Bioorthogonal reactions are a class of chemical reactions that can be carried out in living organisms without interfering with other reactions, possessing high yield, high selectivity, and high efficiency. Since the first proposal of the conception by Professor Carolyn Bertozzi in 2003, bioorthogonal chemistry has attracted great attention and has been quickly developed. As an important chemical biology tool, bioorthogonal reactions have been applied broadly in biomedicine, including bio-labeling, nucleic acid functionalization, drug discovery, drug activation, synthesis of antibody–drug conjugates, and proteolysis-targeting chimeras. Given this, we summarized the basic knowledge, development history, research status, and prospects of bioorthogonal reactions and their biomedical applications. The main purpose of this paper is to furnish an overview of the intriguing bioorthogonal reactions in a variety of biomedical applications and to provide guidance for the design of novel reactions to enrich bioorthogonal chemistry toolkits.

The controllable manipulation and transfer of droplets are fundamental in a wide range of chemical reactions and even life processes. Herein, we present a novel, universal, and straightforward acoustic approach to fabricating biomimetic surfaces for on-demand droplet manipulations like many natural creatures. Based on the capillary waves induced by surface acoustic waves, various polymer films could be deformed into pre-designed structures, such as parallel grooves and grid-like patterns. These structured and functionalized surfaces exhibit impressive ability in droplet transportation and water collection, respectively. Besides these static surfaces, the tunability of acoustics could also endow polymer surfaces with dynamic controllability for droplet manipulations, including programming wettability, mitigating droplet evaporation, and accelerating chemical reactions. Our approach is capable of achieving universal surface manufacturing and droplet manipulation simultaneously, which simplifies the fabrication process and eliminates the need for additional chemical modifications. Thus, we believe that our acoustic-derived surfaces and technologies could provide a unique perspective for various applications, including microreactor integration, biochemical reaction control, tissue engineering, and so on.

Terahertz (THz) wave manipulation, especially the beam deflection, plays an essential role in various applications, such as next-generation communication, space exploration, and high-resolution imaging. Current THz optical components and devices are hampered by their large bulk sizes and passive responses, limiting the development of high-performance, miniaturized THz microsystems. Tunable metasurfaces offer a powerful dynamic optical platform for controlling the propagation of electromagnetic waves. In this article, we presented a mechanically tunable metasurface (MTM), which can achieve terahertz beam deflection and vary the intensity of the anomalous reflected terahertz wave by changing the air gap between the metallic resonator (MR) array with phase discontinuities and Au ground plane. The absence of lossy spacer materials substantially enhances deflection efficiency. The device was fabricated by a combination of the surface and bulk-micromachining processes. The THz beam steering capability was characterized using terahertz time domain spectroscopy. When the air gap is 50 μm, the maximum deflection coefficient reaches 0.60 at 0.61 THz with a deflection angle of ~44.5°, consistent with theoretical predictions. We further established an electrically tunable miniaturized THz device for dynamic beam steering by introducing a micro voice coil motor to control the air gap continuously. It is shown that our designed MTM demonstrates a high modulation depth of deflection coefficient (~ 62.5%) in the target steered angle at the operating frequency. Our results showcase the potential of the proposed MTM as a platform for high-efficiency THz beam manipulation.

Persistent hepatic cellular metabolic stress and liver inflammatory stimuli are key signatures of nonalcoholic steatohepatitis (NASH). DDX3X is a vital molecule involved in cell fate decisions in both pro-survival stress granule (SG) and pro-death NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly in response to stress signals. However, the role of DDX3X in NASH remains unclear. We characterized the cell type-specific roles of DDX3X in NASH. Human liver tissues from NASH patients and normal control subjects were collected to assess DDX3X expression and distribution. Nutritional steatohepatitis models were constructed by feeding macrophage-specific DDX3X knockout (DDX3X^ΔMφ), hepatocyte-specific DDX3X knockout (DDX3X^Δhep), and wild-type control (DDX3X^fl/fl) mice a high-fat and high-cholesterol (HFHC) diet, a methionine- and choline-deficient (MCD) diet, and a high-fat/high-iron/high-fructose/high-cholesterol, low-methionine, and choline-deficient (HFHIHFHC-MCD) diet. The study demonstrated that DDX3X was predominantly expressed in macrophages and hepatocytes in control liver tissues, and its expression was down-regulated in patients or mice with NASH. Compared to DDX3X^fl/fl littermates, DDX3X^ΔMφ mice showed improved liver histology in nutritional steatohepatitis models. Loss of macrophage DDX3X inhibited NLRP3 inflammasome-mediated pyroptosis, causing anti-inflammatory M2 polarization and alleviating hepatocyte steatohepatitic changes. DDX3X^Δhep mice developed marked steatohepatitis in multiple nutritional steatohepatitis models compared to DDX3X^fl/fl littermates. DDX3X-deleted hepatocytes showed impaired SG assembly, leading to increased sensitivity and intolerance to metabolic stimulation and resultant steatohepatitis. In conclusion, DDX3X plays opposite roles in different cell types during the progression of NASH. A better understanding of the cell-specific differences in the crosstalk between SG formation and NLRP3 activation is crucial for developing prospective targeted DDX3X inhibitors for the treatment of NASH.

Posttraumatic stress disorder (PTSD) is a serious psychosis leading to cognitive impairment. To restore cognitive functions for patients, the main treatments are based on medication or rehabilitation training but with limited effectiveness and strong side effects. Here, we demonstrate a new treatment approach for PTSD by using terahertz (THz) photons stimulating the hippocampal CA3 subregion. We verified that this method can nonthermally restore cognitive function in PTSD rats in vivo. After THz photon irradiation, the PTSD rats’ recognitive index improved by about 10% in a novel object recognition test, the PTSD rats’ accuracy improved by about 100% in a shuttler box test, the PTSD rats’ numbers to identify target box was about 5 times lower in a Barnes maze test, and the rate of staying in new arm increased by approximately 40% in a Y-maze test. Further experimental studies found that THz photon (34.5 THz) irradiation could improve the expression of NR2B (increased by nearly 40%) and phosphorylated NR2B (increased by about 50%). In addition, molecular dynamics simulations showed that THz photons at a frequency of 34.5 THz are mainly absorbed by the pocket of glutamate receptors rather than by glutamate molecules. Moreover, the binding between glutamate receptors and glutamate molecules was increased by THz photons. This study offers a nondrug, nonthermal approach to regulate the binding between the excitatory neurotransmitter (glutamate) and NR2B. By increasing synaptic plasticity, it effectively improves the cognitive function of animals with PTSD, providing a promising treatment strategy for NR2B-related cognitive disorders.

With unlimited topological modes in mathematics, the fractional orbital angular momentum (FOAM) demonstrates the potential to infinitely increase the channel capacity in acoustic-vortex (AV) communications. However, the accuracy and stability of FOAM recognition are still limited by the nonorthogonality and poor anti-interference of fractional AV beams. The popular machine learning, widely used in optics based on large datasets of images, does not work in acoustics because of the huge engineering of the 2-dimensional point-by-point measurement. Here, we report a strategy of phase-dislocation-mediated high-dimensional fractional AV communication based on pair-FOAM multiplexing, circular sparse sampling, and machine learning. The unique phase dislocation corresponding to the topological charge provides important physical guidance to recognize FOAMs and reduce sampling points from theory to practice. A straightforward convolutional neural network considering turbulence and misalignment is further constructed to achieve the stable and accurate communication without involving experimental data. We experimentally present that the 32-point dual-ring sampling can realize the 10-bit information transmission in a limited topological charge scope from ±0.6 to ±2.4 with the FOAM resolution of 0.2, which greatly reduce the divergence in AV communications. The infinitely expanded channel capacity is further verified by the improved FOAM resolution of 0.025. Compared with other milestone works, our strategy reaches 3-fold OAM utilization, 4-fold information level, and 5-fold OAM resolution. Because of the extra advantages of high dimension, high speed, and low divergence, this technology may shed light on the next-generation AV communication.

Neddylation plays a vital role in post-translational modification, intricately shaping the regulation of diverse biological processes, including those related to cellular immune responses. In fact, neddylation exerts control over both innate and adaptive immune systems via various mechanisms. Specifically, neddylation influences the function and survival of innate immune cells, activation of pattern recognition receptors and GMP-AMP synthase–stimulator of interferon genes pathways, as well as the release of various cytokines in innate immune reactions. Moreover, neddylation also governs the function and survival of antigen-presenting cells, which are crucial for initiating adaptive immune reactions. In addition, neddylation regulates T cell activation, proliferation, differentiation, survival, and their effector functions, thereby ensuring an appropriate adaptive immune response. In this review, we summarize the most recent findings in these aspects and delve into the connection between dysregulated neddylation events and immunological disorders, especially inflammatory diseases. Lastly, we propose future directions and potential treatments for these diseases by targeting neddylation.

Visualizing cellular structures especially the cytoskeleton and the nucleus is crucial for understanding mechanobiology, but traditional fluorescence staining has inherent limitations such as phototoxicity and photobleaching. Virtual staining techniques provide an alternative approach to addressing these issues but often require substantial amount of user training data. In this study, we develop a generalizable cell virtual staining toolbox (termed CellVisioner) based on few-shot transfer learning that requires substantially reduced user training data. CellVisioner can virtually stain F-actin and nuclei for various types of cells and extract single-cell parameters relevant to mechanobiology research. Taking the label-free single-cell images as input, CellVisioner can predict cell mechanobiological status (e.g., Yes-associated protein nuclear/cytoplasmic ratio) and perform long-term monitoring for living cells. We envision that CellVisioner would be a powerful tool to facilitate on-site mechanobiological research.

Second near-infrared (NIR-II) window optical molecular imaging kicks off a new revolution in high-quality imaging in vivo, but always suffers from the hurdles of inevitable tissue autofluorescence background and NIR-II probe development. Here, we prepare a Förster resonance energy transfer-based ratiometric NIR-II window hydrogen sulfide (H₂S) sensor through the combination of an H₂S-responsive NIR-II cyanine dye (acceptor, LET-1055) and an H₂S-inert rhodamine hybrid polymethine dye (donor, Rh930). This sensor not only exhibits high sensitivity and selectivity, but also shows rapid reaction kinetics (~20 min) and relatively low limit of detection (~96 nM) toward H₂S, allowing in vivo ratiometric NIR-II fluorescence imaging of orthotopic liver and colon tumors and visualization of the drug-induced hepatic H₂S fluctuations. Our findings provide the potential for advancing the feasibility of NIR-II activity-based sensing for in vivo clinical diagnosis.

Immunosenescence refers to the multifaceted and profound alterations in the immune system brought about by aging, exerting complex influences on the pathophysiological processes of diseases that manifest upon it. Using a combination of single-cell RNA sequencing, cytometry by time of flight, and various immunological assays, we investigated the characteristics of immunosenescence in the peripheral blood of aged mice and its impact on the cerebral immune environment after ischemic stroke. Our results revealed some features of immunosenescence. We observed an increase in neutrophil counts, concurrent with accelerated neutrophil aging, characterized by altered expression of aging-associated markers like CD62L and consequential changes in neutrophil-mediated immune functions. Monocytes/macrophages in aged mice exhibited enhanced antigen-presentation capabilities. T cell profiles shifted from naive to effector or memory states, with a specific rise in T helper 1 cells and T helper 17 cells subpopulations and increased regulatory T cell activation in CD4 T cells. Furthermore, regulatory CD8 T cells marked by Klra decreased with aging, while a subpopulation of exhausted-like CD8 T cells expanded, retaining potent immunostimulatory and proinflammatory functions. Critically, these inherent disparities not only persisted but were further amplified within the ischemic hemispheres following stroke. In summary, our comprehensive insights into the key attributes of peripheral immunosenescence provide a vital theoretical foundation for understanding not only ischemic strokes but also other age-associated diseases.

Lignin is the most promising candidate for producing aromatic compounds from biomass. However, the challenge lies in the cleavage of C−C bonds between lignin monomers under mild conditions, as these bonds have high dissociation energy. Electrochemical oxidation, which allows for mild cleavage of C−C bonds, is considered an attractive solution. To achieve low-energy consumption in the valorization of lignin, the use of highly efficient electrocatalysts is essential. In this study, a meticulously designed catalyst consisting of cobalt-doped nickel (oxy)hydroxide on molybdenum disulfide heterojunction was developed. The presence of molybdenum in a high valence state promoted the adsorption of tert-butyl hydroperoxide, leading to the formation of critical radical intermediates. In addition, the incorporation of cobalt doping regulated the electronic structure of nickel, resulting in a lower energy barrier. As a result, the heterojunction catalyst demonstrated a selectivity of 85.36% for cleaving the C_α−C_β bond in lignin model compound, achieving a substrate conversion of 93.69% under ambient conditions. In addition, the electrocatalyst depolymerized 49.82 wt% of soluble fractions from organosolv lignin (OL), resulting in a yield of up to 13 wt% of aromatic monomers. Significantly, the effectiveness of the prepared electrocatalyst was also demonstrated using industrial Kraft lignin (KL). Therefore, this research offers a practical approach for implementing electrocatalytic oxidation in lignin refining.

Triple-negative breast cancer (TNBC) is considered as the most hazardous subtype of breast cancer owing to its accelerated progression, enormous metastatic potential, and refractoriness to standard treatments. Long noncoding RNAs (lncRNAs) are extremely intricate in tumorigenesis and cancerous metastasis. Nonetheless, their roles in the initiation and augmentation of TNBC remain elusive. Here, in silico analysis and validation experiments were utilized to analyze the expression pattern of clinically effective lncRNAs in TNBC, among which a protective lncRNA LYPLAL1-DT was essentially curbed in TNBC samples and indicated a favorable prognosis. Gain- and loss-of-function assays elucidated that LYPLAL1-DT considerably attenuated the proliferative and metastatic properties along with epithelial-mesenchymal transition of TNBC cells. Moreover, forkhead box O1 (FOXO1) was validated to modulate the transcription of LYPLAL1-DT. Mechanistically, LYPLAL1-DT impinged on the malignancy of TNBC mainly by restraining the aberrant reactivation of the Wnt/β-catenin signaling pathway, explicitly destabilizing and diminishing β-catenin protein by interacting with heterogeneous nuclear ribonucleoprotein K (hnRNPK) and constricting the formation of the hnRNPK/β-catenin complex. Conclusively, our present research revealed the anti-oncogenic effects of LYPLAL1-DT in TNBC, unraveling the molecular mechanisms of the FOXO1/LYPLAL1-DT/hnRNPK/β-catenin signaling axis, which shed innovative light on the potential curative medicine of TNBC.

Solar-driven desalination systems have been recognized as an effective technology to address the water crisis. Recently, evaporators prepared based on advanced manufacturing technologies have emerged as a promising tool in enhancing ocean energy utilization. In this review, we discussed the thermal conversion, energy flow, salt deposition mechanisms, and design strategies for solar-driven desalination systems, and explored how to improve the desalination performance and energy use efficiency of the systems through advanced manufacturing technologies. In future perspectives, we determined the feasibility of coupling solar-driven solar desalination systems with multi-stage energy utilization systems and emerging artificial intelligence technologies, for which conclusions are given and new directions for future desalination system development are envisioned. Finally, exciting opportunities and challenges in the face of basic research and practical implementation are discussed, providing promising solutions and blueprints for green and novel desalination technologies while achieving sustainable development.

Owing to the promising therapeutic effect and one-time treatment advantage, gene therapy may completely change the management of eye diseases, especially retinal diseases. Adeno-associated virus (AAV) is considered one of the most promising viral gene delivery tools because it can infect various types of tissues and is considered as a relatively safe gene delivery vector. The eye is one of the most popular organs for gene therapy, since its limited volume is suitable for small doses of AAV stably transduction. Recently, an increasing number of clinical trials of AAV-mediated gene therapy are underway. This review summarizes the biological functions of AAV and its application in the treatment of various ocular diseases, as well as the characteristics of different AAV delivery routes in clinical applications. Here, the latest research progresses in AAV-mediated gene editing and silencing strategies to modify that the genetic ocular diseases are systematically outlined, especially by base editing and prime editing. We discuss the progress of AAV in ocular optogenetic therapy. We also summarize the application of AAV-mediated gene therapy in animal models and the difficulties in its clinical transformation.