Human cytomegalovirus (HCMV) is a frequent complication in kidney transplant recipients (KTRs), often impacting immune regulation. TH9 cells, a subset of CD4+ T cells, are characterized by their secretion of interleukin-9 (IL-9). This study aimed to analyze the phenotypic profile of TH9 cells and their associated cytokine expression in KTRs, and to evaluate mRNA levels of IL-4 and transforming growth factor-β (TGF-β), key cytokines involved in TH9 differentiation. Ten HCMV+ and 10 HCMV- KTRs, along with 10 age- and sex-matched healthy controls, were enrolled. HCMV viral load was quantified using TaqMan real-time polymerase chain reaction. Flow cytometry was used to assess surface markers (CCR6+CCR4-IL-4Rα+CD4+) and intracellular IL-9 expression in TH9 cells. Gene expression levels of IL-4 and TGF-β were also assessed. Surface staining revealed a significantly higher frequency of CD4+CCR4- and CD4+CCR6+ T cells in HCMV- KTRs compared to HCMV+ patients. Conversely, the overall frequency of CD4+ TH9 cells was elevated in HCMV+ KTRs. Intracellular staining demonstrated a significant increase in CD4+IL-9+ and CD4+IL-4Rα+ T cells in the HCMV+ group. Additionally, mRNA expression levels of IL-4 and TGF-β were markedly higher in HCMV+ KTRs than in HCMV- counterparts. These findings suggest a potential role for TH9 cells and their signature cytokine IL-9 in the antiviral immune response in KTRs. While TH9 cells may contribute to HCMV-related immune modulation, further research is needed to fully elucidate their protective mechanisms against viral infections.   Keywords: ; ; ;

In our study, pH-responsive poly(acrylic acid)-Cu2+ hybrid nanoflowers (PAA@Cu2+ hNFs) were fabricated by using poly(acrylic acid) and Cu2+ ions in phosphate-buffered saline solution (PBS). For comparison, pure copper phosphate nanoflowers (Cu NFs) were fabricated. Synthesized PAA@Cu2+ hNFs and Cu NFs were characterized using SEM, EDX, XRD, FTIR, BET, zeta potential, and DLS measurements. Within the pH range of 6-9, PAA@Cu2 + hNFs exhibit a spherical, flower-like porous morphology, with the pH 9 sample showing a more compact, uniform structure and more homogeneous interpetal pores than those at other pH values. Then, hemoglobin (Hb) adsorption studies were also performed using PAA@Cu2+ hNFs and Cu NFs across various parameters, including pH, Hb concentration, ionic strength, temperature, and time. At pH 7, the highest Hb adsorption capacities of PAA@Cu2+ hNFs and Cu NFs were calculated as 961.98 and 94.23 mg/g, respectively. The desorption studies of Hb from the synthesized nanoflowers were performed in an acetate buffer solution including NaCl. The desorption yields of Hb for PAA@Cu2+ hNFs and Cu NFs were calculated as 96.1% and 95.8%, respectively. Then, the reusability of the synthesized nanoflowers for Hb adsorption was evaluated over five cycles. These results suggest that PAA@Cu2 + hNFs are suitable for Hb separation.

Cobamides, the structurally diverse family of cobalt-containing cofactors, are required by most bacteria yet synthesized by a subset of prokaryotes, making cobamide acquisition a major determinant of microbial fitness. Bacteroides thetaiotaomicron, an abundant commensal of the human gut, is auxotrophic for cobamides and relies on environmental scavenging to support its metabolism. To meet this demand in a competitive and diverse cobamide environment of the gut, B. thetaiotaomicron employs a B12-uptake (Btu) system that extends far beyond the well-studied Escherichia coli Btu system. Rather than relying on a single outer membrane (OM) transporter, B. thetaiotaomicron deploys a multiprotein extracellular relay in which surface-exposed BtuJ lipoproteins capture cobamides extracellularly and transfer them to BtuH and BtuG lipoproteins at the OM. BtuG forms a stable complex with the TonB-dependent transporter BtuB, coupling cobamide capture to periplasmic translocation, and the inner membrane BtuFCD complex completes cytoplasmic delivery. BtuJ-enriched OM vesicles further extend cobamide capture into the extracellular environment, and cobamide-dependent riboswitches couple Btu protein expression to the availability and chemical identity of intracellular cobamides. We review the structural and mechanistic evidence for each stage of this relay, propose a model for cobamide import, and identify outstanding questions that will illuminate cobamide scavenging across gut bacteria.

Biofilm-associated wound infections require antibacterial materials that can control attached bacteria while limiting excessive silver exposure. In this study, we prepared a sponge-like hierarchical porous silver-carbon material through in situ glucose foaming and carbonization. The material had a Brunauer-Emmett-Teller surface area of 1067.8 m2 g-1 and a total silver content of 9.22% by weight after complete digestion. During dialysis against phosphate-buffered saline containing 1% bovine serum albumin, the material released approximately 0.27% of its total silver over 72 h. Comparative results showed differences in pore structure and silver transport but did not link release to a specific pore class. The porous silver-carbon material inhibited Escherichia coli and Staphylococcus aureus. The minimum inhibitory and bactericidal concentrations were 4 and 8 μg mL-1, respectively, for Escherichia coli and 8 and 16 μg mL-1, respectively, for Staphylococcus aureus. Propidium iodide staining and scanning electron microscopy were consistent with increased membrane permeability and cell-surface damage. Assays using 2',7'-dichlorodihydrofluorescein diacetate and electron spin resonance measurements supported reactive oxygen species-related stress. Plate-counting assays showed concentration-dependent inhibition of biofilm formation and reduced viable bacterial recovery from established biofilms. Murine fibroblast viability remained above 95%, and hemolysis remained below 5% under the tested conditions. In a full-thickness mouse wound model infected with Escherichia coli, the material and silver nitrate were applied at equal elemental silver doses of approximately 35 μg per wound. The material treatment yielded lower wound-derived colony counts per plate than the silver nitrate treatment on day 4 and reached approximately 95% wound closure by day 14. Endpoint histology showed no obvious structural abnormalities in the examined major organs. These findings suggest that pore structure, dialyzable-silver transport, and bacteria-material interactions should be considered together when designing porous silver-carbon antibacterial materials.

Spin-polarized quantum dot light-emitting diodes (spin-QLEDs) offer a package solution for advanced photonic applications, such as quantum information processing. However, the performance of these devices is threatened by integration of chiral layers due to greatly compromised interfacial hole transport and deteriorate film morphology. In this work, a hybrid hole transport layer (HTL) engineering strategy is proposed to simultaneously tackle the two key issues. On one hand, enhanced surface hydrophilicity of the HTL enables the growth of a high-quality chiral perovskite layer as a spin filter. On the other hand, tri-channel hole transport mechanism is first unraveled theoretically and experimentally to realize high-mobility pathways, stepwise injection, and bypass the resistive limitations of traditional HTL. The resulting spin-QLEDs demonstrated an ultralong T50 lifetimes at 100 cd/m2 to be 3968.9 h which is orders of magnitude higher than other reports. Moreover, the spin-QLEDs exhibit a recorded luminance of 14,370 cd/m2 for red-light-emitting devices, alongside an external quantum efficiency of 6.68% and a circularly polarized electroluminescence asymmetry factor (gCP-EL) of 0.026. This hybrid HTL architecture offers a reliable route toward long-lived and high-brightness spin-optoelectronic devices.

Conventional liquid-phase syntheses of carbon dots (CDs) often involve complex solvent-precursor interactions that induce structural and spectral heterogeneities, severely limiting their optoelectronic performance. Herein, we report a highly controlled, solvent-free, single-precursor strategy utilizing 2,6-diaminonaphthalene to synthesize ultrabright, highly uniform green-emissive CDs (DAN-CDs). Through comprehensive thermal analyses and kinetic modeling, we elucidate a spatiotemporally resolved, dual-pathway formation mechanism: a nitrogen-doped core initially assembles within an oxygen-shielding autogenic precursor melt, followed by controlled, oxygen-mediated surface passivation as the melt barrier attenuates. This self-limiting oxidative capping thoroughly suppresses non-radiative structural defects. Photophysical analyses uncover an efficient intra-particle energy funneling process from the light-harvesting core to these surface traps, yielding excitation-independent green emission with a narrow bandwidth (< 60 nm) and a near-unity photoluminescence quantum yield of 91%. When integrated into self-emissive light-emitting diodes (LEDs), the devices deliver pure green electroluminescence. Notably, the peak external quantum efficiency (EQE) of 2.2% achieved herein through the solvent-free approach stands as the highest value reported to date among LEDs based on green-emissive CDs synthesized via thermal carbonization. These results conclusively underscore the strong potential of rationally designed DAN-CDs as highly efficient, environmentally benign, and heavy-metal-free emitters for next-generation optoelectronics and display applications.

Extracellular targeted protein degradation (eTPD) systems typically utilize lysosome-targeting receptors (LTRs) to redirect extracellular and membrane proteins for lysosomal degradation. Expanding the repertoire of clinically relevant LTRs could broaden the therapeutic potential of eTPD. Here we report trophoblast cell surface antigen-2 (TROP2), a clinically validated tumor-associated antigen targeted by approved antibody-drug conjugates, as a promising LTR for tumor cell-selective eTPD. We develop TROP2-targeting chimeras (TRTACs) by fusing a TROP2-binding nanobody to target-specific nanobodies. This fully genetically encoded, ∼30 kDa nanobody format enables modular construction, broad target adaptability, and favorable tumor penetration. TRTACs induce degradation of diverse membrane proteins, including epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and programmed death-ligand 1 (PD-L1), preferentially in tumor cells rather than in nonmalignant cells. We further designed TRTAC-drug conjugates (TRTAC-DCs) by attaching cytotoxic payloads to TRTACs, enabling enhanced drug delivery together with protein degradation. The HER2-targeted TRTAC-DC reduced SKBR3 cell viability by 50% at 0.2 nM and showed potent antitumor activity in vivo, without significant body weight loss or histological abnormalities in major organs. These findings establish TROP2 as a clinically relevant LTR and provide a modular platform that combines tumor cell-selective extracellular protein degradation with enhanced payload delivery.

Efficient and safe intracellular delivery of macromolecules, like nucleic acids, remains a major challenge in ex vivo cell engineering. While photoporation is a highly attractive method for cytosolic delivery of (macro)molecules, photosensitizers remaining in the photoporated cells may pose safety concerns, especially when the cells are engineered for therapeutic use. In this study we introduce the concept of "detachable photosensitizers" using gold nanoparticles (AuNPs) as photosensitizer. We demonstrate that phenylboronic acid (PBA)-functionalized AuNPs can be anchored to membranes of HeLa cells and Jurkat cells, thereby enabling the efficient intracellular delivery of dextrans and mRNA upon pulsed laser irradiation (photoporation). Subsequently, the PBA-AuNPs can be detached from the cells "on-demand" by adding ATP to the cell medium, as cis-diol groups in ATP displace the boronate ester bonds between the PBA-AuNPs and cell-surface. ICP-MS analysis demonstrated efficient detachment, with the average cell-associated gold mass per viable cell falling below the theoretical mass of a single intact 80 nm AuNP. This "attach-and-detach" strategy offers a robust and effective approach to addressing safety concerns associated with the use of plasmonic nanomaterials as sensitizers for photoporation, and holds significant potential for the safe manufacturing of engineered cells in the context of cell therapy.

The escalating volume of decommissioned lithium cobalt oxide (LCO) batteries necessitates recycling strategies capable of adding value by transforming spent cathodes into high-performance materials. While eutectic molten salt systems have emerged as a promising liquid-solid medium for direct regeneration, the selection of salts has been largely empirical, and the critical role of anions in governing the relithiation efficacy and interface chemistry remains underappreciated. Herein, we demonstrate that the strategic choice of anions in a binary molten salt flux is paramount to achieving structural repair and performance enhancement. We identify that anions with high adsorption energy to the CoO6 slabs and low dissociation energy for Li+, such as Cl-, are optimal. This anion-mediated process directs a preferential crystallographic reconstruction along the c-axis and fosters the development of a Li-O enriched, (104)-facetted surface. Consequently, the upcycled LCO cathode retained over 95% of its original capacity after 1000 cycles at 4.2 V. Even at an elevated voltage of 4.6 V, the upcycled LCO retains 85.5% of its capacity after 100 cycles at 0.5 C. This work underscores that understanding and engineering the anion in molten salts could be a powerful step toward the rational design of advanced upcycling protocols.

Extracellular pore domains of ion channels are emerging as dynamic regulatory surfaces, but whether they can be rationally targeted to achieve selective channel modulation remains unclear. Here, using an optimized hotspot-centric design strategy, we developed Depiv2, a structure-guided peptidic inhibitor of TRPV2 that binds the extracellular pore domain and suppresses channel activity with nanomolar potency and subtype selectivity. Our cryo-EM structure of the TRPV2-Depiv2 complex showed that peptide binding remodels the pore domain and stabilizes a closed, non-conductive conformation. Patch-clamp recordings further revealed that Depiv2 decreases both open probability and single-channel conductance, indicating inhibition through combined allosteric and permeation-coupled mechanisms. In cellular and mouse models of pathological cardiac hypertrophy, Depiv2 blunted disease-associated remodeling. These findings establish the extracellular pore of TRPV2 as a designable allosteric site and illustrate how rational peptide engineering can be used to target extracellular regulatory surfaces in TRP channels.

Hydrogen peroxide (H2O2), as a green oxidizing medium, can be generated and utilized in situ via an electrochemical-chemical cascade, enabling organic transformations while enhancing efficiency and selectivity. However, balancing high H2O2 production, efficient activation, and selective substrate conversion remains challenging. Herein, a series of transition metal-doped CeO2 catalysts were developed for electrocatalytic H2O2 generation and its subsequent use in converting α-hydroxy acids to pyruvate. Among them, Ni-CeO2 exhibited the best performance, achieving a pyruvate production rate of 19.9 mmol g-1 h-1 and a Faradaic efficiency of 55.3%. Mechanistic studies revealed that transition metal doping regulates the local coordination environment and oxygen vacancy concentration, thereby optimizing the adsorption strength of the *OOH intermediate, which governs the two-electron oxygen reduction reaction pathway and H2O2 generation and release. Furthermore, in situ generated H2O2 was selectively activated on the catalyst surface to form a reactive oxygen species network dominated by hydroxyl radicals (·OH) and assisted by singlet oxygen (1O2). Among these, ·OH showed the lowest energy barrier for α-C─H bond activation and subsequent electron rearrangement, making it the key species for pyruvate formation. This work provides a new strategy for the preparation of value-added chemicals.

The existing designs of buffer for all-solid-state Li-metal batteries (ASSLMBs) are mostly limited to static optimization of single functions and lack systematic regulation of the dynamic competition among ionic conduction, electron distribution, and interfacial lithiophilicity. Herein, a conduction-nucleation competition mechanism is proposed firstly, clarifying that lithium deposition is governed by the synergy of these three factors. Guided by this principle, a self-adaptive gradient buffer layer composed of soft carbon and Mg3N2 (SCMN) is designed. After lithiation, the buffer forms a continuous lithiophobic/lithiophilic gradient and subsequently undergoes in-situ conversion into highly ion-conductive Li3N and highly electron-conductive/ lithiophilic Li-C/Li-Mg alloys during electrochemical activation, enabling dynamic interface self-optimization. The gradient structure creates a fast ion-electron dual conduction network, guiding bottom-top lithium deposition within the buffer layer without volume expansion. Consequently, the symmetric cells achieve stable cycling over 1600 h at 1.5 mA cm- 2 and remain stable even under low stack pressure (15 MPa). The LiCoO2-based full cells deliver ultra-stable cycle with 98.5% capacity retention after 200 cycles at 0.1 C. Additionally, the full cells paired with high-voltage LiNi0.8Co0.1Mn0.1O2 cathodes exhibit exceptional cycling stability at high loading (4.45 mg cm-2). This work demonstrates a mechanism-driven design paradigm toward high-energy, long-life ASSLMBs.

Substrate topography, such as curvature, has been recognized as a key physical cue that regulates cell organization and tissue function, yet how curvature influences chiral cell behavior remains unclear. Here, we created curved surfaces (concave or convex) separated by flat regions to investigate the role of cell chirality in curvature-guided multicellular morphogenesis. C2C12 cells showed opposite alignment biases on concave and convex surfaces, and the cells on flat regions adopted a reversed bias compared to those on the adjacent curved areas. Cells with opposite intrinsic or pharmacologically altered chirality exhibited correspondingly reversed alignment patterns. Detailed analyses revealed that local curvature initially directed cell elongation along distinct geometric axes on convex and concave surfaces, followed by biased tilting and migration governed by intrinsic cellular chirality. Together, our findings demonstrate that cell chirality superimposes a directional bias upon curvature-guided elongation, thereby driving collective alignment and migration. This work provides new insights into how cells respond to curvature and highlights a potential mechanism for tissue-level symmetry breaking, regulated by substrate topography.

Microspore-derived embryogenesis (MDE) is essential for doubled haploid (DH) plant breeding, but conventional bulk culture systems are limited by poor scalability and difficulty for automation. Adapting droplet microfluidics for plant cell culture is promising but challenging due to the large size and fragility of plant cells involved in embryogenesis, such as maize microspores (60-85 µm) and their expanding embryo-like structures (200-500 µm). Here, we present a droplet microfluidic platform engineered for large plant cells, integrating a tubing-based loading strategy that minimizes sedimentation losses, robust generation of stable 20 and 200 nL droplets optimized for large-cell encapsulation, and scalable 3D reservoir incubation for long-term culture. Optimized flow conditions and surface treatments enabled cell encapsulation with high fidelity, sustaining viability for over two weeks. Multi-modal viability assessment using fluorescence spectroscopy and microscopy (bright-field and fluorescence) confirmed that droplet culture preserves cell health comparably to bulk methods. The platform supports both single-cell and few-cell encapsulation modes, and increasing droplet volume and cell loading density further enhances embryogenesis rates and total embryo yield, respectively. Together, these advances establish a scalable, modular droplet microfluidic platform for high-throughput embryogenesis analysis and embryo production, offering new opportunities in plant developmental biology, precision breeding, and doubled-haploid technology.

The fabrication of microscale cracks on flexible substrates is a crucial step for potential applications such as human-machine interfaces, biosignal analysis, and structural health monitoring. However, existing crack fabrication methods predominantly rely on externally applied mechanical stimuli such as stretching or bending, which limits the freedom with which cracks can form in terms of their location, density, and geometry. In this study, we introduce a bio-inspired internal stress engineering strategy that enables tunable microscale cracks to be driven by internal stress induced through microsphere expansion. Microscale cracks can be reproducibly formed by exploiting the localized stress concentration and thickness-dependent mechanical property transition of an ultrathin metal film. The crack-based strain sensor exhibits an ultrahigh sensitivity of 24 320 at a strain of 1.6%. The proposed strategy demonstrates excellent sensing performance under both static and dynamic loading conditions, including high repeatability and frequency stability, demonstrating its considerable potential for practical sensing applications. Further, we demonstrate its applicability in wearable sensors for real-time physiological monitoring and structural health monitoring of aircraft structures to verify its versatility across diverse industrial fields.