Formation and non-covalent interactions of binary and ternary complexes based on ß-casein, Lentinus edodes mycelia polysaccharide, and taxifolin.

Polyphenols, polysaccharides, and proteins are essential nutrients and functional substances present in food, and when present together these components often interact with each other to influence their structure and function. Proteins and polysaccharides are also excellent carrier materials for polyphenols. In this context, this study investigated the non-covalent interactions between taxifolin (TAX), Lentinus edodes mycelia polysaccharide (LMP), and ß-casein (ß-CN). ß-CN and LMP spontaneously formed nanocomplexes by hydrogen bonds and van der Waals forces. The quenching constant and binding constant were (1.94 ± 0.02) × 1013 L mol-1 s-1 and (3.22 ± 0.17) × 105 L mol-1 at 298 K, respectively. The altered conformation of ß-CN, resulting from the binding to LMP, affected the interaction with TAX. LMP significantly enhanced the binding affinity of TAX and ß-CN, but did not change the static quenching binding mode. The binding constant for ß-CN-TAX was (3.96 ± 0.09) × 1013 L mol-1, and that for the interaction between TAX and ß-CN-LMP was (32.06 ± 0.05) × 1013 L mol-1. In summary, ß-CN-LMP nanocomplexes have great potential as a nanocarrier for polyphenols, and this study provides a theoretical foundation for the rational design of non-covalent complexes involving LMP and ß-CN, both in binary and ternary configurations.

Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy.

Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making.

Effects of micro/nanoplastics on oxidative damage and serum biochemical parameters in rats and mice: a meta-analysis.

Micro/nanoplastics (MNPs) are emerging as environmental pollutants with potential threats to human health. The accumulation of MNPs in the body can cause oxidative stress and increase the risk of cardiovascular disease (CVD). With the aim to systematically evaluate the extent of MNPs-induced oxidative damage and serum biochemical parameters in rats and mice, a total of 36 eligible articles were included in this meta-analysis study. The results reported that MNPs can significantly increase the levels of oxidants such as reactive oxygen species (ROS) and malondialdehyde (MDA) (P < 0.05), and resulted in notable increase in serum biochemical parameters including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < 0.05). Conversely, MNPs significantly reduced levels of antioxidants such as superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx) and catalase (CAT) (P < 0.05). Subgroup analysis revealed that smaller MNPs with oral administration and prolonged treatment, were associated with more pronounced oxidative stress and enhanced serum biochemical parameters alteration. In addition, after affected by MNPs, the levels of ALT and AST in liver group (SMD = 2.26, 95% CI = [1.59, 2.94] and SMD = 3.10, 95% CI = [1.25, 4.94]) were higher than those in other organs. These comprehensive results provide a scientific foundation for devising strategies to prevent MNPs-induced damage, contributing to solution of this environmental and health challenge.

Leveraging Janus Substrates as a Confined "Interfacial Reactor" to Synthesize Ultrapermeable Polyamide Nanofilms.

Porous substrates act as open "interfacial reactors" during the synthesis of polyamide composite membranes via interfacial polymerization. However, achieving a thin and dense polyamide nanofilm with high permeance and selectivity is challenging when using a conventional substrate with uniform wettability. To overcome this limitation, we propose the use of Janus porous substrates as confined interfacial reactors to decouple the local monomer concentration from the total monomer amount during interfacial polymerization. By manipulating the location of the hydrophilic/hydrophobic interface in a Janus porous substrate, we can precisely control the monomer solution confined within the hydrophilic layer without compromising its concentration. The hydrophilic surface ensures the uniform distribution of monomers, preventing the formation of defects. By employing Janus substrates fabricated through single-sided deposition of polydopamine/polyethyleneimine, we significantly reduce the thickness of the polyamide nanofilms from 88.4 to 3.8 nm by decreasing the thickness of the hydrophilic layer. This reduction leads to a remarkable enhancement in water permeance from 7.2 to 52.0 l/m2·h·bar while still maintaining ~96% Na2SO4 rejection. The overall performance of this membrane surpasses that of most reported membranes, including state-of-the-art commercial products. The presented strategy is both simple and effective, bringing ultrapermeable polyamide nanofilms one step closer to practical separation applications.

CD3ε of a pan T cell marker involved in mouse Aspergillus fumigatus keratitis.

AIM: To explore whether CD3ε is involved in the adaptive immunity of Aspergillus fumigatus (A. fumigatus) keratitis in mice and the role of innate and adaptive immunity in it. METHODS: Mice models of A. fumigatus keratitis were established by intra-stromal injection and corneal epithelial scratching. Subconjunctival injections of natamycin, wedelolactone, LOX-1 inhibitor (poly I) or Dectin-1 inhibitor (laminarin) were used to treat mice with A. fumigatus keratitis. Mice were pretreated by intraperitoneal injection of anti-mouse CD3ε. We observed the corneal infection of mice under the slit lamp microscope and made a clinical score. The protein expression of CD3ε and interleukin-10 (IL-10) was determined by Western blotting. RESULTS: With the disease progresses, the degree of corneal opacity and edema augmented. In the intra-stromal injection models, CD3ε protein expression began to increase significantly on the 2nd day. However, in the scraping epithelial method models, CD3ε only began to increase on the 3rd day. After natamycin treatment, the degree of corneal inflammation in mice was significantly attenuated on the 3rd day. After wedelolactone treatment, the severity of keratitis worsened. And the amount of CD3ε protein was also reduced, compared with the control group. By inhibiting LOX-1 and Dectin-1, there was no significant difference in CD3ε production compared with the control group. After inhibiting CD3ε, corneal ulcer area and clinical score increased, and IL-10 expression was downregulated. CONCLUSION: As a pan T cell marker, CD3ε participate in the adaptive immunity of A. fumigatus keratitis in mice. In our mice models, the corneas will enter the adaptive immune stage faster. By regulating IL-10, CD3ε exerts anti-inflammatory and repairs effects in the adaptive immune stage.

New insights of acylation stimulating protein in modulating the pathological progression of metabolic syndromes.

Obesity is associated with insulin resistance, hypertension, and coronary artery diseases which are grouped as metabolic syndrome. Rather than being a storage for energy, the adipocytes could synthesis and secret diverse hormones and molecules, named as adipokines. Under obese status, the adipocytes are dysfunctional with excessively producing the inflammatory related cytokines, such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor α (TNF-α). Concerning on the vital role of adipokines, it is proposed that one of the critical pathological factors of obesity is the dysfunctional adipocytic pathways. Among these adipokines, acylation stimulating protein, as an adipokine synthesized by adipocytes during the process of cell differentiation, is shown to activate the metabolism of triglyceride (TG) by regulating the catabolism of glucose and free fatty acid (FFA). Recent attention has paid to explore the underlying mechanism whereby acylation stimulating protein influences the biological function of adipocyte and the pathological development of obesity. In the present review, we summarized the progression of acylation stimulating protein in modulating the physiological and hormonal catabolism which affects fat distribution. Furthermore, the potential mechanisms which acylation stimulating protein regulates the metabolism of adipose tissue and the process of metabolic syndrome were also summarized.

Double charge flips of polyamide membrane by ionic liquid-decoupled bulk and interfacial diffusion for on-demand nanofiltration.

Fine design of surface charge properties of polyamide membranes is crucial for selective ionic and molecular sieving. Traditional membranes face limitations due to their inherent negative charge and limited charge modification range. Herein, we report a facile ionic liquid-decoupled bulk/interfacial diffusion strategy to elaborate the double charge flips of polyamide membranes, enabling on-demand transformation from inherently negative to highly positive and near-neutral charges. The key to these flips lies in the meticulous utilization of ionic liquid that decouples intertwined bulk/interfacial diffusion, enhancing interfacial while inhibiting bulk diffusion. These charge-tunable polyamide membranes can be customized for impressive separation performance, for example, profound Cl-/SO42- selectivity above 470 in sulfate recovery, ultrahigh Li+/Mg2+ selectivity up to 68 in lithium extraction, and effective divalent ion removal in pharmaceutical purification, surpassing many reported polyamide nanofiltration membranes. This advancement adds a new dimension to in the design of advanced polymer membranes via interfacial polymerization.

The novel HLA-C*08:273 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*08:273 differs from HLA-C*08:01:01:01 by one nucleotide in exon 2.

Bibliometric and visualized analysis of hydrogels in organoids research.

Over the past decades, there has been ongoing effort to develop complex biomimetic tissue engineering strategies for in vitro cultivation and maintenance of organoids. The defined hydrogels can create organoid models for various organs by changing their properties and various active molecules. An increasing number of researches has been done on the application of hydrogels in organoids, and a large number of articles have been published on the topic. Although there have been existing reviews describing the application of hydrogels in the field of organoids, there is still a lack of comprehensive studies summarizing and analyzing the overall research trends in this field. The citation can be used as an indicator of the scientific influence of an article in its field. This study aims to evaluate the application of hydrogels in organoids through bibliometric analysis, and to predict the hotspots and developing trends in this field.

Promoting the disassemble and enzymatic saccharification of bamboo shoot shells via efficient hydrated alkaline deep eutectic solvent pretreatment.

Pretreatment is a key process restricting the development of biorefinery. This work developed a pretreatment process based on an ethanolamine/acetamide alkaline deep eutectic solvent (ADES). Under microwave assistance, pure ADES pretreatment at 100 °C for 10 min achieved 95.9 % delignification and 95.2 % hemicellulose removal of bamboo shoot shells (BSS). Further, when 75 % water was added to pure DES to prepare hydrated DES (75 %-HADES), impressive delignification (93.2 %), hemicellulose removal (92.2 %) and cellulose recovery (94.8 %) were still achieved. The cellulose digestibility of the 75 %-HADES pretreated solid residue was significantly increased from 12.2 % (the control) to 91.2 %. Meanwhile, the structural features of hemicellulose and lignin macromolecules fractionated by 75 %-HADES pretreatment were well preserved, offering opportunities for downstream utilization. Overall, this work proposes an effective pretreatment strategy with the potential to enable the utilization of all major components of bamboo shoot shells.

Ultrasensitive detection of tyrosinase with click reaction-combined dark-field imaging platform.

Tyrosinase (TYR) is an essential oxidase that is responsible for the regulation of multiple physiological processes and diseases. Achieving the trace and reliable detection of TYR in complex biological samples is of great significance for the diagnosis of TYR-related diseases, but which faces a great challenge. In this study, we developed an ingenious and powerful method for the ultrasensitive detection of TYR by click reaction-combined dark-field microscopy. This method begins with the formation of cuprous ions (Cu+) based on the reduction of copper ions (Cu2+) by ascorbic acid (AA). Subsequently, the formed Cu+ can catalyze the crosslinking between azide- and alkyne-functionalized gold nanoparticles, causing a significant red-shift in the scattering spectrum. However, AA can chelate with TYR, which inhibits the generation of Cu+ and subsequent click reaction, thus achieving TYR-controlled scattering spectral shift. The proposed sensing platform shows a good linear detection range of 0.01-0.8 U/L with a low detection limit of 0.003 U/L, which is three orders of magnitude lower than the best performance of TYR sensing probes reported to date. Most importantly, the strategy has the ability to reliably and accurately detect TYR in serum sample, suggesting its potential clinical application in diagnosing TYR-related diseases. This visual sensing platform offers promising prospects for future research in enzymatic analysis and biomedical diagnostics.

Harmonic amide bond density as a game-changer for deciphering the crosslinking puzzle of polyamide.

It is particularly essential to analyze the complex crosslinked networks within polyamide membranes and their correlation with separation efficiency for the insightful tailoring of desalination membranes. However, using the degree of network crosslinking as a descriptor yields abnormal analytical outcomes and limited correlation with desalination performance due to imperfections in segmentation and calculation methods. Herein, we introduce a more rational parameter, denoted as harmonic amide bond density (HABD), to unravel the relationship between the crosslinked networks of polyamide membranes and their desalination performance. HABD quantifies the number of distinct amide bonds per unit mass of polyamide, based on a comprehensive segmentation of polyamide structure and consistent computational protocols derived from X-ray photoelectron spectroscopy data. Compared to its counterpart, HABD overcomes the limitations and offers a more accurate depiction of the crosslinked networks. Empirical data validate that HABD exhibits the expected correlation with the salt rejection and water permeance of reverse osmosis and nanofiltration polyamide membranes. Notably, HABD is applicable for analyzing complex crosslinked polyamide networks formed by highly functional monomers. By offering a powerful toolbox for systematic analysis of crosslinked polyamide networks, HABD facilitates the development of permselective membranes with enhanced performance in desalination applications.

Comparative pharmacokinetic investigation on crocetin in hyperlipidemia and normal rats after oral administration.

Crocetin as one of the main components of saffron possesses a lot of pharmacological effects, especially the beneficial effects in the treatment of hyperlipidemia. However, the pharmacokinetics of crocetin in the pathological state of hyperlipidemia has not been reported. In present study, the pharmacokinetics of crocetin in hyperlipidemia rats after oral administration of crocetin was investigated and the possible mechanisms for the pharmacokinetics were explored. High-fat diet was used to induce hyperlipidemia in rats. The pharmacokinetics of crocetin was investigated in hyperlipidemia and normal rats after oral and intravenous administration of crocetin, and the possible mechanisms of the pharmacokinetic changes were investigated in terms of metabolism and absorption using in vitro incubation with liver microsomes and the everted gut sac method, respectively. Results indicated that the AUCs of crocetin in hyperlipidemia rats after oral administration of crocetin were remarkably decreased when compared with those in normal rats. Moreover, crocetin was also metabolized more rapidly in the liver microsomes of hyperlipidemia rats and intestinal absorption of crocetin was significantly reduced in hyperlipidemia rats. It suggested that the remarkably decreased AUCs of crocetin in hyperlipidemia rats might partly result from the result of faster metabolic elimination and reduced absorption of crocetin in the hyperlipidemia pathological state. And the present investigations conducted on rats demonstrate that further investigations into the kinetics of crocetin in humans with hyperlipidemia are necessary in order to ensure an adequate dosage in this indication.

Hsa_circ_0014606 Derived from Exosomes Promotes Gastric Carcinoma Tumorigenesis and Proliferation by Sponging miR-514b-3p to Upregulate HNRNPC.

Gastric cancer is a common malignant tumor, and due to its insidious onset and limited screening methods, most patients are diagnosed with advanced disease and have a poor prognosis. The circRNA in exosomes has an essential role in cancer diagnosis and treatment. However, the part of hsa_circ_0014606 within exosomes in gastric cancer progression is unclear. Firstly, we extracted exosomes from the serum of gastric cancer patients and healthy individuals by ultracentrifugation and analyzed the expression of hsa_circ_0014606 in both exosomes; then knocked down hsa_circ_0014606 in vivo and in vitro, respectively, to observe its effect on the physiological function of gastric cancer cells; finally, we used bioinformatics to screen hsa_circ_0014606 targeting miRNAs and mRNAs, and experiments were performed to verify the interrelationship between the three. The results showed that the level of hsa_circ_0014606 in the serum exosomes of gastric cancer patients was significantly higher than that of the healthy population. The knockdown of hsa_circ_0014606 slowed the proliferation of gastric cancer cells, significantly reduced migration and invasion ability, accelerated apoptosis, and reduced tumor size in mice. In addition, the expression of hsa_circ_0014606 was negatively correlated with the expression of miR-514b-3p and positively correlated with the expression of heterogeneous nuclear ribonucleoprotein C (HNRNPC). In conclusion, hsa_circ_0014606 exerted a pro-cancer effect indirectly through miR-514b-3p targeting gene HNRNPC, and this study provides a new potential target for treating gastric cancer.

Genetic variants in the HLA region contribute to the risk of cerebral palsy.

Cerebral palsy (CP) is the most common physical disability in childhood, and genetic factors play an important role in its pathogenesis. However, the genetic contributions remain incompletely elucidated. Here, we conducted a two-stage association study between 1090 CP cases and 1100 healthy controls after whole exome sequencing. The human leukocyte antigen (HLA) allelic predispositions were further analyzed in overall CP and subgroups using multivariate logistic regression. We found a strong signal in the HLA region on chromosome 6, where rs3131787 harbored the most significant association with CP (P = 2.05 × 10-14, OR = 2.22). In comparison to controls, the carrier frequencies of HLA-B*13:02 were significantly higher in children with CP (9.82 % in control vs 19.27 % in CP, P = 1.03 × 10-4, OR = 2.17). Furthermore, the effect of HLA-B*13:02 on increasing the risk of CP mainly existed in cryptogenic CP without exposure to premature birth, low birth weight, birth asphyxia, or periventricular leukomalacia. This study indicated a strong association of HLA variants with CP, which implied that immune dysregulation resulting from immunogenetic variants might underlie the pathogenesis of CP. Our findings provide genetic evidence that an immunomodulator may serve as a promising therapeutic intervention for patients with CP by reinstating the neuroinflammation hemostasis.

Metabolomics and Biomarkers for Paroxysmal and Persistent Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common type of arrhythmia worldwide and is associated with serious complications. This study investigated the metabolic biomarkers associated with AF and the differences in metabolomics and associated metabolic biomarkers between paroxysmal AF (AFPA) and persistent AF. METHODS AND RESULTS: Plasma samples were prospectively collected from patients with AF and patients in sinus rhythm with negative coronary angiography. The patients were divided into 3 groups: AFPA, persistent AF, and sinus rhythm (N=54). Metabolomics (n=36) using ultra-high-performance liquid chromatography mass spectrometry was used to detect differential metabolites that were validated in a new cohort (n=18). The validated metabolites from the validation phase were further analyzed by receiver operating characteristic. Among the 36 differential metabolites detected by omics assay, 4 were successfully validated with area under the curve >0.8 (P<0.05). Bioinformatics analysis confirmed the enrichment pathways of unsaturated fatty acid biosynthesis, glyoxylate and dicarboxylate metabolism, and carbon metabolism. Arachidonic acid was a potential biomarker of AFPA, glycolic acid and L-serine were biomarkers of AFPA and persistent AF, and palmitelaidic acid was a biomarker of AFPA. CONCLUSIONS: In this metabolomics study, we detected 36 differential metabolites in AF, and 4 were validated with high sensitivity and specificity. These differential metabolites are potential biomarkers for diagnosis and monitoring of disease course. This study therefore provides new insights into the precision diagnosis and management of AF.

Fabrication of maleic anhydride-acrylamide copolymer based sodium alginate hydrogel for elimination of metals ions and dyes contaminants from polluted water.

The study explores the synergy of biobased polymers and hydrogels for water purification. Polymer nanomaterial's, synthesized by combining acrylamide copolymer with maleic anhydride, were integrated into sodium alginate biopolymer using an eco-friendly approach. Crosslinking agents, calcium chloride and glutaraladehyde, facilitated seamless integration, ensuring non-toxicity, high adsorption performance, and controlled capacity. This innovative combination presents a promising solution for clean and healthy water supplies, addressing the critical need for sustainable environmental practices in water purification. In addition, the polymer sodium alginate hydrogel (MAH@AA-P/SA/H) underwent characterization via the use of several analytical procedures, such as FTIR, XPS, SEM, EDX and XRD. Adsorption studies were conducted on metals and dyes in water, and pollutant removal methods were explored. We investigated several variables (such as pH, starting concentration, duration, and absorbent quantity) affect a material's capacity to be adsorbed. Moreover, the maximum adsorption towards Cu2+ is 754 mg/g while for Cr6+ metal ions are 738 mg/g, while the adsorption towards Congo Red and Methylene Blue dye are 685 mg/g and 653 mg/g correspondingly, within 240 min. Adsorption results were further analyzed using kinetic and isothermal models, which showed that MAH@AA-P/SA/H adsorption is governed by a chemisorption process. Hence, the polymer prepared from sodium alginate hydrogel (MAH@AA-P/SA/H) has remarkable properties as a versatile material for the significantly elimination of harmful contaminants from dirty water.

Clinical variables and genetic variants associated with perioperative anaphylaxis in Chinese Han population: A pilot study.

Background: Perioperative anaphylaxis (POA) can lead to severe consequences. Identifying clinical risk factors and genetic loci associated with POA through pre-prescription screening may help reduce its incidence. Methods: Using univariate regression and covariate-adjusted multivariate regression, we retrospectively analyzed the association between clinical characteristics and POA in 72 POA patients and 72 non-POA individuals. The discovery study of whole-exome association relied on whole-exome sequencing of 73 POA cases and 1339 healthy individuals. A replication study involving an independent set of 16 POA cases and 1339 healthy individuals confirmed this association. The accurate typing of human leucocyte antigen through exome sequencing (ATHLATES) algorithm and the whole-exome sequencing data were used for genotyping the human leucocyte antigen G (HLA-G) of 73 POA patients. The HLA-G of 16 POA cases and 122 non-POA patients were genotyped through Sanger sequencing. We used Fisher's exact probability method to compare the allele and carrier frequencies between POA patients and healthy individuals or non-POA patients. A Pc (P/Bonferroni correction coefficient) < 0.05 represents statistical significance. Results: Regression analysis identified female sex, an unconfirmed food allergy label, and a history of prior surgery as clinical variables associated with POA. The whole-exome association discovery study identified a strong signal in the major histocompatibility complex region on chromosome 6, with the rs1130356 being the most significant locus (P = 1.5E-10, OR = 3.4, 95% CI = 2.4-4.9). The replication study verified the association between the rs1130356-T allele and POA cases (P = 1.0E-6, OR = 6.3, 95% CI = 3.1-12.7). Compared with non-POA patients, HLA-G∗01:01 (Pc = 2.4E-4, OR = 2.4, 95% CI = 1.6-3.6) was significantly enriched, while HLA-G∗01:04 (Pc = 1.2E-6, OR = 0.3, 95% CI = 0.2-0.5) was lessened in POA patients. Conclusion: Our study suggested an association between POA and the risk factors of female sex, an unconfirmed food allergy label, and prior surgery. HLA-G, located in the human leucocyte antigen (HLA) region, may act as a surrogate genetic marker for POA. This suggests a causal relationship between this specific genomic region and POA. Our findings shed light on the contribution of human exome genetic variants to the susceptibility to POA.