the features of outbreak epidemic, clinical disease progression of the first SARS cases in Beijing and evaluate the efficacy of therapeutic regimen. METHODS: Twenty-nine patients (11 men and 18 women, 20 - 74 years old age range) were diagnosed with infectious SARS and admitted in our hospital from the March 5th to April 14th, 2003 in this study. The data of clinical presentation and disease progression of all the patients including index subject as the infectious SARS resource patient, her family infected members and 21 health care workers were abstracted. RESULTS: The first SARA outbreak in Beijing was characterized with the cluster feature of resource patient family members and health care providers. The incubation period ranged from 2 to 14 days. All the patients had a fever (temperature > 38 degrees C for over 24 hours) and other manifestations as reported before. Serial chest radiographs showed progressive pathologic air-space disease. Twenty patients showed the severe syndrome with various time ranged from 1 day to 14 days. Two patients died of progressive acute respiratory distress disease. The histologic analysis of one death patient showed diffuse alveolar damage in the two lungs. Twenty-six patients receiving the combined therapy including use of corticosteroid, antiviral ribavirin agents after the onset of symptoms and showed they had an acute self-limited disease course. The oldest patient (74 year old, male) received the healthy convalescent plasma infusion (50 ml) from recovered SARS subject and completely recovered within 21 days, having a shorter disease course. CONCLUSION: SARS is a kind of new self-limited and acute infectious disease. Early diagnosis, early isolation, early antiviral therapy for patients and efficient prevention for health care providers are urgently recommended. In particular, a combinational therapy of use of antiviral agents, preventive antibacterial antibiotics and pulsed dosage of corticosteroid can efficiently raise the clinical recovery rate and decrease mortality of SARS patients.

Adult↗