Latest ArticlesAfter years of research and development, flexible sensors are gradually evolving from the traditional “electronic” paradigm to the “ionic” dimension. Smart flexible sensors derived from the concept of ion transport are gradually emerging in the flexible electronics. In particular, ionic hydrogels have increasingly become the focus of research on flexible sensors as a result of their tunable conductivity, flexibility, biocompatibility, and self-healable capabilities. Nevertheless, the majority of existing sensors based on ionic hydrogels still mainly rely on external power sources, which greatly restrict the dexterity and convenience of their applications. Advances in energy harvesting technologies offer substantial potential toward engineering self-powered sensors. This article reviews in detail the self-powered mechanisms of ionic hydrogel self-powered sensors (IHSSs), including piezoelectric, triboelectric, ionic diode, moist-electric, thermoelectric, potentiometric transduction, and hybrid modes. At the same time, structural engineering related to device and material characteristics is discussed. Additionally, the relevant applications of IHSS toward wearable electronics, human–machine interaction, environmental monitoring, and medical diagnostics are further reviewed. Lastly, the challenges and prospective advancement of IHSS are outlined.
Fluorescence imaging, a highly sensitive molecular imaging modality, is being increasingly integrated into clinical practice. Imaging within the second near-infrared biological window (NIR-II; 1,000 to 1,700 nm), also referred to as shortwave infrared, has received substantial attention because of its markedly reduced autofluorescence, deeper tissue penetration, and enhanced spatiotemporal resolution as compared to traditional near-infrared (NIR) imaging. Indocyanine green (ICG), a US Food and Drug Administration-approved NIR fluorophore, has long been used in clinical applications, including blood vessel angiography, vascular perfusion monitoring, and tumor detection. Recent advancements in NIR-II imaging technology have revitalized interest in ICG, revealing its extended tail fluorescence beyond 1,000 nm and reaffirming its potential as a clinically translatable NIR-II fluorophore for in vivo imaging and theranostic applications for diagnosing various diseases. This review emphasizes the notable advances in the use of ICG and its derivatives for NIR-II imaging and image-guided therapy from both fundamental and clinical perspectives. We also provide a concise conclusion and discuss the challenges and future opportunities with NIR-II imaging using clinically approved fluorophores.
This paper reviews recent developments and key advances in terahertz (THz) science, technology, and applications, focusing on 3 core areas: astronomy, telecommunications, and biophysics. In THz astronomy, it highlights major discoveries and ongoing projects, emphasizing the role of advanced superconducting technologies, including superconductor–insulator–superconductor (SIS) mixers, hot electron boundedness spectroscopy (HEB), transition-edge sensors (TESs), and kinetic inductance detectors (KIDs), while exploring prospects in the field. For THz telecommunication, it discusses progress in solid-state sources, new communication technologies operating within the THz band, and diverse modulation methods that enhance transmission capabilities. In THz biophysics, the focus shifts to the physical modulation of THz waves and their impact across biological systems, from whole organisms to cellular and molecular levels, emphasizing nonthermal effects and fundamental mechanisms. This review concludes with an analysis of the challenges and perspectives shaping the future of THz technology.
Metamaterials hold great potential to enhance the imaging performance of magnetic resonance imaging (MRI) as auxiliary devices, due to their unique ability to confine and enhance electromagnetic fields. Despite their promise, the current implementation of metamaterials faces obstacles for practical clinical adoption due to several notable limitations, including their bulky and rigid structures, deviations from optimal resonance frequency, and inevitable interference with the radiofrequency (RF) transmission field in MRI. Herein, we address these restrictions by introducing a flexible and smart metamaterial that enhances sensitivity by conforming to patient anatomies while ensuring comfort during MRI procedures. The proposed metamaterial selectively amplifies the magnetic field during the RF reception phase by passively sensing the excitation signal strength, remaining “off” during the RF transmission phase. Additionally, the metamaterial can be readily tuned to achieve a precise frequency match with the MRI system through a controlling circuit. The metamaterial presented here paves the way for the widespread utilization of metamaterials in clinical MRI, thereby translating this promising technology to the MRI bedside.
Exposure to airborne fine particulate matter (PM2.5) is strongly associated with poor fertility and ovarian damage. However, the mechanism underlying this remains largely unclear. Here, we found that PM2.5 markedly impaired murine ovarian reserve, decreased hormone levels, and aggravated ovarian inflammation. Circulating interleukin-6 (IL-6) was elevated in PM2.5-exposed mice and was further confirmed to mediate this damage by IL-6 recombinant protein intervention. PM2.5 exposure led to increased alveolar macrophage infiltration in the lungs. However, alveolar macrophage clearance with clodronate liposomes could not fully reverse the elevated IL-6 levels and ovarian injury, suggesting that alveolar macrophages were probably not the only source of circulating IL-6. Further experiments indicated that IL-6 mainly targeted ovarian theca–interstitial cells and impaired testosterone synthesis via suppressing the peroxisome proliferator-activated receptor γ (PPARγ) pathway. In addition, apoptosis of granulosa cells and restriction of follicular growth were observed in co-cultures with IL-6-treated theca–interstitial cells, which could be further reversed by the PPARγ agonist. Moreover, IL-6-neutralizing antibodies ameliorated PM2.5-induced ovarian damage. Notably, increased levels of circulating IL-6 were observed in premature ovarian aging patients and were inversely associated with their ovarian function. In summary, our findings offer a mechanistic explanation for PM2.5-induced ovarian dysfunction and verify IL-6 as a biomarker and potential therapeutic target.
The vast potential of medical big data to enhance healthcare outcomes remains underutilized due to privacy concerns, which restrict cross-center data sharing and the construction of diverse, large-scale datasets. To address this challenge, we developed a deep generative model aimed at synthesizing medical data to overcome data sharing barriers, with a focus on breast ultrasound (US) image synthesis. Specifically, we introduce CoLDiT, a conditional latent diffusion model with a transformer backbone, to generate US images of breast lesions across various Breast Imaging Reporting and Data System (BI-RADS) categories. Using a training dataset of 9,705 US images from 5,243 patients across 202 hospitals with diverse US systems, CoLDiT generated breast US images without duplicating private information, as confirmed through nearest-neighbor analysis. Blinded reader studies further validated the realism of these images, with area under the receiver operating characteristic curve (AUC) scores ranging from 0.53 to 0.77. Additionally, synthetic breast US images effectively augmented the training dataset for BI-RADS classification, achieving performance comparable to that using an equal-sized training set comprising solely real images (P = 0.81 for AUC). Our findings suggest that synthetic data, such as CoLDiT-generated images, offer a viable, privacy-preserving solution to facilitate secure medical data sharing and advance the utilization of medical big data.
Spermatogenesis is a sophisticated biological process by which spermatogonial stem cells (SSCs) undergo self-renewal and differentiation into spermatozoa. Molecular mechanisms underlying fate determinations of human SSCs by key genes and signaling pathways remain elusive. Here, we report for the first time that Yes1-associated transcriptional regulator (YAP1) is required for fate determinations of SSCs and male fertility by interacting with RAD21 and targeting NEDD4 in humans and mice. YAP1 was mainly located at cell nuclei of human SSCs. YAP1 silencing resulted in the decreases in proliferation and DNA synthesis as well as an enhancement in apoptosis of human SSCs both in vivo and in vitro. RNA sequencing and real-time polymerase chain reaction assays identified NEDD4 as a target of YAP1, and NEDD4 knockdown inhibited the proliferation of human SSCs and increased their apoptosis. Furthermore, YAP1 interacted with RAD21 to regulate NEDD4 transcription in human SSCs. Importantly, YAP1 abnormalities were found to be associated with non-obstructive azoospermia (NOA) as manifested as lower expression level of YAP1 in testicular tissues of NOA patients and YAP1 single-nucleotide variants (SNVs) in 777 NOA patients. Finally, Yap1 germline conditional knockout (cKO) mice assumed mitotic arrest, low sperm count, and motility. Collectively, these results highlight a critical role of YAP1 in determining the fate determinations of human SSCs and male infertility through the YAP1/RAD21/NEDD4 pathway. This study provides new insights into the genetic regulatory mechanisms underlying human spermatogenesis and the pathogenesis of NOA, and it offers new targets for gene therapy of male infertility.
The NLRP3 inflammasome plays a critical role in various inflammatory conditions. However, despite extensive research in targeted drug development for NLRP3, including MCC950, clinical success remains elusive. Here, we discovered that the activated NLRP3 inflammasome complex (disc-NLRP3) and the activating mutation L351P exhibited resistance to MCC950. Through investigations using the small-molecule compound polydatin, HSP90α was found to stabilize both the resting (cage-NLRP3) and activated state (disc-NLRP3) of NLRP3 complexes, sustaining its activation. Our mechanistic studies revealed that polydatin specifically targets HSP90α, binding to it directly and subsequently interfering with the HSP90α-NLRP3 interaction. This disruption leads to the dissipation of cage-NLRP3, disc-NLRP3 complexes and NLRP3 L351P. Importantly, genetic and pharmacological inactivation of HSP90α effectively reduced NLRP3 inflammasome activation and alleviated cerulein-induced acute pancreatitis. These therapeutic effects highlight the clinical potential of HSP90α inhibition. Our findings demonstrate that HSP90α is crucial for the stability of both the resting and activated states of the NLRP3 inflammasome during its sustained activation, and targeting HSP90α represents a promising therapeutic strategy for diseases driven by the NLRP3 inflammasome.
Living microorganisms can perform directed migration for foraging in response to a chemoattractant gradient. We report a biomimetic strategy that rotary FoF1-ATPase (adenosine triphosphatase)-propelled flasklike colloidal motors exhibit positive chemotaxis resembling the chemotactic behavior of bacteria. The streamlined flasklike colloidal particles are fabricated through polymerization, expansion, surface rupture, and re-polymerizing nanoemulsions composed of triblock copolymers and ribose. The as-synthesized particles enable the incorporation of thylakoid vesicles into the cavity, ensuring a geometric asymmetric nanoarchitecture. The chemical gradient in the neck channel across flasklike colloidal motors facilitates autonomous movement at a speed of 1.19 μm/s in a ΔpH value of 4. Computer simulations reveal the self-actuated flasklike colloidal motors driven by self-diffusiophoretic force. These flasklike colloidal motors display positive directional motion along an adenosine diphosphate (ADP) concentration gradient during adenosine triphosphate (ATP) synthesis. The positive chemotaxis is ascribed that the phosphorylation reaction occurring inside colloidal motors generates 2 distinct phoretic torques at the bottom and the opening owing to the diffusion of ADP, thereby a continuous reorientation motion. Such a biophysical strategy that nanosized rotary protein molecular motors propel the directional movement of a flasklike colloidal motor holds promise for designing new types of biomedical swimming nanobots.