Continuous in vivo monitoring of diverse chemicals, including ions, glucose, and neurotransmitters, is pivotal for elucidating complex physiological processes and identifying various diseases. Existing approaches predominantly rely on transdermal wires to transmit signals from implanted sensors to external devices, which substantially heightens the risk of infection, particularly in immunocompromised patients. To address this problem, we developed an interface-free implants-to-textile wireless system for multiplexed in vivo chemical monitoring. This system integrates fully implanted miniature wireless sensors, roughly the size of a grain of rice, with a conformal textile-based network of intermediate relay coils. These implanted sensors convert chemical signals into distinct resonance frequencies and wirelessly relay them through the textile-coil network to a readout coil. By obviating the need for transdermal wires, our system mitigates infection risk and achieves real-time and simultaneous monitoring of glucose, potassium and calcium ions in vivo. This minimally invasive platform offers safe, real-time, multiplexed chemical analysis, thereby contributing to advancing both disease diagnosis and understanding of intricate physiological dynamics.
Dysmenorrhea is a common gynecological condition with heterogeneous etiologies. Endometriosis is an important condition associated with dysmenorrhea, but the serum steroid and reproductive hormone profiles related to dysmenorrhea, and whether these associations differ by endometriosis status, remain unclear. This study aimed to investigate the associations of serum hormone profiles with dysmenorrhea and pain severity. This exploratory cross-sectional study was conducted from October 2022 to January 2024 at Zhongshan Hospital, Fudan University. A total of 139 premenopausal participants were classified into dysmenorrhea (n = 73) and non-dysmenorrhea (n = 66) groups and further stratified by endometriosis status. Serum steroid and reproductive hormones were measured using liquid chromatography–tandem mass spectrometry and immunoassays. Group comparisons were performed according to data distribution, and false discovery rate (FDR) adjustment was applied for multiple hormone comparisons. Multivariable logistic regression was used to evaluate the association between androstenedione (A4) and dysmenorrhea. In the overall cohort, women with dysmenorrhea showed higher A4 levels and a higher luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio, although these differences did not remain significant after FDR adjustment. After stratification by endometriosis status, these differences were mainly observed among women without endometriosis. In this subgroup, A4 levels were significantly higher in women with dysmenorrhea than in those without dysmenorrhea (0.85 ± 0.36 vs. 0.65 ± 0.28 ng/mL, P = 0.004; FDR-adjusted P = 0.024), as was the LH/FSH ratio (2.11 ± 1.47 vs. 1.44 ± 1.02, P = 0.013; FDR-adjusted P = 0.047). Among women without endometriosis, A4 was modestly correlated with visual analogue scale score (Spearman r = 0.285, P = 0.006) and remained associated with dysmenorrhea after multivariable adjustment (odds ratio = 8.07, 95
Fiber electronics provide the most promising platform for the detection, modulation, and reconstruction of biosignals in the brain. However, preserving stable communication between fiber electronics and cellular-scale targets in the deep brain is critical but challenging because of their mechanical mismatch. Here, our study fills this gap by developing a radial modulus-gradient fiber (RMGF), which can bridge high-modulus conductive components (MPa) and low-modulus brain tissue (kPa) to well eliminate the mechanical mismatch at the entire neural‒device interface. The RMGF exhibits strain-insensitive electrical properties (<0.2% resistance fluctuation over 700,000 stretching‒release cycles). As an example, the RMGF enables unprecedented five-month continuous tracking of single neurons in the dorsal lateral geniculate nucleus of freely moving cats, and allows reconstruction of visual stimuli with the use of only three neurons, with a high correlation coefficient of 0.95, approaching the theoretical limit of the unscented Kalman filter (0.97). The results indicate that dorsal lateral geniculate nucleus neurons maintain stable tuning properties (spatial frequency sensitivity, ON/OFF characteristics, and X-cell classification) and reveal a minimal effective ensemble for efficient encoding of information within deep thalamic circuits. This RMGF represents a platform for chronic recording at the single-cell level and investigating fundamental mechanisms in the deep tissues.
The brain undergoes constant dynamic deformations, which are intricately linked to its intrinsic properties and pathological states. However, continuous monitoring of these deformations presents significant challenges due to the limited temporal and spatial resolutions of conventional imaging techniques. Here, it is developed an implantable deformation array sensor capable of real‐time, continuous monitoring and mapping of brain deformations. The sensor features microcoil arrays embedded in ultrathin films and operates based on the principle of mutual inductance, achieving exceptional temporal resolution (<100 µs) and distance resolution (<5 µm). It is implanted the sensor between the skull and the cortex and successfully tracked continuous brain deformations across four cortical sites in rat models. These experiments are conducted under scenarios of isoflurane inhalation, mechanical impacts, and intracranial hemorrhage, where such detailed monitoring and mapping has not been achieved previously. The results reveal that brain deformations dynamically vary over time in response to both physiological fluctuations and pathological events, with deformation amplitudes decreasing as the distance from the primary site increases. This innovative approach provides a novel platform for exploring brain dynamics and their associations with neurological disorders and disease progression.
Gastroesophageal reflux disease (GERD) is a prevalent chronic condition that affects approximately 33
The functioning of living organisms generates a wide array of physiological signals. Deciphering these signals is crucial for understanding physiological processes and advancing disease diagnostics and therapies. Implantable fiber biosensors (IFBs) have emerged as a promising solution, enabling minimally invasive, real-time, in situ monitoring. However, comprehensive insights into the design principles, fabrication methodologies, biocompatibility, and system integration of IFBs remain limited. This perspective highlights recent advancements in IFB design and their translation into practical applications. Key progress in material strategies, structural assembly, and fabrication technologies are summarized. Biocompatibility considerations including cytotoxicity, mechanical compatibility, hemocompatibility, histocompatibility, and lifecycle management are thoroughly examined. Integration strategies critical for clinical and real-world deployment are also discussed. Finally, this work outlines the major challenges and proposes future directions to guide the continued development of IFBs.
Intravenous leiomyomatosis (IVL) is a histologically well differentiated smooth muscle tumor with aggressive behavior, capable of extending throughout the venous system. Understanding how IVL occurs and develops is really important for diagnosing and treating it. Unfortunately, because IVL is quite rare, there aren’t many comprehensive studies available. In our research, we carried out an extensive multi-omics study, gathering tissue samples from IVL cases, uterine fibroid, and normal myometrium. The single-cell RNA sequencing analysis revealed a notable difference in cell composition between IVL and uterine fibroid. Additionally, H E staining demonstrated more frequent hydropic changes and hyalinization in IVL tissues, along with a reduced vascular density compared to both normal myometrium and uterine fibroid. In our proteomics analysis of eight paired samples of IVL and normal myometrium fresh frozen tissue, we identified proteins that were differentially expressed, mainly related to focal adhesions and regulation of the actin cytoskeleton. The most frequently involved chromosomes included deletions in 10q22.2, 10q24.32, 13q14, and 13q21-31. Correlation analyses highlighted chromosome 10q as the most frequent cytoband, with corresponding proteins involved in regulating focal adhesions and the cytoskeleton. Integrated analysis between pathological and clinical characteristics indicated that chromosome 10q deletion and vascular morphology in IVL could serve as important markers predicting aggressive behavior. Our study sheds light on the pathological and molecular changes linked to IVL, which could pave the way for new treatment approaches.
Mitochondria are dynamic organelles that are essential for cellular energy generation, metabolic regulation, and signal transduction. Their structural complexity enables adaptive responses to diverse physiological demands. In cancer, mitochondria orchestrate multiple cellular processes critical to tumor development. Metabolic reprogramming enables cancer cells to exploit aerobic glycolysis, glutamine metabolism, and lipid alterations, supporting uncontrolled growth, survival, and treatment resistance. Genetic and epigenetic alterations in mitochondrial and nuclear DNA disrupt oxidative phosphorylation, tricarboxylic acid cycle dynamics, and redox homeostasis, driving oncogenic progression. Mitochondrial dysfunction in tumors is highly heterogeneous, influencing disease phenotypes and treatment responses across cancer types. Within the tumor microenvironment, mitochondria profoundly impact immune responses by modulating T-cell survival and function, macrophage polarization, NK cell cytotoxicity, and neutrophil activation. They also mediate stromal cell functions, particularly in cancer-associated fibroblasts and tumor endothelial cells. Although targeting mitochondrial function represents a promising therapeutic strategy, mitochondrial heterogeneity and adaptive resistance mechanisms complicate interventional approaches. Advances in mitochondrial genome editing, proteomics, and circulating mitochondrial DNA analysis have enhanced tumor diagnostic precision. This review synthesizes the developmental landscape of mitochondrial research in cancer, comprehensively summarizing mitochondrial structural dynamics, metabolic plasticity, signaling networks, and interactions with the tumor microenvironment. Finally, we discuss the translational challenges in developing effective mitochondria-based cancer interventions.
INTRODUCTION:Placental weight has been associated with various adult-onset diseases, but the causal relationships and underlying mechanisms remain unclear. METHODS:This two-sample Mendelian randomization (MR) study utilized genome-wide association study (GWAS) data from multiple independent cohorts, primarily of European ancestry. The analysis included over 1.8 million individuals for type 2 diabetes mellitus (T2DM) outcomes. Data from four independent cohorts were used for validation. The inverse variance-weighted method was used for primary analysis, with weighted median, weighted mode, and MR-Egger regression for sensitivity analyses. RESULTS:Each standard deviation increase in genetically predicted placental weight was associated with T2DM (β = -0.109, 95 % CI: -0.184 to -0.034), basal cell carcinoma (β = 0.130, 95 % CI: 0.016 to 0.245), acute upper respiratory infections (β = -0.062, 95 % CI: -0.113 to -0.011), neurological diseases (β = -0.009, 95 % CI: -0.014 to -0.003), and endometrial cancer (β = -0.561, 95 % CI: -0.961 to -0.161). Placental weight also showed significant negative associations with blood glucose levels (β = -0.102, 95 % CI: -0.200 to -0.004). Mediation analyses revealed that dried fruit intake mediated 14.68 % of the total effect on T2DM risk, while immune cell phenotype analysis identified HLA DR on CD33dim HLA DR + CD11b + as a potential mediator in the causal pathway. CONCLUSION:This study provides genetic evidence for a causal relationship between placental weight and T2DM risk, mediated partly through dietary habits and immune pathways. These findings suggest that early-life placental development may influence long-term metabolic health, highlighting the importance of prenatal care in preventing adult-onset diseases.
Fiber electronics booms as a new important field but is currently limited by the challenge of finding both highly flexible and conductive fiber electrodes. Here, all-metal fibers based on nanowires are discovered. Silver nanowires are continuously assembled into robust fibers by salt-induced aggregation and then firmly stabilized by plasmonic welding. The nanowire network structures provide them both high flexibility with moduli at the level of MPa and conductivities up to 106 S m-1. They also show excellent electrochemical properties such as low impedance and high electrochemically active surface area. Their stable chronic single-neuron recording is further demonstrated with good biocompatibility in vivo. These new fiber materials may provide more opportunities for the future development of fiber electronics.
Abstract Researchers have typically studied the brain by monitoring characteristic signals, such as electrophysiology and neurotransmitters by implanted electronics. Here, real‐time monitoring of dynamic deformations of the brain tissue in vivo, is demonstrated, as a new characteristic parameter that is reflective of brain states. As a proof of concept, a thin capacitive deformation sensor is fabricated and implanted between the skull and cortex, and the sensor is shown to effectively monitor dynamic deformations of the cortical surface in the rat brain as induced by respiration and heartbeat under different degrees of anesthesia. This brain monitoring approach based on deformation signals opens up a new direction for understanding the brain.
Flexible fiber electrodes offer new opportunities for bioelectronics and are reliable in vivo applications, high flexibility, high electrical conductivity, and satisfactory biocompatibility are typically required. Herein, we present an all-metal flexible and biocompatible fiber electrode based on a metal nanowire hybrid strategy, i.e., silver nanowires were assembled on a freestanding framework, and further to render them inert, they were plated with a gold nanoshell. Our fiber electrodes exhibited a low modulus of ∼75 MPa and electrical conductivity up to ∼4.8 × 106 S m-1. They can resist chemical erosion with negligible leakage of biotoxic silver ions in the physiological environment, thus ensuring satisfactory biocompatibility. Finally, we demonstrated the hybrid fiber as a neural electrode that stimulated the sciatic nerve of a mouse, proving its potential for applications in bioelectronics.
Metal-backboned polymers (MBPs), with a unique backbone consisting of bonded metal atoms, are promising for optic, electric, magnetic, and thermoelectric fields. However, the application of MBP remains relatively understudied. Here, we develop a shear-induced orientation method to construct a flexible nickel-backboned polymer/carbon nanotube (NBP/CNT) thermoelectric composite fiber. It demonstrated a power factor of 719.48 μW ⋅m −1 K −2 , which is ca. 3.5 times as high as the bare CNT fiber. Remarkably, with the regulation of carrier mobility and carrier concentration of NBP, the composite fiber further showed simultaneous increases in electrical conductivity and Seebeck coefficient in comparison to the bare CNT fiber. The NBP/CNT fiber can be integrated into fabrics to harvest thermal energy of human body to generate an output voltage of 3.09 mV at a temperature difference of 8 K. This research opens a new avenue for the development of MBPs in power supply.
Implantable sensors, especially ion sensors, facilitate the progress of scientific research and personalized healthcare. However, the permanent retention of implants induces health risks after sensors fulfill their mission of chronic sensing. Biodegradation is highly anticipated; while; biodegradable chemical sensors are rare due to concerns about the leakage of harmful active molecules after degradation, such as ionophores. Here, a novel biodegradable fiber calcium ion sensor is introduced, wherein ionophores are covalently bonded with bioinert nanoparticles to replace the classical ion-selective membrane. The fiber sensor demonstrates comparable sensing performance to classical ion sensors and good flexibility. It can monitor the fluctuations of Ca2+ in a 4-day lifespan in vivo and biodegrade in 4 weeks. Benefiting from the stable bonding between ionophores and nanoparticles, the biodegradable sensor exhibits a good biocompatibility after degradation. Moreover, this approach of bonding active molecules on bioinert nanoparticles can serve as an effective methodology for minimizing health concerns about biodegradable chemical sensors.
The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment. Within this landscape, the innate immune system, a critical sentinel protecting against tumor incursion, is a key player. The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway has been found to be a linchpin of innate immunity: activation of this signaling pathway orchestrates the production of type I interferon (IFN-α/β), thus fostering the maturation, differentiation, and mobilization of immune effectors in the tumor microenvironment. Furthermore, STING activation facilitates the release and presentation of tumor antigens, and therefore is an attractive target for cancer immunotherapy. Current strategies to activate the STING pathway, including use of pharmacological agonists, have made substantial advancements, particularly when combined with immune checkpoint inhibitors. These approaches have shown promise in preclinical and clinical settings, by enhancing patient survival rates. This review describes the evolving understanding of the cGAS-STING pathway's involvement in tumor biology and therapy. Moreover, this review explores classical and non-classical STING agonists, providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies. Despite challenges and complexities, the cGAS-STING pathway, a promising avenue for enhancing cancer treatment efficacy, has the potential to revolutionize patient outcomes.
OBJECTIVES:To construct and validate a radiomics nomogram based on T2-sampling perfection with application-optimized contrasts using different flip-angle evolutions (SPACE) images for predicting cochlear and vestibular endolymphatic hydrops (EH) in Meniere's disease patients. METHODS:A total of 156 patients (312 affected ears) with bilateral definite Meniere's disease who underwent delayed enhancement MRI scans were enrolled in this study. All ears of the patients were divided into a training set (n = 218) and an internal validation set (n = 94). A radiomics nomogram was constructed from radiomics features extracted from the T2-SPACE images, and a radiomics score was calculated. Performance of the radiomics nomogram was assessed using receiver operating characteristics analysis. RESULTS:Five features were selected for the construction of the cochlear radiomics nomogram, and seven features for the vestibular radiomics nomogram. The radiomics nomograms exhibited robust performance in differentiating between EH-positive and EH-negative statuses in both training and validation cohorts, with the area under the receiver operating characteristics curve values for cochlear and vestibular radiomic nomograms being 0.703 and 0.728 in the training set, and 0.718 and 0.701 in the validation set, respectively. CONCLUSION:The novel radiomics nomograms based on T2-SPACE images were successfully constructed to predict cochlear and vestibular EH in Meniere's disease. The models showed a solid and superior performance and may play an important role in the EH prediction. CLINICAL RELEVANCE STATEMENT:We constructed a novel radiomics nomogram, which can be a very useful tool for predicting cochlear and vestibular endolymphatic hydrops in Meniere's disease patients. KEY POINTS:• This is the first T2-SPACE-based nomogram to predict cochlear and vestibular endolymphatic hydrops. • The nomogram is of great value to patients who are unable to undergo delayed enhancement MRI scans.
Background: Intravenous leiomyomatosis (IVL) is a rare histologically benign tumor with malignant behavior that can extend throughout the venous system with a certain risk of recurrence. Because of its rarity, systematic studies on IVL are limited. Methods: To investigate the pathological and molecular characteristics of IVL, one paired uterine fibroid and IVL tissue, and 31 paired IVL and normal myometrium were collected, and we performed a multi-omics study by integrating proteomic, genomic and immunohistochemical data. Findings: The single-cell RNA sequencing analysis showed that cell composition was dramatically different between IVL and uterine fibroid. Compared with normal myometrium, edema, hyalization and hypovascularity were the three important pathological changes in IVL. Proteomics analysis revealed that the differentially expressed proteins were mainly enriched in focal adhesions, regulation of the actin cytoskeleton, extracellular matrix-receptor interaction, and complement and coagulation cascades. The whole exosome sequencing results showed that the top mutated genes in IVL included PKD1, CAPN15, ZNF90, SNAPC4, and MUC4. Chromosome deletions were enriched in 10q22, 10q24-32, 13q14, and 13q21-31. Correlation analyses showed that the most frequent cytoband was chromosome 10q, of which the corresponding proteins were also involved in regulating focal adhesions and the cytoskeleton. Both candidate markers, ACTA2 and vinculin, were decreased in IVL samples, with a positive correlation between lower vinculin expression levels and more advanced tumor disease. Interpretation: Our study sheds light on the pathological and molecular changes associated with IVL, and helps establish new directions for IVL treatment.Funding: This study was funded by the Zhongshan Development Program (XK-066).Declaration of Interest: All authors declare no competing interests.Ethical Approval: Our study was conducted in accordance with the Declaration of Helsinki and approved by the ethical committee of the Zhongshan Hospital, Fudan University (Ethics Committee document number: B2021-488R). All patients provided written informed consent.
RATIONALE AND OBJECTIVES:Preoperative prediction of the recurrence risk in patients with advanced sinonasal squamous cell carcinoma (SNSCC) is critical for individualized treatment. To evaluate the predictive ability of radiomics signature (RS) based on deep learning and multiparametric MRI for the risk of 2-year recurrence in advanced SNSCC.MATERIALS AND METHODS:Preoperative MRI datasets were retrospectively collected from 265 SNSCC patients (145 recurrences) who underwent preoperative MRI, including T2-weighted (T2W), contrast-enhanced T1-weighted (T1c) sequences and diffusion-weighted (DW). All patients were divided into 165 training cohort and 70 test cohort. A deep learning segmentation model based on VB-Net was used to segment regions of interest (ROIs) for preoperative MRI and radiomics features were extracted from automatically segmented ROIs. Least absolute shrinkage and selection operator (LASSO) and logistic regression (LR) were applied for feature selection and radiomics score construction. Combined with meaningful clinicopathological predictors, a nomogram was developed and its performance was evaluated. In addition, X-title software was used to divide patients into high-risk or low-risk early relapse (ER) subgroups. Recurrence-free survival probability (RFS) was assessed for each subgroup.RESULTS:The radiomics score, T stage, histological grade and Ki-67 predictors were independent predictors. The segmentation models of T2WI, T1c, and apparent diffusion coefficient (ADC) sequences achieved Dice coefficients of 0.720, 0.727, and 0.756, respectively, in the test cohort. RS-T2, RS-T1c and RS-ADC were derived from single-parameter MRI. RS-Combined (combined with T2WI, T1c, and ADC features) was derived from multiparametric MRI and reached area under curve (AUC) and accuracy of 0.854 (0.749-0.927) and 74.3% (0.624-0.840), respectively, in the test cohort. The calibration curve and decision curve analysis (DCA) illustrate its value in clinical practice. Kaplan-Meier analysis showed that the 2-year RFS rate for low-risk patients was significantly greater than that for high-risk patients in both the training and testing cohorts (p < 0.001).CONCLUSION:Automated nomograms based on multi-sequence MRI help to predict ER in SNSCC patients preoperatively.
Immunogenic cell death (ICD) has been a revolutionary modality in cancer treatment since it kills primary tumors and prevents recurrent malignancy simultaneously. ICD represents a particular form of cancer cell death accompanied by production of damage-associated molecular patterns (DAMPs) that can be recognized by pattern recognition receptors (PRRs), which enhances infiltration of effector T cells and potentiates antitumor immune responses. Various treatment methods can elicit ICD involving chemo- and radio-therapy, phototherapy and nanotechnology to efficiently convert dead cancer cells into vaccines and trigger the antigen-specific immune responses. Nevertheless, the efficacy of ICD-induced therapies is restrained due to low accumulation in the tumor sites and damage of normal tissues. Thus, researchers have been devoted to overcoming these problems with novel materials and strategies. In this review, current knowledge on different ICD modalities, various ICD inducers, development and application of novel ICD-inducing strategies are summarized. Moreover, the prospects and challenges are briefly outlined to provide reference for future design of novel immunotherapy based on ICD effect.
The extracellular potassium ion concentration in the brain exerts a significant influence on cellular excitability and intercellular communication. Perturbations in the extracellular potassium ion level are closely correlated with various chronic neuropsychiatric disorders including depression. However, a critical gap persists in performing real-time and long-term monitoring of extracellular potassium ions, which is necessary for comprehensive profiling of chronic neuropsychiatric diseases. Here, a fiber potassium ion sensor (FKS) that consists of a soft conductive fiber with a rough surface and a hydrophobic-treated transduction layer interfaced with a potassium ion-selective membrane is found to solve this problem. The FKS demonstrates stable interfaces between its distinct functional layers in an aqueous environment, conferring an exceptional stability of 6 months in vivo, in stark contrast to previous reports with working durations from hours to days. Upon implantation into the mouse brain, the FKS enables effective monitoring of extracellular potassium ion dynamics under diverse physiological states including anesthesia, forced swimming, and tail suspension. Using this FKS, tracking of extracellular potassium ion fluctuations that align with behaviors associated with the progression of depression over months is achieved, demonstrating its usability in studying chronic neuropsychiatric disorders from a new biochemical perspective.