Crosstalk Research Articles

The Temporomandibular Joint and the Human Body: A New Perspective on Cross Talk

The Temporomandibular Joint and the Human Body: A New Perspective on Cross Talk

Global Co-regulatory Cross Talk Between m6A and m5C RNA Methylation Systems Coordinate Cellular Responses and Brain Disease Pathways.

N6 adenosine and C5 cytosine modification of mRNAs, tRNAs and rRNAs are regulated by the behaviour of distinct sets of writer, reader and eraser effector proteins which are conventionally considered to function independently. Here, we provide evidence of global cross-regulatory and functional interaction between the m6A and m5C RNA methylation systems. We first show that m6A and m5C effector protein transcripts are subject to reciprocal base modification supporting the existence of co-regulatory post-transcriptional feedback loops. Using global mass spectrometry proteomic data generated after biological perturbation to identify proteins which change in abundance with effector proteins, we found novel co-regulatory cellular response relationships between m6A and m5C proteins such as between the m6A eraser, ALKBH5, and the m5C writer, NSUN4. Gene ontology analysis of co-regulated proteins indicated that m6A and m5C RNA cross-system control varies across cellular processes, e.g. proteasome and mitochondrial mechanisms, and post-translational modification processes such as SUMOylation and phosphorylation. We also uncovered novel relationships between effector protein networks including contributing to intellectual disability pathways. Finally, we provided in vitro confirmation of colocalisation between m6A-RNAs and the m5C reader protein, ALYREF, after synaptic NMDA activation. These findings have important implications for understanding control of RNA metabolism, cellular proteomic responses, and brain disease mechanisms.

The role and clinical applications of exosomes in cancer drug resistance

Tumor-secreted exosomes are heterogeneous multi-signal messengers that support cancer growth and dissemination by mediating intercellular crosstalk and activating signaling pathways. Distinct from previous reviews, we focus intently on exosome-therapeutic resistance dynamics and summarize the new findings about the regulation of cancer treatment resistance by exosomes, shedding light on the complex processes via which these nanovesicles facilitate therapeutic refractoriness across various malignancies. Future research in exosome biology can potentially transform diagnostic paradigms and therapeutic interventions for cancer management. This review synthesizes recent insights into the exosome-driven regulation of cancer drug resistance, illuminates the sophisticated mechanisms by which these nanovesicles facilitate therapeutic refractoriness across various malignancies, and summarizes some strategies to overcome drug resistance.

The Crosstalk of Apoptotic and Non-Apoptotic Signaling in CD95 System

The mechanisms of CD95 (Fas/APO-1)-mediated extrinsic apoptotic pathway in cancer cells have been extensively studied. The majority of human cells express CD95, but not all these cells can induce extrinsic apoptosis. Accumulating evidence has shown that CD95 is a multifunctional protein, and its stimulation can also elicit non-apoptotic or even survival signals. It has become clear that under certain cellular contexts, due to the various checkpoints, CD95 activation can trigger both apoptotic and non-apoptotic signals. The crosstalk of death and survival signals may occur at different levels of signal transduction. The strength of the CD95 stimulation, initial levels of anti-apoptotic proteins, and posttranslational modifications of the core DISC components have been proposed to be the most important factors in the life/death decisions at CD95. Successful therapeutic targeting of CD95 signaling pathways will require a better understanding of the crosstalk between CD95-induced apoptotic and cell survival pathways. In this review, in order to gain a systematic understanding of the crosstalk between CD95-mediated apoptosis and non-apoptotic signaling, we will discuss these issues in a step-by-step way.

Liquid Crystal Display with High Transmittance and Excellent Image Quality

High transmittance and excellent image quality are two crucial requirements for thin-film transistor liquid crystal displays (TFT-LCDs). This work presents a novel pixel structure utilizing a vertical alignment liquid crystal (VA-LC) to improve both transmittance and image quality. The new pixel structure, called TCL-pixel, features a unique transparent conducting layer (TCL) that constructs an electric field shielding layer and a large transparent storage capacitor, resulting in good stability and a large aperture ratio. The 55" 8K product incorporating the TCL-pixel achieves high transmittance (3.87%) and a high contrast ratio (5100:1), attributed to the large aperture ratio. Additionally, it exhibits negligible vertical cross talk (0.7%), low color cross talk (3‰), low horizontal cross talk (JND 2.3), and enhanced variable refresh rate performance, confirming its good stability. Furthermore, the TCL-pixel demonstrates an improved viewing angle (CESI 0.03：65°) due to the multi-domain alignment produced by the transparent conducting layer.

Induced collagen type-I secretion by hepatocytes of the melanoma liver metastasis is associated with a reduction in tumour-infiltrating lymphocytes.

Overall patients with melanoma liver metastasis (MLiM) have a dismal prognosis and poor responses to the standard of care treatment. Understanding the role of the tumour microenvironment (TME) is critical for discovering better strategies to overcome intrinsic therapy resistance in MLiM. The aim was to understand the crosstalk signalling pathways between hepatocytes and metastatic melanoma cells in the TME of MLiM. Hepatocytes and melanoma tumour cells of MLiM were assessed using transcriptomic NanoString GeoMx digital spatial profiling (NGDSP) assay. Functional assays were performed using normal hepatocytes and MLiM-derived cell lines. Validation was performed using multiplex immunofluorescence. In NGDSP analysis adjacent normal hepatocytes (ANH) had higher CXCR4 and COL1A1/2 levels than distant normal hepatocytes (DNH), while melanoma cells had higher TNF-α levels. In vitro, MLiM cell lines released TNF-α which upregulated CXCR4 and CXCL12 levels in ANH. CXCL12 activated CXCR4, which triggered AKT and NFκB signalling pathways. Consequently, AKT signalling induced the upregulation of collagen type I. MLiM were significantly encircled by a shield of collagen, whereas other liver metastases showed reduced levels of collagen. Of all the liver metastasis analyzed, the presence of collagen in melanoma liver metastasis was associated with a reduction in tumour-infiltrating lymphocytes. MLiM modified ANH to increase collagen production and created a physical barrier. The collagen barrier was associated with a reduction of immune cell infiltration which could potentially deter MLiM immune surveillance and treatment responses. Spatial analyses of melanoma liver metastasis show that adjacent normal hepatocytes have increased collagen-type I levels. Melanoma liver metastases tumour cells secrete enhanced levels of TNF-α to stimulate CXCR4/CXCL12 upregulation in adjacent normal hepatocytes. Activation of CXCR4 promotes AKT and NF-κB signalling pathways to promote collagen-type I secretion in adjacent normal hepatocytes. Elevated collagen levels were associated with reduced tumour-infiltrating lymphocytes.

High-performance and scalable polarization splitter-rotator based on photonic crystal nanobeam reflection

The polarization splitter-rotator (PSR) is a key device for polarization processing in polarization diversity systems, which has wide applications in achieving polarization independence and mixed multiplexing. However, it remains a significant challenge to simultaneously achieve a better balance in bandwidth, crosstalk (CT), polarization extinction ratio (PER), and compact footprint of the PSR. In this article, a photonic crystal nanobeam (PCN) structure is introduced to PSR for large bandwidth and compact size, with a device length of only 104 µm. Additionally, to achieve lower CT, a bridge waveguide is introduced for primary filtering. Simulation results show that the insertion loss (IL) is less than 0.55 dB, CT less than -35 dB, and PER greater than 35 dB within a bandwidth exceeding 110 nm, while maintaining a large process tolerance. Furthermore, the proposed PSR design breaks through the limitations of traditional schemes by extending its functionality effectively. To further improve integration, a novel approach to PSR using mode hybridization followed by spatial beam splitting is proposed. By controlling the phase-matching condition of various modes in different waveguides, the designed spatial beam splitting achieves lower CT and better compactness. Simulation results verify that the IL of the improved scheme is less than 1 dB, CT less than -24 dB, and PER greater than 22 dB within an 85 nm bandwidth, while reducing the overall length to less than 20 µm.

Patterned glycopeptide-based supramolecular hydrogel promotes the alignment and contractility of iPSC-derived cardiomyocytes

The functional restoration of a damaged cardiac tissue relies on a synchronized contractile capacity of exogenous and/or endogenous cardiomyocytes, which is challenging to achieve. Here, we explored the potential of the short glycopeptide diphenylalanine glucosamine-6-sulfate (FFGlcN6S) conjugated with an aromatic moiety, namely fluorenylmethoxycarbonyl (Fmoc), to enhance cardiac tissue regeneration. At physiological conditions, Fmoc-FFGlcN6S assembles into nanofibrous hydrated meshes, i.e., matrix mimicking hydrogels. These hydrogels can be further micropatterned allowing co-existence of hierarchical structures at different lenght. The patterned hydrogels support the culture of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and promote their alignment. The cultured iPSC-CMs exhibit anisotropic synchronized contractions, indicating maturation and electrical interconnectivity. Moreover, the cultures express specific cardiac markers including, connexin-43 and sarcomeric-α-actinin, confirming enhanced cell-cell crosstalk, spontaneous contractility, and efficient transmission of electrical signals. Our results showcase the potential of short amphiphilic glycopeptides to mimic physical and biochemical cues that are essential for cardiomyocytes functionality and thus, these conjugates can be used in cardiac tissue engineering and regeneration.

The comparison of surgical correction of recurrent pectus excavatum with crossing wire construction and ravitch technique

Aim of the study. The article compares the method of surgical treatment using a crossing wire construction with the modified Ravitch operation for recurrent pectus excavatum. Methods. Between 2010 and 202, in our center twenty-four patients with recurrent pectus excavatum were operated. 15 patients underwent modified Ravitch technique with sternocostal plate and 9 patients were operated by open toracoplasty with crossing wire construction. The primary end point was Haller index change after operation. The secondary end points included length of stay after operation, short-term and long-term complications. Results and discussion. The mean patient age was 19.1±2.87 years. The mean Haller index was 4.45±2.78, the Gizhitskaya index – 0.7±0.1. A toracoplasty with cross wire construction was performed in 9 patients. There was no perioperative death. The Haller index reduced to 2,9±1,76 after the operation. During the follow-up, there were 1 patient who developed wound marginal necrosis; hemothorax in 2 patients and pneumothorax in 1 patient. Conclusions. Reoperation for recurrent pectus defects is a challenging undertaking. The results of our study showed that patients with recurrent pectus excavatum can safely undergo reoperation by toracoplasty with cross wire construction, and achieve satisfactory results.

Speckle-decoded temperature-insensitive strain identification in a multimode optical fiber.

Fiber-optic sensing systems are significant tools for measuring various physical or biochemical parameters. However, temperature cross-sensitivity prevents accurate recognition of the target input signal when optical sensors are applied in practical scenarios. Herein, leveraging a deep learning algorithm, a speckle-decoded temperature-insensitive strain sensor is proposed and experimentally demonstrated. Scattering patterns are utilized to estimate the axial strain since the external force could change the coherent superposition of the amplitudes of propagating modes. The experimental results show that the recognition accuracy of the sensing system based on a classification model can reach 99.28% within a wide strain range of 0-0.3 N in the presence of temperature cross talk. In addition, the strain prediction demonstrates an average root-mean-square error of 1.02 N%. Such an intelligent speckle sensing strategy has the potential to broaden the applications of fiber-optic sensors in various engineering applications.

Dual-mode 2 × 2 electro-optic switch on a SOI platform.

Mode-division multiplexing (MDM) technology is promising for enhancing the capacity of communication networks. In this Letter, we demonstrate a dual-mode 2 × 2 electro-optical switch on a silicon-on-insulator platform. The dual-mode Mach-Zehnder interferometer switch comprises of four p-i-n phase shifters and two mode-insensitive multimode interferences that can be used for TE0 and TE1, simultaneously. With π/2 phase shifters introduced, push-pull like operation enables the power consumption lower than 2.15 mW. The average insertion loss of the switch in "cross" and "bar" states are 1.31 dB ± 0.19 dB for the TE0 mode and 3.39 dB ± 0.16 dB for the TE1 mode, respectively. The cross talk is less than -16.47 dB in the C band. The compact dual-mode switch is promising to conduct a large-scale, flexible MDM system on chip.

Multifunctional role of the tumor associated monocytes/macrophages in the metastatic potential of inflammatory breast cancer.

Inflammatory breast cancer (IBC) is the most aggressive and lethal phenotype form of breast cancer, which afflicts young women at high incidence in North Africa compared to other continents of the world. IBC is characterized by highly metastatic behavior and possesses specific pathobiological properties different from non-IBC. IBC disease displays unusual common properties at typical presentation, including positive metastatic lymph-nodes, high infiltration of tumor associated monocytes/macrophages, rapid progression to distant metastasis, and possibly the production of a unique repertoire of growth factors, cytokines and chemokines, as well as a striking association with different polarized macrophages compared to non-IBC. Indeed, tumor associated monocytes/macrophages (TAM/M) play a crucial role in breast cancer development. Previously, we showed that cross talk between IBC cells and patient derived TAMs occurs via secretion of inflammatory mediators from TAMs that act on specific extracellular domain receptors activating down-stream signaling pathways that promote the epithelial-to-mesenchymal transition, cancer cell invasion, IBC stem cell properties, drug resistance, local and metastatic recurrence of residual tumor cells and other key markers of malignancy, including in vitro colony formation capacity. In this mini review, we will discuss the role of TAMs in IBC cancer metastatic potential and molecules involved. The review also discusses the recent discoveries in the field of IBC research.

IQGAP3 signalling mediates intratumoral functional heterogeneity to enhance malignant growth

BackgroundThe elevation of IQGAP3 expression in diverse cancers indicates a key role for IQGAP3 in carcinogenesis. Although IQGAP3 was established as a proliferating stomach stem cell factor and a regulator...

An Easy-to-Use Arrayed Brain–Heart Chip

Multi-organ chips are effective at emulating human tissue and organ functions and at replicating the interactions among tissues and organs. An arrayed brain–heart chip was introduced whose configuration comprises open culture chambers and closed biomimetic vascular channels distributed in a horizontal pattern, separated from each other by an endothelial barrier based on fibrin matrix. A 300 μm-high and 13.2 mm-long endothelial barrier surrounded each organoid culture chamber, thereby satisfying the material transport requirements. Numerical simulations were used to analyze the construction process of fibrin barriers in order to optimize the structural design and experimental manipulation, which exhibited a high degree of correlation with experiment results. In each interconnective unit, a cerebral organoid, a cardiac organoid, and endothelial cells were co-cultured stably for a minimum of one week. The permeability of the endothelial barrier and recirculating perfusion enabled cross talk between cerebral organoids and cardiac organoids, as well as between organoids and endothelial cells. This was corroborated by the presence of cardiac troponin I (cTnI) in the cerebral organoid culture chamber and the observation of cerebral organoid and endothelial cells invading the fibrin matrix after one week of co-culture. The arrayed chip was simple to manipulate, clearly visible under a microscope, and compatible with automated pipetting devices, and therefore had significant potential for application.

Ultra-broadband multimode fiber-to-chip edge coupler based on periodically segmented waveguides.

Mode-division multiplexing (MDM) technology demonstrates a bright outlook for enhancing the capacity of chip-scale or fiber-based optical communication. Nevertheless, the fiber-to-chip MDM optical interconnects are hindered by the considerable mode mismatch and inter-modal cross talk between the few-mode fiber (FMF) and on-chip few-mode waveguide (FMW). In this Letter, a new, to the best of our knowledge, multimode coupling solution based on periodically segmented waveguides for the MDM system is proposed, which achieves efficient conversion between LP01, LP11a, and LP11b modes in FMF and E11, E21, and E12 modes in FMW with low refractive index difference. The simulation results show that the coupling loss is less than 0.41, 0.27, and 0.90 dB for the three modes, over the wavelength range of 1100-1800 nm. The fabricated device based on a polymer platform shows low fiber-to-chip coupling losses of less than 1.8, 1.7, and 3.0 dB, respectively, over a 130 nm wavelength. The presented scheme provides a competitive solution for realizing the ultra-efficient integration of prospective fiber-chip optical interconnections and communications.

Neuro-immune cell interactions in the regulation of intestinal immune homeostasis.

Bidirectional regulation between neurons and immune cells in the intestine governs essential physiological processes, including digestion, metabolism and motility, while also controlling intestinal inflammation and maintaining tissue homeostasis. This review covers recent advances and future research challenges focused on the regulatory molecules and potential therapeutic targets in neuron-immune interactions within the intestine. Recently identified molecular and cellular pathways have been shown to regulate neuron-immune cell cross talk in the context of maintaining tissue homeostasis, modulating inflammation, and promoting intestinal repair. Additionally, behaviors governed by the central nervous system, including feeding and stress responses, can play key roles in regulating intestinal immunity and inflammation. This review emphasizes recent progress in understanding the complex interplay between the nervous system and intestinal immune system and outlines future research directions. These advances have the potential to lead to innovative therapies targeting gastrointestinal disorders including inflammatory bowel diseases, allergic responses and cancer.

The heat shock response of plants: new insights into modes of perception and signaling and how hormones contribute.

Plants have evolved specific temperature preferences, and shifts above this range cause heat stress with detrimental effects such as physiological disruptions, metabolic imbalances, and growth arrest. To reduce damage, plants utilize the heat shock response (HSR), signaling cascades that activate the heat shock factors (HSFs), transcription factors that control the heat stress-responsive transcriptome for activation of protective measures. While the core HSR is well-studied, we still know relatively little about heat stress perception and signal integration or cross-talk with other pathways. In the last few years, however, significant progress has been made in this area, which is summarized here. It has emerged that the plant hormones brassinosteroids (BRs) and abscisic acid (ABA) contribute to heat stress tolerance by impacting HSF modes of activity. Also, we began to understand that heat stress is sensed in different cellular compartments and that events in the nucleus, such as nuclear condensate formation via liquid-liquid phase separation, play a key role. In the future, it will be important to explore how these multilayered perception and signaling modes are utilized to understand how environmental context and developmental stage determine the outcome of heat stress effects on plant growth and development.

Thermosetting boron-nitride-filled polybutadiene composites with enhanced thermal conductivity and good dielectric properties

Low dielectric materials with high heat dissipation, low dielectric constant (Dk), and dielectric loss (Df) are urgently needed to address the issues of signal cross-talk and heat accumulation arising from the rapid development of modern communication technology and the integration of microelectronics. Polyolefins, as hydrocarbon polymers, have shown significant potential due to their excellent low dielectric properties. However, their low polarity and flexible structures limit their thermal conductivity and thermomechanical properties. In this study, we developed a method to prepare thermosetting polybutadiene composites with enhanced thermal conductivity and good dielectric performance by modifying hexagonal boron nitride (h-BN) and hydroxyl-terminated polybutadiene (HTPB) with thermally cross-linkable benzocyclobutene (BCB) groups. The properties of the resulting composites were tailored by varying the filler content. With 30 wt% of the BCB-modified filler, the composite (HB-30) displayed excellent dielectric properties (Dk = 2.70; Df = 1.67 × 10−3 @10 GHz). Meanwhile, it exhibited a thermal conductivity of 0.615 W/mK at 35 °C, which was 7.1 times that of pristine HTPB. It also showed significantly enhanced mechanical properties and thermal stability with a storage modulus of 2.7 GPa and a glass transition temperature (Tg) of 208.5 °C. This method proved effective for preparing polymer composites with enhanced thermal conductivity, heat resistance, mechanical properties and good dielectric properties, making them suitable for high-frequency communication applications.

Gene therapy for fat-1 prevents obesity-induced metabolic dysfunction, cellular senescence, and osteoarthritis

Obesity is one of the primary risk factors for osteoarthritis (OA), acting through cross talk among altered biomechanics, metabolism, adipokines, and dietary free fatty acid (FA) composition. Obesity and aging have been linked to cellular senescence in various tissues, resulting in increased local and systemic inflammation and immune dysfunction. We hypothesized that obesity and joint injury lead to cellular senescence that is typically associated with increased OA severity or with aging and that the ratio of omega-6 (ω-6) to omega-3 (ω-3) FAs regulates these pathologic effects. Mice were placed on an ω-6-rich high-fat diet or a lean control diet and underwent destabilization of the medial meniscus to induce OA. Obesity and joint injury significantly increased cellular senescence in subcutaneous and visceral fat as well as joint tissues such as synovium and cartilage. Using adeno-associated virus (AAV) gene therapy for fat-1, a fatty acid desaturase that converts ω-6 to ω-3 FAs, decreasing the serum ω-6:ω-3 FA ratio had a strong senomorphic and therapeutic effect, mitigating metabolic dysfunction, cellular senescence, and joint degeneration. In vitro coculture of bone marrow-derived macrophages and chondrocytes from control and AAV8-fat1-treated mice were used to examine the roles of various FA mediators in regulating chondrocyte senescence. Our results suggest that obesity and joint injury result in a premature "aging" of the joint as measured by senescence markers, and these changes can be ameliorated by altering FA composition using fat-1 gene therapy. These findings support the potential for fat-1 gene therapy to treat obesity- and/or injury-induced OA clinically.

Decoding visceral adipose tissue molecular signatures in obesity and insulin resistance: a multi-omics approach.

Obesity-associated insulin resistance (IR) is responsible for considerable morbidity and mortality globally. Despite vast genomic data, many areas, from pathogenesis to management, still have significant knowledge gaps. We aimed to characterize visceral adipose tissue (VAT) in obesity and IR through a multi-omics approach. We procured data on VAT samples from the Gene Expression Omnibus (GEO) for the following two groups: 1) populations with obesity (n = 34) versus those without (n = 26); and 2) populations with obesity and IR (n = 15) versus those with obesity but without IR (n = 15). Gene set enrichment, protein-protein interaction network construction, hub gene identification, and drug-gene interactions were performed, followed by regulatory network prediction involving transcription factors (TFs) and microRNAs (miRNAs). Interleukin signaling pathways, cellular differentiation, and regulation of immune response revealed a significant cross talk between VAT and the immune system. Other findings include cancer pathways, neurotrophin signaling, and aging. A total of 10 hub genes, i.e., STAT1, KLF4, DUSP1, EGR1, FOS, JUN, IL2, IL6, MMP9, and FGF9, 24 TFs, and approved hub gene-targeting drugs were obtained. A total of 10 targeting miRNAs (e.g., hsa-miR-155-5p, hsa-miR-34a-5p) were associated with obesity and IR-related pathways. Our multi-omics integration method revealed hub genes, TFs, and miRNAs that can be potential targets for investigation in VAT-relatedinflammatory processes and IR, therapeutic management, and risk stratifications.