A comparison of the physicochemical properties, digestibility, and expression patterns of starch-related genes of two supersweet corn hybrids (F1) and their parents.

The quality difference of corn largely depends on parental selection. Herein, the structure, digestive characteristics, and expression patterns of starch-related genes of two supersweet maize hybrids and their parents were studied. The structural analysis revealed that the starch of supersweet corn is round or oval, and the particles are smaller compared to those of normal corn. Hybridization changed the grain morphology, crystal, and helical structure of starch. Parents had a significantly different influence on supersweet corn. Notably, hybridization improved the setback value and digestibility of Shantian1500F1 and Shantian2000F1 compared to that of the parents. ZmBEI, ZmPHOH, and ZmAGPL2 genes had a consistent high expression throughout the whole grain formation phase. The results of this study expand our understanding of the breeding of supersweet corn hybrids and the effect of parents on the new strand. These results provide a useful reference for further breeding and studies of supersweet corn for starch production in corn.

Thermal stability and in vitro digestive behavior of Pickering emulsion stabilized by high-amylose starch nanocrystals.

In this study, high-amylose starch (HAS) was processed using sulfuric acid-ultrasonic cross-linking to produce high-amylose starch nanocrystals (HASNC). These nanocrystals were used to stabilize Pickering emulsions and assess their effectiveness in encapsulating ß-carotene. Normal starch nanocrystals (NSNC) were prepared similarly for comparison. The HASNC retained key HAS properties, such as heat and enzyme resistance, providing several advantages to HASNC-stabilized emulsions. First, after exposure to 100 °C heat and in vitro tests simulating the mouth and stomach, the HASNC-stabilized emulsions demonstrated significantly greater stability and higher ß-carotene retention compared to the NSNC-stabilized emulsions. This enhanced stability is attributed to the lower gelatinization degree and increased resistance to α-amylase hydrolysis of HASNC, which provides stronger steric stabilization of the oil droplets. Second, during in vitro small intestine tests, the greater enzyme resistance of HASNC allowed for the formation of a denser barrier around the oil droplets, effectively preventing lipase and bile salts from contacting the oil droplets. This led to a reduced rate and extent of lipid digestion and facilitated a sustained-release effect. Consequently, HASNC, as a starch-based emulsifier, show great potential as an effective delivery system for the sustained release of bioactive compounds.

The Systemic Genotype-Phenotype Characterization of PAX6-Related Eye Disease in 164 Chinese Families.

Purpose: This study aims to evaluate the genetic and phenotypic characteristics and elucidate the genotype-phenotype correlations of a large Chinese cohort with PAX6-related disorders. Methods: Variants detected with exome sequencing were filtered through multistep bioinformatic and co-segregation analyses, and validated by Sanger sequencing. The related clinical data were collected, and cluster analysis and statistical analysis of the PAX6-related phenotypes across different variant groups were carried out. Parental mosaicism was investigated using cloning analysis and Droplet digital PCR. Results: A total of 119 pathogenic or likely pathogenic PAX6 variants, including 74 truncation, 31 missense, and 14 others, were identified in 228 patients from 164 unrelated families. The most common phenotypes were foveal hypoplasia (97.8%), nystagmus (92.6%), aniridia (76.7%), cataract (36.8%), and iris hypoplasia (22.4%). Mosaicism ranging from 13.9% to 18.8% was identified in 3 unrelated patients' parents with relatively mild phenotypes. Missense variants in the linker region of the paired domain were associated with high myopia, whereas truncation variants in the homeodomain and proline-serine-threonine-rich domain were associated with hyperopia. Similarly, the degree of iris defects, visual acuity, and associated ocular comorbidity varied among the different types and locations of PAX6 variants. Conclusions: Our data indicate that foveal hypoplasia but not aniridia is the most common sign of PAX6-related disorders, contributing to subtle iris changes that might easily be overlooked in clinical practice. Recognition of mosaicism in atypical cases or parents with very mild phenotypes is important in genetic counseling as their offspring are at increased risk of typical aniridia. Recognition of the genotype-phenotype relationship emphasizes involvement of PAX6 regulation in shaping complex ocular phenotypes.

FBXW7-Mediated Downregulation of GPX4 Aggravates Acute Kidney Injury Following Ischemia‒Reperfusion.

Acute kidney injury (AKI) is a prevalent and potentially life-threatening complication characterized by a high incidence and mortality. A large number of studies have emphasized the role of ferroptosis in AKI. Moreover, FBXW7, a ubiquitin ligase, has been implicated in acute organ injury. Analysis of the GEO database (GSE98622) revealed increased FBXW7 mRNA levels in the kidney following ischemia‒reperfusion (IR). However, the role of FBXW7 in AKI has not been elucidated. Therefore, this study aimed to investigate the role of FBXW7 in IR-AKI and its underlying mechanisms. Here, we found that IR could induce AKI and increase FBXW7 expression, while the ferroptosis inhibitor Fer-1 alleviated AKI and decreased FBXW7 expression. Furthermore, we treated HK-2 cells with hypoxia for 12 h and reoxygenation for 4 h (H12R4) to simulate IR-AKI and investigated the impact of modulating FBXW7 expression on ferroptosis by employing ferroptosis-related agonists or inhibitors. Our findings revealed that H12R4 induced HK2 ferroptosis and increased the expression of FBXW7. FBXW7 overexpression in control cells exacerbated erastin-induced ferroptosis, and FBXW7 knockdown inhibited ferroptosis in H12R4-treated cells. Mechanistically, we confirmed that FBXW7 can bind to GPX4, a key molecule that inhibits ferroptosis. The half-life of the GPX4 protein decreased after FBXW7 overexpression, GPX4 ubiquitination increased after H12R4, and GPX4 degradation decreased after FBXW7 knockdown. In conclusion, our results indicated that FBXW7 plays an important role in the development of IR-AKI by promoting ferroptosis through the downregulation of GPX4 expression. This study provides new insight into FBXW7 as a potential target for treating AKI.

Sub-high amylose maize starch: an ideal substrate to generate starch with lower digestibility by fermentation of Qu.

BACKGROUND: The fermentation of Qu (FQ) is a novel method to modify the properties of starch to expand its application and especially to increase the resistant starch (RS) content. Using waxy maize starch (WMS) as a fermentation substrate can increase the RS content significantly but it may be time consuming and not cost effective due to the almost negligible RS content of WMS. To solve this problem, we hypothesized that sub-high amylose starch (s-HAMS), with an amylose content close to 50% could be an ideal substrate for FQ. RESULTS: The results showed that FQ did not change the shape and the particle size of starch granules, the gelatinization peak (Tp), or the conclusion temperature (Tc), but the slowly digested starch content declined. Rapidly digested starch content fluctuated during FQ and the amylose content decreased within 36 h and then increased. Within 24h, FQ significanlty increased these values: the RS content, relative crystallinity (RC), the ratio of FTIR absorbances at 1047/1022cm-1, the diffraction peak at 19.8° in X-ray diffraction (XRD), and the gelatinization onset temperature (To) increased significantly, within 24 h of FQ. However, after 24 h of fermentation, the RS content, RC, the ratio of FTIR absorbances at 1047/1022 cm-1, and gelatinization enthalpy (ΔH) decreased significantly. CONCLUSION: Sub-high amylose starch is more suitable for FQ to produce low digestibility starch, and the increase in RS may be due to the formation of 'amylose-lipid' complexes (RS5). © 2024 Society of Chemical Industry.

Overexpression of the potato VQ31 enhances salt tolerance in Arabidopsis.

Plant-specific VQ proteins have crucial functions in the regulation of plant growth and development, as well as in plant abiotic stress responses. Their roles have been well established in the model plant Arabidopsis thaliana; however, the functions of the potato VQ proteins have not been adequately investigated. The VQ protein core region contains a short FxxhVQxhTG amino acid motif sequence. In this study, the VQ31 protein from potato was cloned and functionally characterized. The complete open reading frame (ORF) size of StVQ31 is 672 bp, encoding 223 amino acids. Subcellular localization analysis revealed that StVQ31 is located in the nucleus. Transgenic Arabidopsis plants overexpressing StVQ31 exhibited enhanced salt tolerance compared to wild-type (WT) plants, as evidenced by increased root length, germination rate, and chlorophyll content under salinity stress. The increased tolerance of transgenic plants was associated with increased osmotic potential (proline and soluble sugars), decreased MDA accumulation, decreased total protein content, and improved membrane integrity. These results implied that StVQ31 overexpression enhanced the osmotic potential of the plants to maintain normal cell growth. Compared to the WT, the transgenic plants exhibited a notable increase in antioxidant enzyme activities, reducing cell membrane damage. Furthermore, the real-time fluorescence quantitative PCR analysis demonstrated that StVQ31 regulated the expression of genes associated with the response to salt stress, including ERD, LEA4-5, At2g38905, and AtNCED3. These findings suggest that StVQ31 significantly impacts osmotic and antioxidant cellular homeostasis, thereby enhancing salt tolerance.

Predicting Marfan Syndrome in Children With Congenital Ectopia Lentis: Development and Validation of a Nomogram.

Purpose: To derive an effective nomogram for predicting Marfan syndrome (MFS) in children with congenital ectopia lentis (CEL) using regularly collected data. Methods: Diagnostic standards (Ghent nosology) and genetic test were applied in all patients with CEL to determine the presence or absence of MFS. Three potential MFS predictors were tested and chosen to build a prediction model using logistic regression. The predictive performance of the nomogram was validated internally through time-dependent receiver operating characteristic curves, calibration curves, and decision curve analysis. Results: Eyes from 103 patients under 20 years old and with CEL were enrolled in this study. Z score of body mass index (odds ratio [OR] = 0.659; 95% confidence interval [CI], 0.453-0.958), corneal curvature radius (OR = 3.397; 95% CI, 1.829-6.307), and aortic root diameter (OR = 2.342; 95% CI, 1.403-3.911) were identified as predictors of MFS. The combination of the above predictors shows good predictive ability, as indicated by area under the curve of 0.889 (95% CI, 0.826-0.953). The calibration curves showed good agreement between the prediction of the nomogram and the actual observations. In addition, decision curve analysis showed that the nomogram was clinically useful and had better discriminatory power in identifying patients with MFS. For better individual prediction, an online MFS calculator was created. Conclusions: The nomogram provides accurate and individualized prediction of MFS in children with CEL who cannot be identified with the Ghent criteria, enabling clinicians to personalize treatment plans and improve MFS outcomes. Translational Relevance: The prediction model may help clinicians identify MFS in its early stages, which could reduce the likelihood of developing severe symptoms and improve MFS outcomes.

ZmSMR10 Increases the Level of Endoreplication of Plants through Its Interactions with ZmPCNA2 and ZmCSN5B.

As a plant-specific endoreplication regulator, the SIAMESE-RELATED (SMR) family (a cyclin-dependent kinase inhibitor) plays an important role in plant growth and development and resistance to stress. Although the genes of the maize (Zea mays) SMR family have been studied extensively, the ZmSMR10 (Zm00001eb231280) gene has not been reported. In this study, the function of this gene was characterized by overexpression and silencing. Compared with the control, the transgenic plants exhibited the phenotypes of early maturation, dwarfing, and drought resistance. Expression of the protein in prokaryotes demonstrates that ZmSMR10 is a small protein, and the results of subcellular localization suggest that it travels functionally in the nucleus. Unlike ZmSMR4, yeast two-hybrid experiments demonstrated that ZmSMR10 does not interact strongly with with some cell cycle protein-dependent protein kinase (CDK) family members ZmCDKA;1/ZmCDKA;3/ZmCDKB1;1. Instead, it interacts strongly with ZmPCNA2 and ZmCSN5B. Based on these results, we concluded that ZmSMR10 is involved in the regulation of endoreplication through the interaction of ZmPCNA2 and ZmCSN5B. These findings provide a theoretical basis to understand the mechanism of the regulation of endoreplication and improve the yield of maize through the use of molecular techniques.

Saikosaponin F ameliorates depression-associated dry eye disease by inhibiting TRIM8-induced TAK1 ubiquitination.

AIMS: Saikosaponin F (SsF) is one of the major active ingredients of Radix Bupleuri, an herb widely used in the treatment of depression. Studies have shown that dry eye disease often occurs together with depression. The aim of this study is to investigate whether SsF can improve depression-associated dry eye disease and explore the underlying mechanism. METHODS: Behavioral test was used to verify the effect of SsF on CUMS-induced depression-like behaviors in mice. Corneal fluorescein staining, phenol red cotton thread test and periodic acid-Schiff (PAS) staining were used to observe the effect of SsF on depression-associated dry eye disease. Western blot (WB) was performed to observe the expression of TAK1 protein and key proteins of NF-κB and MAPK (P38) inflammatory pathways in the hippocampus and cornea. Immunohistochemical staining was used to observe the expression of microglia, and immunoprecipitation was used to observe K63-linked TAK1 ubiquitination. Subsequently, we constructed a viral vector sh-TAK1 to silence TAK1 protein to verify whether SsF exerted its therapeutic effect based on TAK1. The expression of inflammatory factors such as IL-1ß, TNF-α and IL-18 in hippocampus and cornea were detected by ELISA. Overexpression of TRIM8 (OE-TRIM8) by viral vector was used to verify whether SsF improved depression-associated dry eye disease based on TRIM8. RESULTS: SsF treatment significantly improved the depression-like behavior, increased tear production and restored corneal injury in depression-related dry eye model mice. SsF treatment downregulated TAK1 expression and TRIM8-induced K63-linked TAK1 polyubiquitination, while inhibiting the activation of NF-κB and MAPK (P38) inflammatory pathways and microglial expression. In addition, selective inhibition of TAK1 expression ameliorated depression-associated dry eye disease, while overexpression of TRIM8 attenuated the therapeutic effect of SsF on depression-associated dry eye disease. CONCLUSION: SsF inhibited the polyubiquitination of TAK1 by acting on TRIM8, resulting in the downregulation of TAK1 expression, inhibition of inflammatory response, and improvement of CUMS-induced depression-associated dry eye disease.

A modified laser ablation-isotope ratio mass spectrometry method for in situ analysis of sulfur isotope composition of sulfides.

RATIONALE: A novel laser ablation-isotope ratio mass spectrometry (LA-IRMS) method for in situ analysis of sulfur isotopes in sulfides has been developed. Instead of the in situ reaction applied by the traditional laser microprobe, the analyte gas preparation in this method is separated temporally and spatially from the LA, resulting in improved precision and accuracy. METHODS: Our LA-IRMS system combines an ultraviolet LA system, an elemental analyzer (EA), a custom-built cryogenic concentration system, a continuous-flow interface, and an IRMS. The sulfide aerosol particles generated from LA were transferred by a helium carrier gas from the ablation cell into the reaction tube and were then converted into SO2 . Subsequently, SO2 was enriched in two cold traps and was finally introduced into the ion source of the IRMS through the continuous-flow interface. RESULTS: We measured three synthetic and four natural sulfide reference materials to test the performance of this method. Precisions of ±0.25‰-±0.48‰ and ±0.32‰-±0.64‰ (1SD, n = 5) for δ34 S values of synthetic and natural sulfide standards can be obtained for spot sizes ranging from 64 to 80 µm. Measured values and their recommended values showed a good linear relationship (R2 within 0.998 and 0.9995) with the slope of approaching unity (within 1.0509 and 1.1313). CONCLUSIONS: Data from the measurement of reference materials showed that the precision and accuracy of our method were satisfactory. This method is a powerful tool for in situ sulfur isotope measurement of sulfides and can be further applied to in situ carbon and oxygen isotope analyses.

Clinical and Genetic Landscape of Ectopia Lentis Based on a Cohort of Patients From 156 Families.

Purpose: To extend the mutation spectrum and explore the characteristics of genotypes and ocular phenotypes in ectopia lentis (EL). Methods: Variants in all 14 reported EL-associated genes were selected from in-house data sets as well as literature review, and available clinical data were analyzed. Results: Likely pathogenic variants in three genes were identified in 156 unrelated families with EL from the in-house cohort, of which 97.4% resulted from variants in FBN1, whereas the remaining were caused by variants in ADAMTSL4 (1.3%) and LTBP2 (1.3%). A comparative analysis of the in-house data and literature review suggested several characteristics: (1) a higher proportion of cysteine involvement variants in FBN1, either variants introducing or eliminating cysteine, and an earlier diagnosis age were presented in our cohort than in published literature; (2) the axial length (AL) and refractive error increased more rapidly with age in preschool EL children than normal children, and the increased rate of AL was slower in patients with surgery than those without surgery; (3) aberrant astigmatism was common in EL; and (4) worse vision and earlier onset age were observed in patients with non-FBN1 variants (all P < 0.05). Conclusions: Variants in FBN1 are the predominant cause of EL, with the most common cysteine involvement variants. Early-stage EL manifests refractive error but gradually converts to axial myopia through defocus introduced by lens dislocation. Aberrant astigmatism is a suggestive sign of EL. Non-FBN1 variants cause early-onset and severe phenotypes. These results provide evidence for early diagnosis as well as timely treatment for EL.

Intercellular Interactions Mediated by HGF And TGF-Β Promote the 3D Spherical and Xenograft Growth of Liver Cancer Cells.

BACKGROUND: Recently, the importance of the interactions between liver cancer cells and fibroblasts has been increasingly recognized; however, many details remain to be explored. METHODS: In this work, we first studied their intercellular interactions using conditioned medium from mouse embryonic fibroblasts (MEFs), then through a previously established coculture model. RESULTS: Culturing in a conditioned medium from MEFs could significantly increase the growth, migration, and invasion of liver cancer cells. The coculture model further demonstrated that a positive feedback loop was formed between transforming growth factor-ß (TGF-ß) from HepG2 cells and mHGF (mouse hepatocyte growth factor) from MEFs during coculture. In this feedback loop, c-Met expression in HepG2 cells was significantly increased, and its downstream signaling pathways, such as Src/FAK, PI3K/AKT, and RAF/MEK/ERK, were activated. Moreover, the proportion of activated MEFs was also increased. More importantly, the growth-promoting effects caused by the interaction of these two cell types were validated in vitro by a 3D spheroid growth assay and in vivo by a xenograft mouse model. CONCLUSION: Collectively, these findings provide valuable insights into the interactions between fibroblasts and liver cancer cells, which may have therapeutic implications for the treatment of liver cancer.

Schisandrin B Alleviates Renal Tubular Cell Epithelial-Mesenchymal Transition and Mitochondrial Dysfunction by Kielin/Chordin-like Protein Upregulation via Akt Pathway Inactivation and Adenosine 5'-Monophosphate (AMP)-Activated Protein Kinase Pathway Activation in Diabetic Kidney Disease.

Diabetic kidney disease is a common complication of diabetes and remains the primary cause of end-stage kidney disease in the general population. Schisandrin B (Sch B) is an active ingredient in Schisandra chinensis. Our study illustrates that Sch B can mitigate renal tubular cell (RTC) epithelial-mesenchymal transition (EMT) and mitochondrial dysfunction in db/db mice, accompanied by the downregulation of TGF-ß1 and the upregulation of PGC-1α. Similarly, Sch B demonstrated a protective effect by reducing the expression of TGF-ß1, α-SMA, fibronectin, and Col I, meanwhile enhancing the expression of E-cadherin in human RTCs (HK2 cells) stimulated with high glucose. Moreover, under high glucose conditions, Sch B effectively increased mitochondrial membrane potential, lowered ROS production, and increased the ATP content in HK2 cells, accompanied by the upregulation of PGC-1α, TFAM, MFN1, and MFN2. Mechanistically, the RNA-seq results showed a significant increase in KCP mRNA levels in HK2 cells treated with Sch B in a high glucose culture. The influence of Sch B on KCP mRNA levels was confirmed by real-time PCR in high glucose-treated HK2 cells. Depletion of the KCP gene reversed the impact of Sch B on TGF-ß1 and PGC-1α in HK2 cells with high glucose level exposure, whereas overexpression of the KCP gene blocked EMT and mitochondrial dysfunction. Furthermore, the PI3K/Akt pathway was inhibited and the AMPK pathway was activated in HK2 cells exposed to a high concentration of glucose after the Sch B treatment. Treatment with the PI3K/Akt pathway agonist insulin and the AMPK pathway antagonist compound C attenuated the Sch B-induced KCP expression in HK2 cells exposed to a high level of glucose. Finally, molecular autodock experiments illustrated that Sch B could bind to Akt and AMPK. In summary, our findings suggested that Sch B could alleviate RTC EMT and mitochondrial dysfunction by upregulating KCP via inhibiting the Akt pathway and activating the AMPK pathway in DKD.

Ablated Sonic Hedgehog Signaling in the Dentate Gyrus of the Dorsal and Ventral Hippocampus Impairs Hippocampal-Dependent Memory Tasks and Emotion in a Rat Model of Depression.

Specific memory processes and emotional aberrations in depression can be attributed to the different dorsal-ventral regions of the hippocampus. However, the molecular mechanisms underlying the differential functions of the dorsal hippocampus (dHip) and ventral hippocampus (vHip) remain unclear. As Sonic Hedgehog (Shh) is involved in the dorsal-ventral patterning of the neural tube and its signaling is dysregulated by chronic unpredictable mild stress (CUMS), we investigated its role in influencing the differential functions of the dHip and vHip. Here, CUMS downregulated the expression of Shh signaling markers, including Shh and its downstream effectors GLI family zinc finger 12 (Gli1/2), Patched (Ptch), and smoothened (Smo), in both the dHip and vHip of rats, though more so in the vHip. Additionally, Shh knockdown in the dorsal or ventral dentate gyrus (DG) resulted in restrained neurogenic activity in newborn neurons, especially in immature neurons through decreased expression of Shh signaling markers. Furthermore, Shh knockdown in the DG of the dHip led to memory impairment by inhibiting experience-dependent activation of immature neurons, whereas its knockdown in the DG of the vHip led to an emotional handicap by delaying the maturation of immature neurons. Finally, Shh knockdown in either the dDG or vDG of hippocampus abolished the corresponding cognitive enhancement and emotional recovery of fluoxetine. In conclusion, Shh is essential to maintain the functional heterogeneity of dHip and vHip in depressed rat, which was mainly mediating by local changes of dependent activation and maturity of immature neurons, respectively.

Characterization of the Isocitrate Dehydrogenase Gene Family and Their Response to Drought Stress in Maize.

Isocitrate dehydrogenase (IDH) is a key rate-limiting enzyme in the tricarboxylic acid cycle and acts in glutamine synthesis. IDH also participates in plant growth and development and in response to abiotic stresses. We identified 11 maize IDH genes (ZmIDH) and classified these genes into ZmNAD-IDH and ZmNADP-IDH groups based on their different coenzymes (NAD+ or NADP+). The ZmNAD-IDH group was further divided into two subgroups according to their catalytic and non-catalytic subunits, as in Arabidopsis. The ZmIDHs significantly differed in physicochemical properties, gene structure, conserved motifs, and protein tertiary structure. Promoter prediction analysis revealed that the promoters of these ZmIDHs contain cis-acting elements associated with light response, abscisic acid, phytohormones, and abiotic stresses. ZmIDH is predicted to interact with proteins involved in development and stress resistance. Expression analysis of public data revealed that most ZmIDHs are specifically expressed in anthers. Different types of ZmIDHs responded to abiotic stresses with different expression patterns, but all exhibited responses to abiotic stresses to some extent. In addition, analysis of the public sequence from transcription data in an association panel suggested that natural variation in ZmIDH1.4 will be associated with drought tolerance in maize. These results suggested that ZmIDHs respond differently and/or redundantly to abiotic stresses during plant growth and development, and this analysis provides a foundation to understand how ZmIDHs respond to drought stress in maize.

Effectiveness and safety of Xingbei Zhike granules in patients with postinfectious cough: A multicenter, randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Postinfectious cough (PIC) is a common symptom following a respiratory tract infection. Xingbei Zhike (XBZK) granules, a Chinese patent medicine, has been widely used for PIC in clinics. However, there is a lack of evidence on the effectiveness. PURPOSE: To investigate whether treatment with XBZK granules is effective for PIC. STUDY DESIGN: A multicenter, randomized, double-blinded, placebo-controlled trial. METHODS: Eligible participants from fourteen hospitals were randomly assigned in 3:1 ratio to receive either XBZK granules or placebo for 14 days. The primary outcome was the area under the curve (AUC) of a visual analogue scale (VAS) for cough symptoms. Secondary outcomes included cough symptom score (CSS), time and probability of recovery from cough, traditional Chinese medicine (TCM) syndrome score, relief rates of individual symptoms, Leicester Cough Questionnaire (LCQ) score, and the use of reliever drug. RESULTS: A total of 235 patients (176 in XBZK and 59 in placebo groups) were included in the analysis. The AUC for cough VAS scores was lower in the XBZK than placebo group (-8.10, 95 % CI -14.12 to -2.07, p = 0.009), indicating superiority. XBZK decreased CSS (-0.68 points, 95 % CI -1.13 to -0.22, p = 0.01), shortened time to cough recovery (-2 days, hazard ratio [HR] 1.48, 95 % CI 1.03 to 2.13, p = 0.02), enhanced the probability of cough recovery (risk ratio [RR] 1.66, 95 % CI 1.07 to 2.58, p = 0.03), lowered TCM syndrome score (-0.99 points, 95 % CI -1.58 to -0.40, p = 0.004), increased the rate of daytime (RR 1.84, 95 % CI 1.07 to 3.15, p = 0.02) and nighttime (RR 2.07, 95 % CI 1.29 to 3.35, p = 0.004) cough recovery, and reduced the viscosity of sputum (RR 2.92, 95 % CI 1.66 to 5.13, p < 0.001) compared to placebo. There were no significant differences in LCQ scores and taking reliever drugs between groups. No severe adverse events were reported in either group. CONCLUSIONS: XBZK granules are a promising therapy against PIC, effective in lowering the overall severity of cough, shortening the time to cough recovery, and reducing the viscosity of sputum.

Integrating serum metabolomics and network analysis to explore the antidepressant activity of crocin in rats with chronic unexpected mild stress-induced depression.

CONTEXT: Crocin exhibits anti-depressant properties. However, its underlying mechanisms and its relationship with metabolomics remain unclear. OBJECTIVE: This study elucidates the mechanism of action and potential targets of crocin in treating chronic unexpected mild stress (CUMS)-induced depression in rats. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats underwent 4 weeks of CUMS to establish the depression model. The normal control (distilled water), crocin (25 mg/kg), and fluoxetine (5.4 mg/kg) groups were orally administered for 4-weeks. Behavioural tests evaluated the effects of crocin, while liquid chromatography-mass spectrometry metabolomics identified differential metabolites and their associated metabolic pathways. Subsequently, network pharmacology was utilized to predict the targets of crocin. RESULTS: Crocin significantly increased body weight (from 319.16 ± 4.84 g to 325.67 ± 2.84 g), sucrose preference (from 0.46 ± 0.09 to 0.70 ± 0.09), vertical activity (from 2.83 ± 1.94 to 8 ± 2.36), horizontal activity (from 1 ± 0.63 to 4.5 ± 3.08) and decreased immobilization time (from 13.16 ± 2.69 to 3.97 ± 3.00). Metabolomics analysis identified 7 metabolites and 5 associated metabolic pathways. From the combined analysis of network pharmacology and metabolomics, three targets (PRMT1, CYP3A4, and GLB1) are the overlapping targets and the two most important metabolic pathways are tryptophan metabolism and glycerolipid metabolism. DISCUSSION AND CONCLUSIONS: This study provides insights into the antidepressant therapeutic effect of crocin and its underlying mechanisms. The findings contribute to a better understanding of the metabolic mechanism involved in the anti-depressant effect of crocin, establishing a strong foundation for future research in this area.

Strategies for starch customization: Agricultural modification.

Raw starch is commonly modified to enhance its functionality for industrial applications. There is increasing demand for 'green' modified starches from both end-consumers and producers. It is well known that environmental conditions are key factors that determine plant growth and yield. An increasing number of studies suggest growth conditions can expand affect starch structure and functionality. In this review, we summarized how water, heat, high nitrogen, salinity, shading, CO2 stress affect starch biosynthesis and physicochemical properties. We define these treatments as a fifth type of starch modification method - agricultural modification - in addition to chemical, physical, enzymatic and genetic methods. In general, water stress decreases peak viscosity and gelatinization enthalpy of starch, and high temperature stress increases starch gelatinization enthalpy and temperature. High nitrogen increases total starch content and regulates starch viscosity. Salinity stress mainly regulates starch and amylose content, both of which are genotype-dependent. Shading stress and CO2 stress can both increase starch granule size, but these have different effects on amylose content and amylopectin structure. Compared with other modification methods, agricultural modification has the advantage of operating at a large scale and a low cost and can help meet the ever-rising market of clean-label foods and ingredients.

Characteristics and genotype-phenotype correlations in ADAMTS17 mutation-related Weill-Marchesani syndrome.

Weill-Marchesani syndrome (WMS) manifests as ectopia lentis (EL), microspherophakia and short stature, which is caused by ADAMTS10, LTBP2, or ADAMTS17 gene defects. This study aims to investigate the characteristics and genotype-phenotype correlations of WMS with ADAMTS17 mutations. WMS patients with ADAMTS17 variants were identified by whole-exome sequencing from 185 patients with EL. All the included patients underwent comprehensive ocular and systemic examinations. ADAMTS17 variants were reviewed from included patients, published literature, and public databases. Bioinformatics analysis, co-segregation analysis, species sequence analysis, and protein silico modeling were used to verify the pathogenic mutations. A total of six novel ADAMTS17 mutations (c.1297C > T, c.2948C > T, c.1322+2T > C, c.1716C > G, c.1630G > A, and c.1669C > T) were identified in four WMS probands in our EL cohort (4/185, 2.16%). All probands and their biological parents presented with apparent short stature compared with the standard value. In particular, one child was detected with valvular heart disease, which has not previously been reported in patients with ADAMTS17 mutations. Conserved residues were greatly affected by the substitution of amino acids caused by these six mutations. Short stature could be considered a clue for EL patients with ADAMTS17 mutations, and much more attention needs to be paid to heart disorders among these patients. This study not only reported the characteristics of ADAMTS17 mutation-related WMS but also helped to recognize the genotype-phenotype correlations in these patients.

Ocular, cardiovascular, and genetic characteristics and their associations in children with Marfan syndrome and related fibrillinopathies.

PURPOSE: Congenital ectopia lentis (CEL) and heart abnormalities are common clinical symptoms in patients with Marfan syndrome (MFS) and related fibrillinopathies, which is caused by mutations in fibrillin-1 (FBN1) gene. This study aims to explore the ocular and cardiovascular characteristics and their association with genotype in children with MFS and related fibrillinopathies. METHODS: Seventy-nine children diagnosed with CEL and with FBN1 mutations confirmed via whole-exome sequencing were included for genotypes and phenotypes analysis. The axial length (AL), corneal curvature, and refractive status were included for ocular phenotypes analysis. The cardiovascular examination was performed by echocardiography, and aortic root Z score was calculated to evaluate the severity of aortic dilatation. The heart disorders were classified as aortic root dilatation, valvular disorders, and others. Both the ocular and cardiac manifestations were collected for comprehensive analysis and compared among patients with different genotypes, including the mutation involving cysteine substitution or mutation in different regions. RESULTS: In CEL children with FBN1 mutations, 77.2% patients could be diagnosed as MFS. It was observed that children with mutations in exons 22-42 had significant higher aortic root Z score (P = 0.003) and higher incidence of cardiovascular disorders (P = 0.004). Additionally, children with cysteine substitution mutations had significant higher aortic root Z score (P = 0.011), and the aortic root Z score was positively associated with axial length (AL) in children under 6 years old (P = 0.035). Those with long AL (≥ 26 mm) had significant higher incidence of valve disorders (P = 0.023). In addition, nearly half the children with CEL (46.8%) were diagnosed with cardiovascular disease for the first time. CONCLUSIONS: CEL children with FBN1 mutations involving cysteine substitution or mutations in exons 22-42 or with long AL had higher risks of severe cardiovascular complications. Knowing the phenotype may help in anticipating severe cardiovascular disease in CEL patients.