Biology subjects

Luo, Y.

Publications and source records attributed to Luo, Y..

At least 289 records · Page 16Linked to original sources

bioRxiv2022

The highly expressed ERV1 forms virus-like particles for regulating early embryonic development

In mammals, the transcription of transposable elements (TEs) is important for maintaining early embryonic development. Here, we systematically analyzed the expression characteristics of TE-derived transcripts in early embryos by constructing a database of TEs and transcriptome data from goats and using it to study the function of endogenous retroviruses (ERVs) in regulating early embryo development. We found that ERV1 made up the highest proportion of TE sequences and exhibited a stage-specific expression pattern during early embryonic development. Among ERV elements, ERV1 had the potential to encode the Gag protein domain to form virus-like particles (VLPs) in early goat embryos. Knockdown of ERV1_1_574 significantly reduced the embryo development rate and the number of trophoblast cells (P< 0.05). Transcriptome sequencing analysis of morula embryos showed that ERV1_1_574 mainly regulated the expression of genes related to embryo compaction and trophoblast cell differentiation, such as CX43 and CDX2. In summary, we found that ERV1 expression was essential for early embryonic development in goats through regulation of trophoblast cell differentiation.

developmental biology↗

bioRxiv2022

Connexin43 Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Rat Glucocorticoid-Induced Osteonecrosis of the Femoral Head

Glucocorticoids induced osteonecrosis of the femoral head (GIONFH) is a devastating orthopedic disease. Previous studies suggested that connexin43 (Cx43) is involved in the process of osteogenesis and angiogenesis. However, the role of Cx43 potentiates in the osteogenesis and angiogenesis of bone marrow-derived stromal stem cells (BMSCs) in GIONFH is still not investigated. In this study, BMSCs were isolated and transfected with green fluorescent protein (GFP) or the fusion gene encoding GFP and Cx43. The osteogenic differentiation of BMSCs were detected after transfected with Cx43. In addition, the migration abilities and angiogenesis of human umbilical vein endothelial cells (HUVECs) were been detected after induced by transfected BMSCs supernatants in vitro. Our results showed that Cx43 overexpression in BMSCs promoted osteogenic differentiation and angiogenesis in vitro. Finally, we established GC-ONFH rat model, then, a certain amount of transfected or controlled BMSCs were injected into the tibia of the rats. Immunohistological staining and micro-CT scanning results showed that the transplanted experiment group had significantly promoted more bone regeneration, vessel volume and the expressions of Runx2, ALP, COL I, VEGF and CD31 when compared with the effects of the negative or control groups. This study demonstrated for the first time that the Cx43 overexpression in BMSCs could promote bone regeneration as seen in the osteogenesis and angiogenesis process, suggesting that Cx43 may serve as a therapeutic gene target for GIONFH treatment.

cell biology↗

bioRxiv2022

Integrating inflammatory biomarker analysis and artificial intelligence-enabled image-based profiling to identify drug targets for intestinal fibrosis

Intestinal fibrosis is a common complication of several enteropathies with inflammatory bowel disease being the major cause. The progression of intestinal fibrosis may lead to intestinal stenosis and obstruction. Even with an increased understanding of tissue fibrogenesis, there are no approved treatments for intestinal fibrosis. Historically, drug discovery for diseases like intestinal fibrosis has been impeded by a lack of screenable cellular phenotypes. Here we applied Cell Painting, a scalable image-based morphology assay, augmented with machine learning algorithms to identify small molecules that were able to morphologically reverse the activated fibrotic phenotype of intestinal myofibroblasts under pro-fibrotic TNF stimulus. In combination with measuring CXCL10, a common pro-inflammatory cytokine in intestinal fibrosis, we carried out a high-throughput small molecule chemogenomics screen of approximately 5000 compounds with known targets or mechanisms, which have achieved clinical stage or approval by the FDA. Through the use of two divergent analytical methods, we identified several compounds and target classes that are potentially able to treat intestinal fibrosis. The phenotypic screening platform described here represents significant improvements in identifying a wide range of drug targets over conventional methods by integrating morphological analyses and artificial intelligence using pathologically-relevant cells and disease-relevant stimuli.

pharmacology and toxicology↗

bioRxiv2022

Spatiotemporal heterogeneity and the long-term impact of meteorological , environmental and socio-economic factors of scrub typhus in China from 2012 to 2018

Large-scale outbreaks of scrub typhus combined with the emergence of this vector-borne rickettsiosis in new areas indicate that this disease remains seriously neglected. This study aimed to explore the long-term changes and regional leading factors of scrub typhus in China, so as to provide fresh insights for the prevention and control of this disease. In this study, a Bayesian space-time hierarchical model (BSTHM) was used to identify the long-term spatiotemporal heterogeneity of scrub typhus and quantify the association between meteorological factors and scrub typhus in southern and northern China from 2012 to 2018. GeoDetector model was used to quantify the dominant forces of environmental and socioeconomic factors in the Northern and the Southern China. Scrub typhus often appeared in summer and autumn (June to November), and epidemically peaked in October, with obvious temporal seasonality. Spatially, the hot spots (high-risk regions) were concentrated in the south, on the contrary the cold spots (low-risk regions) in the north. In addition, the main meteorological factor, average temperature, gave a significant impact in both areas. The average temperature increased by 1 {degrees}C, resulting in a decrease of 1.10% in southern China and an increase of 0.96% in northern China in the risk of scrub typhus. The determinant environmental and socio-economic factors of scrub typhus in the two areas were altitude and per capita GDP, with q-values of 0.91 and 0.87, respectively. Meteorological, environmental and socio-economic factors had a significant impact on the distribution of scrub typhus, with obvious seasonality and spatial heterogeneity. This study provides helpful suggestions and basis for reasonably allocating resources and controlling the occurrence of scrub typhus. Author summaryScrub typhus is a natural-focus disease caused by the bite of chigger mite larval. In this study, we use BSTHM to capture the overall temporal trend and spatial hot spots of scrub typhus, and quantify the relationship between the disease and major meteorological factors. Meanwhile, Geodetector model was used to quantify the influence of other potential risk factors and estimate the spatio-temporal heterogeneity of scrub typhus. The results showed that scrub typhus had significant seasonality, with a q value of 0.52, and spatial heterogeneity, with a q-value of 0.64. Scrub typhus mainly occurred in summer and autumn, and high-risk areas were mainly distributed in southern China (Yunnan, Hainan and Guangdong). These heterogeneity were closely related to the vector and host. Whether in the South or the north, scrub typhus was closely related to risk factors such as temperature, per capita GDP, NDVI, altitude and the percentage of children aged 0-14. These results suggest that the relevant departments should strengthen the monitoring of the ecological environment, the host and vector of Orientia tsutsugamushi, and strengthen the risk awareness, so as to prevent and control the possible increased risk of scrub typhus under these meteorological, environmental and socio-economic conditions. Considering the differences in different regions, resources should be allocated reasonably.

ecology↗

bioRxiv2022

On the intrinsic curvature of animal whiskers

Facial vibrissae (whiskers) are thin, tapered, and flexible hair-like structures that are an important source of tactile sensory information for many species of animals. In contrast to insect antennae, whiskers have no sensors along their lengths. Instead, when a whisker touches an object, the resulting deformation is transmitted to mechanoreceptors in a follicle at the whisker base. Previous work has shown that the mechanical signals transmitted along the whisker will depend strongly on the whiskers geometric parameters, in particular on its taper (how diameter varies with arc length) and on its intrinsic curvature. Although previous studies have largely agreed on how to define taper, multiple approaches have been used to quantify intrinsic curvature. The present work, compares and contrasts different mathematical methods to quantify intrinsic curvature, including polynomial, fractional exponent, elliptical, and Cesaro. Comparisons are performed across ten species of whiskered animals, ranging from rodents to pinnipeds. The fractional exponent model is shown to be a particularly promising approach for distinguishing between whiskers of different species. We conclude with a discussion of the advantages and disadvantages of using the different models for different modeling situations.

neuroscience↗

bioRxiv2022

Climate and ant richness explain the global distribution of ant-plant mutualisms

Biotic interactions are known to play an important role in shaping species geographic distributions and diversity patterns. However, the role of mutualistic interactions in shaping global diversity patterns remains poorly quantified, particularly with respect to interactions with invertebrates. Moreover, it is unclear how the nature of different mutualisms interacts with abiotic drivers and affects diversity patterns of mutualistic organisms. Here, we present a global-scale biogeographic analysis of three different ant-plant mutualisms, differentiating between plants bearing domatia, extrafloral nectaries (EFNs), and elaiosomes, based on comprehensive geographic distributions of [~]15,000 flowering plants and [~]13,000 ant species. Domatia and extrafloral nectaries involve indirect plant defenses provided by ants, while elaiosomes attract ants to disperse seeds. Our results show distinct biogeographic patterns of different ant-plant mutualisms, with domatium- and EFN-bearing plant richness decreasing sharply from the equator towards the poles, while elaiosome-bearing plants prevail at mid-latitudes. Contemporary climate, especially mean annual temperature and precipitation, emerge as the most important predictor of ant-associated plant diversity. In hot and moist regions, typically the tropics, domatium- and EFN-bearing plant richness increases with related ant guild richness, while in warm regions plants with elaiosomes are strongly linked to interacting ants. Our results suggest that ant richness in combination with climate drives the spatial variation of plants bearing domatia, extrafloral nectaries, and elaiosomes, highlighting the importance of mutualistic interactions for understanding plant biogeography and its response to global change.

ecology↗

bioRxiv2022

Highly efficient healing of critical sized articular cartilage defect in situ using a chemically nucleoside-modified mRNA-enhanced cell therapy

Critical sized cartilage defects heal poorly and MSC-based therapies holds promise functional cartilage regeneration either used alone or in combination with growth factors. However, Recombinant protein growth factors were proven to have minimal benefits while to have adverse side effects and high cost. Nonviral mRNA delivery provides a promising, alternative approach to delivering therapeutic proteins within defect lesion for an extended period of time. Despite successful therapeutic outcome in bone and other vascularized tissues, the therapeutic application of mRNA in poorly vascularized tissues such as cartilage is still facing many challenges and rarely studied. We report here using chemically modified messenger RNA encoding TGF-{beta}3(TGF-{beta}3 cmRNA) to enhance the therapeutic efficacy of BMSCs to efficient repair of cartilage defect. Local administration of TGF-{beta}3 cmRNA enhanced BMSCs therapy restored critical-sized cartilage defects in situ in a rat model within 6 weeks with structural and molecular markers similar to its nature counterparts. In addition, the development of osteoarthritis caused by cartilage damage was prevented by this mRNA-enhanced BMSCs therapy evidenced by minimal late-stage OA pharmacological presentations. This novel mRNA enhanced-MSC technology extend the development of new therapeutic approaches for treating functional cartilage repair.

synthetic biology↗

bioRxiv2022

Trophoblast and blood vessel organoid cultures recapitulate the role of WNT2B in promoting intravillous vascularization in human intrauterine and ectopic pregnancy

Tubal ectopic pregnancy (TEP), a pregnancy complication caused by aberrant implantation in fallopian tubes, accounts for 9-13% pregnancy-related deaths. The lack of models for human TEP hampers the understanding of its pathological mechanisms. Here, we employed multiple models to investigate the crosstalk between human trophoblast development and intravillous vascularization. We found that the severity of TEP, the size of placental villi, and the depth of trophoblast invasion are correlated with the extent of intravillous vascularization. We identified a key pro-angiogenic factor secreted by trophoblasts, WNT2B, that promotes villous vasculogenesis, angiogenesis, and vascular network expansion. In an organoid coculture model consisting of trophoblast organoids and blood vessel organoids, knockdown of WNT2B in trophoblast organoids compromises their pro-angiogenic effect on the development of blood vessel organoids. These organoid-based models reveal an important role for WNT-mediated angiogenesis in pregnancies and could be employed to investigate the commutations between trophoblasts and endothelial/endothelial progenitor cells.

cell biology↗

bioRxiv2022

SOAR: a spatial transcriptomics analysis resource to model spatial variability and cell type interactions

Spatial transcriptomics provides researchers with a better understanding of gene expression within the tissue context. Although large volumes of spatial transcriptomics data have been generated, the lack of systematic curation and analysis makes data reuse challenging. Herein, we present Spatial transcriptOmics Analysis Resource (SOAR), a resource with an extensive, systematically compiled collection of spatial transcriptomics data across tissues, organs, and pathological conditions. SOAR is a comprehensive database with uniformly processed and annotated samples, facilitating future benchmark studies and method development. SOAR also offers multi-pronged analysis capability, including an integrative approach toward drug discovery that allows for efficient exploration of novel and targeted therapeutic uses for existing compounds.

bioinformatics↗

bioRxiv2022

Unique molecular signatures sustained in circulating monocytes and regulatory T cells in Convalescent COVID-19 patients

Over two years into the COVID-19 pandemic, the human immune response to SARS-CoV-2 during the active disease phase has been extensively studied. However, the long-term impact after recovery, which is critical to advance our understanding SARS-CoV-2 and COVID-19-associated long-term complications, remains largely unknown. Herein, we characterized multi-omic single-cell profiles of circulating immune cells in the peripheral blood of 100 patients, including covenlesent COVID-19 and sero-negative controls. The reduced frequencies of both short-lived monocytes and long-lived regulatory T (Treg) cells are significantly associated with the patients recovered from severe COVID-19. Consistently, sc-RNA seq analysis reveals seven heterogeneous clusters of monocytes (M0-M6) and ten Treg clusters (T0-T9) featuring distinct molecular signatures and associated with COVID-19 severity. Asymptomatic patients contain the most abundant clusters of monocyte and Treg expressing high CD74 or IFN-responsive genes. In contrast, the patients recovered from a severe disease have shown two dominant inflammatory monocyte clusters with S100 family genes: S100A8 & A9 with high HLA-I whereas S100A4 & A6 with high HLA-II genes, a specific non-classical monocyte cluster with distinct IFITM family genes, and a unique TGF-{beta} high Treg Cluster. The outpatients and seronegative controls share most of the monocyte and Treg clusters patterns with high expression of HLA genes. Surprisingly, while presumably short-ived monocytes appear to have sustained alterations over 4 months, the decreased frequencies of long-lived Tregs (high HLA-DRA and S100A6) in the outpatients restore over the tested convalescent time (>= 4 months). Collectively, our study identifies sustained and dynamically altered monocytes and Treg clusters with distinct molecular signatures after recovery, associated with COVID-19 severity.

immunology↗

bioRxiv2022

Oscillatory dynamics underlying emotion-cognition integration: differential role of theta and alpha oscillations

A fundamental aspect of human mental life is the seamless ability for integration of emotion and cognition. Despite progress regarding the spatial architecture of Emotion-Cognition Integration (ECI), the time course of ECI processes remains unclear. To examine the temporal organization of brain oscillations underpinning ECI, we simultaneously manipulated emotional valence of stimuli and cognitive task demand while recording electrophysiological responses of 61 participants. They were asked to complete tasks with low (body-part judgement) and high (laterality judgement) cognitive demand while viewing other people photographs that varied on dimensions of laterality (left or right), body-part (hand or foot), and emotional valence (pain or no pain). We found increased reaction times and error rates in pain versus no pain during laterality judgement relative to body-part judgement, suggesting reciprocal inhibition between emotion and cognition. EEG results showed that 1) emotion processing (valence) occurred first in the theta band from 144 to 372 ms; 2) cognitive processing (laterality) took place in the theta band from 332 to 608 ms; 3) emotional and cognitive processes were integrated in the alpha band from 268 ms and lasted to 800 ms. These findings reveal oscillatory dynamics of the processing and integration of emotion and cognition, providing further insights into the underlying neurophysiology. This may ultimately contribute to our understanding of ECI processing in psychopathology.

neuroscience↗

bioRxiv2022

Near telomere-to-telomere nuclear phased chromosomes of the dikaryotic wheat fungus Rhizoctonia cerealis

Rhizoctonia cerealis (Rce), which causes sharp eyespot, is one of the most destructive wheat pathogens. However, the genetic and molecular virulence mechanisms of Rce have not been elucidated. As a dikaryotic organism, the haplotype phasing of this fungus has not been completed so far. We applied a haplotype phasing algorithm to generate a high-quality near telomere-to-telomere nuclear-phased genome sequence of Rce strain R0301. Sixteen pairs of chromosomes were assigned to the A and B genomes with a total size of 83 Mb. Based on a dual-time course RNA-seq, 25308 genes were predicted. Genes for steroid biosynthesis and starch and sucrose metabolism were significantly enriched, together with many genes encoding carbohydrate-active enzymes (CAZymes) and secreted effector proteins, which should be involved in infection of wheat plants. Population genomic analysis of 31 isolates collected in China during the last forty years suggests that this population has not undergone substantial differentiation over time. ImportanceThe finished genome reference is the basis of revealing pathogens biology base. Many efforts have been made to produce the chromosome-scale assembly of fungi. However, the reference of many pathogenic fungi is highly fragmented, which prevents the analysis of genome structure variation, evolution and import pathogenicity genes. Here, we assembly the only chromosome-scale haplotype-phased reference of dikaryotic fungus so far. This assembly achieves the gold standard based on many evaluation software, which indicates that the pipeline developed in this study can be applied to assemble references for other dikaryotic organisms. This work can also promote the research on the globes destructive wheat pathogens, sharp eyespot, caused by R. cerealis.

genomics↗

bioRxiv2022

Seasonality but not photoperiodism affects susceptibility of the two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae) to pesticides

Understanding how endogenous and exogenous factors such as annual seasonal rhythm and photoperiodism affect the toxicity of pesticides can help design integrated pest management strategies. The two-spotted spider mite Tetranychus urticae Koch (Acari: Tetranychidae), a worldwide phytophagous pest species distributed in areas with different time zones, is a good model to explore how the photoperiodism and seasonality affect the pesticide toxicity. In this study, we conducted a laboratory experiment from March 2017 to November 2018 where spider mites were reared at three photoperiod regimes in environmentally controlled incubators. The toxicities of two acaricides, propargite and diafenthiruon, were measured on T. urticae every month. To determine potential mechanisms underlying the changes in the acaricide toxicity, we measured body size and total GSTs activity with the toxicity measurements in 2018. Our results showed that the toxicities of the two acaricides were not significantly different among the three photoperiod regimes. However, both had a consistent trend along the season which increased in the spring and summer and decreased in the winter in all photoperiod regimes for two consecutive years, suggesting seasonality be an endogenous factor affecting the susceptibility of the spider mites to pesticide. Pearsons correlation analyses showed only the body size had a weak negative correlation with the acaricide toxicities, suggesting a minor contribution to the higher toxicity from the smaller size of T. urticae. Our study is the first to show that seasonality can have an endogenous effect on the pesticide toxicity, and the results can inform practical insights into the pest management strategies.

zoology↗

bioRxiv2022

Construction of a High-Density Genetic Map Based on Large-Scale Marker Development in Coix lacryma-jobi L . Using Specifific-Locus Amplifified Fragment Sequencing (SLAF-seq)

Coix lacryma-jobi L. is one of the most important economical and medicine corn. In this study, a high genetic linkage map has been constructed for Coix lacryma-jobi L. from a cross F2 community of "Qianyi NO.2" x "Wenyi NO.2" and their parents through high-throughput sequencing and specfic-locus amplified fragment (SLAF) library construction. After pre-processing, 325.49 Gb of raw data containing 1,628 M reads were obtained. A total of 22,944 high-quality SLAFs were detected, among which 3,952 SLAFs and 3,646 of the polymorphic markers could meet the requirements for construction of a genetic linkage map. The integrated map contains 3,605 high quality SLAFs, which are grouped to 10 genetic linkage groups. The total length of the linkage map is 1,620.39 cM with an average distance of 0.45 cM and 360.5 markers in average of per linkage group. This work will provide an important molecular biology basis for investigating their characteristics, gene cloning, molecular marker-assisted breeding, functional genomics and so on for Jobs tears.

genetics↗

bioRxiv2022

Antibody Evasion Properties of SARS-CoV-2 Omicron Sublineages

The identification of the Omicron variant (B.1.1.529.1 or BA.1) of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in Botswana in November 20211 immediately raised alarms due to the sheer number of mutations in the spike glycoprotein that could lead to striking antibody evasion. We2 and others3-6 recently reported results in this Journal confirming such a concern. Continuing surveillance of Omicron evolution has since revealed the rise in prevalence of two sublineages, BA.1 with an R346K mutation (BA.1+R346K) and B.1.1.529.2 (BA.2), with the latter containing 8 unique spike mutations while lacking 13 spike mutations found in BA.1. We therefore extended our studies to include antigenic characterization of these new sublineages. Polyclonal sera from patients infected by wild-type SARS-CoV-2 or recipients of current mRNA vaccines showed a substantial loss in neutralizing activity against both BA.1+R346K and BA.2, with drops comparable to that already reported for BA.12,3,5,6. These findings indicate that these three sublineages of Omicron are antigenically equidistant from the wild-type SARS-CoV-2 and thus similarly threaten the efficacies of current vaccines. BA.2 also exhibited marked resistance to 17 of 19 neutralizing monoclonal antibodies tested, including S309 (sotrovimab)7, which had retained appreciable activity against BA.1 and BA.1+R346K2-4,6. This new finding shows that no presently approved or authorized monoclonal antibody therapy could adequately cover all sublineages of the Omicron variant.

microbiology↗

bioRxiv2022

Maternally inherited siRNAs initiate piRNA cluster formation

PIWI-interacting RNAs (piRNAs) guide repression of transposable elements in germlines of animals. In Drosophila, piRNAs are produced from heterochromatic genomic loci, called piRNA clusters, that act as a repositories of information about genome invaders. piRNA generation by dual-strand clusters depend on the chromatin-bound Rhino-Deadlock-Cutoff (RDC) complex, which is deposited on clusters guided by piRNAs, forming a feed-forward loop in which piRNAs promote their own biogenesis. However, how piRNA clusters are formed initially, before cognate piRNAs are present, remained unknown. Here we report spontaneous de novo formation of a piRNA cluster from repetitive transgenic sequences. We show that cluster formation occurs gradually over several generations and requires continuous trans-generational transmission of small RNAs from mothers to their progeny. We discovered that maternally-supplied siRNAs are responsible for triggering de novo cluster activation in progeny. In contrast, the siRNA pathway is dispensable for cluster function after its establishment. These results revealed an unexpected cross-talk between the siRNA and piRNA pathways and suggest a mechanism for de novo formation of piRNA clusters triggered by production of siRNAs. Highlights- A transcribed repetitive transgene is spontaneously converted into dual-strand piRNA cluster - Establishment of piRNA cluster occurs over multiple generations and requires cytoplasmic inheritance of cognate small RNA from mothers - Cognate siRNAs initiate the activation of piRNA cluster, but are dispensable after its establishment

molecular biology↗

bioRxiv2022

The effects of electroencephalogram feature-based transcranial alternating current stimulation on working memory and electrophysiology

Transcranial alternating current stimulation (tACS) can influence cognitive functions by modulating brain oscillations. However, results regarding the effectiveness of tACS in regulating cognitive performance have been inconsistent. In the present study, we aimed to find EEG characteristics associated with the improvements in working memory performance, to select tACS stimulus targets and frequency based on this feature, and to explore effects of selected stimulus on verbal working memory. To achieve this goal, we first investigated the EEG characteristics associated with improvements in working memory performance with the aid of EEG analyses and machine learning techniques. These analyses suggested that 8 Hz activity in the prefrontal region was related to accuracy in the verbal working memory task. The tACS stimulus target and pattern were then selected based on the EEG feature. Finally, the selected tACS frequency (8 Hz tACS in the prefrontal region) was applied to modulate working memory. The performance of working memory was improved significantly using the selected stimulation than using 40 Hz and sham stimulation (Especially for participants with low verbal working memory). In conclusion, using EEG features related to positive behavioral changes to select brain regions and stimulation patterns for tACS is an effective intervention for improving working memory. Our results contribute to the groundwork for future tACS closed-loop interventions for cognitive deterioration.

neuroscience↗

bioRxiv2022

Collateral cleavage of 28s rRNA by RfxCas13d causes death of mice

The CRISPR-Cas13 system is an RNA-guided RNA-targeting system, and has been widely used in transcriptome engineering with potentially important clinical applications. However, it is still controversial whether Cas13 exhibits collateral activity in mammalian cells. Here, we found that knocking down gene expression using RfxCas13d in the adult brain neurons caused death of mice, which was not resulted from the loss of target gene function or off-target effects. Mechanistically, we showed that RfxCas13d exhibited collateral activity in mammalian cells, which is positively correlated with the abundance of target RNA. The collateral activity of RfxCas13d could cleave 28s rRNA into two fragments, leading to translation attenuation and activation of the ZAK-JNK/p38-immediate early gene (IEG) pathway. These results provide new mechanistic insights into the collateral activity of RfxCas13d and warn that the biosafety of CRISPR-Cas13 system needs further evaluation before applying it to clinical treatments.

bioengineering↗