Enhancing vitamin D3 bioaccessibility: Unveiling hydrophobic interactions in soybean protein isolate and vitamin D3 binding via an infant in vitro digestion model.

In the domain of infant nutrition, optimizing the absorption of crucial nutrients such as vitamin D3 (VD3) is paramount. This study harnessed dynamic-high-pressure microfluidization (DHPM) on soybean protein isolate (SPI) to engineer SPI-VD3 nanoparticles for fortifying yogurt. Characterized by notable binding affinity (Ka = 0.166 × 105 L·mol-1) at 80 MPa and significant surface hydrophobicity (H0 = 3494), these nanoparticles demonstrated promising attributes through molecular simulations. During simulated infant digestion, the 80 MPa DHPM-treated nanoparticles showcased an impressive 74.4% VD3 bioaccessibility, delineating the pivotal roles of hydrophobicity, bioaccessibility, and micellization dynamics. Noteworthy was their traversal through the gastrointestinal tract, illuminating bile salts' crucial function in facilitating VD3 re-encapsulation, thereby mitigating crystallization and augmenting absorption. Moreover, DHPM treatment imparted enhancements in nanoparticle integrity and hydrophobic properties, consequently amplifying VD3 bioavailability. This investigation underscores the potential of SPI-VD3 nanoparticles in bolstering VD3 absorption, thereby furnishing invaluable insights for tailored infant nutrition formulations.

Synthesis and anti-inflammatory activity of mogrol derivatives modified at C24 site.

Mogrol, the aglycone of well-known sweeter mogrosides, shows potent anti-inflammatory activity. In this study, forty-two mogrol derivatives bearing various pharmacophores with oxygen or nitrogen atoms were designed and synthesized via structural modification at C24 site, and their anti-inflammatory activity were screened against lipopolysaccharide (LPS)-induced RAW264.7 cells. Compared with mogrol, most of derivatives exhibited stronger inhibition of NO production without cytotoxicity. In particular, compound B5 that contained an indole motif effectively suppressed the secretion of inflammatory mediators including TNF-α and IL-6, and inhibited the expression levels of TLR4, p-p65 and iNOS proteins. Molecular docking showed that the active B5 interacted with amino acid residues of iNOS protein through π-π stacking and hydrophobic interactions with binding affinity value of -12.1 kcal/mol, which was much stronger than mogrol (-8.9 kcal/mol). These results suggest that derivative B5 is a promising anti-inflammatory molecule and the strategy of hybridizing indole skeleton on mogrol is worthy for further attention.

Plasmodium vivax tryptophan-rich antigen reduces type I collagen secretion via the NF-κBp65 pathway in splenic fibroblasts.

BACKGROUND: The spleen plays a critical role in the immune response against malaria parasite infection, where splenic fibroblasts (SFs) are abundantly present and contribute to immune function by secreting type I collagen (collagen I). The protein family is characterized by Plasmodium vivax tryptophan-rich antigens (PvTRAgs), comprising 40 members. PvTRAg23 has been reported to bind to human SFs (HSFs) and affect collagen I levels. Given the role of type I collagen in splenic immune function, it is important to investigate the functions of the other members within the PvTRAg protein family. METHODS: Protein structural prediction was conducted utilizing bioinformatics analysis tools and software. A total of 23 PvTRAgs were successfully expressed and purified using an Escherichia coli prokaryotic expression system, and the purified proteins were used for co-culture with HSFs. The collagen I levels and collagen-related signaling pathway protein levels were detected by immunoblotting, and the relative expression levels of inflammatory factors were determined by quantitative real-time PCR. RESULTS: In silico analysis showed that P. vivax has 40 genes encoding the TRAg family. The C-terminal region of all PvTRAgs is characterized by the presence of a domain rich in tryptophan residues. A total of 23 recombinant PvTRAgs were successfully expressed and purified. Only five PvTRAgs (PvTRAg5, PvTRAg16, PvTRAg23, PvTRAg30, and PvTRAg32) mediated the activation of the NF-κBp65 signaling pathway, which resulted in the production of inflammatory molecules and ultimately a significant reduction in collagen I levels in HSFs. CONCLUSIONS: Our research contributes to the expansion of knowledge regarding the functional role of PvTRAgs, while it also enhances our understanding of the immune evasion mechanisms utilized by parasites.

Translation and validation of traditional Chinese version of the pediatric eating assessment Tool-10.

BACKGROUND: /Purpose: The Pediatric Eating Assessment Tool-10 (Pedi-EAT-10) is a caregiver-administrated subjective questionnaire for evaluating swallowing and feeding disorders among children. This study translated the Pedi-EAT-10 into Traditional Chinese and tested the translated version's reliability and validity. METHODS: Pedi-EAT-10 was translated into Traditional Chinese by experts and finalized after discussion and testing. A total of 168 participants, consisting of 32 children with dysphagia from a tertiary medical center and 136 healthy controls from its Children Care Center for Employees, were recruited. All participants were assessed by an otolaryngologist and speech-language pathologist. The reliability, validity, and efficacy of the translated Pedi-EAT-10 were analyzed to ensure it could be used to identify pediatric dysphagia and feeding problems. RESULTS: The Traditional Chinese version of the Pedi-EAT-10 had significant clinical discriminative validity between the dysphagia group and the control group (total score = 9.6 vs. 2.6, P < 0.001), acceptable test-retest reliability (intraclass correlation = 0.63), and excellent internal consistency (Cronbach's α = 0.91 for the entire cohort). The overall performance of the test for distinguishing children with dysphagia from normal controls was acceptable, and the area under the curve was 74.8% (sensitivity = 71.9%; specificity = 69.9%). The optimal cutoff score was ≥3 on the Youdex index. CONCLUSIONS: The Traditional Chinese version of the Pedi-EAT-10 has fair reliability and validity and can be quickly and easily completed by caregivers. The translated Ped-EAT-10 can be used as a first-line tool for assessing the need for further referral and instrumental examination.

Role of Galectin-3 in intervertebral disc degeneration: an experimental study.

BACKGROUND: This study investigated the role of Galectin-3 in the degeneration of intervertebral disc cartilage. METHODS: The patients who underwent lumbar spine surgery due to degenerative disc disease were recruited and divided into Modic I, Modic II, and Modic III; groups. HE staining was used to detect the pathological changes in endplates. The changes of Galectin-3, MMP3, Aggrecan, CCL3, and Col II were detected by immunohistochemistry, RT-PCR, and Western blot. MTT and flow cytometry were used to detect cartilage endplate cell proliferation, cell cycle, and apoptosis. RESULTS: With the progression of degeneration (from Modic I to III), the chondrocytes and density of the cartilage endplate of the intervertebral disc decreased, and the collagen arrangement of the cartilage endplate of the intervertebral disc was broken and calcified. Meanwhile, the expressions of Aggrecan, Col II, Galectin-3, Aggrecan, and CCL3 gradually decreased. After treatment with Galectin-3 inhibitor GB1107, the proliferation of rat cartilage end plate cells was significantly reduced (P < 0.05). GB1107 (25 µmol/L) also significantly promoted the apoptosis of cartilage endplate cells (P < 0.05). Moreover, the percentage of cartilage endplate cells in the G1 phase was significantly higher, while that in the G2 and S phases was significantly lower (P < 0.05). Additionally, the mRNA and protein expression levels of MMP3, CCL3, and Aggrecan in rat cartilage end plate cells were lower than those in the control group. CONCLUSIONS: Galectin-3 decreases with the progression of the cartilage endplate degeneration of the intervertebral disc. Galectin-3 may affect intervertebral disc degeneration by regulating the degradation of the extracellular matrix.

The Association Between the Triglyceride to High-Density Lipoprotein Cholesterol Ratio and the Incidence of Type 2 Diabetes Mellitus in the Japanese Population.

Abstract Aims: To explore whether the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) was independently associated with the risk of incident type 2 diabetes mellitus (T2DM) in a large Japanese cohort. Methods: A secondary analysis was performed using open-access data from a retrospective cohort study. A total of 12,716 eligible participants who had standard medical examinations at the Murakami Memorial Hospital were included in this study. New-onset T2DM was the main outcome during follow-up. The risk of T2DM based on the TG/HDL-C ratio was evaluated using Cox regression analysis and Kaplan-Meier analysis. Subgroup analysis was performed to understand further the significance of the TG/HDL-C ratio in particular populations. To assess the potential of the TG/HDL-C ratio for predicting T2DM, a receiver operating characteristic (ROC) analysis was performed. Results: One hundred fifty new-onset T2DM cases were observed during a median follow-up of 5.39 years. The incidence of T2DM increased with a rise in the TG/HDL-C ratio based on the Kaplan-Meier curves (P < 0.0001). After controlling for potential confounding variables, the TG/HDL-C ratio was positively related to incidence of T2DM (hazard ratio = 1.08, 95% confidence interval: 1.01-1.15, P = 0.0239). In subgroup analysis, those with a body mass index of ≥18.5 and <24 kg/m2 showed a significantly positive relationship. The area under the ROC curve for the TG/HDL-C ratio as a T2DM predictor was 0.684. The optimal TG/HDL-C ratio cutoff value for T2DM was 1.609, with a sensitivity of 54.7% and a specificity of 73.6%. Conclusion: The authors' results showed a significant relationship between the TG/HDL-C ratio and the incidence of T2DM in the Japanese population.

Erratum: [Corrigendum] Hydrogen gas post­conditioning alleviates cognitive dysfunction and anxiety­like behavior in a rat model of subarachnoid hemorrhage.

[This corrects the article DOI: 10.3892/etm.2021.10555.].

UDP-glycosyltransferases act as key determinants of host plant range in generalist and specialist Spodoptera species.

Phytophagous insects have evolved sophisticated detoxification systems to overcome the antiherbivore chemical defenses produced by many plants. However, how these biotransformation systems differ in generalist and specialist insect species and their role in determining insect host plant range remains an open question. Here, we show that UDP-glucosyltransferases (UGTs) play a key role in determining the host range of insect species within the Spodoptera genus. Comparative genomic analyses of Spodoptera species that differ in host plant breadth identified a relatively conserved number of UGT genes in generalist species but high levels of UGT gene pseudogenization in the specialist Spodoptera picta. CRISPR-Cas9 knockouts of the three main UGT gene clusters of Spodoptera frugiperda revealed that UGT33 genes play an important role in allowing this species to utilize the poaceous plants maize, wheat, and rice, while UGT40 genes facilitate utilization of cotton. Further functional analyses in vivo and in vitro identified the UGT SfUGT33F32 as the key mechanism that allows generalist S. frugiperda to detoxify the benzoxazinoid DIMBOA (2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one), a potent insecticidal phytotoxin produced by poaceous plants. However, while this detoxification capacity is conserved in several generalist Spodoptera species, Spodoptera picta, which specializes on Crinum plants, is unable to detoxify DIMBOA due to a nonfunctionalizing mutation in SpUGT33F34. Collectively, these findings provide insight into the role of insect UGTs in host plant adaptation, the mechanistic basis of evolutionary transitions between generalism and specialism and offer molecular targets for controlling a group of notorious insect pests.

Modulation of lipid profile by secretory phospholipase A2 group IIA: Verification with a transgenic mouse model.

We previously demonstrated a positive relation of secretory phospholipase A2 group IIA (sPLA2-IIA) with circulating high-density lipoprotein cholesterol (HDL-C) in patients with coronary artery disease, and sPLA2-IIA increased cholesterol efflux in THP-1 cells through peroxisome proliferator-activated receptor-γ (PPAR-γ)/liver X receptor α/ATP-binding cassette transporter A1 (ABCA1) signaling pathway. The aim of the present study was to examine the role of sPLA2-IIA over-expression on lipid profile in a transgenic mouse model. Fifteen apoE-/- and C57BL/7 female mice received bone marrow transplantation from transgenic SPLA2-IIA mice, and treated with specific PPAR-γ inhibitor GW9662. High fat diet was given after one week of bone marrow transplantation, and animals were sacrificed after twelve weeks. Immunohistochemical staining showed over-expression of sPLA2-IIA protein in the lung and spleen. The circulating level of HDL-C, but not that of low-density lipoprotein cholesterol (LDL-C), total cholesterol, or total triglyceride, was increased by sPLA2-IIA over-expression, and was subsequently reversed by GW9662 treatment. Over-expression of sPLA2-IIA resulted in augmented expression of cholesterol transporter ABCA1 at mRNA level in the aortas, and at protein level in macrophages, co-localized with macrophage specific antigen CD68. GW9662 exerted potent inhibitory effects on sPLA2-IIA-induced ABCA1 expression. Conclusively, we demonstrated the effects of sPLA2-IIA on circulating HDL-C level and the expression of ABCA1, possibly through regulation of PPAR-γ signaling in transgenic mouse model, that is in concert with the conditions in patients with coronary artery disease.

IFN-υ and its receptor subunits, IFN-υR1 and IL10RB in mallard Anas platyrhynchos.

Type IV interferon (IFN) has been shown to be a cytokine with antiviral activity in fish and amphibian. But, it has not been cloned and characterized functionally in avian species. In this study, type IV IFN, IFN-υ, and its 2 possible receptors, IFN-υR1 and IL10RB, were identified from an avian species, the mallard (Anas platyrhynchos). Mallard IFN-υ has a 531 bp open reading frame (ORF), encoding 176 amino acids (aa), and has highly conserved features as reported in different species, with an N-terminal signal peptide and a predicted multi-helix structure. The IFN-υR1 and IL10RB contain 528 and 343 aa, respectively, with IFN-υR1 protein containing JAK1 and STAT binding sites, and IL10RB containing TYK2 binding site. These 2 receptor subunits also possess 3 domains, the N-terminal extracellular domain, the transmembrane domain, and the C-terminal intracellular domain. Expression analysis indicated that IFN-υ, IFN-υR1 and IL10RB were widely expressed in examined organs/tissues, with the highest level observed in pancreas, blood, and kidney, respectively. The expression of IFN-υ, IFN-υR1 and IL10RB in liver, spleen or kidney was significantly upregulated after stimulation with polyI:C. Furthermore, recombinant IFN-υ protein induced the expression of ISGs, and the receptor of IFN-υ was verified as IFN-υR1 and IL10RB using a chimeric receptor approach in HEK293 cells. Taken together, these results indicate that IFN-υ is involved in the host innate immune response in mallard.

[Brain magnetic resonance image registration based on parallel lightweight convolution and multi-scale fusion].

Medical image registration plays an important role in medical diagnosis and treatment planning. However, the current registration methods based on deep learning still face some challenges, such as insufficient ability to extract global information, large number of network model parameters, slow reasoning speed and so on. Therefore, this paper proposed a new model LCU-Net, which used parallel lightweight convolution to improve the ability of global information extraction. The problem of large number of network parameters and slow inference speed was solved by multi-scale fusion. The experimental results showed that the Dice coefficient of LCU-Net reached 0.823, the Hausdorff distance was 1.258, and the number of network parameters was reduced by about one quarter compared with that before multi-scale fusion. The proposed algorithm shows remarkable advantages in medical image registration tasks, and it not only surpasses the existing comparison algorithms in performance, but also has excellent generalization performance and wide application prospects.

The Plasmodium vivax MSP1P-19 is involved in binding of reticulocytes through interactions with the membrane proteins band3 and CD71.

The parasite Plasmodium vivax preferentially invades human reticulocytes. Its merozoite surface protein 1 paralog (PvMSP1P), particularly the 19-kDa C-terminal region (PvMSP1P-19), has been shown to bind to reticulocytes, and this binding can be inhibited by antisera obtained by PvMSP1P-19 immunization. The molecular mechanism of interactions between PvMSP1P-19 and reticulocytes during P. vivax invasion, however, remains unclear. In this study, we analyzed the ability of MSP1P-19 to bind to different concentrations of reticulocytes and confirmed its reticulocyte preference. LC-MS analysis was used to identify two potential reticulocyte receptors, band3 and CD71, that interact with MSP1P-19. Both PvMSP1P-19 and its sister taxon Plasmodium cynomolgi MSP1P-19 were found to bind to the extracellular loop (loop 5) of band3, where the interaction of MSP1P-19 with band3 was chymotrypsin sensitive. Antibodies against band3-P5, CD71, and MSP1P-19 reduced the binding activity of PvMSP1P-19 and Plasmodium cynomolgi MSP1P-19 to reticulocytes, while MSP1P-19 proteins inhibited Plasmodium falciparum invasion in vitro in a concentration-dependent manner. To sum up, identification and characterization of the reticulocyte receptor is important for understanding the binding of reticulocytes by MSP1P-19.

Amyloid pathology mediates the associations between plasma fibrinogen and cognition in non-demented adults.

Though previous studies revealed the potential associations of elevated levels of plasma fibrinogen with dementia, there is still limited understanding regarding the influence of Alzheimer's disease (AD) biomarkers on these associations. We sought to investigate the interrelationships among fibrinogen, cerebrospinal fluid (CSF) AD biomarkers, and cognition in non-demented adults. We included 1996 non-demented adults from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study and 337 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The associations of fibrinogen with AD biomarkers and cognition were explored using multiple linear regression models. The mediation analyses with 10 000 bootstrapped iterations were conducted to explore the mediating effects of AD biomarkers on cognition. In addition, interaction analyses and subgroup analyses were conducted to assess the influence of covariates on the relationships between fibrinogen and AD biomarkers. Participants exhibiting low Aß42 were designated as A+, while those demonstrating high phosphorylated tau (P-tau) and total tau (Tau) were labeled as T+ and N+, respectively. Individuals with normal measures of Aß42 and P-tau were categorized as the A-T- group, and those with abnormal levels of both Aß42 and P-tau were grouped under A+T+. Fibrinogen was higher in the A+ subgroup compared to that in the A- subgroup (p = 0.026). Fibrinogen was higher in the A+T+ subgroup compared to that in the A-T- subgroup (p = 0.011). Higher fibrinogen was associated with worse cognition and Aß pathology (all p < 0.05). Additionally, the associations between fibrinogen and cognition were partially mediated by Aß pathology (mediation proportion range 8%-28%). Interaction analyses and subgroup analyses showed that age and ApoE ε4 affect the relationships between fibrinogen and Aß pathology. Fibrinogen was associated with both cognition and Aß pathology. Aß pathology may be a critical mediator for impacts of fibrinogen on cognition.

Bacteria-mediated resistance of neutrophil extracellular traps to enzymatic degradation drives the formation of dental calculi.

Dental calculi can cause gingival bleeding and periodontitis, yet the mechanism underlying the formation of such mineral build-ups, and in particular the role of the local microenvironment, are unclear. Here we show that the formation of dental calculi involves bacteria in local mature biofilms converting the DNA in neutrophil extracellular traps (NETs) from being degradable by the enzyme DNase I to being degradation resistant, promoting the nucleation and growth of apatite. DNase I inhibited NET-induced mineralization in vitro and ex vivo, yet plasma DNases were ineffective at inhibiting ectopic mineralization in the oral cavity in rodents. The topical application of the DNA-intercalating agent chloroquine in rodents fed with a dental calculogenic diet reverted NET DNA to its degradable form, inhibiting the formation of calculi. Our findings may motivate therapeutic strategies for the reduction of the prevalence of the deposition of bacteria-driven calculi in the oral cavity.