Broadband nonlinear conversion and random quasi-phase-matching in transparent glass composite.

With the development of laser technology, nonlinear optics plays a crucial role in frequency conversion. However, the generation of second harmonics in nonlinear optical crystals is generally subject to rigorous phase-matching conditions that hinder the performance of broadband tunability. It is believed that introducing disorders in nonlinear optical materials is helpful to overcome this obstacle. In this work, we have prepared a nonlinear microcrystal-doped glass (NMG) composite material, allowing for tunable and polarization-independent nonlinear conversion from visible to near-infrared. The linear dependence of SHG intensity versus sample thickness indicated the facilitation of random quasi-phase matching by using the NMG. Our results provide a more stable and promising platform for disordered nonlinear photonic materials and suggest the possibility of more efficient nonlinear conversions using the NMG composite glass fibers in future.

Revealing the Hypoglycemic Effect of Red Yeast Rice: Perspectives from the Inhibition of α-Glucosidase and the Anti-Glycation Capability by Ankaflavin and Monascin.

Red yeast rice dietary supplements have been proven to ameliorate hyperglycemia, but the mechanism was unclear. In this work, ankaflavin (AK) and monascin (MS), as typical pigments derived from red yeast rice, were found to exert noteworthy inhibitory ability against α-glucosidase, with an IC50 of 126.5 ± 2.5 and 302.6 ± 2.5 µM, respectively, compared with acarbose (IC50 = 341.3 ± 13.6 µM). They also exhibited mixed-type inhibition of α-glucosidase in vitro and caused fluorescence quenching through the static-quenching process. Molecular-docking studies indicated that AK and MS bind to amino acid residues outside the catalytic center, which induces structural changes in the enzyme, thus influencing its catalytic activity. The anti-glycation ability of Monascus-fermented products was evaluated, and they exhibited a high inhibition rate of 87.1% in fluorescent advanced glycation end-product formation at a concentration of 0.2 mg mL-1, while aminoguanidine showed a rate of 75.7% at the same concentration. These results will be significant in broadening the application scope of Monascus pigments, especially AK and MS, in treating type 2 diabetes.

Transcriptomic profiling across human serotonin neuron differentiation via the FEV reporter system.

BACKGROUND: The detailed transcriptomic profiles during human serotonin neuron (SN) differentiation remain elusive. The establishment of a reporter system based on SN terminal selector holds promise to produce highly-purified cells with an early serotonergic fate and help elucidate the molecular events during human SN development process. METHODS: A fifth Ewing variant (FEV)-EGFP reporter system was established by CRISPR/Cas9 technology to indicate SN since postmitotic stage. FACS was performed to purify SN from the heterogeneous cell populations. RNA-sequencing analysis was performed for cells at four key stages of differentiation (pluripotent stem cells, serotonergic neural progenitors, purified postmitotic SN and purifed mature SN) to explore the transcriptomic dynamics during SN differentiation. RESULTS: We found that human serotonergic fate specification may commence as early as day 21 of differentiation from human pluripotent stem cells. Furthermore, the transcriptional factors ZIC1, HOXA2 and MSX2 were identified as the hub genes responsible for orchestrating serotonergic fate determination. CONCLUSIONS: For the first time, we exposed the developmental transcriptomic profiles of human SN via FEV reporter system, which will further our understanding for the development process of human SN.

Corticosterone Impairs Hippocampal Neurogenesis and Behaviors through p21-Mediated ROS Accumulation.

Stress is known to induce a reduction in adult hippocampal neurogenesis (AHN) and anxiety-like behaviors. Glucocorticoids (GCs) are secreted in response to stress, and the hippocampus possesses the greatest levels of GC receptors, highlighting the potential of GCs in mediating stress-induced hippocampal alterations and behavior deficits. Herein, RNA-sequencing (RNA-seq) analysis of the hippocampus following corticosterone (CORT) exposure revealed the central regulatory role of the p21 (Cdkna1a) gene, which exhibited interactions with oxidative stress-related differentially expressed genes (DEGs), suggesting a potential link between p21 and oxidative stress-related pathways. Remarkably, p21-overexpression in the hippocampal dentate gyrus partially recapitulated CORT-induced phenotypes, including reactive oxygen species (ROS) accumulation, diminished AHN, dendritic atrophy, and the onset of anxiety-like behaviors. Significantly, inhibiting ROS exhibited a partial rescue of anxiety-like behaviors and hippocampal alterations induced by p21-overexpression, as well as those induced by CORT, underscoring the therapeutic potential of targeting ROS or p21 in the hippocampus as a promising avenue for mitigating anxiety disorders provoked by chronic stress.

Impact of non-aged and UV-aged microplastics on the formation of halogenated disinfection byproducts during chlorination of drinking water and its mechanism.

Microplastics (MPs) are ubiquitously present in source water and undergo ultraviolet (UV) aging in aquatic environments before entering drinking water treatment plants. The presence of MPs in drinking water can impact the formation of halogenated disinfection byproducts (DBPs) during chlorine disinfection, yet the exact effect of MPs on DBP formation remain unclear. In this study, we conducted an investigation into the influence of non-aged and UV-aged MPs on halogenated DBP formation in drinking water and unveiled the underlying mechanisms. In comparison to source water samples devoid of MPs, the total organic halogen concentration was reduced by 19%-43% and 4%-13% in the drinking water samples containing non-aged and aged MPs, respectively. The differing effects on halogenated DBP formation can be attributed to the alternation in physical and chemical characteristics of MPs following UV aging. Aged MPs exhibited larger surface area with signs of wear and tear, heightened hydrophilicity, surface oxidation, increased oxygen-containing functional groups and dechlorination during the UV aging process. Both non-aged and aged MPs possess the capability to adsorb natural organic matter, leading to a reduction in the concentration of DBP precursors in the source water. However, the release of organic compounds from aged MPs outweighed the adsorption of organics. Furthermore, as a result of the surface activation of MPs through the UV aging process, the aged MPs themselves can also serve as DBP precursors. Consequently, the presence of halogenated DBP precursors in source water increased, contributing to a higher level of DBP formation compared to source water containing non-aged MPs. Overall, this study illuminates the intricate relationship among MPs, UV aging, and DBP formation in drinking water. It highlights the potential risks posed by aged MPs in influencing DBP formation and offers valuable insights for optimizing water treatment processes.

Affinity character analysis of magnolol and honokiol based on stepwise frontal analysis coupled with cell membrane chromatography.

Magnolol and honokiol have been reported to exhibit anti-cancer activity. However, few studies are in relation to the interaction of magnolol/honokiol with vascular endothelial growth factor 2 (VEGFR2). In this study, a membrane chromatography method based on VEGFR2 was established for the interaction characteristic analysis between drug and receptor. The selectivity, repeatability and stability of the chromatographic model were evaluated using drugs acting on different receptors. The affinity between VEGFR2 and magnolol/honokiol was verified by cell membrane chromatography. The binding sites of magnolol/honokiol and VEGFR2 were analyzed by zonal elution. Especially, the dissociation equilibrium constants (Kd) of magnolol/honokiol and VEGFR2 were measured by zonal elution and stepwise frontal analysis respectively. In addition, the actions of magnolol/honokiol on VEGFR2 were analyzed by stepwise frontal analysis at different temperatures. The results showed that the binding sites of magnolol and honokiol on VEGFR2 were different from sorafenib, indicating that magnolol and honokiol could be used as competitive agents for self-competitive displacement experiment. The Kd values (order of magnitude) of magnolol/honokiol with VEGFR2 measured by stepwise frontal analysis were consistent with the zonal elution results. Honokiol binds VEGFR2 with higher affinity than magnolol. The main forces that stabilize the interactions of honokiol with VEGFR2 are hydrogen bonds and van der Waal's forces, and the main force of magnolol is electrostatic forces. These discoveries could assist in the prediction of drug activity and understanding for the underlying mechanism.

Critical review on anthocyanins in blue honeysuckle (Lonicera caerulea L.) and their function.

Blue honeysuckle (Lonicera caerulea L.) is an emerging commercial fruit in the world, has been known for its multiple anthocyanins in the berries, cyanidin-3-glucoside (C3G) is a major anthocyanin in berries and it makes up 76-92% of the total anthocyanins content, with high antioxidant capacity, and widely used in food products. In this review, recent studies related to anthocyanins in blue honeysuckle were sorted out, including the current status of research on anthocyanins in blue honeysuckle berries, especially C3G, qualitative and quantitative analysis of anthocyanins in berries, extraction and purification methods of anthocyanins from blue honeysuckle, in addition, biological effects of blue honeysuckle, and recommended utilization. Blue honeysuckle contains polyphenols, flavonoids, anthocyanins, minerals, and multiple bioactive compounds, it has been extensively reported to have significant antioxidant, cardioprotective, anti-inflammatory, neuroprotective, anticancer, and anti-diabetic functions, and has been used in a variety of food products as raw materials.

Uncovering the role of FOXA2 in the Development of Human Serotonin Neurons.

Directed differentiation of serotonin neurons (SNs) from human pluripotent stem cells (hPSCs) provides a valuable tool for uncovering the mechanism of human SN development and the associated neuropsychiatric disorders. Previous studies report that FOXA2 is expressed by serotonergic progenitors (SNPs) and functioned as a serotonergic fate determinant in mouse. However, in the routine differentiation experiments, it is accidentally found that less SNs and more non-neuronal cells are obtained from SNP stage with higher percentage of FOXA2-positive cells. This phenomenon prompted them to question the role of FOXA2 as an intrinsic fate determinant for human SN differentiation. Herein, by direct differentiation of engineered hPSCs into SNs, it is found that the SNs are not derived from FOXA2-lineage cells; FOXA2-knockout hPSCs can still differentiate into mature and functional SNs with typical serotonergic identity; FOXA2 overexpression suppresses the SN differentiation, indicating that FOXA2 is not intrinsically required for human SN differentiation. Furthermore, repressing FOXA2 expression by retinoic acid (RA) and dynamically modulating Sonic Hedgehog (SHH) signaling pathway promotes human SN differentiation. This study uncovers the role of FOXA2 in human SN development and improves the differentiation efficiency of hPSCs into SNs by repressing FOXA2 expression.

A Survey on the Integration of Blockchains and Databases.

The success of blockchain technology in cryptocurrencies reveals its potential in the data management field. Recently, there is a trend in the database community to integrate blockchains and traditional databases to obtain security, efficiency, and privacy from the two distinctive but related systems. In this survey, we discuss the use of blockchain technology in the data management field and focus on the fusion system of blockchains and databases. We first classify existing blockchain-related data management technologies by their locations on the blockchain-database spectrum. Based on the taxonomy, we discuss three types of fusion systems and analyze their design spaces and trade-offs. Then, by further investigating the typical systems and techniques of each type of fusion system and comparing the solutions, we provide insights of each fusion model. Finally, we outline the unsolved challenges and promising directions in this field and believe that fusion systems will take a more important role in data management tasks. We hope this survey can help both academia and industry to better understand the advantages and limitations of blockchain-related data management systems and develop fusion systems that meet various requirements in practice.

Prevalence of neurodevelopmental disorders among US children and adolescents in 2019 and 2020.

Background: Concerning the changes in the prevalence of neurodevelopmental disorders (NDDs), we estimate the prevalence of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disorder (ID), and learning disability (LD) among US children and adolescents aged 3-17 years in 2019 and 2020. Methods: The study includes 14,983 US children and adolescents aged 3-17 years in 2019 and 2020 from the National Health Interview Survey (NHIS). Parents were interviewed about whether their children ever and/or currently had NDDs diagnosed. Prevalence estimates of NDDs were calculated with a survey-based weighting scheme. Logistic regression models were used to estimate the associations between NDDs prevalence and subgroups. Results: The weighted prevalence of ADHD, ASD, ID, and LD was 8.5% (95% CI: 7.9-9.2%), 2.9% (95% CI: 2.6-3.4%), 1.4% (95% CI: 1.2-1.7%), and 6.4% (95% CI: 5.8-7.0%), respectively. A higher prevalence of ADHD, ASD, ID, and LD was observed in boys, those who ever had anxiety or depression symptoms, those with lower family income, those living in a rented house, ever been bullied, and ever lived with anyone mentally ill. Conclusion: The study found the prevalence of ADHD, ASD, ID, and LD was different by demographics, comorbidity/mental problems, household/parental characteristics, and stressful life events.

Key infection stages defending heat stress in high-temperature-resistant Blumeria graminis f. sp. tritici isolates.

With the increase of temperature in the winter wheat-growing regions in China, the high-temperature-resistant Blumeria graminis f. sp. tritici (Bgt) isolates developed in the fields. To clarify the key infection stages and the roles of heat shock protein (HSP) genes of high-temperature-resistant Bgt isolates defending high temperature, 3 high-temperature-resistant and 3 sensitive Bgt isolates were selected from 55 isolates after determination of temperature sensitivity. And then they were used to investigate the infection stages and the expression levels of HSP genes, including Bgthsp60, Bgthsp70, Bgthsp90, and Bgthsp104, at 18°C and 25°C. The formation frequency of abnormal appressoria and inhibition rate of haustoria formation of high-temperature-resistant isolates at 25°C were lower than those of high-temperature-sensitive isolates, while major axis of microcolonies of high-temperature-resistant isolates was higher than those of high-temperature-sensitive isolates at 25°C. The results indicated that haustoria formation and hyphal expansion were the key infection stages of defense against heat stress in high-temperature-resistant isolates. Further analyses of HSP genes found the expression levels of Bgthsp60 and Bgthsp70c were upregulated at 24 and 72 h post-inoculation in high-temperature-resistant isolates, while no significant difference was observed for Bgthsp90 and Bgthsp104 genes. Taken together, the basis of high-temperature-resistant Bgt isolates is associated with induced expression of Bgthsp60 and Bgthsp70c response to heat stress in haustoria formation and hyphal expansion stages.

Caffeine reduces oxidative stress to protect against hyperoxia-induced lung injury via the adenosine A2A receptor/cAMP/PKA/Src/ERK1/2/p38MAPK pathway.

Objectives: Caffeine has been shown to reduce the incidence of bronchopulmonary dysplasia (BPD). To investigate the protective mechanism of caffeine in a hyperoxia-based cell model of BPD in vitro.Methods: Type II alveolar epithelial cells (AECs II) were isolated and randomly divided into 6 groups: the normal, hyperoxia, caffeine (50 µM caffeine), antagonist (5 µM ZM241385), agonist (5 µM CGS21680), and DMSO groups. Transfection with siRNA against adenosine A2A receptor (siA2AR) was performed in AECs II.Results: Caffeine alone or in combination with adenosine A2A receptor (A2AR) antagonist inhibited apoptosis, promoted proliferation and reduced oxidative stress (OS). The cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) mRNA, A2AR mRNA and the protein levels of A2AR, phospho-Src, phospho-ERK1/2, phospho-P38 and cleaved caspase-3 were decreased in the caffeine and antagonist groups compared with that in the hyperoxia group. However, the effects of caffeine above were weakened by the A2AR agonist. Knockdown of A2AR showed similar results to caffeine.Discussion: Caffeine can reduce apoptosis, promote proliferation, and alleviate OS in hyperoxia-induced AECs II injury by inhibiting the A2AR/cAMP/PKA/Src/ERK1/2/p38MAPK signaling pathway. Caffeine and A2AR may serve as a promising therapeutic target for BPD in prematurity.

Effects of high-quality nursing care on quality of life, survival, and recurrence in patients with advanced nonsmall cell lung cancer.

BACKGROUND: Postoperative nursing can improve the quality of life (QoL) and functional prognosis for lung cancer patients. The purpose of this study was to evaluate the effects of high-quality nursing on inflammation and prognosis in postoperative patients with advanced nonsmall cell lung cancer (NSCLC). METHODS: A total of 372 patients with NSCLC were enrolled between the May 2014 and June 2016. Patients were randomly received high-quality nursing (n = 192) or normal nursing (n = 180). Symptom management, QoL, hospital stay, inflammatory score, survival time, recurrence rate, symptoms, anxiety, depression scale and psychological distress were assessed at baseline and 5-year follow up. RESULTS: High-quality nursing significantly shortened hospital stay, improved postoperative inflammation, symptom management, QoL compared to patients received normal nursing. Compare with normal nursing, high-quality nursing decreased anxiety, depression scale and psychological distress for postoperative patients with advanced NSCLC. Outcomes showed that high-quality nursing increased the survival time and decreased recurrence rate for postoperative patients with advanced NSCLC. CONCLUSION: In conclusion, data in the current study indicate that high-quality nursing can decrease inflammation and improve prognosis for the postoperative patients with NSCLC.

Synthesis and Anti-Neuroinflammatory Activity of 1,7-diphenyl-1,4-heptadien-3-ones in LPS-Stimulated BV2 Microglia Via Inhibiting NF-κB/MAPK Signaling Pathways.

A series of 1,7-diphenyl-1,4-heptadien-3-ones with various substituents (HO-, CH3O-, CH3-, Cl-) on the phenyl rings were synthesized and evaluated for anti-neuroinflammatory effects in LPS-stimulated BV2 microglia. The pharmacological results showed that the target compounds bearing methoxy groups greatly inhibited LPS-induced NO release, and that the active compounds CU-19 and CU-21 reduced the level of NO, TNF-α, IL-6 and PGE-2, downregulated the expression of COX-2 and iNOS in LPS-stimulated BV2 cells. A study of the mechanism of action revealed that CU-19 and CU-21 inhibited the nuclear translocation of NF-κB and phosphorylation of MAPKs (ERK, JNK, and p38). A preliminary pharmacokinetic study in rats revealed that the pharmacokinetic properties of CU-19 and CU-21 were dramatically ameliorated in comparison with the pharmacokinetic properties of curcumin.

The Quantitative Analyses for the Effects of Two Wheat Varieties With Different Resistance Levels on the Fungicide Control Efficacies to Powdery Mildew.

Effective strategies to reduce the occurrence of wheat powdery mildew include the use of resistant varieties and application of fungicides. However, most studies rarely focus on the quantitative value of fungicide reduction using resistant varieties. To explore how the fungicides performed on different resistant wheat varieties to powdery mildew, field experiments were conducted during wheat growing seasons in 2018/19 and 2019/20 to investigate the control efficacies of enostroburin⋅epoxiconazole 18% SC and triadimefon 20% EC to wheat powdery mildew on a highly resistant wheat variety ("Baofeng104") and a highly susceptible wheat variety ("Jingshuang16"). The analyses of variance on control efficacies showed that the control efficacies of enostroburin⋅epoxiconazole 18% SC to wheat powdery mildew were mostly significantly higher than triadimefon 20% EC under the same conditions (i.e., varieties, dosages). However, both fungicide and variety resistance made variabilities in the mildew disease index and played a significant role in mildew management. Particularly, the variety resistance made the greatest contribution in mildew-reducing, and the disease index could significantly be reduced on the highly resistant variety even in the absence of fungicide treatment. The control efficacies to mildew on the highly susceptible variety mainly depended on the high efficiency of fungicides whereas the highly resistant variety were mainly by virtue of variety resistance through the comparative analyses of linear regression models. Furthermore, the random-coefficient regression models and quantile models quantificationally expounded that the relationships between active ingredient dosage and disease index or control efficacy varied from the effects of variety, fungicide, and year, particular from variety. Thus, a dosage reference table of enostroburin⋅epoxiconazole 18% SC or triadimefon 20% EC for different resistant wheat varieties were provided; it would be helpful for users to formulate an appropriate dosage of fungicide on mildew management in the field and avoid overusing or superfluous application. Further study needs to consider the effects of fungicide reduction on wheat yields, only then the maximum-economic benefits on mildew management can be determined.

Formation of halogenated disinfection byproducts in chlorinated real water during making hot beverage: Effect of sugar addition.

Chlorine disinfection is widely applied in drinking water treatment plant to inactivate pathogens in drinking water, but it unintentionally reacts with organic matter present in source waters and generates halogenated disinfection byproducts (DBPs). Sugar is one of the most commonly used seasoning in our diet. The addition of sugar could significantly improve the taste of the beverages; however, the effects of sugar on DBP formation and transformation remain unknown. In this study, the effects of sugar type and dose on the halogenated DBP formation in chlorinated boiled real tap water were evaluated during making hot beverages. We found that sugar can react with chlorine residual in tap water and generate halogenated DBPs. As the most commonly used table sugar, the addition of sucrose in the water sample at 100 or 500 mg/L as C could increase the level of total organic halogen (TOX) by ∼35%, when compared with the boiled tap water sample without sugar addition. In addition, fifteen reported and new polar brominated and chlorinated DBPs were detected and proposed from the reaction between chlorine and sucrose; accordingly, the corresponding transformation pathways were also proposed. Moreover, the DBP formation in the chlorinated boiled real tap water samples with the addition of xylose, glucose, sucrose, maltose and lactose were also investigated. By comparing with the TOX levels in the water samples with different sugar addition and their calculated TOX risk indexes, it was suggested that applying xylose as a sweetener in beverages could not only obtain a relatively high sweetness but also minimize the adverse effect inducing by halogenated DBPs during making hot beverages.

Rcor2 Is Required for Somatic Differentiation and Represses Germline Cell Fate.

Rcor2, the corepressor 2 of REST, a transcriptional repressor, is predominantly expressed in embryonic stem cells (ESCs) and plays a major role in regulating ESC pluripotency and neurogenesis. The function of Rcor2 in development of other germ layers is yet unclear. We utilized a Rcor2-/- mouse embryonic stem cell (mESC) line to investigate the role of Rcor2 in mESC differentiation. Rcor2-/- mESC shows reduced proliferation and severely compromised capacity to differentiate to all three germ layers. In contrast, Rcor2 knockout promotes primordial germ cells (PGCs) specific gene expression and possibly PGC formation. Mechanistically, we revealed that Rcor2 inhibits expression of genes required for PGC development, such as Dppa3 and Dazl, by associating to their promoters and enhancing local suppressive H3K9me3 modifications. Our results suggest that Rcor2 plays an important role in somatic cell fate determination by suppressing PGC differentiation through regulating epigenetic modifications of PGC specific genes.

A fluorescent probe derived from Berberrubine for detecting hydrogen polysulfide in food samples.

In this work, we chose the fluorophore Berberrubine to develop a selective probe for hydrogen polysulfide (H2Sn), and applied it into the detection in both food samples and living cells. The developed probe, HER9SS, suggested practical steadiness and serviceability, especially for multi-scene detection. The detecting system was stable in relatively wide pH (7.0-11.0) and temperature (25-45 °C) ranges. Both the storage of BER9SS in solid or in solution could maintain the steadiness over 7 d. BER9SS also indicated advantages including rapid response (within 15 min), high sensitivity (LOD = 0.02 µM; LOQ = 0.01 µM), long linear range (0-15.0 equivalent) and high selectivity among competing analytes. The recovery ranging in 95.23% - 104.8% in the applications in food sources samples (including water and plants) and food samples inferred the practical potential of BER9SS. In biological imaging, BER9SS could achieve both the dose-dependent monitoring and the ß-lapachone-induced generation of H2Sn. Therefore, the information in this work might be useful for the development of fluorescent probes from natural products for multi-scene applications in future, especially with the corresponding attentions on the practicability and serviceability.

Corticosterone induces obesity partly via promoting intestinal cell proliferation and survival.

Introduction: A vicious cycle ensues whereby prolonged exposure to social stress causes increased production of glucocorticoids (GCs), leading to obesity even further. Understanding the role of GCs, the key element in the vicious circle, might be helpful to break the vicious circle. However, the mechanism by which GCs induce obesity remains elusive. Methods: Corticosterone (CORT) was administered to mice for 8 weeks. Food and water intake were recorded; obesity was analyzed by body-weight evaluation and magnetic resonance imaging (MRI); intestinal proliferation and survival were evaluated by H&E staining, EdU-progression test, TUNEL assay and immunofluorescence staining of Ki67 and CC3; RNA-seq was performed to analyze transcriptional alterations in small intestines and livers. Results: Chronic CORT treatment induced obesity, longer small intestines, hepatic steatosis and elevated levels of serum insulin and leptin in mice; CORT-treated mice showed increased cell proliferation and decreased apoptosis of small intestines; RNA-seq results indicate that differentially expressed genes (DEGs) were enriched in several cell growth/death-associated signaling pathways. Discussion: Herein we find that administration of CORT to mice promotes the proliferation and survival of intestinal cells, which might contribute to the longer small intestines and the elongated intestinal villi, thus leading to increased nutrient absorption and obesity in mice. Understanding CORT-induced alterations in intestines and associated signaling pathways might provide novel therapeutic clues for GCs or stress-associated obesity.