Modulation Function Research Articles

The STING signaling pathways and bacterial infection.

As antibiotic-resistant bacteria continue to emerge frequently, bacterial infections have become a significant and pressing challenge to global public health. Innate immunity triggers the activation of host responses by sensing "non-self" components through various pattern recognition receptors (PRRs), serving as the first line of antibacterial defense. Stimulator of interferon genes (STING) is a PRR that binds with cyclic dinucleotides (CDN) to exert effects against bacteria, viruses, and cancer by inducing the production of type I interferon and inflammatory cytokines, and facilitating regulated cell death. Currently, drugs targeting the STING signaling pathway are predominantly applied in the fields of modulating host immune defense against cancer and viral infections, with relatively limited application in treating bacterial infections. Given the significant immunomodulatory functions of STING in the interaction between bacteria and hosts, this review summarizes the research progress on STING signaling pathways and their roles in bacterial infection, as well as the novel functions of STING modulators, aiming to offer insights for the development of antibacterial drugs.

Multi-Terminal DC Transformer for Renewable Energy Cluster Grid Connection

An AC (alternative current) power integration of distributed energies faces multi-fold challenges such as synchronization and weak grid-induced instability. In this study, a multi-terminal DC transformer is proposed for renewable energy clusters grid connection. The DC transformer provides multiple DC input ports for renewable energy collection, while the load port is connected to the medium-voltage DC grid via a modular multilevel converter (MMC). The multi-port topology enables flexible power transfer between multiple input sources to the load without additional components. The carrier layer modulation strategy is implemented to balance the MMC module voltage; bidirectional power transmission between multiple input sources is achieved through the phase shift modulation (PSM) method. First, we provided a detailed introduction of the proposed topology and working principle. A simulation model was built using the SIMULINK, and the simulation results verified the effectiveness of the proposed converter modulation strategy and phase shift modulation method. A corresponding hardware experimental platform was designed and built, and the modulation and voltage equalization functions of modular multilevel rectifiers were presented as well as the measured results of power transmission modulation of the converter under single-input and multi-input conditions. The results indicate that the proposed transformer can achieve multiple DC inputs and has multi-channel power transmission capabilities, making it suitable for renewable energy clusters grid connection.

Crystal structure of the incommensurate modulated high-pressure phase of the potassium guaninate monohydrate.

The crystal structure of the incommensurate modulated phase of potassium guaninate monohydrate has been solved on the basis of high-pressure single-crystal X-ray diffraction data. The modulated structure was described as a `mosaic' sequence of three different local configurations of two neighbouring guaninate rings. In contrast to known examples of incommensurate modulated organic compounds, the modulation functions of all atoms are discontinuous. This is the first example of the experimental detection of an incommensurate modulated crystal structure that can be modelled using the special `soliton mode' modulation function proposed by Aramburu et al. [(1995), J. Phys. Condens. Matter, 7, 6187-6196].

Functional role of myosin-binding protein H in thick filaments of developing vertebrate fast-twitch skeletal muscle.

Myosin-binding protein H (MyBP-H) is a component of the vertebrate skeletal muscle sarcomere with sequence and domain homology to myosin-binding protein C (MyBP-C). Whereas skeletal muscle isoforms of MyBP-C (fMyBP-C, sMyBP-C) modulate muscle contractility via interactions with actin thin filaments and myosin motors within the muscle sarcomere "C-zone," MyBP-H has no known function. This is in part due to MyBP-H having limited expression in adult fast-twitch muscle and no known involvement in muscle disease. Quantitative proteomics reported here reveal that MyBP-H is highly expressed in prenatal rat fast-twitch muscles and larval zebrafish, suggesting a conserved role in muscle development and prompting studies to define its function. We take advantage of the genetic control of the zebrafish model and a combination of structural, functional, and biophysical techniques to interrogate the role of MyBP-H. Transgenic, FLAG-tagged MyBP-H or fMyBP-C both localize to the C-zones in larval myofibers, whereas genetic depletion of endogenous MyBP-H or fMyBP-C leads to increased accumulation of the other, suggesting competition for C-zone binding sites. Does MyBP-H modulate contractility in the C-zone? Globular domains critical to MyBP-C's modulatory functions are absent from MyBP-H, suggesting that MyBP-H may be functionally silent. However, our results suggest an active role. In vitro motility experiments indicate MyBP-H shares MyBP-C's capacity as a molecular "brake." These results provide new insights and raise questions about the role of the C-zone during muscle development.

TRβ activation confers AT2-to-AT1 cell differentiation and anti-fibrosis during lung repair via KLF2 and CEBPA

Aberrant repair underlies the pathogenesis of pulmonary fibrosis while effective strategies to convert fibrosis to normal regeneration are scarce. Here, we found that thyroid hormone is decreased in multiple models of lung injury but is essential for lung regeneration. Moreover, thyroid hormone receptor α (TRα) promotes cell proliferation, while TRβ fuels cell maturation in lung regeneration. Using a specific TRβ agonist, sobetirome, we demonstrate that the anti-fibrotic effects of thyroid hormone mainly rely on TRβ in mice. Cellularly, TRβ activation enhances alveolar type-2 (AT2) cell differentiation into AT1 cell and constrains AT2 cell hyperplasia. Molecularly, TRβ activation directly regulates the expression of KLF2 and CEBPA, both of which further synergistically drive the differentiation program of AT1 cells and benefit regeneration and anti-fibrosis. Our findings elucidate the modulation function of the TRβ-KLF2/CEBPA axis on AT2 cell fate and provide a potential treatment strategy to facilitate lung regeneration and anti-fibrosis.

Mechanisms of Reappeared Period Shifts of Internal Solitary Waves Based on Mooring Array Observations in the Northern South China Sea

AbstractMooring observations have revealed that the daily reappeared time (DRt) of internal solitary waves (ISWs) in the northern South China Sea (SCS) manifests systematic shifts. This study aims to reveal the dynamic mechanisms behind this phenomenon using the theory of modulation of shear flow to the internal tide wave (IT) propagation. Approximate solutions for the frequency modulation function (FMF) and the amplitude modulation function (AMF) of ITs are derived and validated by the mooring array measurements on the northern SCS continental shelf in 2019 and 2020. Namely, the mechanisms of the ISW reappeared period shift (RPS derived from DRt) and amplitude variation are attributed to the modulation of low‐frequency flow with a period of about 7 days to ITs. The FMF is induced by the vorticity of the low‐frequency flow (FS1) and the Doppler shift (FS2). Thus, the sign of the FMF value may be positive (blue shift) and negative (red shift), depending on the algebraic summation of the two terms. The FS2 derived from mooring observed velocities confirms the modulation effects of mean current on the frequency shift and the amplitude variation of ITs and ISWs.

Research of multi-label text classification based on label attention and correlation networks.

Multi-Label Text Classification (MLTC) is a crucial task in natural language processing. Compared to single-label text classification, MLTC is more challenging due to its vast collection of labels which include extracting local semantic information, learning label correlations, and solving label data imbalance problems. This paper proposes a model of Label Attention and Correlation Networks (LACN) to address the challenges of classifying multi-label text and enhance classification performance. The proposed model employs the label attention mechanism for a more discriminative text representation and uses the correlation network based on label distribution to enhance the classification results. Also, a weight factor based on the number of samples and a modulation function based on prediction probability are combined to alleviate the label data imbalance effectively. Extensive experiments are conducted on the widely-used conventional datasets AAPD and RCV1-v2, and extreme datasets EUR-LEX and AmazonCat-13K. The results indicate that the proposed model can be used to deal with extreme multi-label data and achieve optimal or suboptimal results versus state-of-the-art methods. For the AAPD dataset, compared with the suboptimal method, it outperforms the second-best method by 2.05% ∼ 5.07% in precision@k and by 2.10% ∼ 3.24% in NDCG@k for k = 1, 3, 5. The superior outcomes demonstrate the effectiveness of LACN and its competitiveness in dealing with MLTC tasks.

Update in exploring the connection and clinical implications between vitamin D and knee osteoarthritis

Knee osteoarthritis is a prevalent joint disorder characterized by cartilage degeneration, pain, and impaired physical function. Vitamin D might be implicated in the management of knee osteoarthritis through its effects on bone health, cartilage preservation, inflammation modulation, and muscle function. This literature review aims to synthesize the current state of literature to provide information about the correlation between vitamin D and knee osteoarthritis. Methods: We conducted a comprehensive literature search in databases such as PubMed, Web of Science, Scopus, and Google Scholar to identify studies published in the last ten years investigating the association between vitamin D and knee osteoarthritis. Vitamin D deficiency has been linked to cartilage degeneration and more severe symptomatology of knee osteoarthritis. The evidence supports an association between vitamin D levels and knee osteoarthritis, but with some studies showing mixed results, there is a need for further research.

Bifocal lenses with adjustable intensities enabled by bilayer liquid crystal structures.

In this paper, we propose bifocal lenses based on bilayer structures composed of a liquid crystal (LC) cell and LC polymer, and the relative intensity of two foci can be adjusted arbitrarily through applying an external voltage. Two LC layers have different light modulation functions: when circularly polarized light passes through the first layer, part of the outgoing light is converted with PB phase modulation and another part is not converted; followed by the second layer, PB modulation of these two parts would be simultaneously realized but with opposite signs; thus the transmitted left- and right-handed circularly polarized (LCP and RCP) light can be independently controlled. As proof-of-concept examples, longitudinal and transverse bifocal lenses are designed to split an incident LCP light into two convergent beams with orthogonal helicity, and the position of the two foci can be flexibly arranged. Benefitting from the electrically controlled polarization conversion efficiency (PCE) of the LC cell, the relative intensity of the two foci can be adjusted arbitrarily. Experimental results agree well with theoretical calculations. Besides, a broadband polarization and an edge imaging system based on the proposed bifocal LC lenses have also been demonstrated. This paper presents a simple method to design a functional multilayer LC device and the proposed bifocal lenses may have potentials in the optical interconnection, biological imaging, and optical computing.

High-Q resonances based on BIC in graphene-dielectric hybrid double-T metasurfaces for terahertz modulation and sensing

In recent years, there has been a growing interest in bound states in the continuum (BIC) in metasurfaces. One particular area of focus is achieving high-quality (Q) factor resonance, as this is crucial for enhancing the performance of refractive index sensors. In this study, a graphene-dielectric hybrid metasurface that supports the bound states in the continuum is proposed. By varying the width of the dielectric rectangle, quasi-BIC resonances with a high Q factor can be excited, and the Q factor can reach 752724.95 and 272004.759 respectively. The analysis of multipole decomposition reveals that the two quasi-BIC resonances are predominantly influenced by the electric quadrupole and magnetic dipole, respectively. Moreover, the transmittance of the resonance point can be changed rapidly with the change of the chemical potential of graphene, so the function of modulation can be realized by changing the chemical potential of graphene. Based on these findings, we have designed a terahertz wave modulator, which exhibits modulation depths of 98.1% and 99.9% at the two resonance peaks, respectively. The corresponding chemical potential shifts are 50 meV and 0.5 eV. Additionally, we have investigated the sensing performance of the metasurface. By analyzing the magnitude of the frequency shifts of the quasi-BIC resonance peaks at different gas refractive indexes, we have determined sensitivities of 740 GHz RIU−1 and 630 GHz RIU−1 at the two resonance peaks. The maximum figure of merit (FOM) values are 132911.39 RIU−1 and 45000 RIU−1, respectively. This research serves as a valuable reference for the design of dynamic optical modulators and sensors operating in the terahertz band.

Age differences in BOLD modulation to task difficulty as a function of amyloid burden.

Effective cognitive performance often requires the allocation of additional neural resources (i.e. blood-oxygen-level-dependent [BOLD] activation) as task demands increase, and this demand-related modulation is affected by amyloid-beta deposition and normal aging. The present study investigated these complex relationships between amyloid, modulation, and cognitive function (i.e. fluid ability). Participants from the Dallas Lifespan Brain Study (DLBS, n = 252, ages 50-89) completed a semantic judgment task during functional magnetic resonance imaging (fMRI) where the judgments differed in classification difficulty. Amyloid burden was assessed via positron emission tomography (PET) using 18F-florbetapir. A quadratic relationship between amyloid standardized value uptake ratios (SUVRs) and BOLD modulation was observed such that modulation was weaker in those with moderately elevated SUVRs (e.g. just reaching amyloid-positivity), whereas those with very high SUVRs (e.g. SUVR > 1.5) showed strong modulation. Greater modulation was related to better fluid ability, and this relationship was strongest in younger participants and those with lower amyloid burden. These results support the theory that effective demand-related modulation contributes to healthy cognitive aging, especially in the transition from middle age to older adulthood, whereas high modulation may be dysfunctional in those with substantial amyloid deposition.

Biomimetic nanoplatform with microbiome modulation and antioxidant functions ameliorating insulin resistance and pancreatic β-cell dysfunction for T2DM management

Insulin resistance and pancreatic β-cell dysfunction are the main pathogenesis of type 2 diabetes mellitus (T2DM). However, insulin therapy and diabetes medications do not effectively solve the two problems simultaneously. In this study, a biomimetic oral hydrogen nanogenerator that leverages the benefits of edible plant-derived exosomes and hydrogen therapy was constructed to overcome this dilemma by modulating gut microbiota and ameliorating oxidative stress and inflammatory responses. Hollow mesoporous silica (HMS) nanoparticles encapsulating ammonia borane (A) were used to overcome the inefficiency of H2 delivery in traditional hydrogen therapy, and exosomes originating from ginger (GE) were employed to enhance biocompatibility and regulate intestinal flora. Our study showed that HMS/A@GE not only considerably ameliorated insulin resistance and liver steatosis, but inhibited the dedifferentiation of islet β-cell and enhanced pancreatic β-cell proportion in T2DM model mice. In addition to its antioxidant and anti-inflammatory effects, HMS/A@GE augmented the abundance of Lactobacilli spp. and tryptophan metabolites, such as indole and indole acetic acid, which further activated the AhR/IL-22 pathway to improve intestinal-barrier function and metabolic impairments. This study offers a potentially viable strategy for addressing the current limitations of diabetes treatment by integrating gut-microbiota remodelling with antioxidant therapies.

Terahertz-absorbing,dual-polarization converting supersurface structures based on the phase-change material VO2

Dynamically tunable multifunctional hypersurface structures have attracted the interest of researchers due to their good control of electromagnetic waves. Based on this, we have designed a dynamically tunable multifunctional hypersurface structure using the phase change material vanadium dioxide. By changing the state of vanadium dioxide, three functions of efficient broadband wave absorption, linear polarization conversion (LPC) and linear circular polarization conversion (LCPC) can be achieved. At room temperature, the hypersurface is used as a polarization converter to achieve broadband linear polarization conversion in the 0.903 THz range and line-circular polarization conversion with a total bandwidth of 0.608 THz in the 0.522 THz, 0.964 THz and 1.448 THz bands. When the temperature is raised to 68 °C, the hypersurface structure can be used as a broadband absorber, absorbing more than 90% of the incident wave in a wide frequency range of 1.348 THz and showing a large tolerance to variations in the angle of incidence and polarization. The electromagnetic field distribution is used to illustrate the absorption mechanism, and Stokes analysis is introduced to evaluate the polarization transition state. The designed structure can realize three electromagnetic modulation functions by changing the excitation conditions and can cover a wide range of frequency bands. Finally, we used coding to simulate the effect of loss on the wave absorption results in real applications and verified the stability of the structure. Our design provides new ideas for the development of terahertz communication and multifunctional integrated devices.

Quantitative analysis of the contrast modulation for multilateral shearing interferometers

Multilateral shearing interferometers (multi-LSIs) utilize the phase difference information of multiple shear directions with high accuracy and strong noise resistance. However, the interferogram fringe contrast of multi-LSIs can reverse due to the effect of contrast modulation, leading to incorrect measurement result. This issue has lacked comprehensive quantitative research to effectively guide the elimination of its effects. In this work, a quantitative analysis of the contrast modulation is proposed. This paper rigorously derives contrast modulation function, analyzing the effect of aberration and shear ratio on it. It is the first time that a quantitative theoretical model of aberration measurement range and shear ratio has been established, offering guidance in practical application for precise shear ratio adjustment to eliminate modulation effect and extend measurement range. By eliminating modulation effects, phase difference information from multiple directions can be effectively utilized, maximizing the benefits of multi-LSIs. In simulation and experiment, the distribution of fringe contrast reversal bands and the variation of aberration measurement range with shear ratio are consistent with theoretical analysis, which verifies the validity of the proposed approach. This approach aims to address the issue of interferogram fringe contrast inversion caused by modulation in multi-LSIs, providing a theoretical basis and practical guidance for precise measurement.

MTD precise jamming technology based on intra-pulse and inter-pulse frequency-phase joint modulation

For moving target detection (MTD) radar, existing jamming systems face problems such as poor controllability and strong regularity of two-dimensional false target characteristics. Time-frequency-phase modulation technology has great potential for active jamming and has received widespread attention. In this article, we propose a precise jamming method based on intra-pulse and inter-pulse frequency-phase joint modulation to control the two-dimensional distribution of false targets. First, construct periodic phase and segmented frequency modulation functions. Secondly, the intra-pulse phase modulation period Ts1 and frequency modulation amount ξl1 accurately control the positions of multiple false targets; the inter-pulse phase modulation period Ts2 and frequency modulation amount ξl2 accurately control the velocity of multiple false targets. Finally, the amplitude of the two-dimensional false target is accurately controlled by adjusting the phase modulation coefficient φi, phase modulation and frequency modulation duty cycles ηs, ηl. Compared with other jamming algorithms, the jamming distribution is more flexible and controllable, which verifies the superiority of this method.

Advances in Extracellular-Vesicles-Based Diagnostic and Therapeutic Approaches for Ocular Diseases.

Extracellular vesicles (EVs) are nanoscale membrane vesicles of various sizes that can be secreted by most cells. EVs contain a diverse array of cargo, including RNAs, lipids, proteins, and other molecules with functions of intercellular communication, immune modulation, and regulation of physiological and pathological processes. The biofluids in the eye, including tears, aqueous humor, and vitreous humor, are important sources for EV-based diagnosis of ocular disease. Because the molecular cargos may reflect the biology of their parental cells, EVs in these biofluids, as well as in the blood, have been recognized as promising candidates as biomarkers for early diagnosis of ocular disease. Moreover, EVs have also been used as therapeutics and targeted drug delivery nanocarriers in many ocular disorders because of their low immunogenicity and superior biocompatibility in nature. In this review, we provide an overview of the recent advances in the field of EV-based studies on the diagnosis and therapeutics of ocular disease. We summarized the origins of EVs applied in ocular disease, assessed different methods for EV isolation from ocular biofluid samples, highlighted bioengineering strategies of EVs as drug delivery systems, introduced the latest applications in the diagnosis and treatment of ocular disease, and presented their potential in the current clinical trials. Finally, we briefly discussed the challenges of EV-based studies in ocular disease and some issues of concern for better focusing on clinical translational studies of EVs in the future.

The Toxin of VapBC-1 Toxin-Antitoxin Module from Leptospira interrogans Is a Ribonuclease That Does Not Arrest Bacterial Growth but Affects Cell Viability.

Bacterial ubiquitous Toxin-Antitoxin (TA) systems are considered to be important survival mechanisms during stress conditions. In regular environmental conditions, the antitoxin blocks the toxin, whereas during imbalanced conditions, the antitoxin concentration decreases, exposing the bacteria cell to a range of toxic events. The most evident consequence of this disequilibrium is cell growth arrest, which is the reason why TAs are generally described as active in the function of bacterial growth kinetics. Virulence-associated proteins B and C (VapBC) are a family of type II TA system, in which VapC is predicted to display the toxic ribonuclease activity while VapB counteracts this activity. Previously, using in silico data, we designated four VapBC TA modules in Leptospira interrogans serovar Copenhageni, the main etiological agent of human leptospirosis in Brazil. The present study aimed to obtain the proteins and functionally characterize the VapBC-1 module. The expression of the toxin gene vapC in E. coli did not decrease the cell growth rate in broth culture, as was expected to happen within active TA modules. However, interestingly, when the expression of the toxin was compared to that of the complexed toxin and antitoxin, cell viability was strongly affected, with a decrease of three orders of magnitude in colony forming unity (CFU). The assumption of the affinity between the toxin and the antitoxin was confirmed in vivo through the observation of their co-purification from cultivation of E. coli co-expressing vapB-vapC genes. RNAse activity assays showed that VapC-1 cleaves MS2 RNA and ribosomal RNA from L. interrogans. Our results indicate that the VapBC-1 module is a potentially functional TA system acting on targets that involve specific functions. It is very important to emphasize that the common attribution of the functionality of TA modules cannot be defined based merely on their ability to inhibit bacterial growth in a liquid medium.

Monolithically integrated mode converter from terahertz substrateless silicon guide to conductive slotline

Although substrateless micro-scale silicon waveguides are a useful and versatile platform for terahertz waves, the fact that modal fields occupy the volume of the core limits the potential to dynamically manipulate guided waves. To address this, we introduce an aperiodic lattice structure to enable the monolithic co-integration of a Vivaldi antenna-like mode converter with a substrateless silicon waveguide. This broadband transition is experimentally confirmed to exhibit ∼2.5 dB average loss for two couplers, from 220 GHz to 330 GHz, and enables a photoexcited variable attenuator as proof-of-concept demonstration. This is an important enabling step to incorporate general-purpose dynamic reconfigurability, sensing, and modulation functionality into terahertz-range silicon-based integrated circuits, which are currently limited to primarily all-passive structures.

GRB7 Plays a Vital Role in Promoting the Progression and Mediating Immune Evasion of Ovarian Cancer.

Despite breakthroughs in treatment, ovarian cancer (OC) remains one of the most lethal gynecological malignancies, with an increasing age-standardized mortality rate. This underscores an urgent need for novel biomarkers and therapeutic targets. Although growth factor receptor-bound protein 7 (GRB7) is implicated in cell signaling and tumorigenesis, its expression pattern and clinical implications in OC remain poorly characterized. To systematically investigate GRB7's expression in OC, our study utilized extensive datasets from TCGA, GTEx, CCLE, and GEO. The prognostic significance of GRB7 was evaluated by means of Kaplan-Meier and Cox regression analyses. Using a correlation analysis and gene set enrichment analysis, relationships between GRB7's expression and gene networks, immune cell infiltration and immunotherapy response were investigated. In vitro experiments were conducted to confirm GRB7's function in the biology of OC. Compared to normal tissues, OC tissues exhibited a substantial upregulation of GRB7. Reduced overall survival, disease-specific survival, and disease-free interval were all connected with high GRB7 mRNA levels. The network study demonstrated that GRB7 is involved in pathways relevant to the course of OC and has a positive connection with several key driver genes. Notably, GRB7's expression was linked to the infiltration of M2 macrophage and altered response to immunotherapy. Data from single-cell RNA sequencing data across multiple cancer types indicated GRB7's predominant expression in malignant cells. Moreover, OC cells with GRB7 deletion showed decreased proliferation and migration, as well as increased susceptibility to T cell-mediated cytotoxicity. With respect to OC, our results validated GRB7 as a viable prognostic biomarker and a promising therapeutic target, providing information about its function in tumorigenesis and immune modulation. GRB7's preferential expression in malignant cells highlights its significance in the biology of cancer and bolsters the possibility that it could be useful in enhancing the effectiveness of immunotherapy.

Merkel cell polyomavirus small tumor antigen contributes to immune evasion by interfering with type I interferon signaling.

Merkel cell polyomavirus (MCPyV) is the causative agent of the majority of Merkel cell carcinomas (MCC). The virus has limited coding capacity, with its early viral proteins, large T (LT) and small T (sT), being multifunctional and contributing to infection and transformation. A fundamental difference in early viral gene expression between infection and MCPyV-driven tumorigenesis is the expression of a truncated LT (LTtr) in the tumor. In contrast, sT is expressed in both conditions and contributes significantly to oncogenesis. Here, we identified novel functions of early viral proteins by performing genome-wide transcriptome and chromatin studies in primary human fibroblasts. Due to current limitations in infection and tumorigenesis models, we mimic these conditions by ectopically expressing sT, LT or LTtr, individually or in combination, at different time points. In addition to its known function in cell cycle and inflammation modulation, we reveal a fundamentally new function of sT. We show that sT regulates the type I interferon (IFN) response downstream of the type I interferon receptor (IFNAR) by interfering with the interferon-stimulated gene factor 3 (ISGF3)-induced interferon-stimulated gene (ISG) response. Expression of sT leads to a reduction in the expression of interferon regulatory factor 9 (IRF9) which is a central component of the ISGF3 complex. We further show that this function of sT is conserved in BKPyV. We provide a first mechanistic understanding of which early viral proteins trigger and control the type I IFN response, which may influence MCPyV infection, persistence and, during MCC progression, regulation of the tumor microenvironment.