The depth of light penetration and tumor hypoxia restrict the efficacy of photodynamic therapy (PDT) in triple-negative breast cancer (TNBC), while the overproduction of lactate (LA) facilitates the development, aggressiveness, and therapy resistance of TNBC. To address these issues, a self-acting PDT nanosystem (HL@hMnO₂-LOx@HA) is fabricated by loading 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH), luminol, and LA oxidase (LOx) in a hyaluronic acid (HA)-coated hollow manganese dioxide (hMnO₂) nanoparticle. LOx catalyzes the oxidation of LA into pyruvate and hydrogen peroxide (H₂O₂), thus depleting the overproduced intratumoral LA. In the acidic tumor microenvironment, H₂O₂ reacts with luminol and hMnO₂ to yield blue luminescence as well as O₂ and Mn²⁺, respectively. Mn²⁺ could further enhance this chemiluminescence. HPPH is then excited by the chemiluminescence through chemiluminescence resonance energy transfer for self-illuminated PDT. The generated O₂ alleviates the hypoxia state of the TNBC tumor to produce sufficient ¹O₂ for self-oxygenation PDT. The Mn²⁺ performs T₁ magnetic resonance imaging to trace the self-acting PDT process. This work provides a biocompatible strategy to conquer the limits of light penetration and tumor hypoxia on PDT against TNBC as well as LA overproduction.

Deep learning (DL)-driven efficient synthesis planning may profoundly transform the paradigm for designing novel pharmaceuticals and materials. However, the progress of many DL-assisted synthesis planning (DASP) algorithms has suffered from the lack of reliable automated pathway evaluation tools. As a critical metric for evaluating chemical reactions, accurate prediction of reaction yields helps improve the practicality of DASP algorithms in the real-world scenarios. Currently, accurately predicting yields of interesting reactions still faces numerous challenges, mainly including the absence of high-quality generic reaction yield datasets and robust generic yield predictors. To compensate for the limitations of high-throughput yield datasets, we curated a generic reaction yield dataset containing 12 reaction categories and rich reaction condition information. Subsequently, by utilizing 2 pretraining tasks based on chemical reaction masked language modeling and contrastive learning, we proposed a powerful bidirectional encoder representations from transformers (BERT)-based reaction yield predictor named Egret. It achieved comparable or even superior performance to the best previous models on 4 benchmark datasets and established state-of-the-art performance on the newly curated dataset. We found that reaction-condition-based contrastive learning enhances the model's sensitivity to reaction conditions, and Egret is capable of capturing subtle differences between reactions involving identical reactants and products but different reaction conditions. Furthermore, we proposed a new scoring function that incorporated Egret into the evaluation of multistep synthesis routes. Test results showed that yield-incorporated scoring facilitated the prioritization of literature-supported high-yield reaction pathways for target molecules. In addition, through meta-learning strategy, we further improved the reliability of the model's prediction for reaction types with limited data and lower data quality. Our results suggest that Egret holds the potential to become an essential component of the next-generation DASP tools.

An approach utilizing N-heterocyclic carbene for nitrile formation and desymmetrization reaction is developed. The process involves kinetic resolution, with the axially chiral aryl monoaldehydes obtained in moderate yields with excellent optical purities. These axially chiral aryl monoaldehydes can be conveniently transformed into functionalized molecules, showing great potential as catalysts in organic chemistry.

Biocompatible connections between external artificial devices and living organisms show promise for future neuroprosthetics and therapeutics. The study in Science by Zhao and colleagues introduces a cascade-heterogated biphasic gel (HBG) iontronic device, which facilitates electronic-to-multi-ionic signal transduction for abiotic–biotic interfaces. Inspired by neuron signaling, the HBG device demonstrated its biocompatibility by regulating neural activity in biological tissue, paving the way for wearable and implantable devices, including brain–computer interfaces.

Photodynamic therapy (PDT) has emerged as a promising approach for squamous cell carcinoma treatment but hindered by tumor hypoxia, acquired resistance, phototoxicity, and so on. To address these issues, we developed a smart strategy utilizing activable photosensitizers delivered by an aptamer-functionalized DNA probe (ADP). The ADP incorporated an AS1411 aptamer for tumor targeting and a linear antisense oligonucleotide (ASO) for recognition of Survivin mRNA. In the absence of the target, PDT remained quenched, thereby avoiding phototoxicity during circulation and nonselective distribution. With the aid of the aptamer, ADP achieved selective targeting of tumors. Upon internalization, ADP targeted recognized Survivin mRNA, triggering PDT activation, and releasing ASO to down-regulate Survivin expression and reverse tumor resistance. Consequently, the activable photosensitizers exhibited an “AND” logic gate, combining tumor-targeting delivery and tumor-related gene activation, thus enhancing its specificity. Additionally, the incorporation of hemin into the ADP provided catalase activity, converting tumor-abundant H₂O₂ into O₂, thereby ameliorating tumor hypoxia. The resulting functionalized G-quadruplex/hemin–DNA probe complex demonstrated targeted delivery and activation, minimized side effects, and enhanced PDT efficacy in both xenograft tumor-bearing mice and patient-derived xenograft models. This study offers a unique and promising platform for efficient and safe PDT, thus holding great potential for future clinical translation and improved cancer therapy.

In the post-COVID-19 pandemic era, the long-term surveillance of pathogens is still important. The rapid detection of pathogens facilitates the accurate and convenient real-time monitoring of microbial contamination and improves the management of diseases. Here, a novel surface plasmon resonance (SPR)-based point of care testing (POCT) approach of microorganism nucleic acids with the guidance of CRISPR enzyme is described, including the application of optical fiber-based detection of trace SARS-CoV2 virus in sewage water on SPR and validation of the plasmonic biosensor for the detection of single-nucleotide mutations in natural water samples.

Despite the promise of high flexibility and conformability of hydrogel ionic conductors, existing polymeric conductive hydrogels have long suffered from compromises in mechanical, electrical, and cryoadaptive properties due to monotonous functional improvement strategies, leading to lingering challenges. Here, we propose an all-in-one strategy for the preparation of poly(acrylic acid)/cellulose (PAA/Cel) hydrogel ionic conductors in a facile yet effective manner combining acrylic acid and salt-dissolved cellulose, in which abundant zinc ions simultaneously form strong coordination interactions with the two polymers, while free solute salts contribute to ionic conductivity and bind water molecules to prevent freezing. Therefore, the developed PAA/Cel hydrogel simultaneously achieved excellent mechanical, conductive, and cryogenically adaptive properties, with performances of 42.5 MPa for compressive strength, 1.6 MPa for tensile strength, 896.9% for stretchability, 9.2 MJ m⁻³ for toughness, 59.5 kJ m⁻² for fracture energy, and 13.9 and 6.2 mS cm⁻¹ for ionic conductivity at 25 and −70 °C, respectively. Enabled by these features, the resultant hydrogel ionic conductor is further demonstrated to be assembled as a self-powered electronic skin (e-skin) with high signal-to-noise ratio for use in monitoring movement and physiological signals regardless of cold temperatures, with hinting that could go beyond high-performance hydrogel ionic conductors.

This paper addresses a learning-based discontinuous path following control scheme for a biomimetic underwater vehicle (BUV) driven by undulatory fins. Despite the flexibility of the BUV motion, it faces the challenge of dealing with discontinuous paths affected by irregular seafloor topography and underwater vegetation. Therefore, BUV must employ path switching strategy to navigate to the next safe area. We introduce a discontinuous path following control method based on deep reinforcement learning (DRL). This method uses the line of sight (LOS) navigation algorithm to provide the Markov decision process (MDP) state inputs and the soft actor-critic (SAC) algorithm to train the control strategy of the BUV. Unlike the traditional fixed waveform control method, this method encourages the BUV to learn different waveforms and fluctuation frequencies through DRL. At the same time, the BUV has the ability to switch to a new path at necessary moments, such as when encountering underwater rocks. The results of simulations and experiments demonstrate the successful integration of the undulatory fins with the SAC controller, showcasing its efficacy and diversity in discontinuous underwater path following tasks.

Cross-talks (e.g., host-driven iron withdrawal and microbial iron uptake between host gastrointestinal tract and commensal microbes) regulate immunotolerance and intestinal homeostasis. However, underlying mechanisms that regulate the cross-talks remain poorly understood. Here, we show that bacterial products up-regulate iron-transporter transferrin and transferrin acts as an immunosuppressor by interacting with cluster of differentiation 14 (CD14) to inhibit pattern recognition receptor (PRR) signaling and induce host immunotolerance. Decreased intestinal transferrin is found in germ-free mice and human patients with ulcerative colitis, which are characterized by impaired intestinal immunotolerance. Intestinal transferrin and host immunotolerance are returned to normal when germ-free mice get normal microbial commensalism, suggesting an association between microbial commensalism, transferrin, and host immunotolerance. Mouse colitis models show that transferrin shortage impairs host's tolerogenic responses, while its supplementation promotes immunotolerance. Designed peptide blocking transferrin–CD14 interaction inhibits immunosuppressive effects of transferrin. In monkeys with idiopathic chronic diarrhea, transferrin shows comparable or even better therapeutic effects than hydrocortisone. Our findings reveal that by up-regulating host transferrin to silence PRR signaling, commensal bacteria counteract immune activation induced by themselves to shape host immunity and contribute for intestinal tolerance.

Mixtures of active self-propelled and passive colloidal particles promise rich assembly and dynamic states that are beyond reach via equilibrium routes. Yet, controllable transition between different dynamic states remains rare. Here, we reveal a plethora of dynamic behaviors emerging in assemblies of chemically propelled snowman-like active colloids and passive spherical particles as the particle shape, size, and composition are tuned. For example, assembles of one or more active colloids with one passive particle exhibit distinct translating or orbiting states while those composed of one active colloid with 2 passive particles display persistent “8”-like cyclic motion or hopping between circling states around one passive particle in the plane and around the waist of 2 passive ones out of the plane, controlled by the shape of the active colloid and the size of the passive particles, respectively. These morphology-tailored dynamic transitions are in excellent agreement with state diagrams predicted by mesoscale dynamics simulations. Our work discloses new dynamic states and corresponding transition strategies, which promise new applications of active systems such as micromachines with functions that are otherwise impossible.

Subcellular mitochondria serve as sensors for energy metabolism and redox balance, and the dynamic regulation of functional and dysfunctional mitochondria plays a crucial role in determining cells' fate. Selective removal of dysfunctional mitochondria at the subcellular level can provide chondrocytes with energy to prevent degeneration, thereby treating osteoarthritis. Herein, to achieve an ideal subcellular therapy, cartilage affinity peptide (WYRGRL)-decorated liposomes loaded with mitophagy activator (urolithin A) were integrated into hyaluronic acid methacrylate hydrogel microspheres through microfluidic technology, named HM@WY-Lip/UA, that could efficiently target chondrocytes and selectively remove subcellular dysfunctional mitochondria. As a result, this system demonstrated an advantage in mitochondria function restoration, reactive oxygen species scavenging, cell survival rescue, and chondrocyte homeostasis maintenance through increasing mitophagy. In a rat post-traumatic osteoarthritis model, the intra-articular injection of HM@WY-Lip/UA ameliorated cartilage matrix degradation, osteophyte formation, and subchondral bone sclerosis at 8 weeks. Overall, this study indicated that HM@WY-Lip/UA provided a protective effect on cartilage degeneration in an efficacious and clinically relevant manner, and a mitochondrial-oriented strategy has great potential in the subcellular therapy of osteoarthritis.