Discovery of novel cholinesterase inhibitors easily crossing the blood-brain barrier via structure-property relationship investigation: Methylenedioxy-cinnamicamides containing tertiary amine side chain.

In the present investigation, a series of dimethoxy or methylenedioxy substituted-cinnamamide derivatives containing tertiary amine moiety (N. N-Dimethyl, N, N-diethyl, Pyrrolidine, Piperidine, Morpholine) were synthesized and evaluated for cholinesterase inhibition and blood-brain barrier (BBB) permeability. Although their chemical structures are similar, their biological activities exhibit diversity. The results showed that all compounds except for those containing morpholine group exhibited moderate to potent acetylcholinesterase inhibition. Preliminary screening of BBB permeability shows that methylenedioxy substituted compounds have better brain permeability than the others. Compound 10c, containing methylenedioxy and pyrrolidine side chain, showed a better acetylcholinesterase inhibition (IC50: 1.52±0.19 µmol/L) and good blood-brain barrier permeability. Further pharmacokinetic investigation of compound 10c using ultra high performance liquid chromatography-mass/mass spectrometry (UPLC-MS/MS) in mice showed that compound 10c in brain tissue reached its peak concentration (857.72 ± 93.56 ng/g) after dosing 30 min. Its half-life in the serum is 331 min (5.52 h), and the CBrain/CSerum at various sampling points is ranged from 1.65 to 4.71(Mean: 2.76) within 24 hours. This investigation provides valuable information on the chemistry and pharmacological diversity of cinnamic acid derivatives and may be beneficial for the discovery of central nervous system drugs.

Low expression of interleukin-1 receptor antagonist correlates with poor prognosis via promoting proliferation and migration and inhibiting apoptosis in oral squamous cell carcinoma.

BACKGROUND: Biomarkers are biochemical indicators that can identify changes in the structure or function of systems, organs, or cells and can be used to monitor a wide range of biological processes, including cancer. Interleukin-1 receptor antagonist (IL1RA) is an important inflammatory suppressor gene and tumor biomarker. The goal of this study was to investigate the expression of IL1RA, its probable carcinogenic activity, and its diagnostic targets in oral squamous cell carcinoma (OSCC). RESULTS: We discovered that IL1RA was expressed at a low level in OSCC tumor tissues compared to normal epithelial tissues and that the expression declined gradually from epithelial hyperplasia through dysplasia to carcinoma in situ and invasive OSCC. Low IL1RA expression was associated not only with poor survival but also with various clinicopathological markers such as increased infiltration, recurrence, and fatalities. Following cellular phenotyping investigations in OSCC cells overexpressing IL1RA, we discovered that recovering IL1RA expression decreased OSCC cell proliferation, migration, and increased apoptosis. CONCLUSIONS: In summary, our investigation highlighted the possible involvement of low-expression IL1RA in OSCC cells in promoting invasive as well as metastatic and inhibiting apoptosis, as well as the efficacy of IL1RA-focused monitoring in the early detection and treatment of OSCC.

The impact of paramagnetic rim lesions on cortical thickness and gray to white matter contrast in relapsing-remitting multiple sclerosis.

Background: Paramagnetic rim lesions (PRLs) on susceptibility magnetic resonance sequences have been suggested as an imaging marker of disease progression in multiple sclerosis. This retrospective cross-sectional study aimed to investigate the impact of PRLs on cortical thickness and gray matter (GM) to white matter (WM) contrast in relapsing-remitting multiple sclerosis (RRMS). Methods: A total of 82 RRMS patients (40 patients with at least 1 PRL and 42 patients without PRL) and 43 healthy controls (HC) were included in this study. The T1-weighted images (T1WI) were processed with the FreeSurfer pipeline. GM to WM signal intensity ratio (GWR) was obtained from T1WI by dividing the GM signal intensity by the WM signal intensity for each vertex. Group differences in cortical thickness and GWR were tested on reconstructed cortical surface. Results: Compared to HC, patients with PRL had thinner mean cortical thickness (P<0.001), higher mean GWR (P=0.001), and lower brain structure volumes (cortex volume, P=0.001; WM volume, P<0.001; deep GM volume, P<0.001). Vertex-based analysis found significant cortical thinning in several regions and increased GWR in a wider range of regions in patients with PRL. The two types of clusters had both overlapping regions and independent regions. However, in patients without PRL, only a few regions showed significant cortical thickness changes. Correlation analysis found that in patients with PRL, only PRL volume showed a significant negative correlation with mean cortical thickness (P=0.048), and PRL volume and count, non-PRL count, and total lesion volume were significantly and positively correlated with mean GWR (P<0.05). Conclusions: There were significant changes in cortical thickness, GWR, and brain structure volume in RRMS patients with PRL that may contribute to further understanding of the pathological mechanisms underlying neurological tissue damage.

Blocking of FGFR4 signaling by F30 inhibits hepatocellular carcinoma cell proliferation through HMOX1-dependent ferroptosis pathway.

Excessive activation of FGF19/fibroblast growth factor receptor 4 (FGFR4) signaling is associated with poor survival of patients with hepatocellular carcinoma (HCC). FGFR4 inhibitors show promise for HCC treatment. F30, an indazole derivative designed through computer-aided drug design targeting FGFR4, demonstrated anti-HCC activity as described in our previous studies. However, the precise molecular mechanisms underlying F30's anticancer effects remain largely unexplored. We report here that F30 could effectively induce ferroptosis in HCC cells. The concentrations of cellular ferrous iron, the peroxidation of cell membranes and the homeostasis of reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG) were dysregulated by F30, thereby affecting cellular redox status. Induction of ferroptosis in HCC by F30 was inhibited by specific ferroptosis inhibitor ferrostatin-1. F30 upregulates various ferroptosis-related genes, including the heme oxygenase enzymes 1 (HMOX1), a key mediator of redox regulation. Surprisingly, F30-induced ferroptosis in HCC is dependent on HMOX1. The dysregulation of cellular ferrous iron concentrations and cell membrane peroxidation was rescued when knocking down HMOX1 with specific small interfering RNA. These findings shed light on the molecular mechanisms underlying FGFR4-targeting F30's anti-HCC effects and suggest that FGFR4 inactivation could be beneficial for HCC treatment involving ferroptosis.

A nonsymmetrical salamo-like fluorescence chemical sensor for selective identification of Cu2+ and B4O72- ions and practical applications.

An innovative salamo-like fluorescent chemical sensor H2L, has been prepared that can be utilized to selectively detect Cu2+ and B4O72- ions. Cu2+ ions can bind to oxime state nitrogen and phenol state oxygen atoms in the chemosensor H2L, triggering the LMCT effect leading to fluorescence enhancement. The crystal structure of the copper(II) complex, named as [Cu(L)], has been achieved via X-ray crystallography, and the sensing mechanism has been confirmed by further theoretical calculations with DFT. Besides, the sensor H2L recognizes B4O72- ions causing an ICT effect resulting in bright blue fluorescence. Moreover, the sensor has relatively high selectivity and sensitivity for Cu2+ and B4O72- ions, and the detection limits are 1.02 × 10-7 and 2.06 × 10-7 M, respectively. In addition, the good biocompatibility and excellent water solubility of the sensor H2L make it very advantageous in practical applications, using H2L powder for fingerprint visualization, using H2L to identify the phenomenon of B4O72- ions emitting bright blue fluorescence, making it an ink that can print encrypted messages on A4 paper, in addition to this, based on H2L, the real water sample was tested for Cu2+ ion recognition, and finally the test strip experiment was carried out.

Spatiotemporal evolution of agricultural drought and its attribution under different climate zones and vegetation types in the Yellow River Basin of China.

Ecological protection and high-quality development of the Yellow River Basin (YRB) are major national strategies in China. Agricultural drought (AD) is one of the most important stress factors of the ecological security of the YRB. Currently, there is a lack of exploration of the spatiotemporal evolution of AD in the YRB under different climatic zones and vegetation types, and the mechanisms by the driving factors influence AD remain unclear. The Temperature Vegetation Dryness Index (TVDI) for the YRB in China during 2000-2020 was calculated using Land Surface Temperature (LST) and the Normalized Difference Vegetation Index (NDVI). We analyzed the spatiotemporal evolution of AD from the perspective of upstream of the YRB (UYRB), midstream of the YRB (MYRB), and downstream of the YRB (DYRB), as well as different climate zones and vegetation types. The driving factors were selected based on the Pearson correlation analysis, Geographical detector, and Mantel test. Structural equation modeling (SEM) was employed to quantify the direct and indirect effects of the driving factors on AD in the YRB. We found a slowing trend of AD in the YRB, mainly in the Loess Plateau, which is distributed in UYRB and MYRB, but an increasing trend for AD in DYRB. Temperature, which is the most direct influential factor, has exacerbated AD in UYRB and MYRB. However, surface solar radiation (SSR) has the greatest constraining effect on DYRB. AD increased in arid and desert zones, while a decreasing trend is observed for other climatic zones and vegetation types. In arid and semiarid zones, human activities and SSR were the largest indirect factors exacerbating AD. In humid and subhumid zones, the largest indirect factor exacerbating AD was potential evapotranspiration (PET). Temperature is the most direct factor exacerbating AD in cropland and forest, while PET is the largest indirect factor exacerbating AD in grassland. This study elucidates the driving factors and mechanisms of AD in the YRB to provide scientific decision support for mitigating regional drought and promoting regional sustainable development.

A unique N-heterocyclic oligo(N,O-donor) salamo-Ni(II)-based probe for highly selective fluorescence detection of Cr2O72.

A unique fluorescent probe Ni-DAS was developed by a nitrogenous heterocyclic oligo(N,O-donor) salamo-based compound DAS. DAS exhibits AIE and ESIPT effects which are extremely infrequent in salamo-based multi-oxime compounds. In addition, Ni-DAS can be used as a fluorescent probe with high selectivity and sensitivity to recognize Cr2O72- in DMF with 80 % water content, which enhances the value of the probe for application in real environments, and outperforms most similar molecular fluorescence probes. The probe Ni-DAS can recognize Cr2O72- by oxidative hydrolysis of C = N bonds, which promotes further research on theory of C = N bond hydrolysis, and the binding ratio and recognition mechanism were verified and supported by relevant theoretical calculations (DFT & MESP). The experiments showed that the probe Ni-DAS can be used for ion detection in real environments. It provides a new strategy for the oxidative hydrolysis of C = N bond and the structure of salamo-based compounds with AIE nature, and offers new ideas for study ion recognition and acidity detection.

MiRNA-766-3p inhibits gastric cancer via targeting COL1A1 and regulating PI3K/AKT signaling pathway.

Objective MiRNA-766-3p has been shown to be associated with a variety of cancers. However, few studies have been done in gastric cancer (GC). This study explores the mechanism of miR-766-3p in GC. Methods The potential targets of microRNA (miRNA) were predicted using Tarbase and Targetscan databases. The results are intersected with differential genes (DEGs) (fold change > 1.5, P < 0.05) in gastric cancer to obtain potential core targets. The hub targets screened by constructing PPI networks (degree > 5, expression > 0.5). Validating the differential expression and expression in immunohistochemistry of these targets through the database. And the binding sites between miRNAs and mRNAs were verified using dual-luciferase Assay. Finally, qRT-PCR and Western Blot experiments were conducted to validate the hub targets and signal pathways. Results The potential hub targets from the PPI network were THBS2, COL1A1, FGG, FGB, and PLAU. Combining database, luciferase Assay and experimental validation, miR-766-3p can sponge COL1A1 and it plays the most important role in gastric cancer progression. In GC, COL1A1 was upregulated and the enrichment analysis revealed that COL1A1 regulates PI3K/AKT signal pathway, and AKT is also highly expressed in gastric cancer. Conclusion The miR-766-3p can inhibit the progression of gastric cancer by targeting COL1A1 and regulating the PI3K/AKT signal pathway. It could be a potential therapy option for the GC.

Let-7c-3p suppresses lens epithelial-mesenchymal transition by inhibiting cadherin-11 expression in fibrotic cataract.

Fibrotic cataract, including anterior subcapsular cataract (ASC) and posterior capsule opacification, always lead to visual impairment. Epithelial-mesenchymal transition (EMT) is a well-known event that causes phenotypic alterations in lens epithelial cells (LECs) during lens fibrosis. Accumulating studies have demonstrated that microRNAs are important regulators of EMT and fibrosis. However, the evidence explaining how microRNAs modulate the behavior and alter the cellular phenotypes of the lens epithelium in fibrotic cataract is insufficient. In this study, we found that hsa-let-7c-3p is downregulated in LECs in human ASC in vivo as well as in TGFß2-induced EMT in vitro, indicating that hsa-let-7c-3p may participate in modulating the profibrotic processes in the lens. We then demonstrated that overexpression of hsa-let-7c-3p markedly suppressed human LEC proliferation and migration and attenuated TGFß2-induced EMT and injury-induced ASC in a mouse model. In addition, hsa-let-7c-3p mediated lens fibrosis by directly targeting the CDH11 gene, which encodes cadherin-11 protein, an important mediator in the EMT signaling pathway. It decreased cadherin-11 protein expression at the posttranscriptional level but not at the transcriptional level by binding to a specific site in the 3-untranslated region (3'-UTR) of CDH11 mRNA. Moreover, blockade of cadherin-11 expression with a specific short hairpin RNA reversed TGFß2-induced EMT in LECs in vitro. Collectively, these data demonstrated that hsa-let-7c-3p plays a clear role in attenuating ASC development and may be a novel candidate therapeutic for halting fibrosis and maintaining vision.

Automatic Recognition of Concealed Fish Bones under Laryngoscopy: A Practical AI Model Based on YOLO-V5.

BACKGROUND: Fish bone impaction is one of the most common problems encountered in otolaryngology emergencies. Due to their small and transparent nature, as well as the complexity of pharyngeal anatomy, identifying fish bones efficiently under laryngoscopy requires substantial clinical experience. This study aims to create an AI model to assist clinicians in detecting pharyngeal fish bones more efficiently under laryngoscopy. METHODS: Totally 3133 laryngoscopic images related to fish bones were collected for model training and validation. The images in the training dataset were trained using the YOLO-V5 algorithm model. After training, the model was validated and its performance was evaluated using a test dataset. The model's predictions were compared to those of human experts. Seven laryngoscopic videos related to fish bone were used to validate real-time target detection by the model. RESULTS: The model trained in YOLO-V5 demonstrated good generalization and performance, with an average precision of 0.857 when the intersection over union (IOU) threshold was set to 0.5. The precision, recall rate, and F1 scores of the model are 0.909, 0.818, and 0.87, respectively. The overall accuracy of the model in the validation set was 0.821, comparable to that of ENT specialists. The model processed each image in 0.012 s, significantly faster than human processing (p < 0.001). Furthermore, the model exhibited outstanding performance in video recognition. CONCLUSION: Our AI model based on YOLO-V5 effectively identifies and localizes fish bone foreign bodies in static laryngoscopic images and dynamic videos. It shows great potential for clinical application. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2162-2169, 2024.

Rapid detection and quantification of adulteration in saffron by excitation-emission matrix fluorescence combined with multi-way chemometrics.

BACKGROUND: Saffron has gained people's attention and love for its unique flavor and valuable edible value, but the problem of saffron adulteration in the market is serious. It is urgent for us to find a simple and rapid identification and quantitative estimation of adulteration in saffron. Therefore, excitation-emission matrix (EEM) fluorescence combined with multi-way chemometrics was proposed for the detection and quantification of adulteration in saffron. RESULTS: The fluorescence composition analysis of saffron and saffron adulterants (safflower, marigold and madder) were accomplished by alternating trilinear decomposition (ATLD) algorithm. ATLD and two-dimensional principal component analysis combined with k-nearest neighbor (ATLD-kNN and 2DPCA-kNN) and ATLD combined with data-driven soft independent modeling of class analogies (ATLD-DD-SIMCA) were applied to rapid detection of adulteration in saffron. 2DPCA-kNN and ATLD-DD-SIMCA methods were adopted for the classification of chemical EEM data, first with 100% correct classification rate. The content of adulteration of adulterated saffron was predicted by the N-way partial least squares regression (N-PLS) algorithm. In addition, new samples were correctly classified and the adulteration level in adulterated saffron was estimated semi-quantitatively, which verifies the reliability of these models. CONCLUSION: ATLD-DD-SIMCA and 2DPCA-kNN are recommended methods for the classification of pure saffron and adulterated saffron. The N-PLS algorithm shows potential in prediction of adulteration levels. These methods are expected to solve more complex problems in food authenticity. © 2023 Society of Chemical Industry.

Molecular cloning, characterization and expression analysis of the Chinese soft-shelled turtle (Pelodiscus sinensis) chemokine CXCL11.

Chemokines are small, secreted proteins with chemoattractive properties, which play an important role in the recruitment and activation of immune cells. CXCL11 is a CXC chemokine specific for the CXCR3 receptors, which has been shown to mediate the generation of Th1-type immune responses and have bactericidal effects similar to defensins. Herein, we cloned the full-length cDNA of Chinese soft-shelled turtle (Pelodiscus sinensis) CXCL11, designated as PsCXCL11, which consist of an open reading frame (ORF) of 282 bp encoding 93 amino acids, with estimated molecular weight of 10.055 kDa and isoelectric point of 10.37. The deduced PsCXCL11 sequence had a signal peptide, a highly conserved family-specific small cytokine (SCY) domain, one putative N-glycosylation site and ten potential phosphorylation sites. Phylogenetic analysis showed a close relationship between P. sinensis and Chelydra Serpentina CXCL11. P. sinensis CXCL11 basal expression levels were higher in heart, kidney and spleen than in other organs of health turtles. Infections of Aeromonas hydrophila and Staphylococcus aureus led to significant upregulation of P. sinensis CXCL11 in the blood, while significant upregulation of PsCXCL11 were observed in liver and spleen after infection of A. hydrophila, but not S. aureus. PsCXCL11 recombinant protein with His-tag was successfully expressed by an auto-inducible expression system, and purified by Ni-NTA affinity chromatography. These findings laid a solid foundation for further research towards development of the Chinese soft-shelled turtle as a model for the role of CXCL11 in regulating inflammatory responses to stimulation by invading pathogens.

Self-assembled boron nitride nanosheet-based aerogels as support frameworks for efficient thermal energy storage phase change materials.

Phase change materials (PCMs) are promising in many fields related to energy utilization and thermal management. However, the low thermal conductivity and poor shape stability of PCMs restrict their direct thermal energy conversion and storage. The desired properties for PCMs are not only high thermal conductivity and excellent shape stability, but also high latent heat retention. In this study, the boron nitride nanosheets (BNNSs) were bridged by small amounts of GO nanosheets and successfully self-assembled into BNNS/rGO (BG) aerogels by hydrothermal and freeze-drying processes. The BG aerogels with interlaced macro-/micro-pores have been proven to be ideally suited as support frameworks for encapsulating polyethylene glycol (PEG). The obtained composite PCMs exhibit high thermal conductivity (up to 1.12 W m-1 K-1), excellent shape stability (maintain at 90 °C for 10 min), and high latent heat (187.2 J g-1) with a retention of 97.3% of the pure PEG, presenting great potential applications in energy storage systems and thermal management of electronic devices.

An off-on fluorescent nanoprobe for L-cysteine sensing based on the FRET effect.

A self-assembled fluorescent nanosensor for the determination of L-cysteine (Cys) was constructed based on the mechanism of fluorescence resonance energy transfer (FRET). In this system, CdTe/ZnS QDs serve as the energy donor while AuNPs serve as the receptor, resulting in the occurrence of FRET with dramatic fluorescence quenching of the QDs (turn off). Once Cys is added, AuNPs can adsorb Cys, leading to the release of the QDs. The process would inhibit the FRET, which contributed to the recovery of fluorescence (turn on) and an off-on fluorescence aptasensor for Cys detection was constructed accordingly. The linear response range of the fluorescence sensor is from 0.8 to 50 µM, and the detection limit is 0.24 µM. The sensor demonstrates great sensitivity and selectivity to Cys. More importantly, the QD-based sensing platform was successfully used for the detection of Cys in milk samples with high precision and accuracy, indicating the potential of the probe in practical applications.

Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways.

Patients with H3K27M-mutant diffuse midline glioma (DMG) have no proven effective therapies. ONC201 has recently demonstrated efficacy in these patients, but the mechanism behind this finding remains unknown. We assessed clinical outcomes, tumor sequencing, and tissue/cerebrospinal fluid (CSF) correlate samples from patients treated in two completed multisite clinical studies. Patients treated with ONC201 following initial radiation but prior to recurrence demonstrated a median overall survival of 21.7 months, whereas those treated after recurrence had a median overall survival of 9.3 months. Radiographic response was associated with increased expression of key tricarboxylic acid cycle-related genes in baseline tumor sequencing. ONC201 treatment increased 2-hydroxyglutarate levels in cultured H3K27M-DMG cells and patient CSF samples. This corresponded with increases in repressive H3K27me3 in vitro and in human tumors accompanied by epigenetic downregulation of cell cycle regulation and neuroglial differentiation genes. Overall, ONC201 demonstrates efficacy in H3K27M-DMG by disrupting integrated metabolic and epigenetic pathways and reversing pathognomonic H3K27me3 reduction. SIGNIFICANCE: The clinical, radiographic, and molecular analyses included in this study demonstrate the efficacy of ONC201 in H3K27M-mutant DMG and support ONC201 as the first monotherapy to improve outcomes in H3K27M-mutant DMG beyond radiation. Mechanistically, ONC201 disrupts integrated metabolic and epigenetic pathways and reverses pathognomonic H3K27me3 reduction. This article is featured in Selected Articles from This Issue, p. 2293.

A fluorescent Salamo-Salen-Salamo-Zn(II) sensor for bioimaging and biosensing H2PO4- in Zebrafish and plants.

A newly designed and synthesized Salamo-Salen-Salamo-Zn(II) complex sensor (sensor ZT) was extensively explored for anion sensing studies. The selectivity and sensitivity of the sensor ZT towards H2PO4- ions were based on ICT and CHEF effects, and via displacement pathways in DMSO/H2O (9:1, v/v) medium in the presence of other anions like, PO43-, HPO42- and P2O74- in a short time, separately. The prepared ZT sensor has excellent association constant and low detection lines. The sensing mechanism and binding mode of the sensor were studied by UV-Vis spectroscopy, HR-MS, 1H NMR titration and theory calculations (DFT & TD-DFT) for analytes. The time response and stability of the sensor are also given. Meanwhile, the sensor ZT can be widely used as a simple and effective solid-state optical sensor to detect H2PO4- by intuitive fluorescence changes. In addition, besides the environment can be used as a powerful instrument for detecting H2PO4-, based on the good biocompatibility and tissue permeability of ZT, effectively monitoring H2PO4- in cellular distribution by confocal microscopy using Zebrafish and bean sprout.

Design, synthesis and the evaluation of cholinesterase inhibition and blood-brain permeability of daidzein derivatives or analogs.

In the present study, a series of derivatives and analogs of daidzein were designed and synthesized to investigate cholinesterase inhibition and blood-brain barrier permeability. The enzyme assay showed that most of the compounds containing a tertiary amine group exhibit moderate cholinesterase inhibition, 7-hydroxychromone derivatives (absence of B ring of daidzein scaffold) only have a weaker bioactivity, while those compounds without the tertiary amine group have no bioactivity. Among them compound 15a (4'-N,N-dimethylaminoethoxy-7-methoxyisoflavone) appeared the best inhibitory activity (IC50 : 2.14 ± 0.31 µmol/L) and higher selectivity for AChE over BuChE (Ratio: 7.07). It was selected for the further investigation by UPLC-MS/MS. The results show that CBrain/Serum of compound 15a in mice was more than 2.87 within 240 min. This discovery may provide worthy information for the future development of central nervous drugs including but not limited to cholinesterase inhibitors.

Transcriptomics and systems network-based molecular mechanism of herbal formula Huosu-Yangwei inhibited gastric cancer in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: The efficacy of the herbal formula Huosu-Yangwei (HSYW) in the treatment of advanced gastric cancer and chronic atrophic gastritis with precancerous lesions has been reported in clinical trials. However, the molecular mechanisms underlying its inhibition of gastric tumor are not well-understood. AIM OF THE STUDY: Combined with transcriptomics and systems network-based molecular mechanism to explore the potential circRNA-miRNA-mRNA network of HSYW in the treatment of gastric cancer. MATERIALS AND METHODS: Animal experiments were conducted to investigate the effect of HSYW on tumor growth in vivo. RNA sequencing (RNA-seq) was implemented to identify the differentially expressed (DE) genes. Predictive miRNA targets and mRNA were used to construct circRNA-miRNA-mRNA networks and protein-protein interaction (PPI) networks. Quantitative real-time PCR (qRT-PCR) was utilized to verify the accuracy of the proposed circRNA-miRNA-mRNA networks. Additionally, the differentially expressed target proteins between gastric cancer (GC) and normal patients were assessed using data from the TCGA (The Cancer Genome Atlas) and HPA (The Human Protein Atlas) databases. RESULTS: We demonstrate HSYW significantly inhibits tumor growth of N87 cell-bearing Balb/c mice. Transcriptomic analysis revealed the existence of 119 differentially expressed (DE) circRNAs and 200 DE mRNAs between HSYW-treated and model mice. By associating predicted circRNA-miRNA pairs and miRNA-mRNA pairs, we constructed a circRNA-miRNA-mRNA (CMM) network. Furthermore, a protein-protein interaction (PPI) network was developed using the differential expressed mRNAs. Consequently, the reconstructed core CMM network and qRT-PCR validation indicated that 4 circRNAs, 5 miRNAs and 6 mRNAs could potentially serve as biomarkers to assess the therapeutic effects of HSYW-treated N87-bearing Balb/c mice. The TCGA and HPA databases also demonstrated that mRNA KLF15 and PREX1 had substantial differences between gastric cancer (GC) and healthy controls. CONCLUSIONS: By combining the experimental and bioinformatics analysis, this study confirms that the circRNA_00240/hsa-miR-642a-5p/KLF15 and circRNA_07980/hsa-miR-766-3p/PREX1 pathways play critical roles in HSYW-treated gastric cancer.

Structure, in vitro digestive characteristics and effect on gut microbiota of sea cucumber polysaccharide fermented by Bacillus subtilis Natto.

This study aimed to understand the structural, digestion and fecal fermentation behaviors of sea cucumber polysaccharide fermented by Bacillus subtilis Natto. Results showed that both sea cucumber polysaccharide (SP) and fermented sea cucumber polysaccharide (FSP) were sulfated polysaccharides mainly containing fucose. The physicochemical property, molecular weight, thermal property, and functional groups were no significant difference between SP and FSP, but the microscopic morphology and monosaccharide composition of FSP changed. Both SP and FSP showed similar digestion and fecal fermentation characteristics, that is, they could not be digested by saliva and gastric juice, but could be partially degraded by small intestine. Due to the decomposition of glycosidic bonds after intestinal digestion and fecal fermentation, the relative molecular mass of SP and FSP decreased. In terms of impacts on gut microbiota, Lachnospira, Bacteroides finegoldii, and Bifidobacteriaceae were significantly increased in SP, while Acinetobacter was significantly increased in FSP. This study provides a good understanding of the changes in the structure and digestive characteristics of sea cucumber polysaccharides caused by fermentation. That information will be beneficial for the development and application of new fermented sea cucumber products.

Construction of CdTe@γ-CD@RBD nanoprobe for Fe3+-sensing based on FRET mechanism in human serum.

A Fe3+ optical sensor (CdTe@γ-CD@RBD) has been developed by using gamma-cyclodextrin (γ-CD) as a bridge to link CdTe quantum dots (QDs) and a Rhodamine B derivative (RBD). The RBD molecule can enter the cavity of the γ-CD anchored onto the surfaces of the QDs. In the presence of Fe3+, the fluorescence resonance energy transfer (FRET) process from QDs to RBD will be initiated, rendering the nanoprobe to display a response to Fe3+. The degree of fluorescence quenching presented a satisfactory linearity between 10 and 60 µΜ with the incremental concentrations of Fe3+, and the calculated limit of detection was 2.51 µΜ. Through sample pretreatment procedures, the probe has been used in the determination of Fe3+ in human serum. The average recoveries in the spiking levels are ranged from 98.60 % to 107.20 % with a relative standard deviation of around 1.43 %-2.96 %. This finding leads to a method for fluorescent detection of Fe3+ with high sensitivity and exceptional selectivity. We believe that this study can give a new insight into the rational design and application of FRET-based nanoprobes.