Search

Due to an oversight in image editing, an incorrect image of the TPA-QLZ group in Figure 6F was used during manuscript preparation. The image of the TPA-QLZ group in Figure 6F has now been corrected as shown below

Designing molecules with donor-acceptor-donor (D-A-D) architecture plays an important role in obtaining second near-infrared region (NIR-II, 1000-1700 nm) fluorescent dyes for biomedical applications; however, this always comes with a challenge due to very limited electronic acceptors. On the other hand, to endow NIR-II fluorescent dyes with combined therapeutic applications, trivial molecular design is indispensable. Herein, we propose a pyrazine-based planar electronic acceptor with a strong electron affinity, which can be used to develop NIR-II fluorescent dyes. By structurally attaching two classical triphenylamine electronic donors to it, a basic D-A-D module, namely Py-NIR, can be generated. The planarity of the electronic acceptor is crucial to induce a distinct NIR-II emission peaking at ∼1100 nm. The unique construction of the electronic acceptor can cause a twisted and flexible molecular conformation by the repulsive effect between the donors, which is essential to the aggregation-induced emission (AIE) property. The tuned intramolecular motions and twisted D-A pair brought by the electronic acceptor can lead to a remarkable photothermal conversion with an efficiency of 56.1% and induce a type I photosensitization with a favorable hydroxyl radical (OH˙) formation. Note that no additional measures are adopted in the molecular design, providing an ideal platform to realize NIR-II fluorescent probes with synergetic functions based on such an acceptor. Besides, the nanoparticles of Py-NIR can exhibit excellent NIR-II fluorescence imaging towards orthotopic 4T1 breast tumors in living mice with a high sensitivity and contrast. Combined with photothermal imaging and photoacoustic imaging caused by the thermal effect, the imaging-guided photoablation of tumors can be well performed. Our work has created a new opportunity to develop NIR-II fluorescent probes for accelerating biomedical applications. © 2024 The Royal Society of Chemistry

Zheng Tian,1,* Yachen Jiang,1,* Nan Zhang,1 Zhijun Zhang,2 Lan Wang1 1School of Nursing, Tianjin Medical University, Tianjin, 300070, People’s Republic of China; 2Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lan Wang, Email wangl0423@tmu.edu.cmBackground and Aim: COPD nursing plays a crucial role in alleviating disease symptoms, prolonging patient survival, and is therefore of paramount importance. However, authoritative research findings, research hotspots, and development trends in the field of COPD are still unclear. This study aimed to examine authoritative research findings, research hotspots, and trends in the field of COPD nursing. Descriptive statistics and bibliometric and visual analyses of the literature were conducted.Methods: Bibliometric data were obtained from the Web of Science database. Citespace was used to explore publication trends, countries, institutions, journals, authors, keywords, and co-citation characteristics of the included literature in order to summarize the key research in the field of COPD nursing.Results: In total, 693 articles on COPD nursing were published. 1998– 2014 showed a rapid growth period in this research field, which stabilized in 2015– 2022. The research content could mostly be summarized into five categories: acute exacerbation, quality of life, risk, evidence-based nursing, and pulmonary rehabilitation. The research hotspots in 1998– 2014 included randomized controlled trials, education, elderly patients, nursing home residents, nursing homes, rehabilitation, and prevalence. Research in 2015– 2022 focused on impact, palliative care, needs, and predictors. In recent years, research mainly concentrated on symptom management models, cost-effectiveness, and cumulative meta-analysis.Conclusion: Bibl

Zhijun Zhang,1,2 Tiehong Yang,2 Jingwei Wang,2 Zhe Yu,2 Youbei Qiao,2 Chaoli Wang,2 Zhenggang Yue,1 Hong Wu2 1School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, People’s Republic of China; 2Department of Medicine Chemistry and Pharmaceutical Analysis, School of Pharmacy, Air Force Medical University, Xi’an, People’s Republic of ChinaCorrespondence: Hong Wu, Department of Medicine Chemistry and Pharmaceutical Analysis, School of Pharmacy, Air Force Medical University, Xi’an, People’s Republic of China, Tel/Fax +86 29 84776823, Email wuhong@fmmu.edu.cn Zhenggang Yue, School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, People’s Republic of China, Tel +86 18092086211, Email liuxingjian1981@163.comPurpose: The remarkable peroxidase-like activity of single-atom nanozymes (SAzymes) allows them to catalyze the conversion of H2O2 to •OH, rendering them highly promising for antibacterial applications. However, their practical in vivo application is hindered by the near-neutral pH and insufficient H2O2 levels present in physiological systems. This study was aimed at developing a SAzyme-based nanoreactor and investigating its in vivo antibacterial activity.Methods: We developed a hollow mesoporous molybdenum single-atom nanozyme (HMMo-SAzyme) using a controlled chemical etching approach and pyrolysis strategy. The HMMo-SAzyme not only exhibited excellent catalytic activity but also served as an effective nanocarrier. By loading glucose oxidase (GOx) with HMMo-SAzyme and encapsulating it with hyaluronic acid (HA), a nanoreactor (HMMo/GOx@HA) was constructed as glucose-triggered cascade catalyst for combating bacterial infection in vivo.Results: Hyaluronidase (HAase) at the site of infection degraded HA, allowing GOx to convert glucose into gluconic acid and H2O2. An acid environment significantly enhanced the catalytic activity of HMMo-SAzyme to promote the further catalytic conversion of H2O2 to •OH for bacterial elimination. I

Development of type I photosensitizers (PSs) with strong hydroxyl radical ((OH)-O-& BULL;) formation is particularly important in the anaerobic tumor treatment. On the other hand, it is challenging to obtain an efficient solid-state intramolecular motion to promote the development of molecular machine and molecular motor. However, the relationship between them is never revealed. In this work, a pyrazine-based near-infrared type I PS with remarkable donor-acceptor effect is developed. Notably, the intramolecular motions are almost maximized by the combination of intramolecular and intermolecular engineering to simultaneously introduce the unlimited bond stretching vibration and boost the group rotation. The photothermal conversion caused by the intramolecular motions is realized with efficiency as high as 86.8%. The D-A conformation of PS can also induce a very small singlet-triplet splitting of 0.07 eV, which is crucial to promote the intersystem crossing for the triplet sensitization. Interestingly, its photosensitization is closely related to the intramolecular motions, and a vigorous motion may give rise to a strong (OH)-O-& BULL; generation. In view of its excellent photosensitization and photothermal behavior, the biocompatible PS exhibits a superior imaging-guided cancer synergistic therapy. This work stimulates the development of advanced PS for the biomedical application and solid-state intramolecular motions.

Base placement optimization (BPO) is a fundamental capability for mobile manipulation and has been researched for decades. However, it is still very challenging for some reasons. First, compared with humans, current robots are extremely inflexible, and therefore have higher requirements on the accuracy of base placements (BPs). Second, the BP and task constraints are coupled with each other. The optimal BP depends on the task constraints, and in BP will affect task constraints in turn. More tricky is that some task constraints are flexible and non-deterministic. Third, except for fulfilling tasks, some other performance metrics such as optimal energy consumption and minimal execution time need to be considered, which makes the BPO problem even more complicated. In this paper, a Scale-like disc (SLD) representation of the workspace is used to decouple task constraints and BPs. To evaluate reachability and return optimal working pose over SLDs, a reachability map (RM) is constructed offline. In order to optimize the objectives of coverage, manipulability, and time cost simultaneously, this paper formulates the BPO as a multi-objective optimization problem (MOOP). Among them, the time optimal objective is modeled as a traveling salesman problem (TSP), which is more in line with the actual situation. The evolutionary method is used to solve the MOOP. Besides, to ensure the validity and optimality of the solution, collision detection is performed on the candidate BPs, and solutions from BPO are further fine-tuned according to the specific given task. Finally, the proposed method is used to solve a real-world toilet coverage cleaning task. Experiments show that the optimized BPs can significantly improve the coverage and efficiency of the task., Comment: 6 pages

In the era of Artificial Intelligence Generated Content (AIGC), conditional multimodal synthesis technologies (e.g., text-to-image, text-to-video, text-to-audio, etc) are gradually reshaping the natural content in the real world. The key to multimodal synthesis technology is to establish the mapping relationship between different modalities. Brain signals, serving as potential reflections of how the brain interprets external information, exhibit a distinctive One-to-Many correspondence with various external modalities. This correspondence makes brain signals emerge as a promising guiding condition for multimodal content synthesis. Brian-conditional multimodal synthesis refers to decoding brain signals back to perceptual experience, which is crucial for developing practical brain-computer interface systems and unraveling complex mechanisms underlying how the brain perceives and comprehends external stimuli. This survey comprehensively examines the emerging field of AIGC-based Brain-conditional Multimodal Synthesis, termed AIGC-Brain, to delineate the current landscape and future directions. To begin, related brain neuroimaging datasets, functional brain regions, and mainstream generative models are introduced as the foundation of AIGC-Brain decoding and analysis. Next, we provide a comprehensive taxonomy for AIGC-Brain decoding models and present task-specific representative work and detailed implementation strategies to facilitate comparison and in-depth analysis. Quality assessments are then introduced for both qualitative and quantitative evaluation. Finally, this survey explores insights gained, providing current challenges and outlining prospects of AIGC-Brain. Being the inaugural survey in this domain, this paper paves the way for the progress of AIGC-Brain research, offering a foundational overview to guide future work.

The seminal work of Ahn, Guha, and McGregor in 2012 introduced the graph sketching technique and used it to present the first streaming algorithms for various graph problems over dynamic streams with both insertions and deletions of edges. This includes algorithms for cut sparsification, spanners, matchings, and minimum spanning trees (MSTs). These results have since been improved or generalized in various directions, leading to a vastly rich host of efficient algorithms for processing dynamic graph streams. A curious omission from the list of improvements has been the MST problem. The best algorithm for this problem remains the original AGM algorithm that for every integer $p \geq 1$, uses $n^{1+O(1/p)}$ space in $p$ passes on $n$-vertex graphs, and thus achieves the desired semi-streaming space of $\tilde{O}(n)$ at a relatively high cost of $O(\frac{\log{n}}{\log\log{n}})$ passes. On the other hand, no lower bounds beyond a folklore one-pass lower bound is known for this problem. We provide a simple explanation for this lack of improvements: The AGM algorithm for MSTs is optimal for the entire range of its number of passes! We prove that even for the simplest decision version of the problem -- deciding whether the weight of MSTs is at least a given threshold or not -- any $p$-pass dynamic streaming algorithm requires $n^{1+\Omega(1/p)}$ space. This implies that semi-streaming algorithms do need $\Omega(\frac{\log{n}}{\log\log{n}})$ passes. Our result relies on proving new multi-round communication complexity lower bounds for a variant of the universal relation problem that has been instrumental in proving prior lower bounds for single-pass dynamic streaming algorithms. The proof also involves proving new composition theorems in communication complexity, including majority lemmas and multi-party XOR lemmas, via information complexity approaches.

Analysis of human actions in videos demands understanding complex human dynamics, as well as the interaction between actors and context. However, these interaction relationships usually exhibit large intra-class variations from diverse human poses or object manipulations, and fine-grained inter-class differences between similar actions. Thus the performance of existing methods is severely limited. Motivated by the observation that interactive actions can be decomposed into actor dynamics and participating objects or humans, we propose to investigate the composite property of them. In this paper, we present a novel Grammatical Compositional Model (GCM) for action detection based on typical And-Or graphs. Our model exploits the intrinsic structures and latent relationships of actions in a hierarchical manner to harness both the compositionality of grammar models and the capability of expressing rich features of DNNs. The proposed model can be readily embodied into a neural network module for efficient optimization in an end-to-end manner. Extensive experiments are conducted on the AVA dataset and the Something-Else task to demonstrate the superiority of our model, meanwhile the interpretability is enhanced through an inference parsing procedure.

Image reconstruction and captioning from brain activity evoked by visual stimuli allow researchers to further understand the connection between the human brain and the visual perception system. While deep generative models have recently been employed in this field, reconstructing realistic captions and images with both low-level details and high semantic fidelity is still a challenging problem. In this work, we propose UniBrain: Unify Image Reconstruction and Captioning All in One Diffusion Model from Human Brain Activity. For the first time, we unify image reconstruction and captioning from visual-evoked functional magnetic resonance imaging (fMRI) through a latent diffusion model termed Versatile Diffusion. Specifically, we transform fMRI voxels into text and image latent for low-level information and guide the backward diffusion process through fMRI-based image and text conditions derived from CLIP to generate realistic captions and images. UniBrain outperforms current methods both qualitatively and quantitatively in terms of image reconstruction and reports image captioning results for the first time on the Natural Scenes Dataset (NSD) dataset. Moreover, the ablation experiments and functional region-of-interest (ROI) analysis further exhibit the superiority of UniBrain and provide comprehensive insight for visual-evoked brain decoding.

Molecular motions are ubiquitous in nature and they immutably play intrinsic roles in all actions. However, exploring appropriate models to decipher molecular motions is an extremely important but very challenging task for researchers. Considering aggregation-induced emission (AIE) luminogens possess their unique merits to visualize molecular motions, it is particularly fascinating to construct new AIE systems as models to study molecular motion. Herein, a novel quinolizine (QLZ) AIE system was constructed based on the restriction intramolecular vibration (RIV) mechanism. It was demonstrated that QLZ could act as an ideal model to visualize single-molecule motion and macroscopic molecular motion via fluorescence change. Additionally, further elaborate tailoring of this impressive core achieved highly efficient reactive oxygen species production and realized fluorescence imaging-guided photodynamic therapy applications, which confirms the great application potential of this new AIE-active QLZ core. Therefore, this work not only provides an ideal model to visualize molecular motion but also opens a new way for the application of AIEgens. © 2022 Wiley-VCH GmbH

Molecular motions are ubiquitous in nature and they immutably play intrinsic roles in all actions. However, exploring appropriate models to decipher molecular motions is an extremely important but very challenging task for researchers. Considering aggregation-induced emission (AIE) luminogens possess their unique merits to visualize molecular motions, it is particularly fascinating to construct new AIE systems as models to study molecular motion. Herein, a novel quinolizine (QLZ) AIE system was constructed based on the restriction intramolecular vibration (RIV) mechanism. It was demonstrated that QLZ could act as an ideal model to visualize single-molecule motion and macroscopic molecular motion via fluorescence change. Additionally, further elaborate tailoring of this impressive core achieved highly efficient reactive oxygen species production and realized fluorescence imaging-guided photodynamic therapy applications, which confirms the great application potential of this new AIE-active QLZ core. Therefore, this work not only provides an ideal model to visualize molecular motion but also opens a new way for the application of AIEgens. © 2022 Wiley-VCH GmbH

In neuropathic pain (NP), injury or diseases of the somatosensory system often result in highly debilitating chronic pain. Currently, there is no effective drug for the complete and definitive treatment of NP. We investigated the therapeutic potential of conditioned medium (CM) derived from stem cells from human exfoliated deciduous teeth (SHED-CM) against NP using a mouse partial sciatic nerve ligation (PSL) model. Abnormal pain sensation, such as tactile allodynia and hyperalgesia, can be caused by PSL. In the behavioral test, intravenous administration of SHED-CM greatly improved the PSL-induced hypersensitivity. We found that treatment with SHED-CM resulted in the recruitment of M2 macrophages in the injured sciatic nerve and ipsilateral L4/L5 dorsal root ganglion and suppressed microglial activation in the spinal cord. Notably, specific depletion of the anti-inflammatory M2 macrophages by mannosylated-Clodrosome markedly reduced the antinociceptive effect of SHED-CM. Intravenous administration of CM from M2 induced by SHED-CM (M2-CM) ameliorated the PSL-induced hypersensitivity. We found that M2-CM directly suppressed the expression of nociceptive receptors as well as proinflammatory mediators in Schwann cells. Taken together, our data suggest that SHED-CM ameliorates NP through the induction of the analgesic anti-inflammatory M2 macrophages. Thus, SHED-CM may be a novel therapeutic candidate for NP.

In neuropathic pain (NP), injury or diseases of the somatosensory system often result in highly debilitating chronic pain. Currently, there is no effective drug for the complete and definitive treatment of NP. We investigated the therapeutic potential of conditioned medium (CM) derived from stem cells from human exfoliated deciduous teeth (SHED-CM) against NP using a mouse partial sciatic nerve ligation (PSL) model. Abnormal pain sensation, such as tactile allodynia and hyperalgesia, can be caused by PSL. In the behavioral test, intravenous administration of SHED-CM greatly improved the PSL-induced hypersensitivity. We found that treatment with SHED-CM resulted in the recruitment of M2 macrophages in the injured sciatic nerve and ipsilateral L4/L5 dorsal root ganglion and suppressed microglial activation in the spinal cord. Notably, specific depletion of the anti-inflammatory M2 macrophages by mannosylated-Clodrosome markedly reduced the antinociceptive effect of SHED-CM. Intravenous administration of CM from M2 induced by SHED-CM (M2-CM) ameliorated the PSL-induced hypersensitivity. We found that M2-CM directly suppressed the expression of nociceptive receptors as well as proinflammatory mediators in Schwann cells. Taken together, our data suggest that SHED-CM ameliorates NP through the induction of the analgesic anti-inflammatory M2 macrophages. Thus, SHED-CM may be a novel therapeutic candidate for NP.

We consider the problem of finding a maximal independent set (MIS) in the shared blackboard communication model with vertex-partitioned inputs. There are $n$ players corresponding to vertices of an undirected graph, and each player sees the edges incident on its vertex -- this way, each edge is known by both its endpoints and is thus shared by two players. The players communicate in simultaneous rounds by posting their messages on a shared blackboard visible to all players, with the goal of computing an MIS of the graph. While the MIS problem is well studied in other distributed models, and while shared blackboard is, perhaps, the simplest broadcast model, lower bounds for our problem were only known against one-round protocols. We present a lower bound on the round-communication tradeoff for computing an MIS in this model. Specifically, we show that when $r$ rounds of interaction are allowed, at least one player needs to communicate $\Omega(n^{1/20^{r+1}})$ bits. In particular, with logarithmic bandwidth, finding an MIS requires $\Omega(\log\log{n})$ rounds. This lower bound can be compared with the algorithm of Ghaffari, Gouleakis, Konrad, Mitrovi\'c, and Rubinfeld [PODC 2018] that solves MIS in $O(\log\log{n})$ rounds but with a logarithmic bandwidth for an average player. Additionally, our lower bound further extends to the closely related problem of maximal bipartite matching. To prove our results, we devise a new round elimination framework, which we call partial-input embedding, that may also be useful in future work for proving round-sensitive lower bounds in the presence of edge-sharing between players. Finally, we discuss several implications of our results to multi-round (adaptive) distributed sketching algorithms, broadcast congested clique, and to the welfare maximization problem in two-sided matching markets., Comment: Full version of the paper in FOCS 2022, 44 pages

Learning-based methods have effectively promoted the community of image compression. Meanwhile, variational autoencoder (VAE) based variable-rate approaches have recently gained much attention to avoid the usage of a set of different networks for various compression rates. Despite the remarkable performance that has been achieved, these approaches would be readily corrupted once multiple compression/decompression operations are executed, resulting in the fact that image quality would be tremendously dropped and strong artifacts would appear. Thus, we try to tackle the issue of high-fidelity fine variable-rate image compression and propose the Invertible Activation Transformation (IAT) module. We implement the IAT in a mathematical invertible manner on a single rate Invertible Neural Network (INN) based model and the quality level (QLevel) would be fed into the IAT to generate scaling and bias tensors. IAT and QLevel together give the image compression model the ability of fine variable-rate control while better maintaining the image fidelity. Extensive experiments demonstrate that the single rate image compression model equipped with our IAT module has the ability to achieve variable-rate control without any compromise. And our IAT-embedded model obtains comparable rate-distortion performance with recent learning-based image compression methods. Furthermore, our method outperforms the state-of-the-art variable-rate image compression method by a large margin, especially after multiple re-encodings., Comment: Accept to ACMMM2022

Human-Object Interactions (HOI) detection, which aims to localize a human and a relevant object while recognizing their interaction, is crucial for understanding a still image. Recently, transformer-based models have significantly advanced the progress of HOI detection. However, the capability of these models has not been fully explored since the Object Query of the model is always simply initialized as just zeros, which would affect the performance. In this paper, we try to study the issue of promoting transformer-based HOI detectors by initializing the Object Query with category-aware semantic information. To this end, we innovatively propose the Category-Aware Transformer Network (CATN). Specifically, the Object Query would be initialized via category priors represented by an external object detection model to yield better performance. Moreover, such category priors can be further used for enhancing the representation ability of features via the attention mechanism. We have firstly verified our idea via the Oracle experiment by initializing the Object Query with the groundtruth category information. And then extensive experiments have been conducted to show that a HOI detection model equipped with our idea outperforms the baseline by a large margin to achieve a new state-of-the-art result., Comment: Accepted by CVPR2022

While Human-Object Interaction(HOI) Detection has achieved tremendous advances in recent, it still remains challenging due to complex interactions with multiple humans and objects occurring in images, which would inevitably lead to ambiguities. Most existing methods either generate all human-object pair candidates and infer their relationships by cropped local features successively in a two-stage manner, or directly predict interaction points in a one-stage procedure. However, the lack of spatial configurations or reasoning steps of two- or one- stage methods respectively limits their performance in such complex scenes. To avoid this ambiguity, we propose a novel actor-centric framework. The main ideas are that when inferring interactions: 1) the non-local features of the entire image guided by actor position are obtained to model the relationship between the actor and context, and then 2) we use an object branch to generate pixel-wise interaction area prediction, where the interaction area denotes the object central area. Moreover, we also use an actor branch to get interaction prediction of the actor and propose a novel composition strategy based on center-point indexing to generate the final HOI prediction. Thanks to the usage of the non-local features and the partly-coupled property of the human-objects composition strategy, our proposed framework can detect HOI more accurately especially for complex images. Extensive experimental results show that our method achieves the state-of-the-art on the challenging V-COCO and HICO-DET benchmarks and is more robust especially in multiple persons and/or objects scenes., Comment: 11 pages

Molecular motions are ubiquitous in nature and they immutably play intrinsic roles in all actions. However, exploring appropriate models to decipher molecular motions is an extremely important but very challenging task for researchers. Considering aggregation-induced emission (AIE) luminogens possess their unique merits to visualize molecular motions, it is particularly fascinating to construct new AIE systems as models to study molecular motion. Herein, a novel quinolizine (QLZ) AIE system was constructed based on the restriction intramolecular vibration (RIV) mechanism. It was demonstrated that QLZ could act as an ideal model to visualize single-molecule motion and macroscopic molecular motion via fluorescence change. Additionally, further elaborate tailoring of this impressive core achieved highly efficient reactive oxygen species production and realized fluorescence imaging-guided photodynamic therapy applications, which confirms the great application potential of this new AIE-active QLZ core. Therefore, this work not only provides an ideal model to visualize molecular motion but also opens a new way for the application of AIEgens. © 2022 Wiley-VCH GmbH

In recent years, two-photon photodynamic therapy (TP-PDT) has received extensive attention in cancer treatment owing to its unique advantages of deep tissue penetration and high spatial–temporal controls. However, the high oxygen dependency of photosensitizers still remained as the major obstacle which undermined its overall therapeutic efficacy, especially in hypoxic-tolerant tumors. Exploration of new TP-PDT strategy with less-oxygendependency and subcellular organelle-targeting ability is an appealing yet seriously challenging task. In this work, a mitochondrion-targeting TP-PDT protocol based on type-I PSs with aggregation-induced emission (AIE) characteristics is proposed for the first time. Of the two synthesized AIE-active PSs, TPABP-Ir is demonstrated superior reactive oxygen species (ROS) production (both type I&II) owing to the doping of Ir(III). After encapsulation into bovine serum albumin (BSA) matrix, TPABP-Ir@BSA nanoparticles (Ir-NPs) are capable of realizing mitochondrion-targeting, high ROS production, and suppression of tumor growth under 880 nm femtosecond laser excitation. This study provides a novel treatment strategy which maximizes the PDT efficacy and offers a conceptual but practical paradigm for cancer treatment in translational nanomedicine.

Yingying Yin,1,2 Chunming Xie,3 Haisan Zhang,4 Hongxing Zhang,5 Zhijun Zhang,3 Yonggui Yuan1,2 1Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2Institute of Psychosomatics, Medical School of Southeast University, Nanjing, 210009, People’s Republic of China; 3Department of Neurology, ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China; 4Departments of Clinical Magnetic Resonance Imaging, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453002, People’s Republic of China; 5Departments of Psychiatry, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453002, People’s Republic of ChinaCorrespondence: Yonggui Yuan; Yingying Yin, Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Nanjing, 210009, People’s Republic of China, Email yygylh2000@sina.com; 348281107@qq.comBackground: Previous studies revealed different cerebral blood flow (CBF) changes of major depressive disorder (MDD) patients with psychomotor retardation (PMR). These different changes might result from the modulation of other factors, such as genes. This study aimed to investigate the influence of COMT Val158Met polymorphism on the CBF alterations in MDD patients with PMR.Methods: COMT Val158Met genotypes and arterial spin labeling-magnetic resonance imaging (ASL-MRI) data of 103 Chinese Han participants (63 MDD, 40 NCs) were collected in this study. MDD patients were divided into PMR group (N = 23) and NPMR group (N = 40) according to the Salpetriere Retardation Rating Scale score. PMR, NPMR and NCs groups were further divided into two subgroups, respectively, based on the COMT Val158Met genotype. CBF throughout the whole brain was calculated based on the ASL-MRI data. A two-way factorial analysis

The development of multifunctional nanoplatforms has been recognized as a promising strategy for potent photodynamic theranostics. Aggregation-induced emission (AIE) photosensitizers undergoing Type-I reactive oxygen species (ROS) generation pathway appear as potential candidates due to their capability of hypoxia-tolerance, efficient ROS production, and fluorescence imaging navigation. To further improve their performance, a facile and universal method of constructing a type of glutathione (GSH)-depleting and near-infrared (NIR)-regulated nanoplatform for dual-modal imaging-guided photodynamic therapy (PDT) is presented. The nanoplatforms are obtained through the coprecipitation process involving upconversion nanoparticles (UCNPs) and AIE-active photosensitizers, followed by in situ generation of MnO2 as the outer shell. The introduction of UCNPs actualizes the NIR-activation of AIE-active photosensitizers to produce ·OH as a Type-I ROS. Intracellular upregulated GSH-responsive decomposition of the MnO2 shell to Mn2+ realizes GSH-depletion, which is a distinctive approach for elevating intracellular ·OH. Meanwhile, the generated Mn2+ can implement T1-weighted magnetic resonance imaging (MRI) in specific tumor sites, and mediate the conversion of intracellular H2O2 to ·OH. These outputs reveal a triple-jump ·OH production, and this approach brings about distinguished performance in FLI-MRI-guided PDT with high-efficacy, which presents great potential for future clinical translations. © 2021 Wiley-VCH GmbH

Intersystem crossing (ISC) is of great significance in photochemistry, and has a decisive influence on the properties of photosensitizers (PSs) for use in photodynamic therapy (PDT). However, the rationally design PSs with efficient ISC processes to implement superb reactive oxygen species (ROS) production is still a very challenging work. In this contribution, we described how a series of high-performance PSs were constructed through electron acceptor and donor engineering by integrating the smaller singlet-triplet energy gap (Delta EST) and larger spin-orbit coupling (SOC)-beneficial functional groups into the PS frameworks. Among the yielded various PSs, TaTIC was confirmed as the best candidate for application in PDT, which was due to its most outstanding ROS generation capability, bright near-infrared (NIR) fluorescence with peak over 840 nm, as well as desired aggregationinduced emission (AIE) features. Importantly, the ROS generation efficiency of TaTIC was even superior to that of some popularly used PSs, including the most reputable PS of Rose Bengal. In order to further extend therapeutic applications, TaTIC was encapsulated with biocompatible amphiphilic matrix and formulated into water-dispersed nanoparticles (NPs). More excitedly, the as-prepared TaTIC NPs gave wonderful PDT performance on tumor-bearing mouse model, actualizing complete tumor elimination outcomes. Coupled with excellent biosecurity, TaTIC NPs would be a promising theranostic agent for practical clinical application.

Phototheranostics involving both fluorescence imaging and photodynamic therapy has been recognized to be potentially powerful for cancer treatment by virtue of various intrinsic advantages. However, the state-of-the-art materials in this area are still far from ideal toward practical applications, ascribed to their respective and collective drawbacks, such as inefficient imaging quality, inferior reactive oxygen species (ROS) production, the lack of subcellular-targeting capability, and dissatisfactory delivery. In this paper, these shortcomings are successfully addressed through the integration of finely engineered photosensitizers with aggregation-induced emission (AIE) features and well tailored nanocarrier systems. The yielded AIE NPs simultaneously exhibit broad absorption in the visible-light region, bright near-infrared fluorescence emission, high ROS generation, as well as tumor lysosomal acidity-activated and nucleus-targeted delivery functions, making them promising for precise and efficient phototheranostics. Both in vitro and in vivo evaluations show that the presented nanotheranostic systems bearing good photostability and appreciable biosecurity perform well in fluorescence imaging-guided photodynamic cancer therapy. This study thus not only extends the application scopes of AIE nanomaterials but also offers useful insights into constructing advanced cancer phototheranostics.

Photodynamic therapy (PDT) has long been recognized to be a promising approach for cancer treatment. However, the high oxygen dependency of conventional PDT dramatically impairs its overall therapeutic efficacy, especially in hypoxic solid tumors. Exploration of distinctive PDT strategy involving both high-performance less-oxygen-dependent photosensitizers (PSs) and prominent drug delivery system is an appealing yet significantly challenging task. Herein, a precise nuclear targeting PDT protocol based on type-I PSs with aggregation-induced emission (AIE) characteristics is fabricated for the first time. Of the two synthesized AIE PSs, TTFMN is demonstrated to exhibit superior AIE property and stronger type-I reactive oxygen species (ROS) generation efficiency owing to the introduction of tetraphenylethylene and smaller singlet–triplet energy gap, respectively. With the aid of a lysosomal acid-activated TAT-peptide-modified amphiphilic polymer poly(lactic acid)12k–poly(ethylene glycol)5k–succinic anhydride-modified TAT, the corresponding TTFMN-loaded nanoparticles accompanied with acid-triggered nuclear targeting peculiarity can quickly accumulate in the tumor site, effectively generate type-I ROS in the nuclear region and significantly suppress the tumor growth under white light irradiation with minimized systematic toxicity. This delicate “Good Steel Used in the Blade” tactic significantly maximizes the PDT efficacy and offers a conceptual while practical paradigm for optimized cancer treatment in further translational medicine. © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH

Construction of single component theranostic agent with one-for-all features to concurrently afford both multi-modality imaging and therapy is an appealing yet significantly challenging task. Herein, a type of luminogens with aggregation-induced emission (AIE) characteristics are tactfully designed and facilely synthesized. These AIE luminogens (AIEgens) exhibit long emission wavelengths, good photostability, remarkable biocompatibility, good reactive oxygen species (ROS) generation performance and excellent photothermal conversion efficiency, which allow them to be powerfully utilized for in vitro and in vivo cancer phototheranostics. The results show that one of the AIEgens is capable of precisely diagnosing solid tumors of mice by means of combined near-infrared-I/II (NIR-I/II) fluorescence-photoacoustic imaging, meanwhile this AIEgen can activate photodynamic and photothermal synergistic therapy (PDT-PTT) upon laser irradiation, resulting in excellent tumor elimination efficacy with only once injection and irradiation. This study thus provides a versatile platform for practical cancer theranostics. © 2021 Elsevier Ltd

Supramolecular approaches have opened up vast possibilities to construct versatile materials, especially those with stimuli-responsiveness and integrated functionalities of multi-modal diagnosis and synergistic therapeutics. In this study, a hybrid theranostic nanosystem named TTPY-Py⊂CP5@AuNR is constructed via facile host–guest interactions, where TTPY-Py is a photosensitizer with aggregation-induced emission and CP5@AuNR represents the carboxylatopillar[5]arene (CP5)-modified Au nanorods. TTPY-Py⊂CP5@AuNR integrates the respective advantages of TTPY-Py and CP5@AuNR such as the high performance of reactive oxygen species generation and photothermal conversion, and meanwhile shows fluorescence responses to both temperature and pH stimuli. The successful modification of CP5 macrocycles on AuNRs surfaces can eliminate the cytotoxicity of AuNRs and enable them to serve as the nanocarrier of TTPY-Py for further theranostic applications. Significantly, in vitro and in vivo evaluations demonstrate that this supramolecular nanotheranostic system possesses multiple modalities including intensive fluorescence imaging (FLI), photoacoustic imaging (PAI), efficient photodynamic therapy (PDT), and photothermal therapy (PTT), indicating its great potential for FLI-PAI imaging-guided synergistic PDT-PTT therapy. Moreover, TTPY-Py can be released upon activation by the acidic environment of lysosomes and then specifically light up mitochondria. This study demonstrates a new strategy for the design of versatile nanotheranostics for accurate tumor imaging and cancer therapies. © 2021 Wiley-VCH GmbH

Fluorescence imaging in the second near-infrared region (NIR-II) can penetrate tissue at centimeter depths and obtain high image fidelity. However, facile synthesis of small-molecule fluorescent photosensitizers for efficient NIR-II fluorescence imaging as well as photodynamic and photothermal combinatorial therapies is still a challenging task. Herein, a rational design and facile synthesis protocol are reported for a series of novel NIR-emissive zwitterionic luminogens with aggregation-induced emission (AIE) features for cancer phototheranostics. Consistent with the intrinsic features including long emission wavelength, effective reactive oxygen species generation, and excellent photothermal conversion efficiency (35.76%), in vitro and in vivo evaluation show that one of these presented AIE luminogens provides excellent performance in NIR-II fluorescence imaging-guided synergistic phototherapy against cancer. © 2020 Wiley-VCH GmbH

The development of multifunctional nanoplatforms has been recognized as a promising strategy for potent photodynamic theranostics. Aggregation-induced emission (AIE) photosensitizers undergoing Type-I reactive oxygen species (ROS) generation pathway appear as potential candidates due to their capability of hypoxia-tolerance, efficient ROS production, and fluorescence imaging navigation. To further improve their performance, a facile and universal method of constructing a type of glutathione (GSH)-depleting and near-infrared (NIR)-regulated nanoplatform for dual-modal imaging-guided photodynamic therapy (PDT) is presented. The nanoplatforms are obtained through the coprecipitation process involving upconversion nanoparticles (UCNPs) and AIE-active photosensitizers, followed by in situ generation of MnO2 as the outer shell. The introduction of UCNPs actualizes the NIR-activation of AIE-active photosensitizers to produce ·OH as a Type-I ROS. Intracellular upregulated GSH-responsive decomposition of the MnO2 shell to Mn2+ realizes GSH-depletion, which is a distinctive approach for elevating intracellular ·OH. Meanwhile, the generated Mn2+ can implement T1-weighted magnetic resonance imaging (MRI) in specific tumor sites, and mediate the conversion of intracellular H2O2 to ·OH. These outputs reveal a triple-jump ·OH production, and this approach brings about distinguished performance in FLI-MRI-guided PDT with high-efficacy, which presents great potential for future clinical translations. © 2021 Wiley-VCH GmbH

Intersystem crossing (ISC) is of great significance in photochemistry, and has a decisive influence on the properties of photosensitizers (PSs) for use in photodynamic therapy (PDT). However, the rationally design PSs with efficient ISC processes to implement superb reactive oxygen species (ROS) production is still a very challenging work. In this contribution, we described how a series of high-performance PSs were constructed through electron acceptor and donor engineering by integrating the smaller singlet-triplet energy gap (Delta EST) and larger spin-orbit coupling (SOC)-beneficial functional groups into the PS frameworks. Among the yielded various PSs, TaTIC was confirmed as the best candidate for application in PDT, which was due to its most outstanding ROS generation capability, bright near-infrared (NIR) fluorescence with peak over 840 nm, as well as desired aggregationinduced emission (AIE) features. Importantly, the ROS generation efficiency of TaTIC was even superior to that of some popularly used PSs, including the most reputable PS of Rose Bengal. In order to further extend therapeutic applications, TaTIC was encapsulated with biocompatible amphiphilic matrix and formulated into water-dispersed nanoparticles (NPs). More excitedly, the as-prepared TaTIC NPs gave wonderful PDT performance on tumor-bearing mouse model, actualizing complete tumor elimination outcomes. Coupled with excellent biosecurity, TaTIC NPs would be a promising theranostic agent for practical clinical application.

Phototheranostics involving both fluorescence imaging and photodynamic therapy has been recognized to be potentially powerful for cancer treatment by virtue of various intrinsic advantages. However, the state-of-the-art materials in this area are still far from ideal toward practical applications, ascribed to their respective and collective drawbacks, such as inefficient imaging quality, inferior reactive oxygen species (ROS) production, the lack of subcellular-targeting capability, and dissatisfactory delivery. In this paper, these shortcomings are successfully addressed through the integration of finely engineered photosensitizers with aggregation-induced emission (AIE) features and well tailored nanocarrier systems. The yielded AIE NPs simultaneously exhibit broad absorption in the visible-light region, bright near-infrared fluorescence emission, high ROS generation, as well as tumor lysosomal acidity-activated and nucleus-targeted delivery functions, making them promising for precise and efficient phototheranostics. Both in vitro and in vivo evaluations show that the presented nanotheranostic systems bearing good photostability and appreciable biosecurity perform well in fluorescence imaging-guided photodynamic cancer therapy. This study thus not only extends the application scopes of AIE nanomaterials but also offers useful insights into constructing advanced cancer phototheranostics.

Photodynamic therapy (PDT) has long been recognized to be a promising approach for cancer treatment. However, the high oxygen dependency of conventional PDT dramatically impairs its overall therapeutic efficacy, especially in hypoxic solid tumors. Exploration of distinctive PDT strategy involving both high-performance less-oxygen-dependent photosensitizers (PSs) and prominent drug delivery system is an appealing yet significantly challenging task. Herein, a precise nuclear targeting PDT protocol based on type-I PSs with aggregation-induced emission (AIE) characteristics is fabricated for the first time. Of the two synthesized AIE PSs, TTFMN is demonstrated to exhibit superior AIE property and stronger type-I reactive oxygen species (ROS) generation efficiency owing to the introduction of tetraphenylethylene and smaller singlet–triplet energy gap, respectively. With the aid of a lysosomal acid-activated TAT-peptide-modified amphiphilic polymer poly(lactic acid)12k–poly(ethylene glycol)5k–succinic anhydride-modified TAT, the corresponding TTFMN-loaded nanoparticles accompanied with acid-triggered nuclear targeting peculiarity can quickly accumulate in the tumor site, effectively generate type-I ROS in the nuclear region and significantly suppress the tumor growth under white light irradiation with minimized systematic toxicity. This delicate “Good Steel Used in the Blade” tactic significantly maximizes the PDT efficacy and offers a conceptual while practical paradigm for optimized cancer treatment in further translational medicine. © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH

Construction of single component theranostic agent with one-for-all features to concurrently afford both multi-modality imaging and therapy is an appealing yet significantly challenging task. Herein, a type of luminogens with aggregation-induced emission (AIE) characteristics are tactfully designed and facilely synthesized. These AIE luminogens (AIEgens) exhibit long emission wavelengths, good photostability, remarkable biocompatibility, good reactive oxygen species (ROS) generation performance and excellent photothermal conversion efficiency, which allow them to be powerfully utilized for in vitro and in vivo cancer phototheranostics. The results show that one of the AIEgens is capable of precisely diagnosing solid tumors of mice by means of combined near-infrared-I/II (NIR-I/II) fluorescence-photoacoustic imaging, meanwhile this AIEgen can activate photodynamic and photothermal synergistic therapy (PDT-PTT) upon laser irradiation, resulting in excellent tumor elimination efficacy with only once injection and irradiation. This study thus provides a versatile platform for practical cancer theranostics. © 2021 Elsevier Ltd

NV Reddy,1 Huizhen Li,1 Tianyu Hou,1 MS Bethu,2 Zhiqing Ren,1 Zhijun Zhang1 1School of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi Province, People’s Republic of China; 2Pharmacology and Toxicology Division, Indian Institute of Chemical Engineering and Technology, Hyderabad, Telangana State, IndiaCorrespondence: Zhijun ZhangSchool of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi Province 030051, People’s Republic of ChinaEmail sxzzj@163.comPurpose: The present study investigates the phytosynthesis of silver nanoparticles (AgNPs) using Perilla frutescens leaf extract, which acts as a reducing agent for the conversion of silver ions (Ag+) into AgNPs. P. frutescens leaf synthesized AgNPs (PF@AgNPs) were evaluated for biomedical properties including antibacterial, antioxidant and anticancer activities.Materials and Methods: PF@AgNPs were synthesized using P. frutescens leaf extract and silver nitrate solution. The morphology and physical properties of PF@AgNPs were studied by spectroscopic techniques including, UV-Vis, FTIR, TEM, XRD, DLS, and TGA. Antibacterial activity of PF@AgNPs was evaluated by disk diffusion assay. Antioxidant activity of PF@AgNPs was checked by 2.2-diphenyl-1-picrylhydrazyl (DPPH), and 2.2ʹ-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging assays. Anticancer activity of PF@AgNPs was checked by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Cytotoxic effects of PF@AgNPs on most susceptible cancer cell lines were observed by phase contrast microscopy.Results: PF@AgNPs showed surface plasmon resonance peak at 461 nm. XRD pattern showed that the PF@AgNPs were face-centered cubic crystals with a mean size of 25.71 nm. TEM analysis revealed the different shapes (spherical, rhombic, triangle, and rod) of PF@AgNPs. Zeta potential value (− 25.83 mV) indicated that PF@AgNPs were long-term stable and not

The behaviors of grain growth dominate the formation of the microstructure inside polycrystalline materials and thus strongly influence their practical performances. However, grain growth behaviors still remain ambiguous and thus lack a mathematical formula to describe the general evolution despite decades of efforts. Here, we propose a new migration model of grain boundary (GB) and further derive a mathematical expression to depict the general evolution of grain growth in the cellular structures. The expression incorporates the variables influencing growth rate (e.g. GB features, grain size and local grain size distribution) and thus reveals how the normal, abnormal and stagnant behaviors of grain growth occur in polycrystalline systems. In addition, our model correlates quantitatively GB roughening transition with grain growth behavior. The general growth theory may provide new insights into the GB thermodynamics and kinetics during the cellular structure evolution.

Episodic memory (EM) deficit is the core cognitive dysfunction of amnestic mild cognitive impairment (aMCI). However, the episodic retrieval pattern detected by functional MRI (fMRI) appears preserved in aMCI subjects. To address this discrepancy, simultaneous electroencephalography (EEG)-fMRI recording was employed to determine whether temporal dynamics of brain episodic retrieval activity were disturbed in patients with aMCI. Twenty-six aMCI and 29 healthy control (HC) subjects completed a word-list memory retrieval task during simultaneous EEG-fMRI. The retrieval success activation pattern was detected with fMRI analysis, and the familiarity- and recollection-related components of episodic retrieval activity were identified using event-related potential (ERP) analysis. The fMRI-constrained ERP analysis explored the temporal dynamics of brain activity in the retrieval success pattern, and the ERP-informed fMRI analysis detected fMRI correlates of the ERP components related to familiarity and recollection processes. The two groups exhibited similar retrieval success patterns in the bilateral posteromedial parietal cortex, the left inferior parietal lobule (IPL), and the left lateral prefrontal cortex (LPFC). The fMRI-constrained ERP analysis showed that the aMCI group did not exhibit old/new effects in the IPL and LPFC that were observed in the HC group. In addition, the aMCI group showed disturbed fMRI correlate of ERP recollection component that was associated with inferior EM performance. Therefore, in this study, we identified disturbed temporal dynamics in episodic retrieval activity with a preserved spatial activity pattern in aMCI. Taken together, the simultaneous EEG-fMRI technique demonstrated the potential to identify individuals with a high risk of cognitive deterioration.

NV Reddy,1 Huizhen Li,1 Tianyu Hou,1 MS Bethu,2 Zhiqing Ren,1 Zhijun Zhang1 1School of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi Province, People’s Republic of China; 2Pharmacology and Toxicology Division, Indian Institute of Chemical Engineering and Technology, Hyderabad, Telangana State, IndiaCorrespondence: Zhijun ZhangSchool of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi Province 030051, People’s Republic of ChinaEmail sxzzj@163.comPurpose: The present study investigates the phytosynthesis of silver nanoparticles (AgNPs) using Perilla frutescens leaf extract, which acts as a reducing agent for the conversion of silver ions (Ag+) into AgNPs. P. frutescens leaf synthesized AgNPs (PF@AgNPs) were evaluated for biomedical properties including antibacterial, antioxidant and anticancer activities.Materials and Methods: PF@AgNPs were synthesized using P. frutescens leaf extract and silver nitrate solution. The morphology and physical properties of PF@AgNPs were studied by spectroscopic techniques including, UV-Vis, FTIR, TEM, XRD, DLS, and TGA. Antibacterial activity of PF@AgNPs was evaluated by disk diffusion assay. Antioxidant activity of PF@AgNPs was checked by 2.2-diphenyl-1-picrylhydrazyl (DPPH), and 2.2ʹ-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging assays. Anticancer activity of PF@AgNPs was checked by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Cytotoxic effects of PF@AgNPs on most susceptible cancer cell lines were observed by phase contrast microscopy.Results: PF@AgNPs showed surface plasmon resonance peak at 461 nm. XRD pattern showed that the PF@AgNPs were face-centered cubic crystals with a mean size of 25.71 nm. TEM analysis revealed the different shapes (spherical, rhombic, triangle, and rod) of PF@AgNPs. Zeta potential value (− 25.83 mV) indicated that PF@AgNPs were long-term stable and not

Detecting oriented objects along with estimating their rotation information is one crucial step for analyzing remote sensing images. Despite that many methods proposed recently have achieved remarkable performance, most of them directly learn to predict object directions under the supervision of only one (e.g. the rotation angle) or a few (e.g. several coordinates) groundtruth values individually. Oriented object detection would be more accurate and robust if extra constraints, with respect to proposal and rotation information regression, are adopted for joint supervision during training. To this end, we innovatively propose a mechanism that simultaneously learns the regression of horizontal proposals, oriented proposals, and rotation angles of objects in a consistent manner, via naive geometric computing, as one additional steady constraint (see Figure 1). An oriented center prior guided label assignment strategy is proposed for further enhancing the quality of proposals, yielding better performance. Extensive experiments demonstrate the model equipped with our idea significantly outperforms the baseline by a large margin to achieve a new state-of-the-art result without any extra computational burden during inference. Our proposed idea is simple and intuitive that can be readily implemented. Source codes and trained models are involved in supplementary files.

The development of multifunctional nanoplatforms has been recognized as a promising strategy for potent photodynamic theranostics. Aggregation-induced emission (AIE) photosensitizers undergoing Type-I reactive oxygen species (ROS) generation pathway appear as potential candidates due to their capability of hypoxia-tolerance, efficient ROS production, and fluorescence imaging navigation. To further improve their performance, a facile and universal method of constructing a type of glutathione (GSH)-depleting and near-infrared (NIR)-regulated nanoplatform for dual-modal imaging-guided photodynamic therapy (PDT) is presented. The nanoplatforms are obtained through the coprecipitation process involving upconversion nanoparticles (UCNPs) and AIE-active photosensitizers, followed by in situ generation of MnO2 as the outer shell. The introduction of UCNPs actualizes the NIR-activation of AIE-active photosensitizers to produce ·OH as a Type-I ROS. Intracellular upregulated GSH-responsive decomposition of the MnO2 shell to Mn2+ realizes GSH-depletion, which is a distinctive approach for elevating intracellular ·OH. Meanwhile, the generated Mn2+ can implement T1-weighted magnetic resonance imaging (MRI) in specific tumor sites, and mediate the conversion of intracellular H2O2 to ·OH. These outputs reveal a triple-jump ·OH production, and this approach brings about distinguished performance in FLI-MRI-guided PDT with high-efficacy, which presents great potential for future clinical translations. © 2021 Wiley-VCH GmbH

Photodynamic therapy (PDT) has long been recognized to be a promising approach for cancer treatment. However, the high oxygen dependency of conventional PDT dramatically impairs its overall therapeutic efficacy, especially in hypoxic solid tumors. Exploration of distinctive PDT strategy involving both high-performance less-oxygen-dependent photosensitizers (PSs) and prominent drug delivery system is an appealing yet significantly challenging task. Herein, a precise nuclear targeting PDT protocol based on type-I PSs with aggregation-induced emission (AIE) characteristics is fabricated for the first time. Of the two synthesized AIE PSs, TTFMN is demonstrated to exhibit superior AIE property and stronger type-I reactive oxygen species (ROS) generation efficiency owing to the introduction of tetraphenylethylene and smaller singlet–triplet energy gap, respectively. With the aid of a lysosomal acid-activated TAT-peptide-modified amphiphilic polymer poly(lactic acid)12k–poly(ethylene glycol)5k–succinic anhydride-modified TAT, the corresponding TTFMN-loaded nanoparticles accompanied with acid-triggered nuclear targeting peculiarity can quickly accumulate in the tumor site, effectively generate type-I ROS in the nuclear region and significantly suppress the tumor growth under white light irradiation with minimized systematic toxicity. This delicate “Good Steel Used in the Blade” tactic significantly maximizes the PDT efficacy and offers a conceptual while practical paradigm for optimized cancer treatment in further translational medicine. © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH

Fluorescence imaging in the second near-infrared region (NIR-II) can penetrate tissue at centimeter depths and obtain high image fidelity. However, facile synthesis of small-molecule fluorescent photosensitizers for efficient NIR-II fluorescence imaging as well as photodynamic and photothermal combinatorial therapies is still a challenging task. Herein, a rational design and facile synthesis protocol are reported for a series of novel NIR-emissive zwitterionic luminogens with aggregation-induced emission (AIE) features for cancer phototheranostics. Consistent with the intrinsic features including long emission wavelength, effective reactive oxygen species generation, and excellent photothermal conversion efficiency (35.76%), in vitro and in vivo evaluation show that one of these presented AIE luminogens provides excellent performance in NIR-II fluorescence imaging-guided synergistic phototherapy against cancer. © 2020 Wiley-VCH GmbH

Intersystem crossing (ISC) is of great significance in photochemistry, and has a decisive influence on the properties of photosensitizers (PSs) for use in photodynamic therapy (PDT). However, the rationally design PSs with efficient ISC processes to implement superb reactive oxygen species (ROS) production is still a very challenging work. In this contribution, we described how a series of high-performance PSs were constructed through electron acceptor and donor engineering by integrating the smaller singlet-triplet energy gap (Delta EST) and larger spin-orbit coupling (SOC)-beneficial functional groups into the PS frameworks. Among the yielded various PSs, TaTIC was confirmed as the best candidate for application in PDT, which was due to its most outstanding ROS generation capability, bright near-infrared (NIR) fluorescence with peak over 840 nm, as well as desired aggregationinduced emission (AIE) features. Importantly, the ROS generation efficiency of TaTIC was even superior to that of some popularly used PSs, including the most reputable PS of Rose Bengal. In order to further extend therapeutic applications, TaTIC was encapsulated with biocompatible amphiphilic matrix and formulated into water-dispersed nanoparticles (NPs). More excitedly, the as-prepared TaTIC NPs gave wonderful PDT performance on tumor-bearing mouse model, actualizing complete tumor elimination outcomes. Coupled with excellent biosecurity, TaTIC NPs would be a promising theranostic agent for practical clinical application.

Construction of single component theranostic agent with one-for-all features to concurrently afford both multi-modality imaging and therapy is an appealing yet significantly challenging task. Herein, a type of luminogens with aggregation-induced emission (AIE) characteristics are tactfully designed and facilely synthesized. These AIE luminogens (AIEgens) exhibit long emission wavelengths, good photostability, remarkable biocompatibility, good reactive oxygen species (ROS) generation performance and excellent photothermal conversion efficiency, which allow them to be powerfully utilized for in vitro and in vivo cancer phototheranostics. The results show that one of the AIEgens is capable of precisely diagnosing solid tumors of mice by means of combined near-infrared-I/II (NIR-I/II) fluorescence-photoacoustic imaging, meanwhile this AIEgen can activate photodynamic and photothermal synergistic therapy (PDT-PTT) upon laser irradiation, resulting in excellent tumor elimination efficacy with only once injection and irradiation. This study thus provides a versatile platform for practical cancer theranostics. © 2021 Elsevier Ltd

Phototheranostics involving both fluorescence imaging and photodynamic therapy has been recognized to be potentially powerful for cancer treatment by virtue of various intrinsic advantages. However, the state-of-the-art materials in this area are still far from ideal toward practical applications, ascribed to their respective and collective drawbacks, such as inefficient imaging quality, inferior reactive oxygen species (ROS) production, the lack of subcellular-targeting capability, and dissatisfactory delivery. In this paper, these shortcomings are successfully addressed through the integration of finely engineered photosensitizers with aggregation-induced emission (AIE) features and well tailored nanocarrier systems. The yielded AIE NPs simultaneously exhibit broad absorption in the visible-light region, bright near-infrared fluorescence emission, high ROS generation, as well as tumor lysosomal acidity-activated and nucleus-targeted delivery functions, making them promising for precise and efficient phototheranostics. Both in vitro and in vivo evaluations show that the presented nanotheranostic systems bearing good photostability and appreciable biosecurity perform well in fluorescence imaging-guided photodynamic cancer therapy. This study thus not only extends the application scopes of AIE nanomaterials but also offers useful insights into constructing advanced cancer phototheranostics.

Supramolecular approaches have opened up vast possibilities to construct versatile materials, especially those with stimuli-responsiveness and integrated functionalities of multi-modal diagnosis and synergistic therapeutics. In this study, a hybrid theranostic nanosystem named TTPY-Py⊂CP5@AuNR is constructed via facile host–guest interactions, where TTPY-Py is a photosensitizer with aggregation-induced emission and CP5@AuNR represents the carboxylatopillar[5]arene (CP5)-modified Au nanorods. TTPY-Py⊂CP5@AuNR integrates the respective advantages of TTPY-Py and CP5@AuNR such as the high performance of reactive oxygen species generation and photothermal conversion, and meanwhile shows fluorescence responses to both temperature and pH stimuli. The successful modification of CP5 macrocycles on AuNRs surfaces can eliminate the cytotoxicity of AuNRs and enable them to serve as the nanocarrier of TTPY-Py for further theranostic applications. Significantly, in vitro and in vivo evaluations demonstrate that this supramolecular nanotheranostic system possesses multiple modalities including intensive fluorescence imaging (FLI), photoacoustic imaging (PAI), efficient photodynamic therapy (PDT), and photothermal therapy (PTT), indicating its great potential for FLI-PAI imaging-guided synergistic PDT-PTT therapy. Moreover, TTPY-Py can be released upon activation by the acidic environment of lysosomes and then specifically light up mitochondria. This study demonstrates a new strategy for the design of versatile nanotheranostics for accurate tumor imaging and cancer therapies. © 2021 Wiley-VCH GmbH

One of the major pursuits of biomedical science is to develop advanced strategies for theranostics, which is expected to be an effective approach for achieving the transition from conventional medicine to precision medicine. Supramolecular assembly can serve as a powerful tool in the development of nanotheranostics with accurate imaging of tumors and real-time monitoring of the therapeutic process upon the incorporation of aggregation-induced emission (AIE) ability. AIE luminogens (AIEgens) will not only enable fluorescence imaging but will also aid in improving the efficacy of therapies. Furthermore, the fluorescent signals and therapeutic performance of these nanomaterials can be manipulated precisely owing to the reversible and stimuli-responsive characteristics of the supramolecular systems. Inspired by rapid advances in this field, recent research conducted on nanotheranostics with the AIE effect based on supramolecular assembly is summarized. Here, three representative strategies for supramolecular nanomaterials are presented as follows: a) supramolecular self-assembly of AIEgens, b) the loading of AIEgens within nanocarriers with supramolecular assembly, and c) supramolecular macrocycle-guided assembly via host–guest interactions. Meanwhile, the diverse applications of such nanomaterials in diagnostics and therapeutics have also been discussed in detail. Finally, the challenges of this field are listed in this review. © 2020 Wiley-VCH GmbH

Using reverse thinking of the aggregation-induced emission (AIE) principle, we demonstrate an ingenious and universal protocol for amplifying molecular motions to boost photothermal efficiency of fibers. Core–shell nanofibers having the olive oil solution of AIE-active molecules as the core surrounded by PVDF-HFP shell were constructed by coaxial electrospinning. The molecularly dissolved state of AIE-active molecules allows them to freely rotate and/or vibrate in nanofibers upon photoexcitation and thus significantly elevates the proportion of non-radiative energy dissipation, affording impressive heat-generating efficiency. Photothermal evaluation shows that the core–shell nanofibers with excellent durability can reach up to 22.36 % of photothermal conversion efficiency, which is 26-fold as the non-core–shell counterpart. Such a core–shell fiber can be used for photothermal textiles and solar steam generation induced by natural sunlight with green and carbon-zero emission. © 2020 Wiley-VCH GmbH

Inspired by the respective advantages of aggregation-induced emission (AIE)-active photosensitizers and black phosphorus nanomaterials in cancer treatment, the facile construction of novel AIE photosensitizers married to 2D black phosphorus nanosheets and their application for multimodal theranostics are demonstrated. The developed nanomaterial simultaneously possesses distinctive properties and multiple functions including excellent stability, good biocompatibility, intensive fluorescence emission in the NIR region, high-performance reactive oxygen species generation, good photothermal conversion efficiency, outstanding cellular uptake, and effective accumulation at the tumor site. Both in vitro and in vivo evaluation show that the presented nanotheranostic system is an excellent candidate for NIR fluorescence–photothermal dual imaging-guided synergistic photodynamic–photothermal therapies. This study thus not only extends the applications scope of AIE and black phosphorus materials, but also offers useful insights into designing a new generation of cancer theranostic protocol for potential clinical applications. © 2020 Wiley-VCH GmbH

Aiming to achieve versatile phototheranostics with the integrated functionalities of multiple diagnostic imaging and synergistic therapy, the optimum use of dissipated energy through both radiative and nonradiative pathways is definitely appealing, yet a significantly challenging task. To the best of the knowledge, there have been no previous reports on a single molecular species effective at affording all phototheranostic modalities including fluorescence imaging (FLI), photoacoustic imaging (PAI), photothermal imaging (PTI), photodynamic therapy (PDT), and photothermal therapy (PTT). Herein, a simple and highly powerful one-for-all phototheranostics based on aggregation-induced emission (AIE)-active fluorophores is tactfully designed and constructed. Thanks to its strong electron donor–acceptor interaction and finely modulated intramolecular motion, the AIE fluorophore-based nanoparticles simultaneously exhibit bright near-infrared II (NIR-II) fluorescence emission, efficient reactive oxygen species generation, and high photothermal conversion efficiency upon NIR irradiation, indicating the actualization of a balance between radiative and nonradiative energy dissipations. Furthermore, the unprecedented performance on NIR-II FLI-PAI-PTI trimodal-imaging-guided PDT–PTT synergistic therapy is demonstrated by the precise tumor diagnosis and complete tumor elimination outcomes. This study thus brings a new insight into the development of superior versatile phototheranostics for practical cancer theranostics. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Using reverse thinking of the aggregation-induced emission (AIE) principle, we demonstrate an ingenious and universal protocol for amplifying molecular motions to boost photothermal efficiency of fibers. Core–shell nanofibers having the olive oil solution of AIE-active molecules as the core surrounded by PVDF-HFP shell were constructed by coaxial electrospinning. The molecularly dissolved state of AIE-active molecules allows them to freely rotate and/or vibrate in nanofibers upon photoexcitation and thus significantly elevates the proportion of non-radiative energy dissipation, affording impressive heat-generating efficiency. Photothermal evaluation shows that the core–shell nanofibers with excellent durability can reach up to 22.36 % of photothermal conversion efficiency, which is 26-fold as the non-core–shell counterpart. Such a core–shell fiber can be used for photothermal textiles and solar steam generation induced by natural sunlight with green and carbon-zero emission. © 2020 Wiley-VCH GmbH