Different projection neurons of basolateral amygdala participate in the retrieval of morphine withdrawal memory with diverse molecular pathways.

Context-induced retrieval of drug withdrawal memory is one of the important reasons for drug relapses. Previous studies have shown that different projection neurons in different brain regions or in the same brain region such as the basolateral amygdala (BLA) participate in context-induced retrieval of drug withdrawal memory. However, whether these different projection neurons participate in the retrieval of drug withdrawal memory with same or different molecular pathways remains a topic for research. The present results showed that (1) BLA neurons projecting to the prelimbic cortex (BLA-PrL) and BLA neurons projecting to the nucleus accumbens (BLA-NAc) participated in context-induced retrieval of morphine withdrawal memory; (2) there was an increase in the expression of Arc and pERK in BLA-NAc neurons, but not in BLA-PrL neurons during context-induced retrieval of morphine withdrawal memory; (3) pERK was the upstream molecule of Arc, whereas D1 receptor was the upstream molecule of pERK in BLA-NAc neurons during context-induced retrieval of morphine withdrawal memory; (4) D1 receptors also strengthened AMPA receptors, but not NMDA receptors, -mediated glutamatergic input to BLA-NAc neurons via pERK during context-induced retrieval of morphine withdrawal memory. These results suggest that different projection neurons of the BLA participate in the retrieval of morphine withdrawal memory with diverse molecular pathways.

Formation of chronic morphine withdrawal memories requires C1QL3-mediated regulation of PSD95 in the mouse basolateral amygdala.

Chronic morphine withdrawal memory formation is a complex process influenced by various molecular mechanisms. In this study, we aimed to investigate the contributions of the basolateral amygdala (BLA) and complement component 1, q subcomponent-like 3 (C1QL3), a secreted and presynaptically targeted protein, to the formation of chronic morphine (repeat dosing of morphine) withdrawal memory using conditioned place aversion (CPA) and chemogenetic methods. We conducted experiments involving the inhibition of the BLA during naloxone-induced withdrawal to assess its impact on CPA scores, providing insights into the significance of the BLA in the chronic morphine memory formation process. We also examined changes in C1ql3/C1QL3 expression within the BLA following conditioning. Immunofluorescence analysis revealed the colocalization of C1QL3 and the G protein-coupled receptor, brain-specific angiogenesis inhibitor 3 (BAI3) in the BLA, supporting their involvement in synaptic development. Moreover, we downregulated C1QL3 expression in the BLA to investigate its role in chronic morphine withdrawal memory formation. Our findings revealed that BLA inhibition during naloxone-induced withdrawal led to a significant reduction in CPA scores, confirming the critical role of the BLA in this memory process. Additionally, the upregulation of C1ql3 expression within the BLA postconditioning suggested its participation in withdrawal memory formation. The colocalization of C1QL3 and BAI3 in the BLA further supported their involvement in synaptic development. Furthermore, downregulation of C1QL3 in the BLA effectively hindered chronic morphine withdrawal memory formation, emphasizing its pivotal role in this process. Notably, we identified postsynaptic density protein 95 (PSD95) as a potential downstream effector of C1QL3 during chronic morphine withdrawal memory formation. Blocking PSD95 led to a significant reduction in the CPA score, and it appeared that C1QL3 modulated the ubiquitination-mediated degradation of PSD95, resulting in decreased PSD95 protein levels. This study underscores the importance of the BLA, C1QL3 and PSD95 in chronic morphine withdrawal memory formation. It provides valuable insights into the underlying molecular mechanisms, emphasizing their significance in this intricate process.

Prognostic impact of postoperative adjuvant chemotherapy on elderly patients with colorectal adenocarcinoma: A propensity score matching study.

BACKGROUND AND AIM: Currently, the primary treatment modality for patients with colorectal adenocarcinoma (CRA) is radical surgery combined with postoperative adjuvant chemotherapy (PAC). However, many elderly patients decline PAC due to concerns about their underlying physiological condition, and the impact of PAC on the prognosis of elderly patients remains uncertain. METHODS: We extracted data from the SEER database for CRA patients aged 75 and above between 2010 and 2019. Utilizing propensity score matching (PSM), we stratified the patients into a PAC group and a non-PAC group, enabling us to compare the differences in Kaplan-Meier survival curves between these two groups. Furthermore, through univariate and multivariate Cox regression analyses, we identified the clinical factors that influence the survival of elderly CRA patients and compared the prognostic disparities between the two patient groups within specific subgroups of these clinical factors. RESULTS: Following PSM, a total of 3668 patients were included and divided into the PAC group and the non-PAC group, with no statistically significant differences observed in crucial clinical characteristics between the two groups. Kaplan-Meier analysis revealed a significantly better prognosis for patients in the PAC group compared with those in the non-PAC group. In addition, age, chemotherapy, TNM staging, gender, and preoperative CEA levels were all identified as important factors affecting patient prognosis. Moreover, PAC provided survival benefits across the majority of levels within the aforementioned subgroups. However, in specific subgroups (age > 90, Grade IV stage, median household income < $40 000), PAC did not confer any survival benefits. CONCLUSION: PAC can significantly improve the prognosis of elderly CRA patients. Nonetheless, in certain population subsets characterized by specific clinical features, PAC does not provide any survival benefits.

IRF4 induces M1 macrophage polarization and aggravates ulcerative colitis progression by the Bcl6-dependent STAT3 pathway.

Ulcerative colitis (UC) is an idiopathic chronic intestinal inflammation. An increasing body of evidence shows that macrophages play an important role in the pathogenesis of UC. Interferon regulatory factor 4 (IRF4) is crucial for the development of autoimmune diseases via regulating immune cells. This research was designed to explore the function of IRF4 in UC and its association with macrophage polarization. The in vitro model of UC was established by stimulating colonic epithelial cells with tumor necrosis factor α (TNF-α). A mouse model of UC was constructed by injecting C57BL/6 mice with dextran sulfate sodium salt. Flow cytometry was used to assess percentage of CD11b+ CD86+ and CD11b+ CD206+ cells in bone marrow macrophages. Occult blood tests were used to detect hematochezia. Hematoxylin and eosin staining assay was used to assess colon pathological changes. Enzyme-linked immunosorbent assay (ELISA) was used to detect concentrations of inflammatory cytokines. The interaction of IRF4 and B-cell lymphoma 6 (Bcl6) was confirmed using GST pull-down and coimmunoprecipitation assays. Our findings revealed that IRF4 promoted cell apoptosis and stimulated M1 macrophage polarization in vitro. Furthermore, IRF4 aggravated symptoms of the mouse model of UC and aggravated M1 macrophage polarization in vivo. IRF4 negatively regulated Bcl6 expression. Downregulation of Bcl6 promoted apoptosis and M1 macrophage polarization in the presence of IRF4 in vitro and in vivo. Moreover, Bcl6 positively mediated the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In conclusion, IRF4 aggravated UC progression through promoting M1 macrophage polarization via Bcl6/JAK2/STAT3 pathway. These findings suggested that IRF4 might be a good target to competitively inhibit or to treat with UC.

Enhancing physiological recovery and subsequent exercise performance in the heat using a phase-change material cooling blanket.

This study aimed to assess the effect of a phase-change material (PCM) cooling blanket for cooling between exercise bouts on recovery of physiological parameters and subsequent exercise performance in the heat. Eighteen male volunteers were recruited to participate in human trials involving two exhaustive treadmill running bouts (Bout1 for 3 km and Bout2 for 1.5 km) in a climate chamber (temperature = 33 °C; relative humidity = 40%). Participants were randomly subjected to one of two cooling conditions for a 10-min period between exercise bouts: CON: natural cooling; 10-min PCM: with a PCM cooling blanket for 10 min. Several physiological parameters including mean skin temperature (Tskin), oral temperature (Toral), core temperature (Tcore), heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), peripheral capillary oxygen saturation (SpO2), average running speed and rating of perceived exertion (RPE) scale score were analyzed. The results showed that compared to the CON group, participants in the 10-min PCM group had a significant lower Tskin, Tcore, HR and RR at post-cooling, as well as greater reductions in mean skin temperature (ΔTskin) and core temperature (ΔTcore) from post-Bout1 to post-cooling. Additionally, the 10-min PCM group exhibited significantly lower peak Tcore, peak HR and RPE scale score during Bout2, while the average running speed during Bout2 was significantly higher. The present study suggests that cooling with a PCM cooling blanket can enhance physiological recovery and subsequent exercise performance in the heat.

Effect of black wolfberry anthocyanin and maltitol on the gelation and microstructural properties of curdlan/gellan gum hybrid gels.

BACKGROUND: Laboratory scale experiments have shown that curdlan and gellan gum gelled together as curdlan/gellan gum (CG) hybrid gels showed better gel properties than the individual curdlan and gellan gum. In this study, CG and black wolfberry anthocyanin (BWA), CG and maltitol (ML) hybrid gels were constructed using CG hybrid gel as matrix. The effects of BWA or ML on the gel properties and microstructure of CG hybrid gels were investigated and a confectionery gel was developed. RESULTS: The presence of BWA increased the storage modulus (G') value of CG at 0.1 Hz, whereas ML had little effect on the G' value of CG. The addition of BWA (5 g L-1 ) and ML (0.3 mol L-1 ) increased the melting and gelling temperatures of CG hybrid gels to 42.4 °C and 34.1 °C and 44.2 °C and 33.2 °C, respectively. Meanwhile, the relaxation time T22 in CG-ML and CG-BWA hybrid gels was reduced to 91.96 and 410.27 ms, indicating the strong binding between BWA and CG, ML and CG. The hydrogen bond interaction between BWA or ML and CG was confirmed by the shift in the hydroxyl stretching vibration peak. Moreover, the microstructures of CG-ML and CG-BWA hybrid gels were denser than that of CG. In addition, confectionery gel containing CG-BWA-ML has good chewing properties. CONCLUSION: These results indicated that the incorporation of BWA or ML could improve the structure of CG hybrid gels and assign a sustainability potential for the development of confectionery gels based on CG complex. © 2024 Society of Chemical Industry.

[Penile cancer with perineural invasion is more prone to postoperative recurrence].

OBJECTIVE: To explore the correlation between perineural invasion and postoperative recurrence in patients surgically treated for penile cancer. METHODS: We conducted a retrospective analysis of the clinical data on 18 penile cancer patients surgically treated in our hospital from January 2018 to December 2021, 8 with postoperative recurrence (the recurrence group) and the other 10 without (the non-recurrence control group). We compared the two groups of patients in the age of onset, tumor-node-metastasis (TNM) stages, American Joint Committee on Cancer (AJCC) prognosis stages, surgical methods, perineural invasion and recurrence time. We analyzed the differences in postoperative recurrence using the Kaplan Meier plotted survival curve and in independent risk factors in predicting postoperative recurrence using the ROC curve. RESULTS: Compared with the non-recurrence controls, the patients in the recurrence group had a significantly older age of onset (P=0.0411) and severer perineural invasion (P<0.001), and those with perineural invasion had a shorter recurrence time (P<0.001), which was an independent risk factor for postoperative recurrence. The areas under the ROC curves for perineural invasion and age were 0.885 and 0.213, respectively. CONCLUSION: Penile cancer with perineural invasion is more prone to and perineural invasion is an independent risk factor for postoperative recurrence of the malignancy.

Binary hydrogels constructed from lotus rhizome starch and different types of carrageenan for dysphagia management: Nonlinear rheological behaviors and structural characteristics.

This study focused on binary hydrogels constructed from lotus rhizome starch (LRS) and three types of carrageenan (κ-C, ι-C, and λ-C). The enthalpy of LRS gelatinization was reduced by 32.1%-88.4% with the incorporation of carrageenan. Compared with ι-C and λ-C, the conformations of κ-C more facilitated the development of the binary hydrogel network structure. The ability of the LRS/carrageenan binary hydrogel to immobilize water was mainly related to the effect of different types of carrageenan on starch molecular ordering. LRS-based hydrogels were recognized as level 4 in the International Dysphagia Diet Standardization Initiative (IDDSI) framework. Nevertheless, the incorporation of carrageenan significantly reduced the ability of the LRS hydrogel to resist stress under large deformations, which might be favorable to oral processing and swallowing. This research provides preliminary evidence for relevant industries to use carrageenan to adjust LRS hydrogel properties and improve the quality of starch-based foods for dysphagia management.

Comparing surgical and endoscopic resection approaches for colorectal neuroendocrine tumors within the diameter range of 10-20mm: an inverse probability weighting analysis based on the SEER database.

Background: Currently, the primary treatment modalities for colorectal neuroendocrine tumors (CRNET) with a diameter between 10mm and 20mm are surgical resection (SR) and endoscopic resection (ER). However, it remains unclear which surgical approach yields the greatest survival benefit for patients. Methods: This study included data from patients diagnosed with CRNET with tumor diameters ranging from 10mm to 20mm between the years 2004 and 2019, obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized into ER and SR groups based on the respective surgical approaches. Inverse probability weighting (IPTW) was employed to mitigate selection bias. Kaplan-Meier analysis and log-rank tests were utilized to estimate overall survival (OS) and cancer-specific survival (CSS). Cox regression analysis (univariate and multivariate) was performed to evaluate potential factors influencing survival. Results: A total of 292 CRNET patients were included in this study (ER group: 108 individuals, SR group: 184 individuals). Prior to IPTW adjustment, Kaplan-Meier analysis and Cox proportional hazard regression analysis demonstrated that the OS and CSS of the SR group were inferior to those of the ER group. However, after IPTW adjustment, no statistically significant differences in prognosis were observed between the two groups. Subgroup analyses revealed that patients with muscular invasion, positive lymph nodes, or distant metastasis derived greater survival benefits from SR. Significant differences in OS and CSS between the two groups were also observed across different age groups. Conclusion: For patients with mucosal-limited lesions and without local lymph node or distant metastasis, ER is the preferred surgical approach. However, for patients with muscular invasion or positive lymph nodes/distant metastasis, SR offers a better prognosis. The choice of surgical approach should be based on the specific clinical characteristics of patients within different subgroups.

Rheological characterization of chia seed gum as a thickening agent used for dysphagia management.

Dysphagia has emerged as a serious health issue facing contemporary society. Consuming thickened liquids is an effective approach for improving the swallowing safety for dysphagia patients. The thickening effect of chia seed gum (CSG), a novel thickener, in different dispersing media (water, orange juice, and skim milk) was investigated. Moreover, the potential application of CSG for dysphagia management was evaluated by comparison with xanthan gum (XG) and guar gum (GG). The thickened liquids prepared with 0.4 %-1.2 % (w/v) CSG, XG, and GG could be classified into levels 1-4, 2-4, and 1-3, respectively, according to the International Dysphagia Diet Standardization Initiative (IDDSI) framework. All the thickened liquids displayed shear-thinning characteristics that facilitated safe swallowing. The viscosities (η50) of CSG dissolved in water (0.202-1.027 Pa·s) were significantly greater than those of CSG dissolved in orange juice (0.070-0.690 Pa·s) and skim milk (0.081-0.739 Pa·s), indicating that CSG had a greater thickening effect in water than in orange juice and skim milk. Compared with those prepared with GG, the thickened liquids prepared with CSG and XG exhibited greater viscoelasticity, better water-holding capacity, and more compact networks. The findings suggested that CSG can be used as a potential thickener for thickening liquid foods to manage dysphagia.

Gel properties and interactions of hydrogels constructed with low acyl gellan gum and puerarin.

To develop composite hydrogels based on low acyl gellan gum (GG), the effect of puerarin (PUE) on the gel properties of GG was investigated. The results showed that the maximum storage modulus (G') of the 1.2 % GG/0.8 % PUE composite hydrogel was 377.4 Pa at 0.1 Hz, which was enhanced by 4.7-fold compared with that of 1.2 % GG. The melting temperature of this composite hydrogel increased from 74.1 °C to >80.0 °C. LF-NMR results showed that a significant amount of free water was present in the hydrogel matrix. The surface structure aggregation and the shrinkage of the honeycomb meshes in the composite hydrogel proved the cross-linking of PUE and GG. XRD, FTIR and molecular simulation results illustrated that hydrogen bonds were the most important factor controlling the interaction between GG and PUE. Thus, the GG/PUE composite hydrogel has good elasticity, thermal stability and water retention, which lays a good foundation for further application in the food industry.

Construction and characterization of alginate/calcium ß-hydroxy-ß-methylbutyrate hydrogels: Effect of M/G ratios and calcium ion concentration.

Calcium ß-hydroxy-ß-methylbutyrate (CaHMB), a functional calcium salt, is used to maintain and improve muscle health. Here, a new hydrogel material prepared from alginate (ALG) with three M/G ratios (1:1, 2:1, and 1:2) and CaHMB (0-2 mg/mL) was investigated. CaHMB regulates the formation and properties of ALG hydrogels through chelation and hydrogen bonding. When the M/G ratio was 2:1, the anionic groups of CaHMB containing carboxyl and hydroxyl groups formed hydrogen bonds with the polysaccharide chains, hindering the capture of Ca2+ by the G-residue fragments of ALG, which in turn retarded the gelation process. The noncalcium cross-linked polysaccharide chain structure of ALG and the anionic group of CaHMB also affected the water distribution in the hydrogel, especially when M residue content ≥G residue content. Lower M/G ratios and higher CaHMB concentrations could increase the number of "egg box" crosslinking junctions of calcium alginate, and the microstructure was denser in the gel pores, resulting in a stronger gel strength and more free water bound in the gel matrix. This study provides a theoretical and methodological basis for the design of novel hydrogels by studying the crosslinking features of ALG/CaHMB.

Projection neurons from medial entorhinal cortex to basolateral amygdala are critical for the retrieval of morphine withdrawal memory.

The medial entorhinal cortex (MEC) is crucial for contextual memory, yet its role in context-induced retrieval of morphine withdrawal memory remains unclear. This study investigated the role of the MEC and its projection neurons from MEC layer 5 to the basolateral amygdala (BLA) (MEC-BLA neurons) in context-induced retrieval of morphine withdrawal memory. Results show that context activates the MEC in morphine withdrawal mice, and the inactivation of the MEC inhibits context-induced retrieval of morphine withdrawal memory. At neural circuits, context activates MEC-BLA neurons in morphine withdrawal mice, and the inactivation of MEC-BLA neurons inhibits context-induced retrieval of morphine withdrawal memory. But MEC-BLA neurons are not activated by conditioning of context and morphine withdrawal, and the inhibition of MEC-BLA neurons do not influence the coupling of context and morphine withdrawal memory. These results suggest that MEC-BLA neurons are critical for the retrieval, but not for the formation, of morphine withdrawal memory.

Physicochemical Properties of Granular and Gelatinized Lotus Rhizome Starch with Varied Proximate Compositions and Structural Characteristics.

As a traditional and popular dietary supplement, lotus rhizome starch (LRS) has health benefits for its many nutritional components and is especially suitable for teenagers and seniors. In this paper, the approximate composition, apparent amylose content (AAC), and structural characteristics of five LRS samples from different regions were investigated, and their correlations with the physicochemical properties of granular and gelatinized LRS were revealed. LRS exhibited rod-shaped and ellipsoidal starch granules, with AAC ranging from 26.6% to 31.7%. LRS-3, from Fuzhou, Jiangxi Province, exhibited a deeper hydrogel color and contained more ash, with 302.6 mg/kg iron, and it could reach the pasting temperature of 62.6 °C. In comparison, LRS-5, from Baoshan, Yunnan Province, exhibited smoother granule surface, less fragmentation, and higher AAC, resulting in better swelling power and freeze-thaw stability. The resistant starch contents of LRS-3 and LRS-5 were the lowest (15.3%) and highest (69.7%), respectively. The enzymatic digestion performance of LRS was positively correlated with ash content and short- and long-term ordered structures but negatively correlated with AAC. Furthermore, the color and network firmness of gelatinized LRS was negatively correlated with its ash content, and the retrograde trend and freeze-thaw stability were more closely correlated with AAC and structural characteristics. These results revealed the physicochemical properties of LRS from different regions and suggested their advantages in appropriate applications as a hydrogel matrix.