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The antiapoptotic protein myeloid cell leukemia 1 (Mcl-1) has been increasingly identified as a promising potential therapeutic target attributed to its critical regulation effect in diverse cellar physiopathological events. Current fluorescence imaging strategies tend to be susceptible to the cellular microenvironment, and straightforward mapping of Mcl-1's level variation remains challenging. In this paper, an activatable "off-on" fluorescence strategy for Mcl-1 specific labeling was presented based on bio-orthogonal chemistry by introducing tetrazine-functionalized borondipyrromethene ( TB ) as a fluorescent reporter and trans -cyclooctyne-derived indole-2-carboxylic acid ( TI ) as an Mcl-1 targeting moiety. With the click pair of TB and TI , the Mcl-1 expression level in vitro and in vivo was successfully mapped straightforward. Also, the level changes of Mcl-1 upon drug challenge were demonstrated. This work provides a robust fluorescence strategy for Mcl-1 in situ imaging, and the results would further facilitate the comprehensive revelation of the Mcl-1 biological effect.

The mechanisms of action (MoA) have been proposed to further reduce the O 2 dependence of photodynamic therapy (PDT) significantly. However, the triplet states of traditional photosensitizers are relatively short and also are easily deactivated by the quenching of H 2 O or O 2 . This is not conducive for the electron transfer in the photocatalytic process and poses a great obstacle to establish the MoA. Therefore, we selected and synthesized a zirconium(IV) complex (Zr( Mes PDP Ph ) 2 ) reported by Milsmann to address this issue. The specific symmetric and intact geometry endowed Zr( Mes PDP Ph ) 2 NPs with long-lived triplet excited state (τ = 350 μs), desired sensitized ability, and improved anti-interfering performance on O 2 , which was matched with the requirements of photoredox catalyst significantly. The results showed that while PDT (I) and PDT (II) could be achieved simultaneously by leveraging Zr( Mes PDP Ph ) 2 NPs, it also could be served as a rare example of thermally activated delayed fluorescence (TADF)-based photoredox catalyst to implement the MoA of PDT. It involved the oxidation of NADH and the establishment of catalytic cycle collaborating by O 2 and cytochrome c (cyt c ) in normoxia and hypoxia, respectively. As a result, the oxygen-free PDT and tumor-growth inhibition was realized.

Double-network (DN) hydrogels consisting of noncovalent interacting networks are highly desired due to their well-controlled compositions and environmental friendliness, but the low water resistance always impairs their mechanical strength. Here, an anti-swelling hydrogel possessing the core/shell architecture through rational regulation of multiple weak noncovalent interactions is prepared. A composite hydrogel consists of chitosan (CS) and poly(N-acryloyl 2-glycine) (PACG), readily forming the shell-structured DN hydrogel after soaking in a FeCl 3 solution because of in situ formation of chain entanglements, hydrogen bonds, and ionic coordination. The produced DN hydrogels exhibit excellent anti-swelling behaviors and mechanical durability for over half a year, even in some strict situations. Taking the merits of noncovalent bonds in adjustability and reversibility, the swelling property of these hydrogels can be easily customized through control of the ion species and concentrations. A dynamically reversible transition from super-swelling to anti-swelling is realized by breaking up and rebuilding the metal-coordination complexes. This facile but efficient strategy of turning the noncovalent interactions and consequently the mechanics and anti-swelling properties is imperative to achieve the rational design of high-performance hydrogels with specific usage requirements and expand their applicability to a higher stage., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Death happening due to massive hemorrhage has been involved in military conflicts, traffic accidents, and surgical injuries of various human disasters. Achieving rapid and effective hemostasis to save lives is crucial in urgent massive bleeding situations. Herein, a covalent cross-linked AG-PEG glue based on extracellular matrix-like amino-gelatin (AG) and PEG derivatives is developed. The AG-PEG glue gelatinizes fast and exhibits firm and indiscriminate close adhesion with various moist tissues upon being dosed. The formed glue establishes an adhesive and robust barrier to seal the arterial, hepatic, and cardiac hemorrhagic wounds, enabling it to withstand up to 380 mmHg blood pressure in comparison with normal systolic blood pressure of 60-180 mmHg. Remarkably, massive bleeding from a pig cardiac penetrating hole with 6 mm diameter is effectively stopped using the glue within 60 s. Postoperative indexes of the treated pig gradually recover and the cardiac wounds regrow significantly at 14 days. Possessing on-demand solubility, self-gelling, and rapid degradability, the AG-PEG glue may provide a fascinating stop-bleeding approach for clinical hemostasis and emergency rescue., (© 2023 Wiley-VCH GmbH.)

Development of artificial biomaterials by mimicking extracellular matrix of bone tissue is a promising strategy for bone regeneration. Hydrogel has emerged as a type of viable substitute, but its inhomogeneous networks and weak mechanics greatly impede clinical applications. Here, a dual crosslinked gelling system is developed with tunable architectures and mechanics to promote osteogenic capacity. Polyhedral oligomeric silsesquioxane (POSS) is designated as a rigid core surrounded by six disulfide-linked PEG shells and two 2-ureido-4[1H]-pyrimidinone (UPy) groups. Thiol-disulfide exchange is employed to fabricate chemical network because of the pH-responsive "on/off" function. While self-complementary UPy motif is capable of optimizing local microstructure to enhance mechanical properties. Taking the merits of biocompatibility and high-mechanics in periodontal ligament stem cells (PDLSCs) proliferation, attachment, and osteogenesis, hybrid hydrogel exhibits outstanding osteogenic potential both in vitro and in vivo. Importantly, it is the first time that a key epigenetic regulator of ten-eleven translocation 2 (Tet2) is discovered to significantly elevate the continuously active the WNT/β-catenin through Tet2/HDAC1/E-cadherin/β-catenin signaling cascade, thereby promoting PDLSCs osteogenesis. This work represents a general strategy to design the hydrogels with customized networks and biomimetic mechanics, and illustrates underlying osteogenic mechanisms that will extend the design rationales for high-functional biomaterials in tissue engineering., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Hydrogels are extracellular-matrix-like biomimetic materials that have wide biomedical applications in tissue engineering and drug delivery. However, most hydrogels cannot simultaneously fulfill the mechanical and cell compatibility requirements. In the present study, we prepared a semi-interpenetrating network composite gel (CG) by incorporating short chain chitosan (CS) into a covalent tetra-armed poly(ethylene glycol) network. In addition to satisfying physicochemical, mechanics, biocompatibility, and cell affinity requirements, this CG easily encapsulated acetylsalicylic acid (ASA) via electrostatic interactions and chain entanglement, achieving sustained release for over 14 days and thus promoting periodontal ligament stem cell (PDLSC) proliferation and osteogenic differentiation. In vivo studies corroborated the capacity of PDLSCs and ASA-laden CG to enhance new bone regeneration in situ using a mouse calvarial bone defect model. This might be attributed to PDLSCs and host mesenchymal stem cells expressing monocyte chemoattractant protein-1, which upregulated M2 macrophage recruitment and polarization in situ , indicating its appealing potential in bone tissue engineering., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

Achieving persistent room-temperature phosphorescence (p-RTP), particularly those of tunable full-colors, from pure organic amorphous polymers is attractive but challenging. Particularly, those with tunable multicolor p-RTP in response to excitation wavelength and time are highly important but both fundamentally and technically underexplored. Here, a facile and general strategy toward color-tunable p-RTP from blue to orange-red based on amidation grafting of luminophores onto sodium alginate (SA) chains, resulting in amorphous polymers with distinct p-RTP and even impressively excitation-dependent and time-dependent afterglows is reported. p-RTP is associated with the unique semi-rigidified SA chains, effective hydrogen bonding network, and oxygen barrier properties of SA, whereas excitation-dependent and time-dependent afterglows should stem from the formation of diversified p-RTP emissive species with comparable but different lifetimes. These results outline a rational strategy toward amorphous smart luminophores with colorful, excitation-dependent, and time-dependent p-RTP, excellent solution processability, and film-forming ability for versatile applications., (© 2020 Wiley-VCH GmbH.)

It is a textbook knowledge that protein photoluminescence stems from the three aromatic amino acid residues of tryptophan(Trp), tyrosine (Tyr), and phenylalanine (Phe), with predominant contributions from Trp. Recently, inspired by the intrinsic emission of nonaromatic amino acids and poly(amino acids) in concentrated solutions and solids, we revisited protein light emission using bovine serum albumin (BSA) as a model. BSA is virtually nonemissive in dilute solutions (≤0.1 mg mL -1 ), but highly luminescent upon concentration or aggregation, showing unique concentration-enhanced emission and aggregation-induced emission (AIE) characteristics. Notably, apart from well-documented UV luminescence, bright blue emission is clearly observed. Furthermore, persistent room-temperature phosphorescence (p-RTP) is achieved even in the amorphous solids under ambient conditions. This visible emission can be rationalized by the clustering-triggered emission (CTE) mechanism. These findings not only provide an in-depth understanding of the emissive properties of proteins, but also hold strong implications for further elucidating the basis of tissue autofluorescence., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nonconventional biomacromolecular luminogens have attracted extensive interest due to their fundamental importance and potential applications in diverse areas. To explore novel luminogens and, moreover, to gain deeper insights into their emission mechanism, we study the emission behaviors of sodium alginate (SA), a natural anionic polysaccharide composed of mannuronic (M) and guluronic acids (G). We find that the luminescence from aqueous SA solutions exhibits distinct concentration enhanced emission and aggregation-induced emission (AIE) characteristics. Meanwhile, the ratio of M/G also matters. Rheological measurements reveal the distinct regimes of the solutions, which are consistent with the observed emission, indicative of strong association between the chain entanglement and emission. Moreover, we observe persistent room temperature phosphorescence (RTP) in the amorphous SA solids, which is a rare case even in pure organic aromatic luminogens. Such unique emission can be remarkably enhanced via coordination with Ca 2+ ions. These emission behaviors can be well rationalized by the clustering-triggered emission (CTE) mechanism. Namely, the emission is caused by the electron cloud overlap due to the clustering of oxygen atoms and carboxylate units, together with conformation rigidification. Owing to its biocompatibility, intrinsic emission, and, moreover, persistent RTP, SA shows great potential for anticounterfeiting, encryption, intracellular imaging, and so on.