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Cell-surface engineering holds great promise in boosting endogenous stem cell attraction for tissue regeneration. However, challenges such as cellular internalization of ligand and the dynamic nature of cell membranes often complicate ligand-receptor interactions. The aim of this study is to harness the innovative potential of programmable tetrahedral framework nucleic acid (tFNA) to enable precise, tunable ligand-receptor interactions, thereby improving stem cell recruitment efficiency. This approach involves experimental screening and theoretical analysis using dissipative particle dynamics. The results demonstrate that altering the flexibility and topology of ligands on tFNA changes their cellular internalization and membrane binding efficiency. Furthermore, optimizing the distribution of the mesenchymal stem cell (MSC)-binding aptamer 19S (Apt19S) on the tFNA enhances the stem cell capture efficiency. Following successful in vitro MSC capture, Apt19S-modified tFNA is chemically linked to a hyaluronic acid hydrogel, forming an efficient "stem cell catcher" system. Subsequent in vivo experiments demonstrate that this system effectively promotes early stem cell recruitment and accelerates bone regeneration in different bone healing scenarios, including cranial and maxillary defects., (© 2024 Wiley‐VCH GmbH.)

Despite great progress in enhancing tumor immunogenicity, conventional gas therapy cannot effectively reverse the tumor immunosuppressive microenvironment (TIME), limiting immunotherapy. The development of therapeutic gases that are tumor microenvironment responsive and efficiently reverse the TIME for precisely targeted tumor gas-immunometabolic therapy remains a great challenge. In this study, a novel cancer cell membrane-encapsulated pH-responsive nitric oxide (NO)-releasing biomimetic nanosystem (MP@AL) is prepared. Lactate oxidase (Lox) in MP@AL consumed oxygen to promote the decomposition of lactate, a metabolic by-product of tumor glycolysis, and the generation of H 2 O 2 , while L-arginine (L-Arg) in MP@AL is oxidized by H 2 O 2 to generate nitric oxide (NO). For one thing, NO led to mitochondrial dysfunction in tumor cells to reduce oxygen consumption and promote the efficiency of Lox in lactate decomposition, thus reversing lactate-induced TIME; for another, NO effectively triggered immunogenic cell death, activated anti-tumor immune response and long-term immune memory, and ensured a favorable effect in the synergistic interaction with PD-L1 antibody for inhibiting tumor growth and recurrence. Therefore, a novel gas-immunometabolic therapy dual closed-loop nanosystem for enhancing tumor immunogenicity and remodeling lactate-induced TIME is established. Overall, this work will provide new ideas for gas therapy to effectively remodel the TIME to enhance cancer immunotherapy., (© 2024 Wiley‐VCH GmbH.)

Monocytes, as progenitors of macrophages and osteoclasts, play critical roles in various stages of bone repair, necessitating phase-specific regulatory mechanisms. Here, icariin (ICA) prodrug-like microspheres (ICA@GM) are developed, as lipid nanoparticle (LNP) transfection boosters, to construct mRNA-engineered monocytes for remodeling the bone microenvironment across multiple stages, including the acute inflammatory and repair phases. Initially, ICA@GM is prepared from ICA-conjugated gelatin methacryloyl via a microfluidics system. Then, monocyte-targeting IL-4 mRNA-LNPs are then prepared and integrated into injectable microspheres (mRNA-ICA@GM) via electrostatic and hydrogen bond interactions. After bone-defect injection, LNPs are controlled released from mRNA-ICA@GM within 3 days, rapidly transfecting monocytes for monocyte IL-4 mRNA-engineering, which effectively suppressed acute inflammatory responses via polarization programming and paracrine signaling. Afterwards, ICA is sustainably released as well via cleavable boronate esters across multiple stages, cooperatively boosting the mRNA-engineered monocytes to inhibit coenocytic fusion and osteoclastic function. Both in vitro and in vivo data indicated that mRNA-ICA@GM can not only reverse the inflammatory environment but also suppress monocyte-derived osteoclast formation to accelerate bone repair. In summary, mRNA-engineered monocytes and ICA prodrug-like microspheres are combined to achieve long-lasting multi-stage bone microenvironment regulation, offering a promising repair strategy., (© 2024 Wiley‐VCH GmbH.)

The discovery of multiple resonance thermally activated delayed fluorescence (MR-TADF) materials with remarkable narrowband emission has opened a new avenue for the development of organic light-emitting diodes (OLEDs) with high color purity. However, the lack of construction strategies for purely red MR-TADF materials significantly impedes their application in full-color high-definition displays. Herein, we propose a unique and handy approach of spiro-carbon-locking and sulfur-embedding strategy to modify the parent MR-TADF framework, resulting in a red MR-TADF emitter with high color purity. The reported MR-TADF molecule (namely, FSBN) demonstrates a pure red emission with an emission maximum of 621 nm in toluene solution. The OLED with FSBN as emitter exhibits Commission Internationale de l'Éclairage (CIE) coordinates of (0.67, 0.33), which exactly matches the red standard defined by the National Television Standards Committee (NTSC). Importantly, the single-host OLED achieves a high power efficiency (PE) of up to 50.1 lm W -1 , suggesting the potential for the development of low power consumption red OLEDs., (© 2024 Wiley-VCH GmbH.)

The uneven formation of lithium dendrites during electroplating/stripping leads to a decrease in the utilization of active lithium, resulting in poor cycling stability and posing safety hazards to the battery. Herein, introducing a 3D continuously interconnected zirconium-based metal-organic framework (MOF808) network into a polyethylene oxide polymer matrix establishes a synergistic mechanism for lithium dendrite inhibition. The 3D MOF808 network maintains its large pore structure, facilitating increased lithium salt accommodation, and expands anion adsorption at unsaturated metal sites through its diverse large-space cage structure, thereby promoting the flow of Li + . Infrared-Raman and synchrotron small-angle X-ray scattering results demonstrate that the transport behavior of lithium salt ion clusters at the MOF/polymer interface verifies the increased local Li + flux concentration, thereby raising the mobility number of Li + to 0.42 and ensuring uniform Li + flux distribution, leading to dendrite-free and homogeneous Li + deposition. Furthermore, nanoindentation tests reveal that the high modulus and elastic recovery of MOF-based polymer electrolytes contribute to forming a robust, dendrite-resistant interface. Consequently, in symmetric battery systems, the system exhibits minimal overpotential, merely 35 mV, while maintaining stable cycling for over 1800 h, achieving low-overpotential lithium deposition. Moreover, it retains redox stability under high voltages up to 5.3 V., (© 2024 Wiley‐VCH GmbH.)

Reactive astrogliosis is the main cause of secondary injury to the central nerves. Biomaterials can effectively suppress astrocyte activation, but the mechanism remains unclear. Herein, Differentially Expressed Genes (DEGs) are identified through whole transcriptome sequencing in a mouse model of spinal cord injury, revealing the VIM gene as a pivotal regulator in the reactive astrocytes. Moreover, DEGs are predominantly concentrated in the extracellular matrix (ECM). Based on these, 3D injectable electrospun short fibers are constructed to inhibit reactive astrogliosis. Histological staining and functional analysis indicated that fibers with unique 3D network spatial structures can effectively constrain the reactive astrocytes. RNA sequencing and single-cell sequencing results reveal that short fibers downregulate the expression of the VIM gene in astrocytes by modulating the "ECM receptor interaction" pathway, inhibiting the transcription of downstream Vimentin protein, and thereby effectively suppressing reactive astrogliosis. Additionally, fibers block the binding of Vimentin protein with inflammation-related proteins, downregulate the NF-κB signaling pathway, inhibit neuron apoptosis, and consequently promote the recovery of spinal cord neural function. Through mechanism elucidation-material design-feedback regulation, this study provides a detailed analysis of the mechanism chain by which short fibers constrain the abnormal spatial expansion of astrocytes and promote spinal cord neural function., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Nasal administration can bypass the blood-brain barrier and directly deliver drugs to the brain, providing a non-invasive route for central nervous system (CNS) diseases. Inspired by the appearance that a gate can block the outside world and the characteristics of the sol-gel transition can form a "gate" in the nasal cavity, a Drop to Gate nasal drop (DGND) is designed to set a gate in nose, which achieves protecting role from the influence of nasal environment. The DGND demonstrates the efficiency and application prospect of delivering drugs to the brain through the N-to-B. The effective concentration of single administration is increased through the hydrophobic interaction between C 8 -GelMA and SRT1720 (SA), and then cross-linked under UV to form nanogel, which can respond to MMP in the inflammatory microenvironment of sepsis-induced cognitive dysfunction. Finally, the SA/nanogel is compounded into the thermogel, which can respond to the nasal cavity temperature to form DGND in situ, increasing the residence time and delivery efficiency of drugs in the nasal cavity. In vitro, the DGND alleviates lipopolysaccharides (LPS)-induced BV2 inflammation. In vivo, DGND effectively targets the nasal mucosa and deliver drugs to the brain, which activate Sirt1 to alleviate inflammation mediated by microglia and improve cognitive dysfunction in sepsis mice., (© 2024 Wiley‐VCH GmbH.)

Solution-processable conducting polymers open up a new era in organic electronics, fundamentally altering the processing methods of electronic devices. P-type conducting polymers, exemplified by aqueous solution-processed poly(3,4-ethylenedioxythiophene) : poly(styrenesulfonate) (PEDOT : PSS), have been successfully commercialized. However, the performance of electron-transporting (n-type) materials remains considerably poorer. One of the primary challenges lies in striking a balance between conductivity and solvent processability. At present, most n-type conducting polymers necessitate toxic solvents for processing, which contradicts environmentally sustainable principles and impedes their potential for large-scale industrial applications. Herein, we developed an alcohol-processable high-performance n-type conducting polymer, poly(3,7-dihydrobenzo[1,2-b : 4,5-b']difuran-2,6-dione): poly(2-ethyl-2-oxazoline) (PBFDO : PEOx), which utilized electrostatic interactions between PEOx and PBFDO to simultaneously achieve high conductivity and alcohol-processability. The PBFDO : PEOx films exhibited remarkable electrical conductivity exceeding 1000 S cm -1 with outstanding stability even at temperatures up to 250 °C, establishing it as a prominent green solvent-processed n-type conducting polymer that rivals the most advanced p-type counterparts. Various applications including organic thermoelectric, electrochemical transistor, and electrochromic devices were showcased, highlighting the broad potential of PBFDO : PEOx in advancing green organic electronics., (© 2024 Wiley-VCH GmbH.)

Transition metal catalysts are widely used in the 2e - ORR due to their cost-effectiveness. However, they often encounter issues related to low activity. Defect engineering are used on developing highly active catalysts, which can effectively modify active sites and promote electron transfer. Here, carbon-coated Ni 3 S 2 (Ni 3 S 2 @C), where the additional sulfur vacancies (V S ) is prepared induced by the carbon layer is coupled with active nickel sites. Through in situ and ex situ experiments combined with DFT calculations, it is demonstrated that the carbon layer can regulate the quantity of V S in Ni 3 S 2 . Materials with a higher concentration of V S exhibit enhanced 2e - ORR activity and higher H 2 O 2 selectivity. In situ Raman spectroscopy confirms that Ni serves as the key active site in this catalyst. DFT calculations indicate that the OOH binding energy (ΔG) decreases with an increase in the number of V S , favoring the protonation of *OOH to generate H 2 O 2 . Upon performance testing, the average H 2 O 2 selectivity is 92.3%, with the highest yield reaching up to 3860 mmol gcat -1  h -1 . It is noteworthy that Ni 3 S 2 @C exhibits high stability, with only a slight decrease in 2e - pathway selectivity after 5000 cycles of ADT., (© 2024 Wiley‐VCH GmbH.)

The extracellular matrix (ECM) engages in regulatory interactions with cell surface receptors through its constituent proteins and polysaccharides. Therefore, nano-sized extracellular matrix conjugated with doxorubicin (DOX) is utilized to produce extracellular matrix-drug conjugates (ECM-DOX) tailored for targeted delivery to cancer cells. The ECM-DOX nanoparticles exhibit rod-like morphology, boasting a commendable drug loading capacity of 4.58%, coupled with acid-sensitive drug release characteristics. Notably, ECM-DOX nanoparticles enhance the uptake by tumor cells and possess the ability to penetrate endothelial cells and infiltrate tumor multicellular spheroids. Mechanistic insights reveal that the internalization of ECM-DOX nanoparticle is facilitated through clathrin-mediated endocytosis and macropinocytosis, intricately involving hyaluronic acid receptors and integrins. Pharmacokinetic assessments unveil a prolonged blood half-life of ECM-DOX nanoparticles at 3.65 h, a substantial improvement over the 1.09 h observed for free DOX. A sustained accumulation effect of ECM-DOX nanoparticles at tumor sites, with drug levels in tumor tissues surpassing those of free DOX by several-fold. The profound therapeutic impact of ECM-DOX nanoparticles is evident in their notable inhibition of tumor growth, extension of median survival time in animals, and significant reduction in DOX-induced cardiotoxicity. The ECM platform emerges as a promising carrier for avant-garde nanomedicines in the realm of cancer treatment., (© 2024 Wiley‐VCH GmbH.)

Hybrid nanogenerators (HNGs) represent a promising avenue for water energy harvesting, yet their commercial viability faces hurdles such as limited power output, poor coupling, and constrained operational lifespans. Here, a highly coupled triboelectric-electromagnetic magnetic-levitation hybrid nanogenerator (ML-HNG) is introduced that shows great potential for water energy harvesting. The ML-HNG fulfills the challenges of high power output, strong coupling, and long operational lifespans. During the contact-separation process of the triboelectric nanogenerator (TENG), the changing magnetic flux in the electromagnetic generator's coils generates a potential difference between the coils and Cu electrodes. The unique design of the ML-HNG employs a shared coil electrode configuration, which enhances the coupling without adding extra volume. This integration allows the ML-HNG to achieve multi-frequency vibrations and multiple output cycles per external longitudinal movement, a phenomenon known as the frequency multiplication effect. With an average power density of 1.69 W m -3 in water, the ML-HNG provides continuous power for a thermo-hygrometer and can quickly drive a wireless water level alarm system within a minute. This groundbreaking hybrid nanogenerator design holds significant promise for the efficient and consistent harvesting of low-frequency ocean wave energy, marking a substantial advancement in blue energy technology., (© 2024 Wiley‐VCH GmbH.)

Mineralized bio-tissues achieve exceptional mechanical properties through the assembly of rigid inorganic minerals and soft organic matrices, providing abundant inspiration for synthetic materials. Hydrogels, serving as an ideal candidate to mimic the organic matrix in bio-tissues, can be strengthened by the direct introduction of minerals. However, this enhancement often comes at the expense of toughness due to interfacial mismatch. This study reveals that extreme toughening of hydrogels can be realized through simultaneous in situ mineralization and salting-out, without the need for special chemical modification or additional reinforcements. The key to this strategy lies in harnessing the kosmotropic and precipitation behavior of specific anions as they penetrate a hydrogel system containing both anion-sensitive polymers and multivalent cations. The resulting mineralized hydrogels demonstrate significant improvements in fracture stress, fracture energy, and fatigue threshold due to a multiscale energy dissipation mechanism, with optimal values reaching 12 MPa, 49 kJ m -2 , and 2.98 kJ m -2 . This simple strategy also proves to be generalizable to other anions, resulting in tough hydrogels with osteoconductivity for promoting in vitro mineralization of human adipose-derived mesenchymal stem cells. This work introduces a universal route to toughen hydrogels without compromising other parameters, holding promise for biological applications demanding integrated mechanical properties., (© 2024 Wiley‐VCH GmbH.)

Traditional high-dose antibiotic treatments of intracellular methicillin-resistant staphylococcus aureus (MRSA) are highly inefficient and associated with a high rate of infection relapse. As an effective antibacterial technology, sonodynamic therapy (SDT) may be able to break the dilemma. However, indiscriminate reactive oxygen species (ROS) release leads to potential side effects. This study incorporates Staphylococcal Protein A antibody-modified Cu 2+ /tetracarboxyphenylporphyrin nanoparticles (Cu(II)NS-SPA) into hydrogel microspheres (HAMA@Cu(II)NS-SPA) to achieve precise eradication of intracellular bacteria. This eradication is under bioorthogonal activation mediated by bacillithiol (BSH) (internally) and ultrasound (US) (externally). To specify, the US responsiveness of Cu(II)NS-SPA is restored when it is reduced to Cu(I)NS-SPA by the BSH secreted characteristically by intracellular MRSA, thus forming a bioorthogonal activation with the external US, which confines ROS production within the infected MΦ. Under external US activation at 2 W cm -2 , over 95% of intracellular MRSA can be cleared. In vivo, a single injection of HAMA@Cu(II)NS-SPA achieves up to two weeks of antibacterial sonodynamic therapy, reducing pro-inflammatory factor expression by 90%, and peri-implant bone trabeculae numbers exceed the control group by five times. In summary, these micro/nano hydrogel microspheres mediated by internal and external bioorthogonal activation can precisely eliminate intracellular MRSA, effectively treating multi-drug resistant intracellular bacterial infections., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

We have developed a new type of nanoparticles with potent antitumor activity photoactivatable via the combination of molecular photoswitching of spiropyran (SP) and enzymatic reaction of glucose oxidase (GOx). As two key processes involved therein, Fe(III)-to-Fe(II) photoreduction in Fe(III) metal-organic frameworks (MOFs) brings about the release of free Fe 2+ /Fe 3+ while the photoswitching of SP to merocyanine (MC) unlocks the enzymatic activity of GOx that was pre-passivated by SP. The release of free Fe 3+ boosts its hydrolysis and therefore enables the acidification of microenvironment, which is further reinforced by one of the products of the GOx-mediated glucose oxidation reaction, gluconic acid (GlcA). Based on the generation of Fe 2+ and acidic milieu together with another product of the oxidation reaction, hydrogen peroxide (H 2 O 2 ), these two processes jointly present triple enabling factors for generating lethal hydroxyl radicals (⋅OH) species via Fenton reactions and therefore oxidative stress capable of inhibiting tumor. The antitumor potency of such nanoparticle is verified in tumor-bearing model mice in vivo, proclaiming its potential as a potent and safe agent based on the unique mechanism of optically manipulating enzyme activity for synergistic antitumor therapeutics with high spatial precision, enhanced efficacy and minimized side effects., (© 2024 Wiley-VCH GmbH.)

Despite extensive studies has been explored on single-molecule switches and rectifiers, the design of single-molecule inductors has not been explored due to the experimental challenges in the investigation of frequency-dependent charge transport at the single-molecule scale. In this study, we synthesized a helicene-based helical molecular wire and carried out meticulous single-molecule conductance measurements, combined with current-voltage (IV) studies with varying frequencies using the scanning tunneling microscope break junction (STM-BJ) technique. Our results reveal the formation of a single-molecule junction and highlight the unique behavior of the molecular wire in response to different alternating current (AC) varying frequencies. The transport of charges occurs selectively either through the coiled backbone of the conjugated helical structure or vertically via π-π stacking, depending on the frequency of the applied AC. Notably, our investigation demonstrates the functionality of the wire as an inductor at low frequencies, and a capacitor at high frequencies. This work lays the foundation for a systematic approach to designing, fabricating, and implementing single-molecule logic devices such as inductors and wave filters., (© 2024 Wiley-VCH GmbH.)

Conversion-type anode materials with high theoretical capacities play a pivotal role in developing future aqueous rechargeable batteries (ARBs). However, their sustainable applications have long been impeded by the poor cycling stability and sluggish redox kinetics. Here we show that confining conversion chemistry in intercalation host could overcome the above challenges. Using sodium titanates as a model intercalation host, an integrated layered anode material of iron oxide hydroxide-pillared titanate (FeNTO) is demonstrated. The conversion reaction is spatially and kinetically confined within sub-nano interlayer, enabling superlow redox polarization (ca. 4-6 times reduced), ultralong lifespan (up to 8700 cycles) and excellent rate performance. Notably, the charge compensation of interlayer via universal cation intercalation into host endows FeNTO with the capability of operating well in a broad range of aqueous electrolytes (Li + , Na + , K + , Mg 2+ , Ca 2+ , etc.). We further demonstrate the large-scale synthesis of FeNTO thin film and powder, and rational design of quasi-solid-state high-voltage ARB pouch cells powering wearable electronics against extreme mechanical abuse. This work demonstrates a powerful confinement means to access disruptive electrode materials for next-generation energy devices., (© 2024 Wiley-VCH GmbH.)

Shaoyao Gancao Decoction (SGD), a traditional Chinese medicine, has been proven to have a good liver protection effect, but the mechanism and pharmacodynamic substances of SGD in the treatment of acute liver injury are still unclear. In this study, an ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method was established to characterize 107 chemical components of SGD and 12 compounds absorbed in rat plasma samples after oral administration of SGD. Network pharmacology was applied to construct a component-target-pathway network to screen the possible effective components of SGD in acute liver injury. Using lipidomics based on UHPLC-Q-TOF-MS coupled with a variety of statistical analyses, 20 lipid biomarkers were screened and identified, suggesting that the improvement of acute liver injury by SGD was involved in cholesterol metabolism, glycerol-phospholipid metabolism, sphingolipid signaling pathways and fatty acid biosynthesis. In addition, the UHPLC-tandem MS method was established for pharmacokinetics analysis, and 10 potential active components were determined simultaneously within 12 min through the optimization of 0.1% formic acid water and acetonitrile as a mobile phase system. A Pharmacokinetics study showed that paeoniflorin, albiflorin, oxypaeoniflorin, liquiritigenin, isoliquiritigenin, liquiritin, ononin, formononetin, glycyrrhizic acid, and glycyrrhetinic acid as the potential active compounds of SGD curing acute liver injury., (© 2024 Wiley‐VCH GmbH.)

Nanolamellar transition metal carbides are gaining increasing attentions because of the promising application in energy storage of their 2D derivatives. There are in-plane and out-of-plane atomic ordered occupations, which is thought to only be formed in separated systems due to totally different origins and crystallographic structure. In present work, starting from (Mo, Nb) 4 AlC 3 o-MAX phase where out-of-plane ordered occupation is experimentally and theoretically proved for Mo/Nb atoms, rare-earth elements (R = Y, Gd-Tm, Lu) are introduced, and the novel Mo 3.33- x R 0.67 Nb x AlC 3 (x = 1, 1.25, 1.5, 1.75, 2, 2.25, and 2.5) super-ordered (s-) MAX phase is synthesized, where R is ordered at the outer layer in the strict stoichiometry meanwhile Mo/Nb maintains the out-of-plane ordered occupation. By R introduction, s-MAX is easier to be delaminated to obtain the s-MXene with the topochemical ordered vacancies, leading into the enhanced supercapacitance of 114.9 F g -1 in Mo 1.33 Nb 2 C 3 s-MXene compared with 95.1 F g -1 in Mo 2 Nb 2 C 3 o-MXene. By Pt anchoring, very low overpotential of 22 mV at a current density of 10 mA cm -2 is achieved for HER applications. This study demonstrates a novel variety of s-MAX phase and seeks to inspire further exploration of the ordered MAX and MXene families., (© 2024 Wiley‐VCH GmbH.)

Balancing osteoblast-osteoclast (OB-OC) cross-talk is crucial for restoring bone tissue structure and function. Current clinical drugs targeting either osteogenesis or osteoclastogenesis fail to effectively regulate cross-talk, impeding efficient bone repair in osteoporosis patients. Ubiquitin-specific protease 26 (USP26) is shown to coordinate OB-OC cross-talk by independently regulating β-catenin and Iκb-α. However, effective drugs for activating USP26 are still lacking. Here, they constructed bone homeostasis repair microcarriers (BHRC) that encapsulate Usp26 mRNA-loaded lipid nanoparticles (mRNA@LNP) within MMPs-responsive GelMA hydrogel microspheres. These microcarriers target the osteoporotic microenvironment and regulate OB-OC cross-talk, thereby facilitating intervertebral fusion in osteoporotic rats. Results demonstrate that mRNA@LNP exhibits uniform particle size and high transfection efficiency, while GelMA hydrogel microspheres possess excellent biocompatibility and MMP responsiveness, providing favorable cell survival space and controllable release of mRNA@LNP. The released LNP upregulates USP26 protein expression, effectively promoting osteogenesis while suppressing osteoclast formation. In vivo experiments show that injecting BHRC into the defect site of intervertebral discs in osteoporotic rats significantly promotes tail vertebrae fusion by responding to the microenvironment and regulating cell-to-cell cross-talk. Thus, the BHRC holds great potential in regulating osteoporotic homeostasis, particularly in challenging bone defects such as intervertebral fusion in osteoporotic environments., (© 2024 Wiley‐VCH GmbH.)

The variability of CO 2 hydrogenation reaction demands new potential strategies to regulate the fine structure of the catalysts for optimizing the reaction pathways. Herein, we report a dual-site strategy to boost the catalytic efficiency of CO 2 -to-methanol conversion. A new descriptor, τ, was initially established for screening the promising candidates with low-temperature activation capability of CO 2 , and sequentially a high-performance catalyst was fabricated centred with oxophilic Mo single atoms, who was further decorated with Pt nanoparticles. In CO 2 hydrogenation, the obtained dual-site catalysts possess a remarkably-improved methanol generation rate (0.27 mmol g cat. -1  h -1 ). For comparison, the singe-site Mo and Pt-based catalysts can only produce ethanol and formate acid at a relatively low reaction rate (0.11 mmol g cat. -1  h -1 for ethanol and 0.034 mmol g cat. -1  h -1 for formate acid), respectively. Mechanism studies indicate that the introduction of Pt species could create an active hydrogen-rich environment, leading to the alterations of the adsorption configuration and conversion pathways of the *OCH 2 intermediates on Mo sites. As a result, the catalytic selectivity was successfully switched., (© 2024 Wiley-VCH GmbH.)

Excessive cell-free DNA (cfDNA) can induce chronic inflammation by activating intracellular nucleic acid sensors. Intervention in cfDNA-mediated "pro-inflammatory signaling transduction" could be a potential alleviating strategy for chronic inflammation, such as in diabetic wounds. However, effectively and specifically downgrading cfDNA concentration in the pathological microenvironment remains a challenge. Therefore, this work prepares free-standing polydopamine nanosheets through DNA-guided assembly and loaded them into microfluidic hydrogel microspheres. The π─π stacking/hydrogen bonding interactions between polydopamine nanosheets and the π-rich bases of cfDNA, along with the cage-like spatial confinement created by the hydrogel polymer network, achieved cfDNA capture and storage, respectively. Catechol in polydopamine nanosheets can also assist in reducing reactive oxygen species (ROS) levels. Efficient cfDNA binding independent of serum proteins, specific interdiction of abnormal activation of cfDNA-associated toll-like receptor 9, as well as down-regulation of inflammatory cytokines and ROS levels are shown in this system. The chronic inflammation alleviating and the pro-healing effects on the mice model with diabetic wounds are also investigated. This work presents a new strategy for capturing and storing cfDNA to intervene in cell signaling transduction. It also offers new insights into the regulatory mechanisms between inflammatory mediators and biomaterials in inflammation-related diseases., (© 2024 Wiley‐VCH GmbH.)

Copper (Cu) nanomaterials are a unique kind of electrocatalysts for high-value multi-carbon production in carbon dioxide reduction reaction (CO 2 RR), which holds enormous potential in attaining carbon neutrality. However, phase engineering of Cu nanomaterials remains challenging, especially for the construction of unconventional phase Cu-based asymmetric heteronanostructures. Here the site-selective growth of Cu on unusual phase gold (Au) nanorods, obtaining three kinds of heterophase fcc-2H-fcc Au-Cu heteronanostructures is reported. Significantly, the resultant fcc-2H-fcc Au-Cu Janus nanostructures (JNSs) break the symmetric growth mode of Cu on Au. In electrocatalytic CO 2 RR, the fcc-2H-fcc Au-Cu JNSs exhibit excellent performance in both H-type and flow cells, with Faradaic efficiencies of 55.5% and 84.3% for ethylene and multi-carbon products, respectively. In situ characterizations and theoretical calculations reveal the co-exposure of 2H-Au and 2H-Cu domains in Au-Cu JNSs diversifies the CO* adsorption configurations and promotes the CO* spillover and subsequent C-C coupling toward ethylene generation with reduced energy barriers., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Scope: Lactoferrin (LF) is an iron-bound protein with a molecular weight of about 80 kDa. LF has many biological functions such as antibacterial, antiviral, immunomodulatory, and anticancer. The purpose of this study is to explore the research trend of LF through bibliometric analysis., Methods and Results: The search is conducted in the Web of Science Core Collection database, and then the publications information of LF related literature is exported. Based on CiteSpace and VOSviewer software, countries, institutions, authors, journals, keywords, and so on are analyzed. Since 1987, a total of 9382 literature have been included, and the number of papers related to LF has increased year by year. These publications come mainly from 124 countries and 725 institutions. Of the 1256 authors analyzed, Valenti Piera is the one with the most publications. The burst strength of gut microbiota, antioxidant, nanoparticles, and in vitro digestion are 21.3, 15.63, 23.03, and 13.51, respectively. They represent the frontier of research in this field and are developing rapidly., Conclusion: This study shows that LF has important research value. The study of LF nanoparticles and the effects of LF on the gut microbiota are an emerging field that helps to explore new research directions., (© 2024 Wiley‐VCH GmbH.)

Singlet oxygen (term symbol 1 Δ g , hereafter 1 O 2 ), a reactive oxygen species, has recently attracted increasing interest in the field of rechargeable batteries and electrocatalysis and photocatalysis. These sustainable energy conversion and storage technologies are of vital significance to replace fossil fuels and promote carbon neutrality and finally tackle the energy crisis and climate change. Herein, the recent progresses of 1 O 2 for energy storage and conversion is summarized, including physical and chemical properties, formation mechanisms, detection technologies, side reactions in rechargeable batteries and corresponding inhibition strategies, and applications in electrocatalysis and photocatalysis. The formation mechanisms and inhibition strategies of 1 O 2 in particular aprotic lithium-oxygen (Li-O 2 ) batteries are highlighted, and the applications of 1 O 2 in photocatalysis and electrocatalysis is also emphasized. Moreover, the confronting challenges and promising directions of 1 O 2 in energy conversion and storage systems are discussed., (© 2024 Wiley‐VCH GmbH.)

Efferocytosis-mediated inflammatory reversal plays a crucial role in bone repairing process. However, in refractory bone defects, the macrophage continual efferocytosis may be suppressed due to the disrupted microenvironment homeostasis, particularly the loss of apoptotic signals and overactivation of intracellular oxidative stress. In this study, a polydopamine-coated short fiber matrix containing biomimetic "apoptotic signals" to reconstruct the microenvironment and reactivate macrophage continual efferocytosis for inflammatory reversal and bone defect repair is presented. The "apoptotic signals" (AM/CeO 2 ) are prepared using CeO 2 nanoenzymes with apoptotic neutrophil membrane coating for macrophage recognition and oxidative stress regulation. Additionally, a short fiber "biomimetic matrix" is utilized for loading AM/CeO 2 signals via abundant adhesion sites involving π-π stacking and hydrogen bonding interactions. Ultimately, the implantable apoptosis-mimetic nanoenzyme/short-fiber matrixes (PFS@AM/CeO 2 ), integrating apoptotic signals and biomimetic matrixes, are constructed to facilitate inflammatory reversal and reestablish the pro-efferocytosis microenvironment. In vitro and in vivo data indicate that the microenvironment biomimetic short fibers can activate macrophage continual efferocytosis, leading to the suppression of overactivated inflammation. The enhanced repair of rat femoral defect further demonstrates the osteogenic potential of the pro-efferocytosis strategy. It is believed that the regulation of macrophage efferocytosis through microenvironment biomimetic materials can provide a new perspective for tissue repair., (© 2024 Wiley‐VCH GmbH.)

Developing high-efficiency and stable bifunctional electrocatalysts for water splitting remains a great challenge. Herein, NiMoO 4 nanowires as sacrificial templates to synthesize Mo-doped NiFe Prussian blue analogs are employed, which can be easily phosphorized to Mo-doped Fe 2x Ni 2(1-x) P nanotubes (Mo-FeNiP NTs). This synthesis method enables the controlled etching of NiMoO 4 nanowires that results in a unique hollow nanotube architecture. As a bifunctional catalyst, the Mo-FeNiP NTs present lower overpotential and Tafel slope of 151.3 (232.6) mV at 100 mA cm -2 and 76.2 (64.7) mV dec -1 for HER (OER), respectively. Additionally, it only requires an ultralow cell voltage of 1.47 V to achieve 10 mA cm -2 for overall water splitting and can steadily operate for 200 h at 100 mA cm -2 . First-principles calculations demonstrate that Mo doping can effectively adjust the electron redistribution of the Ni hollow sites to optimize the hydrogen adsorption-free energy for HER. Besides, in situ Raman characterization reveals the dissolving of doped Mo can promote a rapid surface reconstruction on Mo-FeNiP NTs to dynamically stable (Fe)Ni-oxyhydroxide layers, serving as the actual active species for OER. The work proposes a rational approach addressed by electron manipulation and surface reconstruction of bimetallic phosphides to regulate both the HER and OER activity., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Electrocatalytic urea synthesis under ambient conditions offers a promising alternative strategy to the traditional energy-intensive urea industry protocol. Limited by the electrostatic interaction, the reduction reaction of anions at the cathode in the electrocatalytic system is not easily achievable. Here, we propose a novel strategy to overcome electrostatic interaction via pulsed electroreduction. We found that the reconstruction-resistant CuSiO x nanotube, with abundant atomic Cu-O-Si interfacial sites, exhibits ultrastability in the electrosynthesis of urea from nitrate and CO 2 . Under a pulsed potential approach with optimal operating conditions, the Cu-O-Si interfaces achieve a superior urea production rate (1606.1 μg h -1  mg cat. -1 ) with high selectivity (79.01 %) and stability (the Faradaic efficiency is retained at 80 % even after 80 h of testing), outperforming most reported electrocatalytic synthesis urea catalysts. We believe our strategy will incite further investigation into pulsed electroreduction increasing substrate transport, which may guide the design of ambient urea electrosynthesis and other energy conversion systems., (© 2024 Wiley-VCH GmbH.)

Neutrophil extracellular traps (NETs) seriously impede diabetic wound healing. The disruption or scavenging of NETs using deoxyribonuclease (DNase) or cationic nanoparticles has been limited by liberating trapped bacteria, short half-life, or potential cytotoxicity. In this study, a positive correlation between the NETs level in diabetic wound exudation and the severity of wound inflammation in diabetic patients is established. Novel NETs scavenging bio-based hydrogel microspheres 'micro-cage', termed mPDA-PEI@GelMA, is engineered by integrating methylacrylyl gelatin (GelMA) hydrogel microspheres with cationic polyethyleneimine (PEI)-functionalized mesoporous polydopamine (mPDA). This unique 'micro-cage' construct is designed to non-contact scavenge of NETs between nanoparticles and the diabetic wound surface, minimizing biological toxicity and ensuring high biosafety. NETs are introduced into 'micro-cage' along with wound exudation, and cationic mPDA-PEI immobilizes them inside the 'micro-cage' through a strong binding affinity to the cfDNA web structure. The findings demonstrate that mPDA-PEI@GelMA effectively mitigates pro-inflammatory responses associated with diabetic wounds by scavenging NETs both in vivo and in vitro. This work introduces a novel nanoparticle non-contact NETs scavenging strategy to enhance diabetic wound healing processes, with potential benefits in clinical applications., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Cluster-like collective cell migration of fibroblasts is one of the main factors of adhesion in injured tissues. In this research, a microdot biomaterial system is constructed using α-helical polypeptide nanoparticles and anti-inflammatory micelles, which are prepared by ring-opening polymerization of α-amino acids-N-carboxylic anhydrides (NCAs) and lactide, respectively. The microdot biomaterial system slowly releases functionalized polypeptides targeting mitochondria and promoting the influx of extracellular calcium ions under the inflammatory environment, thus inhibiting the expression of N-cadherin mediating cell-cell interaction, and promoting apoptosis of cluster fibroblasts, synergistically inhibiting the migration of fibroblast clusters at the site of tendon injury. Meanwhile, the anti-inflammatory micelles are celecoxib (Cex) solubilized by PEG/polyester, which can improve the inflammatory microenvironment at the injury site for a long time. In vitro, the microdot biomaterial system can effectively inhibit the migration of the cluster fibroblasts by inhibiting the expression of N-cadherin between cell-cell and promoting apoptosis. In vivo, the microdot biomaterial system can promote apoptosis while achieving long-acting anti-inflammation effects, and reduce the expression of vimentin and α-smooth muscle actin (α-SMA) in fibroblasts. Thus, this microdot biomaterial system provides new ideas for the prevention and treatment of tendon adhesion by inhibiting the cluster migration of fibroblasts., (© 2024 Wiley‐VCH GmbH.)

Base editors (BEs) are widely used as revolutionary genome manipulation tools for cell evolution. To screen the targeted individuals, it is often necessary to expand the editing window to ensure highly diverse variant library. However, current BEs suffer from a limited editing window of 5-6 bases, corresponding to only 2-3 amino acids. Here, by engineering the CRISPR‒Cas12b, the study develops dCas12b-based CRISPRi system, which can efficiently repress gene expression by blocking the initiation and elongation of gene transcription. Further, based on dCas12b, a new-generation of BEs with an expanded editing window is established, covering the entire protospacer or more. The expanded editing window results from the smaller steric hindrance compared with other Cas proteins. The universality of the new BE is successfully validated in Bacillus subtilis and Escherichia coli. As a proof of concept, a spectinomycin-resistant E. coli strain (BL21) and a 6.49-fold increased protein secretion efficiency in E. coli JM109 are successfully obtained by using the new BE. The study, by tremendously expanding the editing window of BEs, increased the capacity of the variant library exponentially, greatly increasing the screening efficiency for microbial cell evolution., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

The microvascular network plays an important role in providing nutrients to the injured tissue and exchanging various metabolites. However, how to achieve efficient penetration of the injured tissue is an important bottleneck restricting the reconstruction of microvascular network. Herein, the hydrogel precursor solution can efficiently penetrate the damaged tissue area, and ultrasound triggers the release of thrombin from liposomes in the solution to hydrolyze fibrinogen, forming a fibrin solid hydrogel network in situ with calcium ions and transglutaminase as catalysts, effectively solving the penetration impedance bottleneck of damaged tissues and ultimately significantly promoting the formation of microvascular networks within tissues. First, the fibrinogen complex solution is effectively permeated into the injured tissue. Second, ultrasound triggered the release of calcium ions and thrombin, activates transglutaminase, and hydrolyzes fibrinogen. Third, fibrin monomers are catalyzed to form fibrin hydrogels in situ in the damaged tissue area. In vitro studies have shown that the fibrinogen complex solution effectively penetrated the artificial bone tissue within 15 s after ultrasonic triggering, and formed a hydrogel after continuous triggering for 30 s. Overall, this innovative strategy effectively solved the problem of penetration resistance of ultrasound-triggered hydrogels in the injured tissues, and finally activates in situ microvascular networks regeneration., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

A visible-light-induced strategy has been explored for the synthesis of naphtho[2,1-d]thiazol-2-amines through ortho-C-H sulfuration of 2-isocyanonaphthalenes with elemental sulfur and amines under external photocatalyst-free conditions. This three-component reaction, which utilizes elemental sulfur as the odorless sulfur source, molecular oxygen as the clean oxidant, and visible light as the clean energy source, provides a mild and efficient approach to construct a series of naphtho[2,1-d]thiazol-2-amines. Preliminary mechanistic studies indicated that visible-light-promoted photoexcitation of reaction intermediates consisting of thioureas and DBU might be involved in this transformation., (© 2024 Wiley-VCH GmbH.)

A family of hexagonal in-plane chemical ordering (Mo 2/3 R 1/3 ) 2 AlB 2 (R = Tb, Dy, Ho, Er, Tm, and Lu) i-MAB phases are synthesized with R-3m hexagonal structure. The i-MAB phases with R = Tb to Tm are considered to have a nonlinear ferromagnetic-like coupling magnetic ground state with gradually weakened magnetocrystalline anisotropy due to variant R-R distances and 4f electrons. Their 2D derivatives (2D-MBene) with rare-earth (R) atom vacancies are obtained by chemical etching. The delamination solvent, surface functional terminations, and chemical bond of 2D-MBene can be modified by one-step nitridation in environment-friendly nitrogen instead of ammonia. A phase conversion is caused by nitridation at 973 K from 2D-MBene to Mo 2 N, leading to the optimized specific capacitance of 229 F g -1 . Besides exploring more rare-earth-containing laminated boride systems, this work also demonstrates the promising application of their 2D derivatives with R vacancies in supercapacitors., (© 2023 Wiley‐VCH GmbH.)

The dynamic balance between hypoxia and oxidative stress constitutes the oxygen-related microenvironment in injured tissues. Due to variability, oxygen homeostasis is usually not a therapeutic target for injured tissues. It is found that when administered intravenously, mesenchymal stem cells (MSCs) and in vitro induced apoptotic vesicles (ApoVs) exhibit similar apoptotic markers in the wound microenvironment where hypoxia and oxidative stress co-existed, but MSCs exhibited better effects in promoting angiogenesis and wound healing. The derivation pathway of ApoVs by inducing hypoxia or oxidative stress in MSCs to simulate oxygen homeostasis in injured tissues is improved. Two types of oxygen-related environmental stressed ApoVs are identified that directly target endothelial cells (ECs) for the accurate regulation of vascularization. Compared to normoxic and hypoxic ones, oxidatively stressed ApoVs (Oxi-ApoVs) showed the strongest tube formation capacity. Different oxygen-stressed ApoVs deliver similar miRNAs, which leads to the broad upregulation of EC phosphokinase activity. Finally, local delivery of Oxi-ApoVs-loaded hydrogel microspheres promotes wound healing. Oxi-ApoV-loaded microspheres achieve controlled ApoV release, targeting ECs by reducing the consumption of inflammatory cells and adapting to the proliferative phase of wound healing. Thus, the biogenerated apoptotic vesicles responding to oxygen-related environmental stress can target ECs to promote vascularization., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Efferocytosis, an intrinsic regulatory mechanism to eliminate apoptotic cells, will be suppressed due to the delayed apoptosis process in aging-related diseases, such as osteoarthritis (OA). In this study, cartilage lesion-localized hydrogel microspheres are developed to remodel the in situ efferocytosis to reverse cartilage senescence and recruit endogenous stem cells to accelerate cartilage repair. Specifically, aldehyde- and methacrylic anhydride (MA)-modified hyaluronic acid hydrogel microspheres (AHM), loaded with pro-apoptotic liposomes (liposomes encapsulating ABT263, A-Lipo) and PDGF-BB, namely A-Lipo/PAHM, are prepared by microfluidic and photo-cross-linking techniques. By a degraded porcine cartilage explant OA model, the in situ cartilage lesion location experiment illustrated that aldehyde-functionalized microspheres promote affinity for degraded cartilage. In vitro data showed that A-Lipo induced apoptosis of senescent chondrocytes (Sn-chondrocytes), which can then be phagocytosed by the efferocytosis of macrophages, and remodeling efferocytosis facilitated the protection of normal chondrocytes and maintained the chondrogenic differentiation capacity of MSCs. In vivo experiments confirmed that hydrogel microspheres localized to cartilage lesion reversed cartilage senescence and promoted cartilage repair in OA. It is believed this in situ efferocytosis remodeling strategy can be of great significance for tissue regeneration in aging-related diseases., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

General movements (GMs) have been widely used for the early clinical evaluation of infant brain development, allowing immediate evaluation of potential development disorders and timely rehabilitation. The infants' general movements can be captured digitally, but the lack of quantitative assessment and well-trained clinical pediatricians presents an obstacle for many years to achieve wider deployment, especially in low-resource settings. There is a high potential to explore wearable sensors for movement analysis due to outstanding privacy, low cost, and easy-to-use features. This work presents a sparse sensor network with soft wireless IMU devices (SWDs) for automatic early evaluation of general movements in infants. The sparse network consisting of only five sensor nodes (SWDs) with robust mechanical properties and excellent biocompatibility continuously and stably captures full-body motion data. The proof-of-the-concept clinical testing with 23 infants showcases outstanding performance in recognizing neonatal activities, confirming the reliability of the system. Taken together with a tiny machine learning algorithm, the system can automatically identify risky infants based on the GMs, with an accuracy of up to 100% (99.9%). The wearable sparse sensor network with an artificial intelligence-based algorithm facilitates intelligent evaluation of infant brain development and early diagnosis of development disorders., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

The cellular functions, such as tissue-rebuilding ability, can be directly affected by the metabolism of cells. Moreover, the glucose metabolism is one of the most important processes of the metabolism. However, glucose cannot be efficiently converted into energy in cells under ischemia hypoxia conditions. In this study, a high-energy intermediate fructose hydrogel (HIFH) is developed by the dynamic coordination between sulfhydryl-functionalized bovine serum albumin (BSA-SH), the high-energy intermediate in glucose metabolism (fructose-1,6-bisphosphate, FBP), and copper ion (Cu 2+ ). This hydrogel system is injectable, self-healing, and biocompatible, which can intracellularly convert energy with high efficacy by regulating the glucose metabolism in situ. Additionally, the HIFH can greatly boost cell antioxidant capacity and increase adenosine triphosphate (ATP) in the ischemia anoxic milieu by roughly 1.3 times, improving cell survival, proliferation and physiological functions in vitro. Furthermore, the ischemic skin tissue model is established in rats. The HIFH can speed up the healing of damaged tissue by promoting angiogenesis, lowering reactive oxygen species (ROS), and eventually expanding the healing area of the damaged tissue by roughly 1.4 times in vivo. Therefore, the HIFH can provide an impressive perspective on efficient in situ cell energy supply of damaged tissue., (© 2023 Wiley‐VCH GmbH.)

The prevalence of infertility caused by endometrial defects is steadily increasing, posing a significant challenge to women's reproductive health. In this study, injectable "homing-like" bioactive decellularized extracellular matrix short-fibers (DEFs) of porcine skin origin are innovatively designed for endometrial and fertility restoration. The DEFs can effectively bind to endometrial cells through noncovalent dipole interactions and release bioactive growth factors in situ. In vitro, the DEFs effectively attracted endometrial cells through the "homing-like" effect, enabling cell adhesion, spreading, and proliferation on their surface. Furthermore, the DEFs effectively facilitated the proliferation and angiogenesis of human primary endometrial stromal cells (HESCs) and human umbilical vein endothelial cells (HUVECs), and inhibited fibrosis of pretreated HESCs. In vivo, the DEFs significantly accelerated endometrial restoration, angiogenesis, and receptivity. Notably, the deposition of endometrial collagen decreased from 41.19 ± 2.16% to 14.15 ± 1.70% with DEFs treatment. Most importantly, in endometrium-injured rats, the use of DEFs increased the live birth rate from 30% to an impressive 90%, and the number and development of live births close to normal rats. The injectable "homing-like" bioactive DEFs system can achieve efficient live births and intrauterine injection of DEFs provides a new promising clinical strategy for endometrial factor infertility., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Sluggish charge kinetics and low selectivity limit the solar-driven selective organic transformations under mild conditions. Herein, an efficient strategy of halogen-site regulation, based on the precise control of charge transfer and molecule activation by rational design of Cs 3 Bi 2 X 9 quantum dots photocatalysts, is proposed to achieve both high selectivity and yield of benzyl-alcohol oxidation. In situ PL spectroscopy study reveals that the Bi─Br bonds formed in the form of Br-associated coordination can enhance the separation and transfer of photoexcited carriers during the practical reaction. As the active center, the exclusive Bi─Br covalence can benefit the benzyl-alcohol activation for producing carbon-centered radicals. As a result, the Cs 3 Bi 2 Br 9 with this atomic coordination achieves a conversion ratio of 97.9% for benzyl alcohol and selectivity of 99.6% for aldehydes, which are 56.9- and 1.54-fold higher than that of Cs 3 Bi 2 Cl 9 . Combined with quasi-in situ EPR, in situ ATR-FTIR spectra, and DFT calculation, the conversion of C 6 H 5 -CH 2 OH to C 6 H 5 -CH 2 * at Br-related coordination is revealed to be a determining step, which can be accelerated via halogen-site regulation for enhancing selectivity and photocatalytic efficiency. The mechanistic insights of this research elucidate how halogen-site regulation in favor of charge transfer and molecule activation toward efficient and selective oxidation of benzyl alcohol., (© 2023 Wiley‐VCH GmbH.)

The scar repair inevitably causes damage of skin function and loss of skin appendages such as hair follicles (HF). It is of great challenge in wound repair that how to intervene in scar formation while simultaneously remodeling HF niche and inducing in situ HF regeneration. Here, chemical reprogramming techniques are used to identify a clinically chemical cocktail (Tideglusib and Tamibarotene) that can drive fibroblasts toward dermal papilla cell (DPC) fate. Considering the advantage of biomaterials in tissue repair and their regulation in cell behavior that may contributes to cellular reprogramming, the artificial HF seeding (AHFS) hydrogel microspheres, inspired by the natural processes of "seeding and harvest", are constructed via using a combination of liposome nanoparticle drug delivery system, photoresponsive hydrogel shell, positively charged polyamide modification, microfluidic and photocrosslinking techniques. The identified chemical cocktail is as the core nucleus of AHFS. In vitro and in vivo studies show that AHFS can regulate fibroblast fate, induce fibroblast-to-DPC reprogramming by activating the PI3K/AKT pathway, finally promoting wound healing and in situ HF regeneration while inhibiting scar formation in a two-pronged translational approach. In conclusion, AHFS provides a new and effective strategy for functional repair of skin wounds., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Inflammaging is deeply involved in aging-related diseases and can be destructive during aging. The maintenance of pH balance in the extracellular microenvironment can alleviate inflammaging and repair aging-related tissue damage. In this study, the hydrogen ion capturing hydrogel microsphere (GMNP) composed of mineralized transforming growth factor-β (TGF-β) and catalase (CAT) nanoparticles is developed via biomimetic mineralization and microfluidic technology for blocking the NLRP3 cascade axis in inflammaging. This GMNP can neutralize the acidic microenvironment by capturing excess hydrogen ions through the calcium carbonate mineralization layer. Then, the subsequent release of encapsulated TGF-β and CAT can eliminate both endogenous and exogenous stimulus of NLRP3, thus suppressing the excessive activation of inflammaging. In vitro, GMNP can suppress the excessive activation of the TXNIP/NLRP3/IL-1β cascade axis and enhance extracellular matrix (ECM) synthesis in nucleus pulposus cells. In vivo, GMNP becomes a sustainable and stable niche with microspheres as the core to inhibit inflammaging and promote the regeneration of degenerated intervertebral discs. Therefore, this hydrogen ion-capturing hydrogel microsphere effectively reverses inflammaging by interfering with the excessive activation of NLRP3 in the degenerated tissues., (© 2023 Wiley-VCH GmbH.)

Pivotal roles of extracellular vesicles (EVs) in the pathogenesis of central nervous system (CNS) disorders including acute brain injury are increasingly acknowledged. Through the analysis of EVs packaged miRNAs in plasma samples from patients with intracerebral hemorrhage (ICH), it is discovered that the level of EVs packaged miR-143-3p (EVs-miR-143-3p) correlates closely with perihematomal edema and neurological outcomes. Further study reveals that, upon ICH, EVs-miR-143-3p is robustly secreted by astrocytes and can shuttle into brain microvascular endothelial cells (BMECs). Heightened levels of miR-143-3p in BMECs induce the up-regulated expression of cell adhesion molecules (CAMs) that bind to circulating neutrophils and facilitate their transendothelial cell migration (TEM) into brain. Mechanism-wise, miR-143-3p directly targets ATP6V1A, resulting in impaired lysosomal hydrolysis ability and reduced autophagic degradation of CAMs. Importantly, a VCAM-1-targeting EVs system to selectively deliver miR-143-3p inhibitor to pathological BMECs is created, which shows satisfactory therapeutic effects in both ICH and traumatic brain injury (TBI) mouse models. In conclusion, the study highlights the causal role of EVs-miR-143-3p in BMECs' dysfunction in acute brain injury and demonstrates a proof of concept that engineered EVs can be devised as a potentially applicable nucleotide drug delivery system for the treatment of CNS disorders., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Bone defects stemming from tumorous growths, traumatic events, and diverse conditions present a profound conundrum in clinical practice and research. While bone has the inherent ability to regenerate, substantial bone anomalies require bone regeneration techniques. Bone organoids represent a new concept in this field, involving the 3D self-assembly of bone-associated stem cells guided in vitro with or without extracellular matrix material, resulting in a tissue that mimics the structural, functional, and genetic properties of native bone tissue. Within the scientific panorama, bone organoids ascend to an esteemed status, securing significant experimental endorsement. Through a synthesis of current literature and pioneering studies, this review offers a comprehensive survey of the bone organoid paradigm, delves into the quintessential architecture and ontogeny of bone, and highlights the latest progress in bone organoid fabrication. Further, existing challenges and prospective directions for future research are identified, advocating for interdisciplinary collaboration to fully harness the potential of this burgeoning domain. Conclusively, as bone organoid technology continues to mature, its implications for both clinical and research landscapes are poised to be profound., (© 2023 Wiley-VCH GmbH.)

Destruction of cartilage due to the abnormal remodeling of subchondral bone (SB) leads to osteoarthritis (OA), and restoring chondro-bone metabolic homeostasis is the key to the treatment of OA. However, traditional intra-articular injections for the treatment of OA cannot directly break through the cartilage barrier to reach SB. In this study, the hydrothermal method is used to synthesize ultra-small size (≈5 nm) selenium-doped carbon quantum dots (Se-CQDs, SC), which conjugated with triphenylphosphine (TPP) to create TPP-Se-CQDs (SCT). Further, SCT is dynamically complexed with hyaluronic acid modified with aldehyde and methacrylic anhydride (AHAMA) to construct highly permeable micro/nano hydrogel microspheres (SCT@AHAMA) for restoring chondro-bone metabolic homeostasis. In vitro experiments confirmed that the selenium atoms scavenged reactive oxygen species (ROS) from the mitochondria of mononuclear macrophages, inhibited osteoclast differentiation and function, and suppressed early chondrocyte apoptosis to maintain a balance between cartilage matrix synthesis and catabolism. In vivo experiments further demonstrated that the delivery system inhibited osteoclastogenesis and H-vessel invasion, thereby regulating the initiation and process of abnormal bone remodeling and inhibiting cartilage degeneration in SB. In conclusion, the micro/nano hydrogel microspheres based on ultra-small quantum dots facilitate the efficient penetration of articular SB and regulate chondro-bone metabolism for OA treatment., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The uterine epithelium undergoes a dramatic spatiotemporal transformation to enter a receptive state, involving a complex interaction between ovarian hormones and signals from stromal and epithelial cells. Redox homeostasis is critical for cellular physiological steady state; emerging evidence reveals that excessive lipid peroxides derail redox homeostasis, causing various diseases. However, the role of redox homeostasis in early pregnancy remains largely unknown. It is found that uterine deletion of Glutathione peroxidase 4 (GPX4), a key factor in repairing oxidative damage to lipids, confers defective implantation, leading to infertility. To further pinpoint Gpx4's role in different cell types, uterine epithelial-specific Gpx4 is deleted by a lactotransferrin (Ltf)-Cre driver; the resultant females are infertile, suggesting increased lipid peroxidation levels in uterine epithelium compromises receptivity and implantation. Lipid peroxidation inhibitor administration failed to rescue implantation due to carbonylation of major receptive-related proteins underlying high lipid reactive oxygen species. Intriguingly, superimposition of Acyl-CoA synthetase long-chain family member 4 (ACSL4), an enzyme that promotes biosynthesis of phospholipid hydroperoxides, along with uterine epithelial GPX4 deletion, preserves reproductive capacity. This study reveals the pernicious impact of unbalanced redox signaling on embryo implantation and suggests the obliteration of lipid peroxides as a possible therapeutic approach to prevent implantation defects., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Conventional coupling agents (such as polyvinylpyrrolidone, methylcellulose, and polyurethane) are unable to efficiently transport drugs through the skin's dual barriers (the epidermal cuticle barrier and the basement membrane barrier between the epidermis and dermis) when exposed to ultrasound, hindering deep and noninvasive transdermal drug delivery. In this study, nanobubbles prepared by the double emulsification method and aminated hyaluronic acid are crosslinked with aldehyde-based hyaluronic acid by dynamic covalent bonding through the Schiff base reaction to produce an innovative ultrasound-nanobubble coupling agent. By amplifying the cavitation effect of ultrasound, drugs can be efficiently transferred through the double barrier of the skin and delivered to deep layers. In an in vitro model of isolated porcine skin, this agent achieves an effective penetration depth of 728 µm with the parameters of ultrasound set at 2 W, 650 kHz, and 50% duty cycle for 20 min. Consequently, drugs can be efficiently delivered to deeper layers noninvasively. In summary, this ultrasound nanobubble coupling agent efficiently achieves deep-layer drug delivery by amplifying the ultrasonic cavitation effect and penetrating the double barriers, heralding a new era for noninvasive drug delivery platforms and disease treatment., (© 2023 Wiley-VCH GmbH.)

Stem cell tissue engineering is a potential treatment for osteoarthritis. However, the number of stem cells that can be delivered, loss of stem cells during injection, and migration ability of stem cells limit applications of traditional stem cell tissue engineering. Herein, kartogenin (KGN)-loaded poly(lactic-co-glycolic acid) (PLGA) porous microspheres is first engineered via emulsification, and then anchored with chitosan through the amidation reaction to develop a new porous microsphere (PLGA-CS@KGN) as a stem cell expansion vector. Following 3D co-culture of the PLGA-CS@KGN carrier with mesenchymal stem cells (MSCs), the delivery system is injected into the capsule cavity in situ. In vivo and in vitro experiments show that PLGA-CS microspheres have a high cell-carrying capacity up to 1 × 10 4 mm -3 and provide effective protection of MSCs to promote their controlled release in the osteoarthritis microenvironment. Simultaneously, KGN loaded inside the microspheres effectively cooperated with PLGA-CS to induce MSCs to differentiate into chondrocytes. Overall, these findings indicate that PLGA-CS@KGN microspheres held high cell-loading ability, adapt to the migration and expansion of cells, and promote MSCs to express markers associated with cartilage repair. Thus, PLGA-CS@KGN can be used as a potential stem cell carrier for enhancing stem cell therapy in osteoarthritis treatment., (© 2023 Wiley-VCH GmbH.)

Uric acid metabolism disorder triggers metabolic diseases, especially gout. However, increasing uric acid excretion remains a challenge. Here, an accelerative uric acid excretion pathway via an oral intestine-explosive hydrogel microsphere merely containing uricase and dopamine is reported. After oral administration, uricase is exposed and immobilized on intestinal mucosa along with an in situ dopamine polymerization via a cascade reaction triggered by the intestinal specific environment. By this means, trace amount of uricase is required to in situ up-regulate uric acid transporter proteins of intestinal epithelial cells, causing accelerated intestinal uric acid excretion. From in vitro data, the uric acid in fecal samples from gout patients could be significantly reduced by up to 37% by the mimic mucosa-immobilized uricase on the isolated porcine tissues. Both hyperuricemia and acute gouty arthritis in vivo mouse models confirm the uric acid excretion efficacy of intestine-explosive hydrogel microspheres. Fecal uric acid excretion is increased around 30% and blood uric acid is reduced more than 70%. In addition, 16S ribosomal RNA sequencing showed that the microspheres optimized intestinal flora composition as well. In conclusion, a unique pathway via the intestine in situ regulation to realize an efficient uric acid intestinal excretion for gout therapy is developed., (© 2023 Wiley-VCH GmbH.)

Tumor-associated macrophage (TAM) reprogramming is a promising therapeutic approach for cancer immunotherapy; however, its efficacy remains modest due to the low bioactivity of the recombinant cytokines used for TAM reprogramming. mRNA therapeutics are capable of generating fully functional proteins for various therapeutic purposes but accused for its poor sustainability. Inspired by kinetic energy recovery systems (KERS) in hybrid vehicles, a cytokine efficacy recovery system (CERS) is designed to substantially augment the therapeutic index of mRNA-based tumor immunotherapy via a "capture and stabilize" mechanism exerted by a nanostructured mineral coating carrying therapeutic cytokine mRNA. CERS remarkably recycles nearly 40% expressed cytokines by capturing them onto the mineral coating to extend its therapeutic timeframe, further polarizing the macrophages to strengthen their tumoricidal activity and activate adaptive immunity against tumors. Notably, interferon-γ (IFN-γ) produced by CERS exhibits ≈42-fold higher biological activity than recombinant IFN-γ, remarkably decreasing the required IFN-γ dosage for TAM reprogramming. In tumor-bearing mice, IFN-γ cmRNA@CERS effectively polarizes TAMs to inhibit osteosarcoma progression. When combined with the PD-L1 monoclonal antibody, IFN-γ cmRNA@CERS significantly boosts antitumor immune responses, and substantially prevents malignant lung metastases. Thus, CERS-mediated mRNA delivery represents a promising strategy to boost antitumor immunity for tumor treatment., (© 2023 Wiley-VCH GmbH.)