Retrospective analysis of the prognostic factors of fetal corpus callosum dysplasia.

BACKGROUND: To analyze the genetic characteristics and long-term outcomes of fetuses with dysplasia of the corpus callosum (DCC) or partial agenesis of the corpus callosum (PACC). METHODS: A total of 42 fetuses with DCC (n = 36) or PACC (n = 6) were retrospectively analyzed from January 2016 to December 2022 at the Peking University First Hospital. The cohort was categorized into isolated (15/42, 36%) and nonisolated groups (27/42, 64%), and differences in the genetic abnormalities and long-term outcomes between the two groups were analyzed. DCC was subdivided into short CC, thin CC, and thick CC. The outcomes of the three different types of DCC were analyzed and discussed. RESULTS: (1) Thirty-nine of the 42 cases underwent CMA (chromosomal microarray analysis) and CMA + WES (whole exome sequencing), with 13/15 cases in isolated group and 26/27 cases in nonisolated group. Only pathogenic or likely pathogenic (P/LP) variants were considered, identifying P/LP variants in 2/13 cases in isolated group and 12/26 cases in nonisolated group. There was no significant difference between the two groups (χ² = 3.566, P = 0.05897). (2) In the isolated group, 8 cases were terminated, and 7 cases were delivered. Postnatal follow-up detected 1 case of gross motor development delay one year after birth; no obvious abnormalities were found in the other six cases. In the nonisolated group, 21 cases were terminated, and 6 cases were delivered. Postnatal follow-up detected 4 cases of children with different degrees of language, motor and intelligence abnormalities; 1 case died 10 days after birth. No obvious abnormalities were observed in one case. Six cases (86%, 6/7) in the isolated group showed normal development, compared with 1 case (17%, 1/6) in the nonisolated group, with a significant difference (χ² = 6.198, P = 0.01279). (3) In DCC, the delivery rates of short CCs (18 cases), thin CCs (13 cases), and thick CCs (5 cases) were 17% (3/18), 54% (7/13), and 20% (1/5), respectively, with good outcomes observed in 0% (0/3), 71% (5/7), and 0% (0/1), respectively. P/LP variants were found in 6/17 cases of short CC, 3/12 cases of thin CC, and 2/5 cases of thick CC. CONCLUSIONS: Fetuses with DCC or PACC combined with other structural abnormalities had a poor long-term prognosis compared with the isolated group. Patients with thin CCs had a higher probability of a good prognosis than those with short or thick CCs.

Outcomes and prognostic factors of infantile acquired hydrocephalus: a single-center experience.

AIM: To assess the etiologies and adverse outcomes of infantile acquired hydrocephalus and predict prognosis. METHODS: A total of 129 infants diagnosed with acquired hydrocephalus were recruited from 2008 to 2021. Adverse outcomes included death and significant neurodevelopmental impairment which was defined as Bayley Scales of Infant and Toddler Development III score < 70, cerebral palsy, visual or hearing impairment, and epilepsy. Chi-squared was used to evaluate the prognostic factors of adverse outcomes. A receiver operating characteristic curve was calculated to determine the cutoff value. RESULTS: Of 113 patients with outcome data, 55 patients (48.7%) had adverse outcomes. Late surgical intervention time (13 days) and severe ventricular dilation were associated with adverse outcomes. The combination of surgical intervention time and cranial ultrasonography (cUS) indices was a better predictive marker compared with any of them (surgical intervention time, P = 0.05; cUS indices, P = 0.002). Post-hemorrhage (54/113, 48%), post-meningitis (28/113, 25%), and hydrocephalus arising from both hemorrhage and meningitis (17/113, 15%) accounted for a large proportion of the etiologies in our study. Hydrocephalus occurs secondary to post-hemorrhage and had a favorable outcome compared with other etiologies in both preterm and term groups. A significant difference in adverse outcomes between the inherited error of metabolism as a cause and other etiologies (P = 0.02). CONCLUSION: Late surgical treatment times and severe ventricular dilation can predict adverse outcomes in infants with acquired hydrocephalus. It is crucial to identify the causes of acquired hydrocephalus to predict the adverse outcomes. Research into measures of improving adverse outcomes following infantile acquired hydrocephalus is urgently necessary.

Acceleration effect of galacturonic acid on acrylamide generation: evidence in model reaction systems.

BACKGROUND: Acrylamide (AA) is a potential carcinogen formed in food rich in carbohydrate during heating. Recently, AA has been found in several fruit products, such as prune juice, sugarcane molasses and canned black olives. This study focused on the role of galacturonic acid (GalA), the main acid hydrolysis product of fruit pectin, in AA formation in three model systems - asparagine (Asn)/glucose (Glc), Asn/GalA, and Asn/Glc/GalA - during heating under different pH values (pH 3.8-7.8), Glc concentration (0-0.1 mol L-1 ), molar ratio of substrates (Asn/Glc = 1:1, 0.025-0.5 mol L-1 ) and temperature (120-180 °C) for 30 min, respectively. RESULTS: The results suggested that the addition of 0.1 mol L-1 GalA strongly accelerated AA formation in a manner dependent on pH value and temperature (P < 0.05). AA concentration under different Glc concentration and molar ratio of substrates suggested that GalA was more reactive than Glc when reacted with Asn. Furthermore, the Amadori rearrangement product/Schiff base/oxazolidine-5-one were identified as the intermediates formed in the Asn/GalA model system using ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry. CONCLUSION: The results suggested that Maillard reaction between Asn and GalA might contribute to AA formation. This study is significant in elucidating the contribution of interaction between components for AA formation in fruit products. © 2022 Society of Chemical Industry.

Mitigation effects of high methoxyl pectin on acrylamide formation in the Maillard model system.

Acrylamide (AA) is a potential carcinogen formed during the process of food heating. Pectin is natural food additive widely presented in fruits and vegetables. This study aimed at investigating the influence of the addition of high methoxyl apple pectin (esterification degree: 82.6%) on AA inhibition in the asparagine (Asn)/glucose (Glc) model system. Results showed that temperature (120-180 °C), pH value (6.0-7.2), pectin addition (0.2-1.0%, w/v), substrate concentration (0.01-0.5 M) and molar ratio of Asn/Glc (5:1-1:10) had significant influence on inhibition of pectin on AA formation. With adding 1.0% (w/v) pectin, the pH value, Glc consumption and Schiff base abundance declined in Asn/Glc model system. Moreover, heating treatment decreased the pH value, molecular weight, esterification degree and galacturonic acid content of pectin. Finally, the pectin degradation product was identified, which might compete with Glc for Asn in Maillard reaction, led to AA reduction. This study provided distinct evidence for controlling AA formation.

Inhibition of acrylamide by glutathione in asparagine/glucose model systems and cookies.

The inhibition effects of glutathione (GSH) on acrylamide (AA) in the asparagine/glucose model systems and cookies were investigated. The formation of AA was significantly inhibited by GSH addition in the model systems. The decreasing levels of AA were in the range of 38-86%, 57-82%, and 3-41% at 120, 140, and 160 °C, respectively. In addition, the presence of GSH in cookies also inhibited the AA formation, but with no corresponding relationship between the GSH level and the inhibition ratio. The addition of 0.05 g/kg GSH in cookie dough resulted in the decreasing of AA by 48%, some improvement in cookie lightness, but no influence on cookie texture. Kinetic analysis showed that the application of GSH not only inhibited the formation of AA but also improved the elimination of AA. In the summary, GSH could be a potential inhibitor to reduce the AA formation in food during the heating process.

Molecular selectivity design of mitogen-inducible gene-derived phosphopeptides between oncogenic HER kinases.

Mitogen-inducible gene (MIG) is a natural negative regulator of the oncogenic HER kinase signaling by binding at the activation interface of kinase domain to disrupt the kinase dimerization. In this study, we systematically examine the binding structures, dynamics and energetics of MIG region 2 to four HER kinases based on their crystal or modeled complex structures, and identify an 8-mer phosphopeptide segment pYpY from the core strand sequence of MIG region 2 as the binding hotspot of MIG protein to HER kinases. We demonstrate that the small pYpY phosphopeptide can partially restore the binding affinity of full-length MIG protein, but exhibit a moderate selectivity over different HER kinases (S = 2.3-fold). In addition, the two phosphotyrosine residues pTyr394 and pTyr395 play an essential role in MIG-HER binding; dephosphorylation of them would fully eliminate the binding capability. A machine evolution algorithm is used to optimize the wild-type pYpY phosphopeptide, aiming to simultaneously improve affinity for these kinases and to maximize the affinity gap between different kinases. Consequently, a population is computationally evolved as selective phosphopeptide candidates; the dissociation constants of four representatives with HER kinases are systematically determined using binding affinity analysis, from which their selectivity is derived. The designed pYpYp3 phosphopeptide possesses a high selectivity over different HER kinases (S = 4.8-fold) and satisfactory affinity profile to these kinase (KD = 140-1000 µM). Structural analysis observes that the global binding modes of pYpYp3 to different kinases are roughly consistent, but its local conformation may vary considerably, thus conferring specificity to the phosphopeptide.

Role of glutathione on acrylamide inhibition: Transformation products and mechanism.

Glutathione (GSH) is a potential inhibitor for acrylamide (AA) in heated food. In the present study, the inhibition pathways of GSH on AA were investigated in the asparagine(Asn)/glucose(Glc)/GSH model system. In comparison to the Asn/Glc model system, three unique molecular ions (m/z 470, 379, and 193) were identified in the Asn/Glc/GSH model system. Those molecular ions were confirmed as the Amadori rearrangement products which formed in the reaction between Glc and GSH, as well as the addition reaction products between AA and the sulfhydryl group (-SH) of GSH and cysteine (Cys). The competition between Asn and GSH for Glc in the competitive reactions was assumed to be the major pathway. Additionally, the elimination reaction between AA and GSH or between AA and Cys also played a minor role in the inhibition of AA. The variances of precursors, intermediates, and final products provided quantitative evidence for the above pathways.

Epigallocatechin Gallate (EGCG) Decorating Soybean Seed Ferritin as a Rutin Nanocarrier with Prolonged Release Property in the Gastrointestinal Tract.

The instability and low bioavailability of polyphenols limit their applications in food industries. In this study, epigallocatechin gallate (EGCG) and soybean seed ferritin deprived of iron (apoSSF) were fabricated as a combined double shell material to encapsulate rutin flavonoid molecules. Firstly, due to the reversible assembly characteristics of phytoferritin, rutin was successfully encapsulated within apoSSF to form a ferritin-rutin complex (FR) with an average molar ratio of 28.2: 1 (rutin/ferritin). The encapsulation efficiency and loading capacity of rutin were 18.80 and 2.98 %, respectively. EGCG was then bound to FR to form FR-EGCG composites (FRE), and the binding number of EGCG was 27.30 ± 0.68 with a binding constant K of (2.65 ± 0.11) × 10(4) M(-1). Furthermore, FRE exhibited improved rutin stability, and displayed prolonged release of rutin in simulated gastrointestinal tract fluid, which may be attributed to the external attachment of EGCG to the ferritin cage potentially reducing enzymolysis in GI fluid. In summary, this work demonstrates a novel nanocarrier for stabilization and sustained release of bioactive polyphenols.