Counterion influence on near-infrared-II heptamethine cyanine salts for photothermal therapy.

Photothermal therapy (PTT) has attracted extensive attention in cancer treatment. Heptamethine cyanine dyes with near-infrared (NIR) absorption performance have been investigated for PTT. However, they are often accompanied by poor photostability, suboptimal photothermal conversion and limited therapeutic efficacy. The photophysical properties of fluorescent organic salts can be tuned through counterion pairing. However, whether the counterion can influence the photostability and photothermal properties of heptamethine cyanine salts has not been clarified. In this work, we investigated the effects of eleven counter anions on the physical and photothermal properties of NIR-II heptamethine cyanine salts with the same heptamethine cyanine cation. The anions have great impacts on the physiochemical properties of dyes in solution including aggregation, photostability and photothermal conversion efficiency. The physical tuning enables the control over the cytotoxicity and phototoxicity of the dyes. The selected salts have been demonstrated to significantly suppress 4T1 breast tumor growth with low toxicity. The findings that the counterion has great effects on the photothermal properties of cationic NIR-II heptamethine cyanine dyes will provide a reference for the preparation of improved photothermal agents through counterion pairing with possible translation to humans.

Neuromodulation in the developing visual cortex after long-term monocular deprivation.

Neural dynamics are altered in the primary visual cortex (V1) during critical period monocular deprivation (MD). Synchronization of neural oscillations is pertinent to physiological functioning of the brain. Previous studies have reported chronic disruption of V1 functional properties such as ocular dominance, spatial acuity, and binocular matching after long-term monocular deprivation (LTMD). However, the possible neuromodulation and neural synchrony has been less explored. Here, we investigated the difference between juvenile and adult experience-dependent plasticity in mice from intracellular calcium signals with fluorescent indicators. We also studied alterations in local field potentials power bands and phase-amplitude coupling (PAC) of specific brain oscillations. Our results showed that LTMD in juveniles causes higher neuromodulatory changes as seen by high-intensity fluorescent signals from the non-deprived eye (NDE). Meanwhile, adult mice showed a greater response from the deprived eye (DE). LTMD in juvenile mice triggered alterations in the power of delta, theta, and gamma oscillations, followed by enhancement of delta-gamma PAC in the NDE. However, LTMD in adult mice caused alterations in the power of delta oscillations and enhancement of delta-gamma PAC in the DE. These markers are intrinsic to cortical neuronal processing during LTMD and apply to a wide range of nested oscillatory markers.

Regional integration policies and urban green innovation: Fresh evidence from urban agglomeration expansion.

Climate change is a non-traditional security crisis affecting the global economy and diplomatic progress. In order to curtail carbon emissions and alleviate the perils of climate change at their roots, urban green innovation (UGI) has emerged as a pivotal technological solution. Using the expansion of the Yangtze River Delta urban agglomeration in China as a case study, this paper develops a quasi-experimental model to analyze the effects of regional integration policies on UGI. The main findings are: (1) Regional integration policies significantly enhance UGI and their impact is more pronounced with the expansion of urban agglomerations; (2) Regional integration policies contribute to the advancement of exploitative green innovation while tending to diminish exploratory green innovation; (3) The green innovation effects (GIEs) created by the expansion of regional integration policies are largely influenced by governmental mechanisms on environmental governance as well as residents' green preferences. Based on these findings, recommendations are put forward to promote UGI from the perspective of policy implementation.

Study on the Antifungal Activity of Gallic Acid and Its Azole Derivatives against Fusarium graminearum.

The wheat scab caused by Fusarium graminearum (F. graminearum) has seriously affected the yield and quality of wheat in China. In this study, gallic acid (GA), a natural polyphenol, was used to synthesize three azole-modified gallic acid derivatives (AGAs1-3). The antifungal activity of GA and its derivatives against F. graminearum was studied through mycelial growth rate experiments and field efficacy experiments. The results of the mycelial growth rate test showed that the EC50 of AGAs-2 was 0.49 mg/mL, and that of AGAs-3 was 0.42 mg/mL. The biological activity of AGAs-3 on F. graminearum is significantly better than that of GA. The results of field efficacy tests showed that AGAs-2 and AGAs-3 significantly reduced the incidence rate and disease index of wheat scab, and the control effect reached 68.86% and 72.11%, respectively. In addition, preliminary investigation was performed on the possible interaction between AGAs-3 and F. graminearum using density functional theory (DFT). These results indicate that compound AGAs-3, because of its characteristic of imidazolium salts, has potential for use as a green and environmentally friendly plant-derived antifungal agent for plant pathogenic fungi.

Inhibition of protein phosphatase 2A by okadaic acid induces translocation of nucleocytoplasmic O-GlcNAc transferase.

Post-translational modification (PTM) is crucial for many biological events, such as the modulation of bone metabolism. Phosphorylation and O-GlcNAcylation are two examples of PTMs that can occur at the same site in the protein: serine and threonine residues. This phenomenon may cause crosstalk and possible interactions between the molecules involved. Protein phosphatase 2 A (PP2A) is widely expressed throughout the body and plays a major role in dephosphorylation. At the same location where PP2A acts, O-GlcNAc transferase (OGT) can introduce uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) molecules and mediates O-GlcNAc modifications. To examine the effects of PP2A inhibition on OGT localization and expression, osteoblastic MC3T3-E1 cells were treated with Okadaic Acid (OA), a potent PP2A inhibitor. In the control cells, OGT was strictly localized in the nucleus. However, OGT was observed diffusely in the cytoplasm of the OA-treated cells. This change in localization from the nucleus to the cytoplasm resulted from an increase in mitochondrial OGT expression and translocation of the nucleocytoplasmic isoform. Furthermore, knockdown of PP2A catalytic subunit α isoform (PP2A Cα) significantly affected OGT expression (p < 0.05), and there was a correlation between PP2A Cα and OGT expression (r = 0.93). These results suggested a possible interaction between PP2A and OGT, which strengthens the notion of an interaction between phosphorylation and O-GlcNAcylation.

NUPR1 contributes to radiation resistance by maintaining ROS homeostasis via AhR/CYP signal axis in hepatocellular carcinoma.

BACKGROUND: Radiotherapy (RT) is one of the major therapeutic approaches to hepatocellular carcinoma (HCC). Ionizing radiation (IR) inducing the generation of reactive oxygen species (ROS) leads to a promising antitumor effect. However, the dysregulation of the redox system often causes radioresistance and impairs the efficacy of RT. Increasing evidence indicates that nuclear protein 1 (NUPR1) plays a critical role in redox reactions. In this study, we aim to explore the role of NUPR1 in maintaining ROS homeostasis and radioresistance in HCC. METHODS: The radioresistant role of NUPR1 was determined by colony formation assay, comet assay in vitro, and xenograft tumor models in vivo. Probes for ROS, apoptosis assay, and lipid peroxidation assay were used to investigate the functional effect of NUPR1 on ROS homeostasis and oxidative stress. RNA sequencing and co-immunoprecipitation assay were performed to clarify the mechanism of NUPR1 inhibiting the AhR/CYP signal axis. Finally, we analyzed clinical specimens to assess the predictive value of NUPR1 and AhR in the radiotherapeutic efficacy of HCC. RESULTS: We demonstrated that NUPR1 was upregulated in HCC tissues and verified that NUPR1 increased the radioresistance of HCC in vitro and in vivo. NUPR1 alleviated the generation of ROS and suppressed oxidative stress, including apoptosis and lipid peroxidation by downregulating cytochrome P450 (CYP) upon IR. ROS scavenger N-acetyl-L-cysteine (NAC) and CYP inhibitor alizarin restored the viability of NUPR1-knockdown cells during IR. Mechanistically, the interaction between NUPR1 and aryl hydrocarbon receptor (AhR) promoted the degradation and decreased nuclear translation of AhR via the autophagy-lysosome pathway, followed by being incapable of CYP's transcription. Furthermore, genetically and pharmacologically activating AhR abrogated the radioresistant role of NUPR1. Clinical data suggested that NUPR1 and AhR could serve as novel biomarkers for predicting the radiation response of HCC. CONCLUSIONS: Our findings revealed the role of NUPR1 in regulating ROS homeostasis and oxidative stress via the AhR/CYP signal axis upon IR. Strategies targeting the NUPR1/AhR/CYP pathway may have important clinical applications for improving the radiotherapeutic efficacy of HCC.

Photostability investigation of a near-infrared-II heptamethine cyanine dye.

The development of small-molecule organic fluorophores in the second near-infrared region (NIR-II, 1000-1700 nm) has recently received immense attention due to deep tissue light penetration and reduced autofluorescence. Polymethine cyanine dyes as important building blocks are frequently used to design NIR-II light-activated fluorophores. However, applications of these fluorophores were restricted by their poor photostability. Herein, we synthesized a NIR-II heptamethine cyanine dye 4 as the model compound to investigate its photostability and identify its photoproducts. Compound 4 shows improved photostability compared to ICG, and remains relatively stable even under sunlight irradiation. The cyanine scaffold's good photostability promoted its stable photothermal properties. The effective photothermal activity of cyanine dye 4 and the low toxicity of its one major photoproduct demonstrated its potential for further photo-therapeutic applications. This work would pave the way for the development of NIR-II cyanines with photostability through delicate structure design.

Effects of Phytochelatin-like Gene on the Resistance and Enrichment of Cd2+ in Tobacco.

Phytochelatins (PCs) are class III metallothioneins in plants. They are low molecular-weight polypeptides rich in cysteine residues which can bind to metal ions and affect the physiological metabolism in plants. Unlike other types of metallothioneins, PCs are not the product of gene coding but are synthesized by phytochelatin synthase (PCS) based on glutathione (GSH). The chemical formula of phytochelatin is a mixture of (γ-Glu-Cys)n-Gly (n = 2-11) and is influenced by many factors during synthesis. Phytochelatin-like (PCL) is a gene-encoded peptide (Met-(α-Glu-Cys)11-Gly) designed by our laboratory whose amino acid sequence mimics that of a natural phytochelatin. This study investigated how PCL expression in transgenic plants affects resistance to Cd and Cd accumulation. Under Cd2+ stress, transgenic plants were proven to perform significantly better than the wild-type (WT), regarding morphological traits and antioxidant abilities, but accumulated Cd to higher levels, notably in the roots. Fluorescence microscopy showed that PCL localized in the cytoplasm and nucleus.

Does the construction of innovative cities promote urban green innovation?

As a typical example of an innovative governance environment, innovative city has become the focus of political and academic circles. Discussing the green innovation effect of this policy is beneficial in providing decision support for enhancing urban green innovation capability and solving the dilemma of urban resources. Based on data from 241 cities in China from 2005 to 2017, this paper takes innovative city construction as a "quasi-natural experiment" and uses the difference-in-differences method to empirically study the impact of China's innovative city construction on urban green innovation. The results show that innovative urban construction: has a positive effect on improving urban green innovation, and that this effect will gradually increase with time; promotes urban green innovation by expanding the scope of technology application, improving the efficiency of resource allocation and promoting the adjustment of industrial structure; and presents heterogeneity in cities' location, size and hierarchy. Finally, this paper proposes that the government should promote innovative policies in an orderly manner on the basis of following the principle of adapting measures to local conditions, as well as incorporating green innovation performance into the evaluation system for innovative city construction.

Visuoauditory Associative Memory Established with Cholecystokinin Under Anesthesia Is Retrieved in Behavioral Contexts.

Plastic change in neuronal connectivity is the foundation of memory encoding. It is not clear whether the changes during anesthesia can alter subsequent behavior. Here, we demonstrated that in male rodents under anesthesia, a visual stimulus (VS) was associated with electrical stimulation of the auditory cortex or natural auditory stimulus in the presence of cholecystokinin (CCK), which guided the animals' behavior in a two-choice auditory task. Auditory neurons became responsive to the VS after the pairings. Moreover, high-frequency stimulation of axon terminals of entorhinal CCK neurons in the auditory cortex enabled LTP of the visual response in the auditory cortex. Such pairing during anesthesia also generated VS-induced freezing in an auditory fear conditioning task. Finally, we verified that direct inputs from the entorhinal CCK neurons and the visual cortex enabled the above neural plasticity in the auditory cortex. Our findings suggest that CCK-enabled visuoauditory association during anesthesia can be translated to the subsequent behavior action.SIGNIFICANCE STATEMENT Our study provides strong evidence for the hypothesis that cholecystokinin plays an essential role in the formation of cross-modal associative memory. Moreover, we demonstrated that an entorhinal-neocortical circuit underlies such neural plasticity, which will be helpful to understand the mechanisms of memory formation and retrieval in the brain.

Inhibition of Nav1.7 channel by a novel blocker QLS-81 for alleviation of neuropathic pain.

Voltage-gated sodium channel Nav1.7 robustly expressed in peripheral nociceptive neurons has been considered as a therapeutic target for chronic pain, but there is no selective Nav1.7 inhibitor available for therapy of chronic pain. Ralfinamide has shown anti-nociceptive activity in animal models of inflammatory and neuropathic pain and is currently under phase III clinical trial for neuropathic pain. Based on ralfinamide, a novel small molecule (S)-2-((3-(4-((2-fluorobenzyl) oxy) phenyl) propyl) amino) propanamide (QLS-81) was synthesized. Here, we report the electrophysiological and pharmacodynamic characterization of QLS-81 as a Nav1.7 channel inhibitor with promising anti-nociceptive activity. In whole-cell recordings of HEK293 cells stably expressing Nav1.7, QLS-81 (IC50 at 3.5 ± 1.5 µM) was ten-fold more potent than its parent compound ralfinamide (37.1 ± 2.9 µM) in inhibiting Nav1.7 current. QLS-81 inhibition on Nav1.7 current was use-dependent. Application of QLS-81 (10 µM) caused a hyperpolarizing shift of the fast and slow inactivation of Nav1.7 channel about 7.9 mV and 26.6 mV, respectively, and also slowed down the channel fast and slow inactivation recovery. In dissociated mouse DRG neurons, QLS-81 (10 µM) inhibited native Nav current and suppressed depolarizing current pulse-elicited neuronal firing. Administration of QLS-81 (2, 5, 10 mg· kg-1· d-1, i.p.) in mice for 10 days dose-dependently alleviated spinal nerve injury-induced neuropathic pain and formalin-induced inflammatory pain. In addition, QLS-81 (10 µM) did not significantly affect ECG in guinea pig heart ex vivo; and administration of QLS-81 (10, 20 mg/kg, i.p.) in mice had no significant effect on spontaneous locomotor activity. Taken together, our results demonstrate that QLS-81, as a novel Nav1.7 inhibitor, is efficacious on chronic pain in mice, and it may hold developmental potential for pain therapy.

Molten hydroxide for detoxification of chlorine-containing waste: Unraveling chlorine retention efficiency and chlorine salt enrichment.

Hazardous waste dechlorination reduces the potential of creating dioxins during the incineration process. To investigate the salt effect on waste dechlorination, molten hydroxides with a low melting temperature were utilized for the pre-dechlorination and decomposition of chlorine-containing organic wastes (COWs) including trichlorobenzene (TCB), perchloroethylene, hexachlorobenzene and chlordane. The results showed that a eutectic mixture of caustic sodium and potassium hydroxides (41 wt.% NaOH and 59 wt.% KOH) led to a low melting point below 300°C and a relatively high chlorine retention efficiency (CRE) with TCB as a representative COWs. The amounts of hydroxides, reaction time, and temperature all had notable influence on CRE. When the mass ratio of hydroxides to TCB reached 30:1, approximately 98.1% of the TCB was destroyed within 2.5 hr at 300°C with CRE of 71.6%. According to the residue analysis, the shapes of reaction residues were irregular with particles becoming swollen and porous. The benzene ring and C-Cl bonds disappeared, while carboxyl groups formed in the residues. The stripped chlorine was retained and condensed to form chloride salts, and the relative abundance of the chloride ions associated with the mass of TCB in residues increased from 0 to 75.0% within the 2.5 hr reaction time. The observed concentration of dioxins in residues was 5.6 ngTEQ/kg. A reaction pathway and possible additional reactions that occur in this dechlorination system were proposed. Oxidizing agents may attack TCB and facilitate hydrogenation/dechlorination reactions, making this process a promising and environmentally friendly approach for chlorine-containing organic waste treatment.

7ß-Methyl substituent is a structural locus associated with activity cliff for nepenthone analogues.

With the purpose of identifying novel selective κ opioid receptor (KOR) antagonists as potential antidepressants from nepenthone analogues, starting from N-nor-N-cyclopropylmethyl-nepenthone (SLL-020ACP), a highly selective and potent KOR agonist, a series of 7ß-methyl-nepenthone analogues was conceived, synthesized and assayed on opioid receptors based on the concept of hybridization. According to the pharmacological results, the functional reversal observed in orvinol analogues by introduction of 7ß-methyl substituent could not be reproduced in nepenthone analogues. Alternatively, introduction of 7ß-methyl substituent was associated with substantial loss of both subtype selectivity and potency but not efficacy for nepenthone analogues, which was not found in 7ß-methyl orvinol analogues. Surprisingly, SLL-603, a 7ß-methyl analogue of SLL-020ACP, was identified to be a KOR full agonist. The possible molecular mechanism for the heterogeneity in activity cliff was also investigated. In conclusion, 7ß-methyl substituent was a structural locus associated with activity cliff and demonstrated as a pharmacological heterogeneity between nepenthone and orvinol analogues that warrants further investigations.

Exploring Different Ultrasonic Parameters and Treatment Conditions to Optimize In Vitro Sonodynamic Therapeutic Effects in Cancer Cells.

The effects of ultrasonic parameters and treatment conditions on the in vitro cellular experiments of sonodynamic therapy (SDT) have not been fully studied. Exploring the factors that affect the efficacy of SDT can provide a reference for screening effective sonosensitizers in vitro. The aim of this work is to investigate the factors that affected the SDT effects in cancer cells. Cancer cells in culture plates were exposed to ultrasound and sonosensitizers. The intracellular drug concentration was measured by using flow cytometry and the cell viability was determined by MTT assay. The SDT effects of cancer cells treated with different ultrasonic parameters under the same sonosensitizer concentration were different. The ultrasonic parameters, intracellular drug concentration, drug treatment time, cell amount, and cell status could affect the sonodynamic therapeutic effects. It is necessary to select appropriate ultrasound conditions and optimize the cellular status to make the results of the in vitro cellular experiments more reliable.

Mechanism of effect of stenting on hemodynamics at iliac vein bifurcation.

When performing stent intervention for iliac vein compression syndrome, the operator selects the appropriate stent and determines its implantation depth according to the type and severity of iliac vein stenosis in the patient. However, there is still uncertainty regarding how the structure of the stent and its implantation depth affect hemodynamics at the site of lesion. In this paper, we analyzed three commonly used stents (Vena stent from Venmedtch, Venovo from Bard, and Smart stent from Cordis) with different implantation depths (0, 10, 20 mm) using computational fluid dynamics (CFD). We focused on evaluating hemorheological parameters such as time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), etc., within one pulsatile cycle after stent implantation. The correlation between geometric parameters of the stents and hemodynamic indicators was assessed using Pearson correlation coefficient (r), which was further validated through PIV velocity measurement experiment. The results revealed that an increase in implantation depth led to a more pronounced disturbance effect on blood flow at bifurcation for densely arranged support body-type stents. This effect was particularly significant during periods of smooth blood flow. On the other hand, crown-shaped Vena stents exhibited relatively less disruption to blood flow post-implantation. Implantation depth showed a strong negative correlation with TAWSS but a strong positive correlation with OSI and RRT. These findings suggest an increased risk of thrombosis at iliac vein bifurcation following stent placement. Amongst all three tested stents, Vena Stent demonstrated more favorable periodic parameters after implantation compared to others. These results provide valuable theoretical insights into understanding contralateral circulation thrombosis associated with iliac vein stenting.

A carrier-free tri-component nanoreactor for multi-pronged synergistic cancer therapy.

Non-invasive therapies such as photodynamic therapy (PDT) and chemodynamic therapy (CDT) have received wide attention due to their low toxicity and side effects, but their efficacy is limited by the tumor microenvironment (TME), and monotherapy cannot achieve satisfactory efficacy. In this work, a multifunctional nanoparticle co-assembled from oleanolic acid (OA), chlorin e6 (Ce6) and hemin was developed. The as-constructed nanoparticle named OCH with diameters of around 130 nm possessed good biostability, pH/GSH dual-responsive drug release properties, and remarkable cellular internalization and tumor accumulation capabilities. OCH exhibited prominent catalytic activities to generate •OH, deplete GSH, and produce O2 to overcome the hypoxia TME, thus potentiating the photodynamic and chemodynamic effect. In addition, OCH can induce the occurrence of ferroptosis in both ferroptosis-sensitive and ferroptosis-resistant cancer cells. The multi-pronged effects of OCH including hypoxia alleviation, GSH depletion, ferroptosis induction, CDT and PDT effects jointly facilitate excellent anticancer effects in vitro and in vivo. Hence, this work will advance the development of safe and effective clinically transformable nanomedicine by employing clinically-applied agents to form drug combinations for efficient multi-pronged combination cancer therapy.

Reconfigurable Tri-Mode Metasurface for Broadband Low Observation, Wide-Range Tracing, and Backscatter Communication.

In the current prevalent complex electromagnetic (EM) environment, intelligent methods for versatile and integrated control of EM waves using compact devices are both essential and challenging. These varied wave control objectives can at times conflict with one another, such as the need for broad absorption to remain inconspicuous, while also requiring enhanced backward scattering for highly reliable tracing and secure communication. To address these sophisticated challenges, a microwave-frequency reconfigurable tri-mode metasurface (RTMM) is introduced. The proposed innovation enables three distinct operational modes: broadband low observation, enhanced EM wave tracing, and backscatter communication over a wide-angle range by simple control of the PIN diodes embedded in each meta-atom. The proof-of-concept demonstration of the fabricated prototype verified the switchable tri-mode performance of the RTMM. This proposed RTMM can be adapted to various applications, including EM shielding, target detection, and secure communication in complex and threatening EM environments, paving the way for environmentally-adaptive EM wave manipulation.

Minimizing endogenous cryptic plasmids to construct antibiotic-free expression systems for Escherichia coli Nissle 1917.

The probiotic bacterium Escherichia coli Nissle 1917 (EcN) holds significant promise for use in clinical and biological industries. However, the reliance on antibiotics to maintain plasmid-borne genes has overshadowed its benefits. In this study, we addressed this issue by engineering the endogenous cryptic plasmids pMUT1 and pMUT2. The non-essential elements were removed to create more stable derivatives pMUT1NR△ and pMUT2HBC△. Synthetic promoters by integrating binding motifs on sigma factors were further constructed and applied for expression of Bacteroides thetaiotaomicron heparinase III and the biosynthesis of ectoine. Compared to traditional antibiotic-dependent expression systems, our newly constructed antibiotic-free expression systems offer considerable advantages for clinical and synthetic biology applications.

[Effect of multimodal-antiemetic therapy on postoperative nausea and vomiting in patients undergoing gynecological laparoscopy: a randomized controlled study].

OBJECTIVE: To evaluate the efficacy of multimodal-antiemetic therapy on postoperative nausea and vomiting (PONV) in patients undergoing gynecological laparoscopy. METHODS: 129 patients scheduled for gynecological laparoscopy were randomly allocated to a multimodal-antiemetic group (group M, with 65 cases) or an ondansetron control group (group C, with 64 cases). In group M patients received a target-controlled infusion of propofol and remifentanil, prophylactic dexamethasone 10 mg and tropisetron 4 mg were given and parecoxib sodium 40 mg was used 30 minutes before the end of surgery. In group C patients received sevoflurane and 50% nitrous oxide. Prophylactic ondansetron 4 mg was given to patients 30 min before the end of surgery. The incidence of nausea and vomiting, use of rescue antiemetic drugs were recorded for 24 h. RESULTS: 24 h after surgery, the incidence of patients who suffered PONV was significantly lower in Group M compared with Group C (29% vs 70%, P < 0.05). At 0 - 2 h, 2 - 6 h, 6 - 24 h after surgery, the incidences of PONV were 8%, 6% and 25% for group M respectively, significantly lower than those for group C, which were 33%, 30% and 66% respectively(P < 0.05). CONCLUSIONS: Multimodal-antiemetic therapy; a regimen including total intravenous anaesthesia with propofol and remifentanil, prophylactic antiemetic (dexamethasone at induction and tropisetron at end of surgery), and multimodal analgesia with parecoxib sodium could significantly reduce the incidence of PONV after gynecological laparoscopy.

The potential role of the cholecystokinin system in declarative memory.

As one of the most abundant neuropeptides in the central nervous system, cholecystokinin (CCK) has been suggested to be associated with higher brain functions, including learning and memory. In this review, we examined the potential role of the CCK system in declarative memory. First, we summarized behavioral studies that provide evidence for an important role of CCK in two forms of declarative memory-fear memory and spatial memory. Subsequently, we examined the electrophysiological studies that support the diverse roles of CCK-2 receptor activation in neocortical and hippocampal synaptic plasticity, and discussed the potential mechanisms that may be involved. Last but not least, we discussed whether the reported CCK-mediated synaptic plasticity can explain the strong influence of the CCK signaling system in neocortex and hippocampus dependent declarative memory. The available research supports the role of CCK-mediated synaptic plasticity in neocortex dependent declarative memory acquisition, but further study on the association between CCK-mediated synaptic plasticity and neocortex dependent declarative memory consolidation and retrieval is necessary. Although a direct link between CCK-mediated synaptic plasticity and hippocampus dependent declarative memory is missing, noticeable evidence from morphological, behavioral, and electrophysiological studies encourages further investigation regarding the potential role of CCK-dependent synaptic plasticity in hippocampus dependent declarative memory.