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Zeng, G.

Publications and source records attributed to Zeng, G..

16 recordsLinked to original sources

The mechanism of Hsa_circ_0000629 in bronchial asthma through sponge adsorption of miR-212-5p/NLRP3

To explore the mechanism of Hsa_circ_0000629 adsorbing miR-212-5p/ nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) through sponge in bronchial asthma. Twenty BALB/C mice were randomly divided into a normal control group and an asthma group. Pathological changes in lung tissue were observed via HE staining. Human bronchial epithelial cells (16HBE) were transfected with Hsa_circ_0000629 overexpression group (Hsa_circ_0000629-over), Hsa_circ_0000629 siRNA (Hsa_circ_0000629-si), mimic NC, miR-212-5p mimic, inhibitor NC, miR-212-5p inhibitor, and LPS+Hsa_circ_0000629 si. LPS-induced asthmatic cell models (LPS group) and untransfected 16HBE cells (NC group) served as controls. qRT-PCR was used to measure Hsa_circ_0000629, miR-212-5p and NLRP3 expression. ELISA assessed interleukin 18 (IL-18), interleukin 1{beta} (IL-1{beta}), interleukin 6 (IL-6) and tumor necrosis factor - (TNF-) levels. Cell proliferation and the apoptosis were evaluated by EDU assay and flow cytometry, respectively. Western blot analyzed Cleaved-caspase 1, 3 and 9 proteins expression. Dual-luciferase assay verified the binding sites of Hsa_circ_0000629 to miR-212-5p and NLRP3 to miR-212-5p. HE staining revealed inflammatory cell infiltration, bronchial wall thickening, smooth muscle hyperplasia, and alveolar destruction in asthmatic mice. Compared with the controls, Hsa_circ_0000629 and NLRP3 expression were significantly increased, while miR-212-5p expression was decreased in asthmatic lung tissues. In 16HBE cells, Hsa_circ_0000629-over and LPS groups showed elevated Hsa_circ_0000629 and NLRP3 expression but reduced miR-212-5p levels. Silencing Hsa_circ_0000629 in LPS-treated cells (LPS+Hsa_circ_0000629-si) reversed these effects. Overexpression of miR-212-5p counteracted Hsa_circ_0000629-induced NLRP3 upregulation, while miR-212-5p inhibition enhanced NLRP3 expression. LPS exposure increased TNF-, IL-18, IL-6, and IL-1{beta} levels, reduced cell proliferation, and promoted apoptosis. These changes were attenuated by Hsa_circ_0000629 silencing or miR-212-5p overexpression. Western blot confirmed that Hsa_circ_0000629 overexpression upregulated Cleaved-Caspase 1, 3, and 9, whereas miR-212-5p mimic or Hsa_circ_0000629-si reversed this trend. Dual-luciferase assays demonstrated targeted interactions among Hsa_circ_0000629, miR-212-5p, and NLRP3. Interference with Hsa_circ_0000629 expression can alleviate LPS induced apoptosis in 16HBE cells and inhibit the expression of inflammatory factors by targeting the miR-212-5p/NLRP pathway, which may be a new target for the treatment of asthma.

immunology↗

Geometry-Encoded Microtrenches Stabilize Endothelium on High Shear Biomaterial Surfaces

Maintaining a confluent, antithrombotic endothelium on cardiovascular biomaterial surfaces remains a major barrier to long-term hemocompatibility, as endothelial cells (ECs) rapidly denude under supraphysiological shear in prosthetic devices. Here, we hypothesized that mesoscale surface geometry ([~]100-200 {micro}m) could reorganize near-wall hemodynamics, preserving endothelial coverage and function under extreme shear. Engineered microtrenches were introduced onto an implant biomaterial to generate spatially defined shear environments. Under supraphysiological near-wall shear ([~]250 dyn/cm{superscript 2}), microtrenched geometries created attenuated shear and vorticity gradients. Endothelial monolayers were sustained in these flow domains for 120 hours, whereas flat controls rapidly denuded. Endothelial retention in 22.5{degrees} angled trenches increased dramatically, from an EC of 33 to 101 dyn/cm{superscript 2}. 45{degrees} angled trenches further increased endothelial shear resistance to an EC of 207 dyn/cm{superscript 2}. Endothelial monolayers demonstrated collective mechano-adaptation to ultra-high shear through VE-cadherin junction thickening and coordinated cytoskeletal and nuclear alignment. Mechanoadapted monolayers exhibited increased eNOS expression correlated with local shear and elevated nitrite production (45{degrees}: 50.4 {+/-} 6.1 {micro}M; 22.5{degrees}: 35.7 {+/-} 3.3 {micro}M; 0{degrees}: 28.4 {+/-} 6.8 {micro}M). In contrast, interfaces with abrupt shear transitions or elevated rotational flow exhibited reduced coverage, junctional thinning, and re-emergence of VCAM-1 and PAI-1, indicating inflammatory and pro-thrombotic activation. Structural, functional, and inflammatory readouts exhibited peak responses within a shared shear-vorticity regime. Multivariate regression identified shear-vorticity coupling as the dominant predictor of endothelial persistence, with optima clustering within a mechanical range ({approx}0.8-2.9 x 10 dyn{middle dot}cm-{superscript 2}{middle dot}s-{superscript 1}). These findings establish geometry-driven modulation of near-wall flow as a predictive, material-agnostic strategy for endothelialization and vasoprotection of high-shear cardiovascular implants.

bioengineering↗

RNA structural heterogeneity in a eukaryotic cell influences its heat shock response

RNA structure-based gene regulation remains under-explored in eukaryotes. While RNA can form different conformations in solution, the extent to which it folds into structure ensembles and how the different conformations regulate gene expression still needs to be fully understood. We coupled the SHAPE compound NAI-N3 with direct RNA sequencing to identify structure modifications along a single RNA molecule (sm-PORE-cupine). Using a combination of base mapping and direct signal alignment, we boosted the percentage of mappable RNA molecules from direct RNA sequencing. Using Bernoulli Mixture Model (BMM) clustering, we show that we can separate RNA structure ensembles from ligand-bound and unbound riboswitches accurately, identify isoform-specific structure ensembles along the SARS-CoV-2 genome, and determine RNA structure ensembles in the transcriptome of a eukaryote, C. albicans, at yeast (30{degrees}C) and hyphae (37{degrees}C) states. We observed that RNAs are more structurally homogenous at 37{degrees}C compared to 30{degrees}C, are more variable in vivo than in vitro, and show higher homogeneity in 3UTRs than in the coding region. We also identified structure ensembles that are associated with changes in translation efficiency and decay in C. albicans at 30{degrees}C and 37{degrees}C and validated translational changes using reporter assays. Our work shows that single-molecule RNA structure probing using direct RNA sequencing can be applied to diverse transcriptomes to study the complexity and function of RNA structures.

molecular biology↗

Neonatal mimicry of caregivers at home: feasibility of an asynchronous online paradigm

While early life sets the stage for later learning, comparatively less is known about newborns cognition than that of older infants. A striking example is the lack of consensus regarding the extent to which newborns spontaneously mimic gestures, and whether such behavior drives bonding and learning. Despite the theoretical importance of these questions, practical challenges limit researchers ability to engage newborns in behavioral research. Webcam-based, asynchronous online studies have expanded developmental sciences capacity to reach older infants. However, such scalable and replicable methods have yet to be deployed with younger infants. Taking a commonly-used neonatal mimicry paradigm as a test case, we assessed the feasibility of leveraging an open-source online platform (Children Helping Science) for asynchronous research with 0-6-week-olds and their caregivers. Caregivers modeled face movements to their 4-45 days-old infants (N = 29, N = 17 included) while webcams filmed their infants responses; 13 dyads participated more than once (72 included test videos). There was preliminary, moderate evidence against group-level neonatal mimicry of caregivers tongue protrusions (Bayes Factor [~] [1/3]), and inconclusive evidence for or against mimicry of caregivers mouth openings ([1/3] < BF < 3). Simulations identified a target sample size for more conclusive evidence. Finally, we asked whether caregivers perceived their newborns behavior as imitative. Caregivers perceptions of mimicry reflected infants behaviors but did not align with an often-used metric of mimicry ("imitators"). These results demonstrate the feasibility of asynchronous online behavioral studies with newborns and provide a foundation for future research on neonatal mimicry of caregivers.x1

neuroscience↗

Single-Cell Genomics Elucidates Molecular Variations and Regulatory Mechanisms in Circulating Immune Cells

The human peripheral blood displays diverse molecular characteristics across populations, understanding the drivers and underlying mechanisms of which remains challenging. Here, we introduce the Chinese Immune Multi-Omics Atlas (CIMA), elucidating sex-, age-, and genetic-related molecular variations by analyzing multi-omics data from 428 adults with over 10 million immune cells. CIMA generated an enhancer-driven gene regulatory network, identifying 237 high-quality regulons and revealing cell type-specific regulatory mechanisms. Additionally, 11,521 lead cis-expression quantitative trait loci (eQTLs) and 46,339 chromatin accessibility QTLs (caQTLs) were identified at cell type level. CIMA also uncovered pleiotropic associations among immune-related disease risk loci, eQTLs, and caQTLs in a cell type-specific manner. Lastly, a novel cell language model, CIMA-CLM, was developed to predict chromatin accessibility and noncoding variant effects using chromatin sequences and gene expressions. This work represents a population-scale multi-omics resource of human immune cells, providing a valuable reference for future investigation of immune-related diseases.

immunology↗

Multi-omics Reveals Immune Response and Metabolic Profiles during High-Altitude Mountaineering

The physiological perturbations induced by high-altitude exposure in mountain climbers, manifesting as metabolic and immunologic deviations, have been previously reported but are not fully understood. In this study, we obtained longitudinal multi-omic profiles of blood samples for healthy mountain climbers during two mountaineering stages (acclimatization and extreme altitude mountaineering). Our integrative assay included metabolomics and lipidomics profiling of plasma coupled with single-cell transcriptomic analysis of 375,722 immune cells. Longitudinal analysis revealed dynamic immune response profiles, during the acclimatization period, characterized by the downregulation of inflammatory responses in monocytes and classical dendritic cells (cDCs) and an increase in the proportion of cytotoxic CD8+ T cells with enhanced immune effector processes. In contrast, during extreme altitude mountaineering, the activation of inflammatory responses and impairment of T cell effector function were observed, concomitant with an increased cellular response to hypoxia and oxidative stress pathways. Furthermore, we found upregulated glycolysis and antioxidant gene expression during extreme altitude mountaineering, which was primarily orchestrated by HIF1A and NFE2L2, while decreased expression of these genes was observed in dysregulated plasmacytoid dendritic cells (pDCs). Finally, high-resolution plasma metabolic analysis revealed significant alterations in the metabolism of climbers, involving enhanced glutamine and fatty acid metabolism.

bioinformatics↗

Dynamics of the epigenetic landscape during development and in response to drought stress in sorghum

Sorghum bicolor is a C4 plant with the characteristics of high stress tolerance, which may be conferred partly by the underlying epigenetic mechanism unique to sorghum. In this study, we revealed some epigenomic features in sorghum that have never been reported before. The long H3K27me3 regions clustered in four areas, which we defined as H3K27me3 islands, were identified in sorghum. H3K36me3 plays some role in inhibiting the deposition of both H3K27me3 and H2A.Z, which may serve as partial motivation for the removal of H3K27me3 and H2A.Z in leaf and root. All the 7 histone marks are involved in the regulation of tissue-specific genes, especially the specific expression of C4 genes in leaf and peroxidase (POD) encoding genes in root, which are involved in the photosynthesis in leaf and lignin synthesis in root, respectively. These marks except H3K36me3 and H3K27me3 also engage in the regulation of stress genes in response to PEG treatment. However, we found that differential enrichment of histone marks on many tissue-specific genes was observed only between leaf and root but hardly in response to PEG treatment, although expression of these genes changed after PEG treatment.

plant biology↗

Correlation analysis between drug resistance and virulence genes of carbapenem-resistant Acinetobacter baumannii In Western Guilin

BackgoundIn order to detect the resistance of Acinetobacter baumannii to {beta}-lactam antibiotics in western Guilin, analyze the reasons for its resistance, and provide laboratory basis for clinical treatment; method for the {beta}-lactamase gene of Acinetobacter baumannii, and to explore the relationship between the presence of the {beta}-lactamase gene of Acinetobacter baumannii and multidrug resistance. MethodsFrom November 2020 to June 2022, 78 non-repeated Acinetobacter baumannii strains from the Second Affiliated Hospital of Guilin Medical University were collected, and their resistance to carbapenem antibiotics was analyzed. PCR was used to detect resistance-related genes (blaOXA-23, blaOXA-51, blaOXA-58, blaOXA-24, blaIMP and blaSIM) and virulence genes (cusE, abaI and bfmS). To analyze the relationship between drug resistance and virulence genes of Acinetobacter baumannii. ResultsMost of the 165 non-enterobacteriaceae bacteria we collected from the hospital were Acinetobacter baumannii and Pseudomonas aeruginosa, and most of the specimen types were from sputum and secretions, and most of them were from respiratory and critical care diseases area and intensive care unit, among them, there are 78 strains of Acinetobacter baumannii studied this time. After screening, 78 Acinetobacter baumannii strains were resistant to Cefazolin, Ampicillin, Amoxicillin/Clavulanate, Aztreonam, Chloramphenicol, Tetracycline, Cefotaxime, Ampicillin/Sulbactam, Piperacillin, Gentamicin, Ciprofloxacin, Levofloxacin, Moxifloxacin, Cefepime, Ceftazidime, Piperacillin/Tazobactam, Compound Sulfonamide, Meropenem, Imipenem, Amikacin, Polymyxin, resistance rates were 98.72%, 98.72%, 96.16%, 96.15%, 96.15%, 66.67%, 60.26%, 58.98%, 58.97%, 57.69%, 57.69%, 57.69%, 57.69%, 57.69%, 56.41%, 55.13%, 53.85%, 52.56%, 52.56%, 50%, 0%. Among them, 17 strains with drug resistance gene blaOXA-51 were detected,accounting for 21.79%; drug gene blaOXA-23, blaOXA-24, blaIMP, blaOXA-58, blaSIM gene were not detected; 17 strains with virulence gene bfmS was detected, accounting for 21.79%; abaI, csuE virulence gene was not detected. ConclusionAcinetobacter baumannii in the hospital is highly resistant to carbapenems, mainly carrying blaOXA-51 resistance genes. Drug resistance is closely related to the virulence gene bfmS.

microbiology↗

DeDoc2 identifies and characterizes the hierarchy and dynamics of chromatin TAD-like domains in the single cells

Topologically associating domains (TAD) are functional chromatin units with hierarchical structure. However, the existence, prevalence and dynamics of such hierarchy in single cells remain unexplored. Here, we report a new generation TAD-like domain (TLD) detection algorithm, named deDoc2, to decode the hierarchy of TLDs in single cells. With dynamic programming, deDoc2 seeks genome partitions with global minimal structure entropy for both whole and local contact matrix. Compared to state-of-the-art tools, deDoc2 can uniquely identify the hierarchy of TLDs in single cells, in addition to outperforming its competitors. By applying deDoc2, we showed that the hierarchy of TLDs in single cells is highly dynamic during cell cycle, as well as among human brain cortex cells, and that it is associated with cellular identity and functions. Thus, our results demonstrated the abundance of information potentially encoded by TLD hierarchy for functional regulation. The deDoc2 can be freely accessed at https://github.com/zengguangjie/deDoc2.

bioinformatics↗

A potential interacting network identified by quantitative proteomics for the sole adenylyl cyclase Cyr1 of Candida albicans

Cyr1, the sole adenylyl cyclase of the fungal pathogen Candida albicans, is a central component of the cAMP/PKA signaling pathway that controls the yeast-to-hyphal morphogenesis. Cyr1 functions as a multivalent senor and integrator of various external and internal signals. To better understand how these signals are relayed to Cyr1 and how Cyr1 activity is regulated, we sought to identify global interacting partners of Cyr1 using stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics. From the proteins co-immunoprecipitated with Myc-tagged Cyr1, 38 were assigned as authentic Cyr1-interacting partners, including two previously characterized Cyr1-binding proteins, Cap1 and Act1. Many of the identified proteins remain uncharacterized, but some can be classified into several functional groups, such as actin regulatory proteins, cell wall components, and mitochondrial proteins. We used biochemical and genetic methods to further characterize the interaction of Cyr1 with Mp65, a cell surface mannoprotein previously reported to have a role in cell wall integrity and possess several virulence-related traits. Taken together, our comprehensive analysis of the Cyr1-interacting proteins provides important information for establishing the Cyr1 interactome and uncovers a potential role for cell wall proteins in Cyr1-mediated cAMP signaling.

microbiology↗

Reversible supramolecular assembly of the anti-microbial peptide plectasin into helical non-amyloid fibrils

Self-assembly and fibril formation play important roles in protein behavior. Amyloid fibrils formation is well-studied due to its role in neurodegenerative diseases and characterized by refolding of the protein into predominant {beta}-sheet form. However, much less is known about the assembly of proteins into other types of supramolecular structures. Using cryo-electron microscopy at a resolution of 1.97 [A], we show that a triple-mutant of the anti-microbial peptide plectasin assembles reversibly into helical non-amyloid fibrils. Plectasin contains a cysteine-stabilized -helix-{beta}-sheets structure, which remains intact upon fibril formation. Two fibrils form a right-handed superstructure with each fibril consisting of double helical, left-handed structures. The fibril formation is reversible and follows sigmoidal kinetics with a pH-dependent equilibrium between soluble monomer and protein fibril. The anti-microbial activity does not appear compromised by fibril formation. This is the first high-resolution structure of this type of /{beta} protein fibrils.

biophysics↗

Landscape of microenvironment in Randall's plaque by single-cell sequencing

Randalls plaque is significantly associated with the occurrence of nephrolithiasis. However, the microenvironment of Randalls plaque is poorly characterized. To investigate the microenvironment of Randalls plaque, we analyzed single-cell RNA data of 3 Randalls plaque and 3 normal renal papillae tissue and identified 11 different cell types. We screened differentially expressed genes among all cell types between Randalls plaque and normal renal papillae. The microenvironment showed two cell types with multiple stone formation-associated transcriptomic programs. Contrary to previous studies, we did not observe macrophage M1/M2 imbalance. Notably, we detected ossification-associated macrophage is enriched in Randalls plaque and validated GPNMB and ACP5 were potential biomarkers on the ossification-associated macrophage. We also identified an endothelial subset harboring active communication (COL15A1+ PCDH17+ endothelial, DPECs) with other cells. Together with Immunofluorescence, we validated ossification-associated macrophage and DPECs are enriched in Randalls plaque tissue. Finally, cell-to-cell communication revealed that Loop of Henle, DPECs, and osteoblasts-associated macrophages was the main source of SPP1 signaling. Our work will further the understanding of the microenvironment among Randalls plaque tissues and provide deep insight into immune modulation.

bioinformatics↗

Genome recombination-mediated tRNA up-regulation conducts general antibiotic resistance of bacteria at early stage

Bacterial antibiotic resistance sets a great challenge to human health. It seems that the bacteria can spontaneously evolve resistance against any antibiotic within short time without the horizontal transfer of heterologous genes and before accumulating drug-resistant mutations. We have shown that the tRNA-mediated translational regulation counteracts the reactive oxygen species in bacteria. In this study, we demonstrated that isolated and subcultured Escherichia coli elevated its tRNAs under antibiotic stress to rapidly provide antibiotic resistance, especially at the early stage, before upregulating the efflux pump and evolving resistance mutations. The DNA recombination system repaired the antibiotic-induced DNA breakage in the genome, causing numerous structural variations. These structural variations are overrepresented near the tRNA genes, which indicated the cause of tRNA up-regulation. The strains knocking out the recombination system could not up-regulate tRNAs, and coincidently, they could hardly evolve antibiotic resistance in multiple antibiotics, respectively. With these results, we proposed a multi-stage model of bacterial antibiotic resistance in an isolated scenario: the early stage (recombination - tRNA up-regulation - translational regulation); the medium stage (up-regulation of efflux pump); the late stage (resistance mutations). These results also indicated that the bacterial DNA recombination system and tRNA could be targeted to retard the bacterial spontaneous drug resistance.

microbiology↗

Establishment and imaging evaluation of Guangxi Ba-Ma mini pigs as a model of cerebral hernia induced by acute intracranial hypertension

In order to establish an animal model of cerebral hernia induced by acute intracranial hypertension for subsequent research in emergency medicine. Six Guangxi Ba-Ma mini-pigs which were injected with autologous arterial blood by micropump to induce intracranial hematoma in the frontal and temporal parietal lobes. Changes in intracranial pressure (ICP), mean arterial blood pressure (MAP) and cerebral perfusion pressure (CPP)were observed during hematoma formation. Morphological changes and the occupying effects of intracranial hematoma were analyzed using computed tomography (CT) and magnetic resonance imaging (MRI) of the head. ICP, MAP and CPP gradually increased during blood injection, and they began to slowly decrease at 10 min after injection, though they remained higher than before injection. These three parameters were significantly different before blood injection, immediately after injection and at 10 min after injection (P< 0.05). Head CT and MRI showed cerebral hernia induced by acute intracranial hypertension. These results demonstrate micropump injection of autologous arterial blood can lead to acute intracranial hypertension in mini-pigs, which may be a useful model of cerebral hernia.

neuroscience↗

A novel function of Galactomyces candidum in highly efficient ammonia nitrogen removal from low C:N wastewater

A strain of bacteria that demonstrated efficient nitrogen removal potential under low C:N conditions was screened from landfill leachate. The strain was identified as Galactomyces candidum by ITS sequencing, and growth density and removal of ammonia nitrogen were assessed after 24 h of incubation. The results showed that the optimum ammonia nitrogen reduction conditions for G. candidum was at pH 8.0 and 30 {degrees}C, with a C:N ratio of 1.5:1; the highest rate of ammonia nitrogen removal was 93.1%. This novel function of G. candidum offers great potential in the removal of ammonia nitrogen from sewage, especially in low C:N wastewater. Our study provides a new theoretical basis for the industrial application of bacteria in the biochemical treatment of wastewater and reduces environmental pollution.\n\nA novel function and potential of Galamyces candidum in the removal of ammonia nitrogen from wastewater treatment was found, which provides a theoretical basis for the treatment of ammonia in wastewater.

microbiology↗

High-throughput fitness profiling of Zika virus E protein reveals different roles for N-linked glycosylation during infection of mammalian and mosquito cells

Zika virus (ZIKV) infection causes Guillain-Barre syndrome and severe birth defects. ZIKV envelope (E) protein is the major viral protein involved in cell receptor binding and entry and therefore considered one of the major determinants in ZIKV pathogenesis. Here, we report a gene-wide mapping of functional residues of ZIKV E protein using a mutant library with changes covering every nucleotide position. By comparing the replication fitness of every viral mutant between mosquito and human cells, we identified that mutations affecting N-linked glycosylation at N154 position display the most divergence. Through characterizing individual mutants, we show that, while ablation of N-linked glycosylation selectively benefits ZIKV infection of mosquito cells by enhancing cell entry, it either had little impact on ZIKV infection on certain human cells or decreased infection through entry factor DC-SIGN. In conclusion, we define the roles of individual residues of ZIKV envelope protein, which contribute to ZIKV replication fitness in human and mosquito cells.\n\nHighlightsO_LIGene-wide mapping of functional residues of E protein in human and mosquito cells.\nC_LIO_LIMutations affecting N-linked glycosylation display the most dramatic difference.\nC_LIO_LIN-linked glycosylation decreases ZIKV entry into mosquito cells.\nC_LIO_LIN-linked glycosylation is important for DC-SIGN mediated infection of human cells.\nC_LI

microbiology↗