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.

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.

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.

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.

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.

Molecular Organization and Functional Analysis of a Novel Plasmid-Borne cps Gene Cluster from Lactiplantibacillus plantarum YC41.

Capsular polysaccharide (CPS) can tightly attach to bacterial surfaces and plays a critical role in protecting microorganisms from environmental stresses. However, the molecular and functional properties of some plasmid-borne cps gene clusters are poorly understood. In this study, comparative genomics of the draft genomes of 21 Lactiplantibacillus plantarum strains revealed that the specific gene cluster for CPS biosynthesis was observed only in the 8 strains with a ropy phenotype. Furthermore, the complete genomes showed that the specific gene cluster cpsYC41 was located on the novel plasmid pYC41 in L. plantarum YC41. In silico analysis confirmed that the cpsYC41 gene cluster contained the dTDP-rhamnose precursor biosynthesis operon, the repeating-unit biosynthesis operon, and the wzx gene. The insertional inactivation of the rmlA and cpsC genes abolished the ropy phenotype and reduced the CPS yields by 93.79% and 96.62%, respectively, in L. plantarum YC41 mutants. These results revealed that the cpsYC41 gene cluster was responsible for CPS biosynthesis. Moreover, the survival rates of the YC41-rmlA- and YC41-cpsC- mutants under acid, NaCl, and H2O2 stresses were decreased by 56.47 to 93.67% compared to that of the control strain. Furthermore, the specific cps gene cluster was also confirmed to play a vital role in CPS biosynthesis in L. plantarum MC2, PG1, and YD2. These findings enhance our understanding of the genetic organization and gene functions of plasmid-borne cps gene clusters in L. plantarum. IMPORTANCE Capsular polysaccharide is well known to protect bacteria against various environmental stresses. The gene cluster for CPS biosynthesis is typically organized in the chromosome in bacteria. It is worth noting that complete genome sequencing showed that a novel plasmid pYC41-borne cpsYC41 gene cluster was identified in L. plantarum YC41. The cpsYC41 gene cluster included the dTDP-rhamnose precursor biosynthesis operon, the repeating-unit biosynthesis operon, and the wzx gene, which was verified by the significantly decreased CPS yield and the absent ropy phenotype in the corresponding mutants. The cpsYC41 gene cluster plays an important role in bacterial survival under environmental stress, and the mutants had decreased fitness under stress conditions. The vital role of this specific cps gene cluster in CPS biosynthesis was also confirmed in other CPS-producing L. plantarum strains. These results advanced a better understanding of the molecular mechanisms of plasmid-borne cps gene clusters and the protective functionality of CPS.

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.

Evaluating and forecasting the associated main flavor components in Baijiu (Chinese distilled spirits) with alcohol metabolism and hangover symptoms through mice acute withdrawal model.

Over the past few decades, more alcohol-problem concerns focused on reducing the risk of hangover caused by the alcoholic beverages over-consumption. Chinese distilled spirits (Baijiu) is one of the most favorite alcoholic beverages. The intention of this study is to explore the associations of main flavor components in Baijiu and hangover symptoms using mice acute alcohol withdrawal model. The behaviors of each mouse were assessed by open-field tests using separate groups of mice with the treatment of sauce-aroma Baijiu, light-aroma Baijiu, strong-aroma Baijiu, pure alcohol, and distilled water, respectively. The behavioral data including total move distance and immobile time were used as indicators for the evaluation of the liquor intoxicating effects. Alcohol and acetaldehyde concentrations in mice plasma and the neurotransmitter contents of GABA and Glu in mice cerebellum were detected afterward. The results showed that the mice with the treatment of Baijiu samples displayed unusual exciting behaviors including increased alcohol metabolization with alleviating drunken and hangover symptoms, compared with that of pure alcohol control groups after 2-4 h. Moreover, the sauce-aroma Baijiu treatment group showed lessening intoxicated symptoms than those of light-aroma Baijiu and strong-aroma Baijiu. In addition, there were significant differences between Baijiu and pure alcohol treatment groups at the inhibitory neurotransmitter GABAergic levels and its receptor GABA-AR1 activating levels in the mice neuron cells. Furthermore, the Principal Component Analysis (PCA) analysis inferred that the flavor compounds acetic acid, ethyl acetate, ethyl lactate, and 1-propanol in the sauce-aroma Baijiu were played the major roles in the drunk behaviors that caused by the hangover. While, the acetic acid in the sauce-aroma Baijiu was speculated as a major flavor component to accelerate the alcohol metabolism and retard hangover symptoms.

Deep MCANC: A deep learning approach to multi-channel active noise control.

Traditional multi-channel active noise control (MCANC) is based on adaptive filtering and usually uses a separate control unit for each channel. This paper introduces a deep learning based approach for multi-channel active noise control (ANC). The proposed approach, called deep MCANC, encodes optimal control parameters corresponding to different noises and environments, and jointly computes the multiple canceling signals to cancel or attenuate the primary noises captured at error microphones. A convolutional recurrent network (CRN) is employed for complex spectral mapping where the summated power of error signals is used as the loss function for CRN training. Deep MCANC is a fixed-parameter ANC approach and large-scale multi-condition training is employed to achieve robustness against a variety of noises. We explore the performance of deep MCANC with different setups and investigate the impact of factors such as the number of loudspeakers and microphones, and the position of a secondary source, on ANC performance. Experimental results show that deep MCANC is effective for wideband noise reduction and generalizes well to untrained noises. Moreover, the proposed approach is robust against variations in reference signals and works well in the presence of nonlinear distortions.