Biology subjects

Luo, J.

Publications and source records attributed to Luo, J..

At least 91 records · Page 5Linked to original sources

bioRxiv2025

Deficiency of Mesencephalic Astrocyte-derived Neurotrophic Factor Aggravates Acute Pancreatitis in Mice

Acute pancreatitis (AP) is a complex and potentially severe inflammatory disorder of the pancreas and is one of the most common causes of gastrointestinal hospitalization. Although environmental risk factors such as alcohol and gallstones are well recognized, only a subset of exposed individuals develop AP, suggesting that intrinsic factors, including genetic susceptibility, influence disease onset and progression. Endoplasmic reticulum (ER) stress has emerged as a key mechanism in AP pathogenesis, because ER is essential for protein synthesis, folding, degradation and secretion (proteostasis). Mesencephalic astrocyte-derived neurotrophic factor (MANF), an ER stress-inducible protein highly expressed in the pancreas, plays a critical role in maintaining proteostasis, yet its involvement in AP remains unclear. To investigate the functional role of MANF in AP, we generated pancreas-specific MANF knockout (MANF-KO) mice using the Cre/loxP system and subjected them to moderate experimental AP, that is caerulein- or alcohol-induced AP in mice. In the caerulein model, MANF deficiency exacerbated pancreatic injury in both sexes, as indicated by increased apoptosis (cleaved caspase-3, caspase-12), ER stress markers (eIF2, p-eIF2, GRP78), inflammation (IL-6, TNF), regenerative activity (Ki67), and pancreatic lipase levels. Notably, male MANF-KO mice exhibited enhanced inflammation (HMGB1), macrophage infiltration (CD68), and oxidative stress (DNP, HNE), which were not observed in females. In the alcoholic AP model, both male and female MANF-KO mice showed increased ER stress (p-IRE1, p-eIF2, GRP78), apoptosis, inflammation, macrophage infiltration, regeneration, and lipase levels, whereas elevated HMGB1 expression and oxidative stress again predominantly occurred in male MANF-KO mice. Together, these findings reveal a critical and sex-specific role for MANF in regulating pancreatic stress responses and inflammatory injury, supporting its potential contribution as a genetic factor in AP pathogenesis.

pathology↗

bioRxiv2025

Age-Related Alterations in the Expression of Mesencephalic Astrocyte-derived Neurotrophic Factor in the Brain and Their Impact on Neurobehavioral Functions

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic protein localized in the endoplasmic reticulum (ER) and pivotally involved in maintaining ER homeostasis. MANF plays an important role in mitigating neurodegenerative processes. Aging, the primary risk factor for neurodegenerative diseases (NDDs), is associated with significant alterations in ER function. The ER, central to protein synthesis, folding, degradation and secretion (proteostasis), experiences considerable stress in NDDs, which activates the unfolded protein response (UPR). We hypothesized that MANF and UPR is crucial for maintaining proteostasis during aging, but their efficacy declines with age, therefore increasing vulnerability to NDDs. We measured MANF levels in the brain and plasma of 1-, 4-, 11-, and 22-month-old male and female mice. A progressive decline of MANF levels was observed, with the lowest levels detected in 22 months. Reduced MANF expression was found in aged mice across several brain areas, including the cerebral cortex, olfactory bulb, thalamus, hypothalamus, hippocampus, and cerebellum. There was a sex difference in MANF levels in aged mice. Aging also altered the expression of UPR and MANF interacting proteins. Using cerebellar Purkinje cell (PC)-specific MANF deficient mice, we showed that MANF deficiency impaired motor coordination in female, but not male mice. MANF deficiency weakened spatial learning and memory in both male and female mice. Male MANF deficient mice displayed increased sociability, whereas female mice exhibit social withdrawal. Taken together, MANF expression in the brain declined with age and MANF deficiency impacted neurobehaviors in the aging animal in a sex-specific manner.

neuroscience↗

bioRxiv2025

Representation Transfer via Invariant Input-driven Neural Manifolds for Brain-inspired Computations

Domain adaptation is a core challenge for embodied AI deployed in unpredictable, noisy environments. Conventional deep models degrade under domain shifts and require costly retraining. Inspired by biological brains, we propose a modular framework where each module is a recurrent neural network pretrained via a simple, task-agnostic protocol to learn robust, transferable features. This shapes stable yet flexible representations as invariant input-driven continuous attractor manifolds embedded in high-dimensional latent space, supporting robust transfer and resilience to noise. At deployment, only a lightweight adapter needs training, enabling rapid few-shot adaptation. Evaluated on the DVS Gesture benchmark and a custom RGB rehabilitation dataset, our framework matches or surpasses leading C3D and ViViT models while using ten times fewer parameters and only one training epoch. By unifying biologically inspired attractor dynamics with cortical-like modular composition, our approach offers a practical path toward robust, continual adaptation for real-world embodied AI. TeaserInvariant input-driven attractors enable representation transfer and domain adaptation in brain-inspired AI.

neuroscience↗

bioRxiv2025

Integrating Artificial Intelligence-Driven Digital Pathology and Genomics to Establish Patient-Derived Organoids as a Novel Alternative Model for Drug Response in Head and Neck Cancer

Patient-derived organoids (PDOs) are emerging as advanced 3D ex vivo novel alternative method (NAM) preclinical models, offering significant advantages over traditional cell lines and monolayer cultures for therapeutic development. In this study, we established PDOs from surgically resected fresh tissues of human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) across anatomical sites, tumor T-categories, and sample types. These PDOs faithfully recapitulate the tumors pathology, mutational profile, and drug response. To enable rapid classification of PDO identity, we developed a new convolutional neural network (CNN) model, TransferNet-PDO, which accurately distinguished tumor versus normal PDOs in culture using digital histopathology images (AUC[≥]0.88). PDOs maintained stable cultures and were cryopreserved between passages 5 and 12. Immunohistochemistry (IHC) staining (PanCK, p63, Cytokeratin 13, Ki67) confirmed squamous phenotype and histologic aggression of the original tumor. For tumors harboring TP53 mutations by whole-exome sequencing (WES), PDOs retained the corresponding p53 functional status as confirmed by IHC (enhanced or loss of expression). Somatic mutational landscape revealed that PDOs preserved driver somatic mutations, copy number variations (CNVs), and clonal architecture including low-prevalence subclones. Drug sensitivity assessment of PDOs showed that cisplatin reduced cell viability, whereas cetuximab and lenvatinib had minimal effects. Chemoradiation led to greater tumor organoid killing compared to radiation or chemotherapy alone. This study presents an integrated HNSCC PDO platform combining tissue biobanking, organoid establishment, multi-omics characterization, functional drug screening, and AI-driven histopathologic classification, providing a comprehensive and scalable system for translational cancer research.

cancer biology↗

bioRxiv2025

Spatial Transcriptomics Analysis Uncovers ER stress in MANF-deficient Purkinje Cells Underlying Alcohol-induced Cerebellar Vulnerability in Mice

Cerebellar Purkinje cells (PCs) are among the most vulnerable neurons to alcohol neurotoxicity. Alcohol can induce endoplasmic reticulum (ER) stress and alter the structure and function of PCs. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress inducible protein highly expressed in PCs. It is neuroprotective in various pathological conditions where ER stress is induced. However, it is unknown whether MANF plays a role in protecting PCs from alcohol induced ER stress. In this study, we generated PC-specific MANF knockout (KO) mouse model to test the hypothesis that MANF deficient PCs are more susceptible to binge alcohol exposure induced ER stress and neurodegeneration in the adult brain. We found that PC-specific MANF KO animals show moderate motor function deficit, which was exacerbated by alcohol exposure. Interestingly, female KOs were more sensitive than male KOs to alcohol-induced motor function impairments. In accordance with the behavior changes, alcohol exposure also caused UPR activation, increased intranuclear expression of calcium binding protein Calbindin, and PC degeneration in female but not male MANF KO mice. Spatial transcriptomics and high throughput in situ analyses demonstrated that MANF deficiency altered the transcriptomic landscape in PCs in a sex-specific manner and triggered the expression of genes involved in protein folding and response to ER stress. These results suggests that MANF KO PCs may be predisposed with a higher risk to UPR activation and ER stress in a sex dependent manner, contributing to their vulnerability to alcohol neurotoxicity.

molecular biology↗

bioRxiv2025

{Psi}-Atlas: an integrated atlas for pseudouridine epitranscriptome

Pseudouridine ({Psi}) is a C5 glycoside isomer of uridine, formed by breaking the N1 glycosyl bond and undergoing a 180{degrees} base rotation. This modification stands as one of the most widespread post-transcriptional alterations in RNA and is universally distributed among diverse RNA species. The pervasiveness of this modification enhances RNA structural integrity, bestows unique structural and functional attributes upon the RNA molecules it adorns, and facilitates additional hydrogen bonding. However, the absence of a convenient and integrated intuitive visualization database encompassing all currently reported species and RNA types is evident. Here, we present the {Psi}-Atlas, an extensive database meticulously curated for the comprehensive collection and annotation of RNA pseudouridine. This database encompasses 554,895 pseudouridine modification sites across various RNA categories, including mRNA, ncRNA, tRNA, rRNA, and others, in 55 distinct species reported in current literature. The sequencing methodologies employed comprise the next-generation sequencing (NGS) techniques such as {Psi}-Seq, Pseudo-Seq, CeU-Seq, PSI-Seq, RBS-Seq, HydraPsiSeq, BID-Seq, PRAISE-Seq, as well as third-generation sequencing methods like Direct RNA sequencing (DRS). {Psi}-Atlas as the most comprehensive and integrated resource for RNA pseudouridine modifications to date. And the {Psi}-Atlas database offers an intuitive interface for information display and a myriad of analytical tools, including PsiVar and PsiFinder. In essence, this platform serves as a robust search and visualization tool for the study of pseudouridylation in epitranscriptomics. {Psi}-Atlas is available at https://rnainformatics.org.cn/PsiAtlas.

bioinformatics↗

bioRxiv2025

Alcohol Disrupts Neural Differentiation Through Endoplasmic Reticulum Stress and PERK Pathway Activation

Prenatal alcohol exposure (PAE) can lead to fetal alcohol spectrum disorder (FASD), a condition marked by developmental brain defects that result in neurobehavioral and cognitive impairments. However, the underlying molecular mechanisms remain poorly understood. Brain development is a highly regulated process, with neurogenesis playing a crucial role. A key stage in this process is neural differentiation, which is essential for proper brain function. This study aims to investigate how alcohol disrupts neural differentiation. NE-4C cells, a neural stem cell line derived from the mouse embryonic brain, were utilized as an in vitro model. As an in vivo model, pregnant mice were exposed to alcohol between gestation days 14 and 16, after which newly formed neurons in the ventricular zone (VZ) were analyzed. To examine the role of endoplasmic reticulum (ER) stress, tunicamycin (TM), and MANF-deficient NE-4C cells were employed. Neural differentiation was assessed using immunofluorescence, immunoblotting and flow cytometry. Alcohol impaired the differentiation of NE-4C cells into neurons and astrocytes without impacting cell migration. It also induced ER stress, preferably activating the PERK pathway. Similarly, ER stress caused by TM and MANF deficiency disrupted neural differentiation and activated PERK. Inhibiting PERK mitigated alcohol-induced impairment of neuronal differentiation. PAE decreased the number of newly formed neurons in the VZ of fetal brain while having little effects on cell survival and proliferation. Inhibiting PERK partially reversed the reduction of new neurons caused by PAE. Thus, alcohol-induced ER stress, particularly PERK activation, may contribute to impaired neurogenesis linked to FASD.

pharmacology and toxicology↗

bioRxiv2025

EGR1 drives sex-differences in glioblastoma tumorigenicity

Although progress has been made in treating glioblastoma (GBM), with fewer than 5% of patients surviving more than 5 years after diagnosis. For reasons that are not well understood, females are roughly 60% as likely as males to develop GBM, and female patients consistently respond better to treatment than do males. Understanding the molecular etiology of these sex differences in tumor progression and resiliency to treatment could reveal potent new therapeutic targets, ultimately improving survival of both male and female GBM patients. Here we show that the transcription factor Egr1 is a primary mediator of sex differences in multiple GBM tumorigenic phenotypes. In multivariate analysis, high levels of EGR1 expression are correlated with shortened survival for male GBM patients only. To investigate the molecular mechanisms underlying this sex difference, we performed a genomic analysis in our established ex vivo murine model of sex differences, which showed that the transcription factors Egr1 and Klf5 preferentially recruit the transcriptional activator Brd4 to enhancers in male cells relative to female cells, explaining a previously made observation that Brd4 inhibitors reverse sex differences in GBM. Next, using murine and human primary GBM cells, we demonstrated that the small molecule compound SR18662, which downregulates Egr1 and its downstream target Klf5, abrogates GBM growth, migration, invasion, clonogenicity, and response to radiation in a sex-biased fashion. Finally, we knocked down Egr1 and Klf5 via CRISPRi in both untreated and SR18662-treated GBM cells to reveal the sex-biased anti-tumorigenic effects of SR18662 were largely due to Egr1 downregulation, independent of Klf5 downregulation. This result was replicated in vivo. Our results strongly indicate that an Egr1 regulon is a key determinant of sex differences in GBM. As EGR1 is implicated in the cancer biology of many cancers that also display sex differences in incidence and treatment response, our results are likely to be broadly applicable in oncology.

cancer biology↗

bioRxiv2025

Synaptic proteins that aggregate and degrade slower with aging accumulate in microglia

Neurodegenerative diseases affect 1 in 12 people globally and remain incurable. Central to their pathogenesis is a loss of neuronal protein maintenance and the accumulation of protein aggregates with aging1,2. We engineered bioorthogonal tools3 which allowed us to tag the nascent neuronal proteome and study its turnover with aging, its propensity to aggregate, and its interaction with microglia. We discovered neuronal proteins degraded on average twice as slowly between 4- and 24-month-old mice with individual protein stability differing between brain regions. Further, we describe the aged neuronal aggregome encompassing 574 proteins, nearly 30% of which showed reduced degradation. The aggregome includes well-known proteins linked to disease as well as a trove of proteins previously not associated with neurodegeneration. Unexpectedly, we found 274 neuronal proteins accumulated in microglia with 65% also displaying reduced degradation and/or aggregation with age. Among these proteins, synaptic proteins were highly enriched, suggesting a cascade of events emanating from impaired synaptic protein turnover and aggregation to the disposal of these proteins, possibly by the engulfment of synapses by microglia. These findings reveal the dramatic loss of neuronal proteome maintenance with aging which could be causal for age-related synapse loss and cognitive decline.

neuroscience↗

bioRxiv2025

ECCFP: a consecutive full pass based bioinformatic analysis for eccDNA identification using Nanopore sequencing data

It is commonly known that extrachromosomal circular DNA (eccDNA) has the potential as a molecular marker because of its close relationship with cancer progress and its prevalent existence in eukaryotic organisms. The mainstream technique of eccDNA detection is using high-throughput sequencing supported by bioinformatics analysis. Although these have various analysis pipelines for sequencing data, they are restricted by sequencing platforms or have shortcomings in accuracy and efficiency. To address these limitations, we design ECCFP, a bioinformatic analysis pipeline that detects eccDNAs amplified by rolling circle amplification (RCA) from long-read sequencing data and outputs eccDNA genomic coordinates and consensus sequences. This pipeline proposes a rigorous algorithm to retain all consecutive full passes derived from individual reads to obtain candidate eccDNAs, followed by systematic consolidation of candidate eccDNAs to detect unique eccDNAs. Using simulated datasets and experimental eccDNA sequencing datasets, we estimated ECCFP in several aspects and compared it with other existing pipelines. It exhibits a marked reduction in false positive rates compared with eccDNA_RCA_nanopore and superior sensitivity relative to CReSIL and FLED. Besides, inverse PCR and Sanger sequencing further validated the existence and accuracy of the position of detected eccDNAs by ECCFP. Collectively, ECCFP provides a more efficient choice for eccDNA detection from long-read sequencing data.

bioinformatics↗

bioRxiv2025

Triple-N Dataset: Non-human Primate Neural Responses to Natural Scenes

Understanding the neural mechanisms of visual perception requires data that encompass both large-scale cortical activity and the fine-grained dynamics of individual neurons. While the Natural Scenes Dataset (NSD) has provided substantial insights into visual processing in humans (Allen et al., 2022), its reliance on functional magnetic resonance imaging (fMRI) limits the exploration of individual neuron contributions. To bridge this gap, we present a new dataset: the Triple-N (Non-human Primate Neural Responses to Natural Scenes) dataset, which extends the NSD framework to non-human primates, incorporating single-neuron activity and fMRI recorded from the inferotemporal (IT) cortex. Using Neuropixels probes, we recorded neural responses from five macaques as they passively viewed 1,000 shared NSD images. The dataset includes 59 sessions across 27 sub-regions, capturing over 30,000 visual responsive units. Many recordings were obtained from fMRI-defined category-selective regions, such as face-, body-, scene-, and color-selective areas. Our dataset enables in-depth exploration of neural responses at multiple levels - from population dynamics to single-neuron activity, providing new insights into various aspects of visual processing, including the heterogeneity of object selectivity within functional regions and the temporal dynamics of responses to natural images. Furthermore, the dataset enables joint cross-species analyses, by integrating the macaque neural recordings with human fMRI data, offering a framework for comparing and aligning visual representations across primate species. Overall, our dataset provides a valuable resource for advancing our understanding of visual perception, bridging the gap between large-scale neuroimaging and fine-grained electrophysiological signals, while also facilitating the development of computational models of the high-level visual system.

neuroscience↗

bioRxiv2025

Codon-dependent regulation of mRNA translation and stability by ZC3H7A and ZC3H7B RNA-binding proteins

Decelerated translation elongation caused by non-optimal codons can reduce mRNA stability through codon optimality-mediated mRNA degradation. A key element of this process is the coupling of sensing the mRNA codon usage with the regulation of translation efficiency and stability. We report that two paralog RNA-binding proteins (ZC3H7A and ZC3H7B), which are only found in Chordates, preferentially bind to and reduce the stability and translation of mRNAs enriched in non-optimal codons with A/U at their wobble sites (A/U3 codons). ZC3H7A/B engage with ribosomes that lack elongation factors and induce mRNA degradation or block translation initiation through their interactions with the CCR4-NOT and the GIGYF2/4EHP translation repressor complex, respectively. Depletion of ZC3H7A/B or 4EHP impairs the repression of non-optimal A/U3-rich mRNAs. This study provides insights into a unique mechanism in higher eukaryotes that couples codon usage with the regulation of translation efficiency and mRNA stability.

cell biology↗

bioRxiv2025

Super Recombinator (SuRe): An in vivo recombination system for scalable and efficient transgene assembly at a single genomic locus

The capacity to engineer organisms with multiple transgenic components is crucial to synthetic biology and basic biology research. For the former field, transgenic organisms allow the creation of novel biological functions; for the latter, such organisms provide potent means of dissecting complex biological pathways. However, the size limitations of a single transgenesis event and challenges associated with the assembly of multiple DNA fragments hinder the efficient integration of multiple transgenes. To overcome these hurdles, here we introduce a building block for synthetic design termed an integrated genetic array (IGA), which incorporates all genetic components into a single locus to prevent their separation during genetic manipulations. Since the natural recombination rate for genes located in the same locus is near zero, to construct IGAs we developed the Super Recombinator (SuRe) system, which uses CRISPR/Cas9, alone or in combination with site-specific serine recombinases, for in vivo transgene recombination at a single genomic locus. SuRe effectively doubles the number of elements assembled in each recombination round, exponentially accelerating IGA construction. By preventing the separation of transgenic elements, SuRe greatly reduces screening burdens, as validated here through studies of Drosophila melanogaster and Caenorhabditis elegans. To optimize SuRe, we compared CRISPR/Cas9-induced homology-directed recombination to site-specific recombination using various serine recombinases. Optimized versions of SuRe achieved efficiency and fidelity values near their theoretical maxima and allowed the generation of recombinant products up to 4.2 Mbp in size in Drosophila. Using SuRe, we created fruit flies with 12 transgenic elements for fluorescence voltage imaging of neural activity in precisely defined cell-types. Mathematical modeling of the scalability of SuRe to large transgene assemblies showed that integration times and gene assembly workloads respectively scale logarithmically and linearly with the number of transgenes, both major improvements over conventional approaches. Overall, SuRe enables the efficient integration of multiple genes at individual loci, up to the chromosomal scale.

synthetic biology↗

bioRxiv2025

TUCL-Seq for miRNA single molecule sequencing

MicroRNAs (miRNAs) are pivotal regulatory molecules in gene expression, and their precise quantification is essential for elucidating their roles in diverse biological processes. This research paper introduces a pioneering workflow for the single molecule sequencing (SMS) of miRNA, integrating advanced miRNA sample preparation with SMS sequencing. Central to our approach is TUCL-Seq, which is an automated, on-chip miRNA library preparation method designed to streamline the sequencing process. This innovative approach incorporates the addition of sequencing adaptor to RNA samples in solution, and converts it to cDNA on a sequencing flow cell for sequencing. Coupled with single molecule sequencing instrument and base-call software, our workflow significantly reduces sample-to-result time, and decreases the need for manual interventions compared to traditional SMS and next-generation sequencing methods. We demonstrate the efficacy of TUCL-Seq by accurately quantifying synthetic miRNA samples with a 24-hour workflow, showcasing its potential for high-throughput miRNA profiling. Our findings highlight the promise of this integrated workflow for advancing miRNA research and applications in diagnostics and therapeutics.

biochemistry↗

bioRxiv2025

Binomial order is a speech marker of psychosis and thought disorder

Thought disorder, characterized by disruptions in syntactic and semantic elements in language, is a core symptom of psychotic disorders. Understanding this language impairment is key to uncovering the underlying neuropathology and predicting treatment outcomes for individuals with schizophrenia and other psychotic disorders. Binomial ordering preferences (e.g. "salt and pepper" instead of "pepper and salt"), may be a quantifiable correlate of thought disorder and underlying linguistic impairments. We tested whether atypical binomial ordering can serve as a linguistic marker for psychosis symptoms. Participants with early-stage psychotic disorders and controls were recruited, and video-recorded interviews were transcribed for analysis. Identified binomial pairs were assessed using both the Google N-gram database and a logistic regression model to determine ordering preferences. Results showed that while both psychotic participants and controls preferred conventional binomial orderings, participants with psychotic disorders exhibited a higher rate of atypical binomial orderings. The use of atypical orderings was correlated with thought disorder, but not with other psychiatric symptoms or medications. Tracking binomial ordering can be a valuable marker of thought disorder but future studies are needed to determine whether this link remains stable or if it changes with disease progression.

neuroscience↗

bioRxiv2025

Deep Spatial Sequencing Revealing Differential Immune Responses in Human Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most lethal cancers for humans. HCC is highly heterogeneous. In this study, we performed ultra-depth ([~]1 million reads per spot) spatial sequencing on a case of HCC. Sixteen distinct spatial expression clusters were identified. Each of these clusters was spatially contiguous and had distinct gene expression patterns. In contrast, benign liver tissues showed minimal heterogeneity in terms of gene expression. Numerous immune cell-enriched spots were identified in both HCC and benign liver regions. Cells adjacent to these immune cell-enriched spots showed significant alterations in their gene expression patterns. Interestingly, the responses of HCC cells to the nearby immune cells were significantly more intense and broader, while the responses of benign liver cells to immune cells were somewhat narrow and muted, suggesting an innate difference in immune cell activities towards HCC cells in comparison with benign liver cells. When standard-depth sequencing was performed, significant numbers of genes and pathways that were associated with these changes disappeared. Qualitative differences in some pathways were also found. These results suggest that deep spatial sequencing may help to uncover previously unidentified mechanisms of liver cancer development.

cancer biology↗

bioRxiv2025

Experimental transmission of African swine fever virus by Ornithodoros lahorensis (Acari: Argasidae)

African swine fever (ASF) is an acute, highly contagious infectious disease that affects both domestic and wild pigs, caused by the African swine fever virus (ASFV). ASFV is the only known DNA virus transmitted by arthropod vectors, with acute infection in pigs leading to morbidity and mortality rates as high as 100%.The virus can persist in a transmission cycle among wild boars, soft ticks, and domestic pigs. To date, nine Ornithodoros spp. have been confirmed to be capable of transmitting ASFV worldwide. However, the potential soft tick species capable of transmitting ASFV in China remain unclear. In this study, we compared the ability of Argasidae spp. Ornithodoros lahorensis and Argas persicus, as well as Ixodidae spp., Haemaphysalis longicornis, Rhipicephalus sanguineus and Dermacentor silvarum, to transmit ASFV via animal transmission experiments. The results revealed that O. lahorensis soft ticks, but not A. persicus or Ixodes, could act as competent vectors through transstadial and transovarial transmission of ASFV. The virus titers horizontally transmitted ASFV to ticks were 105.83, 106.59 and 104.31, HAD50/ml respectively. These viruses were detected in the nymphs developed from larvae, adults developed from nymphs, and larvae hatched from eggs by adults. Thus, O. lahorensis ticks are likely an important natural vectors of ASFV, although both mammalian and tick hosts are likely required for the maintenance of ASFV in the sylvatic cycle.

microbiology↗

bioRxiv2025

Synthetic derivatives of vinpocetine as antiproliferative agents

Vincamine is an indole alkaloid initially isolated from plants of the Vinca genus and has previously been demonstrated to have antioxidant, hypoglycemic, and hypolipidemic activities. Vinpocetine, a synthetic derivative of vincamine with an enhanced pharmacological profile, has demonstrated promising antiproliferative properties. While previously reported vinpocetine derivatives have undergone extensive investigation for their pharmacological properties, the role of the E-ring ethyl ester in the anticancer properties of compounds with this scaffold has not yet been fully described. Here, we report the antiproliferative activity of two vinpocetine analogs with modifications at the E-ring. MTT assays revealed that reduction of the ethyl ester to an alcohol exhibited strong dose-dependent antiproliferative activity across five mammalian cell lines, but did not induce significant markers of apoptosis or necrotic death as determined by FITC/Annexin V and cell cycle flow cytometry, respectively. We further observe that vinpocetine and both analogs exhibit dose-dependent modulation of a TCF/LEF reporter cell, which appears to be decoupled from trends in antiproliferative activity Altogether, this work demonstrates the potential for E-ring modifications of vinpocetine as anticancer agents.

cancer biology↗