Bidirectional Interactions Research Articles

Digital Twin for Amputees: A Bidirectional Interaction Modeling and Prototype with Convolutional Neural Network

With over 2 million amputees in the U.S., they have been facing significant employment challenges. However, several physical prostheses still lack usability to be able for them to work in person. Therefore, this study explores an innovative application of digital twin approach, focusing on bidirectional interaction modeling and prototyping using convolutional neural networks (CNNs). We developed a simplified digital twin environment integrating electromyography (EMG) sensors and virtual reality (VR) to enable real-time interaction between the virtual and physical worlds. The CNN model, trained to classify hand movement from EMG data, achieved a test accuracy of 99%, demonstrating its effectiveness for practical applications. Our framework facilitates remote control of physical devices through VR gestures, potentially allowing amputees to perform meaningful work from home, thus overcoming physical limitations and fostering greater independence. This preliminary study underscores the possibility of digital twin technology to redefine workplace accessibility, offering amputees opportunities for potential employment.

Relation-aware interaction spatio-temporal network for 3D human pose estimation

3D human pose estimation is a fundamental task in analyzing human behavior, which has many practical applications. However, existing methods suffer from high time complexity and weak capability to acquire the relations at the human joint level and the spatio-temporal level. To this end, the Relation-aware Interaction Spatio-temporal Network (RISNet) is presented to achieve a better speed-accuracy trade-off in a parallel interactive architecture. Firstly, the Spatial Kinematics Modeling Block (SKMB) is proposed to encode spatially positional correlations among human joints, thereby capturing cross-joint kinematic dependencies in each frame. Secondly, the Temporal Trajectory Modeling Block (TTMB) is employed to further process the temporal motion trajectory of individual joints at several various frame scales. Besides, the bi-directional interaction modules across branches are presented to enhance modeling abilities at the spatio-temporal level. Experiments on Human 3.6M, HumanEva-I and MPI-INF-3DHP benchmarks indicate that the RISNet gains significant improvement compared to several state-of-the-art techniques. In conclusion, the proposed approach elegantly extracts critical features of body joints in the spatio-temporal domain with fewer model parameters and lower time complexity.

Transport disadvantage and social inclusion: Exploring the role of smartphone use for transport purposes

The link between transport disadvantage and social exclusion is now firmly-established. Smartphones emerge as an integral part of daily life with a strong potential to influence this link by improving people’s capacity to access transport information and availability, and enabling direct connections with others in society. However, the role of smartphone use for transport purposes in influencing people’s daily mobility and quality of life remains under-studied, in part impeding a more concrete discourse on how it can be better evaluated and considered in policymaking. This study seeks to shed light on the above issue through probing into the interrelationships among smartphone use, transport disadvantage and social inclusion, and their relation to subjective well-being. Using Beijing as a case study, we tested a series of hypotheses through structural equation models (SEM). Our findings highlighted potentially bidirectional interactions between smartphone use and transport disadvantage. By and large, smartphone use for both normal purposes and new modes can help mitigate transport disadvantage, and this may further stimulate more smartphone use as a proactive solution. Furthermore, the link between smartphone use for new modes and transport cost, and their consequent effect on social inclusion and subjective well-being were found to vary between low- and high-income groups. Findings suggest that smartphones and smart apps should be carefully integrated in policymaking to reduce the risk for people of being socially excluded due to a lack of transport options and improve subjective well-being.

Neural Circuitries between the Brain and Peripheral Solid Tumors.

The recent discovery of the pivotal role of central nervous system (CNS) in controlling tumor initiation and progression has opened a new field of research. Increasing evidence suggests a bidirectional interaction between the brain and tumors. The brain influences the biological behavior of tumor cells through complex neural networks involving the peripheral nervous system, the endocrine system, and the immune system, while tumors can establish local autonomic and sensory neural networks to transmit signals into the CNS, thereby affecting brain activity. This review aims to summarize the latest research in brain-tumor crosstalk, exploring neural circuitries between the brain and various peripheral solid tumors, analyzing the roles in tumor development and the related molecular mediators and pathological mechanisms, and highlighting the critical impact on the understanding of cancer biology. Enhanced understanding of reciprocal communication between the brain and tumors will establish a solid theoretical basis for further research and could open avenues for repurposing psychiatric interventions in cancer treatment.

From awareness to action: Understanding the relationship between circular economy and favourable evaluation towards sustainable development

AbstractThis study examines the effects of heightened awareness of circular economy (CE) principles on individuals' evaluations of sustainable development within Brazil's resource‐rich yet environmentally challenged context. Employing social learning theory (SLT) as our theoretical framework, we investigate how increased knowledge of CE influences individuals' cognitive perceptions, enhancing their understanding and favourable assessment of sustainable practices. Data were collected through a nationwide survey of the general public, incorporating five CE dimensions: waste management, rational use of resources, technical cycle, sustainable products/packaging and dematerialization/collaborative consumption. Our results reveal that a deeper awareness of CE significantly improves individuals' positive evaluations concerning the environment, future generations' survival, socio‐economic development and engagement between people and institutions in sustainable practices. These positive evaluations are indicative of a shift in perception that precedes and may catalyse sustainable behaviours, suggesting that cognitive engagement is a critical precursor to actionable change. The study confirms that SLT effectively elucidates the bidirectional and complex interaction between cognition and evaluation within environmental contexts, thereby enriching the understanding of how sustainable practices can be adopted and promoted. The implications of our research are profound, suggesting that educational and policy interventions aimed at increasing CE knowledge could substantially impact sustainable development outcomes.

Influence of dexamethasone-induced matrices on the TM transcriptome

Pathologic bidirectional interactions between the extracellular matrix (ECM) and cells within the human trabecular meshwork (hTM) contribute to ocular hypertension. An in vitro model is needed to study these cell-matrix interactions and their effect on outflow homeostasis. This study aimed to determine whether pathogenic ECM derived from dexamethasone (DEX)-treated hTM cultures induces clinically relevant glaucoma-like changes in healthy hTM cells at the transcriptional level. Corneoscleral rims from non-glaucoma donors were used to isolate primary hTM cells after validation according to the consensus recommendations for TM culture. Normal hTM cells (n = 5) were plated on a coverslip and treated with 100 nM DEX or ethanol for four weeks. These cultures were then decellularized, plated with primary hTM cells, and allowed to grow for another 72 h. RNA was extracted from these hTM cells for stranded total RNA-Seq. Sequencing libraries prepared using the Zymo-Seq RiboFree Total RNA library kit were pooled and sequenced using Illumina NovaSeq 6000. After quality control, sequence reads were aligned to the human genome build hg19. Differential expression (DE) analyses were performed using paired multi-factorial ANOVA. The expression of several DE genes associated with glaucoma (ANGPTL2, PDE7B, C22orf23, COL4A1, ADAM12, IFT122, SEMA6C) was validated using EvaGreen-based Droplet Digital PCR (ddPCR) assays. Gene ontology analyses of the DE genes were performed using the PANTHER and NDEx IQA databases, and functional analyses were performed with the DAVID Bioinformatics software. Using a cutoff of p-value <0.05 and fold change ≥2.0, our differential analysis identified 267 up- and 135 down-regulated genes in DEX-induced ECM-treated cells compared to the control. These differentially expressed genes were found to play a significant role in pathways such as cytokine and oxidative stress-induced inflammation, integrin signaling, matrix remodeling, and angiogenesis. These findings were further supported by previously performed proteomics studies using the same model. Using ddPCR, we validated the expression of seven genes associated with the risk of primary open-angle glaucoma. These results not only provide support for the pathogenic ECM model of steroid-induced glaucoma, but also demonstrate that the pathologic changes induced by this model are indeed found at the transcriptional level. These findings further demonstrate that matrix changes significantly influence cell expression profiles, which enable further understanding of the molecular mechanisms underlying glaucomatous changes in the TM. However, future studies with a larger and more diverse set of samples and longer time points are needed to confirm the utility of this model for mechanistic studies.

Expansion and Maturation of Innate Lymphoid Cell Precursors Using Human iPSC-Derived Intestinal Organoids.

Innate lymphoid cells (ILC) are enriched at mucosal barrier sites where they play critical roles in development and disease. Mucosal organoids offer a robust platform for the simultaneous differentiation and expansion of all subsets of mature ILC from a shared peripheral blood precursor. Critically, organoid identity drives tissue-specific imprinting of the culture-derived mature innate lymphoid cells, allowing for the study of bidirectional interactions between, e.g., intestinal organoids and intestine-specific ratios and populations of ILC. This protocol reduces the need for feeder cell lines and complex cytokine cocktails used to mature and maintain ILC, instead relying on a native niche of protein signals provided by mucosal epithelial cells. This protocol details the generation of human intestinal organoids (HIO) from human-induced pluripotent stem cells (hiPSC), and the subsequent establishment of co-cultures between HIO and ILC precursors for expansion and maturation. This approach has extensive applications for mechanistic studies of fundamental biological processes and as a potential GMP-compatible source of ILC for future cell therapies.

Coordinated measurement of marine economy: High-quality and low-carbon development in China

The marine economy needs high-quality development, as severe greenhouse effect has become a global concern and carbon emission reduction has been an essential target of marine economy growth. However, a lack of synergistic research in the field of marine economy development and carbon emissions has hindered progress. This study explores the critical interactive relationship between the high-quality and low-carbon development in China's marine economy, aiming to foster green development in coastal urban agglomerations and enhance ecological security alongside economic growth. Despite the importance, comprehensive analysis across multiple dimensions of high-quality and low-carbon development of marine economy remains scarce. This paper establishes a systematic and scientific evaluation index system, utilizing text analysis technology and the Panel Vector Autoregression Model (PVAR) to quantitatively assess the complex system relationship between these dimensions. The results including: (1) The development of a 23 nodes tree structure through a bottom-up, multi-level coding method, effectively addressing the complexity of the current evaluation system for high-quality development of the marine economy. (2) Moran's I of subsystems are all negative, presenting an obvious high-low agglomeration characteristics. The discovery that intra-group differences exceed inter-group ones in marine economic development, indicates that the need for synergistic development among the provinces within marine economic circles. (3) The identification of significant bidirectional interactions between open and shared high-quality development and low-carbon development, with a notable lag effect in responses. The predominant role of innovation in all subsystems underscores the centrality of the marine innovation environment and factors as key drivers in the synergy of high-quality and low-carbon development in the marine economy.

DAT-Net: Deep Aggregation Transformer Network for automatic nuclear segmentation

Detection and segmentation of cell nuclei in hematoxylin and eosin-stained tissue images pose critical clinical challenges, including intricate backgrounds, variable nuclear appearances, overlapping nuclei, and unclear boundaries. These complexities render automated instance segmentation a difficult research area. Thus, this paper proposes a deep aggregation transformer network for automatic nucleus instance segmentation. The method employs a robust Vision Transformer-based backbone to extract informative features from images. To fuse multi-level information, we propose the group aggregation multi-level feature fusion module, which merges low-level features for shape representation and high-level features for pixel edge segmentation, enhancing overall model performance. The depthwise integrated multilayer perceptron module enhances feature learning by combining the global context-dependent representation of MLP and the local representation of convolution through channel separation. This fosters feature learning across different modes, thereby improving network representation. The bidirectional path interaction feature processing module is introduced for multi-scale information extraction and fusion. This module enhances the entire feature pyramid hierarchy by transferring deep semantic information to shallow layers with robust spatial information via bidirectional paths. The Large kernel Attention module at each layer extensively improves feature extraction through a large receptive field. Our approach outperforms state-of-the-art models, including StarDIST, CPP-Net, TSFD-Net and TransNuSeg, by 7.8%, 6.3%, 1.5% and 3.5% in average panoptic quality for different cell nuclei segmentation categories across tissues of the Pannuke dataset. Furthermore, DAT-Net outperforms all other state-of-the-art models in terms of the F1 score for the five classes of cell nuclei in the PanNuke dataset.

On mathematical analysis of synchronization of bidirectionally coupled Kuramoto oscillators under inertia effect

In this article, we analyze the phase synchronization and frequency synchronization for the bidirectionally coupled Kuramoto model under the effect of inertia. Unlike the classical Kuramoto model equipped with all-to-all coupled interaction, in the setting of this model, each oscillator θi only interacts directly with θi+1 and θi−1. The bidirectional interaction is a typical setting of the concatenation in power systems. Additionally, it is necessary to impose the effect of inertia in the Kuramoto model in the applications such as power systems and Josephson junction array. In this article, we first present a theory of the global convergence for frequency synchronization for the identical case. For the non-identical case, we prove that the second-order bidirectionally coupled Kuramoto model exhibits a frequency synchronization if the coupling strength is large, inertia is small, and all oscillators are initially confined to a sector. We emphasize that the arc length of this sector possesses a positive lower bound which is independent of the number of oscillators. If, in addition, all natural frequencies are identical, we further show that the phase synchronization emerges. Moreover, we demonstrate the numerical simulations to support the main results. On the other hand, we observe that the model equipped with large inertia can exhibit the synchronization. Exploring the synchronization theory for large inertia case is left as the future work.

Evaluating interaction between tumor educated platelets and cancer stem cells on breast cancer subtypes.

5 Background: Thrombocytosis has been reported to be responsible for poor prognosis of numerous malignancies. This swarm of platelets acts as foe for the body but as mate for the cancer cells by providing a protective shield around them, helping them to escape immunosurveillance process. A bidirectional interaction between platelets and tumor cells promote their conversion to an activated tumor educated platelet (TEP) state. The present report reveals the critical role played by TEPs to promote metastasis in BC subtypes by interacting with cancer stem cells (CSCs). Methods: Status of intra-tumoral and humoral TEPs (CD41+/CD62P+) was screened in luminal A (LumA) and triple negative (TNBC) BC subgroups. The impact of TEPs on lin-/CD44+/CD24- CSCs of both the categories in-vitro, was deciphered by performing mammosphere assay, clonogeneic and migration assays, with final validation in murine system. Effect on various genes and proteins related to stemness, metastasis and angiogenesis as a result of this interaction was elucidated by RT-PCR, flow cytometry and western blotting. Results: High percentage of TEPs in the peripheral blood is a potential biomarker and responsible for poor prognosis in BC subtypes. Both Lum A and TNBC patients had elevated TEP frequency, compared to healthy blood. Further, patients in the pre-carcinogenic stage had platelet count of &gt;3.5 lakhs. Additionally, screening of breast tumor sections revealed intra-tumoral enrichment of TEPs, comparatively to a greater extent in TNBC than LumA, supporting their role in disease aggression. Also, a positive correlation was noted between TEP and CSC frequencies proving their synergistic interactions. Moreover, in-vitro, TEP influenced CSCs exhibited enormous clonogenic and tumorigenic potentialities. Their metastatic nature was confirmed by their enhanced migratory, invasive, angiogenic capacities with higher VIMENTIN and TWIST along with HIF1α, CD31 and MMP9 expression compared to E-CADHERIN. In line with in-vitro observations, in-vivo too, TEP~CSC produced metastatic colonies in murine lungs. Upon investigation, it was disclosed that it is through WNT-βcatenin-VEGFR2 axis that this mutual interdependency was functioning. Conclusions: This study advocates for the importance of TEPs as potential biomarker in BC diagnosis. Their alliance with vicious CSCs to promote disease advancement acquiesce them as a novel restorative agent.

Bidirectional Interactions Between Obstructive Sleep Apnea and Chronic Kidney Disease- A Review

Bidirectional Interactions Between Obstructive Sleep Apnea and Chronic Kidney Disease- A Review

Bi-Directional Modification to Quench Detrimental Redox Reactions and Minimize Interfacial Energy Offset for NiOX/Perovskite-Based Solar Cells.

The quality of the buried heterojunction of nickel oxide (NiOX)/perovskite is crucial for efficient charge carrier extraction and minimizing interfacial non-radiative recombination in inverted perovskite solar cells (PSCs). However, NiOX has limitations as a hole transport layer (HTL) due to energy level mismatch, low conduction, and undesirable redox reactions with the perovskite layer, which impede power conversion efficiency (PCE) and long-term stability. In this study, para-amino 2,3,5,6-tetrafluorobenzoic acid (PATFBA) is proposed as a bifacial defect passivator to tailor the NiOX/perovskite interface. The acid group and adjacent fluorine atoms of PATFBA effectively passivate NiOX surface defects, thereby improving its Ni3+/Ni2+ ratio, hole extraction capability, and energy band alignment with perovskite, while also providing active sites for homogenous nucleation. Meanwhile, the amine and adjacent fluorine atomsstabilize the buried perovskite interface by passivating interfacial defects, resulting in higher crystalline perovskite films with supressed non-radaitive recombination. Furthermore, the PATFBA buffer layer prevents redox reactions between Ni3+ and perovskite.These synergistic bi-directional interactions lead to optimized inverted PSCs with a PCE of 20.51% compared to 16.89% for pristine devices and the unencapsulated PATFBA-modified devices exhibit outstanding thermal and long-term stability. This work provides a new engineering approach to buried interfaces through the synergy of functional groups.

Development, Acceptability, and Initial Implementation of an Interactive Text-Messaging Program for Fathers with Low Income.

This study describes the development, acceptability, and implementation of an interactive text messaging program to engage fathers enrolled in home visitation programs. We used an iterative development approach that integrated rapid testing of intervention content with acceptability feedback from program participants to examine the processes of implementation. In Study 1, we describe the rapid testing framework and present data from 171 men who provided feedback on Text4Dad content via three online surveys. In Study 2, a case study, we use administrative data from 108 fathers with whom we pilot-tested Text4Dad in three community-based home visiting programs, with the program implemented by fatherhood program community health workers (F-CHWs). Content analysis of exchanges between F-CHWs and fathers describes the specific use of Text4Dad. Across all three online surveys, fathers reported positive reviews of the Text4Dad content. The F-CHWs used Text4Dad mainly to push out information, especially that related to home visit scheduling and local events, instead of engaging in bidirectional interactions with fathers. We conclude with a set of recommendations for social service and maternal and child health providers regarding the feasibility of implementing text messaging to support home visiting in community-based settings.

THE INFLUENCE OF INTESTINAL MICROBIOTA ON DEPRESSIVE DISORDER: A literature review

The gut-brain axis and its bidirectional interaction have been associated with the gut microbiota and the development of mood disorders such as depression and anxiety. This axis modulates various key processes through the vagus nerve, including the production of microbial metabolites and immune mediators, leading to changes in neurotransmission, neuroinflammation, and behavior. In this sense, the aim of this study was to understand the relationship between gut microbiota and depressive disorder. O this end, an integrative literature review was conducted using scientific articles in Portuguese and English published between 2018 and 2023, employing the descriptors intestinal microbiota, gut-brain-microbiota axis, and depressive disorder. The search was carried out in the databases Pubmed, Science Direct, and Scielo. Eight articles were selected for analysis. The results demonstrated a connection between the brain, microbiota, and depressive disorder through the vagus nerve, enteric nervous system, and immune system pathways, as well as showing that the intake of probiotics and prebiotics improves dysbiosis and depressive symptoms. Thus, the findings suggest that interventions aimed at modulating the microbiota, such as supplementation with probiotics and prebiotics, may represent a promising approach in the complementary treatment of depression, acting both in correcting dysbiosis and improving depressive symptoms. These discoveries reinforce the ongoing need for research in this area to develop more effective and personalized therapeutic strategies for managing depressive disorder.

Traffic sounds in office spaces: PLS-SEM study on audio-visual perception with open or closed windows and biophilic design

Herein, we investigated the audio–visual perception of indoor greenery and intruding traffic sounds through open or closed windows in a shared office context that accommodates two people. A set of 32 audio–visual stimuli was used, featuring combinations of greenery dosages (0 %, 7 %, 10 % and 13 %) and traffic sound levels (50 dBA, 55 dBA, 60 dBA and 65 dBA), for both open and closed windows. These stimuli were presented to 42 participants in an indoor office environment using two-dimensional screens and over-ear headphones. We employed a partial least squares structural equation model to integrate greenery dosages, traffic sound levels and perceptual attributes such as pleasantness, eventfulness, appropriateness, preference and visual aesthetics. The findings demonstrate the impact of traffic sound levels on visual perception, highlighting a bidirectional interaction between auditory and visual perceptions. Indoor greenery indirectly enhances the pleasantness of the auditory environment, supporting the implementation of biophilic design in office spaces that are visually appealing and acoustically pleasant. Furthermore, the study contributes to discussions on adaptive acoustic comfort in naturally ventilated spaces, providing evidence of how visual perception impacts the acoustic environment. While the research results highlight the positive impact of open windows on the appropriateness ratings of traffic sounds, it is important to consider the limitation of assessing outdoor-recorded traffic sounds at high sound pressure levels (50–65 dBA) without the filtering effect of the facade. This limitation reduces the realism and ecological validity of the experiment, which should be considered when interpreting these results.

Efficient image super-resolution based on transformer with bidirectional interaction

In single-image super-resolution (SISR) tasks, many methods benefit from the local and global contexts of the image. Despite that, no methods use the bidirectional interaction between these two contexts. So, we were inspired by the fully adaptive Transformer for high-level vision. We propose a fully adaptive Transformer super-resolution (FATSRN) for SISR. The model uses local and global information and their bidirectional interaction in a context-aware manner. The model is based on fully adaptive self-attention (FASA) as the main block, which uses self-modulated convolutions to extract local representation adaptively. Also, the FASA uses self-attention in down-sampled space to extract global representation. In addition, this FASA uses a bidirectional adaptation process between local and global representation to model the interaction. Moreover, a fine-grained downsampling strategy is used to improve the down-sampled self-attention mechanism. Based on the FASA, we built a fully adaptive self-attention block (FASAB) as the main block of our model. Then, the fully adaptive self-attention group (FASAG) is used as the backbone for our FATSRN. Extensive experiments are done to show the efficiency of the model against the state-of-the-art methods. For example, our model improved the PSNR from 27.69 to 27.73 compared to the SwinIR-light for the B100 dataset at the scale of × 4. In addition, our model achieved 0.04 dB better PSNR compared to the state-of-the-art STSN model for the Set5 dataset at the scale of × 2 with 64% and 48% fewer parameters and Mult-adds.

Interactions between eosinophils and IL-5Rα–positive mast cells in nonadvanced systemic mastocytosis

Bidirectional interactions between eosinophils and mast cells (MCs) have been reported in various allergic diseases. Bone marrow (BM) eosinophilia, and to a lesser extent blood eosinophilia, is common in systemic mastocytosis (SM), but its significance remains unknown. To describe blood and BM eosinophil characteristics in SM. A large collection of BM biopsies was analyzed using immunohistochemical staining and whole-slide imaging. Eosinophil and extracellular granules were detected by eosinophil peroxidase (EPX) staining, and MCs by KIT staining. Complementary analyses were conducted using flow cytometry and immunofluorescence. Eosinophil infiltrates and large areas of eosinophil degranulation were observed within or around BM MC infiltrates in SM. EPX staining surface, highlighting intact eosinophils and eosinophil degranulation, was higher in non-advanced-SM (n=37 BM biopsies) compared to both controls (n=8, p=0.0003) and to advanced SM (n=24, p=0.014). In non-advanced SM, positive correlations were observed between serum tryptase levels and percentages of eosinophil counts in BM aspirations (Spearman r coefficient r=0.38, p=0.038), eosinophils count in BM biopsies (r=0.45, p=0.007), EPX staining (r=0.37, p=0.035) and eosinophil degranulation (r=0.39, p=0.023). Eosinophil counts in BM biopsies also correlated with MC counts (r=0.47, p=0.006) and KIT staining surface (r=0.49, p=0.003). BM MCs expressed interleukin-5 receptor and other usual eosinophil cytokine/chemokine receptors, and blood eosinophils display several increased surface markers compared to controls, suggesting an activated state. Our data suggest a possible crosstalk between MCs and eosinophils, supporting MC tryptase release and MC activation-related symptoms. This suggests a rationale for targeting eosinophils in non-advanced-SM not fully controlled by other therapies.

Bidirectional Interaction of CNN and Transformer Feature for Visual Tracking

Bidirectional Interaction of CNN and Transformer Feature for Visual Tracking

Circadian rhythms and breast cancer: unraveling the biological clock's role in tumor microenvironment and ageing.

Breast cancer (BC) is one of the most common and fatal malignancies among women worldwide. Circadian rhythms have emerged in recent studies as being involved in the pathogenesis of breast cancer. In this paper, we reviewed the molecular mechanisms by which the dysregulation of the circadian genes impacts the development of BC, focusing on the critical clock genes, brain and muscle ARNT-like protein 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK). We discussed how the circadian rhythm disruption (CRD) changes the tumor microenvironment (TME), immune responses, inflammation, and angiogenesis. The CRD compromises immune surveillance and features and activities of immune effectors, including CD8+ T cells and tumor-associated macrophages, that are important in an effective anti-tumor response. Meanwhile, in this review, we discuss bidirectional interactions: age and circadian rhythms, aging further increases the risk of breast cancer through reduced vasoactive intestinal polypeptide (VIP), affecting suprachiasmatic nucleus (SCN) synchronization, reduced ability to repair damaged DNA, and weakened immunity. These complex interplays open new avenues toward targeted therapies by the combination of clock drugs with chronotherapy to potentiate the immune response while reducing tumor progression for better breast cancer outcomes. This review tries to cover the broad area of emerging knowledge on the tumor-immune nexus affected by the circadian rhythm in breast cancer.