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Fucoxanthin (FN), a carotenoid derived from brown seaweed and algae, offers significant health benefits. However, its unique structure leads to challenges in stability and bioavailability. To overcome these issues, we successfully encapsulated fucoxanthin in solid lipid nanoparticles (SLNs) utilizing health-safe materials, achieving remarkable results. SLNs exhibited a nanoscale size of 248.98 ± 4.0 nm, along with an impressive encapsulation efficiency of 98.30% ± 0.26% and a loading capacity of 5.48% ± 0.82% in lipid. The polydispersity index (PDI) was measured at 0.161 ± 0.03, indicating a narrow size distribution, while the high negative zeta potential of −32.93 ± 1.2 mV suggests excellent stability. Pharmacokinetic studies conducted in Sprague–Dawley rats revealed an exceptional oral bioavailability of 2723.16% compared to fucoxanthin crystals, likely attributed to the enhanced stability and improved cellular uptake of the SLNs. To further improve bioavailability, we creatively applied enteric coatings to the freeze-dried SLNs, effectively protecting fucoxanthin from gastric degradation, which is supported by in vitro digestion results. These findings underscore the potential of SLNs as a superior delivery system for fucoxanthin, significantly enhancing its therapeutic efficacy and broadening its application in the food and pharmaceutical industries.

In the present study, we showed evidence of an integration between two unconscious semantic representations. In experiment 1, two masked Chinese words of the same or different categories (“orange apple” or “grape hammer”) were simultaneously presented in the prime, followed by two Chinese words also of same or different categories in the target. We examined possible prime/target visual feature priming, semantic category priming and motor response priming effects. Moreover, two ISI intervals (53, 163 ms) between the prime and the target words were used to examine the positive and negative priming. The results revealed a negative motor response priming and a positive semantic category priming effect independent of the ISI when the target words were of the same category. Experiment 2 eliminated an alternative interpretation of the effect based on different number of category words changed across the prime and the target. Experiment 3 eliminated a potential confound of unequal numbers of trials for motor congruent and incongruent conditions in Experiment 1. Overall, these results indicated an integration between the meanings of the two subliminally perceived words in the prime. The difference between simultaneous and sequential presentations, and the reason why positive priming was not observed when the interval between the prime and the target was short were discussed in the context of unconscious semantic integration.

Infiltrated macrophages are an important constituent of the tumor microenvironment and play roles in tumor initiation and progression by promoting immune evasion. However, the molecular mechanism by which macrophage-derived cytokines foster immune escape of colorectal cancer (CRC) is unclear. Here, we demonstrated that macrophage infiltration induced by lipopolysaccharide (LPS) or a high-cholesterol diet (HCD) significantly promoted CRC growth. Similarly, LPS and poly (I:C) remarkably increased the volume of CT26 cell allograft tumors. C-C motif chemokine ligand 5 (CCL5), which is secreted by macrophages, inhibited T-cell-mediated killing of HT29 cells and promoted immune escape by stabilizing PD-L1 in vitro and in vivo. Mechanistically, CCL5 resulted in formation of nuclear factor kappa-B p65/STAT3 complexes, which bound to the COP9 signalosome 5 (CSN5) promoter, leading to its upregulation. Moreover, CSN5 modulated the deubiquitination and stability of PD-L1. High expression of CSN5 in CRC was associated with significantly shorter survival. Furthermore, compound-15 was identified as an inhibitor of CSN5, and destabilized PD-L1 to alleviate the tumor burden. Our results suggest that the novel CCL5-p65/STAT3-CSN5-PD-L1 signaling axis is significantly activated by LPS or HCD-driven macrophage infiltration in an animal model of CRC, which likely has therapeutic and prognostic implications for human cancers.

Intracerebral hemorrhage (ICH) refers to bleeding in the brain and is associated with the release of large amount of inflammasomes, and the activation of different cell death pathways. These cell death pathways lead to removal of inactivated and damaged cells and also result in neuronal cell damage. Pyroptosis is a newly discovered cell death pathway that has gained attention in recent years. This pathway mainly depends on activation of caspase-1-mediated cascades to cause cell death. We tested a well-known selective inhibitor of caspase-1, AC-YVAD-CMK, which has previously been found to have neuroprotective effects in ICH mice model, to ascertain its effects on the activation of inflammasomes mediated pyroptosis. Our results showed that AC-YVAD-CMK could reduce caspase-1 activation and inhibit IL-1β production and maturation, but has no effect on NLRP3 expression, an upstream inflammatory complex. AC-YVAD-CMK administration also resulted in reduction in M1-type microglia polarization around the hematoma, while increasing the number of M2-type cells. Furthermore, AC-YVAD-CMK treated mice showed some recovery of neurological function after hemorrhage especially at the hyperacute and subacute stage resulting in some degree of limb movement. In conclusion, we are of the view that AC-YVAD-CMK could inhibit pyroptosis, decrease the secretion or activation of inflammatory factors, and affect the polarization of microglia resulting in improvement of neurological function after ICH.

The cryopreservation of biological samples is hindered by ice formation and the need to maintain samples under cryogenic conditions during storage and transportation. Silicification offers a simple method for preserving life within refractory, amorphous silicon dioxide, which is analogous to vitreous ice but does not melt and thereby avoids cold-chain issues.

Objectives This study investigated the effectiveness of a deep convolutional neural network (CNN) in diagnosing and staging caries lesions in quantitative light-induced fluorescence (QLF) images taken by a self-manufactured handheld device. Methods A small toothbrush-like device consisting of a 400 nm UV light-emitting lamp with a 470 nm filter was manufactured for intraoral imaging. A total of 133 cases with 9,478 QLF images of teeth were included for caries lesion evaluation using a CNN model. The database was divided into development, validation, and testing cohorts at a 7:2:1 ratio. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC) were calculated for model performance. Results The overall caries prevalence was 19.59%. The CNN model achieved an AUC of 0.88, an accuracy of 0.88, a specificity of 0.94, and a sensitivity of 0.64 in the validation cohort. They achieved an overall accuracy of 0.92, a sensitivity of 0.95 and a specificity of 0.55 in the testing cohort. The model can distinguish different stages of caries well, with the best performance in detecting deep caries followed by intermediate and superficial lesions. Conclusions Caries lesions have typical characteristics in QLF images and can be detected by CNNs. A QLF-based device with CNNs can assist in caries screening in the clinic or at home. Trial registration The clinical trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2300073487, Date: 12/07/2023).

Background: Although pericallosal artery aneurysms (PAAs) are relatively uncommon, accounting for only 1–9% of all intracranial aneurysms (IAs), they exhibit a considerably high propensity to rupture. Nevertheless, our current knowledge of the risk factors for PAA rupture is still very limited. To fill this gap, we investigated rupture risk factors for PAAs based on morphological computer-assisted semiautomated measurement (CASAM) and hemodynamic analysis. Methods: Patients with PAAs were selected from the IA database in our institute and their baseline data were collected. Morphological parameters were measured in all enrolled patients by applying CASAM. Computational fluid dynamics simulation (CFD) was performed to evaluate the hemodynamic difference between ruptured and unruptured PAAs. Results: From June 2017 to June 2020, among 2141 patients with IAs in our institute, 47 had PAAs (2.2%). Thirty-one patients (mean age 57.65 ± 9.97 years) with 32 PAAs (20 unruptured and 12 ruptured) were included in the final analysis. Comparing with unruptured PAAs, ruptured PAAs had significantly higher aspect ratio (AR), mean normalized wall shear stress (NWSS), and mean oscillatory shear index (OSI) values than the unruptured PAAs (all P < 0.05) in univariate analyses. Multivariable analysis showed that a high mean OSI was an independent risk factor for PAA rupture (OR = 6.45, 95% CI 1.37–30.32, P = 0.018). Conclusion: This preliminary study indicates that there are morphological and hemodynamic differences between ruptured and unruptured PAAs. In particular, a high mean OSI is an independent risk factor for PAA rupture. Further research with a larger sample size is warranted in the future.

The optimal treatment endpoints and duration of continuous therapy for multicentric Castleman disease (MCD) remain controversial. We retrospectively analyzed data from 123 patients with Human Herpesvirus (HHV)-8 negative MCD. We demonstrated that continuous therapy significantly enhanced progression-free survival (PFS) in patients who achieved an optimal response after initial treatment. These findings underscore the critical role of continuous therapy in HHV-8 negative MCD. Further studies with larger cohorts are required to validate these findings.

Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide. Although treatment guidelines have been developed, no best treatment option or medicine for this condition exists. Recently, mesenchymal stem cells (MSCs)-derived exosomes have shown lots of promise for the treatment of brain disorders, with some results highlighting the neuroprotective effects through neurogenesis and angiogenesis after TBI. However, studies focusing on the role of exosomes in the early stages of neuroinflammation post-TBI are not sufficient. In this study, we investigated the role of bone mesenchymal stem cells (BMSCs)-exosomes in attenuating neuroinflammation at an early stage post-TBI and explored the potential regulatory neuroprotective mechanism. We administered 30 μg protein of BMSCs-exosomes or an equal volume of phosphate-buffered saline (PBS) via the retro-orbital route into C57BL/6 male mice 15 min after controlled cortical impact (CCI)-induced TBI. The results showed that the administration of BMSCs-exosomes reduced the lesion size and improved the neurobehavioral performance assessed by modified Neurological Severity Score (mNSS) and rotarod test. In addition, BMSCs-exosomes inhibited the expression of proapoptosis protein Bcl-2-associated X protein (BAX) and proinflammation cytokines, tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β, while enhancing the expression of the anti-apoptosis protein B-cell lymphoma 2 (BCL-2). Furthermore, BMSCs-exosomes modulated microglia/macrophage polarization by downregulating the expression of inducible nitric oxide synthase (INOS) and upregulating the expression of clusters of differentiation 206 (CD206) and arginase-1 (Arg1). In summary, our result shows that BMSCs-exosomes serve a neuroprotective function by inhibiting early neuroinflammation in TBI mice through modulating the polarization of microglia/macrophages. Further research into this may serve as a potential therapeutic strategy for the future treatment of TBI.

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