Single Atom Ag Bonding Between PF3T Nanocluster and TiO2 Leads the Ultra-Stable Visible-Light-Driven Photocatalytic H2 Production.

Atomic Ag cluster bonding is employed to reinforce the interface between PF3T nano-cluster and TiO2 nanoparticle. With an optimized Ag loading (Ag/TiO2 = 0.5 wt%), the Ag atoms will uniformly disperse on TiO2 thus generating a high density of intermediate states in the band gap to form the electron channel between the terthiophene group of PF3T and the TiO2 in the hybrid composite (denoted as T@Ag05-P). The former expands the photon absorption band width and the latter facilitates the core-hole splitting by injecting the photon excited electron (from the excitons in PF3T) into the conduction band (CB) of TiO2. These characteristics enable the high efficiency of H2 production to 16 580 µmol h-1 g-1 and photocatalysis stability without degradation under visible light exposure for 96 h. Compared to that of hybrid material without Ag bonding (TiO2@PF3T), the H2 production yield and stability are improved by 4.1 and 18.2-fold which shows the best performance among existing materials in similar component combination and interfacial reinforcement. The unique bonding method offers a new prospect to accelerate the development of photocatalytic hydrogen production technologies.

Hyperdimensional Brain-Inspired Learning for Phoneme Recognition With Large-Scale Inferior Colliculus Neural Activities.

OBJECTIVE: Develop a novel and highly efficient framework that decodes Inferior Colliculus (IC) neural activities for phoneme recognition. METHODS: We propose using Hyperdimensional Computing (HDC) to support an efficient phoneme recognition algorithm, in contrast to widely applied Deep Neural Networks (DNN). The high-dimensional representation and operations in HDC are rooted in human brain functionalities and naturally parallelizable, showing the potential for efficient neural activity analysis. Our proposed method includes a spatial and temporal-aware HDC encoder that effectively captures global and local patterns. As part of our framework, we deploy the lightweight HDC-based algorithm on a highly customizable and flexible hardware platform, i.e., Field Programmable Gate Arrays (FPGA), for optimal algorithm speedup. To evaluate our method, we record IC neural activities on gerbils while playing the sound of different phonemes. RESULTS: We compare our proposed method with multiple baseline machine learning algorithms in recognition quality and learning efficiency, across different hardware platforms. The results show that our method generally achieves better classification quality than the best-performing baseline. Compared to the Deep Residual Neural Network (i.e., ResNet), our method shows a speedup up to 74×, 67×, 210× on CPU, GPU, and FPGA respectively. We achieve up to 15% (10%) higher accuracy in consonant (vowel) classification than ResNet. CONCLUSION: By leveraging brain-inspired HDC for IC neural activity encoding and phoneme classification, we achieve orders of magnitude runtime speedup while improving accuracy in various challenging task settings. SIGNIFICANCE: Decoding IC neural activities is an important step to enhance understanding about human auditory system. However, these responses from the central auditory system are noisy and contain high variance, demanding large-scale datasets and iterative model fine-tuning. The proposed HDC-based framework is more scalable and viable for future real-world deployment thanks to its fast training and overall better quality.

Ji-Ni-De-Xie ameliorates type 2 diabetes mellitus by modulating the bile acids metabolism and FXR/FGF15 signaling pathway.

Introduction: Ji-Ni-De-Xie (JNDX) is a traditional herbal preparation in China. It is widely used to treat type 2 diabetes mellitus (T2DM) in traditional Tibetan medicine system. However, its antidiabetic mechanisms have not been elucidated. The aim of this study is to elucidate the underlying mechanism of JNDX on bile acids (BAs) metabolism and FXR/FGF15 signaling pathway in T2DM rats. Methods: High-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ-MS) and UPLC-Q-Exactive Orbitrap MS technology were used to identify the constituents in JNDX. High-fat diet (HFD) combined with streptozotocin (45 mg∙kg-1) (STZ) was used to establish a T2DM rat model, and the levels of fasting blood-glucose (FBG), glycosylated serum protein (GSP), homeostasis model assessment of insulin resistance (HOMA-IR), LPS, TNF-α, IL-1ß, IL-6, TG, TC, LDL-C, HDL-C, and insulin sensitivity index (ISI) were measured to evaluate the anti-diabetic activity of JNDX. In addition, metagenomic analysis was performed to detect changes in gut microbiota. The metabolic profile of BAs was analyzed by HPLC-QQQ-MS. Moreover, the protein and mRNA expressions of FXR and FGF15 in the colon and the protein expressions of FGF15 and CYP7A1 in the liver of T2DM rats were measured by western blot and RT-qPCR. Results: A total of 12 constituents were identified by HPLC-QQQ-MS in JNDX. Furthermore, 45 chemical components in serum were identified from JNDX via UPLC-Q-Exactive Orbitrap MS technology, including 22 prototype components and 23 metabolites. Using a T2DM rat model, we found that JNDX (0.083, 0.165 and 0.33 g/kg) reduced the levels of FBG, GSP, HOMA-IR, LPS, TNF-α, IL-1ß, IL-6, TG, TC, and LDL-C, and increased ISI and HDL-C levels in T2DM rats. Metagenomic results demonstrated that JNDX treatment effectively improved gut microbiota dysbiosis, including altering some bacteria (e.g., Streptococcus and Bacteroides) associated with BAs metabolism. Additionally, JNDX improved BAs disorder in T2DM rats, especially significantly increasing cholic acid (CA) levels and decreasing ursodeoxycholic acid (UDCA) levels. Moreover, the protein and mRNA expressions of FXR and FGF15 of T2DM rats were significantly increased, while the expression of CYP7A1 protein in the liver was markedly inhibited by JNDX. Discussion: JNDX can effectively improve insulin resistance, hyperglycemia, hyperlipidemia, and inflammation in T2DM rats. The mechanism is related to its regulation of BAs metabolism and activation of FXR/FGF15 signaling pathway.

Characterizing and decoding the key odor-active compounds in fresh, pasteurized, and high pressure processing sea buckthorn (Hippophae rhamnoides L.) juice.

The non-thermal and thermal effects on aroma of sea buckthorn juice have rarely been investigated. In this study, 57 odor compounds were identified in fresh sea buckthorn juice (FSBJ), high pressure processing sea buckthorn juice (HSBJ), and pasteurized sea buckthorn juice (PSBJ), including 29 esters, 8 aldehydes, 1 ketone, 5 alcohols, 5 acids, 6 terpenoids, and 3 others. Ethyl 2-methylbutanoate, ethyl 3-methylbutanoate, ethyl hexanoate, and ethyl 2-hydroxy-3-methylbutanoate with flavor dilution factors ranging from 729 to 59,049 contributed to the fruity odors of FSBJ and HSBJ. Besides, the formation of off-odor compounds including hexanal, nonanal, furfural, 3-methylbutanoic acid, and dimethyl disulfide with odor activity values ≥ 1, imparts fatty, roasted, sweaty, and cooked odor in PSBJ. The variations of vitamin C and reducing sugar are significantly associated with changes in odor-active compounds during pasteurized processing. These findings provide new insights that high pressure processing minimizes the adverse effects of pasteurization.

Purification and characterization of limonin D-ring lactone hydrolase from sweet orange (Citrus sinensis (L.) Osbeck) seeds.

BACKGROUND: Citrus products often suffer from delayed bitterness, which is generated from the conversion of non-bitter precursors (limonoate A-ring lactone, LARL) to limonin under the catalysis of limonin D-ring lactone hydrolase (LDLH). In this study, LDLH was isolated and purified from sweet orange seeds, and a rapid and accurate high-performance liquid chromatography method to quantify LARL was developed and applied to analyze the activity and enzymatic properties of purified LDLH. RESULTS: Purified LDLH (25.22 U mg-1) showed bands of 245 kDa and 17.5 kDa molecular weights in native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate PAGE analysis respectively. After a 24 h incubation under strongly acidic (pH 3) or strongly alkaline (pH 9) conditions, LDLH still retained approximately 100% activity. Moreover, LDLH activity was not impaired by thermal treatment at 50 °C for 120 min. Enzyme inhibition assays showed that LDLH was inactivated only after ethylenediaminetetraacetic acid treatment, and other enzyme inhibitors showed no significant effect on its activity. In addition, the LDLH activity of calcium ion (Ca2+) intervention was 108% of that in the blank group, and that of zinc ion (Zn2+) intervention was 71%. CONCLUSION: LDLH purified in this study was a multimer containing 17.5 kDa monomer with a wide pH tolerance range (pH 3-9) and excellent thermal stability. Moreover, LDLH might be a metallopeptidase, and its activity was stimulated by Ca2+ and significantly inhibited by Zn2+. These findings improve our understanding of LDLH and provide some important implications for reducing the bitterness in citrus products in the future. © 2024 Society of Chemical Industry.

Gut virome alterations in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is one of the primary causes of mortality and morbidity worldwide. The gut microbiome, particularly the bacteriome, has been demonstrated to contribute to the progression of COPD. However, the influence of gut virome on the pathogenesis of COPD is rarely studied. Recent advances in viral metagenomics have enabled the rapid discovery of its remarkable role in COPD. In this study, deep metagenomics sequencing of fecal virus-like particles and bacterial 16S rRNA sequencing was performed on 92 subjects from China to characterize alterations of the gut virome in COPD. Lower richness and diversity of the gut virome were observed in the COPD subjects compared with the healthy individuals. Sixty-four viral species, including Clostridium phage, Myoviridae sp., and Synechococcus phage, showed positive relationships with pulmonary ventilation functions and had markedly declined population in COPD subjects. Multiple viral functions, mainly involved in bacterial susceptibility and the interaction between bacteriophages and bacterial hosts, were significantly declined in COPD. In addition, COPD was characterized by weakened viral-bacterial interactions compared with those in the healthy cohort. The gut virome showed diagnostic performance with an area under the curve (AUC) of 88.7%, which indicates the potential diagnostic value of the gut virome for COPD. These results suggest that gut virome may play an important role in the development of COPD. The information can provide a reference for the future investigation of diagnosis, treatment, and in-depth mechanism research of COPD. IMPORTANCE: Previous studies showed that the bacteriome plays an important role in the progression of chronic obstructive pulmonary disease (COPD). However, little is known about the involvement of the gut virome in COPD. Our study explored the disease-specific virome signatures of patients with COPD. We found the diversity and compositions altered of the gut virome in COPD subjects compared with healthy individuals, especially those viral species positively correlated with pulmonary ventilation functions. Additionally, the declined bacterial susceptibility, the interaction between bacteriophages and bacterial hosts, and the weakened viral-bacterial interactions in COPD were observed. The findings also suggested the potential diagnostic value of the gut virome for COPD. The results highlight the significance of gut virome in COPD. The novel strategies for gut virome rectifications may help to restore the balance of gut microecology and represent promising therapeutics for COPD.

TAK1 in Vascular Signaling: "Friend or Foe"?

The maintenance of normal vascular function and homeostasis is largely dependent on the signaling mechanisms that occur within and between cells of the vasculature. TGF-ß-activated kinase 1 (TAK1), a multifaceted signaling molecule, has been shown to play critical roles in various tissue types. Although the precise function of TAK1 in the vasculature remains largely unknown, emerging evidence suggests its potential involvement in both physiological and pathological processes. A comprehensive search strategy was employed to identify relevant studies, PubMed, Web of Science, and other relevant databases were systematically searched using keywords related to TAK1, TABs and MAP3K7.In this review, we discussed the role of TAK1 in vascular signaling, with a focus on its function, activation, and related signaling pathways. Specifically, we highlight the TA1-TABs complex is a key factor, regulating vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) involved in the processes of inflammation, vascular proliferation and angiogenesis. This mini review aims to elucidate the evidence supporting TAK1 signaling in the vasculature, in order to better comprehend its beneficial and potential harmful effects upon TAK1 activation in vascular tissue.

Mental health and insomnia problems in healthcare workers after the COVID-19 pandemic: A multicenter cross-sectional study.

BACKGROUND: Healthcare workers (HCWs) are at increased risk of contracting coronavirus disease 2019 (COVID-19) as well as worsening mental health problems and insomnia. These problems can persist for a long period, even after the pandemic. However, less is known about this topic. AIM: To analyze mental health, insomnia problems, and their influencing factors in HCWs after the COVID-19 pandemic. METHODS: This multicenter cross-sectional, hospital-based study was conducted from June 1, 2023 to June 30, 2023, which was a half-year after the end of the COVID-19 emergency. Region-stratified population-based cluster sampling was applied at the provincial level for Chinese HCWs. Symptoms such as anxiety, depression, and insomnia were evaluated by the Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Insomnia Severity Index. Factors influencing the symptoms were identified by multivariable logistic regression. RESULTS: A total of 2000 participants were invited, for a response rate of 70.6%. A total of 1412 HCWs [618 (43.8%) doctors, 583 (41.3%) nurses and 211 (14.9%) nonfrontline], 254 (18.0%), 231 (16.4%), and 289 (20.5%) had symptoms of anxiety, depression, and insomnia, respectively; severe symptoms were found in 58 (4.1%), 49 (3.5%), and 111 (7.9%) of the participants. Nurses, female sex, and hospitalization for COVID-19 were risk factors for anxiety, depression, and insomnia symptoms; moreover, death from family or friends was a risk factor for insomnia symptoms. During the COVID-19 outbreak, most [1086 (76.9%)] of the participating HCWs received psychological interventions, while nearly all [994 (70.4%)] of them had received public psychological education. Only 102 (7.2%) of the HCWs received individual counseling from COVID-19. CONCLUSION: Although the mental health and sleep problems of HCWs were relieved after the COVID-19 pandemic, they still faced challenges and greater risks than did the general population. Identifying risk factors would help in providing targeted interventions. In addition, although a major proportion of HCWs have received public psychological education, individual interventions are still insufficient.

A Co-Localization Algorithm for Underwater Moving Targets with an Unknown Constant Signal Propagation Speed and Platform Errors.

Underwater mobile acoustic source target localization encounters several challenges, including the unknown propagation speed of the source signal, uncertainty in the observation platform's position and velocity (i.e., platform systematic errors), and economic costs. This paper proposes a new two-step closed-form localization algorithm that jointly estimates the angle of arrival (AOA), time difference of arrival (TDOA), and frequency difference of arrival (FDOA) to address these challenges. The algorithm initially introduces auxiliary variables to construct pseudo-linear equations to obtain the initial solution. It then exploits the relationship between the unknown and auxiliary variables to derive the exact solution comprising solely the unknown variables. Both theoretical analyses and simulation experiments demonstrate that the proposed method accurately estimates the position, velocity, and speed of the sound source even with an unknown sound speed and platform systematic errors. It achieves asymptotic optimality within a reasonable error range to approach the Cramér-Rao lower bound (CRLB). Furthermore, the algorithm exhibits low complexity, reduces the number of required localization platforms, and decreases the economic costs. Additionally, the simulation experiments validate the effectiveness of the proposed localization method across various scenarios, outperforming other comparative algorithms.

A review of lactate-lactylation in malignancy: its potential in immunotherapy.

Lactic acid was formerly regarded as a byproduct of metabolism. However, extensive investigations into the intricacies of cancer development have revealed its significant contributions to tumor growth, migration, and invasion. Post-translational modifications involving lactate have been widely observed in histone and non-histone proteins, and these modifications play a crucial role in regulating gene expression by covalently attaching lactoyl groups to lysine residues in proteins. This discovery has greatly enhanced our comprehension of lactic acid's involvement in disease pathogenesis. In this article, we provide a comprehensive review of the intricate relationship between lactate and tumor immunity, the occurrence of lactylation in malignant tumors, and the exploitation of targeted lactate-lactylation in tumor immunotherapy. Additionally, we discuss future research directions, aiming to offer novel insights that could inform the investigation, diagnosis, and treatment of related diseases.

Attention-Modulated Cortical Responses as a Biomarker for Tinnitus.

Attention plays an important role in not only the awareness and perception of tinnitus but also its interactions with external sounds. Recent evidence suggests that attention is heightened in the tinnitus brain, likely as a result of relatively local cortical changes specific to deafferentation sites or global changes that help maintain normal cognitive capabilities in individuals with hearing loss. However, most electrophysiological studies have used passive listening paradigms to probe the tinnitus brain and produced mixed results in terms of finding a distinctive biomarker for tinnitus. Here, we designed a selective attention task, in which human adults attended to one of two interleaved tonal (500 Hz and 5 kHz) sequences. In total, 16 tinnitus (5 females) and 13 age- and hearing-matched control (8 females) subjects participated in the study, with the tinnitus subjects matching the tinnitus pitch to 5.4 kHz (range = 1.9-10.8 kHz). Cortical responses were recorded in both passive and attentive listening conditions, producing no differences in P1, N1, and P2 between the tinnitus and control subjects under any conditions. However, a different pattern of results emerged when the difference was examined between the attended and unattended responses. This attention-modulated cortical response was significantly greater in the tinnitus than control subjects: 3.9-times greater for N1 at 5 kHz (95% CI: 2.9 to 5.0, p = 0.007, ηp2 = 0.24) and 3.0 for P2 at 500 Hz (95% CI: 1.9 to 4.5, p = 0.026, ηp2 = 0.17). We interpreted the greater N1 modulation as local neural changes specific to the tinnitus frequency and the greater P2 as global changes to hearing loss. These two cortical measures were used to differentiate between the tinnitus and control subjects, producing 83.3% sensitivity and 76.9% specificity (AUC = 0.81, p = 0.006). These results suggest that the tinnitus brain is more plastic than that of the matched non-tinnitus controls and that the attention-modulated cortical response can be developed as a clinically meaningful biomarker for tinnitus.

Highly Efficient Carbon Dioxide Electroreduction via DNA-Directed Catalyst Immobilization.

Electrochemical reduction of carbon dioxide (CO2) is a promising route to up-convert this industrial byproduct. However, to perform this reaction with a small-molecule catalyst, the catalyst must be proximal to an electrode surface. Efforts to immobilize molecular catalysts on electrodes have been stymied by the need to optimize the immobilization chemistries on a case-by-case basis. Taking inspiration from nature, we applied DNA as a molecular-scale "Velcro" to investigate the tethering of three porphyrin-based catalysts to electrodes. This tethering strategy improved both the stability of the catalysts and their Faradaic efficiencies (FEs). DNA-catalyst conjugates were immobilized on screen-printed carbon and carbon paper electrodes via DNA hybridization with nearly 100% efficiency. Following immobilization, a higher catalyst stability at relevant potentials is observed. Additionally, lower overpotentials are required for the generation of carbon monoxide (CO). Finally, high FE for CO generation was observed with the DNA-immobilized catalysts as compared to the unmodified small-molecule systems, as high as 79.1% FE for CO at -0.95 V vs SHE using a DNA-tethered catalyst. This work demonstrates the potential of DNA "Velcro" as a powerful strategy for catalyst immobilization. Here, we demonstrated improved catalytic characteristics of molecular catalysts for CO2 valorization, but this strategy is anticipated to be generalizable to any reaction that proceeds in aqueous solutions.

Field physical model tests on the mechanism of river blocking by debris flow in the middle reaches of the Dadu River, Southwest China.

Debris flow is a typical natural disaster in the middle reaches of the Dadu River, Southwest China. Field physical model tests were conducted to reveal the mechanism of river blocking by debris flow in the middle reaches of the Dadu River. The dynamic processes of riHver blocking by debris flows were revealed, and based on which three typical river-blocking modes of debris flow are observed, i.e. thrust-type river blocking, mixed-flow-type river blocking and progressive river blocking. The test results showed that the material composition of debris flows plays an important role in the river-blocking mode, only the tests that adopted the mixed soil and gravel exhibited the thrust-type river blocking mode. The material composition has a controlling effect on the thrust-type river-blocking model. Mixed-flow-type river-blocking mode appears most often in the tests with an intersection angle of 60°, because the small intersection angle is conducive to the mixing of the debris flow and the water in the main channel. The debris flows composed of sand tend to block the river with mixed-flow-type river-blocking mode, accounting for 50% of the occurrences in the model tests. The high flow rate and discharge in the main channel and the low flow rate and discharge in the branch channel are the key factors controlling the progressive river-blocking mode. The test results in this study can support the debris flow disaster prevention and mitigation in this area.

Structural and functional properties of whey protein isolate-inulin conjugates prepared with ultrasound or wet heating method.

BACKGROUND: Whey protein isolate (WPI) generally represents poor functional properties such as thermal stability, emulsifying activity and antioxidant activity near its isoelectric point or high temperatures, which limit its application in the food industry. The preparation of WPI-polysaccharide covalent conjugates based on Maillard reaction is a promising method to improve the physical and chemical stability and functional properties of WPI. In this research, WPI-inulin conjugates were prepared through wet heating method and ultrasound method and their structural and functional properties were examined. RESULTS: In conjugates, the free amino acid content was reduced, the high molecular bands were emerged at sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), new C-N bonds were formed in Fourier-transform infrared (FTIR) spectroscopy, and fluorescence intensity was reduced compared with WPI. Furthermore, the result of circular dichroism (CD) spectroscopy also showed that the secondary structure of conjugates was changed. Conjugates with ultrasound treatment had better structural properties compared with those prepared by wet heating treatment. The functional properties such as thermal stability, emulsifying activity index (EAI), emulsion stability (ES) and antioxidant activity of conjugates with wet heating treatment were significantly improved compared with WPI. The EAI and ES of conjugates with ultrasound treatment were the highest, but the thermal stability and antioxidant activity were only close to that of the conjugates with wet heating treatment for 2 h. CONCLUSION: This study revealed that WPI-inulin conjugates prepared with ultrasound or wet heating method not only changed the structural characteristics of WPI but also could promote its functional properties including thermal stability, EAI, ES and antioxidant activity. © 2024 Society of Chemical Industry.

Recent advances in the contribution of glucosinolates degradation products to cruciferous foods odor: factors that influence degradation pathways and odor attributes.

As one of the most important vegetables and oils consumed globally, cruciferous foods are appreciated for their high nutritional value. However, there is no comprehensive knowledge to sufficiently unravel the "flavor mystery" of cruciferous foods. The present review provides a comprehensive literature on the recent advances regarding the contribution of glucosinolates (GSL) degradation products to cruciferous foods odor, which focuses on key GSL degradation products contributing to distinct odor of cruciferous foods (Brassica oleracea, Brassica rapa, Brassica napus, Brassica juncea, Raphanus sativus), and key factors affecting GSL degradation pathways (i.e., enzyme-induced degradation, thermal-induced degradation, chemical-induced degradation, microwave-induced degradation) during different processing and cooking. A total of 93 volatile GSL degradation products (i.e., 36 nitriles, 33 isothiocyanates, 3 thiocyanates, 5 epithionitriles, and 16 sulfides) and 29 GSL (i.e., 20 aliphatic, 5 aromatic, and 4 indolic) were found in generalized cruciferous foods. Remarkably, cruciferous foods have a distinctive pungent, spicy, pickled, sulfur, and vegetable odor. In general, isothiocyanates are mostly present in enzyme-induced degradation of GSL and are therefore often enriched in fresh-cut or low-temperature, short-time cooked cruciferous foods. In contrast, nitriles are mainly derived from thermal-induced degradation of GSL, and are thus often enriched in high-temperature, long-time cooked cruciferous foods.

Processing and cooking can cause degradation of glucosinolates and formation of volatiles.Structure­odor relationship of glucosinolates degradation products is discussed.Nitriles, isothiocyanates, and sulfides play an important role in cruciferous foods odor.Both enzyme- and thermal-induced degradation of glucosinolates is strongly pH-dependent.

Qudit-based high-dimensional controlled-not gate.

High-dimensional quantum systems expand quantum channel capacity and information storage space. By implementing high-dimensional quantum logic gates, the speed of quantum computing can be practically enhanced. We propose a deterministic 4 × 4-dimensional controlled-not (CNOT) gate for a hybrid system without ancillary qudits required, where the spatial and polarization states of a single photon serve as a control qudit of four dimensions, whereas two electron-spin states in nitrogen-vacancy (NV) centers act as a four-dimensional target qudit. As the control qudits are easily operated employing simple optical elements and the target qudits are available for storage, the CNOT gate works in a deterministic way, and it can be flexibly extended to n × n-dimensional (n > 4) quantum gates for other hybrid systems or different photonic degrees of freedoms. The efficiency and fidelity of the CNOT gate are analyzed aligning with current technological capabilities, finding that they have satisfactory performances.

Laser-Induced Intracellular Delivery: Exploiting Gold-Coated Spiky Polymeric Nanoparticles and Gold Nanorods under Near-Infrared Pulses for Single-Cell Nano-Photon-Poration.

This study explores the potential of laser-induced nano-photon-poration as a non-invasive technique for the intracellular delivery of micro/macromolecules at the single-cell level. This research proposes the utilization of gold-coated spiky polymeric nanoparticles (Au-PNPs) and gold nanorods (GNRs) to achieve efficient intracellular micro/macromolecule delivery at the single-cell level. By shifting the operating wavelength towards the near-infrared (NIR) range, the intracellular delivery efficiency and viability of Au-PNP-mediated photon-poration are compared to those using GNR-mediated intracellular delivery. Employing Au-PNPs as mediators in conjunction with nanosecond-pulsed lasers, a highly efficient intracellular delivery, while preserving high cell viability, is demonstrated. Laser pulses directed at Au-PNPs generate over a hundred hot spots per particle through plasmon resonance, facilitating the formation of photothermal vapor nanobubbles (PVNBs). These PVNBs create transient pores, enabling the gentle transfer of cargo from the extracellular to the intracellular milieu, without inducing deleterious effects in the cells. The optimization of wavelengths in the NIR region, coupled with low laser fluence (27 mJ/cm2) and nanoparticle concentrations (34 µg/mL), achieves outstanding delivery efficiencies (96%) and maintains high cell viability (up to 99%) across the various cell types, including cancer and neuronal cells. Importantly, sustained high cell viability (90-95%) is observed even 48 h post laser exposure. This innovative development holds considerable promise for diverse applications, encompassing drug delivery, gene therapy, and regenerative medicine. This study underscores the efficiency and versatility of the proposed technique, positioning it as a valuable tool for advancing intracellular delivery strategies in biomedical applications.

Syllable-rate-adjusted-modulation (SRAM) predicts clear and conversational speech intelligibility.

Introduction: Objectively predicting speech intelligibility is important in both telecommunication and human-machine interaction systems. The classic method relies on signal-to-noise ratios (SNR) to successfully predict speech intelligibility. One exception is clear speech, in which a talker intentionally articulates as if speaking to someone who has hearing loss or is from a different language background. As a result, at the same SNR, clear speech produces higher intelligibility than conversational speech. Despite numerous efforts, no objective metric can successfully predict the clear speech benefit at the sentence level. Methods: We proposed a Syllable-Rate-Adjusted-Modulation (SRAM) index to predict the intelligibility of clear and conversational speech. The SRAM used as short as 1 s speech and estimated its modulation power above the syllable rate. We compared SRAM with three reference metrics: envelope-regression-based speech transmission index (ER-STI), hearing-aid speech perception index version 2 (HASPI-v2) and short-time objective intelligibility (STOI), and five automatic speech recognition systems: Amazon Transcribe, Microsoft Azure Speech-To-Text, Google Speech-To-Text, wav2vec2 and Whisper. Results: SRAM outperformed the three reference metrics (ER-STI, HASPI-v2 and STOI) and the five automatic speech recognition systems. Additionally, we demonstrated the important role of syllable rate in predicting speech intelligibility by comparing SRAM with the total modulation power (TMP) that was not adjusted by the syllable rate. Discussion: SRAM can potentially help understand the characteristics of clear speech, screen speech materials with high intelligibility, and convert conversational speech into clear speech.