Unveiling the Twisted Aromatic Donor Effect on the Nonlinear Response of D-π-A Type Malononitrile-Derived Chromophores.

This study presents the design, synthesis, and comprehensive characterization of a novel series of D-π-A type malononitrile-derived chromophores, BTC-1-BTC-4. Combining various spectroscopic techniques, nonlinear Z-scan measurements, and quantum chemical calculations, we revealed the intricate relationship between nonlinear optical properties and the interplay of molecular structure, intramolecular charge transfer (ICT), and dipole moments (µ). Our experimental and computational findings corroborate that the polarization degree in the ground state, the charge separation in the excited state and twisted intramolecular charge transfer (TICT) collectively dictate the nonlinear optical properties of the compounds. Notably, BTC-1 exhibits an exceptional nonlinear absorption coefficient ß value (2×10-8 m W-1), attributed to its optimized charge transfer efficiency and pronounced degree of charge separation. Our findings provide actionable insights for the rational design of high-performance organic Nonlinear optics (NLO) materials with potential applications in advanced photonic devices.

Atomic Magnetometer Achieves Visual Salience Analysis in Drosophila.

An atomic magnetometer (AM) was used to non-invasively detect the tiny magnetic field generated by the brain of a single Drosophila. Combined with a visual stimulus system, the AM was used to study the relationship between visual salience and oscillatory activity of the Drosophila brain by analyzing changes in the magnetic field. Oscillatory activity of Drosophila in the 1-20 Hz frequency band was measured with a sensitivity of 20 fT/Hz. The field in the 20-30 Hz band under periodic light stimulation was used to explore the correlation between short-term memory and visual salience. Our method opens a new path to a more flexible method for the investigation of brain activity in Drosophila and other small insects.

Effect of FoxO1 on Cardiomyocyte Apoptosis and Inflammation in Viral Myocarditis via Modultion of the TLR4/NF-κB Signaling Pathway.

To investigate the possible effect of FoxO on coxsackievirus B3 (CVB3) -induced cardiomyocyte inflammation and apoptosis via modulation of the TLR4/NF-κB signaling pathway.Viral myocarditis (VMC) models were establied via CVB3 infection both in vivo and in vitro. Western blotting was adopted to detect FoxO1 and TLR4 expressions in myocardial tissues and cells. Cardiomyocytes of suckling mouse were divided into the control, CVB3, CVB3 + pcDNA, CVB3 + pcDNA-FoxO1, CVB3 + TLR4 siRNA, and CVB3 + pcDNA-FoxO1 + TLR4 siRNA groups. Flow cytometry was employed to evaluate cell apoptosis. The expressions of inflammatory factors including TNF-α, IL-1ß, and IL-6 were detected via quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Then, TLR4/NF-κB pathway-related proteins were determined via Western blotting.VMC mice had increased FoxO1 and TLR4 expressions in myocardial tissues. Cardiomyocytes with CVB3 infection also had upregulated protein expressions of p-FoxO1/FoxO1 and TLR4. Compared with those in the control group, the cardiomyocytes in the CVB3 group were increased in LDH and CK-MB levels, cell apoptosis rate and inflammatory factors (TNF-α, IL-1ß and IL-6), as well as protein expressions of TLR4 and p-p65/p65. Compared with those in the CVB3 group, the cardiomyocytes in the CVB3 + pcDNA-FoxO1 group were further upregulated whereas those in the CVB3 +TLR4 siRNA group were downregulated in the aforementioned indicators. Furthermore, TLR4 siRNA can reverse the effect of pcDNA-FoxO1 on the aggravation of cardiomyocyte injury induced by CVB3 infection.FoxO1 can upregulate the TLR4/NF-κB signaling pathway to promote cardiomyocyte apoptosis and inflammatory injury in CVB3-induced VMC.

A Comprehensive Review of Natural Flavonoids with Anti-SARS-CoV-2 Activity.

The COVID-19 pandemic caused by SARS-CoV-2 has majorly impacted public health and economies worldwide. Although several effective vaccines and drugs are now used to prevent and treat COVID-19, natural products, especially flavonoids, showed great therapeutic potential early in the pandemic and thus attracted particular attention. Quercetin, baicalein, baicalin, EGCG (epigallocatechin gallate), and luteolin are among the most studied flavonoids in this field. Flavonoids can directly or indirectly exert antiviral activities, such as the inhibition of virus invasion and the replication and inhibition of viral proteases. In addition, flavonoids can modulate the levels of interferon and proinflammatory factors. We have reviewed the previously reported relevant literature researching the pharmacological anti-SARS-CoV-2 activity of flavonoids where structures, classifications, synthetic pathways, and pharmacological effects are summarized. There is no doubt that flavonoids have great potential in the treatment of COVID-19. However, most of the current research is still in the theoretical stage. More studies are recommended to evaluate the efficacy and safety of flavonoids against SARS-CoV-2.

Phosphatidylglucose alleviates atherosclerosis by increasing cholesterol alienation to bile acids and cholesterol efflux in ApoE-/- mice.

BACKGROUND: Phosphatidylcholine (PC) is considered to be the major dietary source for choline, which is associated with atherosclerosis progress. Thus, phosphatidylglucose (PG) was prepared by enzymatic modification of PC to investigate the effects on atherosclerosis in apolipoprotein E deficient (ApoE-/- ) mice, as well as to investigate its dose-response relationship. RESULTS: The results showed that dietary PG significantly decreased the atherosclerotic lesion area in a dose-dependent manner. Further studies found that intervention with a 0.8 g kg-1 and 2 g kg-1 PG diet for 4 months significantly decreased free cholesterol level and thus reduced total cholesterol levels in serum. The results of cholesterol distribution among lipoproteins showed that dietary PG significantly decreased low-density lipoprotein levels in ApoE-/- mice. In addition, only administration of high-dose PG significantly reduced total cholesterol levels in liver tissues by 31.2%. Furthermore, mice treated with high-dose PG had an expanded bile acid pool and increased the ratio of conjugated bile acids to unconjugated bile acids in the liver, serum and gallbladder by increasing hepatic gene expression of primary and conjugated bile acid synthesis. Additionally, low-dose and high-dose PG significantly increased total fecal sterols by 20.8% and 11.9%, respectively, by increasing sitosterol and ethylcoprostanol levels. CONCLUSION: These results indicate that PG alleviated atherosclerosis in a dose-dependent manner by increasing cholesterol alienation to bile acids and cholesterol efflux. © 2023 Society of Chemical Industry.

Comparative evaluation of phosphatidylcholine and phosphatidylserine with different fatty acids on nephrotoxicity in vancomycin-induced mice.

Phospholipids reportedly alleviate drug-induced acute kidney injury. However, no study has compared the effect of phospholipids with different fatty acids and polar heads on drug-induced nephrotoxicity. In the present study, we aimed to compare the possible nephroprotection afforded by phosphatidylcholine and phosphatidylserine with different fatty acids in a mouse model of vancomycin-induced nephrotoxicity. Pretreatment with phospholipids rich in docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) doubled the survival time when compared with the model group. Moreover, phospholipids rich in DHA/EPA significantly reduced the serum levels of renal function biomarkers and ameliorated kidney pathologies. In terms of alleviating renal damage, no significant differences were observed between different polar heads in DHA-enriched phospholipids, while phosphatidylserine from soybean was better than phosphatidylcholine in mitigating renal injury. Furthermore, DHA/EPA-enriched phospholipids inhibited vancomycin-induced nephrotoxicity mainly by inhibiting apoptosis and oxidative stress. These results provide a scientific basis for phospholipids as potential ingredients to prevent acute kidney injury.

RCOR1 directly binds to MED28 and weakens its inducing effect on cancer stem cell-like activity of oral cavity squamous cell carcinoma cells.

BACKGROUND: Mediator is a multiprotein complex that acts as an essential transcriptional coactivator in eukaryotic cells for successful transcription. In this study, we aimed to explore the expression profile of 33 mediator subunit genes in oral cavity squamous cell carcinoma (OCSCC) and the functional role of MED28 in cellular behaviors of OCSCC cells. METHODS: Single-cell (sc)RNA-seq data from OCSCC cells (Puram 2017's dataset) and bulk-seq data of the OCSCC subgroup of TCGA-head and neck squamous cell carcinoma (HNSC) were used for bioinformatic analysis. SCC9 cells were used in in-vitro and in-vivo analysis. RESULTS: Among the 33 genes subjected to screening, MED28 showed the best prognostic value and its upregulation might independently predict shorter OS (HR: 3.699, 95% CI: 1.383-9.892, P = .009) and PFS (HR: 2.769, 95% CI: 1.462-5.244, P = .002). MED28 expression was positively correlated with cancer stem cell (CSC)-like properties of SCC9 cells, including colony/sphere formation, and the expression of CSC markers (CD44, KLF4, NANOG, and OCT4). RCOR1 could suppress the CSC-like properties of SCC9 cells and had direct interaction with MED28. Its overexpression partly abrogated MED28-induced expression of CSC markers. RCOR1 expression was associated with promoter hypermethylation, while MED28 expression was positively correlated with its MED28 copy number (Pearson's r = .44) in OCSCC tissues. CONCLUSION: Among the mediator complex subunits, MED28 might serve as a potential biomarker of unfavorable survival. Its overexpression increased CSC-like activity of OCSCC cells, the effect of which could be abrogated by RCOR1 via direct interaction.

Peptide-free Synthetic Nicotine Vaccine Candidates with α-Galactosylceramide as Adjuvant.

Peptides are generally needed as T-helper epitopes in nicotine vaccines to induce effective antibody responses, but the highly polymorphic property of major histocompatibility complex (MHC) molecules may limit opportunities of B cell to receive CD4+ T-cell help. Invariant natural killer T (iNKT) cells recognize lipid antigens presented by the nonpolymorphic CD1d molecule that is conserved in mammals to a great extent. iNKT cells also display some similar functions to conventional CD4+ T-helper cells, especially they license dendritic cells stimulate antibody isotype switching by B cells. Herein, α-galactosylceramide (αGalCer), a classical iNKT cell agonist, serves as an adjuvant in synthetic nicotine vaccine candidates absent of peptide or protein. Our study reveals that αGalCer displays better adjuvant activity than Pam3CSK4 (a commonly used lipopeptide TLR agonist). Remarkably, the covalent linker between the nicotine hapten and αGalCer is not critical. Self-assembly of the lipid-tailed nicotine and αGalCer into the liposome represents a structurally simple but immunologically effective way to develop nicotine vaccines. This is the first time to introduce the iNKT cell agonist as an adjuvant to an antidrug vaccine. This discovery may contribute to improving the efficacy of clinical candidate nicotine vaccines in the future.

Toward a Spatiotemporal Understanding of Dolomite Dissolution in Sandstone by CO2-Enriched Brine Circulation.

In this study, we introduce a stochastic method to delineate the mineral effective surface area (ESA) evolution during a recycling reactive flow-through transport experiment on a sandstone under geologic reservoir conditions, with a focus on the dissolution of its dolomite cement, Ca1.05Mg0.75Fe0.2(CO3)2. CO2-enriched brine was circulated through this sandstone specimen for 137 cycles (∼270 h) to examine the evolution of in situ hydraulic properties and CO2-enriched brine-dolomite geochemical reactions. The bulk permeability of the sandstone specimen decreased from 356 mD before the reaction to 139 mD after the reaction, while porosity increased from 21.9 to 23.2% due to a solid volume loss of 0.25 mL. Chemical analyses on experimental effluents during the first cycle yielded a dolomite reactivity of ∼2.45 mmol m-3 s-1, a corresponding sample-averaged ESA of ∼8.86 × 10-4 m2/g, and an ESA coefficient of 1.36 × 10-2, indicating limited participation of the physically exposed mineral surface area. As the dissolution reaction progressed, the ESA is observed to first increase and then decrease. This change in ESA can be qualitatively reproduced employing scanning electron microscopy-image-based stochastic analyses on dolomite dissolution. These results provide a new approach to analyze and upscale the ESA during geochemical reactions, which are involved in a wide range of geoengineering operations.

Paeonol ameliorates monosodium urate-induced arthritis in rats through inhibiting nuclear factor-κB-mediated proinflammatory cytokine production.

Moutan Cortex has been widely used to treat various types of arthritis in traditional Chinese medicine. Paeonol is isolated as an active ingredient from Moutan Cortex. However, the effect and potential mechanism of paeonol on gouty arthritis have not been evaluated. In this study, rats were treated intragastrically with paeonol for consecutive 7 days. On Day 5, rats were intra-articularly injected with monosodium urate (MSU) crystals in the ankle joints to induce MSU-induced arthritis (MIA). Paw volume was detected at various time points. Gait score was measured at 24 hr after MSU crystal injection. Ankle joints were collected for evaluation of histological score and expression of proinflammatory cytokines using hematoxylin and eosin staining and immunohistochemistry staining, respectively. Nuclear level of nuclear factor (NF)-κBp65 in synovial tissues was analyzed by western blot assay. NF-κB DNA-binding activity was measured by enzyme linked immunosorbent assay. Paeonol markedly lowered the paw volume, gait score, and histological score in MIA rats. Mechanistically, paeonol markedly reduced the expression of TNF-α, IL-1ß, and IL-6 in synovial tissues of MIA rats. In addition, the elevated level of p65 in nucleus and NF-κB DNA-binding activity in synovial tissues of MIA rats were reduced significantly by paeonol treatment. These findings suggest that paeonol exerts anti-inflammatory effect in MIA rats through inhibiting expression of proinflammatory cytokines and NF-κB activation.

An evidence-based etiology study of synovial cyst of knee cruciate ligament: a real or pseudo-cyst.

PURPOSE: Synovial cyst of knee cruciate ligament (SCKCL) is a rare condition but can cause severe knee pain. The understanding of its etiology is relatively poor. This current study aimed to elucidate the pathogenesis of SCKCL based on a series of histo- and cytopathological examination. METHODS: Ten SCKCL patients who underwent arthroscopy were enrolled, among five patients claimed past knee injury. Hematoxylin & eosin staining was conducted to the cyst wall tissue sections and Papanicolaou staining to the cyst fluid smear. Prussian blue staining was employed to both the wall section and fluid smear. Immumohistochemical staining for mesothelial cells (MC), epithelial cells (CK), vascular endothelial cells (CD31), monocytes (CD68), and hematogenous stem cells (CD117) were taken to elucidate the possible involvement of various cell types in the development of SCKCL. RESULTS: No erythrocyte was discovered in the fluid; however, Prussian blue stained hemosiderin particles were found in the cyst wall and fluid, suggesting past hemorrhage in all patients. Abundant lymphocytes and plasmocytes were observed in the cyst wall and fluid. In addition, the cyst lining was infiltrated with abundant CD68(+) monocytes while only few MC(+) mesothelial cells were sporadically observed in four samples. The cyst submucosa was also diffused with abundant CD68(+) monocytes and proliferated capillaries stained with CD31. CD117-positve hematogenous stem cells were sporadically observed in eight specimens. CONCLUSION: Our findings provided evidence that SCKCL is not a mature synovial cyst but rather an inflammatory pseudo-cyst. It may have resulted from past minor hemorrhage and intra-ligament chronic inflammation.

Tomographic Reservoir Imaging with DNA-Labeled Silica Nanotracers: The First Field Validation.

This study presents the first field validation of using DNA-labeled silica nanoparticles as tracers to image subsurface reservoirs by travel time based tomography. During a field campaign in Switzerland, we performed short-pulse tracer tests under a forced hydraulic head gradient to conduct a multisource-multireceiver tracer test and tomographic inversion, determining the two-dimensional hydraulic conductivity field between two vertical wells. Together with three traditional solute dye tracers, we injected spherical silica nanotracers, encoded with synthetic DNA molecules, which are protected by a silica layer against damage due to chemicals, microorganisms, and enzymes. Temporal moment analyses of the recorded tracer concentration breakthrough curves (BTCs) indicate higher mass recovery, less mean residence time, and smaller dispersion of the DNA-labeled nanotracers, compared to solute dye tracers. Importantly, travel time based tomography, using nanotracer BTCs, yields a satisfactory hydraulic conductivity tomogram, validated by the dye tracer results and previous field investigations. These advantages of DNA-labeled nanotracers, in comparison to traditional solute dye tracers, make them well-suited for tomographic reservoir characterizations in fields such as hydrogeology, petroleum engineering, and geothermal energy, particularly with respect to resolving preferential flow paths or the heterogeneity of contact surfaces or by enabling source zone characterizations of dense nonaqueous phase liquids.

The Past, Present, and Future of Dentoalveolar Surgery in China.

Dentoalveolar surgery, formerly known as dental surgery or oral surgery, is one of the basic branches of oral and maxillofacial surgery. While it has a long history; however, there are great differences in its evolution globally. This article presents a brief review on the development of dentoalveolar surgery internationally. Furthermore, a systematic review on its development in China, is detailed in 6 stages. However, while its development in China since 2005 has been most profound, improvements are still needed in treatment concepts, instruments, treatment processes, attention to high-risk populations and cooperation with other dental/medical disciplines. Future projections based on present standards of care are also presented.

Constituents from the Roots of Actinidia chinensis and Their Cytochrome P450 Enzyme Inhibitory Activities.

A newly discovered triterpenoid, (2α,3ß)-2,3,23-trihydroxyurs-13(18)-en-28-oic acid (1), along with twelve known compounds (2 - 13), were isolated from the roots of Actinidia chinensis Planch (Actinidiaceae). Their chemical structures were determined by 1D- and 2D-NMR spectra and mass spectrometry (MS). The crude extracts and six main constituents (8 - 13) were tested for cytochrome P450 (CYPs) enzyme inhibitory activity. The results showed that, except for compound 8, compounds 9 - 13 had different inhibitory effects on the cytochrome P450 (CYPs) enzyme, and compound 9 significantly inhibited the catalytic activities of CYP3A4 to < 10% of its control activities.

Does the calcification of adamantinomatous craniopharyngioma resemble the calcium deposition of osteogenesis/odontogenesis?

AIMS: Calcification in adamantinomatous craniopharyngioma (ACP) is troublesome for surgical intervention. The aim of this study was to examine the osteogenic proteins that play important roles in the calcium deposition of the odontogenic/osteogenic tissues in craniopharyngioma. METHODS AND RESULTS: Craniopharyngiomas (n = 89) were investigated for the presence and expression pattern of the osteoinductive/odontoinductive factor bone morphogenetic protein-2 (Bmp2) and two osteoblastic differentiation makers, Runt-related transcription factor-2 (Runx2) and Osterix, using immunohistochemistry and Western blotting. Our results showed that Bmp2, Runx2 and Osterix levels increased in cases with high calcification and correlated positively with the degree of calcification in ACP, whereas they showed little or no expression in squamous papillary craniopharyngioma. In ACP, Bmp2 was expressed primarily in the stellate reticulum and whorl-like array cells; Runx2 and Osterix tended to be expressed in calcification-related epithelia, including whorl-like array cells and epithelia in/around wet keratin and calcification lesions. CONCLUSIONS: Our study indicated, for the first time, that osteogenic factor Bmp2 may play an important role in the calcification of ACP via autocrine or paracrine mechanisms. Given the presence of osteogenic markers (Runx2 and Osterix), craniopharyngioma cells could differentiate into an osteoblast-like lineage, and the process of craniopharyngioma calcification resembles that which occurs in osteogenesis/odontogenesis.

Experimental observation of permeability changes in dolomite at CO2 sequestration conditions.

Injection of cool CO2 into geothermally warm carbonate reservoirs for storage or geothermal energy production may lower near-well temperature and lead to mass transfer along flow paths leading away from the well. To investigate this process, a dolomite core was subjected to a 650 h, high pressure, CO2 saturated, flow-through experiment. Permeability increased from 10(-15.9) to 10(-15.2) m(2) over the initial 216 h at 21 °C, decreased to 10(-16.2) m(2) over 289 h at 50 °C, largely due to thermally driven CO2 exsolution, and reached a final value of 10(-16.4) m(2) after 145 h at 100 °C due to continued exsolution and the onset of dolomite precipitation. Theoretical calculations show that CO2 exsolution results in a maximum pore space CO2 saturation of 0.5, and steady state relative permeabilities of CO2 and water on the order of 0.0065 and 0.1, respectively. Post-experiment imagery reveals matrix dissolution at low temperatures, and subsequent filling-in of flow passages at elevated temperature. Geochemical calculations indicate that reservoir fluids subjected to a thermal gradient may exsolve and precipitate up to 200 cm(3) CO2 and 1.5 cm(3) dolomite per kg of water, respectively, resulting in substantial porosity and permeability redistribution.

Non-invasive measurement of rat auditory evoked fields using an optically pumped atomic magnetometer: Effects of task manipulation.

Optically pumped magnetometers (OPMs) have become a favorable tool for magnetoencephalography (MEG) measurement, offering a non-invasive method of measurement. OPMs do not require cryogenic environments, sensors can be more closely aligned with the brain. We employed a passive single-stimulus paradigm in conjunction with OPMs with a sensitivity of 20 fT/ Hz to investigate the auditory response of rats to inter-stimulus interval (ISI) and frequencies, recording the rat auditory event-related magnetic fields (ERMFs). Our findings include: (1) Auditory evoked fields can be detected non-invasively by OPMs; (2) The amplitude of the rat auditory ERMFs varies with changes in ISI, with more pronounced amplitude changes observed after 5 s; (3) When the sound stimulus frequency is altered at the same ISI, the amplitude of the rats ERMFs changes with frequency, indicating significant differences in attention. Our method offers a valuable tool for the clinical application of a single stimulus paradigm and opens up a new avenue for research on the brain magnetic field detections.

The Dynamics of Per- and Polyfluoroalkyl Substances (PFAS) at Interfaces in Porous Media: A Computational Roadmap from Nanoscale Molecular Dynamics Simulation to Macroscale Modeling.

Managing and remediating perfluoroalkyl and polyfluoroalkyl substance (PFAS) contaminated sites remains challenging. The major reasons are the complexity of geological media, partly unknown dynamics of the PFAS in different phases and at fluid-fluid and fluid-solid interfaces, and the presence of cocontaminants such as nonaqueous phase liquids (NAPLs). Critical knowledge gaps exist in understanding the behavior and fate of PFAS in vadose and saturated zones and in other porous media such as concrete and asphalt. The complexity of PFAS-surface interactions warrants the use of advanced characterization and computational tools to understand and quantify nanoscale behavior of the molecules. This can then be upscaled to the microscale to develop a constitutive relationship, in particular to distinguish between surface and bulk diffusion. The dominance of surface diffusion compared to bulk diffusion results in the solutocapillary Marangoni effect, which has not been considered while investigating the fate of PFAS. Without a deep understanding of these phenomena, derivation of constitutive relationships is challenging. The current Darcy scale mass-transfer models use constitutive relationships derived from either experiments or field measurements, which makes their applicability potentially limited. Here we review current efforts and propose a roadmap for developing Darcy scale transport equations for PFAS. We find that this needs to be based on systematic upscaling of both experimental and computational studies from nano- to microscales. We highlight recent efforts to undertake molecular dynamics simulations on problems with similar levels of complexity and explore the feasibility of conducting nanoscale simulations on PFAS dynamics at the interface of fluid pairs.

TCERG1L hypermethylation is a risk factor of diabetic retinopathy in Chinese children with type 1 diabetes.

AIM: To identify the differential methylation sites (DMS) and their according genes associated with diabetic retinopathy (DR) development in type 1 diabetes (T1DM) children. METHODS: This study consists of two surveys. A total of 40 T1DM children was included in the first survey. Because no participant has DR, retina thinning was used as a surrogate indicator for DR. The lowest 25% participants with the thinnest macular retinal thickness were included into the case group, and the others were controls. The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay, and compared between the case and control groups. Four DMS with a potential role in diabetes were identified. The second survey included 27 T1DM children, among which four had DR. The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing. RESULTS: In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δß|>0.1 and Adj.P<0.05), and 328 of these were identified with a significance of Adj.P<0.01. Among these, 319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls. Pyrosequencing revealed that the transcription elongation regulator 1 like (TCERG1L, cg07684215) gene was hypermethylated in the four T1DM children with DR (P=0.018), which was consistent with the result from the first survey. The methylation status of the other three DMS (cg26389052, cg25192647, and cg05413694) showed no difference (all P>0.05) between participants with and without DR. CONCLUSION: The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

A conjugate vaccine strategy that induces protective immunity against arecoline.

Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec-CONH-BSA, blunted analgesia and attenuated hypothermia for arecoline.