Biology subjects

Zhu, L.

Publications and source records attributed to Zhu, L..

At least 109 records · Page 6Linked to original sources

bioRxiv2025

High-Quality Cell Capture Reveals Transcriptomic Changes After Single-Axon Injury of Mauthner Cells

In vivo single-cell capture methods based on micropipettes are essential for correlating morphological characteristics with transcriptomic profiling under physiological conditions. However, they often suffer from significant contamination of off-target cells. Consequently, we developed Hip-seq, which significantly reduces heavily contaminated cells, decreases contamination levels, improves cell reproducibility, and enhances data analysis accuracy compared to patch-seq. Using Hip-seq, we found that axon regeneration failure could be due to abnormal activation of translation and the circadian clock. Axon-regenerable central neurons reactivated axon development-related genes during regeneration. And one-to-one associated analysis helped identify pro-regenerative genes.

neuroscience↗

bioRxiv2025

C9orf50 is a Targetable Spliceosome Regulator for Cancer Immunotherapy

Cancer cells harbor cell-intrinsic programs capable of sculpting immunogenic landscapes, yet molecular brakes that enforce immune evasion remain poorly defined. Here, we identify C9ORF50, a previously uncharacterized intrinsically disordered protein, as a liquid-liquid phase separation-driven regulator of RNA processing and actionable immunotherapy target. Genetic ablation of C9ORF50 induces selective intron retention in spliceosome component transcripts, leading to cytoplasmic accumulation of immunogenic double-stranded RNA (dsRNA). This dsRNA activates type I interferon pathway that in turn orchestrates a chemokine secretory program critical for T cell recruitment. The resultant enhancement of tumor immunogenicity and reprogramming of tumor immune microenvironment drives robust antitumor immunity, effectively converting immunologically "cold" tumors to "hot" phenotypes. Therapeutic targeting of C9ORF50 via RNA interference achieved robust tumor suppression in syngeneic models, suggesting its translational relevance. Notably, C9ORF50 exhibits tumor-predominant expression, with minimal baseline levels detected in healthy tissues or immune cell populations, underscoring its potential safety as a therapeutic target. Our study not only identifies C9ORF50 as a novel LLPS-dependent regulator of RNA splicing but also establishes it as a promising and potentially safe therapeutic target for cancer immunotherapy.

cancer biology↗

bioRxiv2025

Exogenous melatonin mitigates drought stress by promoting the living cortical area of roots in cotton

The root cortex plays a critical role in water absorption, influencing root function and metabolic activity. However, the effects of melatonin on root cortical cells and its role in drought resistance remain unclear. This study examines the impact of exogenous melatonin on the root cortex of cotton under drought stress, focusing on its relationship with water uptake and drought resilience. Cotton plants were treated with 8% PEG6000 for drought stress and 100 {micro}M melatonin by foliar application. The results demonstrated that melatonin application significantly increased the living cortical area of roots under drought stress, with notable increases of 26.34% and 59.00% at distances of 1 cm and 13 cm from the root tip, respectively. Melatonin also enhanced root cortical thickness, promoted osmotic regulation, increased respiratory enzyme activity, and improved water and nutrient uptake. Furthermore, melatonin application promoted both root and shoot growth. Notably, the living cortical area positively correlated with osmotic substance accumulation, root respiration, and absorption capacity under drought conditions. In conclusion, exogenous melatonin alleviates drought-induced damage by enhancing the living cortical area, optimizing osmotic regulation, and improving root absorption, thus promoting cotton growth and drought resistance. These findings highlight melatonin as a promising regulator for enhancing drought resistance. HighlightExogenous melatonin increases root cortical integrity of cotton roots under drought stress, improves the absorption of water and nutrients, promotes the growth of cotton, and enhances its drought resistance.

physiology↗

bioRxiv2025

Optimized antibody with W32I mutation enhances antiviral efficacy against influenza

The influenza virus has caused a global pandemic with significant morbidity and mortality, highlighting the need to optimize antibodies for improved antiviral efficacy. The 3E1 antibody effectively neutralizes influenza subtypes H1 and H5 by inhibiting acid-induced conformational changes of hemagglutinin (HA). This study aimed to optimize the antibodys bioactivity by modifying amino acid residues, resulting in single-point mutants (3E1-L [W32I], 3E1-H [F103I]) and a double mutant (3E1-H+L [F103I, W32I]). The binding affinity, neutralizing activity, and antiviral mechanisms of the mutants were evaluated. Notably, the 3E1-L mutant showed significantly enhanced antiviral activity against H1N1 and H3N2 compared to wild-type 3E1, inhibiting both viral entry and release. The prophylactic and therapeutic efficacy of the 3E1-L mutant was validated. Molecular dynamics simulations of the 3E1-L/HA complex showed that the W32I mutation reduces steric hindrance between tryptophan at position 32 and the complementarity-determining region (CDR) L1 loop of HA. In conclusion, the W32I substitution enhances the antiviral activity of wild-type 3E1, making the optimization of 3E1-L a promising strategy for developing more effective influenza therapies.

immunology↗

bioRxiv2025

A method for inducing a senescence trend in mesenchymal stem cells using D-galactose

The aging of the body is accompanied by a decline in tissue function, and this decline mainly stems from the aging of tissue stem cells. Therefore, they play a crucial role in the aging of the body.This study explores the biological characteristics of senescent hUCMSCs by establishing a replicative senescence model of hUCMSCs and a rapid senescence model induced by D - galactose (D-Gal), and analyzing the proliferative capacity, cell viability, cell cycle, pluripotency, and reactive oxygen species (ROS) levels of senescent hUCMSCs.

cell biology↗

bioRxiv2025

Detection of Diffuse to Focal Myocardial Fibrosis by Cardiovascular Magnetic Resonance Against Histology in Mini-Swine

BackgroundMyocardial fibrosis predicts adverse outcomes in myocardial infarction (MI) and other cardiovascular conditions. Cardiovascular magnetic resonance (CMR) can non-invasively detect focal and diffuse myocardial fibrosis, but comprehensive validation against histology remains scarce. AimsTo assess the comparative diagnostic performance of CMR methods in detecting myocardial fibrosis, using a mini-swine model and histology as gold standard. MethodsEighteen mini-swine (16 MI; 2 healthy) underwent CMR cine, LGE, T1- and ECV-mapping. Two commonly-used T1-mapping methods - MOLLI 5(3)3 and ShMOLLI 5(1)1(1)1 - were included. Pathological sections were categorized as infarcted, peri-infarct, remote and healthy myocardium based on triphenyl tetrazolium chloride staining. Fibrotic burden was quantified by collagen volume fraction (CVF) into severe (CVF[≥]30%), moderate (CVF=10-25%), and mild (CVF=3-14%). The relationships between LGE, T1, ECV and CVF, and diagnostic performance using area-under-the-curve (AUC), were analyzed. ResultsFor detecting severe fibrosis, LGE, T1 and ECV all had excellent diagnostic performance (AUC: LGE=0.93, ECVShMOLLI=0.96, T1ShMOLLI=0.91, T1MOLLI=0.93, ECVMOLLI=0.88). ECVShMOLLI showed significantly better discriminatory accuracy than ECVMOLLI in detecting severe fibrosis and MI (both p<0.05), with the highest correlation to CVF (ECVShMOLLI r=0.86, ECVMOLLI r=0.82, T1ShMOLLI r=0.77, T1MOLLI r=0.77, semi-quantitative LGE r=0.75). Only T1ShMOLLI and ECVShMOLLI, but not LGE or T1MOLLI/ECVMOLLI, differentiated remote myocardium with mild fibrosis (CVF=8.23%) from healthy myocardium (CVF=2.01%). ConclusionsCMR can detect severe to mild myocardial fibrosis as validated against histology. For low-grade fibrosis, T1-mapping significantly outperformed LGE. Choice of CMR methodologies matters for myocardial fibrosis detection, which has importance for clinical trial design.

pathology↗

bioRxiv2025

MiRNA Locker: A Modularized DNA Assembly As miRNA Inhibitors

MicroRNAs (miRNAs) are vital post-transcriptional regulators that govern key cellular processes such as proliferation, migration, and apoptosis. Current loss-of-function approaches, including chemically modified antisense oligonucleotides (ASOs), face significant challenges, including high costs, limited scalability, and off-target effects. To overcome these limitations, we developed "miRNA Locker", a novel miRNA inhibition platform created using the Overlapped Oligo Assembly (OOA) method. This innovative platform constructs highly stable dumbbell-shaped single-stranded DNA structures, offering improved target specificity, scalability, and cost-effectiveness. Using miR-214 as a proof-of-concept target, we demonstrated that miRNA Lockers effectively bind Argonaute-miRNA complexes, reduce miRNA levels, and induce downstream changes in gene expression and cellular phenotypes, surpassing the performance of commercial antagomirs. Furthermore, applying miRNA Lockers to miR-654 validated the regulatory role of miR-654 in modulating RNF8 expression and promoting epithelial-mesenchymal transition (EMT) in lung cancer cells. Our results highlight the potential of miRNA Lockers as a versatile tool for studying miRNA function and advancing miRNA-based therapies. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/632138v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@c6ac1eorg.highwire.dtl.DTLVardef@14e2698org.highwire.dtl.DTLVardef@1c7d84aorg.highwire.dtl.DTLVardef@148f9c1_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2025

Gut meta-virome reveals potential zoonotic pathogens and environmental RNA viruses carried by non-human primates

The majority of human infectious diseases originate from mammals and are inherently zoonotic. Non-human primates (NHPs) are not only carriers of many zoonotic pathogens, but also the best intermediary for virus shift from harmless to harmful due to their similar phylogenetic relationship with humans. Knowledge of NHP viral composition and its underlying information can therefore provide an assessment of the risk of cross-species transmission and spillover of zoonotic diseases. However, studies that have successfully eliminated the effects of different natural habitat environments on viral carriage have been limited, making it difficult to identify which zoonotic viruses and potentially species-barrier-crossing viruses are carried by widely distributed NHP hosts. Here, we analyze viruses excreted in feces from NHP hosts and reveal the presence of possible zoonotic pathogens. Most of the viruses found come from plants that are eaten by them. Analysis of the evolutionary relationships of potential pathogens suggests that other clinical isolates are genetically correlated to HIV, PBV, and EV we identified. This study provides foundational data for surveillance of NHP enteroviruses that could help to be challenging to track potential human viruses carried by NHP in the absence of clinical surveillance. ImportanceAs a result of internationalization and other factors, many viruses have broken through the limits of geographical units and spread into human society, causing many emerging and re-emerging infectious disease hazards. However, the virus spreads and is by no means infectious to humans overnight. There is a phenomenon of host shift, in which the virus does not necessarily cause disease in an intermediate host, but causes significant damage when transmitted to humans. We focus on captive non-human primates, close relatives of humans in cities, because the phenomenon of host shifts is related to both biological similarity and geographical proximity of the host. Primates may carry zoonotic viruses and viruses that are currently incapable of infecting humans but have evolved with pathogenic potential. In summary, comprehensive viral surveillance and screening of captive nonhuman primates is necessary.

ecology↗

bioRxiv2024

A non-canonical glucose metabolic rewiring enables resistance to cancer targeted therapy

Targeting glucose metabolism for cancer therapy is a long-lasting pursuit but with disappointing translational success. Revelation of actionable distinctions between the malignancy traits to achieve selectivity is a prerequisite for fulfilling a therapeutic window. We discover a non-canonical glucose transporter GLUT6-facilitated, lactate-independent, glucose metabolic rewiring that selectively enables resistance to targeted therapy in lung cancer. Downstream, GLUT6 facilitated glucose influx and straying to methylglyoxal which dimerized KEAP1 and upregulated NRF2 pathway to confer resistance. Upstream, GLUT6 was transcriptionally upregulated by therapy-induced MAZ activation. Targeting GLUT6 prevented and overcame resistance to EGFR and KRAS inhibitors and the MAZ-GLUT6-NRF2 signaling correlated with clinical therapy response and relapse. Our findings uncover an unrecognized non-genetic, metabolic mechanism for drug resistance and a scenario specifically determined by a distinct glucose metabolic rewiring in cancer. The preferential dependance of the non-canonical, general-homeostasis-less-perturbing transporter GLUT6 implies a promise for resistance overcoming and for glucose metabolism-targeting strategy, two long and urgent quests.

cancer biology↗

bioRxiv2024

METTL7A improves bovine IVF embryo competence by attenuating oxidative stress

In vitro fertilization (IVF) is a widely used assisted reproductive technology to achieve a successful pregnancy. However, the acquisition of oxidative stress in embryo in vitro culture impairs its competence. Here, we demonstrated that a nuclear coding gene, methyltransferase- like protein 7A (METTL7A), improves the developmental potential of bovine embryos. We found that exogenous METTL7A modulates expression of genes involved in embryonic cell mitochondrial pathways and promotes trophectoderm development. Surprisingly, we discovered that METTL7A alleviates mitochondrial stress and DNA damage and promotes cell cycle progression during embryo cleavage. In summary, we have identified a novel mitochondria stress eliminating mechanism regulated by METTL7A that occurs during the acquisition of oxidative stress in embryo in vitro culture. This discovery lays the groundwork for the development of METTL7A as a promising therapeutic target for IVF embryo competence. Summary statement (Graphic abstract)We describe a molecule acts in the pre-implantation period to attenuate oxidative stress that enhances embryo development to the blastocyst stage and subsequent pregnancy in cattle. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/628915v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@12863c7org.highwire.dtl.DTLVardef@aec66aorg.highwire.dtl.DTLVardef@648ccaorg.highwire.dtl.DTLVardef@1572927_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2024

ABA increases fatty acids levels in apple roots to boost colonization by arbuscular mycorrhizal fungi

The roots of most land plants are in symbiosis with arbuscular mycorrhizal (AM) fungi. The fungus promotes nutrient uptake from the soil while receiving plant photosynthate as lipids and sugars. Nutrient exchange must be regulated by both partners, but the mechanisms underlying the regulation of lipid supplement from the plant to the AM fungus remain elusive. Here, we conducted a molecular study on the role of increased abscisic acid (ABA) levels during AM fungus infection in the roots of apple (Malus spp.). AM fungus induced the expression of two ABA synthesis genes, MdNCED3.1 and 3.2, in apple roots and increased the ABA content, which promoted the growth of the AM fungus. The effect of ABA on symbiosis was confirmed in transgenic apple roots either overexpressing or silencing MdNCED3.1 or MdNCED3.2. Transcriptome analysis and transgenic manipulation revealed that the transcription factor MdABF2 played a key role in the ABA-mediated formation of symbiosis during AM infection and that MdABF2 could regulate the expression levels of genes related to fatty acid (FA) synthesis (e.g., MdKASIII) and translocation (such as MdSTR2) in apple roots. Activation of these genes boosted the levels of available fatty acids in the roots and increased the AM fungal colonization and arbuscule development in the roots. These results revealed a molecular pathway in which positive regulation of FA synthesis and transport by the ABA signaling pathway increases supplementation to AM fungi and promotes AM symbiosis.

molecular biology↗

bioRxiv2024

scPrediXcan integrates advances in deep learning and single-cell data into a powerful cell-type-specific transcriptome-wide association study framework

Transcriptome-wide association studies (TWAS) help identify disease causing genes, but often fail to pinpoint disease mechanisms at the cellular level because of the limited sample sizes and sparsity of cell-type-specific expression data. Here we propose scPrediXcan which integrates state-of-the-art deep learning approaches that predict epigenetic features from DNA sequences with the canonical TWAS framework. Our prediction approach, ctPred, predicts cell-type-specific expression with high accuracy and captures complex gene regulatory grammar that linear models overlook. Applied to type 2 diabetes and systemic lupus erythematosus, scPrediXcan outperformed the canonical TWAS framework by identifying more candidate causal genes, explaining more genome-wide association studies (GWAS) loci, and providing insights into the cellular specificity of TWAS hits. Overall, our results demonstrate that scPrediXcan represents a significant advance, promising to deepen our understanding of the cellular mechanisms underlying complex diseases.

genetics↗

bioRxiv2024

Melanin concentrating hormone projections to the nucleus accumbens enhance the reward value of food consumption and do not induce feeding or REM sleep

Regulation of food intake and energy balance is critical to survival. Hunger develops as a response to energy deficit and drives food-seeking and consumption. However, motivations to eat are varied in nature, and promoted by factors other than energy deficit. When dysregulated, non-homeostatic drives to consume can contribute to disorders of food intake, adding to the increasing prevalence of restrictive eating disorders and obesity. Melanin-concentrating hormone (MCH) neurons have been implicated in the regulation of feeding behavior, in addition to a number of other fundamental behaviors including sleep, anxiety, and maternal behavior. Several studies suggest that MCH peptide increases food consumption, while studies of MCH neurons show effects only on cued feeding, and others show no effect of MCH neuron manipulation on feeding. MCH neurons have widespread projections to diverse downstream brain regions yet few studies have investigated the function of specific projections or differentiated the behaviors they regulate. Here we use optogenetics, in combination with different behavioral paradigms, to elucidate the role of MCH projections to the nucleus accumbens (NAc) in sleep and feeding behavior. We show that MCH neurons projecting to the NAc do not induce changes in baseline feeding or REM sleep, but do enhance the preference for a food paired with optogenetic stimulation. Furthermore, this effect is diminished in female mice relative to males, in line with previous results suggesting sex differences in the functional role of MCH neurons. These results suggest that MCH projections to the NAc can enhance the rewarding value of consumed food. Significance StatementWhile feeding is often driven by hunger, there are non-homeostatic reasons why animals consume food. Melanin-concentrating hormone (MCH) neurons have been implicated in the regulation of many fundamental behaviors, including feeding, sleep and reward. They project broadly throughout the brain, suggesting that they may mediate this diverse set of behaviors independently via specific projections to downstream regions. We used optogenetic activation of MCH neurons and their projections to the nucleus accumbens (NAc) in combination with complex behavioral paradigms to demonstrate that MCH projections to the NAc do not induce baseline feeding or increases in REM sleep but do enhance the value of a paired food. These results suggest that MCH neurons contribute to non-homeostatic consumption via projections to the NAc.

neuroscience↗

bioRxiv2024

Geographic-specific Diversification of Vaginal Microbiota in China

The vaginal microbiota is pivotal to womens reproductive health, with significant geographic and ethnic heterogeneity suggesting evolutionary adaptations to environmental, climatic, and lifestyle factors. In this multi-centric study, we analyzed vaginal microbiome samples from women across five provinces in China, each characterized by distinct climatic, ethnic, and lifestyle traits. Our results indicate that the vaginal microbiota among Chinese women is characterized by low alpha diversity, with Lactobacillus crispatus being the dominant species in Community State Type (CST) I, especially in the northern regions. While most participants exhibited stable CSTs throughout their menstrual cycles, fluctuations were observed in some individuals. We also detected low-abundance bacterial species such as Fannyhesea vaginae and Sneathia vaginalis. Comparative genomic analysis of high-quality metagenome-assembled genomes of L. crispatus revealed minimal single nucleotide polymorphism (SNP) variations within individuals but substantial diversity between individuals, delineating a distinct separation between vaginal-associated populations (VAP) and gut-associated populations (GAP). These findings highlight the intricate dynamics of the vaginal microbiome, which are markedly influenced by geographic and individual determinants. This study offers an in-depth phylogenetic and genomic analysis of the vaginal microbiota among Chinese women, underscoring the imperative for further research into the impact of regional and individual variations on microbial community composition. Such knowledge could facilitate the development of personalized vaginal health management strategies that accommodate the unique microbiome profiles specific to different geographical regions. ImportanceThis study provides a groundbreaking analysis of the vaginal microbiota among Chinese women, offering insights into the population structure and evolutionary dynamics of this critical component of womens reproductive health. The research reveals that Lactobacillus crispatus, a key species in vaginal health, has a recent evolutionary emergence and exhibits significant geographic variation in prevalence, being more common in northern China. This discovery, along with the identification of distinct vaginal-associated and gut-associated populations, underscores the importance of understanding the vaginal microbiotas complexity. The findings have profound implications for developing personalized strategies to manage vaginal health, tailored to regional microbiome characteristics. This work not only advances our understanding of the vaginal microbiotas role in health and disease but also sets the stage for future research into the factors that shape microbial community structures across diverse populations.

microbiology↗

bioRxiv2024

Medial septum parvalbumin-expressing inhibitory neurons are impaired in a mouse model of Dravet Syndrome

Dravet syndrome (DS) is a severe neurodevelopmental disorder caused by pathogenic variants in the SCN1A gene, which encodes the voltage-gated sodium channel Nav1.1 subunit. Experiments in animal models of DS - including the haploinsufficient Scn1a+/- mouse - have identified impaired excitability of interneurons in the hippocampus and neocortex; this is thought to underlie the treatment-resistant epilepsy that is a prominent feature of the DS phenotype. However, additional brain structures, such as the medial septum (MS), also express SCN1A. The medial septum is known to play an important role in cognitive function and thus may contribute to the intellectual impairment that also characterizes DS. In this study, we employed whole cell patch clamp recordings in acute brain slices to characterize the electrophysiological properties of MS neurons in Scn1a+/- mice versus age-matched wild-type littermate controls. We found no discernible genotype-related differences in MS cholinergic (ChAT) neurons, but significant dysfunction within MS parvalbumin-expressing (PV) inhibitory neurons in Scn1a+/- mice. We further identified heterogeneity of firing patterns among MS PV neurons, and additional genotype differences in the proportion of subtype representation. These results confirm that the MS is an additional locus of pathology in DS, that may contribute to co- morbidities such as cognitive impairment.

neuroscience↗

bioRxiv2024

Revolutionizing large-scale DNA synthesis with microchip-based massive in parallel synthesis system

DNA synthesis serves as the fundamental enabling technology of engineering biology, aiming to provide DNA molecules of designed composition, length, and complexity at scale and low cost. Current high-throughput DNA synthesis technologies rely on intricate chip manufacturing and microfluidic systems to provide large-scale synthetic oligonucleotides, at the expense of low concentration and limited compatibility in the processing of longer DNA constructs assembly. Here, we report a microchip-based massive in parallel synthesis (mMPS), pioneering an "identification-sorting-synthesis-recycling" iteration mechanism to microchips for high throughput DNA synthesis. In comparison to microarray-based methods, we demonstrate that our method can increase the DNA product concentration by 4 magnitudes (to picomole-scale per sequence) and greatly simplifies the downstream processes for large-scale gene synthesis construction. By the construction of 1.97 million-diversity variant libraries that cover 1,254 human protein domains, we demonstrated the uniformity of the constructed variant libraries using mMPS-derived oligos is greatly improved, with amino acid distribution highly consistent as designed. In addition, by synthesizing 285 1kb-to-3kb genes with varying degrees of sequence complexity from previously reported strains A501 and 3DAC, potential ancestor of early archaea and bacteria, our result shows that the overall gene assembly success rate using mMPS-derived oligos is increased by 10-fold in comparison to other methods. Our mMPS technology holds the potential to close the gap between the quality and cost of writing DNA in increasing demand across many sectors of research and industrial activities.

synthetic biology↗

bioRxiv2024

Fucoidan-Copper Nanoparticles to Potentiate Synergistic Cancer Cell Cuproptosis and Immunotherapy

Cuproptosis, a newly characterized form of regulated cell death initiated by copper binding to lipoylated components of the tricarboxylic acid cycle, presents a promising target for cancer therapy. Here, we report the development of fucoidan-copper nanoparticles (Fu-Cu) that exploit this mechanism to selectively induce cytotoxicity in HuH-7 liver cancer cells. The Fu-Cu was synthesized using fucoidan, a sulfated polysaccharide with inherent anticancer properties, as a natural nanocarrier for copper ions. Characterization confirmed successful copper incorporation and the formation of stable nanoparticles. Fu-Cu treatment enhanced intracellular copper levels and oxidative stress, triggering cuproptosis mediated by mitochondrial carrier homolog 2. Knockout of ferredoxin 1 in HuH-7 cells mitigated the cytotoxic effects, underscoring its critical role in copper-induced cell death. In vivo studies using a subcutaneous tumor model in BALB/c nude mice demonstrated that Fu-Cu effectively inhibited tumor growth and stimulated antitumor immunity, evidenced by increased infiltration of T cells, natural killer cells, and macrophages within the tumor microenvironment. These findings highlight Fu-Cu as a novel therapeutic strategy for HCC, leveraging the mechanism of cuproptosis and immune activation to suppress tumor progression.

cancer biology↗

bioRxiv2024

Targeting long non-coding RNA RP11-502I4.3 delays the trend of angiogenesis in diabetic retinopathy

Based on our previous findings, we hypothesized that the long non-coding RNA RP11-502I4.3 may be involved in angiogenesis associated with Diabetic retinopathy (DR). We investigated the role of RP11-502I4.3 in DR by examining its regulation of vascular endothelial growth factor (VEGF). We assessed differences in RP11-502I4.3 expression between the normal control group and streptozotocin-induced diabetic rats or high glucose (HG)-stimulated human retinal microvascular endothelial cells (HRMECs). VEGF expression was measured with and without lentiviral vectors overexpressing RP11-502I4.3. We analyzed the structural and functional alterations related to DR. Our analysis revealed that RP11-502I4.3 expression was lower in the retinas of diabetic rats and in HG-stimulated HRMECs compared with normal glucose conditions. Overexpressing of RP11-502I4.3 resulted in decreased VEGF levels. Diabetic rats exhibited retinopathy characterized by thinning of the retinal layer thickness, structural changes in the inner and outer nuclear layers, a reduced count of retinal ganglion cells, and the presence of acellular capillaries. The proliferative activity, migration count, and tube formation ability of HG-treated HRMECs were significantly higher than those of the normal control group; however, these changes were delayed by RP11-502I4.3 overexpression. RP11-502I4.3 downregulation in DR appears to promote angiogenesis.

zoology↗