Latest ArticlesComorbid anxiety in chronic pain is clinically common, with a comorbidity rate of over 50%. The main treatments are based on pharmacological, interventional, and implantable approaches, which have limited efficacy and carry a risk of side effects. Here, we report a terahertz (THz, 1012 Hz) wave stimulation (THS) technique, which exerts nonthermal, long-term modulatory effects on neuronal activity by reducing the binding between nano-sized glutamate molecules and GluA2, leading to the relief of pain and comorbid anxiety-like behaviors in mice. In mice with co-occurring anxiety and chronic pain induced by complete Freund's adjuvant (CFA) injection, hyperactivity was observed in glutamatergic neurons in the anterior cingulate cortex (ACCGlu). Using whole-cell recording in ACC slices, we demonstrated that THS (34 THz) effectively inhibited the excitability of ACCGlu. Moreover, molecular dynamics simulations showed that THS reduced the number of hydrogen bonds bound between glutamate molecules and GluA2. Furthermore, THS target to the ACC in CFA-treatment mice suppressed ACCGlu hyperactivity and, as a result, alleviated pain and anxiety-like behaviors. Consistently, inhibition of ACCGlu hyperactivity by chemogenetics mimics THS-induced antinociceptive and antianxiety behavior. Together, our study provides evidence for THS as an intervention technique for modulating neuronal activity and a viable clinical treatment strategy for pain and comorbid anxiety.
Atrazine (AT), a widely utilized chemical herbicide, causes widespread contamination of agricultural water bodies. Recently, exposure to AT has been linked to the development of age-related neurodegenerative diseases (NDs), suggesting its neurotoxicity potential. As an endocrine disruptor, AT targets the hypothalamus, a crucial part of the neuroendocrine system. However, the toxicological mechanism of AT exposure to the hypothalamus and its correlation with ND development remain unexplored. Our results indicated that AT exposure caused significant morphological and structural damage to the hypothalamus, leading to the loss of mature and intact neurons and microglial activation. Furthermore, hypothalamic neural stem cells (HtNSCs) were recruited to areas of neuronal damage caused by AT. Through in vivo and in vitro experiments, we clarified the outcomes of AT-induced HtNSC recruitment alongside the loss of mature/intact neurons. Mechanistically, AT induces senescence in these recruited HtNSCs by activating integrated stress response signaling. This consequently hinders the repair of damaged neurons by inhibiting HtNSC proliferation and differentiation. Overall, our findings underscore the pivotal role of the integrated stress response pathway in AT-induced HtNSC senescence and hypothalamic damage. Additionally, the present study offers novel perspectives to understand the mechanisms of AT-induced neurotoxicity and provides preliminary evidence linking AT contamination to the development of NDs.
Cryogenic crystal bolometer plays a crucial role in searching for neutrinoless double-beta (0νββ) decay, which is a rare process that could determine the Majorana nature of neutrinos. The flagship bolometer experiment—CUORE (Cryogenic Underground Observatory for Rare Events)—operating at the Gran Sasso underground laboratory [Laboratori Nazionali del Gran Sasso (LNGS)] as the world's first ton-scale bolometric detector has achieved great success and well demonstrated advantages of the bolometric technology for the 0νββ study. The proposed upgrade of CUORE—the CUPID project—aims to achieve higher sensitivity with orders of magnitude background reduction by utilizing scintillating crystals and dual readout technology to exclude most of the background events dominated by alpha particles. Although CUPID has outstanding advantages over CUORE, further increasing the detection capability to fully explore the effective neutrino mass region for the inverted neutrino mass hierarchy and possibly to discover Majorana neutrinos remains a technical challenge ahead. In this prospective, we discuss strategies toward future technology development to further enhance the experimental sensitivity.
MXenes, a class of 2-dimensional transition metal carbides and nitrides, have garnered important attention due to their remarkable electrical and thermal conductivity, high photothermal conversion efficiency, and multifunctionality. This review explores the potential of MXene materials in various thermal applications, including thermal energy storage, heat dissipation in electronic devices, and the mitigation of electromagnetic interference in wearable technologies. Recent advancements in MXene composites, such as MXene/bacterial cellulose aerogel films and MXene/polymer composites, have demonstrated enhanced performance in phase change thermal storage and electromagnetic interference shielding, underscoring their versatility and effectiveness. Although notable progress has been made, challenges remain, including the need for a deeper understanding of photothermal conversion mechanisms, improvements in mechanical properties, exploration of diverse MXene types, and the development of sustainable synthesis methods. This paper discusses these aspects and outlines future research directions, emphasizing the growing importance of MXenes in addressing energy efficiency, health, and safety concerns in modern applications.
Disease-associated microglia (DAM) are observed in neurodegenerative diseases, demyelinating disorders, and aging. However, the spatiotemporal dynamics and evolutionary trajectory of DAM during the progression of amyotrophic lateral sclerosis (ALS) remain unclear. Using a mouse model of ALS that expresses a human SOD1 gene mutation, we found that the microglia subtype DAM begins to appear following motor neuron degeneration, primarily in the brain stem and spinal cord. Using reverse transcription quantitative polymerase chain reaction, RNAscope in situ hybridization, and flow cytometry, we found that DAM increased in number as the disease progressed, reaching their peak in the late disease stage. DAM responded to disease progression in both SOD1G93A mice and sporadic ALS and C9orf72-mutated patients. Motor neuron loss in SOD1G93A mice exhibited 2 accelerated phases: P90 to P110 (early stage) and P130 to P150 (late stage). Some markers were synchronized with the accelerated phase of motor neuron loss, suggesting that these proteins may be particularly responsive to disease progression. Through pseudotime trajectory analysis, we tracked the dynamic transition of homeostatic microglia into DAM and cluster 6 microglia. Interestingly, we used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia in SOD1G93A mice and observed that DAM survival is independent of CSF1R. An in vitro phagocytosis assay directly confirmed that DAM could phagocytose more beads than other microglia subtypes. These findings reveal that the induction of the DAM phenotype is a shared cross-species and cross-subtype characteristic in ALS. Inducing the DAM phenotype and enhancing its function during the early phase of disease progression, or the time window between P130 and P150 where motor neuron loss slows, could serve as a neuroprotective strategy for ALS.
Photoelectrochemistry provides an important application in the production of high-value-added chemicals. However, photoelectrochemical organic transformation with high product selectivity remains a challenge. Until now, various technologies have been developed to promote the selectivity of photoelectrochemical high-value-added chemical production. Herein, a novel ion-shielding heterogeneous photoelectrocatalysis strategy for the production of trifluoromethyl group (CF3)-containing compounds with high selectivity is described.
Personalized healthcare monitoring is a transformative tool for preventing potential risks and enhancing health status, particularly through molecular-level insights. Advances in nanotechnology, smart devices, and artificial intelligence (AI) have revolutionized personalized healthcare, especially in point-of-care testing (POCT), enabling early detection and timely intervention. Recently, surface-enhanced Raman spectroscopy (SERS) technology, particularly with flexible chips, has shown immense promise in this field due to its in situ, rapid, specific, and efficient detection capabilities. In this review, we highlight recent advancements in flexible SERS chips for personalized healthcare monitoring, demonstrating their effectiveness in target sampling and detection. Importantly, we provide a comprehensive overview of potential applications of flexible SERS chips in personalized healthcare, address current challenges, and propose future development directions. We also explore the future development of miniaturized Raman devices to broaden their applications in personalized healthcare monitoring. Additionally, we underscore the important role of AI in enhancing data processing and analysis. Our aim is to offer a thorough guide on integrating SERS into personalized healthcare monitoring, promising a new era of health management.
The effective and translational strategy to regenerate knee meniscal fibrocartilage remained challenging. Herein, we first identified vascular smooth muscle cells (VSMCs) transdifferentiated into fibrochondrocytes and participated in spontaneous meniscal regeneration using smooth muscle cell lineage tracing transgenic mice meniscal defect model. Then, we identified low-intensity pulsed ultrasound (LIPUS) acoustic stimulus enhanced fibrochondrogenic transdifferentiation of VSMCs in vitro and in vivo. Mechanistically, LIPUS stimulus could up-regulate mechanosensitive ion channel Piezo1 expression and then activate the transforming growth factor β1 (TGFβ1) signal, following repression of the Notch signal, consequently enhancing fibrochondrogenic transdifferentiation of VSMCs. Finally, we demonstrated that the regular LIPUS stimulus enhanced anisotropic native-like meniscal fibrocartilage tissue regeneration in a beagle canine subtotal meniscectomy model at 6 months postoperatively. The single-cell RNA sequencing analysis confirmed the role of VSMC fibrochondrogenic transdifferentiation in meniscal regeneration.
The current biopsychosocial medical models have substantial limitations and require to form an improved scientific medical model. This new model should consider human health holistically, emphasizing the integrity of life and focusing on the impact of physiological spaces, natural factors, and the interaction between individuals and their environment. We propose a “life–society–nature medical model” that provides novel perspectives for innovation in basic medical theory, the integration of Traditional Chinese and Western medicine, disease diagnosis, therapy and prevention, as well as the development of new therapeutic agents, scientific instruments, and approaches to medical education.
Photonic synapses combining photosensitivity and synaptic function can efficiently perceive and memorize visual information, making them crucial for the development of artificial vision systems. However, the development of high-performance photonic synapses with low power consumption and rapid optical erasing ability remains challenging. Here, we propose a photon-modulated charging/discharging mechanism for self-powered photonic synapses. The current hysteresis enables the devices based on CsPbBr3/solvent/carbon nitride multilayer architecture to emulate synaptic behaviors, such as excitatory postsynaptic currents, paired-pulse facilitation, and long/short-term memory. Intriguingly, the unique radiation direction-dependent photocurrent endows the photonic synapses with the capability of optical writing and rapid optical erasing. Moreover, the photonic synapses exhibit exceptional performance in contrast enhancement and noise reduction owing to the notable synaptic plasticity. In simulations based on artificial neural network (ANN) algorithms, the pre-processing by our photonic synapses improves the recognition rate of handwritten digit from 11.4% (200 training epochs) to 85% (~60 training epochs). Furthermore, due to the excellent feature extraction and memory capability, an array based on the photonic synapses can imitate facial recognition of human retina without the assistance of ANN.