Yongye Liang

It has been highly challenging to reliably detect various cancers at an early stage when tumors are just millimeters in size. To address this, we developed a tumor microenvironment (TME)-responsive nanoprobe, PR-KAd@CD-AuNC, enabling cross-validated cancer detection through in vivo second near-infrared (NIR-II) fluorescence imaging and in vitro colorimetric urinalysis. The nanoprobe consists of three integrated components: a renal-clearable signal-output segment (cyclodextrin-functionalized gold nanocluster, CD-AuNC), a tumor-targeting and size-controlling component (PR), and a matrix metalloproteinase-2 (MMP2)-cleavable linker (KAd). PR, composed of 8-arm poly(ethylene glycol) for prolonged circulation and c(RGDfK) peptides for α_vβ₃ integrin targeting, directed selective tumor accumulation after intravenous injection of PR-KAd@CD-AuNC. The intrinsic emission of CD-AuNC above 1100 nm enabled high-resolution, real-time NIR-II fluorescence imaging with attenuated photon scattering, allowing precise tumor delineation. Within the TME, specifically overexpressed MMP2 cleaved the KAd linker, releasing ∼2 nm CD-AuNC fragments from the ∼10 nm parent nanoprobe. Being smaller than the ∼5.5 nm renal filtration threshold, these fragments were renally excreted. Concurrently, the peroxidase-like activity of CD-AuNC catalyzed tetramethylbenzidine oxidation to produce a visible blue signal, providing a simple and low-cost urinalysis method suitable for broad cancer screening applications. This dual-modality strategy effectively distinguished cancers from inflammation and other diseases, detecting small tumors for multiple cancer types with a sensitivity surpassing that of computed tomography (CT) imaging, which makes it a promising early detection approach. Furthermore, it was also employed to dynamically assess cancer therapeutic efficacy (i.e., immunotherapy, chemotherapy, and surgical resection), suggesting clinical value for guiding treatment decisions.

Hydrophilization of small-molecule NIR-II fluorophores empowers their applications in biological imaging with high signal-to-background ratio. Aggregation properties should be tuned to afford enhanced photophysical properties.

Near‐infrared II (NIR‐II, 1000–1700 nm) emissive molecules are highly valued for biomedical imaging, phototherapy, and optoelectronic applications due to their deep tissue penetration, reduced autofluorescence, and high signal‐to‐noise ratio. However, their rational design remains challenging, as conventional discovery relies heavily on labor‐intensive synthesis, limited quantum chemical calculations, and inefficient trial‐and‐error exploration. To overcome these limitations, an iterative AI‐driven molecular evolution strategy (AI4NIR‐II 1.0) is introduced that integrates time‐dependent density functional theory (TDDFT), transformer‐based predictive modeling, and generative molecular design. Starting from donor‐acceptor‐donor (D‐A‐D) and donor‐donor‐acceptor‐donor‐donor (D‐D‐A‐D‐D) fragment scaffolds, a predictive model for both absorption and emission properties was trained based on a high quality dataset containing ∼16,000 molecules annotated by the optimally‐tuned range‐separated LC‐ωHPBE* (OTRS) functional. A fine‐tuned generative model was subsequently incorporated into a self‐refining‐loop workflow that cycles through molecular generation, property screening, and dataset augmentation. The model achieves excellent predictive performance for both emission and absorption properties, that is mean absolute errors of 19 nm for emission peak wavelengths and of 11 nm for absorption peak wavelengths, and correlation coefficient ( R ² ) exceeding 0.98 for wavelengths and oscillator strengths compared to OTRS‐TDDFT calculations. In addition, the resulting framework efficiently identifies promising NIR‐II candidates with accurate photophysical property predictions, and achieves speed improvements of three to four orders of magnitude over TDDFT calculations. Beyond accelerating NIR‐II fluorophore discovery, this self‐driven approach establishes a scalable and generalizable paradigm for NIR‐II molecular design, with applicability extending to optoelectronic materials and therapeutic compounds.

The electrochemical nitrate reduction reaction offers a promising route for sustainable ammonia synthesis and environmental nitrate remediation. However, the inherent complexity of the reaction, involving multiple electron‐proton transfer steps and diverse intermediates, poses significant challenges to achieving efficient and selective conversion. Herein, we report a molecularly well‐defined tandem catalyst that facilitates the stepwise optimization of nitrate‐to‐nitrite reduction followed by nitrite‐to‐ammonia conversion. Iron phthalocyanine (FePc) is initially identified for its superior nitrate adsorption capability, while the introduction of electron‐withdrawing cyano substituents (─CN) further lowers the reaction overpotential. The enhanced activities, however, result in the accumulation of the nitrite intermediate, which can be alleviated by the introduction of cobalt phthalocyanine (CoPc) sites with higher intrinsic activity toward nitrite reduction. The optimized catalyst with FePc─CN and CoPc co‐anchored on carbon nanotubes demonstrates highly selective ammonia production over a wide current density window. Mechanistic investigations reveal the tandem reduction pathway and highlight the critical role of proximal cooperation between the two active sites. This work presents a promising design strategy for tandem molecular catalysts in complex multistep electrocatalytic transformations.

Fluorescence imaging in the near-infrared-IIb (NIR-IIb, 1500–1700 nm) window offers high signal-to-background ratios (SBRs). However, the development of bright NIR-IIb fluorophores remains challenging due to the trade-off between long-wavelength absorption and brightness. In this study, we present a molecular design strategy that bypasses this limitation by inducing J-aggregation to redshift the absorption while maintaining an optimized bandgap with a high radiative decay rate. A quinoidal thieno[3,4-b]thiophene π-bridge is incorporated to synthesize a fused-ring acceptor fluorophore, CTTIC-4F, affording J-aggregation in encapsulated nanoparticles (NPs) with enhanced brightness. The CTTIC-4F NPs display strongly red-shifted absorption peaked at 1017 nm and an improved fluorescence quantum yield of 0.44% in aqueous solutions, outperforming counterparts with conventional π-bridges. The molecular dynamics simulations indicate compact and spherical aggregates of CTTIC-4F due to strong π–π interactions in aqueous solutions, consistent with J-type packing. In vivo imaging demonstrates that the CTTIC-4F NPs achieve a high SBR of 8.26 in vascular imaging and ultrahigh SBRs for lymph system imaging under the 1064 nm laser excitation, enabling high-contrast NIR-IIb lymph system imaging and image-guided resection of tumor-draining sentinel lymph nodes. These results demonstrate the effectiveness of aggregation-regulated molecular design for NIR-IIb fluorophores.

Due to their high selectivity, nickel phthalocyanine (NiPc) based molecular electrocatalysts supported on carbon nanotubes have been regarded as promising candidates for electrochemical CO₂-to-CO conversion. However, it lacks effective strategies to simultaneously enhance the intrinsic activity and stability of NiPc electrocatalysts. Here, we show that fluorine tuning of NiPc can address this limitation. As a bridging study, incorporating polytetrafluoroethylene (PTFE) is shown to facilitate CO desorption near active sites, thereby enhancing electrochemical stability but reducing activity due to partial site masking. Building on this insight, β-site fluorination of NiPc affords a robust electrocatalyst (NiPc–F) with enhanced intrinsic CO₂-to-CO activity and durability. Microenvironment and operando studies reveal that fluorination improves CO₂ adsorption and enhances CO desorption, resulting in intact Ni–N₄ coordination during electrocatalysis. The optimized NiPc-F catalyst delivers stable operation at −300 milliamperes per square centimeter for 45 hours in neutral electrolytes, with CO Faradaic efficiencies over 98 percent.

The electrocatalytic reduction of nitrate (NO ₃ ⁻ ) to ammonia (NH ₃ ) offers a sustainable pathway for NH ₃ synthesis. Metal porphyrins are promising electrocatalysts for the NO ₃ ⁻ reduction reactions (NO ₃ RR) due to their tunable molecular structures, yet effective strategies for enhancing their performance are still lacking. Herein, we develop an efficient composite electrocatalyst based on cobalt tetraphenylporphyrin (CoTPP) for electrochemical NH ₃ synthesis by mitigating hydroxide (OH ⁻ ) interference and optimizing active hydrogen supply. CoTPP is identified as a superior catalyst with a strong affinity for NO ₃ ⁻ adsorption, and neutral condition is adopted to suppress the competitive OH ⁻ adsorption. Poly(benzodifurandione) (PBFDO) is further introduced as an active hydrogen support cocatalyst. The optimized composite catalyst of CoTPP+carbon nanotube (CNT)+PBFDO shows high Faradaic efficiencies (FEs) of NH ₃ near 100% across a broad potential range, and a high NH ₃ yield rate (5.3 mg h ⁻¹ cm ⁻² ) is achieved, increasing by fivefold when compared to the catalyst without PBFDO. This work provides mechanistic insights into enhancing the activity of molecular electrocatalysts for the conversion of NO ₃ ⁻ to NH ₃ .

The electrocatalytic reduction of nitrate (NO ₃ ⁻ ) to ammonia (NH ₃ ) offers a sustainable pathway for NH ₃ synthesis. Metal porphyrins are promising electrocatalysts for the NO ₃ ⁻ reduction reactions (NO ₃ RR) due to their tunable molecular structures, yet effective strategies for enhancing their performance are still lacking. Herein, we develop an efficient composite electrocatalyst based on cobalt tetraphenylporphyrin (CoTPP) for electrochemical NH ₃ synthesis by mitigating hydroxide (OH ⁻ ) interference and optimizing active hydrogen supply. CoTPP is identified as a superior catalyst with a strong affinity for NO ₃ ⁻ adsorption, and neutral condition is adopted to suppress the competitive OH ⁻ adsorption. Poly(benzodifurandione) (PBFDO) is further introduced as an active hydrogen support cocatalyst. The optimized composite catalyst of CoTPP+carbon nanotube (CNT)+PBFDO shows high Faradaic efficiencies (FEs) of NH ₃ near 100% across a broad potential range, and a high NH ₃ yield rate (5.3 mg h ⁻¹ cm ⁻² ) is achieved, increasing by fivefold when compared to the catalyst without PBFDO. This work provides mechanistic insights into enhancing the activity of molecular electrocatalysts for the conversion of NO ₃ ⁻ to NH ₃ .

Non‐invasive fluorescence endoscopy of deep biological tissues beyond the mucosa, or trans‐intestinal imaging in live mammals with high spatiotemporal resolution, remains challenging due to light scattering. Here, we developed a near‐infrared II (NIR‐II) microendoscopy with imaging wavelength extended to 1700 nm, enabling deep intestinal imaging beyond the mucosa and transrectal imaging at sub‐10‐µm resolution without any invasive surgery. It facilitated real‐time visualization of the relative motion of vascular networks across different layers of the mouse rectum. Featuring a specially designed large field of view, the NIR‐II microendoscopy enabled non‐invasive transrectal imaging of the entire lumbar lymph node for the first time, revealing abnormal lymphatic drainage in tumor‐bearing mice. In vivo longitudinal imaging of healthy mice and colitis‐bearing mice mapped distinct fluorescence patterns in rectal vasculature and lumbar lymph nodes, enabling observation of lesions in acute colitis at the initial stage, and opening new possibilities for studying the interaction between the intestinal microenvironment and lymphatic systems.