Enhanced Sonodynamic Therapy for Deep Tumors Using a Self-Assembled Organoplatinum(II) Sonosensitizer.

Despite the promising advances in photodynamic therapy (PDT), it remains challenging to target and treat deep-seated solid tumors effectively. Herein, we developed an organoplatinum(II) complex (Pt-TPE) with self-assembly properties for sonodynamic therapy (SDT). Pt-TPE forms a nanofiber network structure through Pt-Pt and π-π stacking interactions. Notably, under ultrasound (US), Pt-TPE demonstrates unique self-assembly-induced singlet oxygen (1O2) generation due to a significantly enhanced singlet-triplet intersystem crossing (ISC). This generation of 1O2 occurs exclusively in the self-assembled state of Pt-TPE. Additionally, Pt-TPE exhibits sono-cytotoxicity against cancer cells by impairing mitochondrial membrane potential (MMP), inhibiting glucose uptake, and aerobic glycolysis. Furthermore, US-activated Pt-TPE significantly inhibits deep solid tumors in mice, achieving remarkable therapeutic efficacy even at penetration depths greater than 10 cm. This study highlights the potential of self-assembled metal complexes to enhance the efficacy of SDT for treating deep tumors.

Tuneable stimuli-responsive behaviour, spectroscopic signatures and redox properties of indolo[3,2-b]carbazole-based diradicals.

During the last decade, there has been an increasing interest in the rationalisation of how structural changes stabilise (or destabilise) diradical systems. Demonstrated herein is that indolocarbazole (ICz) diradicals, substituted with dicyanomethylene (DCM) groups, are useful motifs for dynamic covalent chemistry by self-assembling from isolated monomers to cyclophane structures. The comparison of ICz-based systems substituted with DCM groups in para- or meta-positions (p-ICz-CN and m-ICz-CN) and their short-chain carbazole analogues (p-Cz-CN and m-Cz-CN) may identify new potential design strategies for stimuli-responsive materials. The principal objectives of this investigation are the elucidation of (i) the connection between diradical character and the cyclophane stability, (ii) the spatial disposition of the cyclophane structures, (iii) the monomer/cyclophane interconversion both in solution and solid state in response to external stimuli and (iv) the impact that the different π-conjugation and electronic communication between the DCM terminals exerts on the electronic adsorption of the diradicals and their redox behavior. The spontaneous nature of the cyclophane structure is supported by the negative relative Gibbs free energies calculated at 298 K and experimentally by UV-Vis and Raman spectroscopy of the initial yellow solid powder. The conversion to monomeric species having diradical character was demonstrated by variable-temperature (VT) EPR, UV-Vis, Raman and IR measurements, resulting in appreciable chromic changes. In addition, electrochemical oxidation and reduction convert the cyclophane dimer (m-ICz-CN)2 to the monomer monocations and dianions, respectively. This research demonstrates how the chemical reactivity and physical properties of π-conjugated diradicals can be effectively tuned by subtle changes in their chemical structures.

As Aggregation-Induced Emission Meets with Noncovalent Conformational Locks: Subtly Regulating NIR-II Molecules for Multimodal Imaging-Navigated Synergistic Therapies.

Phototheranostics is growing into a sparking frontier in disease treatment. Developing single molecular species synchronously featured by powerful absorption capacity, superior second near-infrared (NIR-II) fluorescence and prominent photothermal conversion ability is highly desirable for phototheranostics, yet remains formidably challenging. In this work, we propose a molecular design philosophy that the integration of noncovalent conformational locks (NoCLs) with aggregation-induced emission (AIE) in a single formulation is able to boost multiple photophysical properties for efficient phototheranostics. The introduction of NoCLs skeleton with conformation-locking feature in the center of molecular architecture indeed elevates the structural planarity and rigidity, which simultaneously promotes the absorption capacity and bathochromic-shifts the emission wavelength centered in NIR-II region. Meanwhile, the AIE tendency mainly originated from flexibly propeller-like geometry at the ends of molecular architecture eventually endows the molecule with satisfactory emission intensity and photothermal conversion in aggregates. Consequently, by utilizing the optimized molecule, unprecedented performance on NIR-II fluorescence-photoacoustic-photothermal trimodal imaging-guided photothermal-chemo synergistic therapy is demonstrated by the precise tumor diagnosis and complete tumor ablation.

Cobalt-Catalyzed Cascade C-H Activation/Annulation Polymerizations toward Diversified and Multifunctional Sulfur-Containing Fused Heterocyclic Polymers.

Transition-metal-catalyzed C-H activation has greatly benefited the synthesis and development of functional polymer materials, and the construction of multifunctional fused (hetero)cyclic polymers via novel C-H activation-based polyannulations has emerged as a charming but challenging area in recent years. Herein, we report the first cobalt(III)-catalyzed cascade C-H activation/annulation polymerization (CAAP) approach that can efficiently transform readily available aryl thioamides and internal diynes into multifunctional sulfur-containing fused heterocyclic (SFH) polymers. Within merely 3 h, a series of SFH polymers bearing complex and multisubstituted S,N-doped polycyclic units are facilely and efficiently produced with high molecular weights (absolute Mn up to 220400) in excellent yields (up to 99%), which are hard to achieve by traditional methods. The intermediate-terminated SFH polymer can be used as a reactive macromonomer to controllably extend or modify polymer main chains. The structural diversity can be further enriched through facile S-oxidation and N-methylation reactions of the SFH polymers. Benefiting from the unique structures, the obtained polymers exhibit excellent solution processability, high thermal and morphological stability, efficient and readily tunable aggregate-state fluorescence, stimuli-responsive properties, and high and UV-modulatable refractive indices of up to 1.8464 at 632.8 nm. These properties allow the SFH polymers to be potentially applied in diverse fields, including metal ion detection, photodynamic killing of cancer cells, fluorescent photopatterning, and gradient-index optical materials.

Photosensitive AIEgens sensitize bacteria to oxidative damage and modulate the inflammatory responses of macrophages to salvage the photodynamic therapy against MRSA.

The urgent need for antimicrobial agents to combat infections caused by multidrug-resistant bacteria facilitates the exploration of alternative strategies such as photosensitizer (PS)-mediated photoinactivation. However, increasing studies have discovered uncorrelated bactericidal activities among PSs possessing similar photodynamic and pathogen-targeted properties. To optimize the photodynamic therapy (PDT) against infections, we investigated three type-I PSs of D-π-A AIEgens TI, TBI, and TTI. The capacities of reactive oxygen species (ROS) generation of TI, TBI, and TTI did not align with their bactericidal activities. Despite exhibiting the lowest photodynamic efficiency, TI exhibited the highest activities against methicillin-resistant Staphylococcus aureus (MRSA) by impairing the anti-oxidative responses of bacteria. By comparison, TTI, characterized by the strongest ROS production, inactivated intracellular MRSA by potentiating the inflammatory response of macrophages. Unlike TI and TTI, TBI, despite possessing moderate photodynamic activities and inducing ROS accumulation in both MRSA and macrophages, did not exhibit any antibacterial activity. Therefore, relying on the disturbed anti-oxidative metabolism of pathogens or potentiated host immune responses, transient ROS bursts can effectively control bacterial infections. Our study reevaluates the contribution of photodynamic activities of PSs to bacterial elimination and provides new insights into discovering novel antibacterial targets and agents.

An Electron Donor-Acceptor Structured Rhenium(I) Complex Photo-Sensitizer Evokes Mutually Reinforcing "Closed-Loop" Ferroptosis and Immunotherapy.

The hypoxic microenvironment of solid tumors severely lowers the efficacy of oxygen-dependent photodynamic therapy (PDT). The development of hypoxia-tolerant photosensitizers for PDT is an urgent requirement. In this study, a novel rhenium complex (Re-TTPY) to develop a "closed-loop" therapy based on PDT-induced ferroptosis and immune therapy is reported. Due to its electron donor-acceptor (D-A) structure, Re-TTPY undergoes energy transfer and electron transfer processes under 550 nm light irradiation and displays hypoxia-tolerant type I/II combined PDT capability, which can generate 1O2, O2 -, and ·OH simultaneously. Further, the reactive oxygen species (ROSs) leads to the depletion of 1,4-dihydronicotinamide adenine dinucleotide (NADH), glutathione peroxidase 4 (GPX4), and glutathione (GSH). As a result, ferroptosis occurs in cells, simultaneously triggers immunogenic cell death (ICD), and promotes the maturation of dendritic cells (DCs) and infiltration of T cells. The release of interferon-γ (IFN-γ) by CD8+ T cells downregulates the expression of GPX4, further enhancing the occurrence of ferroptosis, and thereby, forming a mutually reinforcing "closed-loop" therapeutic approach.

Thiophene π-Bridge Manipulation of NIR-II AIEgens for Multimodal Tumor Phototheranostics.

The fabrication of a multimodal phototheranostic platform on the basis of single-component theranostic agent to afford both imaging and therapy simultaneously, is attractive yet full of challenges. The emergence of aggregation-induced emission luminogens (AIEgens), particularly those emit fluorescence in the second near-infrared window (NIR-II), provides a powerful tool for cancer treatment by virtue of adjustable pathway for radiative/non-radiative energy consumption, deeper penetration depth and aggregation-enhanced theranostic performance. Although bulky thiophene π-bridges such as ortho-alkylated thiophene, 3,4-ethoxylene dioxythiophene and benzo[c]thiophene are commonly adopted to construct NIR-II AIEgens, the subtle differentiation on their theranostic behaviours has yet to be comprehensively investigated. In this work, systematical investigations discovered that AIEgen BT-NS bearing benzo[c]thiophene possesses acceptable NIR-II fluorescence emission intensity, efficient reactive oxygen species generation, and high photothermal conversion efficiency. Eventually, by using of BT-NS nanoparticles, unprecedented performance on NIR-II fluorescence/photoacoustic/photothermal imaging-guided synergistic photodynamic/photothermal elimination of tumors was demonstrated. This study thus offers useful insights into developing versatile phototheranostic systems for clinical trials.

Transradial versus transfemoral access for posterior circulation endovascular intervention: A systematic review and meta-analysis.

OBJECTIVE: Transradial access (TRA) provides a more direct entry to posterior circulation system for endovascular therapy compared to transfemoral access (TFA). This meta-analysis aims to evaluate the safety and feasibility of TRA in neurointervention of posterior circulation. MATERIALS AND METHODS: A systematic search was conducted in the Wanfang Data, CBM, PubMed, Embase, Cochrane Library, Web of Science databases. The primary outcomes included total complications and access site complications. Secondary outcomes were single puncture success, procedural success, access cross-over, catheter retention time and fluoroscopy time. RESULTS: Six studies encompassing 297 patients were included in the meta-analysis. Compared to the TFA group, the TRA group showed significantly decreased total complications (odds ratio [OR] = 0.29, 95% confidence interval [CI] [0.12, 0.73], p < 0.01) and access site complications (OR = 0.19, 95%CI [0.06, 0.62], p < 0.01), yet it had a longer catheter retention time (mean difference [MD] = 0.80, 95%CI [0.60, 1.00], p < 0.01). There were no significant differences in single puncture success (OR = 3.68, 95%CI[0.38, 35.86], p = 0.26), procedural success (OR = 0.30，95%CI [0.05, 1.73], p = 0.18), access cross-over (OR = 2.29, 95%CI [0.19, 28.26], p = 0.52), fluoroscopy time (MD = 0.97, 95%CI [- 0.91, 2.84], p = 0.31) between the TRA and TFA groups. CONCLUSION: This meta-analysis demonstrated that TRA is a safe and feasible alternative to TFA for neurointervention in the posterior circulation. TRA showed significantly decreased total complications and access site complications, yet it had a longer catheter retention time than TFA.

Endoplasmic Reticulum-Targeted Aggregation-Induced Emission Luminogen for Synergetic Tumor Ablation with Glibenclamide.

Photodynamic therapy based on fluorescence illumination of subcellular organelles and in situ bursts of reactive oxygen species (ROS) has been recognized as a promising strategy for cancer theranostics. However, the short life of ROS and unclarified anticancer mechanism seriously restrict the application. Herein, we rationally designed and facilely synthesized a 2,6-dimethylpyridine-based triphenylamine (TPA) derivative TPA-DMPy with aggregation-induced emission (AIE) features and production of type-I ROS. Except for its selective binding to the endoplasmic reticulum (ER), TPA-DMPy, in synergy with glibenclamide, a medicinal agent used against diabetes, induced significant apoptosis of cancer cells in vitro and in vivo. Additionally, TPA-DMPy greatly incited the release of calcium from ER upon light irradiation to further aggravate the depolarization of ER membrane potential caused by glibenclamide, thus inducing fatal ER stress and crosstalk between ER and mitochondria. Our study extends the biological design and application of AIE luminogens and provides new insights into discovering novel anticancer targets and agents.

Attentive Training: A New Training Framework for Speech Enhancement.

Dealing with speech interference in a speech enhancement system requires either speaker separation or target speaker extraction. Speaker separation has multiple output streams with arbitrary assignments while target speaker extraction requires additional cueing for speaker selection. Both of these are not suitable for a standalone speech enhancement system with one output stream. In this study, we propose a novel training framework, called Attentive Training, to extend speech enhancement to deal with speech interruptions. Attentive training is based on the observation that, in the real world, multiple talkers very unlikely start speaking at the same time, and therefore, a deep neural network can be trained to create a representation of the first speaker and utilize it to attend to or track that speaker in a multitalker noisy mixture. We present experimental results and comparisons to demonstrate the effectiveness of attentive training for speech enhancement.

Low-Latency Active Noise Control Using Attentive Recurrent Network.

Processing latency is a critical issue for active noise control (ANC) due to the causality constraint of ANC systems. This paper addresses low-latency ANC in the context of deep learning (i.e. deep ANC). A time-domain method using an attentive recurrent network (ARN) is employed to perform deep ANC with smaller frame sizes, thus reducing algorithmic latency of deep ANC. In addition, we introduce a delay-compensated training to perform ANC using predicted noise for several milliseconds. Moreover, a revised overlap-add method is utilized during signal resynthesis to avoid the latency introduced due to overlaps between neighboring time frames. Experimental results show the effectiveness of the proposed strategies for achieving low-latency deep ANC. Combining the proposed strategies is capable of yielding zero, even negative, algorithmic latency without affecting ANC performance much, thus alleviating the causality constraint in ANC design.

Ferulic Acid Induces Autophagy and Apoptosis in Colon Cancer CT26 Cells via the MAPK Pathway.

Ferulic acid (FA) is a bioactive compound found in traditional Chinese herbal medicine; for example, it is present in Xinjiang Ferula, but also in strong-flavor Chinese baijiu. FA has been shown to play a crucial role in treating oxidative stress, skin whitening, and eye diseases. In this study, the potential role of FA as a means of inducing apoptosis and inhibiting colon cancer induced by the transplantation of CT26 cells was investigated. The results show that FA adjuvant treatment caused an upregulation in the expression of genes related to autophagy while simultaneously suppressing the expression of inflammatory response elements and improving the bodyweight, glutamic pyruvic transaminase (ALT), and glutamic oxaloacetic transaminase (AST) in vivo. Furthermore, FA inhibited the proliferation of CT26 cells and induced apoptosis, specifically by activating the phosphorylation of ERK and JNK to enhance the essential proteins BCL-2 and BAX in the apoptosis pathway. These results suggest that FA could be a promising auxiliary therapeutic agent for the treatment of colon cancer. Further research is needed to better understand the mechanisms underlying the beneficial effects of FA and its synergistic effects with other compounds.

Precise Planar-Twisted Molecular Engineering to Construct Semiconducting Polymers with Balanced Absorption and Quantum Yield for Efficient Phototheranostics.

Semiconducting polymers (SPs) have shown great feasibility as candidates for near-infrared-II (NIR-II) fluorescence imaging-navigated photothermal therapy due to their strong light-harvesting ability and flexible tunability. However, the fluorescence signal of traditional SPs tends to quench in their aggregate states owing to the strong π-π stacking, which can lead to the radiative decay pathway shutting down. To address this issue, aggregation-induced emission effect has been used as a rational tactic to boost the aggregate-state fluorescence of NIR-II emitters. In this contribution, we developed a precise molecular engineering tactic based on the block copolymerizations that integrate planar and twisted segments into one conjugated polymer backbone, providing great flexibility in tuning the photophysical properties and photothermal conversion capacity of SPs. Two monomers featured with twisted and planar architectures, respectively, were tactfully incorporated via a ternary copolymerization approach to produce a series of new SPs. The optimal copolymer (SP2) synchronously shows desirable absorption ability and good NIR-II quantum yield on the premise of maintaining typical aggregation-induced emission characteristics, resulting in balanced NIR-II fluorescence brightness and photothermal property. Water-dispersible nanoparticles fabricated from the optimal SP2 show efficient photothermal therapeutic effects both in vitro and in vivo. The in vivo investigation reveals the distinguished NIR-II fluorescence imaging performance of SP2 nanoparticles and their photothermal ablation toward tumor with prominent tumor accumulation ability and excellent biocompatibility.

Mechanistic Understanding of Efficient Polyethylene Hydrocracking over Two-Dimensional Platinum-Anchored Tungsten Trioxide.

Chemical upcycling of polyethylene (PE) can convert plastic waste into valuable resources. However, engineering a catalyst that allows PE decomposition at low temperatures with high activity remains a significant challenge. Herein, we anchored 0.2 wt.% platinum (Pt) on defective two-dimensional tungsten trioxide (2D WO3 ) nanosheets and achieved hydrocracking of high-density polyethylene (HDPE) waste at 200-250 °C with a liquid fuel (C5-18 ) formation rate up to 1456 gproducts ⋅ gmetal species -1 ⋅ h-1 . The reaction pathway over the bifunctional 2D Pt/WO3 is elucidated by quasi-operando transmission infrared spectroscopy, where (I) well-dispersed Pt immobilized on 2D WO3 nanosheets trigger the dissociation of hydrogen; (II) adsorption of PE and activation of C-C cleavage on WO3 are through the formation of C=O/C=C intermediates; (III) intermediates are converted to alkane products by the dissociated H. Our study directly illustrates the synergistic role of bifunctional Pt/WO3 catalyst in the hydrocracking of HDPE, paving the way for the development of high-performance catalysts with optimized chemical and morphological properties.

Progress made in the efficacy and viability of deep-learning-based noise reduction.

Recent years have brought considerable advances to our ability to increase intelligibility through deep-learning-based noise reduction, especially for hearing-impaired (HI) listeners. In this study, intelligibility improvements resulting from a current algorithm are assessed. These benefits are compared to those resulting from the initial demonstration of deep-learning-based noise reduction for HI listeners ten years ago in Healy, Yoho, Wang, and Wang [(2013). J. Acoust. Soc. Am. 134, 3029-3038]. The stimuli and procedures were broadly similar across studies. However, whereas the initial study involved highly matched training and test conditions, as well as non-causal operation, preventing its ability to operate in the real world, the current attentive recurrent network employed different noise types, talkers, and speech corpora for training versus test, as required for generalization, and it was fully causal, as required for real-time operation. Significant intelligibility benefit was observed in every condition, which averaged 51% points across conditions for HI listeners. Further, benefit was comparable to that obtained in the initial demonstration, despite the considerable additional demands placed on the current algorithm. The retention of large benefit despite the systematic removal of various constraints as required for real-world operation reflects the substantial advances made to deep-learning-based noise reduction.

Achieving Tunable Organic Afterglow and UV-Irradiation-Responsive Ultralong Room-Temperature Phosphorescence from Pyridine-Substituted Triphenylamine Derivatives.

Amorphous polymers with ultralong room-temperature phosphorescence (RTP) are highly promising for various applications. Particularly, polymer-based RTP materials with multiple functions such as color-tunability or stimulus-response are highly desirable for multilevel anti-counterfeiting but are rarely reported. Herein, a facile strategy is presented to achieve a series of polymer-based RTP materials with ultralong lifetime, multicolor afterglow, and reversible response to UV irradiation by simply embedding pyridine-substituted triphenylamine derivatives into the polymer matrix poly(vinyl alcohol) (PVA) and poly(methyl methacrylate) (PMMA), respectively. Notably, the pyridine group with the capabilities of promoting intersystem crossing and forming hydrogen-bonding interactions is essential for triggering ultralong RTP from the doping PVA system, among which the doping film TPA-2Py@PVA exhibits excellent RTP property with an ultralong lifetime of 798.4 ms and a high quantum yield of 15.2%. By further co-doping with the commercially available fluorescent dye, multicolor afterglow is obtained via phosphorescence energy transfer. Meanwhile, the doped PMMA system exhibits reversible photoactivated ultralong RTP properties under continuous UV irradiation. Finally, potential applications of these doped PVA and PMMA systems with ultralong lifetime, multicolor afterglow, and photoactivated ultralong RTP in multidimensional anti-counterfeiting are demonstrated.

DMSO/tBuONa/O2-mediated efficient syntheses of diverse quinoxalines through α-imino radicals.

Herein, we describe an efficient method involving the synthesis of diverse quinoxalines using the DMSO/tBuONa/O2 system as a single-electron oxidant to form α-imino radicals and nitrogen radicals for the direct construction of C-N bonds. This methodology provides a novel approach to form α-imino radicals with good reactivity.

A comparison of bilateral and unilateral cerebral perfusion for total arch replacement surgery for non-marfan, type A aortic dissection.

OBJECTIVES: Acknowledging lacking of consensus exist in total aortic arch (TAA) surgery for acute type A aortic dissection (AAD), this study aimed to investigate the neurologic injury rate between bilateral and unilateral cerebrum perfusion on the specific population. METHODS: A total of 595 AAD patients other than Marfan syndrome receiving TAA surgery since March 2013 to March 2022 were included. Among them, 276 received unilateral cerebral perfusion (via right axillary artery, RCP) and 319 for bilateral cerebral perfusion (BCP). The primary outcome was neurologic injury rate. Secondary outcomes were 30-day mortality, serum inflammation response (high sensitivity C reaction protein, hs-CRP; Interleukin-6, IL-6; cold-inducible RNA binding protein, CIRBP) and neuroprotection (RNA-binding motif 3, RBM3) indexes. RESULTS: The BCP group reported a significantly lower permanent neurologic deficits [odds ratio: 0.481, Confidence interval (CI): 0.296-0.782, p = 0.003] and 30-day mortality (odds ratio: 0.353, CI: 0.194-0.640, p < 0.001) than those received RCP treatment. There were also lower inflammation cytokines (hr-CRP: 114 ± 17 vs. 101 ± 16 mg/L; IL-6: 130 [103,170] vs. 81 [69,99] pg/ml; CIRBP: 1076 [889, 1296] vs. 854 [774, 991] pg/ml, all p < 0.001), but a higher neuroprotective cytokine (RBM3: 4381 ± 1362 vs 2445 ± 1008 pg/mL, p < 0.001) at 24 h after procedure in BCP group. Meanwhile, BCP resulted in a significantly lower Acute Physiology, Age and Chronic Health Evaluation (APACHE) Ⅱscore (18 ± 6 vs 17 ± 6, p < 0.001) and short stay in intensive care unit (4 [3,5] vs. 3 [2,3] days, p < 0.001) and hospital (16 ± 4 vs 14 ± 3 days, p < 0.001). CONCLUSIONS: This present study indicated that BCP compared with RCP was associated with lower permanent neurologic deficits and 30-day mortality in AAD patients other than Marfan syndrome receiving TAA surgery.