A dynamic one-dimensional model for simulating unsteady air-water stratified flow in sewer pipes.

Ventilation is paramount in sanitary and stormwater sewer systems to mitigate odor problems and avert pressure surges. Existing numerical models have constraints in practical applications in actual sewer systems due to insufficient airflow modeling or suitability only for steady-state conditions. This research endeavors to formulate a mathematical model capable of accurately simulating various operational conditions of sewer systems under the natural ventilation condition. The dynamic water flow is modeled using a shock-capturing MacCormack scheme. The dynamic airflow model amalgamates energy and momentum equations, circumventing laborious pressure iteration computations. This model utilizes friction coefficients at interfaces to enhance the description of the momentum exchange in the airflow and provide a logical explanation for air pressure. A systematic analysis indicates that this model can be easily adapted to include complex boundary conditions, facilitating its use for modeling airflow in real sewer networks. Furthermore, this research uncovers a direct correlation between the air-to-water flow rate ratio and the filling ratio under natural ventilation conditions, and an empirical formula encapsulating this relationship is derived. This finding offers insights for practical engineering applications.

The interdependence of happiness and filial piety within the family: a study in Vietnam.

BACKGROUND: Filial piety is one of the most important values in Vietnam, as it is in a number of East Asian countries. It is an expression of children's respect, gratitude, and care for their parents. While filial piety may bring joy to parents and is a personal duty for offspring, it can also be a pressure for children. Hence, in recent years, some studies have considered filial piety as two dimensions instead of one dimension.Participants And Procedure This study focused on clarifying the relationship between filial piety and perceived family happiness with 385 adult offspring who lived in Vietnam at the time of the study. The Dual Filial Piety Scale (DFPS) and the Interdependent Happiness Scale (IHS) were used. Results: The results showed that participants regularly engaged in aspects of filial piety and there was no contradiction between authoritarian filial piety (AFP) and reciprocal filial piety (RFP). Filial piety can predict family happiness at a fairly high level. CONCLUSIONS: These results, besides showing the importance and value to the family, also give a multi-dimensional and comprehensive view of filial piety. At the social level, upholding the value of filial piety is the basis for building family happiness as well as making an important contribution to the implementation of social security in the family.

Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells.

Telomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high expression is associated with poor prognosis. Flavokavain B derivative FKB04 potently inhibited TRF2 expression in liver cancer cells while having limited effects on the other five shelterin subunits. Moreover, FKB04 treatment induced telomere shortening and increased the amounts of telomere-free ends, leading to the destruction of T-loop structure. Consequently, FKB04 promoted liver cancer cell senescence without modulating apoptosis levels. In corroboration with these findings, FKB04 inhibited tumor cell growth by promoting telomeric TRF2 deficiency-induced telomere shortening in a mouse xenograft tumor model, with no obvious side effects. These results demonstrate that TRF2 is a potential therapeutic target for liver cancer and suggest that FKB04 may be a selective small-molecule inhibitor of TRF2, showing promise in the treatment of liver cancer.

Nanoplatform-Based In Vivo Gene Delivery Systems for Cancer Therapy.

Gene therapy uses modern molecular biology methods to repair disease-causing genes. As a burgeoning therapeutic, it has been widely applied for cancer therapy. Since 1989, there have been numerous clinical gene therapy cases worldwide. However, a few are successful. The main challenge of clinical gene therapy is the lack of efficient and safe vectors. Although viral vectors show high transfection efficiency, their application is still limited by immune rejection and packaging capacity. Therefore, the development of non-viral vectors is overwhelming. Nanoplatform-based non-viral vectors become a hotspot in gene therapy. The reasons are mainly as follows. 1) Non-viral vectors can be engineered to be uptaken by specific types of cells or tissues, providing effective targeting capability. 2) Non-viral vectors can protect goods that need to be delivered from degradation. 3) Nanoparticles can transport large-sized cargo such as CRISPR/Cas9 plasmids and nucleoprotein complexes. 4) Nanoparticles are highly biosafe, and they are not mutagenic in themselves compared to viral vectors. 5) Nanoparticles are easy to scale preparation, which is conducive to clinical conversion and application. Here, an overview of the categories of nanoplatform-based non-viral gene vectors, the limitations on their development, and their applications in cancer therapy.

Ki-67 Change in Anthracyline-containing Neoadjuvant Chemotherapy Response in Breast Cancer.

OBJECTIVE: Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy (NAC) for breast cancer (BC) at present. However, 30% of early breast cancer (EBC) patients are resistant to anthracycline-containing chemotherapy, leading to poor prognosis and higher mortality. Ki-67 is associated with the prognosis and response to therapy, and it changes after NAC. METHODS: A total of 105 BC patients who received anthracycline-containing NAC were enrolled. Then, the optimal model of Ki-67 was selected, and its predictive efficacy was analyzed. Immunohistochemistry (IHC) was used to determine the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) status and Ki-67 level. Fluorescent in situ hybridization (FISH) was used to verify the HER-2 when the IHC score was 2+. RESULTS: The post-NAC Ki67 level after treatment with anthracycline drugs was lower than pre-NAC Ki-67 (19.6%±23.3% vs. 45.6%±23.1%, P<0.001). Furthermore, patients with the Ki-67 decrease had a border line higher pathological complete response (pCR) rate (17.2% vs. 0.0%, P=0.068), and a higher overall response rate (ORR) (73.6% vs. 27.8%, P<0.001), when compared to patients without the Ki-67 decrease. The ΔKi-67 and ΔKi-67% were valuable markers for the prediction of both the pCR rate and ORR. The area under the curve (AUC) for ΔKi-67 on pCR and ORR was 0.809 (0.698-0.921) and 0.755 (0.655-0.855), respectively, while the AUC for ΔKi-67% on pCR and ORR was 0.857 (0.742-0.972) and 0.720 (0.618-0.822), respectively. Multivariate logistic regression model 1 revealed that ΔKi-67 was an independent predictor for both pCR [odds ratio (OR)=61.030, 95% confidence interval (CI)=4.709-790.965; P=0.002] and ORR (OR=10.001, 95% CI: 3.044-32.858; P<0.001). Multivariate logistic regression model 2 revealed that ΔKi-67% was also an independent predictor for both pCR (OR=408.922, 95% CI=8.908-18771.224; P=0.002) and ORR (OR=5.419, 95% CI=1.842-15.943; P=0.002). CONCLUSIONS: The present study results suggest that ΔKi67 and ΔKi67% are candidate predictors for anthracycline-containing NAC response, and that they may provide various information for further systematic therapy after surgery in clinical practice.

Amide proton transfer-weighted magnetic resonance imaging for application in renal fibrosis: A radiological-pathological based analysis.

BACKGROUND: Renal fibrosis (RF) being the most important pathological change in the progression of CKD, is currently assessed by the evaluation of a biopsy. This present study aimed to apply a novel functional MRI (fMRI) protocol named amide proton transfer weighting (APTw) to evaluate RF non-invasively. METHODS: Male Sprague-Dawley (SD) rats were initially subjected to bilateral kidney ischemia/reperfusion injury (IRI), unilateral ureteral obstruction (UUO) and Sham operation, respectively. All rats underwent APT mapping on the 7th and the 14th day after operation. Besides, 26 patients undergoing renal biopsy at the Nephrology Department of Shanghai Tongji Hospital between July 2022 and May 2023. Patients underwent APT and apparent diffusion coefficient (ADC) mappings within 1 week before biopsy. MRI results of both patients and rats were calculated by comparing with gold standard histology for fibrosis assessment. RESULTS: In animal models, the cortical APT (cAPT) and medullary APT (mAPT) values were positively correlated with the degree of renal fibrosis. Compared to the sham group, IRI group showed significantly increased cAPT and mAPT values on the 7th and 14th day after surgery, but no group differences were found in ADC values. Similar results were found in human patients. Cortical/medullary APT values were significantly increased in patients with moderate-to-severe fibrosis than patients with mild fibrosis. ROC curve analysis indicated that APT value displayed a better diagnostic value for RF. Furthermore, combination of cADC and cAPT improved fibrosis detection by imaging variables alone (p<0.1). CONCLUSION: APT values had better diagnostic capability at early stage of RF compared to ADC values, and the addition of APT imaging to conventional ADC will significantly improve the diagnostic performance for predicting kidney fibrosis.

Human genetics and molecular genomics of Chiari malformation type 1.

Chiari malformation type 1 (CM1) is the most common structural brain disorder involving the craniocervical junction, characterized by caudal displacement of the cerebellar tonsils below the foramen magnum into the spinal canal. Despite the heterogeneity of CM1, its poorly understood patho-etiology has led to a 'one-size-fits-all' surgical approach, with predictably high rates of morbidity and treatment failure. In this review we present multiplex CM1 families, associated Mendelian syndromes, and candidate genes from recent whole exome sequencing (WES) and other genetic studies that suggest a significant genetic contribution from inherited and de novo germline variants impacting transcription regulation, craniovertebral osteogenesis, and embryonic developmental signaling. We suggest that more extensive WES may identify clinically relevant, genetically defined CM1 subtypes distinguished by unique neuroradiographic and neurophysiological endophenotypes.

Evaluation of potential radiological hazards of unfired construction materials containing fly ash in Vietnam.

In this study, the specific activities of 226Ra, 232Th and 40K in the unfired construction materials (solid card bricks, 4-hole bricks, pavement bricks) containing fly ash and bottom ash from a coal-fired thermal power plant in Vietnam were measured using the low-level gamma-ray spectrometer with HPGe detector. Also, the 222Rn concentrations in these materials were analyzed using RAD7 radon monitor and then radon mass exhalation rate and emanation fraction of these materials were calculated. The potential radiological hazards for residents living in the model room made of these materials were evaluated. The average specific activity of 226Ra, 232Th and 40K were found as 67.7, 79.3 and 703.5 Bq kg-1, respectively. The total annual effective dose (due to external gamma exposure and internal radon exposure for resident living in the CEN model room made of the unfired brick samples) was found as 0.9 mSv y-1 which is lower than the worldwide average dose of 2.4 mSv y-1. Calculations from ResRad-Build code showed that the doses due to radon exposure account for from 62.3% (at the first year) to 98.8% (at the next 30 years) of the total gamma and radon dose. Under low air exchange to the outside environment, from the 6th year onwards, the total dose may exceed the average dose value from natural radiation exposure sources.

Risk assessment of 3-MCPD esters and glycidyl esters from the formulas for infants and young children up to 36 months of age.

Esters of 2-monochloropropane-1,2-diol (2-MCPD), 3- monochloropropane-1,2-diol (3-MCPD), and glycidol are present in infant formulas, follow-on foods and similar compositions. They arise mainly from the vegetable oil content and may cause harmful effects in consumers. The contents of these substances in formulas were determined indirectly by converting the esters to the free form, followed by derivatization and analysis by gas chromatography-tandem mass spectrometry (GC-MS/MS). The validation results demonstrate that the method had sufficient specificity and adequate accuracy. The limits of detection (LOD) and limits of quantification (LOQ) for each of 2-MCPDE, 3-MCPDE, and GE were 1.5 and 5 µg/kg, respectively. Formula intake by children up to 36 months of age was surveyed, and the data was used to assess the risks due to 3-MCPD esters (3-MCPDE) and glycidyl esters (GE). The mean exposure dose of 3-MCPDE for different age groups ranged from 0.51 to 1.13 µg/kg bw per day. The corresponding mean GE exposure ranged from 0.031 to 0.069 µg/kg bw per day. Neither mean values nor the percentile 95% values of 3-MCPDE exposure doses exceed the recommended provisional maximum tolerable daily intake (PMTDI).

Genetic dysregulation of an endothelial Ras signaling network in vein of Galen malformations.

To elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and severe congenital brain arteriovenous malformation, we performed an integrated analysis of 310 VOGM proband-family exomes and 336,326 human cerebrovasculature single-cell transcriptomes. We found the Ras suppressor p120 RasGAP ( RASA1 ) harbored a genome-wide significant burden of loss-of-function de novo variants (p=4.79×10 -7 ). Rare, damaging transmitted variants were enriched in Ephrin receptor-B4 ( EPHB4 ) (p=1.22×10 -5 ), which cooperates with p120 RasGAP to limit Ras activation. Other probands had pathogenic variants in ACVRL1 , NOTCH1 , ITGB1 , and PTPN11 . ACVRL1 variants were also identified in a multi-generational VOGM pedigree. Integrative genomics defined developing endothelial cells as a key spatio-temporal locus of VOGM pathophysiology. Mice expressing a VOGM-specific EPHB4 kinase-domain missense variant exhibited constitutive endothelial Ras/ERK/MAPK activation and impaired hierarchical development of angiogenesis-regulated arterial-capillary-venous networks, but only when carrying a "second-hit" allele. These results illuminate human arterio-venous development and VOGM pathobiology and have clinical implications.

Mechanosensitive ion channel Piezo1 mediates mechanical ventilation-exacerbated ARDS-associated pulmonary fibrosis.

INTRODUCTION: Pulmonary fibrosis is a major cause of the poor prognosis of acute respiratory distress syndrome (ARDS). While mechanical ventilation (MV) is an indispensable life-saving intervention for ARDS, it may cause the remodeling process in lung epithelial cells to become disorganized and exacerbate ARDS-associated pulmonary fibrosis. Piezo1 is a mechanosensitive ion channel that is known to play a role in regulating diverse physiological processes, but whether Piezo1 is necessary for MV-exacerbated ARDS-associated pulmonary fibrosis remains unknown. OBJECTIVES: This study aimed to explore the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis. METHODS: Human lung epithelial cells were stimulated with hydrochloric acid (HCl) followed by mechanical stretch for 48 h. A two-hitmodel of MV afteracidaspiration-inducedlunginjuryin mice was used. Mice were sacrificed after 14 days of MV. Pharmacological inhibition and knockout of Piezo1 were used to delineate the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis. In some experiments, ATP or the ATP-hydrolyzing enzyme apyrase was administered. RESULTS: The stimulation of human lung epithelial cells to HCl resulted in phenotypes of epithelial-mesenchymal transition (EMT), which were enhanced by mechanical stretching. MV exacerbated pulmonary fibrosis in mice exposed to HCl. Pharmacologicalinhibitionorknockout of Piezo1 attenuated the MV-exacerbated EMT process and lung fibrosis in vivo and in vitro. Mechanistically, the observed effects were mediated by Piezo1-dependent Ca2+ influx and ATP release in lung epithelial cells. CONCLUSIONS: Our findings identify a key role for Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis that is mediated by increased ATP release in lung epithelial cells. Inhibiting Piezo1 may constitute a novelstrategyfor the treatment of MV-exacerbated ARDS-associated pulmonary fibrosis.

Regularity of prescriptions for sick sinus syndrome based on latent structure combined with association rules / 中国中药杂志

This study aims to mine the regularity of traditional Chinese medicine(TCM) prescriptions for sick sinus syndrome(SSS) and provide a reference for clinical syndrome differentiation and treatment. The relevant papers were retrieved from CNKI, Wanfang, VIP, and SinoMed with the time interval from inception to January 31, 2023. The relevant information from qualified papers was extracted to establish a library. Lantern 5.0 and Rstudio were used to analyze the latent structure and association rules of TCMs with the frequency ≥3%, which combined with frequency descriptions, were used to explore the rules of TCM prescriptions for SSS. A total of 192 TCM prescriptions were included, involving 115 TCMs with the cumulative frequency of 1 816. High-frequency TCMs include Aconiti Lateralis Radix Praeparata, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Astragali Radix, and Salviae Miltiorrhizae Radix et Rhizoma. The high-frequency medicines mainly had the effects of tonifying, releasing exterior with pungent-warm, and activating blood and resolving stasis. The analysis of the latent structure model yielded 13 hidden variables, 26 hidden classes, 8 comprehensive cluster models, and 21 core prescriptions. Accordingly, the common syndromes of SSS were inferred as heart-Yang Qi deficiency, heart-spleen Yang deficiency, heart-kidney Yang deficiency, Yang deficiency and blood stasis, both Qi and Yin deficiency and blood stasis, and Yin and Yang deficiency. The analysis of association rules predicted 30 strong association rules, among which Ginseng Radix et Rhizoma-Aconiti Lateralis Radix Praeparata had the highest support. SSS is a syndrome with Yang deficiency and Qi deficiency as the root causes and cold, phlegm, and stasis as the manifestations. The clinical treatment of SSS should focus on warming Yang and replenishing Qi, which should be supplemented with the therapies of activating blood and resolving stasis, warming interior and dissipating cold, or regulating Qi movement for resolving phlegm according to the patients' syndromes.

Prognostic Value of an Integrin-Based Signature in Hepatocellular Carcinoma and the Identification of Immunological Role of LIMS2.

Objective: Evidence proves that integrins affect almost every step of hepatocellular carcinoma (HCC) progression. The current study aimed at constructing an integrin-based signature for prognostic prediction of HCC. Methods: TCGA-LIHC and ICGC-LIRI-JP cohorts were retrospectively analyzed. Integrin genes were analyzed via univariate Cox regression, followed by generation of a prognostic signature with LASSO approach. Independent factors were input into the nomogram. WGCNA was adopted to select this signature-specific genes. Gene Ontology (GO) enrichment together with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to explore the function of the dysregulated genes. The abundance of tumor microenvironment components was estimated with diverse popular computational methods. The relative importance of genes from this signature was estimated through random-forest method. Results: Eight integrin genes (ADAM15, CDC42, DAB2, ITGB1BP1, ITGB5, KIF14, LIMS2, and SELP) were adopted to define an integrin-based signature. Each patient was assigned the riskScore. High-riskScore subpopulation exhibited worse overall survival, with satisfying prediction efficacy. Also, the integrin-based signature was independent of routine clinicopathological parameters. The nomogram (comprising integrin-based signature, and stage) accurately inferred prognostic outcome, with the excellent net benefit. Genes with the strongest positive interaction to low-riskScore were primarily linked to biosynthetic, metabolic, and catabolic processes and immune pathways; those with the strongest association with high-riskScore were principally associated with diverse tumorigenic signaling. The integrin-based signature was strongly linked with tumor microenvironment components. Among the genes from this signature, LIMS2 possessed the highest importance, and its expression was proven through immunohistochemical staining. Conclusion: Altogether, our study defined a quantitative integrin-based signature that reliably assessed HCC prognosis and tumor microenvironment features, which possessed the potential as a tool for prognostic prediction.

Target Capture Reveals the Complex Origin of Vietnamese Ginseng.

The global market of the medicinal plant ginseng is worth billions of dollars. Many ginseng species are threatened in the wild and effective sustainable development initiatives are necessary to preserve biodiversity at species and genetic level whilst meeting the demand for medicinal produce. This is also the case of Panax vietnamensis Ha & Grushv., an endemic and threatened ginseng species in Vietnam that is locally cultivated at different scales and has been the object of national breeding programs. To investigate the genetic diversity within cultivated and wild populations of P. vietnamensis we captured 353 nuclear markers using the Angiosperm-353 probe set. Genetic diversity and population structure were evaluated for 319 individuals of Vietnamese ginseng across its area of distribution and from wild and a varying range of cultivated areas. In total, 319 individuals were sampled. After filtering, 1,181 SNPs were recovered. From the population statistics, we observe high genetic diversity and high genetic flow between populations. This is also supported by the STRUCTURE analysis. The intense gene flow between populations and very low genetic differentiation is observed regardless of the populations' wild or cultivated status. High levels of admixture from two ancestral populations exist in both wild and cultivated samples. The high gene flow between populations can be attributed to ancient and on-going practices of cultivation, which exist in a continuum from understorey, untended breeding to irrigated farm cultivation and to trade and exchange activities. These results highlight the importance of partnering with indigenous peoples and local communities and taking their knowledge into account for biodiversity conservation and sustainable development of plants of high cultural value.

Preparation of Cellulose Nanocrystals from Jujube Cores by Fractional Purification.

Jujube cores are fiber-rich industrial waste. Dewaxing, alkali treatment, bleaching, and sulfuric acid hydrolysis were used to generate cellulose nanocrystals (CNCs) from the jujube cores in this study. The morphological, structural, crystallinity, and thermal properties of the fibers were investigated using FE-SEM, TEM, AFM, FT-IR, XRD, and TGA under various processes. CNCs' zeta (ζ) potential and water contact angle (WAC) were also investigated. The findings demonstrate that non-fibrous components were effectively removed, and the fiber particles shrunk over time because of many activities. CNCs had a rod-like shape, with a length of 205.7 ± 52.4 nm and a 20.5 aspect ratio. The crystal structure of cellulose Iß was preserved by the CNCs, and the crystallinity was 72.36%. The temperature of the fibers' thermal degradation lowered during the operations, although CNCs still had outstanding thermal stability (>200 °C). Aside from the CNCs, the aqueous suspension of CNCs was slightly agglomerated; thus, the zeta (ζ) potential of the CNCs' suspension was −23.72 ± 1.7 mV, and the powder had high hydrophilicity. This research will be valuable to individuals who want to explore the possibility for CNCs made of jujube cores.

[Discovery of exogenous ligands for orphan receptor BRS-3 from Chinese herbs].

Bombesin receptor subtype-3(BRS-3) is an orphan receptor in the bombesin receptor family. Its signal transduction mechanism and biological function have attracted much attention. Seeking the ligand for BRS-3 is of great significance for exploring its function. Considering the fact that the activation of BRS-3 receptor can induce the change in intracellular Ca~(2+) concentration, the fluo-rometric imaging plate reader(FLIPR) was utilized for ligand screening at the cellular level. Among more than 400 monomeric compounds isolated from Chinese herbs, yuanhunine from Corydalis Rhizoma and sophoraisoflavanone A and licoriphenone from Glycyrrhizae Radix et Rhizoma antagonized BRS-3 to varying degrees. It was confirmed in HEK293 cells expressing BRS-3 that yuanhunine, sophoraisoflavanone A, and licoriphenone inhibited the calcium current response after the activation of BRS-3 by [D-Phe~6,ß-Ala~(11),Phe~(13),Nle~(14)]bombesin-(6-14) in a dose-dependent manner with the IC_(50) values being 8.58, 4.10, and 2.04 µmol·L~(-1), respectively. Further study indicated that yuanhunine and sophoraisoflavanone A exhibited good selectivity for BRS-3. In this study, it was found for the first time that monomers derived from Chinese herbs had antagonistic activity against orphan receptor BRS-3, which has provided a tool for further study of BRS-3 and also the potential lead compounds for new drug discovery. At the same time, it provides reference for the research and development of innovative drugs based on the active ingredients of Chinese herbs.

Making Polyol Gummies by 3D Printing: Effect of Polyols on 3D Printing Characteristics.

With growth of confectionery industry, there is a great demand for candy shape, and 3D printing technology is way to achieve it. The printing properties of gummy, which is formed of gelatin and low acyl gellan as gel, maltol, erythritol, sorbitol, and xylitol as sweeteners, were tested in this study. Gummies' rheological properties, 3D printing properties, and textural qualities were measured using a rheometer, FTIR, and SEM in this study. The strength of the hydrogen bonds will be affected by the addition of polyol, after which the excluded volume effect of polyol and viscosity will become the most important aspect. Polyols increased the gelation temperature (Tgelation), improved the gel network, and improved hydrogen bonding in the gel, according to the findings. Yield stress, shear recovery performance, and gel strength were initially increased, then decreased, when polyol concentration was increased. It had a 40.59 °C gelation temperature, an 82.99% recovery rate, noticeable shear thinning features, high self-supporting performance, and textural qualities when ink with 35 g maltitol and 30 g erythritol gave the best printing performance. This research serves as a foundation for the development of individualized, bespoke 3D printed gummies in the future.

Chemical constituents of Aglaia elaeagnoidea and Aglaia odorata and their cytotoxicity.

Two new rocaglamides, 8b-O-5-oxohexylrocaglaol (1) and elaeagnin (2), together with twelve known compounds, were isolated from the bark of Aglaia elaeagnoidea and the whole tree of A. odorata. Their structures were determined using spectroscopic methods, mainly 1D and 2D NMR. Cytotoxic activity against HepG2 human liver cancer cells of the isolated compounds was evaluated in vitro using the SRB assay. Three rocaglamide derivatives, dehydroaglaiastatin (13), 8b-O-5-oxohexylrocaglaol (1) and rocaglaol (5), exhibited significant effects with IC50 values of 0.69, 4.77 and 7.37 µM, respectively.

Discovery of exogenous ligands for orphan receptor BRS-3 from Chinese herbs / 中国中药杂志

Bombesin receptor subtype-3(BRS-3) is an orphan receptor in the bombesin receptor family. Its signal transduction mechanism and biological function have attracted much attention. Seeking the ligand for BRS-3 is of great significance for exploring its function. Considering the fact that the activation of BRS-3 receptor can induce the change in intracellular Ca~(2+) concentration, the fluo-rometric imaging plate reader(FLIPR) was utilized for ligand screening at the cellular level. Among more than 400 monomeric compounds isolated from Chinese herbs, yuanhunine from Corydalis Rhizoma and sophoraisoflavanone A and licoriphenone from Glycyrrhizae Radix et Rhizoma antagonized BRS-3 to varying degrees. It was confirmed in HEK293 cells expressing BRS-3 that yuanhunine, sophoraisoflavanone A, and licoriphenone inhibited the calcium current response after the activation of BRS-3 by [D-Phe~6,β-Ala~(11),Phe~(13),Nle~(14)]bombesin-(6-14) in a dose-dependent manner with the IC_(50) values being 8.58, 4.10, and 2.04 μmol·L~(-1), respectively. Further study indicated that yuanhunine and sophoraisoflavanone A exhibited good selectivity for BRS-3. In this study, it was found for the first time that monomers derived from Chinese herbs had antagonistic activity against orphan receptor BRS-3, which has provided a tool for further study of BRS-3 and also the potential lead compounds for new drug discovery. At the same time, it provides reference for the research and development of innovative drugs based on the active ingredients of Chinese herbs.

Novel API Coated Catheter Removes Amyloid-ß from Plasma of Patients with Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of dementia, characterized by the deposition of Amyloid-beta (Aß) plaques in the brain. We have previously developed Amytrap peptide (the active pharmacological ingredient, API) and linked it to a sepharose bead matrix by click chemistry to form Amytrapper matrix, which was able to bind and remove Aß from human sera and plasma spiked with biotinylated Aß42 (bio-Aß42) in vitro. To extend the logic of the previous studies, the current study investigates whether the Amytrap peptide coated inside a medically viable polycarbonate catheter (Amytrapper catheter) could bind and retain Aß from the human sera. The Amytrapper matrix and the novel Amytrapper catheter were able to bind and retain spiked bio-Aß42 from human sera or native Aß from plasma of AD patients. Additional characteristics of the Amytrapper catheter are evaluated and presented in this study. The results presented here provide a proof-of-principle for the first time that extracorporeal Amytrapper device aids clearance of native Aß (from plasma of AD patients). Thus, our device Amytrapper, either in the form of Sepharose matrix or catheter, could become a novel therapeutic strategy to remove Aß from circulation in AD patients.