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This study puts forth a novel terminal group design to develop medium-bandgap Y-series acceptors beyond conventional side-chain engineering. We focused on the strategical integration of an electron-donating methoxy group and an electron-withdrawing halogen atom at benzene-fused terminal groups. This combination precisely modulated the dipole moment and electron density of terminal groups, effectively attenuating intramolecular charge transfer effect, and widening the bandgap of acceptors. The incorporation of these terminal groups yielded two asymmetric acceptors, named BTP-2FClO and BTP-2FBrO, both of which exhibited open-circuit voltage (VOC) as high as 0.96 V in binary devices, representing the highest VOCs among the asymmetric Y-series small molecule acceptors. More importantly, both BTP-2FClO and BTP-2FBrO exhibit modest aggregation behaviors and molecular crystallinity, making them suitable as a third component to mitigate excess aggregation of the PM6: BTP-eC9 blend and optimize the devices' morphology. As a result, the optimized BTP-2FClO-based ternary organic solar cells (OSCs) achieved a remarkable power conversion efficiency (PCE) of 19.34%, positioning it among the highest-performing OSCs. Our study highlights the molecular design importance on manipulating dipole moments and electron density in developing medium-bandgap acceptors, and offers a highly efficient third component for high-performance ternary OSCs.

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In organic-inorganic hybrid perovskite solar cells (PSCs), hydrogen defects introduce deep-level trap states, significantly influencing non-radiative recombination processes. Those defects are primarily observed in MA-PSCs rather than FA-PSCs. As a result, MA-PSCs demonstrated a lower efficiency of 23.6% compared to 26.1% of FA-PSCs. In this work, both hydrogen vacancy (VH -) and hydrogen interstitial (Hi -) defects in MAPbI3 bulk and on surfaces, respectively are investigated. i) Bulk VH - defects have dramatic impact on non-radiative recombination, with lifetime varying from 67 to 8 ns, depending on whether deprotonated MA0 are ion-bonded or not. ii) Surface H-defects exhibited an inherent self-healing mechanism through a chemical bond between MA0 and Pb2+, indicating a self-passivation effect. iii) Both VH - and Hi - defects can be mitigated by alkali cation passivation; while large cations are preferable for VH - passivation, given strong binding energy of cation/perovskite, as well as, weak band edge non-adiabatic couplings; and small cations are suited for Hi - passivation, considering the steric hindrance effect. The dual passivation strategy addressed diverse experimental outcomes, particularly in enhancing performance associated with cation selections. The dynamic connection between hydrogen defects and non-radiative recombination is elucidated, providing insights into hydrogen defect passivation essential for high-performance PSCs fabrication.

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Selective macroautophagy/autophagy in metazoans involves the conserved receptors NBR1 and SQSTM1/p62. Both autophagy receptors manage ubiquitinated cargo recognition, while SQSTM1 has an additional, distinct role of facilitating liquid-liquid phase separation (LLPS) during autophagy. Given that plants lack SQSTM1, it is postulated that plant NBR1 may combine activities of both metazoan NBR1 and SQSTM1. However, the precise mechanism by which plant NBR1 recognizes non-ubiquitinated substrates and its ability to undergo LLPS during selective autophagy remain elusive. Here, we implicate both the ZZ-type zinc finger motif and the four-tryptophan domain of Arabidopsis NBR1 (AtNBR1) in the recognition of non-ubiquitinated cargo proteins. Additionally, we reveal that AtNBR1 indeed undergoes LLPS prior to ATG8-mediated autophagosome formation, crucial for heat stress resistance in Arabidopsis. Our findings unveil the dual roles of AtNBR1 in both cargo recognition and LLPS during plant autophagy and advance our understanding of NBR1-mediated autophagy in plants compared to metazoans.Abbreviations: ATG8: autophagy 8; Co-IP: co-immunoprecipitation; EXO70E2: exocyst subunit EXO70 family protein E2; FRAP: fluorescence recovery after photobleaching; FW domain: four-tryptophan domain; GFP: green fluorescent protein; HS: heat stress; LLPS: liquid-liquid phase separation; LIR: LC3-interacting region; NBR1: next to BRCA1 gene 1; PAS: phagophore assembly site; PB1 domain: Phox and Bem1 domain; RFP: red fluorescent protein; ROF1: rotamase FKBP 1; SARs: selective autophagy receptors; UBA domain: ubiquitin-associated domain; Y2H: yeast two-hybrid; ZZ domain: ZZ-type zinc finger motif domain.

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Membrane vesicles (MVs) are produced by species across all domains of life and have diverse physiological functions as well as promising applications. While the mechanisms for vesiculation in Gram-negative bacteria are well-established, the genetic determinants and regulatory factors responsible for MV biogenesis in Gram-positive bacteria remain largely unknown. Here, we demonstrate that a Q225P substitution in the alternative sigma factor B (SigB) triggers MV production in Staphylococcus aureus strain Newman by hindering the specific binding of SigB to the asp23 promoter, thereby repressing expression of alkaline shock protein 23 (Asp23). Isogenic deletion of asp23 also promotes MV formation in Newman, confirming the critical roles played by sigB and asp23 in modulating S. aureus vesiculation. While bacterial growth and cytoplasmic membrane fluidity are not impaired, mutation of asp23 weakens the cell wall and enhances autolysis, consistent with decreased expression of alpha-type psm and lrgAB that modulate murein hydrolase activity. TEM and proteomic analysis show that Newman and asp23 deletion mutant generate MVs with nearly identical morphology and composition, but virulence-associated factors are significantly enriched in MVs from the asp23 mutant. Overall, this study reveals novel genetic determinants underlying S. aureus vesiculation and advances the understanding of the physiology of MV biogenesis in S. aureus.

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Antithrombin (AT) deficiency in the extracorporeal circulation during cardiac surgery leads to uncontrolled inflammation and vascular damage in patients. AT levels decrease in sepsis, major trauma, extracorporeal membrane oxygenation, and eclampsia. Monitoring plasma AT levels facilitates the accurate restoration of AT to baseline values through precise supplementation. Traditional methods of chromogenic assay and enzyme-linked immunosorbent assay (ELISA) kits encounter challenges, such as interference, inconsistency, and delayed response times, making real-time, reliable antithrombin monitoring a clinical gap. To address this critical need, we develop a heparin-bead extraction enhanced fluoroGenic aptamer-thrombin composite reporter (HExGATOR) for the rapid, sensitive, and precise detection of functional AT in plasma. Our design employs thrombin-binding aptamers and a fluorescence "turn on" technology such that a signal is produced upon the interaction of AT with the otherwise "turned off" aptamer-thrombin complex. The prominent signal-background interference originating from plasma is remarkably diminished by using a heparin-bead solid-phase extraction of AT. We achieved highly sensitive and rapid detection of AT in 5 to 20 min with a limit of detection of 15.11 nM. This approach offers a promising alternative to traditional AT tests in clinical settings, potentially facilitating personalized anticoagulant therapy.

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OBJECTIVE: To evaluate the effectiveness and feasibility of combined treatment with compound fluocinolone acetonide cream and guaiazulene in patients with neurodermatitis. METHODS: A prospective study was conducted on 92 outpatient patients diagnosed with neurodermatitis at our dermatology department from January 2022 to December 2023. Using a random number table, these patients were evenly divided into a control group and an experimental group, with 46 individuals in each group. The control group received treatment with compound fluocinolone acetonide alone, while the experimental group additionally received oral guaiazulene tablets. Clinical symptom and sign scores, Visual Analog Scale (VAS) scores, skin lesion itching scores, comprehensive efficacy, treatment onset time, adverse reactions, and quality of life were monitored, recorded, and compared. RESULTS: In the 2-week treatment period, patients in the experimental group showed significant improvement in skin symptoms and signs, with scores significantly lower than those in the control group (P < 0.05). After treatment, VAS and skin lesion itching scores in the experimental group were significantly reduced (P < 0.05), demonstrating a more pronounced therapeutic advantage compared to the control group (P < 0.05). Although the effective rate in the experimental group was as high as 86.96%, there was no significant advantage compared to the control group, and the difference in treatment efficacy was not significant (P > 0.05). The treatment onset time in the experimental group was significantly shorter than that in the control group (P < 0.05), and the incidence of adverse reactions was lower (P < 0.05). The quality of life in the experimental group improved significantly after treatment, with DLQI scores lower than those in the control group (P < 0.05). CONCLUSION: Combined treatment with compound fluocinolone acetonide cream and guaiazulene demonstrates excellent efficacy and feasibility in the management of neurodermatitis. Compared to standard treatment alone, it yields superior clinical outcomes.

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Double-fibril network morphology (DFNM), in which the donor and the acceptor can self-assemble into a double-fibril structure, is beneficial for exciton dissociation and charge transport in organic solar cells. Herein, it is demonstrated that such DFNM can be constructed and optimized in all-polymer solar cells (all-PSCs) with the assistance of 2-alkoxynaphthalene volatile solid additives. It is revealed that the incorporation of 2-alkoxynaphthalene can induce a stepwise regulation in the aggregation of donor and acceptor molecules during film casting and thermal annealing processes. Through altering the alkoxy of 2-alkoxynaphthalene solid additives, both the intermolecular interactions and molecular miscibility with the host materials can be precisely tuned, which allows for the optimization of the molecular aggregation process and facilitation of molecular self-assembly, and thus leading to reinforced molecular packing and optimized DFNM. As a result, an unprecedented efficiency of 19.50% (certified as 19.1%) is obtained for 2-ethoxynaphthalene-processed PM6:PY-DT-X all-PSCs with excellent photostability (T80 = 1750 h). This work reveals that the optimization of DFNM via solid additive strategy is a promising avenue to boosting the performance of all-PSCs.

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The Span-based model can effectively capture the complex entity structure in the text, thus becoming the mainstream model for nested named entity recognition (Nested NER) tasks. However, traditional Span-based models decode each entity span independently. They do not consider the semantic connections between spans or the entities' positional information, which limits their performance. To address these issues, we propose a Bi-Directional Context-Aware Network (Bi-DCAN) for the Nested NER. Specifically, we first design a new span-level semantic relation model. Then, the Bi-DCAN is implemented to capture this semantic relationship. Furthermore, we incorporate Rotary Position Embedding into the bi-affine mechanism to capture the relative positional information between the head and tail tokens, enabling the model to more accurately determine the position of each entity. Experimental results show that compared to the latest model Diffusion-NER, our model reduces 20M parameters and increases the F1 scores by 0.24 and 0.09 on the ACE2005 and GENIA datasets respectively, which proves that our model has an excellent ability to recognise nested entities.

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Current high-efficiency organic solar cells (OSCs) are generally fabricated in an inert atmosphere that limits their real-world scalable manufacturing, while the efficiencies of air-processed OSCs lag far behind. The impacts of ambient factors on solar cell fabrication remain unclear. In this work, the effects of ambient factors on cell fabrication are systematically investigated, and it is unveiled that the oxidation and doping of organic light absorbers are the dominant reasons causing cell degradation when fabricated in air. To address this issue, a new strategy for fabricating high-performance air-processed OSCs by introducing an antioxidant additive (4-bromophenylhydrazine, BPH) into the precursor solutions, is developed. BPH can effectively inhibit oxygen infiltration from the ambient to the photoactive layer and suppress trap formation caused by oxidation. Compared with conventional air-processed OSCs, this strategy remarkably increases the cell power conversion efficiency (PCE) from 16.7% to 19.3% (independently certified as 19.2%), representing the top value of air-processed OSCs. Furthermore, BPH significantly improves the operational stability of the cells in air by two times with a T80 lifetime of over 500 h. This study highlights the potential of using antioxidant additives to fabricate high-efficiency and stable OSCs in air, significantly promoting the industrialization of OSCs.

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The underlying mechanism of thermotolerance, which is a key virulence factor essential for pathogenic fungi such as Cryptococcus neoformans, is largely unexplored. In this study, our findings suggest that Set302, a homolog of Set3 and a subunit of histone deacetylase complex Set3C, contributes to thermotolerance in C. neoformans. Specifically, the deletion of the predicted Set3C core subunit, Set302, resulted in further reduction in the growth of C. neoformans at 39°C, and survival of transient incubation at 50°C. Transcriptomics analysis revealed that the expression levels of numerous heat stress-responsive genes altered at both 30°C and 39°C due to the lack of Set302. Notably, at 39°C, the absence of Set302 led to the downregulation of gene expression related to the ubiquitin-proteasome system (UPS). Based on the GFP-α-synuclein overexpression model to characterize misfolded proteins, we observed a pronounced accumulation of misfolded GFP-α-synuclein at 39°C, consequently inhibiting C. neoformans thermotolerance. Furthermore, the loss of Set302 exacerbated the accumulation of misfolded GFP-α-synuclein during heat stress. Interestingly, the set302∆ strain exhibited a similar phenotype under proteasome stress as it did at 39°C. Moreover, the absence of Set302 led to reduced production of capsule and melanin. set302∆ strain also displayed significantly reduced pathogenicity and colonization ability compared to the wild-type strain in the murine infection model. Collectively, our findings suggest that Set302 modulates thermotolerance by affecting the degradation of misfolded proteins and multiple virulence factors to mediate the pathogenicity of C. neoformans.IMPORTANCECryptococcus neoformans is a pathogenic fungus that poses a potential and significant threat to public health. Thermotolerance plays a crucial role in the wide distribution in natural environments and host colonization of this fungus. Herein, Set302, a critical core subunit for the integrity of histone deacetylase complex Set3C and widely distributed in various fungi and mammals, governs thermotolerance and affects survival at extreme temperatures as well as the formation of capsule and melanin in C. neoformans. Additionally, Set302 participates in regulating the expression of multiple genes associated with the ubiquitin-proteasome system (UPS). By eliminating misfolded proteins under heat stress, Set302 significantly contributes to the thermotolerance of C. neoformans. Moreover, Set302 regulates the pathogenicity and colonization ability of C. neoformans in a murine model. Overall, this study provides new insight into the mechanism of thermotolerance in C. neoformans.

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The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain.

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The objective of this study was to investigate the mechanism underlying LW-1-induced resistance to TMV in wild-type and salicylic acid (SA)-deficient NahG transgenic tobacco plants. Our findings revealed that LW-1 failed to induce antivirus infection activity and increase SA content in NahG tobacco, indicating the crucial role of SA in these processes. Meanwhile, LW-1 triggered defense-related early-signaling nitric oxide (NO) generation, as evidenced by the emergence of NO fluorescence in both types of tobacco upon treatment with LW-1, however, NO fluorescence was stronger in NahG compared to wild-type tobacco. Notably, both of them were eliminated by the NO scavenger cPTIO, which also reversed LW-1-induced antivirus activity and the increase of SA content, suggesting that NO participates in LW-1-induced resistance to TMV, and may act upstream of the SA pathway. Defense-related enzymes and genes were detected in tobacco with or without TMV inoculation, and the results showed that LW-1 regulated both enzyme activity (ß-1,3-glucanase [GLU], catalase [CAT] and phenylalanine ammonia-lyase [PAL]) and gene expression (PR1, PAL, WYKY4) through NO signaling in both SA-dependent and SA-independent pathways.

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An increasing body of research has underscored the significant impact of non-consumptive effects on the dynamics of prey pests, encompassing growth, development, reproduction, and metabolism across various vertebrate and invertebrate taxa, rivaling the influence of consumption effects. In our investigation, we delved into the non-consumptive effects exerted by the natural predatory enemy Harmonia axyridis on the reproductive capacity and metabolism of Spodoptera frugiperda adults. Our findings revealed a substantial decrease in the reproductive ability of S. frugiperda adults when exposed to the non-consumptive effects of H. axyridis. Concurrently, we observed an elevation in hydrogen peroxide (H2O2) content and the activities of antioxidant enzymes such as superoxide dismutases (SODs), catalases (CATs), and peroxidases (PODs). Furthermore, notable alterations were detected in energy metabolism, characterized by heightened triglyceride levels and diminished glycogen and trehalose concentrations. These outcomes underscored the adaptive response of the pest aimed at mitigating non-consumptive adverse effects by augmenting antioxidant enzyme activity to counteract oxidative stress and minimize cellular damage. Nonetheless, this defensive mechanism entails a significant expenditure of energy resources, resulting in shifts in energy utilization. Elevated triglyceride levels and reduced glycogen and trehalose concentrations diminish available resources for reproductive processes, such as egg laying, ultimately culminating in decreased fecundity. This study contributes novel insights into the non-consumptive effects observed in insects, while also furnishing valuable insights into the mechanisms underlying insect stress responses.

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The nanoscale morphology of the photoactive layer notably impacts the performance of organic solar cells (OSCs). Conventional methods to tune the morphology are typically chemical approaches that adjust the properties (such as solubility and miscibility) of the active components including donor, acceptor, and/or additive. Here, we demonstrate a completely different approach by applying an external electric field (EEF) on the active layer during the wet coating. The EEF-coating method is perfectly compatible with an ambient blade coating using environmentally friendly solvents, which are essential requirements for industrial production of OSCs. A record 18.6% efficiency is achieved using the EEF coating, which is the best value for open-air, blade-coated OSCs to date. Our findings suggest broad material applicability and attribute-enhanced performance to EEF-induced fiber formation and long-range ordering of microstructures of acceptor domains. This technique offers an effective method for producing high-performance OSCs, especially suited for industry OSC production based on open-air printing.

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Indoor photovoltaics (IPVs) are garnering increasing attention from both the academic and industrial communities due to the pressing demand of the ecosystem of Internet-of-Things. All-polymer solar cells (all-PSCs), emerging as a sub-type of organic photovoltaics, with the merits of great film-forming properties, remarkable morphological and light stability, hold great promise to simultaneously achieve high efficiency and long-term operation in IPV's application. However, the dearth of polymer acceptors with medium-bandgap has impeded the rapid development of indoor all-PSCs. Herein, a highly efficient medium-bandgap polymer acceptor (PYFO-V) is reported through the synergistic effects of side chain engineering and linkage modulation and applied for indoor all-PSCs operation. As a result, the PM6:PYFO-V-based indoor all-PSC yields the highest efficiency of 27.1% under LED light condition, marking the highest value for reported binary indoor all-PSCs to date. More importantly, the blade-coated devices using non-halogenated solvent (o-xylene) maintain an efficiency of over 23%, demonstrating the potential for industry-scale fabrication. This work not only highlights the importance of fine-tuning intramolecular charge transfer effect and intrachain coplanarity in developing high-performance medium-bandgap polymer acceptors but also provides a highly efficient strategy for indoor all-PSC application.

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Developing a new end group for synthesizing asymmetric small molecule acceptors (SMAs) is crucial for achieving high-performance organic photovoltaics (OPVs). Herein, an asymmetric small molecule acceptor, BTP-BO-4FO, featuring a new difluoro-methoxylated end-group is reported. Compared to its symmetric counterpart L8-BO, BTP-BO-4FO exhibits an upshifted energy level, larger dipole moment, and more sequential crystallinity. By adopting two representative and widely available solvent additives (1-chloronaphthalene (CN) and 1,8-diiodooctane (DIO)), the device based on PM6:BTP-BO-4FO (CN) photovoltaic blend demonstrates a power conversion efficiency (PCE) of 18.62% with an excellent open-circuit voltage (VOC) of 0.933 V, which surpasses the optimal result of L8-BO. The PCE of 18.62% realizes the best efficiencies for binary OPVs based on SMAs with asymmetric end groups. A series of investigations reveal that optimized PM6:BTP-BO-4FO film demonstrates similar molecular packing motif and fibrillar phase distribution as PM6:L8-BO (DIO) does, resulting in comparable recombination dynamics, thus, similar fill factor. Besides, it is found PM6:BTP-BO-4FO possesses more efficient charge generation, which yields better VOC-JSC balance. This study provides a new ending group that enables a cutting-edge efficiency in asymmetric SMA-based OPVs, enriching the material library and shed light on further design ideas.

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BACKGROUND: The pathogenesis of ulcerative colitis (UC) is complex, and recent therapeutic advances remain unable to fully alleviate the condition. AIM: To inform the development of novel UC treatments, bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC. METHODS: The GEO database was searched for UC-related datasets that included healthy controls who met the screening criteria. Differential analysis was conducted to obtain differentially expressed genes (DEGs). Autophagy-related targets were collected and intersected with the DEGs to identiy differentially expressed autophagy-related genes (DEARGs) associated with active UC. DEARGs were then subjected to KEGG, GO, and DisGeNET disease enrichment analyses using R software. Differential analysis of immune infiltrating cells was performed using the CiberSort algorithm. The least absolute shrinkage and selection operator algorithm and protein-protein interaction network were used to narrow down the DEARGs, and the top five targets in the Dgree ranking were designated as core targets. RESULTS: A total of 4822 DEGs were obtained, of which 58 were classified as DEARGs. SERPINA1, BAG3, HSPA5, CASP1, and CX3CL1 were identified as core targets. GO enrichment analysis revealed that DEARGs were primarily enriched in processes related to autophagy regulation and macroautophagy. KEGG enrichment analysis showed that DEARGs were predominantly associated with NOD-like receptor signaling and other signaling pathways. Disease enrichment analysis indicated that DEARGs were significantly linked to diseases such as malignant glioma and middle cerebral artery occlusion. Immune infiltration analysis demonstrated a higher presence of immune cells like activated memory CD4 T cells and follicular helper T cells in active UC patients than in healthy controls. CONCLUSION: Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients.

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The rhizosphere microbiome plays critical roles in plant growth and provides promising solutions for sustainable agriculture. While the rhizosphere microbiome frequently fluctuates with the soil environment, recent studies have demonstrated that a small proportion of the microbiome is consistently assembled in the rhizosphere of a specific plant genotype regardless of the soil condition, which is determined by host genetics. Based on these breakthroughs, which involved exploiting the plant-beneficial function of the rhizosphere microbiome, we propose to divide the rhizosphere microbiome into environment-dominated and plant genetic-dominated components based on their different assembly mechanisms. Subsequently, two strategies to explore the different rhizosphere microbiome components for agricultural production are suggested, that is, the precise management of the environment-dominated rhizosphere microbiome by agronomic practices, and the elucidation of the plant genetic basis of the plant genetic-dominated rhizosphere microbiome for breeding microbiome-assisted crop varieties. We finally present the major challenges that need to be overcome to implement strategies for modulating these two components of the rhizosphere microbiome.

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The development of high-efficiency organic solar cells (OSCs) processed from non-halogenated solvents is crucially important for their scale-up industry production. However, owing to the difficulty of regulating molecular aggregation, there is a huge efficiency gap between non-halogenated and halogenated solvent processed OSCs. Herein, we fabricate o-xylene processed OSCs with approaching 20 % efficiency by incorporating a trimeric guest acceptor named Tri-V into the PM6:L8-BO-X host blend. The incorporation of Tri-V effectively restricts the excessive aggregation of L8-BO-X, regulates the molecular packing and optimizes the phase-separation morphology, which leads to mitigated trap density states, reduced energy loss and suppressed charge recombination. Consequently, the PM6:L8-BO-X:Tri-V-based device achieves an efficiency of 19.82 %, representing the highest efficiency for non-halogenated solvent-processed OSCs reported to date. Noticeably, with the addition of Tri-V, the ternary device shows an improved photostability than binary PM6:L8-BO-X-based device, and maintains 80 % of the initial efficiency after continuous illumination for 1380 h. This work provides a feasible approach for fabricating high-efficiency, stable, eco-friendly OSCs, and sheds new light on the large-scale industrial production of OSCs.

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Arecoline, the predominant bioactive substance extracted from areca nut (AN), is the world's fourth most frequently used psychoactive material. Research has revealed that chewing AN can affect the central nervous system (CNS) and may lead to neurocognitive deficits that are possibly linked to the action of arecoline. However, the mechanism behind the neurotoxicity caused by arecoline remains unclear. This study aimed to investigate the neurotoxic effects of arecoline and its underlying mechanism. The results showed that arecoline caused cytotoxicity against HT22 cells in a dose-dependent manner and induced apoptosis by upregulating the expression of pro-apoptotic caspase and Bcl-2 family proteins. Furthermore, arecoline escalated intracellular reactive oxygen species (ROS) levels and Ca2+ concentration with increasing doses, thereby motivating endoplasmic reticulum stress (ERS) and ERS-associated apoptotic protein expression. Additionally, the study found that arecoline attenuates intracellular antioxidant defense by inhibiting the translocation of NF-E2-related factor-2 (Nrf2) into the nucleus and decreasing downstream Heme oxygenase-1 (HO-1) levels. The specific inhibitor Sodium 4-phenylbutyrate (4-PBA) can dramatically attenuate arecoline-mediated cell apoptosis and ERS-associated apoptotic pathway expression by blocking ERS. The antioxidant N-Acetylcysteine (NAC) also effectively reverses the arecoline-mediated increase of ERS-related apoptotic pathway protein levels by scavenging intracellular ROS accumulation. In conclusion, this study suggests that arecoline induces neurotoxicity in HT22 cells via ERS mediated by oxidative stress- and Ca2+ disturbance, as well as by downregulation of the Nrf2/HO-1 pathway.

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