Signal Response Research Articles

The rational design of ratiometric probe based on fluorescence carbon dots and its PVA film platform for the detection of Hg2+: tunable mechanism and the performance

Carbon dots (CDs) are recognized as sensitive probes for the detection of Hg2+ due to their remarkable fluorescent properties and ease of synthesis. However, drawbacks such as high costs, intricate synthesis, and non-portability hinder their broader applications. This study reported the synthesis of tunable multicolor CDs, including blue (B-CDs), green (G-CDs), and orange (O-CDs), by using hydrothermal methods while adjusting precursors and temperature. The observed fluorescence redshift from B-CDs to G-CDs or O-CDs arose from interactions among particle size, sp² conjugation, and surface oxidation, while the redshift from G-CDs to O-CDs was linked to surface fluorophores. Moreover, a ratiometric probe was developed by mixing B-CDs (response signal) and O-CDs (reference signal). Hg2+ significantly quenched B-CDs fluorescence due to static quenching from electron transfer. The probe demonstrated excellent stability and sensitivity, with limits of detection (LOD) of 4.8nM in the 0-0.6μM range and 9.2nM in a broader range (0-50μM). A portable smartphone-assisted detection platform was further developed by integrating the probe into polyvinyl alcohol (PVA) hydrogel. Both methods manifested the capability to accurately quantify Hg2+ in real water samples. This research provides innovative strategies for multicolor CDs and a sensing platform for rapid on-site Hg2+ detection.

3D-printing and MATLAB assisted ratiometric-sensing platform for visual on-site sensing of tetracycline using color conversion strategy

In this research, a ratiometric-sensing platform (ZIF-8/CDs) that combines non-fluorescence metal–organic frameworks (ZIF-8) with blue-green fluorescent carbon dots (CDs) has been developed for the determination of tetracycline (TC) with high sensitivity and selectivity in real samples. For this purpose, ZIF-8 with polyhedral structure was synthesized, which could form aggregation-induced emission (AIE) effect through electrostatic, hydrogen bonding, π-π stacking, and coordination interactions in the presence of TC, leading to enhanced intensity with a bright yellow fluorescence at 516 nm, acting as a response signal. However, the fluorescence intensity of blue-green fluorescent CDs maintained practically constant at 466 nm, serving as a reference signal. Furthermore, we integrate MATLAB algorithm and 3D-printing technology with the ZIF-8/CDs complex into a ratiometric-sensing platform for semi-quantitative detection of TC, in which 3D-printing technology is responsible for engineering an integrated dark chamber to achieve the fluorescence images of real samples, whereas MATLAB with the image processing functions and data processing capabilities utilizes to develop a mini program for calculating the RGB values of the obtained images. Consequently, the ratiometric-sensing platform in a simple, rapid, and economic way without any complicated process and expensive instruments could be used for visual/onsite detection of TC in real samples.

Time-Domain Load Identification and Dynamic Displacement Inversion of Discharge Sluice in Large Hydropower Stations Based on the Conjugate Gradient Least Squares Iteration Algorithm

The identification of flow-induced vibration loads is the key to solving the vibration problem of hydraulic structures induced by high-speed water flow. In this study, a time-domain load identification method for discharge sluices in large hydropower stations based on the conjugate gradient least squares (CGLS) iteration algorithm is proposed. The main idea of this method is to first construct a mathematical model through the response signal and the structural modal parameters for solving the equivalent load acting on the sluice structure. Then, it uses the iterative regularization method to solve the ill-posed problem in the load identification process of the traditional time-domain method. Numerical simulations show that, in comparison to the traditional Tikhonov regularization algorithm, the CGLS algorithm is capable of reducing the relative error of the identified dynamic loads by approximately 100%, with higher accuracy and noise immunity. In this study, the CGLS algorithm is used to identify the external dynamic loads acting on the sluice structure during the flood discharge process of a large hydropower station in China. Three equivalent dynamic loads acting on the pier and the bottom plate are obtained. The positive analysis of the vibration response of the discharge structure is conducted using the equivalent load. The results show that the error between the measured vibration response signals and the vibration response signals obtained from the positive analysis is relatively minor, with the exception of a few individual measurement points. The displacement response mean square error is less than 10%, thereby substantiating the accuracy and validity of the CGLS load identification method proposed in this study in the actual engineering.

Genome-wide identification of gap junction gene family and their expression profiles under low temperature stress in noble scallop Chlamys nobilis

Gap junctions, formed by gap junction proteins (GJ), play crucial roles in cell signaling and immune responses. The structure and function of the GJ from vertebrates (called connexins) have been extensively studied. However, little is known about the proteins forming gap junctions in invertebrates (called innexins). In this study, 14 GJ genes of Chlamys nobilis were identified. GJ proteins are mainly distributed on the plasma membrane, and all proteins are hydrophilic Phylogenetic tree analysis showed that the GJ proteins in C. nobilis were distantly related to those in vertebrates but closely related to those in invertebrates. Conserved motifs analysis of these GJ proteins in C. nobilis identified to have 10 conserved motifs, similar to gap junction proteins in other bivalves. Moreover, expression profiles of CnGJ genes under chronic and acute low temperature stress were also investigated. Results showed that chronic low temperature stress had a significant effect on the expression levels of CnGJ genes, and the expression profiles of CnGJ genes showed significantly variation under acute low temperature stress. All these results indicated that CnGJ genes play important roles in environmental adaptation in scallops. The present study initially elucidated the function of gap junction genes in noble scallop C. nobilis, which provides new insights into the GJ genes in mollusks and will help us better understand their roles in environmental stress in scallops.

SARS-CoV-2 disrupts host gene networks: unveiling key hub genes as potential therapeutic targets for COVID-19 management

Although the end of COVID-19 as a public health emergency was declared on May 2023, still new cases of the infection are reported and the risk remains of new variants emerging that may cause new surges in cases and deaths. While clinical symptoms have been rapidly defined worldwide, the basic body responses and pathogenetic mechanisms acting in patients with SARS-CoV-2 infection over time until recovery or death require further investigation. The understanding of the molecular mechanisms underlying the development and course of the disease is essential in designing effective preventive and therapeutic approaches, and ultimately reducing mortality and disease spreading. The current investigation aimed to identify the key genes engaged in SARS-CoV-2 infection. To achieve this goal high-throughput RNA sequencing of peripheral blood samples collected from healthy donors and COVID-19 patients was performed. The resulting sequence data were processed using a wide range of bioinformatics tools to obtain detailed modifications within five transcriptomic phenomena: expression of genes and long non-coding RNAs, alternative splicing, allel-specific expression and circRNA production. The in silico procedure was completed with a functional analysis of the identified alterations. The transcriptomic analysis revealed that SARS-CoV-2 has a significant impact on multiple genes encoding ribosomal proteins (RPs). Results show that these genes differ not only in terms of expression but also manifest biases in alternative splicing and ASE ratios. The integrated functional analysis exposed that RPs mostly affected pathways and processes related to infection-COVID-19 and NOD-like receptor signaling pathway, SARS-CoV-2-host interactions and response to the virus. Furthermore, our results linked the multiple intronic ASE variants and exonic circular RNA differentiations with SARS-CoV-2 infection, suggesting that these molecular events play a crucial role in mRNA maturation and transcription during COVID-19 disease. By elucidating the genetic mechanisms induced by the virus, the current research provides significant information that can be employed to create new targeted therapeutic strategies for future research and treatment related to COVID-19. Moreover, the findings highlight potentially promising therapeutic biomarkers for early risk assessment of critically ill patients.

Elucidation of molecular mechanisms, pathways, and diseases modulated by arsenicals through toxogenomics and multi-omics analysis

Arsenic compounds exist in inorganic and organic forms with inorganic form confirmed as a potent carcinogen. Toxogenomics and multi-omics analysis were used to explore the molecular mechanisms of carcinogenecity induced by arsenicals. Comparative toxogenomics revealed sodium arsenite and arsenate as the most toxic arsenicals to humans, interacting with various genes and altering gene expression through mRNA binding proteins. Both metalloids were classified as Class II toxins by the ProTox II prediction tool, with a lethal dose (LD50) of 149mg/kg body weight. The most frequently interacting genes were HMOX1, CAT, NFE2L2, CASP3, MAPK1, CXCL8, PARP1, TNF, and PYGM. Analysis of TCGA pan-cancer data revealed that 46% of hepatocellular carcinoma patients exhibited alterations in the genes HMOX1, CAT, NFE2L2, CASP3, MAPK1, CXCL8, PARP1, TNF, and PYGM, suggesting their significant role in the development of this disease. The alteration in the gene list decreased the overall patient survival but insignificantly in the Kaplan-Meier curves revealing insignificant role in survival. GSEA suggested significant enrichment of the gene list in pathways involved in the G2M checkpoint, apoptosis, hypoxia, TNFA signaling via NFKB, PI3K AKTMTOR signaling, P53, IFN gamma and inflammatory response pathways revealing the involvement of these pathways. Ten microRNAs (miRNAs) regulated the expressions of the genes involved in the above-mentioned pathways with the significant enrichment in miR-21-3p, miR-206 and mir486a-5p. The relevant pathway and graphical representation of the network of miRNA-target interactions identified by the enrichment analysis along with disease ontologies were predicted. This study will be helpful insight into setting of laboratory experiments.

Identification and functional network analysis of inflammatory and apoptosis-related genes associated with infectious chronic rhinosinusitis: Thermal modeling of medical biological systems

The aim of this study was to identify inflammatory and apoptotic genes associated with infectious chronic sinusitis and to analyze their functional networks in medical biological systems by thermal modeling. Bioinformatics analysis was used to identify genes involved in apoptosis and inflammation and construct their functional networks. Finally, thermal modeling techniques were used to explore the dynamic changes of these genes in the pathogenesis of chronic sinusitis. In a comparative analysis, thermal modeling analysis revealed that these genes play important roles in apoptosis, immune response, and inflammatory signaling pathways. In addition, the heat model also revealed the interaction network between different genes, providing a new perspective for understanding the coordination mechanism of inflammation and apoptosis. Through the identification of genes associated with infectious chronic sinusitis and thermal modeling analysis of their functional networks, this study revealed the complex interaction between apoptosis and inflammation in the disease process.

Toxicogenomic Assessment of In Vitro Macrophages Exposed to Profibrotic Challenge Reveals a Sustained Transcriptomic Immune Signature.

Immune signalling is a crucial component in the progression of fibrosis. However, approaches for the safety assessment of potentially profibrotic substances, that provide information on mechanistic immune responses, are underdeveloped. This study aimed to develop a novel framework for assessing the immunotoxicity of fibrotic compounds. We exposed macrophages in vitro to multiple sublethal concentrations of the profibrotic agent bleomycin, over multiple timepoints, and generated RNA sequencing data. Using a toxicogenomic approach, we performed dose-dependent analysis to discover genes dysregulated by bleomycin exposure in a dose-responsive manner. A subset of immune genes displayed a sustained dose-dependent and differential expression response to profibrotic challenge. An immunoassay revealed cytokines and proteinases responding to bleomycin exposure that closely correlated to transcriptomic alterations, underscoring the integration between transcriptional immune response and external immune signalling activity. This study not only increases our understanding of the immunological mechanisms of fibrosis, but also offers an innovative framework for the toxicological evaluation of substances with potential fibrogenic effects on macrophage signalling. Our work brings a new immunotoxicogenomic direction for hazard assessment of fibrotic compounds, through the implementation of a time and resource efficient in vitro methodology.

Enhancement of the signal resolution in aptamer assay upon target binding by employing DNA probes and dual fluorophores

In this study, we aimed to significantly enhance the resolution of aptamer assays by using DNA probes and dual fluorophores. The resolution is defined as the smallest change in the target concentration that causes a reliable and distinguishable signal change. Therefore, resolution enhancement in the aptamer assay ensures improved analytical performance. We first examined four aptamer-probe combinations in the aptamer assay and investigated the resolution by observing a percentage signal response difference (% ΔAAD/SYBR). A large % ΔAAD/SYBR means a discernable signal change for a certain concentration difference, which indicates a high-resolution assay. Consequently, significant resolution enhancement (approximately 3–7 times) was achieved using two DNA probes. The improved analytical performance of the resolution-enhanced aptamer assay was further demonstrated by a wide working range of quantification (i.e., 10−2–102 mg/L, four orders of magnitude), a regression curve with improved fitness, and a lower limit of detection (LOD) response (2–6 times lower).

Pomegranate peel extract for green synthesis of magnetite (Fe3O4) nanozymes as a colorimetric probe for determination of diclofenac

A nanozyme based on Fe3O4 was constructed for colorimetric detection of diclofenac in pharmaceutical formulations. Firstly, an eco-friendly, rapid, and simple green approach was introduced to synthesize magnetite (Fe3O4) nanoparticles. Pomegranate peel extract was employed as a green reducing and stabilizing agent. The synthesized magnetite NPs were characterized by field emission scanning electron microscopy, transmission electron microscopy, Fourier transform infrared, ultraviolet–visible spectroscopy, energy-dispersive X-ray spectroscopy, BET, X-ray diffraction, and zeta potential (Ƶ) techniques and have an average size of 14.24 nm. In the presence of hydrogen peroxide, a redox interaction takes place, and the resulting hydroxyl promotes a colorimetric conversion from colorless to blue in the presence of 3,3′,5,5′-tetra-methyl-benzidine (TMB). In addition, diclofenac can inhibit colorimetric conversion once it competes with TMB’s interaction with hydroxyl. There is a relationship between the colorimetric distinction and the target amount. It is also obvious that there is a colorimetric distinction between diclofenac and TMB due to their competition. The signal responses to diclofenac are linear in the range of 0.1–75 mg/L, and the limit of detection is 0.01 mg/L. In practical assays of diclofenac in pharmaceutical formulations, the relative standard deviation of the sample tests is 0.51 %, and the recovery for the spiked assays is 96.93 % with an RSD of 1.68 %. The effects of different interferences were studied with recovery ranging from 95.02 to 99.93 %

Astaxanthin‐S‐Allyl Cysteine Ester Protects Pancreatic β‐Cell From Glucolipotoxicity by Suppressing Oxidative Stress, Endoplasmic Reticulum Stress and mTOR Pathway Dysregulation

ABSTRACTGlucolipotoxicity (GLT) has emerged as established mechanism in the progression of diabetes. Identifying compounds that mitigate GLT‐induced deleterious effect on β‐cells are considered important strategy to overcome diabetes. Hence, in the present study, astaxanthin‐s‐allyl cysteine (AST‐SAC) diester was studied against GLT in β‐cells. Mus musculus pancreatic β‐cell line (βTC‐tet) was treated with high glucose (25 mM; HG) and 95 μM palmitate (PA) for 24 h to induce GLT. AST‐SAC at various concentrations (5, 10, and 15 μg/ml) were treated to understand the protective effect against HG + PA exposure in β‐cells. Under HG + PA exposure conditions oxidative stress, deregulation of mTOR pathway and endoplasmic reticulum (ER) stress are witnessed. AST‐SAC treatment eased oxidative stress, mitochondrial depolarization, DNA damage, calcium overload and accumulation of autophagosome against HG + PA exposure conditions thereby protected the cell viability of β‐cells. AST‐SAC maintained the level of proteins involved in mTOR pathway under HG + PA exposure conditions. Also, AST‐SAC treatment has mitigated the increased expression of genes and proteins such as IRE1 and PERK involved in ER stress‐mediated unfolded protein response (UPR) signaling pathways. In correspondence to it, the expression of genes involved in insulin secretion was preserved by AST‐SAC. Due to these protective effects of AST‐SAC the insulin secretion was well‐maintained in β‐cells under HG + PA exposure conditions. AST‐SAC through normalizing antioxidant status and mTOR axis as well as preventing the harmful effect of ER‐stress mediated UPR pathway has promoted the β‐cell survival and insulin secretion against GLT. Simultaneously targeting oxidative stress/mTOR axis/ER stress is required to efficiently overcome GLT in β‐cells.

Time-dependent changes in genome-wide gene expression and post-transcriptional regulation across the post death process in silkworm.

Despite death marking the end of life, several gene expression and miRNA-mediated post-transcriptional regulation events may persist or be initiated. The silkworm (Bombyx mori) is a valuable model for exploring life processes, including death. In this study, we combined transcriptomics and miRNAomics analyses of young, old, and postmortem silkworms across the entire process after death to unravel the dynamics of gene expression and miRNA-mediated post-transcriptional regulation. In total, 171 genes exhibited sustained differential expression in postmortem silkworms compared to the pre-death state, which are primarily involved in nerve signaling, transport, and immune response. Postmortem time-specific genes were associated with cell cycle regulation, thermogenesis, immunity, and zinc ion homeostasis. We found that the down-regulated expression of 36 genes related to transcription, epigenetic modification, and homeostasis resulted in a significant shift in global gene expression patterns at 2h post-death. We also identified five mRNA-miRNA pairs (i.e., bmo-miR-2795-mhca, 2784-achi, 2762-oa1, 277-5p-creb, and 1000-tcb1) associated with stress hormone regulation, transcription activity, and signal transduction. The roles of these pairs were validated through in vivo experiments using miRNA mimics in silkworms. The findings provide valuable insights into the intricate mechanisms underlying the transcriptional and miRNA-mediated post-transcriptional regulation events in animals after death.

Dichotomous outcomes of TNFR1 and TNFR2 signaling in NK cell-mediated immune responses during inflammation.

Natural killer (NK) cell function is regulated by a balance of activating and inhibitory signals. Tumor necrosis factor (TNF) is an inflammatory cytokine ubiquitous across homeostasis and disease, yet its role in regulation of NK cells remains unclear. Here, we find upregulation of the immune checkpoint protein, T cell immunoglobulin and mucin domain 3 (Tim3), is a biomarker of TNF signaling in NK cells during Salmonella Typhimurium infection. In mice with conditional deficiency of either TNF receptor 1 (TNFR1) or TNF receptor 2 (TNFR2) in NK cells, we find TNFR1 limits bacterial clearance whereas TNFR2 promotes it. Mechanistically, via single cell RNA sequencing we find that both TNFR1 and TNFR2 induce the upregulation of Tim3, while TNFR1 accelerates NK cell death but TNFR2 promotes NK cell accumulation and effector function. Our study thus highlights the complex interplay of TNF-based regulation of NK cells by the two TNF receptors during inflammation.

Contact area and tissue growth dynamics shape synthetic juxtacrine signaling patterns.

Cell-cell communication through direct contact, or juxtacrine signaling, is important in development, disease, and many areas of physiology. Synthetic forms of juxtacrine signaling can be precisely controlled and operate orthogonally to native processes, making them a powerful reductionist tool with which to address fundamental questions in cell-cell communication in vivo. Here we investigate how cell-cell contact length and tissue growth dynamics affect juxtacrine signal responses through implementing a custom synthetic gene circuit in Drosophila wing imaginal discs alongside mathematical modeling to determine synthetic Notch (synNotch) activation patterns. We find that the area of contact between cells largely determines the extent of synNotch activation, leading to the prediction that the shape of the interface between signal-sending and signal-receiving cells will impact the magnitude of the synNotch response. Notably, synNotch outputs form a graded spatial profile that extends several cell diameters from the signal source, providing evidence that the response to juxtacrine signals can persist in cells as they proliferate away from source cells, or that cells remain able to communicate directly over several cell diameters. Our model suggests the former mechanism may be sufficient, since it predicts graded outputs without diffusion or long-range cell-cell communication. Overall, we identify that cell-cell contact area together with output synthesis and decay rates likely govern the pattern of synNotch outputs in both space and time during tissue growth, insights that may have broader implications for juxtacrine signaling in general.

Expression analysis of genes related to abscisic acid biosynthesis and signaling in response to flooding stress in sweetpotato

Expression analysis of genes related to abscisic acid biosynthesis and signaling in response to flooding stress in sweetpotato

Gene expression profiling reveals host defense strategies for restricting Candida albicans invasion and gastritis to the limiting ridge of the murine stomach.

Candida albicans is a fungal constituent of the human gastrointestinal microbiota that can tolerate acidic environments like the stomach, where it can be associated with ulcers and chronic gastritis. In mice, C. albicans induces gastritis without concurrent intestinal inflammation, suggesting that the stomach is particularly prone to fungal infection. We previously showed that C. albicans invasion in the limiting ridge does not extend to or elicit an inflammatory response in the adjacent glandular region, indicating regionalized gastritis in the murine stomach. However, the molecular pathways involved in the host response to C. albicans specifically in the limiting ridge have not been investigated. Here, we found that gastric dysbiosis was associated with C. albicans limiting ridge colonization and gastritis. We isolated the limiting ridge and evaluated the expression of over 90 genes involved in mucosal responses. C. albicans infection triggered a type 3 immune response marked by elevated Il17a, Il17f, Il1b, Tnf, and Il36g, as well as an upregulation of Il12a, Il4, Il10, and l13. Chemokine gene induction (including Ccl2, Ccl3, Ccl4, Ccl1l, Cxcl1, Cxcl2, Cxcl9, and Cxcl10) coincided with an influx of neutrophils, monocytes/macrophages, and eosinophils. Hyphal invasion caused tissue damage, epithelial remodeling, and upregulation of genes linked to epithelium signaling and antimicrobial responses in the limiting ridge. Our findings support a need for continued exploration into the interactions between the immunological milieu, the host microbiota, and clinical interventions such as the use of antibiotics and immunotherapeutic agents and their collective impact on invasive candidiasis risk.

Tai/NCOA2 suppresses the Hedgehog pathway by directly targeting the transcription factor Ci/GLI

The Hedgehog (Hh) pathway plays diverse roles in cellular processes by activating the transcription factor Cubitus interruptus (Ci). Abnormal regulation of this pathway has been linked to various human diseases. While previous studies have focused on how Ci is regulated in the cytoplasm, the control of nuclear Ci remains poorly understood. In this study, we have found that the transcriptional cofactor Taiman (Tai) functions as an inhibitor of the Hh pathway. Tai interferes with the response of Hh signal, rather than Hh secretion. Our epistatic analyses reveal that Tai works in parallel with Ci to reduce its activity, thereby counteracting organ overgrowth and the activation of target genes caused by Ci overexpression. Specifically, Tai interacts with Ci to decrease its binding to target gene promoters. The Hh signal weakens the interaction between Ci and Tai, releasing the inhibition on Ci. Importantly, this regulatory mechanism is conserved from Drosophila to mammalian cells. Moreover, NCOA1-3 are the mammalian ortholog of Drosophila protein Tai, but only NCOA2 plays a similar role in inhibiting the Hh pathway. These findings reveal an additional way to modulate the transcriptional activity of nuclear Ci.

Surface-Enhanced Raman Scattering-Based Multimodal Techniques: Advances and Perspectives.

Surface-enhanced Raman scattering (SERS) spectroscopy is a versatile molecular fingerprinting technique with rapid signal readout, high aqueous compatibility, and portability. To translate SERS for real-world applications, it is pertinent to overcome inherent challenges, including high sample variability and heterogeneity, matrix effects, and nonlinear SERS signal responses of different analytes in complex (bio)chemical matrices with numerous interfering species. In this perspective, we highlight emerging SERS-based multimodal techniques to address the key roadblocks to improving the sensitivity, specificity, and reliability of (bio)chemical detection, bioimaging, theragnosis, and theragnostic. SERS-based multimodal techniques can be broadly categorized into two categories: (1) complementary methods or systems that work together to achieve a common goal where each method compensates for the weaknesses of the other to culminate in a single enhanced outcome or (2) orthogonal techniques that are independent and provide separate but corroborating results simultaneously without interfering with each other. These multimodal techniques maximize information gained from a single experiment to achieve enhanced qualitative or quantitative analysis and broaden the range of detectable analytes from small molecules to tissues. Finally, we discuss emerging directions in multimodal platform design, instrument integration, and data analytics that aim to push the analytical limits of holistic detection.

Anchorage of bacterial effector at plasma membrane via selective phosphatidic acid binding to modulate host cell signaling.

Binding phospholipid is a simple, yet flexible, strategy for anchorage of bacterial effectors at cell membrane to manipulate host signaling responses. Phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-biphosphate are the only two phospholipid species known to direct bacterial effectors to establish inner leaflet localization at the plasma membrane. Here, selectivity of phosphatidic acid (PA) by bacterial effectors for the plasma membrane anchorage and its molecular entity was identified. C-terminal BID domain of Bartonella T4SS effectors (Beps) directed the plasma membrane localization of Beps in host cells through binding with PA. A hydrophobic segment of the 'HOOK' subdomain from BID is inserted into the bilayer to enhance the interaction of positively charged residues with the lipid headgroups. Mutations of a conserved arginine facilitating the electrostatic interaction, a conserved glycine maintaining the stability of the PA binding groove, and hydrophobic residues determining membrane insertion, prevented the anchorage of Beps at the plasma membrane. Disassociation from plasma membrane to cytosol attenuated the BepC capacity to induce stress fiber formation and cell fragmentation in host cells. The substitution of alanine with aspartic acid at the -1 position preceding the conserved arginine residue hindered BepD anchoring at the plasma membrane, a vital prerequisite for its ability to elicit IL-10 secretion in host macrophages. In conclusion, our findings reveal the PA-binding properties of bacterial effectors to establish plasma membrane localization and will shed light on the intricate mechanisms employed by bacterial effectors within host cells.

Investigation on the variations of dynamic characteristics of anchor bolts considering transverse inertia effects under tensile loads

Abstract In the case where tunnel anchor bolts are located in strata with limited surrounding rock boundaries, the response signals of the anchor bolts are affected by the tensile load and the transverse inertia effect, resulting in a decrease in the reliability of the non-destructive testing (NDT) results. To accurately assess the anchorage quality under these disturbances, a vibration energy loss model for anchor bolts after excitation was proposed. NDT experiments and numerical simulation studies were conducted on intact and defective anchor bolts under different conditions, analyzing the variation patterns of structural dynamic characteristics such as the the first-order natural frequency, the first-order damping ratio, and the vibration energy loss under the influence of tensile load and transverse inertia effect. The results show that during the gradual increase of the tensile load, the first-order natural frequency and the first-order damping ratio exhibit an overall trend of first increasing and then decreasing, while the rate of the energy loss initially decreases and then increases. The presence of anchorage defects leads to a reduction in the first-order natural frequency, the first-order damping ratio, and the energy loss of the anchor bolt. As the transverse inertia effect intensifies, the first-order natural frequency initially increases and then decreases, the first-order damping ratio decreases, and the energy loss initially decreases slightly before increasing. The numerical simulation verifies the applicability of the theoretical model and explores the influence of defect location on energy loss. The results indicate that the closer the defect location is to the free end, the less the vibration energy loss of the anchor bolt.