Biology subjects

Ji, R.

Publications and source records attributed to Ji, R..

31 records · Page 2Linked to original sources

bioRxiv2024

CREEPING STEM1 Regulates Directional Auxin Transport for Lodging Resistance in Soybean

Soybean, a staple crop on a global scale, frequently encounters challenges due to lodging under high planting densities, which results in significant yield losses. Despite extensive research, the fundamental genetic mechanisms governing lodging resistance in soybeans remain elusive. In this study, we identify and characterize the Creeping Stem 1 (CS1) gene, which plays a crucial role in conferring lodging resistance in soybeans. The CS1 gene encodes a HEAT-repeat protein that modulates hypocotyl gravitropism by regulating amyloplast sedimentation. Functional analysis reveals that the loss of CS1 activity disrupts polar auxin transport, vascular bundle development, and the biosynthesis of cellulose and lignin, ultimately leading to premature lodging and aberrant root development. Conversely, increasing CS1 expression significantly enhances lodging resistance and improves yield under conditions of high planting density. Our findings shed light on the genetic mechanisms that underlie lodging resistance in soybeans and highlight the potential of CS1 as a valuable target for genetic engineering to improve crop lodging resistance and yield.

plant biology↗

bioRxiv2024

Dysfunctional S1P/S1PR1 signaling in the dentate gyrus drives vulnerability of chronic pain-related memory impairment

Memory impairment in chronic pain patients is substantial and common, and few therapeutic strategies are available. Chronic pain-related memory impairment has susceptible and unsusceptible features. Therefore, exploring the underlying mechanisms of its vulnerability is essential for developing effective treatments. Here, combining two spatial memory tests (Y-maze test and Morris water maze), we segregated chronic pain mice into memory impairment-susceptible and -unsusceptible subpopulations in a chronic neuropathic pain model induced by chronic constrictive injury of the sciatic nerve. RNA-seq analysis and gain/loss-of-function study revealed that S1P/S1PR1 signaling is a determinant for vulnerability to chronic pain-related memory impairment. Knockdown of the S1PR1 in the DG promoted a susceptible phenotype and led to structural plasticity changes of reduced excitatory synapse formation and abnormal spine morphology as observed in susceptible mice, while overexpression of the S1PR1 and pharmacological administration of S1PR1 agonist in the DG promoted an unsusceptible phenotype and prevented the occurrence of memory impairment, and rescued the morphological abnormality. Finally, GO enrichment analysis and biochemical evidence indicated that down-regulation of S1PR1 in susceptible mice may impair DG structural plasticity via interaction with actin cytoskeleton rearrangement-related signaling pathways including Itga2 and its downstream Rac1/Cdc42 signaling and Arp2/3 cascade. These results reveal a novel mechanism and provide a promising preventive and therapeutic molecular target for vulnerability to chronic pain-related memory impairment.

neuroscience↗

bioRxiv2024

The under-recognized dominance of magnetosome gene cluster-containing bacteria in oxygen-stratified freshwater ecosystems

Magnetotactic bacteria (MTB) capable of magnetosome organelle biomineralization and magnetotaxis are widespread in chemically stratified aquatic environments. Conventionally, it has long been considered that the overall abundance of MTB in microbiota is not very high and that Magnetococcia is the most frequently identified and predominant MTB members. However, the diversity and distribution of MTB in chemically stratified environments remain elusive due to the lack of large-scale systematic analyses. Here we conduct a comprehensive survey of genomes containing magnetosome gene clusters (MGCs), a group of genes responsible for magnetosome biomineralization and magnetotaxis, in 267 metagenomes from 38 oxygen-stratified freshwater environments. A total of 63 MGC-containing genomes belonging to eight bacterial phyla are reconstructed, including the newly identified Myxococcota. We discover an unexpectedly high relative abundance of putative MTB (up to 15.4% of metagenomic reads) in hypoxic and anoxic water columns, in which Deltaproteobacteria, rather than traditionally considered Magnetococcia, are the most ubiquitous and predominant MGC-containing bacteria. Our analysis reveals a depth-specific taxonomy and function of MGC-containing bacteria in stratified water columns shaped by physicochemical conditions. These findings underscore the unrecognized ecophysiological importance of MTB in freshwater ecosystems.

microbiology↗

bioRxiv2024

Non-invasive and painless mid-infrared modulation increases collagen in human and mouse skin

Stimulating collagen production in skin helps to enhance vitality while decelerating aging- associated processes in skin tissue. However, current approaches to enhancing collagen production are commonly limited by accompanying pain and trauma. Here, we report that mid-infrared modulation (MIMO) at an intensity of 70 mW/cm2 promotes collagen production in human or mouse skin in vivo without generating excessive heat. We found that protein levels of the collagen- degrading endopeptidase, MMP-1, were decreased in the skin of mice following MIMO treatment, whereas the collagen synthesis-related factors, TGF-{beta}, HSP47, and HSP70, were all increased. In addition, MIMO stimulated collagen secretion in human dermal fibroblasts in vitro. This work demonstrates that MIMO is an effective, non-invasive, and painless intervention for in vivo enhancement of collagen production in the skin. One Sentence SummaryMid-infrared modulation promotes collagen production

molecular biology↗

bioRxiv2024

Transcranial Functional Ultrasound Imaging Detects Focused Ultrasound Neuromodulation Induced Hemodynamic Changes in Mouse and Nonhuman Primate Brains In Vivo

BackgroundFocused ultrasound (FUS) is an emerging non-invasive technique for neuromodulation in the central nervous system (CNS). Functional ultrasound imaging (fUSI) leverages ultrafast Power Doppler Imaging (PDI) to detect changes in cerebral blood volume (CBV), which correlate well with neuronal activity and thus hold promise to monitor brain responses to FUS. ObjectiveInvestigate the immediate and short-term effects of transcranial FUS neuromodulation in the brain with fUSI by characterizing hemodynamic responses. MethodsWe designed a setup that aligns a FUS transducer with a linear array to allow immediate subsequent monitoring of the hemodynamic response with fUSI during and after FUS neuromodulation (FUS-fUSI) in lightly anesthetized mice. We investigated the effects of varying pressures and transducer positions on the hemodynamic responses. ResultsWe found that higher FUS pressures increase the size of the activated brain area, as well as the magnitude of change in CBV and could show that sham sonications did not produce hemodynamic responses. Unilateral sonications resulted in bilateral hemodynamic changes with a significantly stronger response on the ipsilateral side. FUS neuromodulation in mice with a cranial window showed distinct activation patterns that were frequency-dependent and different from the activation patterns observed in the transcranial model. ConclusionfUSI is hereby shown capable of transcranially monitoring online and short-term hemodynamic effects in the brain during and following FUS neuromodulation.

bioengineering↗

bioRxiv2024

Secondary microglia formation center in the human fetal brain

Yolk sac-derived microglia migrate and populate the brain during development, constituting 10-15% of the total brain cells. The human brain is the largest and most complex brain with the highest cognitive capacity among all species. Therefore, the limitations of rodent brain studies in interpreting the human brain are evident. By co-immunostaining microglia in 50 {micro}m fetal brain sections from 7.5 to 16 gestational weeks (gw) and combining high-resolution scanning, we identified a highly proliferative microglia aggregate (0.108-2.129 mm2) that expanded in Downs Syndrome fetal brain (4.168 mm2) and was located near the ganglion eminence, in which Ki67+ microglia accounted for 23.4% of total microglia compared to 6.3% in other brain regions. The microglia in the aggregates lack phagocytic bulbs, membrane ruffles, and long/branching processes compared to microglia in other brain regions. Introducing human microglia into cortical organoids, but not macrophages, replicated proliferative microglial aggregates on the brain organoid surface and sufficiently penetrated deeper regions of the cortical organoids. Penetrating microglia display phagocytic capacity, enhance immunity, and accelerate the maturation of brain organoids. The large proliferative microglial aggregate may be a unique secondary microglial formation center in the human fetal brain to compensate for the enormous microglial demands during brain expansion.

neuroscience↗

bioRxiv2023

Logic Gate Activated Lysosome Targeting DNA Nanodevice for Controlled Proteins Degradation

Targeted protein degradation (TPD) is a powerful technique for regulation of protein homeostasis. Current TPD mainly focuses on the therapeutical consequences rather than the operation processes of the molecular tools. Herein, we construct a platform for precisely manipulate the protein degradation by activatable lysosome targeting DNA nanodevices. In the design, a lysosome-targeting CD63 aptamer is locked by the single-stranded DNA with a photocleavable group and a disulfide bond. This locked CD63 aptamer is connected with the aptamer targeting the protein of interest via double-stranded DNA linkages to form the logic-gate activated lysosome targeting DNA nanodevice (LALTD). With the UV light and endogenous GSH as inputs, AND logic-gate is built to efficiently manipulate the protein delivery processes by LALTD. The protein of interest could be degraded via efficient lysosome hydrolysis. Further studies shows that the logic-gate operation could be used for modulating the T cell-mediated antitumor immunity. The modularly designed activatable lysosome targeting DNA nanodevices exhibits good stability, controllability, programmability and universality, providing a new prospect for accurate protein degradation and precise therapy. Entry for the Table of ContentsThrough rational integration of dual molecular switches with bispecific aptamer systems, a logic-gate activated lysosome targeting DNA nanodevice (LALTD) was developed for precisely controlled process of protein hydrolysis in living cells. The designed LALTD system provide a general platform for designing accurate protein degradation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=162 SRC="FIGDIR/small/555427v1_ufig1.gif" ALT="Figure 1"> View larger version (87K): org.highwire.dtl.DTLVardef@1b3afc1org.highwire.dtl.DTLVardef@1d7c893org.highwire.dtl.DTLVardef@1b14268org.highwire.dtl.DTLVardef@7ed354_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

Characterization and contribution of RPE senescence to Age-related macular degeneration in Tnfrsf10 knock out mice

BackgroundRetinal pigment epithelial cells (RPE) play vital role in the pathogenesis of age-related macular degeneration (AMD). Our laboratory has shown that RPE cellular senescence contributed to the pathophysiology of experimental AMD, and SASP members are involved in this process. Recently, we presented confirmatory evidence to earlier GWAS studies that dysregulation of tumor necrosis factor receptor superfamily 10A (TNFRSF10A) dysregulation leads to AMD development and is linked to RPE dysfunction. This study aims to investigate the contribution of RPE senescence to AMD pathophysiology using TNFRSF10A silenced human RPE (hRPE) cells and Tnfrsf10 KO mice. MethodsSub-confluent primary hRPE cells and TNFRSF10A silenced hRPE were exposed to stress-induced premature senescence with H2O2 (500 M, 48h), and senescence-associated markers ({beta}gal, p16, and p21) were analyzed by RT-PCR and WB analysis. The effect of H2O2-induced senescence in non-silenced and silenced hRPE on OXPHOS and glycolysis was determined using Seahorse XF96 analyzer. Male C57BL/6J Tnfrsf10 KO (Tnfrsf10-/-) mice were used to study the regulation of senescence by TNFRSF10A in vivo. Expression of p16 and p21 in control and KO mice of varying ages were determined by RT-PCR, WB, and immunostaining analysis. ResultsThe senescence-associated p16 and p21 showed a significant (p < 0.01) upregulation with H2O2 induction at the gene (1.8- and 3-fold) and protein (3.2- and 4-fold) levels in hRPE cells. The protein expression of p16 and p21 was further significantly increased by co-treatment with siRNA (p < 0.05 vs. H2O2). Mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) (pmol/min/total DNA) increased with senescence induction by H2O2 for 48h in control RPE, and knockdown of TNFRSF10A caused a further increase in OCR and ECAR. In addition, co-treatment with PKC activator significantly improved all parameters. Similarly, in vivo studies showed upregulation of p16 and p21 by RT-PCR, WB, and immunostaining analysis in RPE/choroid of Tnfrsf10 KO mice. When subjected to examination across distinct age groups, namely young (1-3 months), middle (6-9 months), and old (12-15 months) mice, a discernible age-related elevation in the expression of p16 and p21 was observed. ConclusionsOur findings suggest that TNRSF10A is a regulator of regulates in RPE senescence. Further work on elucidating pathways of senescence will facilitate the development of new therapeutic targets for AMD.

pathology↗

bioRxiv2022

Focused ultrasound-mediated brain genome editing

Gene editing in the mammalian brain has been challenging because of the restricted transport imposed by the blood-brain barrier (BBB). Current approaches rely on local injection to bypass the BBB. However, such administration is highly invasive and not amenable to treating certain delicate regions of the brain. We demonstrate a safe and effective gene editing technique by using focused ultrasound (FUS) to transiently open the BBB for the transport of intravenously delivered CRISPR/Cas9 machinery to the brain.

bioengineering↗

bioRxiv2022

Corticosteroid Activation of Atlantic Sea Lamprey Corticoid Receptor: Allosteric Regulation by the N-terminal Domain

Lampreys are jawless fish that evolved about 550 million years ago at the base of the vertebrate line. Modern lampreys contain a corticoid receptor (CR), the common ancestor of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), which first appear in cartilaginous fish, such as sharks. Until recently, 344 amino acids at the amino terminus of adult lamprey CR were not present in the lamprey CR sequence in GenBank. A search of the recently sequenced lamprey germline genome identified two CR sequences, CR1 and CR2, containing the 344 previously un-identified amino acids. CR1 also contains a novel four amino acid insertion in the DNA-binding domain (DBD). We studied corticosteroid and progesterone activation of CR1 and CR2 and found their strongest response was to 11-deoxycorticosterone and 11-deoxycortisol, the two circulating corticosteroids in lamprey. Based on steroid specificity, both CRs are close to elephant shark MR and distant from elephant shark GR. HEK293 cells that were transfected with full-length CR1 or CR2 and the MMTV promoter have about 3-fold higher steroid-mediated activation compared to HEK293 cells transfected with these CRs and the TAT3 promoter. Deletion of the amino-terminal domain (NTD) of lamprey CR1 and CR2 to form truncated CRs decreased transcriptional activation by about 70% in HEK293 cells that were transfected with MMTV, but increased transcription by about 6-fold in cells transfected with TAT3. This indicated that the promoter has an important effect on NTD regulation of transcriptional activation of the CR by steroids. Our results also indicate that the entire lamprey CR sequence is needed for an accurate determination of steroid-mediated transcription.

evolutionary biology↗

bioRxiv2021

Regional Cell Atlas of Human Intestine Shapes Distinct Immune Surveillance

Regional intestinal immune surveillance remains obscure. In this study, we integrated single-cell RNA sequencing and spatial transcriptomics to create a regional atlas of fetal and adult intestines, consisting of 59 cell subsets, of which eight new subsets and ILCs transition states were identified. Results revealed that microenvironment determines in-situ cell differentiation and shapes the regional molecular characteristics, allowing different intestinal segments with diverse functions. We characterized the regional expression of mucins, immunoglobulins, and antimicrobial peptides (AMPs) and their shift during development and in inflammatory bowel disease. Notably, -defensins expressed most abundantly in small intestinal LGR5+ stem cells, rather than in Paneth cells, and down-regulated as cell maturing. Common upstream transcription factors controlled the AMPs expression, illuminating the concurrent change of AMPs during epithelial differentiation, and the spatial co-expression patterns. We demonstrated the correspondence of cell focus of risk genes to diseases location susceptibility and identified distinct cell-cell crosstalk and spatial heterogeneity of immune cell homing in different gut segments. Overall, a cross-spatiotemporal approach to transcriptomes at single-cell resolution revealed that the regional milieu of the human intestine determined cellular and molecular cues of immune surveillance, dictating gut homeostasis and disease.

cell biology↗

bioRxiv2021

Metabolic characteristics of taste differences under the soil and hydroponic cultures of sweet potato leaves by using non-targeted metabolomics

Sweet potato leaves are consumed as green leafy vegetables in most of the world due to their nutritional and functional values, and the taste characteristics determine their commodity value and consumer acceptance. However, the metabolic composition and formation mechanism of taste quality in its leaves are not clear. In this study, we found that sweet potato leaves under different growing patterns, soil culture and hydroponic culture, which result in different taste quality. In particular, the taste quality in leafy sweet potato was effectively improved under hydroponic culture. Meanwhile, we further profiled metabolites in leaves of sweet potatoes under different growing patterns by using GC-QToF-MS. A total of 200 metabolites were identified, covering most of the metabolic pathways in plants. A comparison of the good taste and poor taste of sweet potato leaves resulted in 71 metabolites related to taste quality formation. In addition, the leaves with poor taste had lower levels of metabolites regarding amino acids metabolism, whereas was accompanied by high levels of metabolites in carbohydrates and secondary metabolism. This study provides new insights into the improvement of taste quality in leafy sweet potato.

plant biology↗

bioRxiv2018

Molecular mechanism of the Orai channel activation

The Orai channel is characterized by voltage independence, low conductance and high Ca2+ selectivity and plays an important role in Ca2+ influx through the plasma membrane. How the channel is activated and promotes Ca2+ permeation are not well understood. Here, we report the crystal structure and cryo-electron microscopy reconstruction of a Drosophila melanogaster Orai mutant (P288L) channel that is constitutively active according to electrophysiology. The open state of the Orai channel showed a hexameric assembly in which six TM1 helices in the center form the ion-conducting pore, and six TM4 helices in the periphery form extended long helices. Orai channel activation requires conformational transduction from TM4 to TM1 and eventually causes the basic section of TM1 to twist outward. The wider pore on the cytosolic side aggregates anions to increase the potential gradient across the membrane and thus facilitate Ca2+ permeation. The open-state structure of the Orai channel offers insights into channel assembly, channel activation and Ca2+ permeation.

biochemistry↗