Latest ArticlesTo explore whether the metabolic state reprogramming approach may be used to explore previously unknown metabolic pathways that contribute to antibiotic resistance, especially those that have been neglected in previous studies, pyruvate reprogramming was performed to reverse the resistance of multidrug-resistant Edwardsiella tarda. Surprisingly, we identified a pyruvate-regulated glutathione system that occurs by boosting glycine, serine, and threonine metabolism. Moreover, cysteine and methionine metabolism played a key role in this reversal. This process involved pyruvate-depressed glutathione and pyruvate-promoted glutathione oxidation, which was attributed to the elevated glutathione peroxidase and depressed glutathione reductase that was inhibited by glycine. This regulation inhibited reactive oxygen species (ROS) degradation and thereby elevated ROS to eliminate E. tarda. Loss of metB, gpx, and gor of the metabolic pathways increased and decreased resistance, respectively, both in vitro and in vivo, thereby supporting the hypothesis of a pyruvate–cysteine–glutathione system/glycine–ROS metabolic pathway. The role of this metabolic pathway in drug resistance and reprogramming reversal was demonstrated in laboratory-evolved gentamicin-resistant E. tarda and other clinically isolated multidrug- and carbapenem-resistant pathogens. Thus, we reveal a less studied antibiotic resistance metabolic pathway along with the mechanisms involved in its reversal.
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.
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.
Neutrophils are essential in combating invading pathogens such as Plasmodium parasites, but the participation of their subpopulations and mechanisms in resistance to parasite infection are not fully understood. Our study identified a marked increase in Ly6G+ neutrophils in response to P. berghei ANKA infection. Depletion of these cells rendered mice more susceptible to infection. Elevated interleukin-17 (IL-17) levels, which increased the Ly6G+ neutrophil population, were also found to contribute to this protective effect. IL-17 depletion led to reduced neutrophil numbers and increased susceptibility. Furthermore, dihydroartemisinin (DHA) treatment enhanced neutrophil-mediated immune responses through up-regulation of CD18 and CXCR4 factors. These findings revealed key mechanisms of neutrophil and IL-17 interactions in malaria protection and highlighted DHA’s potential to promote neutrophil function in combating malaria.
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.
Radiative cooling has witnessed substantial progress while its performance is constrained by the thermal reciprocal Kirchhoff’s law. Violating Kirchhoff’s law to pursue nonreciprocal radiative cooling seems promising; however, the energy conservation requirement and radiant flux integrated over the entire hemisphere make the nonreciprocal benefit insignificant. This commentary discusses the practical limits of nonreciprocal radiative cooling and points toward the future direction of directional radiative cooling.
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.
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.
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.
Artificial intelligence of things systems equipped with flexible sensors can autonomously and intelligently detect the condition of the surroundings. However, current intelligent monitoring systems always rely on an external computer with the capability of machine learning rather than integrating it into the sensing device. The computer-assisted intelligent system is hampered by energy inefficiencies, privacy issues, and bandwidth restrictions. Here, a flexible, large-scale sensing array with the capability of low-power in-sensor intelligence based on a compression hypervector encoder is proposed for real-time recognition. The system with in-sensor intelligence can accommodate different individuals and learn new postures without additional computer processing. Both the communication bandwidth requirement and energy consumption of this system are significantly reduced by 1,024 and 500 times, respectively. The capability for in-sensor inference and learning eliminates the necessity to transmit raw data externally, thereby effectively addressing privacy concerns. Furthermore, the system possesses a rapid recognition speed (a few hundred milliseconds) and a high recognition accuracy (about 99%), comparing with support vector machine and other hyperdimensional computing methods. The research holds marked potential for applications in the integration of artificial intelligence of things and flexible electronics.