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Plastic scintillators with pulse shape discrimination (PSD) capability, when combined with silicon photo-multipliers (SiPMs), enable the development of compact neutron detectors with lower power consumption and insensitivity to magnetic fields. However, the SiPM array has a significantly large pulse width of the output signal, which leads to discrimination difficulties at high counting rates. There are two outputs of a SiPM array: a standard output for energy measurement and a fast output for timing measurement. The pulse width of the standard output signal is in the range of hundreds nanoseconds, while the pulse width of the other one is in the range of tens nanoseconds. Fast output signals have traditionally been considered suitably for fast timing, however utilizing them for PSD has been little explored. In our previous work, we successfully implemented PSD by using fast output signals from a SiPM. Despite the obvious negative overshoot in fast signals, we achieved PSD of fast signals by using longer sampling times. However, this approach was still limited at high counting rates. This study proposes a compensation network for fast output signals, which is composed of a compensation unit consisting of a resistor and a capacitor. This design effectively compensates the overshoot of the fast output and shortens the pulse width from 60 ns to 44 ns. Additionally, it highlights the frequency amplitude differences between the neutron and gamma signals from fast output in the high-frequency component, thus improving the PSD capability of the fast output. [ABSTRACT FROM AUTHOR]

Random skin flap grafting is one of the most commonly used techniques in plastic and orthopedic surgery. However, necrosis resulting from ischemia and ischemia-reperfusion injury in the distal part of the flap can severely limit the clinical application of the flap. Studies have revealed that naringenin reduces pyroptosis, apoptosis, and necroptosis, inhibits oxidative stress, and promotes autophagy. In this study, the effects of Naringenin on flap viability and its underlying mechanism were evaluated. Mice with random skin flaps were randomly allocated to control, Naringenin, and Naringenin + 3-methyladenine groups. On postoperative day 7, flap tissues were collected to estimate angiogenesis, necroptosis, apoptosis, pyroptosis, oxidative stress, and autophagy via hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry. The results revealed that naringenin promoted the viability of the random flaps as well as angiogenesis, while inhibiting oxidative stress and decreasing pyroptosis, apoptosis, and necroptosis. These effects were reversed by the autophagy inhibitor 3-methyladenine. The findings indicated that naringenin treatment could promote flap survival by inhibiting pyroptosis, apoptosis, necroptosis, and alleviating oxidative stress, caused by the activation of autophagy. [ABSTRACT FROM AUTHOR]

Fu brick tea (FBT) is a traditional tea manufactured by solid-state fermentation of tea leaves (Camellia sinensis). Although anti-obesity effects have been reported for FBT, the associated role of FBT polysaccharides (PSs) and the underlying mechanisms remain unknown. In this study, we found that FBTPSs inhibited obesity, hyperlipidemia, and inflammation; improved intestinal barrier function; and alleviated gut microbiota dysbiosis in high-fat diet-fed rats. Akkermansia muciniphila, Bacteroides, Parasutterella, Desulfovibrio , and Blautia were the core microbes regulated by FBTPSs. FBTPSs regulated the production of gut microbiota-related metabolites, including short-chain fatty acids (SCFAs), branched-chain amino acids, and aromatic amino acids throughout the development of obesity, and regulated the SCFA-GPR signaling pathway. FBTPS-treated fecal microbiota transplant ameliorated obesity, alleviated gut microbiota dysbiosis, and improved gut microbiota-associated metabolites, suggesting that the anti-obesity effect of FBTPSs was gut microbiota-dependent. FBTPSs may serve as novel prebiotic agents for the treatment of obesity and dysbiosis of gut microbiota. [Display omitted] [ABSTRACT FROM AUTHOR]

Glioma stem cells (GSCs) are thought to be responsible for the initiation and progression of glioblastoma (GBM). GBM presents highly invasive growth with a very high recurrence rate, so it has become a clinical problem to be solved urgently. RNAseq demonstrates that thrombospondin 1 (THBS1) acts not only in the angiogenic core of glioma but also with a high degree of invasiveness and infiltration. Nevertheless, defects in the signaling pathway research lead to a poor prognosis in glioma patients. To investigate the relevant molecular mechanism and signal pathway of glioma stem cell behavior mediated by THBS1 , U251 astroglioma cells and GSCs were taken as model cells for in vitro experiments. The biological effects of THBS1 on glioma proliferation, migration, and adhesion were evaluated using Cell Counting Kit-8(CCK8) assays, EdU incorporation assays, migration assays, Transwell assays, Western blotting, and RNAseq. We found that the knockout of the THBS1 gene by CRISPR/Cas9 promoted proliferation and migration in U251 cells and GSCs, as well as influencing cell cycle progression by regulating the TNF/MAPK/NF-κB and TGF-β/Smad signaling pathways. Moreover, U251 cells and GSCs showed different responses to THBS1 knockout, suggesting specific and potential targets for GSCs in signaling pathways mediated by THBS1. • U251 astroglioma cells and GSCs were taken as model cells for in vitro experiments. • Knockout of the THBS1 gene by CRISPR/Cas9 promoted proliferation and migration in U251 cells and GSCs. • THBS1 gene influencing cell cycle progression by regulating the TNF/MAPK/NF-κB and TGF-β/Smad signaling pathways. • U251 cells and GSCs showed different responses to THBS1 knockout. [ABSTRACT FROM AUTHOR]

In this work, LaFeO 3 core-shell spheres functionalized with different amounts of Au nanoparticles (NPs) were successfully synthesized through a facile hydrothermal method. Various characterization methods were conducted to confirm the morphology, microstructure, and surface properties of the samples. The results demonstrated that the morphology of Au-LaFeO 3 has a uniform core-shell structure. Besides, gas sensing investigation indicated that compared with pure LaFeO 3 , gas sensors based on 4 wt. % Au-LaFeO 3 core-shell spheres exhibited remarkably enhanced sensing properties (5 times higher) toward n -butanol. The sensor has a response value of 115 for 100 ppm n -butanol at 225 °C and has a low limit of detection (500 ppb, 1.2). The enhancement can be mainly ascribed to the Schottky barrier between Au NPs and LaFeO 3. The possible adsorption configuration, the adsorption energy and charge transfer amount of the adsorbate in the absence or presence of Au NPs are calculated based on the first principles. n -Butanol has the highest adsorption energy and is easier to adsorb than other gases. n -Butanol loses more electrons after the functionalization of Au NPs which become negative charge centers and have a spillover effect. This work also provided a new candidate sensing material for high-performance n -butanol sensors. • Au functionalized core-shell LaFeO 3 nanospheres were synthesized by one step. • Au-LaFeO 3 core-shell nanospheres exhibited excellent n -butanol gas sensing property. • Au-LaFeO 3 possesses high response of 115 (100 ppm) and low detection limit (500 ppb). • The spillover effect is considered to be the main reason for the sense enhancement. • First-principles calculations explain positive effects of Au NPs on gas adsorption. [ABSTRACT FROM AUTHOR]

The hydrolyzed biomass, a green and renewable resource, was used as a reducing agent to achieve the harmless treatment of chromium ore processing residue (COPR). This paper proposes a detoxification process of two-stage sulfuric acid leaching accompanied by biomass reduction of hexavalent chromium and a one-step combined leaching and reduction process. The orthogonal tests and single factor tests allowed to propose the most suitable operating conditions of different stages such as biomass hydrolysis, two-stage acid leaching, reduction of the acid leachate and combined leaching and reduction. The Cr(VI) content in both the leach residue and reduction solution reached the discharge criterion. The FTIR and XPS measurements showed that the reducing sugars produced by the hydrolysis of biomass reacted with the leached Cr(VI) to generate chromium sulfate adsorbed on the surface of COPR. In addition, XRD, SEM-EDS showed that the gypsum was generated after COPR detoxification, which can be used for resource utilization, providing a new idea and reference for the harmless treatment of COPR producing Cr(III) and gypsum. [Display omitted] • Distinct detoxification of COPR (>98%) can be achieved with the hydrolyzed biomass. • The optimum conditions of hydrolysis of biomass was 65 °C, 80 wt% H 2 SO 4 , 30 min. • Biomass hydrolysis can produce reducing sugars (>240 mg/g), which react with Cr(VI). • The gypsum was generated for resourcefulness after the detoxification of COPR. [ABSTRACT FROM AUTHOR]

The two-stage electrostatic precipitator (ESP) is widely used for indoor air cleaning field, while both the Particle Image Velocimetry (PIV) observations and well-characterized quantitative descriptions are probably scarce. In this work, we propose to use vortex analysis, which is the main quantitative method for flow field, and the relative residence time method (RRT) to evaluate the electrohydrodynamic flow (EHD) in a plate-plate ESP. The effects of electrical energization, pre-charger polarity and primary gas flow velocity are studied. Two vortex indexes sort the particle flow as five patterns and increase almost linearly with applied voltage. Four final particle statuses, penetrated, collected, stagnant and back-mixed are clarified by RRT method. The data generated by RRT are utilized to derive the PIV index for further analysis of the ESP performance. The trend, which rises first and drops later, suggests PIV index is expected to pave a new way to clarify the relationship between the ESP flow patterns and particle collection efficiency. [ABSTRACT FROM AUTHOR]

Arterialized venous flap (AVF) is limited in clinical application because its survival remains inconsistent and its exact survival mechanism is still unclear. Hirudin is an effective thrombin specific inhibitor, which is isolated from the salivary gland secretions of the leech. Our study evaluated the impact of hirudin on the viability of AVFs in rabbits. Thirty-six rabbits were randomly divided into three groups: sham group (physiological perfusion), control group (AVF), and hirudin group (AVF + hirudin). In hirudin group, 20 antithrombin units (ATU) hirudin (2.5 ml) were injected into each flap. In sham group and control group, the same amount of normal saline was injected into each flap. Status of flap survival, water content, vascular perfusion, histopathology, expression of CD34, VEGF, eNOS and HIF-1α were analyzed in each group. Analysis of oxidative stress was performed by measuring the activity of superoxide dismutase (SOD) and malondialdehyde (MDA). Compared with flaps in sham group with physiological perfusion mode, results of survival rate, perfusion status, SOD activity, expression of CD34, VEGF, and eNOS of AVFs in control group were significantly lower, while water content, MDA level and expression of HIF-1α were higher. The flap condition of AVFs injected with hirudin in hirudin group was improved significantly, and the results were similar to sham group. Our findings revealed that hirudin can effectively improve survival of AVF. [ABSTRACT FROM AUTHOR]

Plasmids are widely used gene vectors in gene therapy, yet their efficient delivery remains a major challenge for achieving optimal therapeutic outcomes. Recently, poly(β-amino esters) (PBAEs) have emerged as promising carriers for non-viral gene delivery due to their tunable structures and high delivery efficiency. Nonetheless, the cationic nature of PBAEs raises toxicity concerns, and their lack of tissue-specific targeting capability limits their clinical application. Herein, a novel PBAE for efficient plasmid delivery is constructed, which contains disulfide bonds in the backbone and N-acetylgalactosamine (GalNAc) moieties at the terminals (GalNAc-PBAEs). To address the potential reduction in nucleic acid condensing capacity caused by end-capping PBAE with GalNAc, the commonly used end-capping amines in conventional PBAE are employed as monomers to create GalNAc-PBAEs with tertiary amine side chains. Through side-chain screening, the optimized GalNAc-PBAE exhibits enhanced transfection efficiency, surpassing that of the conventional top-performing PBAE, C28-E7, and rivaling the commercial transfection reagent Lipo2000. Importantly, the GalNAc moieties enable the plasmid-PBAE polyplex to efficiently target the liver. In a mouse model with acute liver fibrosis, the efficient delivery and expression of a representative plasmid encoding HGF significantly mitigate liver fibrosis and improve liver function, demonstrating the potential of the designed PBAE in gene therapy., (© 2025 Wiley‐VCH GmbH.)

Background: With the escalating use of digital devices, blue light (BL) exposure has emerged as a critical concern due to its potential to cause ocular damage. This study explores the protective effects of notoginsenoside R1 (NR1), a bioactive compound from Panax notoginseng (Burkill) F.H. Chen (Sanqi), against BL-induced corneal epithelial injury., Purpose: This research aims to investigate the protective effects of NR1 on BL-induced corneal injury and wound healing delay., Methods: Human corneal epithelial cells (hCECs) were pretreated with NR1 (0-50 μM) or N-acetylcysteine (NAC, 10 mM), then exposed to BL (570 μW/cm²) for 24 h. Cell viability, proliferation, migration, and ROS levels were assessed using various techniques. In mice, NR1 (25 μM and 50 μM) and NAC (0.3 %) eye drops were administered during BL exposure. Corneal injury, healing rates, cell proliferation, migration, ROS, and inflammation were evaluated. RNA-sequencing, bioinformatics, and molecular binding validation identified tribbles homolog 1 (TRIB1) as a key molecule mitigating BL damage with NR1. Functional studies via gene silencing, overexpression, and pharmacological modulation further explored TRIB1's role in BL exposure., Results: NR1 significantly reduced BL-induced inflammation, ROS production, and inhibited migration and proliferation in hCECs and murine corneas. It also alleviated BL-induced corneal injury and delayed healing in mice. NR1 inhibited TRIB1 upregulation, a marker of BL-induced injury and healing delay. Overexpression of TRIB1 negated NR1's therapeutic effects on hCECs, while TRIB1 silencing mitigated functional impairment. In mice, increased Trib1 expression caused corneal injury and delayed healing, reversed by NR1 treatment., Conclusion: NR1 shows potential as a therapeutic agent by inhibiting TRIB1 elevation in response to BL exposure, providing a novel promising target for corneal injury and wound healing delay induced by BL, and offering a comprehensive strategy for clinical pharmacological intervention., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2025. Published by Elsevier GmbH.)

To achieve a long cycle life and high-capacity performance for Li-O 2 batteries, it is critical to rationally modulate the formation and decomposition pathway of the discharge product Li 2 O 2 . Herein, we designed a highly efficient catalyst containing dual catalytic active sites of Pt single atoms (Pt SAs ) paired with high-entropy alloy (HEA) nanoparticles for oxygen reduction reaction (ORR) in Li-O 2 batteries. HEA is designed with a moderate d-band center to enhance the surface adsorbed LiO 2 intermediate (LiO 2 (ads)), while Pt SAs active sites exhibit weak adsorption energy and promote the soluble LiO 2 pathway (LiO 2 (sol)). An optimal ratio between LiO 2 (ads) and LiO 2 (sol) pathway was realized to modulate Pt SAs and HEA active sites via regulating the etching conditions in the dealloying synthesis process for obtaining high-performance Li-O 2 batteries. The ORR kinetics are accelerated, and the parasitic reactions are restrained in the Li-O 2 batteries. As a result, Li-O 2 batteries based on the HEA@Pt-Pt SAs catalyst demonstrate an ultralow overpotential (0.3 V) and ultralong cycling performance of 470 cycles at 1000 mA g -1 . The insights into the synthetic strategies and the importance of balancing the ORR pathways will offer guidance for devising multisite synergistic catalysts to accelerate redox-reaction kinetics for Li-O 2 batteries.

Purpose: This study aimed to evaluate the effect of functional loading on microgaps and microleakage at implant-abutment interfaces (IAIs) in the aesthetic zone when using different abutments and to provide a clinical reference for abutment selection., Methods: This study included 30 patients with 36 implants divided into three groups: zirconia (Zr)-one-piece custom abutment, titanium (Ti)-custom abutment, and Ti-original abutment. Scanning electron microscopy was used to examine alterations in the microgaps at the IAIs under functional loading. Changes in the bacterial endotoxin levels within the inner cavities of the implant were evaluated using a quantitative chromogenic Tachypleus amebocyte lysate test. These findings were subjected to statistical analysis using SPSS 18.0., Results: Before functional loading, there were no significant differences in the microgaps between groups (P > 0.05). In the Zr one-piece custom abutment group, the lingual microgaps significantly increased after 24 months of functional loading (P < 0.05). The bacterial endotoxin content significantly increased after 24 months of functional loading compared to the pre-loading levels (P < 0.05); however, no statistically significant difference was observed among the groups (P > 0.05)., Conclusions: Considering the limitations of this study, individualized one-piece Zr abutments exhibited a significant increase in lingual microgaps and comparable changes in microleakage to Ti abutments after 24 months of functional loading. Patients should be alert to the potential risks associated with the use of these abutments when they have heightened aesthetic expectations during functional loading.

Electrochemical and shake flask tests were used to examine the corrosion characteristics of typical gangue minerals in biometallurgical systems and their impact on microbial communities. The results show that the solubility order of the three gangue minerals is feldspar, mica, and quartz in descending order. Their corrosion processes are mainly controlled by cathodic electron-donating processes. They are subjected to triple resistance, which is defined as solution-resistant, colloidal silica passivation, and iron precipitation (ferric hydroxide or jarosite passivation). Fe 3+ and microorganisms both greatly improve the corrosion capacity of the system for the three gangue minerals. The community diversity may rise to 9.3, 8.6, and 4.4 times that of the initial HQ0211 strain, respectively, in the presence of feldspar, mica, and quartz.. The proportions of autotrophic microorganisms Leptospirillum, Sulfobacillus, and Acidiplasma decreased significantly, and the mixed trophic archaeon Ferroplasma and heterotrophic archaeon Cuniculiplasma became the dominant microorganisms in the system. Finally, the dissolution mechanism of gangue minerals in biometallurgical systems is discussed. The results enrich the theory of the gangue mineral corrosion process, which can lay a foundation for the effective regulation of biometallurgical processes., Competing Interests: Declarations. Ethical Approval: Not applicable. Consent to Participate: Not applicable. Consent to Publish: Not applicable. Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Evidence suggests that diethylhexyl phthalate (DEHP) may disrupt thyroid hormone homeostasis by targeting multiple components of the hypothalamic-pituitary-thyroid (HPT) axis, potentially harming human health. However, the relationship between DEHP exposure and thyroid function remains debated. We performed a meta-analysis to clarify the association between DEHP exposure and thyroid function., Methods: We searched Medline, Embase, the Cochrane Library, and Web of Science for relevant studies that provided quantitative data on the association between DEHP and thyroid hormones. The ROBINS-E tool was used to assess the quality of included studies. Pearson correlation coefficients or regression coefficients (β) with 95% confidence intervals (CIs) were calculated to evaluate the relationship between DEHP exposure and thyroid hormone levels., Results: Twenty-three studies were included. In adults, thyroxine (TT4) levels (pooled coefficient -0.05, 95% CI [-0.08, -0.03]) and free thyroxine (FT4) levels (pooled coefficient -0.04, 95% CI [-0.06, -0.02]) were negatively associated with urinary DEHP concentration. Additionally, DEHP exposure in adults was positively correlated with thyroid-stimulating hormone (TSH) levels (pooled coefficient 0.03, 95% CI [0.02, 0.04]). In pregnant women, urinary DEHP concentration was negatively correlated with FT4 levels (pooled correlation coefficient -0.04, 95% CI [-0.06, -0.02]). However, no significant association was observed between DEHP exposure and thyroid function in children and adolescents., Conclusion: This meta-analysis demonstrates a significant association between DEHP exposure and serum thyroid hormone levels in adults. However, DEHP exposure appears to have no significant effect on thyroid function in children and adolescents., Competing Interests: None., (AJTR Copyright © 2024.)

Recent research highlights the significant impact of methionine metabolism on glioma progression. An increasing amount of compelling evidence bridges long non-coding RNAs to abnormal metabolism in gliomas. However, the specific role of long non-coding RNAs in methionine metabolism regulating glioma progression remains unclear. This study reveals that methionine deprivation inhibits the proliferation, migration, and invasion capabilities of gliomas. Interestingly, the expression of TP53TG1, a long non-coding RNA, is also suppressed. TP53TG1 is highly expressed in gliomas and associated with poor patient outcomes. Subsequently, our data proves that inhibition of TP53TG1 suppresses glioma cell proliferation and the epithelial-mesenchymal transition process both in vitro and in vivo. Ultimately, we found that the underlying mechanism involves a competing endogenous RNA regulating network, in which TP53TG1 modulates the target protein STK17B by competitively binding to miR-96-5p, thus regulating glioma progression. These findings suggest that targeting methionine deprivation could be a promising approach for the clinical treatment of glioma., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All experimental ethics and animal research were approved by the ethics committee of the First Affiliated Hospital of Harbin Medical University and adhered to the principles of the Declaration of Helsinki., (© 2024. The Author(s).)

Industrial hemp (Cannabis sativa L.) is a multifaced crop that has the potential to be exploited for many industrial applications, and making use of salt lands is considered to be a sustainable development strategy for the hemp industry. However, no elite salt-tolerant hemp varieties have been developed, and therefore supplementing appropriate exogenous substances to saline soil is one possible solution. Calcium-containing compounds are well-known for their salt tolerance enhancing effects, but the underlying molecular mechanisms remain largely unclear. Here, we first assessed the ameliorative effects of calcium amendments on salt-stressed hemp plants and then investigated these mechanisms on hemp using integrative analysis of proteomics and metabolomics. The stress phenotypes could be lessened by Ca 2+ treatment. Certain concentrations of Ca 2+ maintained relative electrical conductivity and the contents of malondialdehyde and chlorophyll. Ca 2+ treatment also generally led to greater accumulations of soluble proteins, soluble carbohydrates and proline, and enhanced the activities of superoxide dismutase and peroxidase. Through functional classification, pathway enrichment, and network analysis, our data reveal that accumulation of dipeptides is a prominent metabolic signature upon exogenous Ca 2+ treatment, and that changes in mitochondrial properties may play an important role in enhancing the salt tolerance. Our results outline the complex metabolic alternations involved in calcium-mediated salt stress resistance, and these data and analyses would be useful for future functional studies., Competing Interests: Declarations Conflict of interest The authors declare no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

In recent years, concerns have escalated regarding eye health problems arising from Light-emitting diode (LED), which emits high-energy blue light (BL), potentially causing corneal epithelial dysfunctions (CEpD). Nevertheless, the mechanisms underlying this damage remain poorly comprehended. This study endeavors to explore the specific mechanisms through which BL exposure induces CEpD. The study carried out diverse assays and treatments to investigate the toxicological effects of BL exposure. 48 hours (h) of 440 nm of BL exposure decreased the migration of human corneal epithelial cells (hCEpCs) while augmenting reactive oxygen species (ROS) production and apoptosis. RNA-Sequencing and bioinformatic analysis indicated that cellular oxidation and reduction equilibrium, wound healing, the positive regulation of the apoptotic process, and the Phosphoinositide 3-kinase (PI3K)/AKT pathway were significantly influenced by BL exposure. Treatment with N-acetylcysteine (NAC), a ROS scavenger, restored cell viability and AKT/S6 kinase (S6K) activation, suggesting the involvement of ROS in BL-induced damage. NAC also reversed BL-induced apoptosis and migration. Blocking AKT/S6K replicated detrimental effects, while pre-treatment with SC79 (SC), an AKT activator, alleviated the changes caused by BL exposure in hCEpCs. Furthermore, in mice, the combination of AKT inhibition and BL exposure led to CEpD. However, treatment with SC and NAC restored CEpD caused by BL exposure. These results imply that the regulation of the ROS/PI3K/AKT/S6K axis is implicated in BL-induced CEpD. Collectively, this study offers insights into the molecular mechanisms of BL-induced CEpD and proposes targeting the ROS/PI3K/AKT/S6K cascade as a potential therapeutic approach. The findings contribute to ocular health knowledge and establish the basis for developing interventions to safeguard the cornea from the detrimental effects of excessive BL exposure., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ye Shen reports financial support was provided by National Natural Science Foundation of China. Xiawei Wang reports financial support was provided by Traditional Chinese innovative talent support program. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Worldwide, osteoarthritis (OA) is regarded as the most widespread, distressing, and limiting chronic disease that affects degenerative joints. Currently, there is no treatment available to modify the progression of OA. The pathogenesis of OA is significantly linked with oxidative stress and pyroptosis. Astaxanthin (Ast) is a natural ketocarotenoid pigment with potent antioxidant activity and is shown to effectively alleviate cartilage damage in OA. However, its bioavailability is greatly limited due to poor water solubility, high sensitivity to light, temperature, and pH. In this study, Ast-loaded tetrahedral framework nucleic acids (tFNAs) or tFNA/Ast complexes (TAC) for Ast delivery are developed. Compared with free Ast and tFNA alone, TAC exhibits improved drug stability and cellular uptake. Most importantly, TAC effectively protects chondrocytes against oxidative stress-induced pyroptosis while promoting extracellular matrix anabolism by chondrocytes, and ultimately alleviates cartilage damage in a mouse destabilization of the medial meniscus (DMM) model. Thus, TAC holds great promise for the treatment of OA patients., (© 2024 Wiley‐VCH GmbH.)

The current systematic review and meta-analysis examined the effect of racemic ketamine or esketamine on suicidal ideation in individuals with uni- or bipolar depression. We searched the MEDLINE, Embase, Central, PsycINFO, and Web of Science databases to identify randomized controlled trials that examined the effect of racemic ketamine or esketamine monotherapy on suicidal ideation (SI) in individuals with uni- or bipolar depression. The two monotherapies were compared; the primary outcome was the rate of remission of SI, and the secondary outcome was the SI score. The risk ratio was used as an effect size measure for binary variables, while the standardized mean difference was used as an effect size measure for continuous variables. Our meta-analysis included 13 randomized controlled trials involving 1,1109 individuals with uni- or bipolar depression. Patients receiving racemic ketamine monotherapy had a significantly higher acute SI remission rate than those receiving placebo or midazolam (RR = 2.06, 95% CI 1.47 to 2.91, P < 0.0001). Racemic ketamine also led to significantly lower SI scores than placebo or midazolam (SMD = -0.36, 95% CI -0.71 to -0.01, P = 0.04). The evidence for the treatment of SI with esketamine was inconsistent. The pooled effect sizes for long-term anti-SI effects did not reveal significant differences between therapies. Our study indicated the efficacy of racemic ketamine monotherapy for rapidly and transiently reducing SI in individuals with uni- or bipolar depression, but the efficacy of racemic ketamine monotherapy against long-term suicidal ideation remains unclear. There is not -sufficient evidence to support the anti-suicidal effects of esketamine monotherapy.Protocol registration: Prospero registration number: CRD42023434380., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: This study aimed to investigate the psychological stress experienced by frontline medical staff during the Yangbi Earthquake and to understand how coping strategies and social support influence stress responses., Methods: From days 3 to 14 post-earthquake, online questionnaires were administered to frontline medical staff to assess perceived social support, coping strategies, and psychological stress responses using the Perceived Social Support Scale (PSSS), Trait Coping Strategies Questionnaire (TCSQ), and Stress Response Questionnaire (SRQ). Data analysis included correlation analysis to explore relationships between variables, multiple linear regression to identify key predictors of stress, and path analysis to determine direct and indirect effects., Results: A total of 253 valid questionnaires were analyzed, with a participant composition of 81.82% females and 18.18% males, and the majority being nurses (62.06%). Psychological stress responses varied by gender and age, with females and older age groups showing higher physical stress responses (P < 0.05). Correlation and regression analyses indicated that negative coping and lower levels of social support were associated with increased stress responses (P < 0.05). Path analysis revealed that intra-family and extra-family support influenced stress responses directly and indirectly through coping strategies (P < 0.05)., Conclusion: This study suggests that perceived social support directly influences stress responses in frontline medical personnel during disasters, with coping strategies mediating this effect. Future research should explore these dynamics over time through longitudinal studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Ye, Yang, Sun, Yan, Yuan, Peng and Tang.)

Several studies have been devoted to seeking some beneficial plant-related microorganisms for a long time, and on this basis, it has been found that arbuscular mycorrhizal fungi (AMF) have a considerable positive impact on plant health as a biological fungal agent. In this study, we focused on the effects of different AMF on the growth dynamics and root configuration of licorice under saline and alkali conditions. The metabolites of licorice under different AMF were assessed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Funneliformis mosseae (Fm) and Rhizophagus intraradices (Ri) were added as different AMF treatments, while the sterilized saline-alkali soil was treated as a control. Samples were taken in the R1 period (15 d after AMF treatment) and the R2 period (45 d after AMF treatment). The results showed that the application of AMF significantly increased the root growth of licorice and significantly increased the biomass of both shoot and root. A total of 978 metabolites were detected and divided into 12 groups including lipids, which accounted for 15.44%; organic acids and their derivatives, at 5.83%; benzene compounds and organic heterocyclic compounds, at 5.42%; organic oxides, at 3.78%; and ketones, accounting for 3.17%. Compared with the control, there were significant changes in the differential metabolites with treatment inoculated with AMF; the metabolic pathways and biosynthesis of secondary metabolites were the main differential metabolite enrichment pathways in the R1 period, and those in the R2 period were microbial metabolism in diverse environments and the degradation of aromatic compounds. In conclusion, the use of AMF as biofertilizer can effectively improve the growth of licorice, especially in terms of the root development and metabolites, in saline-alkali soil conditions.

Osteoarthritis (OA) is one of the most prevalent joint diseases and severely affects the quality of life in the elderly population. However, there are currently no effective prevention or treatment options for OA. Oxidative stress and pyroptosis play significant roles in the development and progression of OA. To address this issue, we have developed a novel therapeutic approach for OA that targets oxidative stress and pyroptosis. We synthesized tetrahedral framework nucleic acid (tFNAs) to form framework nucleic acid complexes (TNCs), which facilitate the delivery of the naturally occurring polymethoxyflavonoid nobiletin (Nob) to chondrocytes. TNC has demonstrated favorable bioavailability, stability, and biosafety for delivering Nob. Both in vitro and in vivo experiments have shown that TNC can alleviate OA and protect articular cartilage from damage by eliminating oxidative stress, inhibiting pyroptosis, and restoring the extracellular matrix anabolic metabolism of chondrocytes. These findings suggest that TNC has significant potential in the treatment of OA and cartilage injury., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Anterior cruciate ligament (ACL) tears are prevalent knee injures, particularly among active individuals. Accurate and timely diagnosis is essential for determining the optimal treatment strategy and assessing patient prognosis. Various previous studies have demonstrated the successful application of deep learning techniques in the field of medical image analysis. This study aimed to develop a deep learning model for detecting ACL tears in knee magnetic resonance Imaging (MRI) to enhance diagnostic accuracy and efficiency. The proposed model consists of three main modules: a Dual-Scale Data Augmentation module (DDA) to enrich the training data on both the spatial and layer scales; a selective group attention module (SG) to capture relationships across the layer, channel, and space scales; and a fusion module to explore the inter-relationships among various perspectives to achieve the final classification. To ensure a fair comparison, the study utilized a public dataset from MRNet, comprising knee MRI scans from 1250 exams, with a focus on three distinct views: axial, coronal, and sagittal. The experimental results demonstrate the superior performance of the proposed model, termed SGNET, in ACL tear detection compared with other comparison models, achieving an accuracy of 0.9250, a sensitivity of 0.9259, a specificity of 0.9242, and an AUC of 0.9747.

Background: The impact of chronic hepatic infection on antigen non-specific immune cells in circulation remains poorly understood. We reported lasting global hyperfunction of peripheral CD8 T cells in HCV-infected individuals with cirrhosis. Whether gene expression patterns in bulk CD8 T cells are associated with the severity of liver fibrosis in HCV infection is not known., Methods: RNA sequencing of blood CD8 T cells from treatment naïve, HCV-infected individuals with minimal (Metavir F0-1 ≤ 7.0 kPa) or advanced fibrosis or cirrhosis (F4 ≥ 12.5 kPa), before and after direct-acting antiviral therapy, was performed. CD8 T cell function was assessed by flow cytometry., Results: In CD8 T cells from pre-DAA patients with advanced compared to minimal fibrosis, Gene Ontology analysis and Gene Set Enrichment Analysis identified differential gene expression related to cellular function and metabolism, including upregulated Hedgehog (Hh) signaling, IFN-α, -γ, TGF-β response genes, apoptosis, apical surface pathways, phospholipase signaling, phosphatidyl-choline/inositol activity, and second-messenger-mediated signaling. In contrast, genes in pathways associated with nuclear processes, RNA transport, cytoskeletal dynamics, cMyc/E2F regulation, oxidative phosphorylation, and mTOR signaling, were reduced. Hh signaling pathway was the top featured gene set upregulated in cirrhotics, wherein hallmark genes GLI1 and PTCH1 ranked highly. Inhibition of Smo-dependent Hh signaling ablated the expression of IFN-γ and perforin in stimulated CD8 T cells from chronic HCV-infected patients with advanced compared to minimal fibrosis. CD8 T cell gene expression profiles post-DAA remained clustered with pre-DAA profiles and disparately between advanced and minimal fibrosis, suggesting a persistent perturbation of gene expression long after viral clearance., Conclusions: This analysis of bulk CD8 T cell gene expression in chronic HCV infection suggests considerable reprogramming of the CD8 T cell pool in the cirrhotic state. Increased Hh signaling in cirrhosis may contribute to generalized CD8 T cell hyperfunction observed in chronic HCV infection. Understanding the lasting nature of immune cell dysfunction may help mitigate remaining clinical challenges after HCV clearance and more generally, improve long term outcomes for individuals with severe liver disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Vranjkovic, Read, Delaney, Stanford, Cooper and Crawley.)

Cirratiomycin, a heptapeptide with antibacterial activity, was isolated and characterized in 1981; however, its biosynthetic pathway has not been elucidated. It contains several interesting nonproteinogenic amino acids, such as (2S,3S)-2,3-diaminobutyric acid ((2S,3S)-DABA) and α-(hydroxymethyl)serine, as building blocks. Here, we report the identification of a cirratiomycin biosynthetic gene cluster in Streptomyces cirratus. Bioinformatic analysis revealed that several Streptomyces viridifaciens and Kitasatospora aureofaciens strains also have this cluster. One S. viridifaciens strain was confirmed to produce cirratiomycin. The biosynthetic gene cluster was shown to be responsible for cirratiomycin biosynthesis in S. cirratus in a gene inactivation experiment using CRISPR-cBEST. Interestingly, this cluster encodes a nonribosomal peptide synthetase (NRPS) composed of 12 proteins, including those with an unusual domain organization: a stand-alone adenylation domain, two stand-alone condensation domains, two type II thioesterases, and two NRPS modules that have no adenylation domain. Using heterologous expression and in vitro analysis of recombinant enzymes, we revealed the biosynthetic pathway of (2S,3S)-DABA: (2S,3S)-DABA is synthesized from l-threonine by four enzymes, CirR, CirS, CirQ, and CirB. In addition, CirH, a glycine/serine hydroxymethyltransferase homolog, was shown to synthesize α-(hydroxymethyl)serine from d-serine in vitro. These findings broaden our knowledge of nonproteinogenic amino acid biosynthesis., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Nowadays, second near-infrared window (NIR-II) dyes are almost excited by laser diodes, but none of the white light (400-700 nm) excited NIR-II imaging has been studied because of the lack of suitable optical probes. Herein, a novel blue-shifted NIR-II dye, TPA-TQT, has been selected for use in multi-wavelength white light emitting diode (LED) excited NIR-II imaging. This white LED barely caused photo-quenching of the dyes, especially indocyanine green (ICG), whereas the ICG's brightness decreased by 90% under continuous 808 nm laser irradiation. Compared to single-wavelength LED, multi-wavelength LED showed a lower background and similar signal-to-background ratios. This system provided high image resolution to identify blood vessels (103 μm), lymphatic capillaries (129.8 μm), and to monitor hindlimb ischemia-reperfusion and lymphatic inflammation. Furthermore, white LED excited NIR-II fluorescence imaging-guided surgery (FIGS) was successfully performed in 4T1 tumor-bearing mice. Impressively, the lighting LED-based NIR-II FIGS was found to clearly delineate small lesions of metastatic tumors of about ∼350 μm diameter and further was able to guide surgical removal. Overall, multi-wavelength LED-based NIR-II imaging is a promising imaging strategy for tumor delineation and other biomedical applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

To mitigate the adverse effects of fine-grained lithium mica tailings and other solid wastes generated from the extraction of lithium ore mining, as well as the limitations of traditional cement-based binders for lithium mica fine tailings, this study explores the feasibility of using a binder composed of ordinary Portland cement, lithium slag, fly ash, and desulfurization gypsum to stabilize lithium fine tailings into cemented lithium tailings backfill. Compared with traditional cementitious binders, an extensive array of experiments and analyses were conducted on binders formed by various material proportion combinations, employing uniaxial compressive strength tests, microstructural morphology, grayscale analyses, and flowability tests. The results show the following: (1) In this study, an LSB binder exhibiting superior mechanical properties compared to traditional cementitious binders was identified, with an optimal OPC:LS:FA:DG ratio of 2:1:1:1. (2) In the context of cemented lithium mica fine tailings, the LSB-CLTB material exhibits higher unconfined compressive strength and lower self-weight compared to OPC-CLTB materials. At a binder content of 10 wt%, the UCS values achieved by the LSB-CLTB material at curing periods of 7 days, 14 days, and 28 days are 0.97 MPa, 1.52 MPa, and 2.1 MPa, respectively, representing increases of 40.6%, 34.5%, and 44.8% over the compressive strength of OPC-based materials under the same conditions. (3) The LSB binder not only exhibits enhanced pozzolanic reactivity but also facilitates the infilling of detrimental pores through its inherent particle size and the formation of AFt and C-(A)-S-H gels via hydration reactions, thereby effectively improving the compressive strength performance of fine-grained tailings backfill.

Objective: Our study aimed to evaluate the cost-effectiveness of the addition of serplulimab to chemotherapy (cisplatin and fluorouracil) for programmed death-ligand 1 (PD-L1) positive advanced esophageal squamous cell carcinoma (ESCC) as the first-line treatment in China., Methods: A three-state Markov model was established to assess the incremental cost-effectiveness ratio (ICER) for serplulimab plus chemotherapy versus chemotherapy alone. Survival data were extrapolated from the ASTRUM-007 trial, cost data were derived from local sources, and utilities were derived from published literature. Health outcomes were measured as quality-adjusted life-years (QALYs). Sensitivity and probability sensitivity analyses were used to investigate the robustness of the model., Results: In the base-case analysis, compared with chemotherapy alone, serplulimab gained an additional 0.16 QALYs with an incremental cost of $29,547.88, leading to an ICER of $184,674.25/QALY. Additionally, the subgroup analyses presented that the ICERs of serplulimab plus chemotherapy were $157,892.50/QALY and $127,996.45/QALY in advanced ESCC patients with 1≤ CPS< 10 and CPS≥ 10, respectively. These ICERs significantly exceeded the Chinese willingness-to-pay (WTP) threshold. The deterministic sensitivity analysis illustrated that the cost of progression-free survival in serplulimab plus chemotherapy group was the parameter with the strongest influence on the ICERs., Conclusion: In the Chinese health care system, with 3 times China's per capita gross domestic product as the WTP threshold, compared with chemotherapy alone, serplulimab combined chemotherapy is not economical for PD-L1-positive advanced ESCC in the first-line setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zheng, Li, Wen and Su.)

The teaching of the optimization algorithm is a new kind of swarm intelligence optimization technique, which is superior in optimizing many simple functions. Still, it is not evident in processing some complex problems (group and teaching classification). Achieving automatic matching and knowledge transfer in online courses is imperative in mathematics education. This study proposes a design scheme MTCBO-LR (multiobjective capability optimizer-logistic regression), based on multitask optimization, which enables precise knowledge transfer and data interaction among many educators. It incorporates the standard TLBO algorithm to optimize, provides a variety of learning tactics for students at different stages of mathematics instruction, and is capable of adaptively adjusting these strategies in response to actual teaching needs. Experimental results on various datasets reveal that the proposed method enhances searchability and group diversity in various optimization extremes and outperforms similar methods in resolving to multitask teaching problems., Competing Interests: The authors declare that they have no competing interests., (© 2023 Li et al.)

Diagnosis of primary brain tumors relies heavily on histopathology. Although various computational pathology methods have been developed for automated diagnosis of primary brain tumors, they usually require neuropathologists' annotation of region of interests or selection of image patches on whole-slide images (WSI). We developed an end-to-end Vision Transformer (ViT) - based deep learning architecture for brain tumor WSI analysis, yielding a highly interpretable deep-learning model, ViT-WSI. Based on the principle of weakly supervised machine learning, ViT-WSI accomplishes the task of major primary brain tumor type and subtype classification. Using a systematic gradient-based attribution analysis procedure, ViT-WSI can discover diagnostic histopathological features for primary brain tumors. Furthermore, we demonstrated that ViT-WSI has high predictive power of inferring the status of three diagnostic glioma molecular markers, IDH1 mutation, p53 mutation, and MGMT methylation, directly from H&E-stained histopathological images, with patient level AUC scores of 0.960, 0.874, and 0.845, respectively., Competing Interests: The authors have declared no competing interests., (© 2022 The Author(s).)

The development of injectable cement-like biomaterials via a minimally invasive approach has always attracted considerable clinical interest for modern bone regeneration and repair. Although α-tricalcium phosphate (α-TCP) powders may readily react with water to form hydraulic calcium-deficient hydroxyapatite (CDHA) cement, its long setting time, poor anti-collapse properties, and low biodegradability are suboptimal for a variety of clinical applications. This study aimed to develop new injectable α-TCP-based bone cements via strontium doping, α-calcium sulfate hemihydrate (CSH) addition and liquid phase optimization. A combination of citric acid and chitosan was identified to facilitate the injectable and anti-washout properties, enabling higher resistance to structure collapse. Furthermore, CSH addition (5 %-15 %) was favorable for shortening the setting time (5-20 min) and maintaining the compressive strength (10-14 MPa) during incubation in an aqueous buffer medium. These α-TCP-based composites could also accelerate the biodegradation rate and new bone regeneration in rabbit lateral femoral bone defect models in vivo. Our studies demonstrate that foreign ion doping, secondary phase addition and liquid medium optimization could synergistically improve the physicochemical properties and biological performance of α-TCP-based bone cements, which will be promising biomaterials for repairing bone defects in situations of trauma and diseased bone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

It is highly important and challenging to develop donor-acceptor-donor structured small-molecule second near-infrared window (NIR-II) dyes with excellent properties such as water-solubility and chem/photostability. Here, we discovery an electron acceptor, 6,7-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TQT) with highest stability in alkaline conditions, compared with conventional NIR-II building block benzobisthiadiazole (BBT) and 6,7-diphenyl-[1,2,5] thiadiazolo[3,4-g]quinoxaline (PTQ). The sulfonated hydrophilic dye, FT-TQT, is further synthesized with 2.13-fold increased quantum yield than its counterpart FT-BBT with BBT as acceptor. FT-TQT complexed with FBS is also prepared and displays a 16-fold increase in fluorescence intensity compared to FT-TQT alone. It demonstrates real-time cerebral and tumor vessel imaging capability with µm-scale resolution. Dynamic monitoring of tumor vascular disruption after drug treatment is achieved by NIR-II fluorescent imaging. Overall, TQT is an efficient electron acceptor for designing innovative NIR-II dyes. The acceptor engineering strategy provides a promising approach to design next generation of NIR-II fluorophores which open new biomedical applications., (© 2022. The Author(s).)

Immunosuppressive tumor microenvironment is a crucial factor that impedes the success of tumor immunotherapy, and tumor-associated macrophages (TAMs) are essential for the formation of tumor immunosuppressive microenvironment. Hyaluronic acid (HA) is highly important brick for glioblastoma microenvironment, but whether it contributes to TAM polarization and glioblastoma immunosuppressive microenvironment is less well known. In our study, we observed that disrupting glioblastoma HA synthesis or blocking HA binding to its receptor CD44 on macrophages increased the proportion of M1 macrophages by upregulating SIRPα in macrophages, the underlying mechanism was elevated SIRPα enhanced STAT1 phosphorylation and suppressed STAT3 phosphorylation in macrophages. Subsequently, the induced macrophages could inhibit glioblastoma growth via a feedback effect. In addition, 4-methylumbelliferone (4MU), a cholecystitis drug, can disrupt the CD47/SIRPα axis by disturbing glioblastoma HA synthesis. Collectively, these findings indicated that HA plays a crucial role in macrophages polarization and CD47/SIRPα signaling between glioblastoma cells and macrophages, and suppressing the HA pathway may be a new immunotherapeutic approach for glioblastoma., (© 2022. The Author(s).)

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19., (© 2021. The Author(s).)

Brasenia schreberi J. F. Gmel, a perennial floating-leaved macrophyte with high economic value as an aquatic vegetable, has been listed as first-class endangered species in China, mainly due to its habitat loss. Protected cultivation is a potential strategy to meet the demand of both plant conservation and vegetable market, whereas pre-experiments are still needed before series of parameters can be properly set for the large-scale growth of the plants indoor. Light quality is one of the major factors controlling the development of plants and consequently becomes an important factor when planting B. schreberi indoor. This experiment used three artificial light sources to investigate the response of B. schreberi seedlings to different light qualities, including the red-blue LED light (red: blue = 5:1, RB-LED), the white LED light (W-LED) and the white fluorescent (W-Fluo). Our results indicated that the responses of B. schreberi towards varied light qualities differed from those of most terrestrial plants. The total leaf number of the RB-LED treatment was the highest; the number of the submerged leaf and the rolled leaf of the RB-LED treatment was higher than that of the other two treatments, but the number of floating leaves was the lowest. Both the specific leaf weight and the pigment contents per unit leaf area were the lowest in the RB-LED treatment. Quantum yield of PSⅡ ( Φ PSⅡ ), electron transport rate (ETR) and photochemical quenching ( q P) measured through light induction curves followed the sequence from high to low as W-Fluo > W-LED > RB-LED, whereas the trend of non-photochemical quenching (NPQ) reversed. The maximum potential ETR ( P s ) and maximum ETR (ETR m ) derived from ETR curves further verified the trends., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

The use of perforator flaps is a common surgical technique in wound repair. However, the area surrounding the multiterritory perforating flap often becomes necrotic due to ischemia. Hydroxysafflor yellow A (HSYA), a traditional Chinese medicine extracted from edible safflower, can be used medicinally to promote angiogenesis, inhibit apoptosis, and alleviate oxidative stress and other biological activities. Here, we investigated the effect of HSYA on perforator flap survival and its potential mechanism. Our results demonstrate that HSYA significantly improves the survival area of perforator flaps, increases blood supply, reduces tissue edema, and increases mean vascular density. HSYA treatment promotes angiogenesis and inhibits oxidative stress, apoptosis, and autophagy in perforator flaps, suggesting many potential mechanisms for flap survival., Competing Interests: None., (AJTR Copyright © 2020.)

Anaplastic thyroid cancer (ATC), usually derived from well-differentiated thyroid cancers is one of the most lethal human endocrine malignancies. In the present study, we report that in human ATC tumor tissue samples exist undetectable Notch1 and the active Notch1 intracellular domain could not be detected in ATC-CAL-62 cells. Interesting, suberoyl bis-hydroxamic acid (SBHA) administration could induce Notch1 intracellular domain levels in a dose-dependent manner, coupled with the increase of p53 and p21. Furthermore, ectopic expression of Notch1 or deletion of p53 with small-interfering RNA was able to abolish the effects of SBHA to elevation of Notch1 and p53 in ATC cells. As a result, SBHA treatment efficiently induced ATC cell apoptosis. These results indicate that SBHA may play antitumor functions via regulating Notch1/p53 signals, and highlight that SBHA could have clinical potential to benefit the therapy of ATC patients.