Biology subjects

Du, A.

Publications and source records attributed to Du, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Hydrogel microneedle patch for low-cost, colorimetric, continuous glucose monitoring

Diabetes is a chronic condition characterized by dysregulated blood glucose levels. Continuous glucose monitors (CGMs) enable minimally invasive, real-time monitoring of glucose levels, but broader access requires devices that are both effective and affordable. Popular CGMs such as Dexcom and FreeStyle Libre have high accuracy and are integrated with mobile applications to display real-time data and alerts but are limited by high cost. We developed a low-cost, electronic-free, microneedle hydrogel patch CGM that utilizes colorimetric detection to continuously monitor glucose levels. The proposed patch penetrates the skin and absorbs interstitial fluid (ISF) containing glucose. This glucose reacts with glucose oxidase (GOx) enzyme embedded in the hydrogel, producing gluconic acid and decreasing the pH of the hydrogel. As glucose levels increase, decreasing pH levels are reported by the loaded pH indicator bromocresol purple (BCP) via a color change from purple to yellow. This system was validated through a combination of in vitro experiments and COMSOL computational modeling to assess performance at physiologically relevant glucose concentrations. The resulting hydrogels demonstrated reversible and dynamic color changes in response to glucose levels ranging from 3.5-10 mmol/L (63-180 mg/dL), supporting their potential for continuous monitoring applications. A quantitative, image-based analysis method enabled estimation of glucose concentration from photographs, demonstrating strong predictive performance (RMSE=8.59 mg/dL, R2=0.94). Although optimization of mechanical strength and diffusion kinetics remain necessary, these findings highlight the promise of integrating colorimetric sensing with microneedle-based sampling for affordable, user-friendly glucose monitoring.

bioengineering↗

bioRxiv2026

Pattern-dependent low-intensity repetitive magnetic stimulation enhances spinal cord repair through modulation of neuroinflammation

Spinal cord injuries (SCI) are traumatic lesions of the spinal cord that commonly result from physical trauma. They can lead to severe and permanent impairments in motor, sensory, and/or autonomic functions, often resulting in paraplegia or tetraplegia. Despite advances in this field, effective restorative treatments for SCI remain limited. Over the past few years, several therapeutic strategies have been investigated to promote functional recovery after SCI, including neuromodulation approaches. Repetitive magnetic stimulation has emerged as a promising non-invasive strategy, with encouraging results when the stimulation is applied directly over the spinal cord. However, most studies have focused on high-intensity stimulation, while the key parameters underlying its therapeutic efficacy remain poorly understood. In this study, we investigated the effects of low-intensity repetitive trans-spinal magnetic stimulation (LI-rTSMS) following SCI in mice, using BMS, histological and RNA sequencing approaches. We aimed to determine the optimal protocol by comparing three stimulation patterns (10 Hz, iTBS and BHFS) and two coil sizes. Our results show that LI-rTSMS modulates the injured spinal cord in a pattern- and coil size-dependent manner, with distinct effects on fibrotic, neural, and inflammatory responses. Notably, the BHFS pattern produced the most marked tissue-remodeling effects, reducing fibrosis, reactive astrogliosis, and phagocytosis of myelin debris. This reduction in phagocytosis was also observed with a smaller coil, supporting an effect of LI-rTSMS on this process. We also identified distinct inflammatory signatures depending on the stimulation pattern and time after injury. Transcriptomic analyses revealed a common early inflammatory response to LI-rTSMS, whereas each stimulation pattern subsequently led to distinct molecular signatures after 2 weeks stimualtion. In addition, ependymal cells are known to retain endogenous regenerative potential following SCI. We found that LI-rTSMS increased ependymal cell proliferation and migration toward the lesion site, without detectable changes in their differentiation. Finally, we assessed c-Fos expression as a marker of early transcriptional changes in neurons. LI-rTSMS did not result in significant changes, suggesting that the observed effects were unlikely to be mediated by early, widespread neuronal activation. Altogether, this study provides mechanistic insights into the pattern-dependent effects of LI-rTSMS and highlights its potential role for future clinical translation.

neuroscience↗

bioRxiv2026

Juvenile AAV-Mediated MEF2C Gene Replacement Ameliorates Selected Phenotypes in Mef2c-Haploinsufficient Mice

MEF2C haploinsufficiency syndrome is a severe neurodevelopmental disorder for which no disease-directed treatment is available. We investigated whether neuron-directed adeno- associated virus (AAV) delivery of a functional MEF2C coding sequence during the juvenile period could modify disease-relevant phenotypes in mice heterozygous for a Mef2c exon 4 deletion. Transcript-level analysis identified a brain-enriched MEF2C isoform containing the 1 and {beta} regions (nMEF2C) and a skeletal-muscle-enriched isoform containing 2 but lacking {beta} (mMEF2C). Separate human-synapsin-driven AAV vectors encoding either isoform were administered at postnatal day 28. Control-treated Mef2c heterozygous mice retained baseline sociability but lacked social-novelty preference. Mice treated with either nMEF2C or mMEF2C displayed social-novelty preference and improved selected responses to a new social partner, whereas open-field effects were limited. nMEF2C replacement also corrected dark-phase wakefulness and non-rapid eye movement sleep abnormalities and modified selected state- dependent electroencephalographic ratios, without broadly changing absolute band amplitudes or social-contact electroencephalographic activity. Atlas-based whole-brain mapping revealed region-selective reductions in parvalbumin-immunoreactive profiles; direct statistical evidence of cellular rescue was confined to the secondary motor area after nMEF2C treatment. These findings show that selected MEF2C-dependent phenotypes remain modifiable during the juvenile period and support further optimization of MEF2C gene replacement with respect to isoform, dose, expression control, and cellular targeting.

neuroscience↗

bioRxiv2026

Long-read RNA-seq resolves isoform-level and context-specific regulatory architecture of complex traits in cattle

Traditional short-read RNA-seq lacks the resolution to fully capture full-length isoforms and complex alternative splicing, leaving a "missing regulation" gap in existing molecular atlases. Here, we present a population-scale, multi-omics dissection of bovine complex traits using matched deep whole-genome sequencing (30x), long-read (ONT) and short-read RNA-seq, as well as metabolome data from 432 dairy cows across four distinct lactation stages. We expanded the bovine transcript atlas with 13,177 novel isoforms and fine-mapped 1,088,900 regulatory effects across 11 diverse molecular phenotypes. Notably, long-read mapping uncovered 606 genes with isoform expression quantitative trait loci (12.8%, eQTL) and 1,116 genes with detailed splicing QTL (sQTL) (31.8%) that were missed by conventional short-read mapping. We further showed that lactation-specific regulation was profoundly mediated by the metabolic microenvironment (46.8%) and cellular composition (4.3%). Across genome-wide associations (GWAS) of 90 bovine complex traits, isoform-level and context-specific regulatory effects captured GWAS loci missed by short-read eQTL and sQTL analyses, increasing colocalized loci from 35.2% to 60.3%. These regulatory variants also exhibited evolutionary constraints with human immune and metabolic loci. Our study establishes an invaluable resource (https://cattleblr.farmgtex.org) demonstrating that long-read transcriptomics is essential for resolving the complexity of regulatory mechanisms underlying mammalian physiology.

genetics↗

bioRxiv2026

An ASXL3-thyroid hormone axis in parvalbumin interneurons controls autism-like behaviors

Pathogenic variants in ASXL3 underlie autism spectrum disorder (ASD), but how they perturb neural circuits and whether defects are reversible remain unclear. Here we show that Asxl3 haploinsufficiency in mice reduces cortical thickness and upper-layer projection neurons while increasing parvalbumin (PV) interneuron density and producing ASD-like behavioral abnormalities. Mechanistically, Asxl3 loss derepresses the thyroid hormone (TH)-inactivating enzyme DIO3 via altered histone H2A monoubiquitination, depleting brain TH. Conditional deletion of the TH receptor Thra in inhibitory neuron progenitors phenocopies the PV interneuron expansion, linking impaired TH signaling to PV circuit remodeling. Neonatal, but not adolescent, TH supplementation restores PV interneuron numbers and rescues behavior in Asxl3+/- mice, defining a critical early window for intervention. An intein-based AAV system that reconstitutes full-length ASXL3 normalizes cortical architecture and behavior in Asxl3+/- mice and drives efficient ASXL3 expression in non-human primate brain, establishing an ASXL3-TH-PV interneuron axis as a targetable pathway in ASD.

neuroscience↗

bioRxiv2026

Integrative multi-omics and multi-trait analysis prioritizes regulatory mechanisms and genes for metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition that progresses from simple steatosis to advanced fibrosis, significantly affecting liver function and systemic health. Despite its widespread impact, therapeutic options are limited, highlighting the urgent need for comprehensive exploration to identify potential therapeutic targets. In this study, we created an analysis pipeline anchored on liver gene expression, integrating differential meta-analysis of transcriptomic data across three MASLD stages, transcriptome-wide Mendelian randomization (MR), and transcriptome-wide association studies (TWAS), to identify 39 candidate genes potentially involved in MASLD progression. Furthermore, we prioritized these genes using a scoring system that incorporated gene expression-clinical phenotype correlation meta-analysis, proteome-wide association studies (PWAS), and external genetic data from the GWAS Catalog and ExPheWAS. Single-nucleus RNA sequencing (snRNA-seq) analysis of liver cells from healthy to cirrhotic stages revealed stage- and cell-type-specific expression patterns of these prioritized genes. Through experimental validation in a lipid overload hepatocyte model, we confirmed the role of MLIP in lipid metabolism. These findings, available through an interactive web portal (masldportal.net), provide valuable insights into MASLD mechanisms and offer an easy-accessible resource for the research community. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/706502v2_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@184c03eorg.highwire.dtl.DTLVardef@6965ccorg.highwire.dtl.DTLVardef@19a5937org.highwire.dtl.DTLVardef@576b53_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2025

AAV-mediated CSNK2B gene replacement rescues ASD-relevant phenotypes and establishes EEG biomarkers for translation in Csnk2b haploinsufficient mice

De novo CSNK2B variants are strongly associated with autism spectrum disorder (ASD) and early-onset epilepsy, yet in vivo therapeutic evidence and translatable biomarkers remain limited. We generated Csnk2b haploinsufficient (Csnk2b+/-) mice that recapitulate core clinical features--ASD-like social and cognitive deficits, heightened anxiety, spontaneous seizures, cortical and hippocampal structural compromise, and reduced PV-interneuron density with impaired cortical inhibition. Neonatal brain-wide AAV-PHP.eB-mediated CSNK2B replacement (hsyn or CAG promoters, retro-orbital P3) restored cortical/hippocampal structure, normalized neuronal numbers, prolonged survival, and ameliorated seizures and ASD-like behaviors with comparable efficacy across promoters. Critically, treatment also corrected quantitative EEG signatures that are directly deployable in human trials: theta and gamma band power were normalized, theta/gamma (and beta/gamma) ratios recovered, and inter-areal coherence and gamma-band effective connectivity were restored, indicating re-established excitation/inhibition balance and large-scale network coordination. These EEG endpoints constitute a compact, noninvasive biomarker panel of target engagement and physiological efficacy that can be harmonized with clinical EEG to support dose finding, early decision-making, and longitudinal monitoring in CSNK2B gene-therapy trials. Together, our data provide preclinical proof-of-concept that early AAV-mediated CSNK2B replacement is therapeutically effective and nominate band-limited EEG metrics as translational readouts to accelerate first-in-human studies for CSNK2B-linked neurodevelopmental disorders.

neuroscience↗

bioRxiv2025

Exacerbation of a Subset of Behavioral Phenotypes by Early Treatment with AAV FOXG1 Gene Replacement Therapy in a Mouse Model of FOXG1 Syndrome

FOXG1 syndrome is a severe neurodevelopmental disorder characterized by microcephaly, profound intellectual disability with communication deficits including lack of speech, impaired social interaction, increased anxiety, hyperkinetic/dyskinetic movements, seizures and abnormal sleep patterns. Mutations in a single allele of the FOXG1 gene cause disease, likely due to loss-of-function. However, current therapies do not target this root cause of FOXG1 syndrome and have little to modest therapeutic benefit on only a small subset of symptoms. Recently, we reported the beneficial effects of adeno-associated virus (AAV) human FOXG1 gene replacement therapy administered by intracerebroventricular (ICV) injection at postnatal day 6 (P6) on several behavioral deficits that are relevant to key features of human FOXG1 syndrome, in male FOXG1 mice that were engineered with a highly prevalent, patient-specific Q84P mutation. Here, we report the behavioral effects of AAV human FOXG1 gene replacement therapy administered by ICV injection in female as well as male mice and at an earlier age - postnatal day 2 (P2). Although the earlier studies had suggested that AAV FOXG1 gene replacement therapy is a promising approach for the treatment of a subset of functional deficits in human FOXG1 syndrome with no toxicity observations, our current study shows that certain motor behaviors can be negatively impacted or exacerbated by P2 treatment with AAV FOXG1 gene replacement therapy, in female but not male FOXG1 mice. Given these results, the risk-benefit balance of AAV FOXG1 gene replacement therapy in patients with FOXG1 syndrome should be carefully considered, especially in female patients.

neuroscience↗

bioRxiv2025

Repetitive Trans-spinal magnetic stimulation Promotes Repair in Inflammatory Spinal Cord Injury Through Sex-Dependent Immune Modulation

Spinal cord injuries (SCI), whether traumatic or inflammatory such as transverse myelitis (TM), are characterized by severe neuroinflammation, demyelination, and long-term disabilities. Current treatments remain limited, highlighting the need for novel non-invasive therapeutic approaches. Repetitive magnetic stimulation (RMS) has emerged as a promising strategy, but its mechanisms and efficacy in inflammatory contexts remain poorly described. Here, we investigated the effects of RMS applied as trans-spinal RMS (rTSMS) in a mouse model of focal spinal cord demyelination induced by lysophosphatidylcholine (LPC). When applied one day after LPC injection, rTSMS reduced inflammation, demyelination, and fibroglial scar formation, while promoting early locomotor recovery in both sexes. In contrast, when treatment was initiated three days after LPC injection, corresponding to the peak of motor deficits, rTSMS conferred tissue protection and functional benefits only in female mice. RNA sequencing analyses revealed sex-dependent immune modulation: in females, rTSMS primarily regulated adaptive T cell-related pathways, whereas in males, it mainly targeted innate immune responses such as neutrophil activity and phagocytosis. Complementary in vitro experiments using microglial and macrophage cultures further demonstrated that RMS modulates transcriptomic responses differently depending on cell type and inflammatory state. Specifically, RMS attenuated IL-1-induced pro-inflammatory signaling in macrophages and completely abolished these effects in microglia. Altogether, our findings establish rTSMS as a non-invasive therapy capable of reducing neuroinflammation and demyelination in inflammatory SCI, with pronounced sex-dependent effects. By uncovering distinct immune pathways engaged in male and female mice, this study provides mechanistic insights into rTSMS action and opens perspectives for its translational use in neuroinflammatory diseases.

neuroscience↗

bioRxiv2025

Behavioral Efficacy of AAV FOXG1 Gene Replacement Therapy in a Mouse Model of FOXG1 Syndrome

FOXG1 syndrome is a severe neurodevelopmental disorder characterized by microcephaly, profound intellectual disability with communication deficits including lack of speech, impaired social interaction, increased anxiety, hyperkinetic/dyskinetic movements, seizures and abnormal sleep patterns. Mutations in a single allele of the FOXG1 gene cause disease, likely due to loss-of-function. However, current therapies do not target this root cause of FOXG1 syndrome and have little to modest therapeutic benefit on only a small subset of symptoms. To date, the therapeutic potential of restoring FOXG1 levels in the brain with adeno-associated virus (AAV) FOXG1 gene replacement therapy has only been reported in a Foxg1fl/+;NexCre mouse model that lacks one Foxg1 allele but does not express mutant FOXG1, and with only neuroanatomical endpoints evaluated. Here, in a FOXG1 mouse model that contains a highly prevalent, patient-specific Q84P mutation, we describe the beneficial effects of AAV human FOXG1 gene replacement therapy administered by intracerebroventricular (ICV) injection at postnatal day 6 (P6) on several behavioral deficits that are relevant to key features of human FOXG1 syndrome. Our studies demonstrate that AAV FOXG1 gene replacement therapy is a promising approach for the treatment of a subset of functional deficits in human FOXG1 syndrome.

neuroscience↗

bioRxiv2024

Exploration of the link between COVID-19 and gastric cancer from the perspective of bioinformatics and systems biology

BackgroundCoronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused a global pandemic. Gastric cancer (GC) poses a great threat to peoples health, which is a high- risk factor for COVID-19. Previous studies have found some associations between GC and COVID-19, whereas the underlying molecular mechanisms are not well understood. MethodsWe used a bioinformatics and systems biology approach to investigate the relationship between GC and COVID-19. The gene expression profiles of COVID-19 (GSE196822) and GC (GSE179252) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the shared differentially expressed genes (DEGs) for GC and COVID-19, functional annotation, protein-protein interaction (PPI) network, hub genes, transcriptional regulatory networks and candidate drugs were analyzed. ResultsA total of 209 shared DEGs were identified to explore the linkages between COVID-19 and GC. Functional analyses showed that Immune-related pathway collectively participated in the development and progression of COVID-19 and GC. In addition, there are selected 10 hub genes including CDK1, KIF20A, TPX2, UBE2C, HJURP, CENPA, PLK1, MKI67, IFI6, and IFIT2. The transcription factor/gene and miRNA/gene interaction networks identified 38 transcription factors (TFs) and 234 miRNAs. More importantly, we identified ten potential therapeutic agents, including ciclopirox, resveratrol, etoposide, methotrexate, trifluridine, enterolactone, troglitazone, calcitriol, dasatinib and deferoxamine, some of which have been reported to improve and treat GC and COVID-19. This study also provides insight into the diseases most associated with mutual DEGs, which may provide new ideas for research on the treatment of COVID-19. ConclusionsThis research has the possibility to be contributed to effective therapeutic in COVID-19 and GC.

bioinformatics↗

bioRxiv2024

High-fidelity enhanced AsCas12a knock-in mice for efficient multiplexed gene editing, disease modeling and orthogonal immunogenetics

The advancement of CRISPR gene editing technology, especially the development of Cas9 knock-in mice, has significantly boosted the functional discovery of various genetics factors in diverse fields including genetics, genomics, immunology, and the biology of cancer. However, the pleiotropic effects on human disease and the complex nature of gene interaction networks require a knock-in mouse model capable of simultaneous multiplexed gene perturbation. Here, we present the generation and applications of Cre-dependent conditional and constitutive high-fidelity, enhanced AsCas12a (enAsCas12a-HF1) Rosa26-knock-in mice in the C57BL/6 background. With these mouse strains, we demonstrate highly efficient and multiplexed in vivo and ex vivo genome engineering as applied to lipid nanoparticle (LNP)-RNA-based liver protein targeting, AAV-based tumor modeling, and retrovirus-based immune cell engineering. By integrating with a dCas9-SPH CRISPR activation transgenic strain, we establish a simultaneous dual gene activation and knockout (DAKO) system that showcases the modular potential of these enAsCas12a-HF1 mice. Importantly, constitutive expression of enAsCas12a-HF1 does not lead to any discernable pathological differences as compared to the C57BL/6 background strain. These knock-in mice and the accompanying delivery methods would empower the deconvolution of complex gene interaction networks in broad areas of research.

bioengineering↗

bioRxiv2023

Tumor-wide RNA splicing aberrations generate immunogenic public neoantigens

T-cell-mediated immunotherapies are limited by the extent to which cancer-specific antigens are homogenously expressed throughout a tumor. We reasoned that recurrent splicing aberrations in cancer represent a potential source of tumor-wide and public neoantigens, and to test this possibility, we developed a novel pipeline for identifying neojunctions expressed uniformly within a tumor across diverse cancer types. Our analyses revealed multiple neojunctions that recur across patients and either exhibited intratumor heterogeneity or, in some cases, were tumor-wide. We identified CD8+ T-cell clones specific for neoantigens derived from tumor-wide and conserved neojunctions in GNAS and RPL22, respectively. TCR-engineered CD8+ T-cells targeting these mutations conferred neoantigen-specific tumor cell eradication. Furthermore, we revealed that cancer-specific dysregulation in splicing factor expression leads to recurrent neojunction expression. Together, these data reveal that a subset of neojunctions are both intratumorally conserved and public, providing the molecular basis for novel T-cell-based immunotherapies that address intratumoral heterogeneity.

cancer biology↗

bioRxiv2023

Duckweed evolution: from land back to water

Terrestialization is supposedly an important evolutionary process plant experience. However, directions of land back to water acquired little attention. Here we integrate multiproxy evidence to elucidate the evolution of duckweed. Three genera of duckweed show chronologically gradient degeneration in roots structure and stomatal function and decrease in lignocellulose content, accompanied by gradual contraction in relevant gene numbers and/or decline in transcription. The gene numbers in the main phytohormonal pathway are also gradually decreased. The co-action of auxin and rhizoid development gene causes a gradual decrease in adventitious roots. The significant expansion of the flavonoid pathway is also related to the adaptation of duckweed to floating growth. This study reconstructs the evolution history of duckweeds from land back to water, reverse to that of early land plants. SummaryWith terrestrialization being the popularly acknowledged plant evolutionary process, little is known about the evolution of higher plant from land back to water. Here we integrate multiproxy evidence to elucidate the gradual reverse evolution of duckweed. Three genera of duckweed show chronologically gradient degeneration in the structure of roots, the function of stomata, and decrease in lignocellulose content, accompanied by gradient contraction in relevant gene numbers and/or decline in transcript expression. The gene numbers in the main phytohormonal pathway are also gradually decreased. The co-action of auxin and rhizoid development gene causes a gradual decrease in adventitious roots. The significant expansion of the flavonoid pathway is also highly related to the adaptation of duckweed to floating growth. Our study combined with the fossil evidence reconstruct the evolution history of duckweeds from land back to water, reverse to that of early land plants. This study reconstructed the process of how a land plant returns to water, a reverse evolutionary approach which is different from what we studied in textbook about plant terrestrialization. This finding could be helpful for us to deeply and widely understand the adaptation of plant to the environment, and to expand and deepen the knowledge of evolution theory.

evolutionary biology↗

bioRxiv2023

Artificially cultivated duckweed: a high-efficiency starch producer

The increasing demand for starch has been a social struggle. We report a new technology that efficiently produces starch from duckweed. Although Landoltia punctata has a dramatic contraction of gene families, its starch content and productivity reached 72.2% (dry basis) and 10.4 g m-2 d-1 in 10 days, equivalent to a yield of 38.0 t ha-1 y-1 under nutrient limitation and CO2 elevation treatment. Meanwhile, we also examined the mechanism of duckweeds high starch accumulation. This is exhibited in the regulation of DNA methylation and transcription factors as well as the significantly up-regulated transcription levels and the increased enzyme activities of key genes in starch biosynthesis. Meantime, while nitrogen redistribution was enhanced, sucrose biosynthesis and transportation, and lignocellulose biosynthesis were all reduced. These alterations led to a reduction in lignocellulose and protein content and ultimately an increase in an accumulation of starch in the chloroplast. This work demonstrates duckweeds potential of being a highly efficient starch producer.

plant biology↗

bioRxiv2023

Cas12a/Cpf1 knock-in mice enable efficient multiplexed immune cell engineering

Cas9 transgenic animals have drastically accelerated the discovery of novel immune modulators. But due to its inability to process its own CRISPR RNAs (crRNAs), simultaneous multiplexed gene perturbations using Cas9 remains limited, especially by pseudoviral vectors. Cas12a/Cpf1, however, can process concatenated crRNA arrays for this purpose. Here, we created conditional and constitutive LbCas12a knock-in transgenic mice. With these mice, we demonstrated efficient multiplexed gene editing and surface protein knockdown within individual primary immune cells. We showed genome editing across multiple types of primary immune cells including CD4 and CD8 T cells, B cells, and bone-marrow derived dendritic cells. These transgenic animals, along with the accompanying viral vectors, together provide a versatile toolkit for a broad range of ex vivo and in vivo gene editing applications, including fundamental immunological discovery and immune gene engineering.

genetics↗

bioRxiv2023

Exploration of the Link Between COVID-19 and Alcoholic Hepatitis from the Perspective of Bioinformatics and Systems Biology

ObjectiveSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been suggested to purpose threats to health of mankind. Alcoholic hepatitis (AH) is a life-threatening acute and chronic liver failure that takes place in sufferers who drink excessively. During the epidemic, AH has an increasing incidence of severe illness and mortality. However, for these two diseases, the intrinsic relationship of molecular pathogenesis, as well as common therapeutic strategies are still poorly understood. MethodsThe transcriptome of the COVID-19 and AH has been compared to obtain the altered genes and hub genes were screened out through protein-protein interaction (PPI) network analysis. Via gene ontology (GO), pathway enrichment and transcription regulator analysis, a deeper appreciation of the interplay mechanism between hub genes were established. ResultsWith 181 common differentially expressed genes (DEGs) of AH and COVID-19 were obtained, 10 hub genes were captured. Follow-up studies located that these 10 genes typically mediated the diseases occurrence by regulating the activities of the immune system. Other results suggest that the common pathways of the two ailments are enriched in regulating the function of immune cells and the release of immune molecules. ConclusionThis study reveals the common pathogenesis of COVID-19 and AH and assist to discover necessary therapeutic targets to combat the ongoing pandemic induced via SARS-CoV-2 infection and acquire promising remedy strategies for the two diseases.

bioinformatics↗

bioRxiv2022

A robotic system for automated genetic manipulation and analysis of Caenorhabditis elegans on agar media

The nematode Caenorhabditis elegans is one of the most widely studied organisms in biology due to its small size, rapid life cycle, and manipulable genetics. Research with C. elegans depends on labor-intensive and time-consuming manual procedures, imposing a major bottleneck for many studies, especially those involving large numbers of animals. Here we describe the first general-purpose tool, WormPicker, a robotic system capable of performing complex genetic manipulations and other tasks by imaging, phenotyping, and transferring C. elegans on standard agar media. Our system uses a motorized stage to move an imaging system and a robotic arm over an array of plates. Machine vision tools identify animals and assay developmental stage, morphology, sex, expression of fluorescent reporters, and other phenotypes. Based on the results of these assays the robotic arm selectively transfers individual animals using an electrically self-sterilized wire loop, with the aid of machine vision and electrical capacitance sensing. Automated C. elegans manipulation shows reliability and throughput comparable to standard manual methods. We developed software to enable the system to autonomously carry out complex protocols. To validate the effectiveness and versatility of our methods we used the system to perform a collection of common C. elegans procedures, including genetic crossing, genetic mapping, and genomic integration of a transgene. Our robotic system will accelerate C. elegans research and opens possibilities for performing genetic and pharmacological screens that would be impractical using manual methods. Significance StatementThe nematode Caenorhabditis elegans is a powerful genetic model organism in life sciences due to its compact anatomy, short life cycle, and optical transparency. Current methods for worm genetics rely on laborious, time-consuming, and error-prone manual work. Here, we describe the first general-purpose automated tool capable of genetically manipulating C. elegans. Our robotic system will accelerate a broad variety of C. elegans research and opens possibilities for performing genetic and pharmacological screens that would be impractical using manual methods.

bioengineering↗