Tip-enhanced Raman spectroscopy (TERS) is a valuable method for surface analysis with nanometer to angstrom-scale resolution; however, the accurate simulation of particular TERS signals remains a computational challenge. We approach this challenge by combining the two main contributors to plasmon-enhanced Raman spectroscopy and to the high resolution in TERS, in particular, the electromagnetic and the chemical effect, into one quantum mechanical simulation. The electromagnetic effect describes the sample’s interaction with the strong, highly localized, and inhomogeneous electric fields associated with the plasmonic tip and is typically the thematic focus for most mechanistic studies. On the other hand, the chemical effect covers the different responses to the extremely close-range and highly position-sensitive chemical interaction between the apex tip atom(s) and the sample, and, as we could show in previous works, plays an often underestimated role. Starting from a (time-dependent) density functional theory description of the chemical model system, comprised of a tin(II) phthalocyanine sample molecule and a single silver atom as the tip, we introduce the electromagnetic effect through a series of static point charges that recreate the electric field in the vicinity of the plasmonic Ag nanoparticle. By scanning the tip over the molecule along a 3D grid, we can investigate the system’s Raman response on each position for nonresonant and resonant illumination. Simulating both effects on their own already hints at the achievable signal enhancement and resolution, but the combination of both creates even stronger evidence that TERS is capable of resolving submolecular features.

Characterized by nucleus pulposus (NP) cell senescence and extracellular matrix (ECM) degradation, disc degeneration is a common pathology for various degenerative spinal disorders. To date, effective treatments for disc degeneration are absent. Here, we found that Glutaredoxin3 (GLRX3) is an important redox-regulating molecule associated with NP cell senescence and disc degeneration. Using a hypoxic preconditioning method, we developed GLRX3+ mesenchymal stem cell-derived extracellular vehicles (EVs-GLRX3), which enhanced the cellular antioxidant defense, thus preventing reactive oxygen species (ROS) accumulation and senescence cascade expansion in vitro. Further, a disc tissue-like biopolymer-based supramolecular hydrogel, which was injectable, degradable, and ROS-responsive, was proposed to deliver EVs-GLRX3 for treating disc degeneration. Using a rat model of disc degeneration, we demonstrated that the EVs-GLRX3-loaded hydrogel attenuated mitochondrial damage, alleviated the NP senescence state, and restored ECM deposition by modulating the redox homeostasis. Our findings suggested that modulation of redox homeostasis in the disc can rejuvenate NP cell senescence and thus attenuate disc degeneration.

Thin lithium (Li) metal foils have been proved to be indispensable yet elusive for practical high-energy-density lithium batteries. Currently, the realization of such thin foils (<50 μm) is impeded by the inferior mechanical processability of metallic Li. In this work, we demonstrate that the combination of solid solution strengthening and second phase strengthening, achieved by the addition of silver fluoride (AgF) to Li metal, can substantially enhance both the strength and ductility of metallic Li. Benefiting from the improved machinability, we succeed in fabricating an ultrathin (down to 5 μm), freestanding, and mechanically robust Li-AgF composite foil. More interestingly, the in situ-formed LixAg-LiF skeleton in the composite facilitates Li diffusion kinetics and uniform Li deposition, where the thin Li-AgF electrode displays a prolonged cycle life over 500 h at 1 mA cm–2 and 1 mAh cm–2 in a carbonate electrolyte. Coupled with a commercial LiCoO2 cathode (3.4 mAh cm–2), the LiCoO2||Li-AgF cell delivers a notable capacity retention of ∼90% over 100 cycles at 0.5 C with a low negative/positive ratio of 2.5.

The moiré potential, induced by stacking two monolayer semiconductors with slightly different lattice mismatches, acts as periodic quantum confinement for optically generated excitons, resulting in spatially ordered zero-dimensional quantum systems. However, there are limitations to exploring intrinsic optical properties of moiré excitons due to ensemble emissions and broadened emissions from many peaks caused by the inhomogeneity of the moiré potential. In this study, we proposed a microfabrication technique based on focused Ga+ ion beams, which enables us to control the number of peaks originating from the moiré potential and thus explore unknown moiré optical characteristics of WSe2/MoSe2 heterobilayer. By taking advantage of this approach, we reveal emissions from a single moiré exciton and charged moiré exciton (trion) under electrostatic doping conditions. We show the momentum dark moiré trion state above the bright trion state with a splitting energy of approximately 4 meV and clarify that the dynamics are determined by the initial trion population in the bright state. Furthermore, the degree of negative circularly polarized emissions and their valley dynamics of moiré trions are dominated by a very long valley relaxation process lasting ∼700 ns. Our findings on microfabricated heterobilayer could be viewed as an extension of our groundbreaking efforts in the field of quantum optics application using moiré superlattices.

Starvation therapy has been considered a promising strategy in cancer treatment for altering the tumor microenvironment (TME) and causing a cascade of therapeutic effects. However, it is still highly challenging to establish a therapeutic strategy for precisely and potently depriving tumoral nutrition. In this study, a glucose oxidase (GOx) and thrombin-incorporated erythrocyte vesicle (EV) with cyclic (Arg-Gly-Asp) (cRGD) peptide modification, denoted as EV@RGT, were synthesized for precisely depriving tumoral nutrition and sequentially inducing second near-infrared region (NIR-II) photothermal therapy (PTT) and immune activation. The EV@RGT could specifically accumulate at the tumor site and release the enzymes at the acidic TME. The combination of GOx and thrombin exhausts tumoral glucose and blocks the nutrition supply at the same time, resulting in severe energy deficiency and reactive oxygen species (ROS) enrichment within tumor cells. Subsequently, the abundant clotted erythrocytes in tumor vessels present outstanding localized NIR-II PTT for cancer eradication owing to the hemoglobin. Furthermore, the abundant ROS generated by enhanced starvation therapy repolarizes resident macrophages into the antitumor M1 phenotype via a DNA damage-induced STING/NF-κB pathway, ultimately contributing to tumor elimination. Consequently, the engineered EV@RGT demonstrates powerful antitumor efficiency based on precise nutrition deprivation, sequential NIR-II PTT, and immune activation effect. This work provides an effective strategy for the antitumor application of enzyme-based reinforced starvation therapy.

Today’s huge amount of data generation and transfer induced an urgent requirement for long-term data storage. Here, we demonstrate and discuss a concept for long-term storage using NV centers inside nanodiamonds. The approach is based upon the radiation-induced generation of additional vacancies (so-called GR1 states), which quench the initial NV centers, resulting in a reduced overall fluorescence lifetime of the NV center. Using the tailored fluorescence lifetime of the NV center to code the information, we demonstrate a “beyond binary” data storage density per bit. We also demonstrate that this process is reversible by heating the sample or the spot of information. This proof of principle shows that our technique may be a promising alternative data storage technology, especially in terms of long-term storage, due to the high stability of the involved color centers. In addition to the proof-of-principle demonstration using macroscopic samples, we suggest and discuss the usage of focused electron beams to write information in nanodiamond materials, to read it out with focused low-intensity light, and to erase it on the macro-, micro-, or nanoscale.

Tumour hypoxia plays an important role in modulating tumorigenesis, angiogenesis, invasion, immunosuppression, resistance to treatment, and even maintenance of the stemness of cancer stem cells (CSCs). Moreover, the targeting and treatment of hypoxic cancer cells and CSCs to reduce the influence of tumor hypoxia on cancer therapy remains an imperative clinical problem that needs to be addressed. Since cancer cells upregulate the expression of glucose transporter 1 (GLUT1) through the Warburg effect, we considered the possibility of GLUT1-mediated transcytosis in cancer cells and developed a tumor hypoxia-targeting nanomedicine. Our experimental results indicate that glucosamine-labeled liposomal ceramide can be efficiently transported between cancer cells by GLUT1 transporters and substantially accumulated in the hypoxic area in in vitro CSC spheroids and in vivo tumor xenografts. We also verified the effects of exogenous ceramide on tumor hypoxia, including important bioactivities such as upregulation of p53 and retinoblastoma protein (RB), downregulation of hypoxia-inducible factor-1 alpha (HIF-1α) expression, disruption of the OCT4-SOX2 network of stemness, and inhibition of CD47 and PD-L1 expression. To achieve an ideal therapeutic outcome, we combined treatment of glucosamine-labeled liposomal ceramide with paclitaxel and carboplatin, and we found an excellent synergistic effect, with tumor clearance being noted in three-fourths of the mice. Overall, our findings provide a potential therapeutic strategy for the treatment of cancer.

Nano/micro-electromechanical (NEM/MEM) contact switches have great potential as energy-efficient and high-temperature-operable computing units to surmount those limitations of transistors. However, despite recent advances, the high-temperature operation of the mechanical switch is not fully stable nor repetitive due to the melting and softening of the contact material in the mechanical switch. Herein, MEM switches with carbon nanotube (CNT) arrays capable of operating at high temperatures are presented. In addition to the excellent thermal stability of CNT arrays, the absence of a melting point of CNTs allows the proposed switches to operate successfully at up to 550 °C, surpassing the maximum operating temperatures of state-of-the-art mechanical switches. The switches with CNTs also show a highly reliable contact lifetime of over 1 million cycles, even at a high temperature of 550 °C. Moreover, symmetrical pairs of normally open and normally closed MEM switches, whose interfaces are initially in contact and separated, respectively, are introduced. Consequently, the complementary inverters and logic gates operating at high temperatures can be easily configured such as NOT, NOR, and NAND gates. These switches and logic gates reveal the possibility for developing low-power, high-performance integrated circuits for high-temperature operations.

Driven by the rapid development of autonomous vehicles, ultrasensitive photodetectors with high signal-to-noise ratio and ultraweak light detection capability are urgently needed. Due to its intriguing attributes, the emerging van der Waals material, indium selenide (In2Se3), has attracted extensive attention as an ultrasensitive photoactive material. However, the lack of an effective photoconductive gain mechanism in individual In2Se3 inhibits its further application. Herein, we propose a heterostructure photodetector consisting of an In2Se3 photoactive channel, a hexagonal boron nitride (h-BN) passivation layer, and a CsPb(Br/I)3 quantum dot gain layer. This device manifests a signal-to-noise ratio of 2 × 106 with responsivity of 2994 A/W and detectivity of 4.3 × 1014 Jones. Especially, it enables the detection of weak light as low as 0.03 μW/cm2. These performance characteristics are ascribed to the interfacial engineering. In2Se3 and CsPb(Br/I)3 with type-II band alignment promote the separation of photocarriers, while h-BN passivates the impurities on CsPb(Br/I)3 and promises a high-quality carrier transport interface. Furthermore, this device is successfully integrated into an automatic obstacle avoidance system, demonstrating promising application prospects in autonomous vehicles.

Intestinal metabolism-related diseases, such as constipation, inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer, could be associated with the dysfunction of intestinal mitochondria. The mitochondria of intestinal epithelial cells are of great significance for promoting intestinal motility and maintaining intestinal metabolism. It is necessary for the prophylaxis and therapy of intestinal metabolism-related diseases to improve mitochondrial function. We investigated the effect of 4,6-diamino-2-pyrimidinethiol-modified gold nanoparticles (D-Au NPs) on intestinal mitochondria and studied the regulatory role of D-Au NPs on mitochondria metabolism-related disease. D-Au NPs improved the antioxidation capability of mitochondria, regulated the mitochondrial metabolism, and maintained intestinal cellular homeostasis via the activation of AMPK and regulation of PGC-1α with its downstream signaling (UCP2 and DRP1), enhancing the intestinal mechanical barrier. D-Au NPs improved the intestinal mitochondrial function to intervene in the emergence of constipation, which could help develop drugs to treat and prevent mitochondrial metabolism-related diseases. Our findings provided an in-depth understanding of the mitochondrial effects of Au NPs for improving human intestinal barriers.

The van der Waals semiconductor metamagnet CrSBr offers an ideal platform for studying the interplay between optical and magnetic properties in the two-dimensional limit. Here, we carried out an exhaustive optical characterization of this material by means of temperature- and magnetic-field-dependent photoluminescence (PL) on flakes of different thicknesses down to the monolayer. We found a characteristic emission peak that is quenched upon switching the ferromagnetic layers from an antiparallel to a parallel configuration and exhibits a temperature dependence different from that of the peaks commonly ascribed to excitons. The contribution of this peak to the PL is boosted around 30–40 K, coinciding with the hidden order magnetic transition temperature. Our findings reveal the connection between the optical and magnetic properties via the ionization of magnetic donor vacancies. This behavior enables a useful tool for the optical reading of the magnetic states in atomically thin layers of CrSBr and shows the potential of the design of 2D heterostructures with magnetic and excitonic properties.

Malaria infected erythrocytes utilize the parasite protein VAR2CSA to bind to a unique presentation of chondroitin sulfate (CS) for their placenta specific tropism. Interestingly, many cancers express a similar form of CS, thereby termed oncofetal CS (ofCS). The distinctive tropism of malaria infected erythrocytes and the identification of oncofetal CS, therefore, represent potentially potent tools for cancer targeting. Here we describe an intriguing drug delivery platform that effectively mimics infected erythrocytes and their specificity for ofCS. We used a lipid catcher-tag conjugation system for the functionalization of erythrocyte membrane-coated drug carriers with recombinant VAR2CSA (rVAR2). We show that these malaria mimicking erythrocyte nanoparticles (MMENPs) loaded with docetaxel (DTX) specifically target and kill melanoma cells in vitro. We further demonstrate effective targeting and therapeutic efficacy in a xenografted melanoma model. These data thus provide a proof of concept for the use of a malaria biomimetic for tumor targeted drug delivery. Given the broad presentation of ofCS found across various types of malignancies, this biomimetic may therefore show potential as a broadly targeted cancer therapy against multiple tumor indications.

“Structure subserves function” is one fundamental biological maxim, and so the biological membrane that delimits the regions primarily serves as the margin between life and death for individual cells. Here, an Oswald ripening mechanism-guided solvothermal method was proposed for the synthesis of uniform MnS nanocapsules assembled with metastable γ-MnS nanocrystals. Through designing the physicochemical properties, MnS nanocapsules would disaggregate into small γ-MnS nanocrystals in a tumor acidic environment, with the surface potential switched from negative to positive, thus showing conspicuous delivery performance. More significantly, the specific accumulation of Mn2+ in mitochondria was promoted due to the downregulation of mitochondrial calcium uptake 1 (MICU1) by the formed H2S, thus leading to serious mitochondrial Mn-poisoning for membrane permeability increase and then tumor apoptosis. This study provides a synthesis strategy of metal sulfide nanocapsules and encourages multidisciplinary researchers to focus on ion–cancer crosstalk for the development of an antitumor strategy.

Proton activity in electrolytes plays a crucial role in deciding the electrochemical performance of aqueous batteries. On the one hand, it can influence the capacity and rate performance of host materials because of the high redox activity of protons. On the other hand, it can also cause a severe hydrogen evolution reaction (HER) when the protons are aggregated near the electrode/electrolyte interface. The HER dramatically limits the potential window and the cycling stability of the electrodes. Therefore, it is critical to clarify the impact of electrolyte proton activity on the battery macro-electrochemical performance. In this work, using an aza-based covalent organic framework (COF) as a representative host material, we studied the effect of electrolyte proton activity on the potential window, storage capacity, rate performance, and cycle stability in various electrolytes. A tradeoff relationship between proton redox reactions and the HER in the COF host is revealed by utilizing various in situ and ex situ characterizations. Moreover, the origin of proton activity in near-neutral electrolytes is discussed in detail and is confirmed to be related to the hydrated water molecules in the first solvation shell. A detailed analysis of the charge storage process in the COFs is presented. These understandings can be of importance for utilizing the electrolyte proton activity to build high-energy aqueous batteries.

Mitochondria-specific photosensitizer accumulation is highly recommended for photodynamic therapy and mitochondrial DNA (mtDNA) oxidative damage-based innate immunotherapy but remains challenging. 5-Aminolevulinic acid (ALA), precursor of photosensitizer protoporphyrin IX (PpIX), can induce the exclusive biosynthesis of PpIX in mitochondria. Nevertheless, its photodynamic effect is limited by the intracellular biotransformation of ALA in tumors. Here, we report a photosensitizer metabolism-regulating strategy using ALA/DNAzyme-co-loaded nanoparticles (ALA&Dz@ZIF-PEG) for mitochondria-targeting photodynamic immunotherapy. The zeolitic imidazolate framework (ZIF-8) nanoparticles can be disassembled and release large amounts of zinc ions (Zn2+) within tumor cells. Notably, Zn2+ can relieve tumor hypoxia for promoting the conversion of ALA to PpIX. Moreover, Zn2+ acts as a cofactor of rationally designed DNAzyme for silencing excessive ferrochelatase (FECH; which catalyzes PpIX into photoinactive Heme), cooperatively promoting the exclusive accumulation of PpIX in mitochondria via the “open source and reduced expenditure” manner. Subsequently, the photodynamic effects derived from PpIX lead to the damage and release of mtDNA and activate the innate immune response. In addition, the released Zn2+ further enhances the mtDNA/cGAS-STING pathway mediated innate immunity. The ALA&Dz@ZIF-PEG system induced 3 times more PpIX accumulation than ALA-loaded liposome, significantly enhancing tumor regression in xenograft tumor models.

Metabolic therapy targeting the metabolic addictions driven by gain-of-function mutations in KRAS is promising in fighting cancer through selective killing of malignant cells without hurting healthy cells. However, metabolic compensation and heterogeneity make current metabolic therapies ineffective. Here, we proposed a biomimetic “Nutri-hijacker” with “Trojan horse” design to induce synthetic lethality in KRAS-mutated (mtKRAS) malignant cells by hitchhiking and reprogramming the metabolic addictions. Nutri-hijacker consisted of the biguanide-modified nanoparticulate albumin that impaired glycolysis and a flavonoid that restrained glutaminolysis after the macropinocytosis of Nutri-hijacker by mtKRAS malignant cells. Nutri-hijacker suppressed the proliferation and spread of mtKRAS malignant cells while lowering tumor fibrosis and immunosuppression. Nutri-hijacker significantly extended the lifespan of pancreatic ductal adenocarcinoma (PDAC)-bearing mice when combined with the hydroxychloroquine-based therapies that failed in clinical trials. Collectively, our findings demonstrated that Nutri-hijacker is a strong KRAS mutation-customized inhibitor and the synthetic lethality based on mtKRAS-driven metabolic addictions might be a promising strategy against PDAC.

Easy recurrence and strong treatment side effects significantly limit the clinical treatment of allergic dermatitis. The human trace element selenium (Se) plays essential roles in redox regulation through incorporation into selenoproteins in the form of 21st necessary amino acid selenocysteine, to participates in the pathogenesis and intervention of chronic inflammatory diseases. Therefore, based on the safe and elemental properties of Se, we construct a facile-synthesis strategy for antiallergic selenium nanoparticles (LET-SeNPs), and scale up the production by employing a spray drying method with lactose (Lac-LET-SeNPs) or maltodextrin (Mal-LET-SeNPs) as encapsulation agents realizing larger scale production and a longer storage time. As expected, these as-prepared LET-SeNPs could effectively activate the Nrf2-Keap1 signaling pathway to enhance the expression of antioxidative selenoprotein at mRNA and protein levels, then inhibit mast cell activation to achieve efficient antiallergic activity. Interestingly, LET-SeNPs undergo metabolism to seleno-amino acids to promote biosynthesis of selenoproteins, which could suppress ROS-induced cyclooxygenase-2 (COX-2) and MAPKs activation to suppress the release of histamine and inflammatory cytokines. Allergic mouse and Macaca fascicularis models further confirm that LET-SeNPs could increase the Se content and selenoprotein expression in the skin, decrease mast cells activation and inflammatory cells infiltration, and finally exhibit the high therapeutic effects on allergic dermatitis. Taken together, this study not only constructs facile large-scale synthesis of translational Se nanomedicine to break through the bottleneck problem of nanomaterials but also sheds light on its application in the intervention and treatment of allergies.

We study the early time carrier drift dynamics in CsPbI3 nanocrystal thin films with a sub 25 ps time resolution. Prior to trapping, carriers exhibit band-like transport characteristics, which is similar to those of traditional semiconductor solar absorbers including Si and GaAs due to optical phonon and carrier scattering at high temperatures. In contrast to the popular polaron scattering mechanism, the CsPbI3 nanocrystal thin film demonstrates the strongest optical phonon scattering mechanism among other inorganic–organic hybrid perovskites, Si, and GaAs. This ultrafast dynamics study establishes a foundation for understanding the fundamental carrier drift properties that drive perovskite nanocrystal optoelectronics.

Detection of viable viruses in the air is critical in order to determine the level of risk associated with the airborne diffusion of viruses. Different methods have been developed for the isolation, purification, and detection of viable airborne viruses, but they require an extensive processing time and often present limitations including low physical efficiency (i.e., the amount of collected viruses), low biological efficiency (i.e., the number of viable viruses), or a combination of all. To mitigate such limitations, we have employed an efficient technique based on the magnetic levitation (Maglev) technique with a paramagnetic solution and successfully identified distinct variations in levitation and density characteristics among bacteria (Escherichia coli), phages (MS2), and human viruses (SARS-CoV-2 and influenza H1N1). Notably, the Maglev approach enabled a significant enrichment of viable airborne viruses in air samples. Furthermore, the enriched viruses obtained through Maglev exhibited high purity, rendering them suitable for direct utilization in subsequent analyses such as reverse transcription-polymerase chain reaction (RT-PCR) or colorimetric assays. The system is portable, easy to use, and cost-efficient and can potentially provide proactive surveillance data for monitoring future outbreaks of airborne infectious diseases and allow for the induction of various preventative and mitigative measures.

Zn anodes of aqueous Zn metal batteries face challenges from dendrite growth and side reactions. Building Zn(002) texture mitigates the issues but does not eradicate them. Zn(002) still faces severe challenges from corrosive electrolytes and dendrite growth, especially after hundreds of cycles. Therefore, it is necessary to have a passivation layer covering Zn(002). Here, Zn(002) texture and surface coating are achieved on Zn foils by an one-step annealing process, as demonstrated by ZnS, ZnSe, ZnF2, Zn3(PO4)2 (ZPO), etc. Using ZPO as a model, the coupling between surface coating and Zn(002) is illustrated in terms of dendrite-suppressing ability and diffusion energy barrier of Zn2+. The modified Zn foils (Zn(002)@ZPO) exhibit the excellent electrochemical performance, far superior to Zn(002) or ZPO alone. In the full cells, the performance is greatly improved even under harsh conditions, i.e., high areal capacity and limited Zn resource. This work achieves crystal engineering and surface coating on Zn anodes simultaneously and discloses the in-depth insights about the synergy of crystal orientation and passivation layers.