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Cancer, ranked as the second leading cause of global mortality with a prevalence of 1 in 6 deaths, necessitates innovative approaches for effective treatment. Combinatorial drug therapy for cancer treatment targets several key pathways simultaneously and potentially enhances anti-cancer efficacy without intolerable side effects. However, it demands precise and accurate control of drug-dose combinations and their release. In this study, we demonstrated a selectively cross-linked hydrogel-based platform that can quantify and release drugs simultaneously for in-parallel cocktail drug screening. PDMS was used as the flow channel substrate and the poly (ethylene glycol) diacrylate (PEGDA) hydrogel array was formed by UV exposure using the photomask. Employing our platform, cocktails of anticancer drugs are precisely loaded and simultaneously released in-parallel into HCT-116 colon cancer cells, facilitating combinatorial drug screening. The integration of an artificial intelligence-based complex system response (AI-CSR) platform successfully identifies optimal drug-dose combinations from a pool of ten approved drugs. Notably, our cocktail drug chip demonstrates exceptional efficiency, screening 155 drug-dose combinations within a brief two and a half hours, a marked improvement over traditional methods. Furthermore, the device exhibits low drug consumption, requiring a mere 1 μL per patch of chip. Thus, our developed PDMS drug-loaded hydrogel platform presents a novel and expedited approach to quantifying drug concentrations, promising to be a faster, efficient and more precise approach for conducting cocktail drug screening experiments. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Most breast cancer-related deaths are caused by distant metastases and drug resistance. It is important to find appropriate biomarkers to monitor the disease and to predict patient responses after treatment early and accurately. Many studies have found that clustered circulating tumor cells, with more correlations with metastatic cancer and poor survival of patients than individual ones, are promising biomarkers. Methods: Eighty samples from eleven patients with breast cancer during follow-up visits were examined. By using a microfluidic chip and imaging system, the number of circulating tumor cells and microemboli (CTC/CTM) were counted to assess the distribution in stratified patients and the potential in predicting the disease condition of patients after treatments during follow-up visits. Specific components and subtypes of CTM were also preliminarily investigated. Results: Compared to CTC, CTM displayed a distinguishable distribution in stratified patients, having a better AUC value, in predicting the disease progression of breast cancer patients during follow-up visits in this study. Four subtypes were categorized from the identified CTM by considering different components. In combination with CEA and CA153, enumerated CTC and CTM from individual patients were applied to monitor the disease condition and patient response to the therapy during follow-up visits. Conclusions: The CTM and its subtypes are promising biomarkers and valuable tools for studying cancer metastasis and longitudinally monitoring cancer patients during follow-up visits. [ABSTRACT FROM AUTHOR]

In this paper, we demonstrate the use of machine learning to optimize the continuous flow process of a crucial intermediate in the production of Nemonoxacin. Our focus is to achieve the good yield and enantioselectivity in the construction of chiral methyl group utilize the initial 29 experimental datasets and consider six important variables. Employing Single-Objective Bayesian optimization (SOBO), we achieved an impressive predicted yield of up to 89.7%, which is consistent with the experimental results, with a yield of 89.5%. Additionally, A Multi-Objective Bayesian Optimization (MOBO) algorithm, namely qNEHVI, to strike a balance between yield and enantioselectivity in the continuous flow system is applied. The algorithm's prediction, with a yield of 81.8% and enantioselectivity of 97.85%, was experimentally validated, yielding 83.8% and 97.2%, respectively. This study effectively demonstrates that Bayesian optimization is a powerful tool for optimizing the continuous process in the production of active pharmaceutical ingredients (APIs). [ABSTRACT FROM AUTHOR]

Senescence of skeletal muscle (SkM) has been a primary contributor to senior weakness and disability in recent years. The gradually declining SkM function associated with senescence has recently been connected to an imbalance between damage and repair. Macrophages (Mac) are involved in SkM aging, and different macrophage subgroups hold different biological functions. Through comprehensive single-cell transcriptomic analysis, we first compared the metabolic pathways and biological functions of different types of cells in young (Y) and old (O) mice SkM. Strikingly, the Mac population in mice SkM was also explored, and we identified a unique Mac subgroup in O SkM characterized by highly expressed SPP1 with strong senescence and adipogenesis features. Further work was carried out on the metabolic and biological processes for these Mac subgroups. Besides, we verified that the proportion of the SPP1+ Mac was increased significantly in the quadriceps tissues of O mice, and the senotherapeutic drug combination dasatinib + quercetin (D + Q) could dramatically reduce its proportion. Our study provides novel insight into the potential role of SPP1+ Mac in SkM, which may serve as a senotherapeutic target in SkM aging. [ABSTRACT FROM AUTHOR]

In this study, antagonistic endophytic fungi were isolated from postharvest chestnut fruits; endophytic antagonistic fungi and their combination of inhibitory effects on the fungal pathogen Neofusicoccum parvum were evaluated. A total of 612 endophytic fungi were isolated from 300 healthy chestnut kernels, and 6 strains out of them including NS-3, NS-11, NS-38, NS-43, NS-56, and NS-58 were confirmed as antagonistic endophytic fungi against Neofusicoccum parvum; these were separately identified as Penicillium chermesinum, Penicillium italicum, Penicillium decaturense, Penicillium oxalicum, Talarmyces siamensis, and Penicillium guanacastense. Some mixed antagonistic endophytic fungi, such as NS-3-38, NS-11-38, NS-43-56, and NS-56-58-38, exhibited a much stronger antifungal activity against N. parvum than that applied individually. Among them, the mixture of NS-3-38 showed the highest antifungal activity, and the inhibition rate was up to 86.67%. The fermentation broth of NS-3, NS-38, and their combinations exhibited an obvious antifungal activity against N. parvum, and the ethyl acetate phase extract of NS-3-38 had the strongest antifungal activity, for which the inhibitory rate was up to 90.19%. The NS-3-38 fermentation broth combined with a chitosan coating significantly reduced N. parvum incidence in chestnuts from 100% to 19%. Furthermore, the fruit decay and weight loss of chestnuts during storage were significantly decreased by the NS-3-38 fermentation broth mixture along with a chitosan coating. Therefore, a mixture of P. chermesinum and P. decaturense could be used as a potential complex biocontrol agent to control postharvest fruit decay in chestnuts. [ABSTRACT FROM AUTHOR]

Background: Listeriosis is caused by the facultative anaerobic bacterium Listeria monocytogenes. Infection from Listeria-contaminated food or water is the main etiology. If Listeria travels outside the intestines, it can cause invasive listeriosis, such as sepsis, meningitis, and meningoencephalitis. Invasive illness is especially dangerous for pregnant women and their newborns, elderly people, and people with compromised immune systems or medical conditions such as end-stage kidney disease (ESKD) patients receiving long-term dialysis. Purpose: Describe the manifestations and hospital outcomes of invasive listeriosis and identify the risk factors for in-hospital and one-year mortality in ESKD patients receiving long-term dialysis. Patients and Methods: This retrospective observational study examined hospitalized patient records at a Taiwanese tertiary medical center from August 1, 2000, to August 31, 2021. ESKD patients on chronic dialysis were identified with invasive listeriosis by blood culture and discharge diagnosis. Over 21 years, we accurately recorded 26 cases. Results: ESKD patients on chronic dialysis with invasive listeriosis have a poor prognosis. Only 53.8% of chronic dialysis patients with invasive listeriosis survived their first hospital episode. 42.3% of hospitalized ESKD patients with invasive listeriosis survived one year later. In univariate analysis, shock, tachypnea (RR ≥ 22), respiratory failure, qSOFA score ≥ 2, and lower initial platelet count were linked to greater in-hospital mortality rates. Conclusion: ESKD patients with invasive listeriosis have a grave prognosis. Our research reveals that an early blood sample for a bacterial culture may identify invasive listeriosis in chronic dialysis patients with fever, nausea or vomiting, confusion, and respiratory distress. This study is the first to identify a lower platelet count and qSOFA score ≥ 2 as markers of high-risk invasive listeriosis in ESKD patients. [ABSTRACT FROM AUTHOR]

Although the telephone band (0.3–3 kHz) provides sufficient information for speech recognition, the contribution of the non-telephone band (<0.3 and >3 kHz) is unclear. To investigate its contribution, speech intelligibility and talker identification were evaluated using consonants, vowels, and sentences. The non-telephone band produced relatively good intelligibility for consonants (76.0%) and sentences (77.4%), but not vowels (11.5%). The non-telephone band supported good talker identification only with sentences (74.5%), but not vowels (45.8%) or consonants (10.8%). Furthermore, the non-telephone band cannot produce satisfactory speech intelligibility in noise at the sentence level, suggesting the importance of full-band access in realistic listening. [ABSTRACT FROM AUTHOR]

Autonomic nerve dysfunction is a common non-motor symptom of Parkinson's disease (PD). It has a high incidence and involves multiple organ system disorders with various manifestations, seriously affecting the quality of life. Autonomic nerve dysfunction can be a major symptom of advanced PD and a major cause of disability. Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced PD, and its improvement of motor symptoms in PD patients has been widely recognized. However, the effect of STN - DBS on the symptoms of autonomic nerve dysfunction in PD patients is still unclear. Here, the efficacy of STN - DBS on PD autonomic nerve dysfunction is briefly reviewed. Therefore, we should pay more attention to the symptoms of autonomic nerve dysfunction in PD patients, and conduct preoperative evaluation of DBS in PD patients, so as to comprehensively consider the postoperative efficacy, target selection, stimulus parameter setting, drug adjustment, develop an individualized treatment plan. [ABSTRACT FROM AUTHOR]

Although the telephone band (0.3–3 kHz) provides sufficient information for speech recognition, the contribution of the non-telephone band (<0.3 and >3 kHz) is unclear. To investigate its contribution, speech intelligibility and talker identification were evaluated using consonants, vowels, and sentences. The non-telephone band produced relatively good intelligibility for consonants (76.0%) and sentences (77.4%), but not vowels (11.5%). The non-telephone band supported good talker identification only with sentences (74.5%), but not vowels (45.8%) or consonants (10.8%). Furthermore, the non-telephone band cannot produce satisfactory speech intelligibility in noise at the sentence level, suggesting the importance of full-band access in realistic listening. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In the paper, the possibility of two complete conversions is investigated, one is from the two‐photon hyperentangled Knill–Laflamme–Milburn (KLM) state to hyperentangled Bell states, the other is from three‐photon KLM state to the hyperentangled Greenberger–Horne–Zeilinger states, for photonic systems hyper‐encoded in polarization and spatial degrees of freedom assisted by error‐heralded quantum units (EHQUs). The system inhomogeneity and/or the imperfect photon scattering often restrict the performance of effective conversions of two types of hyperentangled states, and result in the reductions of the fidelity and the efficiency in tangible quantum information technologies. The polarization EHQU and spatial EHQU are two critical tools for actualizing two hyperentangled conversions in a heralded way, as the errors stemming from the system inhomogeneity and practically imperfect scattering are converted into efficacious responses of the detectors in our protocols. Thus, the fidelities of these conversion cases keep unchanged and have close to unity fidelities, which deepen the understanding of the properties of hyperentanglement. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-β-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

As the most widespread juice produced and consumed globally, citrus juice (mandarin juice, orange juice, and grapefruit juice) is appreciated for its attractive and distinct aroma. While the decrease of characteristic aroma-active compounds and the formation of off-flavor compounds are easy to occur in processing and storage conditions. This review provides a comprehensive literature of recent research and discovery on citrus juice off-flavor, primarily focusing on off-flavor compounds induced during processing and storage (i.e., thermal, storage, light, oxygen, package, fruit maturity, diseases, centrifugal pretreatment, and debittering process), formation pathways (i.e., terpene acid-catalyzed hydration, caramelization reaction, Maillard reaction, Strecker degradation, and other oxidative degradation) of the off-flavor compounds, effective inhibitor pathway to off-flavor (i.e., electrical treatments, high pressure processing, microwave processing, ultrasound processing, and chemical treatment), as well as odor assessment techniques based on molecular sensory science. The possible precursors (terpenes, sulfur-containing amino acids, carbohydrates, carotenoids, vitamins, and phenolic acids) of citrus juice off-flavor are listed and are also proposed. This review intends to unravel the regularities of aroma variations and even off-flavor formation of citrus juice during processing and storage. Future aroma analysis techniques will evolve toward a colorimetric sensor array for odor visualization to obtain a "marker" of off-flavor in citrus juice. (1) Processing and storage can cause the degradation of nutrients in citrus juice and the formation of off-flavor compounds. (2) Terpene degradation products, sulfur-containing compounds, phenols, acids, and furans are contributed to citrus juice off-flavor. (3) Nonthermal techniques such as electrical treatments, high pressure, microwave, and ultrasound processing is beneficial to preservation of the original aroma and sensory qualities of citrus juice. (4) Potential off-flavor compounds (especially trace level) explored by molecular sensory science also significantly impact the aroma of citrus juice. [ABSTRACT FROM AUTHOR]

Flash flood disasters are one of the major natural disasters in the world, and rapid and accurate early identification of flash flood disasters is the key to preventing and controlling them. In recent years, computer and spatial information technology development has promoted the advancement of early identification technology for flash floods. However, previous research has mainly focused on the impact of 'water' and neglected the impact of 'sediment' deposition on the rise of water levels. To gain a more comprehensive understanding of flash floods and improve the accuracy of early identification, this article first uses bibliometric methods to review the spatiotemporal distribution, internal relationships, and research hotspots of literature in this field over the past 42 years. Then, the research practice of considering the impact of sediment on the early identification of flash floods was introduced from three aspects: mechanism, model, and uncertainty. Finally, the existing problems in current research were discussed, and future research directions were proposed. The research results have shown that the number of publications in this field has been increasing yearly and will continue to increase, but the cooperation between authors is not close. The coupling effect between sediment replenishment and floods cannot be ignored. Taking into account multiple uncertainties can greatly improve recognition accuracy. This study can provide a panoramic literature perspective and practical research experience for relevant researchers and decision-makers and support further improving flash flood prevention and control capabilities. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bactrocera minax is a devastating pest of citrus fruits. However, there have been no effective control measures before. Few reports on the sex pheromones of B. minax are available. RESULTS: In this study, nine of the volatile compounds in adult females were identified using headspace solid‐phase microextraction (HS‐SPME) in combination with gas chromatography–mass spectrometry (GC–MS). Among them, d‐limonene, caprolactam, 2‐Nitro‐1H‐imidazole, and creatinine could evoke antennal responses in males. Field bioassays showed that only d‐limonene could lure male flies, with a relative lure rate of 78.18% in all tested samples, which was significantly higher than that of paraffin oil control, while all volatile compounds did not have any lure effective to female flies. Moreover, d‐limonene was diluted with paraffin oil into differential concentrations, the lure effect on males was better at 100, 500, and 800 μL d‐limonene mL−1 than pure d‐limonene (1000 μL mL−1). The relative male lure rate of d‐limonene at 100 μL mL−1 was 85.88%, which was significantly higher than that of food−baits (14.12%) on day 3. However, d‐limonene was unattractive to female and male Bactrocera dorsalis and Zeugodacus tau. Further kinetic analysis showed that female adults released d‐limonene around 15‐day post eclosion. Electroantennography 1 results showed that 500 μL mL−1 d‐limonene evoked the strongest responses to antennae of 10‐ to 25‐day‐old male flies. CONCLUSION: Our results indicated that d‐limonene could be a sex pheromone from female flies of B. minax, and it could be used as a male‐specific sex attractant for B. minax. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Entanglement concentration protocol (ECP), as a practical technique, can be use to preclude degraded fidelity and improve security in long-haul quantum communication. We propose an efficient ECP for less-entangled unknown W states with simple linear-optics elements and effective single-photon detectors, resorting to time-delay degree of freedom. Moreover, in contrast to previous ECPs proposed for W states, the scheme has the advantages over requiring less quantum resource without auxiliary photons, comparatively simplified circuits, involving neither post-selection techniques nor photon-number-resolving detectors to distinguish the parity outcome, and being provided with a higher success probability by reusing the less-entangled states. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Stroke can lead to long - term motor disorders and reduced quality of life. Despite advances in conventional rehabilitation, many patients are still faced with limited efficacy of rehabilitation. Neuromodulation techniques have shown breakthrough therapeutic potential. The purpose of this article is to provide an overview of the mechanism of poststroke neuroplasticity, to explore the mechanism of dentate nucleus deep brain stimulation (DN - DBS) to improve poststroke motor function, and to summarize the progress of the study, in order to provide a scientific basis and a new therapeutic perspective for clinical practice of DN-DBS. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) has been widely used for Parkinson's disease, essential tremor, dystonia, drug - resistant epilepsy and other diseases. The operation procedure of this surgical method is complicated, and it also has certain complications in clinical application, including surgical complications such as intracranial hemorrhage and infection, hardware complications such as lead fracture and displacement, and stimulation complications such as paresthesia and muscle spasm, in which lead fracture and erosion and infection of the skin behind the ear are common and troublesome complications. In clinical practice, we found that lead fracture and erosion and infection of the skin were mainly located behind the ear. Since 2012, Beijing Tiantan Hospital, Capital Medical University had applied the retroauricular bone grinding groove technology in DBS, which significantly reduced the incidence of lead fracture and erosion and infection of the skin. Therefore, the retroauricular bone grinding groove technology can effectively solve the above problems. This paper mainly introduces the retroauricular bone grinding groove technology and the clinical application attention matters, providing references for colleagues. [ABSTRACT FROM AUTHOR]

A study published in the National Science Review examined the use of variable frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) to improve freezing of gait (FOG) in patients with Parkinson's disease (PD). Traditional high-frequency stimulation (HFS) does not effectively control axial symptoms such as gait dysfunction and FOG. The study found that the novel paradigm of variable frequency stimulation (VFS) with alternating HFS and low-frequency stimulation (LFS) resulted in significant improvements in gait speed, reduction in freezing episodes, and control of tremors, bradykinesia, and rigidity. The study suggests that VFS could be a long-term management option for PD patients with intractable gait dysfunction. [Extracted from the article]

BACKGROUND: 60Co‐γ irradiation can simulate the effects of aging and enhance the flavor of distilled spirits. The present study aimed to investigate the effects of 0, 2, 4, 6, 8 and 10 kGy 60Co‐γ irradiation doses on the key aroma components in newly produced navel orange distilled spirits and thus determine the mechanism of their aging distilled spirits. RESULTS: The identification of aroma compounds demonstrated that ethyl hexanoate, d‐limonene, ethyl octanoate, 3‐methyl‐1‐butanol and linalool are the key aroma compounds in navel orange distilled spirits, which were increased except for linalool with irradiation doses of 2–6 kGy. Irradiation treatment simulated the effects of the aging of navel orange distilled spirits by promoting the content of total acids, total esters and aldehydes. Irradiation doses of 2–6 kGy increased the aroma intensity of navel orange distilled spirits, reaching an optimum at 6 kGy. However, irradiation doses as high as 8 and 10 kGy decreased the content of esters in navel orange distilled spirits, which led to a deterioration of the spirit flavor. CONCLUSION: Low doses of 60Co‐γ irradiation can simulate the effects of the aging by increasing the content of key aromatic compounds in navel orange distilled spirits. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Endovascular therapy (EVT) is effective in the treatment of large vascular occlusive stroke. However, many factors are associated with the outcomes of acute ischemic stroke (AIS) after EVT. This study aimed to identify the main factors related to the prognosis of AIS patients after EVT. We analyzed the clinical data of AIS patients in the neurology department of our medical center from June 2017 to August 2021 following treatment with EVT. The data included the patients' blood pressure upon admission, blood glucose concentration, National Institutes of Health Stroke Scale (NIHSS) score, 90-day modified Rankin scale (mRs) score follow-up data, and time from LKN to the successful groin puncture (GP). A good outcome was defined as a 90-day mRs score of 0–2, and a poor outcome was defined as a 90-day mRs score of 3–6. A total of 144 patients were included in the study. Admission, smoking, and LKN-to-GP time, NIHSS score of 6–12 was found to be relevant to the prognosis. The results of multivariate analysis showed that prognosis was significantly influenced by baseline NIHSS (odds ratio = 3.02; 95% confidence interval, 2.878–4.252; P = 0.001), LKN-to-GP time (odds ratio = 2.17; 95% confidence interval, 1.341–2.625; P = 0.003), and time stratification (6–12 h) (odds ratio = 4.22; 95% confidence interval, 2.519–5.561; P = 0.001). Our study indicated that smoking, baseline NIHSS score, and LKN-to-GP time were the risk factors for a poor outcome in stroke patients following an EVT. Quitting smoking and shortening LKN time to GP should improve the outcome of AIS after EVT. [ABSTRACT FROM AUTHOR]

Debris flow is a typical natural disaster in the middle reaches of the Dadu River, which seriously threatens the safety of life and property of local residents. However, there is currently a lack of a comprehensive analysis methods applicable to the blockage of river channels by debris flow in the Dadu River basin, limiting disaster prevention and mitigation in this area. Based on previous large-scale model tests carried out in the middle reaches of the Dadu River, the debris flows are divided into dam-type debris flows and submerged debris flows. The calculation formulas for the maximum travel distance of the two kinds of debris flows entering the river are obtained via theoretical derivation. The formulas for calculating the length and volume of debris flow accumulation are derived, and the relationship between the debris flow loss coefficient and river blocking degree in the middle part of the Dadu River is analyzed. An identification method of river blocking by debris flow is put forward in this study. By calculating the maximum blocking degree, S (the ratio of the maximum driving distance of the debris flow to the width of the river), and the volume of the source materials needed to form a debris flow dam under the conditions that the debris flow does not reach the opposite bank (V1), reaches the opposite bank but does not block the river (V2), and reaches the opposite bank (V3), the form of debris flow blocking the river is distinguished. When S = 1, V > V3, complete blockage occurs; when S = 1, V > V2, the river is mostly blocked; when S < 1, V > V1, the river is half-blocked. This study established an identification method of river blocking by debris flow, providing a basis for early warning for river blocking and disaster prevention in the middle reaches of the Dadu River. [ABSTRACT FROM AUTHOR]

Mechanistic insight is achieved only when experiments are employed to test formal or computational models. Furthermore, in analogy to lesion studies, phantom perception may serve as a vehicle to understand the fundamental processing principles underlying healthy auditory perception. With a special focus on tinnitus—as the prime example of auditory phantom perception—we review recent work at the intersection of artificial intelligence, psychology and neuroscience. In particular, we discuss why everyone with tinnitus suffers from (at least hidden) hearing loss, but not everyone with hearing loss suffers from tinnitus. We argue that intrinsic neural noise is generated and amplified along the auditory pathway as a compensatory mechanism to restore normal hearing based on adaptive stochastic resonance. The neural noise increase can then be misinterpreted as auditory input and perceived as tinnitus. This mechanism can be formalized in the Bayesian brain framework, where the percept (posterior) assimilates a prior prediction (brain's expectations) and likelihood (bottom-up neural signal). A higher mean and lower variance (i.e. enhanced precision) of the likelihood shifts the posterior, evincing a misinterpretation of sensory evidence, which may be further confounded by plastic changes in the brain that underwrite prior predictions. Hence, two fundamental processing principles provide the most explanatory power for the emergence of auditory phantom perceptions: predictive coding as a top-down and adaptive stochastic resonance as a complementary bottom-up mechanism. We conclude that both principles also play a crucial role in healthy auditory perception. Finally, in the context of neuroscience-inspired artificial intelligence, both processing principles may serve to improve contemporary machine learning techniques. [ABSTRACT FROM AUTHOR]

As debris flow disasters are becoming increasingly severe worldwide, it is necessary to deepen the research on disaster losses, especially the impact and role of disaster mitigation measures. Based on the regional disaster system theory, this paper sets an influencing factor system of debris flow losses. Then, from the perspective of networked risk, the risk propagation network is established through the Delphi method. Finally, the social network analysis method is introduced to discuss the risk propagation relationship between these factors from two aspects of the overall network analysis and node centrality analysis. The results reveal the chain-like influence characteristics of factors and clarify the main points relevant departments should emphasise in disaster risk reduction. Environmental and engineering mitigation measures strongly influence other factors, thus dominating the risk propagation in forming debris flow losses. The peril of debris flow, residents' escape ability, and emergency rescue can be easily influenced by other factors, so increasing the resistance of these sensitive factors to the source of influence would support loss reduction. The research results can be applied to risk assessment and loss reduction of debris flow disasters. [ABSTRACT FROM AUTHOR]

Cell patterning is a powerful technique for the precise control and arrangement of cells, enabling detailed single-cell analysis with broad applications in therapeutics, diagnostics, and regenerative medicine. This study presents a novel and efficient technique that enables massively parallel high throughput cell patterning and precise delivery of small to large biomolecules into patterned cells. The innovative cell patterning device proposed in this study is a standalone, ultrathin 3D SU-8 micro-stencil membrane, with a thickness of 10 μm. It features an array of micro-holes ranging from 40 μm to 80 μm, spaced apart by 50 μm to 150 μm. By culturing cells on top of this SU-8 membrane, the technique achieves highly efficient cell patterns varying from single-cell to cell clusters on a Petri dish. Utilizing this technique, we have achieved a remarkable reproducible patterning efficiency for mouse fibroblast L929 (80.5%), human cervical SiHa (81%), and human neuroblastoma IMR32 (89.6%) with less than 1% defects in undesired areas. Single-cell patterning efficiency was observed to be highest at 75.8% for L929 cells. Additionally, we have demonstrated massively parallel high throughput uniform transfection of large biomolecules into live patterned cells by employing an array of titanium micro-rings (10 μm outer diameter, 3 μm inner diameter) activated through infrared light pulses. Successful delivery of a wide range of small to very large biomolecules, including propidium iodide (PI) dye (668.4 Da), dextran (3 kDa), siRNA (13.3 kDa), and β-galactosidase enzyme (465 kDa), was accomplished in cell patterns for various cancer cells. Notably, our platform achieved exceptional delivery efficiencies of 97% for small molecules like PI dye and 84% for the enzyme, with corresponding high cell viability of 100% and 90%, respectively. Furthermore, the compact and reusable SU-8-based membrane device facilitates highly efficient cell patterning, transfection, and cell viability, making it a promising tool for diagnostics and therapeutic applications. [ABSTRACT FROM AUTHOR]

Aging is a major risk factor for cardiovascular diseases. Our previous studies demonstrate that aging impairs the caveolar T‐type CaV3.2‐RyR axis for extracellular Ca2+ influx to trigger Ca2+ sparks in vascular smooth muscle cells (VSMCs). We hypothesize that the administration of senolytics, which can selectively clear senescent cells, could preserve the caveolar CaV3.2‐RyR axis in aging VSMCs. In this study, 10‐month‐old mice were administered the senolytics cocktail consisting of dasatinib (5 mg/kg) and quercetin (50 mg/kg) or vehicle bi‐weekly for 4 months. Using VSMCs from mouse mesenteric arteries, we found that Ca2+ sparks were diminished after caveolae disruption by methyl‐β‐cyclodextrin (10 mM) in cells from D + Q treated but not vehicle‐treated 14‐month‐old mice. D + Q treatment promoted the expression of CaV3.2 in 14‐month‐old mesenteric arteries. Structural analysis using electron tomography and immunofluorescence staining revealed the remodeling of caveolae and co‐localization of CaV3.2‐Cav‐1 in D + Q treatment aged mesenteric arteries. In keeping with theoretical observations, Cav3.2 channel inhibition by Ni2+ (50 μM) suppressed Ca2+ in VSMCs from the D + Q group, with no effect observed in vehicle‐treated arteries. Our study provides evidence that age‐related caveolar CaV3.2‐RyR axis malfunction can be alleviated by pharmaceutical intervention targeting cellular senescence. Our findings support the potential of senolytics for ameliorating age‐associated cardiovascular disease. [ABSTRACT FROM AUTHOR]

By harnessing weak cross‐Kerr nonlinearities, it proposes two deterministic hyperparallel quantum control gates, including the hyperparallel controlled‐NOT (hyper‐CNOT) gate and hyperparallel Fredkin (hyper‐Fredkin) gate for photonic systems in the polarization and spatial degrees of freedom (DoFs), which are composed of two procedures for the implementations of the first polarized control (CNOT and Fredkin) gates and the second spatial control (CNOT and Fredkin) ones in turn. Moreover, compared with the two two‐photon CNOT gates (three‐photon Fredkin gates) in one DoF, the hyper‐CNOT (hyper‐Fredkin) gate is provided with more straightforward quantum circuits, lower computational costs of resource overhead (without the assistance of single photons or entangled states), less cross‐Kerr nonlinear interactions between three photons and the coherent states, and reduces the effect caused by photon‐loss noise. The success probabilities of two quantum control gates are approximated unit by performing the corresponding classical feed‐forward operations based on the different measuring outcomes of the X‐homodyne detectors to be aimed at the coherent states, and they are robust against the photon loss as well, which are feasible with the current technology and convenient in practical applications. [ABSTRACT FROM AUTHOR]

This paper proposes a Swiss-roll-type mini-reformer employing a copper–zinc catalyst for high-efficient SRM process. Although the commercially available copper–zinc catalysts commonly used in cylindrical-type reformers provide decent conversion rates in the short term, their long-term durability still requires improvement, mainly due to temperature variations in the reformer, catalyst loading, and thermal sintering issues. This Swiss-roll-shaped mini-reformer is designed to improve thermal energy preservation/temperature uniformity by using dual spiral channels to improve the long-term durability while maintaining methanol-reforming efficiency. It was fabricated on a copper plate that was 80 mm wide, 80 mm long, and 4 mm high with spiral channels that were 2 mm deep, 4 mm wide, and 350 mm long. To optimize the design and reformer operation, the catalyst porosity, gas hourly speed velocity (GHSV), operation temperature, and fuel feeding rate are investigated. Swiss-roll-type reformers may require higher driving pressures but can provide better thermal energy preservation and temperature uniformity, posing a higher conversion rate for the same amount of catalyst when compared with other geometries. By carefully adjusting the catalyst bed porosity, locations, and catalyst loading amount as well as other conditions, an optimized gas hourly space velocity (GHSV) can be obtained (14,580 mL/g·h) and lead to not only a high conversion rate (96%) and low carbon monoxide generation rate (0.98%) but also a better long-term durability (decay from 96% to 88.12% after 60 h operation time) for SRM processes. The decay rate, 0.13%/h, after 60 h of operation, is five-folds lower than that (0.67%/h, 0.134%/h) of a commercial cylindrical-type fixed-bed reactor with a commercial catalyst. [ABSTRACT FROM AUTHOR]

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High‐efficiency quantum information processing is equivalent to the fewest quantum resources and simplest operations by means of logic qubit gates. Based on the reflection geometry of a single photon interacting with a three‐level Λ‐type atom‐cavity system, the authors present some refined protocols for realizing controlled‐not (CNOT), Fredkin, and Toffoli gates on hybrid systems. The first control qubit of gates is encoded on a flying photon, and the remaining qubits are encoded on the atoms in the optical cavity. Moreover, these quantum gates can be extended to the optimal synthesis of multi‐qubit CNOT, Fredkin, and Toffoli gates with O(n)$ O(n)$ optical elements without auxiliary photons or atoms. Further, the simplest single‐qubit operations are applied to the photon only, which make these logic gates experimentally feasible with current technology. [ABSTRACT FROM AUTHOR]

Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), that can improve patients' motor and non‐motor symptoms. However, there are differences in the improvement of patients' emotional symptoms and cognitive function. Objective: To investigate the impact of active contact location and the volume of tissue activated (VTA) on patients' emotional symptoms and cognitive function in STN‐DBS in PD. Methods: A total of 185 PD patients were included in this study. We evaluated them using the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale, Hamilton Anxiety Scale (HAM‐A), Hamilton Depression Scale (HAM‐D), Montreal Cognitive Assessment (MoCA), and Mini‐Mental State Examination (MMSE) scales at the preoperative, 1‐ and 12‐month postoperative time points. Leads were positioned in standard space using the Lead‐DBS toolbox, and VTA was calculated for analysis. Results: When the lead active contact was closer to the ventral side of the STN, the patients' HAM‐A improvement rate was higher, and when the active contact was closer to the anterior and dorsal sides of the STN, the patients' MoCA improvement rate was higher. Stimulation of the sensorimotor zone was more favorable to the improvement of HAM‐A and HAM‐D in patients. And, the stimulation of the associative zone was more favorable to the improvement of MoCA in patients. Conclusion: Our results provide evidence that the 12‐month outcomes of cognitive function and emotional symptoms in PD patients with STN‐DBS were closely related to the specific location of the active contacts in the STN and influenced by the VTA. [ABSTRACT FROM AUTHOR]

Redox flow batteries (RFBs) are hindered by complex failure modes, particularly crossover through the membrane, resulting in capacity fade and reduced cycling efficiencies. Redox‐active oligomers (RAOs) have recently been proposed for mitigating this phenomenon while maintaining sufficient transport properties; however, to date, few studies have quantified how the chemical and electrochemical properties of RAOs influence their performance in redox flow cells. Here, we demonstrate that oligomeric derivatives of 2,2,6,6‐tetramethylpiperidine 1‐oxyl (TEMPO) exhibit lower diffusivities than the monomeric species but retain facile charge transfer characteristics. The size‐dependent variations in mass transport rates directly translate to differences in flow cell polarization and symmetric cycling performance. Post‐mortem analyses reveal that oligomerization does not meaningfully alter decay processes as evinced by similar capacity fade across all species. Broadly, these findings corroborate and extend upon previously developed relationships between molecular size, electrochemical properties, and flow cell performance. [ABSTRACT FROM AUTHOR]

BACKGROUND: (+)‐Nootkatone is a highly valuable sesquiterpene compound that can be used as an aromatic in the food industry because of its grapefruit flavor and low sensory threshold. The unconventional yeast Yarrowia lipolytica has many unique physical and chemical properties, metabolic characteristics, and genetic structure, which has aroused the interest of researchers. Previous research showed that Y. lipolytica possesses the ability to transform the sesquiterpene (+)‐valencene to (+)‐nootkatone. The aim of this study was to isolate, purify, and identify the enzyme involved in the (+)‐valencene bioconversion to (+)‐nootkatone by Y. lipolytica. RESULTS: In this study, ultrasonic‐assisted extraction, ammonium sulfate precipitation, anion‐exchange chromatography, and gel‐filtration chromatography were used to separate and purify the enzyme involved in the (+)‐valencene bioconversion by Y. lipolytica. The protein was identified as aldehyde dehydrogenase (ALDH) (gene0658) using sodium dodecyl sulfate polyacrylamide gel electrophoresis and liquid chromatography–tandem mass spectrometry analysis. The ALDH had the highest activity when the pH value was 6.0 and the temperature was 30 °C. The activity of ALDH was significantly stimulated by ferrous ions and inhibited by barium, calcium, and magnesium ions. CONCLUSION: This is the first time that ALDH was found to participate in (+)‐valencene biotransformation by Y. lipolytica. It may be involved in regulating the microbial transformation of (+)‐valencene to (+)‐nootkatone through redox characteristics. This study provides a theoretical basis and reference for the biological synthesis of citrus flavor (+)‐nootkatone. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The nanoscale photothermal effect and the optofluidic convection around plasmonic nanoparticles drive the application of such nanoparticles in micro-environment. In this work, heat transfer and fluid flow around Au nanospheres and nanorods in water medium under continuous and pulsed wave laser irradiance was investigated using an FEM based numerical framework. Au nanospheres of a wide range of diameter: 40 nm ≤ Diameter (D) ≤ 180 nm and relatively large nanorods (diameter: 50 nm) with varying aspect ratio (1 ≤ Aspect ratio (A) ≤ 5) and orientation (0° ≤ θ ≤ 90°, ϕ = 0°, 90°) with respect to the incident EM radiation were investigated for continuous wave (CW) and pulsed wave laser. It was found that although nanorods can attain much higher temperature than nanospheres, orientation of a nanorod is an important factor to be carefully considered in applications. In micro-scale spherical and hemispherical confinements (diameter < 14.4 μm), the convective velocity fields around nanoparticles is in the order of 10–9 m/s, with only a weak effect of the slip or no-slip boundary condition on the confining walls. Importantly, the size of the confinement has a strong effect leading to an order of magnitude stronger convection for 14.4 μm (diameter) spherical confinement as compared to 3.6 μm confinement. Additionally close proximity of the nanoparticles to the confining walls strongly reduces (by an order of magnitude) the convective currents. The results reported herein provides important insights for the use of photothermal nanoparticles in microscale confined space (e.g. cellular environment) for applications such as optical tweezers, photoporation, etc. [ABSTRACT FROM AUTHOR]

Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury. [ABSTRACT FROM AUTHOR]

Neuroinflammation is a key feature in the pathogenesis of entrapment neuropathies. Clinical trial evidence suggests that perineural injection of glucose in water at entrapment sites has therapeutic benefits beyond a mere mechanical effect. We previously demonstrated that 12.5–25 mM glucose restored normal metabolism in human SH-SYFY neuronal cells rendered metabolically inactive from TNF-α exposure, a common initiator of neuroinflammation, and reduced secondary elevation of inflammatory cytokines. In the present study, we measured the effects of glucose treatment on cell survival, ROS activity, gene-related inflammation, and cell cycle regulation in the presence of neurogenic inflammation. We exposed SH-SY5Y cells to 10 ng/mL of TNF-α for 24 h to generate an inflammatory environment, followed by 24 h of exposure to 3.125, 6.25, 12.5, and 25 mM glucose. Glucose exposure, particularly at 12.5 mM, preserved apoptotic SH-SY5Y cell survival following a neuroinflammatory insult. ROS production was substantially reduced, suggesting a ROS scavenging effect. Glucose treatment significantly increased levels of CREB, JNK, and p70S6K (p < 0.01), pointing to antioxidative and anti-inflammatory actions through components of the MAPK family and Akt pathways but appeared underpowered (n = 6) to reach significance for NF-κB, p38, ERK1/2, Akt, and STAT5 (p < 0.05). Cell regulation analysis indicated that glucose treatment recovered/restored function in cells arrested in the S or G2/M-phases. In summary, glucose exposure in vitro restores function in apoptotic nerves after TNF-α exposure via several mechanisms, including ROS scavenging and enhancement of MAPK family and Akt pathways. These findings suggest that glucose injection about entrapped peripheral nerves may have several favorable biochemical actions that enhance neuronal cell function. [ABSTRACT FROM AUTHOR]

Temperature governs the reactivity of a wide range of biomolecules in the cellular environment dynamically. The complex cellular pathways and molecules in solid tumors substantially produce temperature gradients in the tumor microenvironment (TME). Hence, visualization of these temperature gradients at the cellular level would give physiologically relevant spatio-temporal information about solid tumors. This study used fluorescent polymeric nano-thermometers (FPNTs) to measure the intratumor temperature in co-cultured 3D tumor spheroids. A temperature-sensitive rhodamine-B dye and Pluronic F-127 were conjugated through hydrophobic and hydrophobic interactions and then cross-linked with urea–paraformaldehyde resins to form the FPNTs. The characterization results exhibit monodisperse nanoparticles (166 ± 10 nm) with persistent fluorescence. The FPNTs exhibit a linear response with a wide temperature sensing range (25–100 °C) and are stable toward pH, ionic strength, and oxidative stress. FPNTs were utilized to monitor the temperature gradient in co-cultured 3D tumor spheroids and the temperature difference between the core (34.9 °C) and the periphery (37.8 °C) was 2.9 °C. This investigation demonstrates that the FPNTs have great stability, biocompatibility, and high intensity in a biological medium. The usage of FPNTs as a multifunctional adjuvant may demonstrate the dynamics of the TME and they may be suitable candidates to examine thermoregulation in tumor spheroids. [ABSTRACT FROM AUTHOR]