Magterpenes A-C: Three Meroterpenoids with an Unprecedented 6/6/6/6/6 Polycyclic Skeleton Extracted from Magnolia officinalis Rehd. et Wils.

Magterpenes A-C (1-3), three unprecedented meroterpenoids featuring a unique 6/6/6/6/6 polycyclic skeleton, were isolated from the ethanol extract of Magnolia officinalis Rehd. et Wils. The compounds were obtained as racemic mixtures that were completely resolved through chiral columns. Their structures were elucidated by extensive analyses of one-dimensional (1D) and 2D nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, chemical calculations of 1H/13C NMR, and electronic circular dichroism calculations. The compounds were constructed via two Diels-Alder reactions in the proposed biosynthetic pathway. All isolates were evaluated for their nephroprotective and hepatoprotective activities. The results demonstrated that (+)-1 and (-)-1 possessed promising nephroprotective activities in a dose-dependent manner, while (-)-2 and (+)-3 exhibited moderate hepatoprotective activities.

Identifying the mechanism of polysaccharopeptide against breast cancer based on network pharmacology and experimental verification.

Polysaccharopeptide (PSP) is a potential active component in traditional Chinese medicine because of its anticancer effects on a variety of cancer cells and as immune enhancers of the immune system. Previous studies on the role of PSP in breast cancer have been limited, and the mechanism has not been clarified. This study is based on network pharmacology and molecular docking technology to predict the possible target of PSP treatment of breast cancer, and use experiments to verify the effect and mechanism of PSP on breast cancer. In this study, 287 PSP targets were obtained using SwissTargetPrediction database and PharmMapper database, and 183 breast cancer targets were obtained using DisGenNET database. By intersections of PSP targets and breast cancer targets, a total of 10 intersections were obtained. GO functional enrichment, KEGG pathway enrichment and molecular docking of these 10 target genes were performed to obtain the potential targets of PSP on breast cancer. In vitro experiments, we found that PSP significantly inhibited the proliferation and induced apoptosis of breast cancer cell lines MDA-MB-231, SUM-159 and MCF-7. Western Blot results showed that PSP could down-regulate the expression of p-JAK2 and p-STAT3 proteins. Similarly, the results of in vivo experiments showed that PSP can directly inhibit the tumor of MDA-MB-231 tumor-bearing mice, and the mechanism of action is mainly to inhibit the JAK2-STAT3 pathway. The above results were consistent with the results of network pharmacology, which provides a scientific basis for the clinical application of PSP in breast cancer patients.

Extension and Fusion of Cyclic Polyantimony Units.

The synthesis and characterization of a series of polyantimony anionic clusters are reported. The products [(NbCp)2Sb10]2-, [MSb13]3- (M = Ru/Fe), and [MSb15]3- (M = Ru/Fe) were isolated as either K(18-crown-6) or K([2.2.2]-crypt) salts. The Sb10 ring contained in the [(NbCp)2Sb10]2- cluster can be viewed as an extension of two envelope-like cyclo-Sb5 units and represents by far the largest monocyclic all-antimony species. The clusters [MSb13]3- and [MSb15]3- (M = Ru/Fe) illustrate the variability of crown-like Sb8 ring motifs and reveal the fusion of different antimony fragments featuring unique Sb-Sb chain-like units. The reported synthetic approaches involve the fabrication of a variety of distinctive polyantimony anionic clusters, enhancing our understanding of the coordination chemistry of heavier group 15 elements.

OTU deubiquitinase 7B facilitates the hyperthermia-induced inhibition of lung cancer progression through enhancing Smac-mediated mitochondrial dysfunction.

Hyperthermia, as an adjuvant therapy, has shown promising anti-tumor effects. Ovarian tumor domain-containing 7B (OTUD7B) is a deubiquitinating enzyme that is frequently found in a variety of cancers. The aim of this study is to investigate the role of OTUD7B in lung cancer hyperthermia and the underlying mechanism. A549 and CALU-3 cells were respectively exposed to 42 or 44°C for the indicated times (0, 1, 3, or 6 h) followed by incubation at 37°C for 24 h. We found a temperature- and time-dependent decrease in cell viability and an increase in apoptosis levels. Compared with 0 h, heat treatment for 3 h inhibited the proliferation and invasion of A549 cells, reduced the expression levels of mitochondrial membrane potential, IAP family members (cIAP-1 and XIAP) proteins and ubiquitination of Smac, and increased Smac protein expression. Treatment with 10 µM Smac mimic BV6 further enhanced the anti-tumor effect of hyperthermia. Next, co-IP validation showed that OTUD7B interacted with Smac and stabilized Smac through deubiquitination. OTUD7B overexpression induced damage in A549 and CALU-3 cells, while silencing OTUD7B caused opposite effects. Overexpressing OTUD7B enhanced the anti-cancer effect of hyperthermia, while si-OTUD7B reversed the anti-cancer effect of hyperthermia, which was verified in the xenograft tumor model in nude mice. Taken together, OTUD7B may serve as a potential anticancer factor with potential clinical efficacy in the thermotherapeutic treatment of lung cancer.

A murine monoclonal antibody against H5N1 avian influenza virus cross-reacts with human kidney cortex cells.

To investigate the biological characteristics of monoclonal antibodies (mAbs) against avian influenza virus (AIV) and the possible mechanism of AIV-related kidney injury. BALB/c mice were immunized with inactivated H5N1 AIV to prepare monoclonal antibody H5-32, and its subtype, titer and cross-reactivity with other influenza viruses were identified. The reactivity of monoclonal antibody with normal human tissue was analyzed by immunohistochemistry. Immunofluorescence and confocal laser scanning technique were used to detect the binding sites between mAb and human renal cortical cells, and Western blotting was used to detect the size of binding fragments. Immunohistochemical analysis confirmed that monoclonal antibody H5-32 cross-reacted with normal human kidney tissue. In human kidney, mAb H5-32 was localized in the cytoplasm of human renal tubular epithelial cells, and its binding fragment size was about 43 kDa. H5N1 AIV appears to bind to human renal tubular epithelial cells, which may be one of the mechanisms of kidney injury caused by AIV infection.

Effect of Artificial Aging Treatment on the Mechanical Properties and Regulation of Precipitated Phase Particles of High-Pressure Die-Cast Thin-Wall AlSi10MnMg Longitudinal Carrier.

This study investigates the artificial aging treatment process for AlSi10MnMg longitudinal carriers with optimal strength and ductility. Experimental results illustrate that the peak strength is observed under single-stage aging at 180 °C × 3 h, with a tensile strength of 332.5 MPa, Brinell hardness of 133.0 HB, and elongation of 5.56%. As aging time increases, tensile strength and hardness initially increase and then decrease, while elongation displays an inverse pattern. The amount of secondary phase particles at grain boundaries increases with aging temperature and holding time, but stabilizes as aging progresses; the secondary phase particles begin to grow, eventually weakening the alloy's strengthening effect. The fracture surface exhibits mixed fracture characteristics, including ductile dimples and brittle cleavage steps. Range analysis indicates that the influence of distinct parameters on mechanical properties post-double-stage aging is as follows: first-stage aging time, first-stage aging temperature, followed again by second-stage aging time, and second-stage aging temperature. For peak strength, the optimal double-stage aging process includes a first-stage aging temperature of 100 °C × 3 h and a second-stage aging temperature of 180 °C × 3 h.

Exercise preconditioning attenuates cerebral ischemia-induced neuronal apoptosis, Th17/Treg imbalance, and inflammation in rats by inhibiting the JAK2/STAT3 pathway.

BACKGROUND: Exercise preconditioning (EP) is essential for preventing ischemic stroke. Recent studies have shown that EP exerts neuroprotective effects in the cerebral ischemia-reperfusion injury model. Nonetheless, there have been few reports on the relationship between EP and the Th17/Treg balance. Moreover, it is unclear whether the JAK2/STAT3 pathway is responsible for the neuroprotective effect of EP. Therefore, we aimed to explore the impact of EP, other than the anti-inflammatory and antiapoptotic functions, on the Th17/Treg balance via the JAK2/STAT3 pathway in a middle cerebral artery occlusion (MCAO)-induced model. RESULTS: Fifty rats were randomly allocated into five groups, including the sham group (n = 10), EP+sham group (n = 10), MCAO group (n = 10), EP+MCAO group (n = 10), and EP+MCAO+JAK2/STAT3 pathway agonist (coumermycin A1, CA1) group (n = 10). The results indicated that EP alleviated neurological deficits, reduced infarct volume, and ameliorated neuronal apoptosis induced by MCAO. Additionally, the MCAO-induced Th17/Treg imbalance could be rectified by EP. The decreased levels of IL-10 and Foxp3 and increased IL-17 and RORα in the MCAO group were reversed by EP treatment. Regarding inflammation, EP reduced the concentrations of IL-6 and IL-17 and elevated those of IL-10 and TGF-ß. The neuroprotective effects of EP were accompanied by decreased phosphorylation of JAK2 and STAT3. Furthermore, CA1 pretreatment diminished all the beneficial effects of EP partially. CONCLUSION: Our findings suggest that EP contributes to attenuating neuronal apoptosis, Th17/Treg imbalance, and inflammation induced by MCAO via inhibiting the JAK2/STAT3 pathway, indicating its therapeutic potential in ischemic stroke.

Identification of Heterophilic Epitopes of H1N1 Influenza Virus Hemagglutinin.

Our previous studies found that the H1-50 monoclonal antibody (mAb) of influenza A virus hemagglutinin (HA) cross-reacted with pancreatic tissue and islet ß-cells, and further studies showed that H1-50 mAb binds to prohibitin (PHB) protein of islet ß-cells. These suggest that there are heterophilic epitopes between influenza virus HA and pancreatic tissue, which may be involved in the pathogenesis of type 1 diabetes. To further investigate these heterophilic epitopes, we screened binding epitopes of H1-50 mAb using a phage 12-peptide library. DNA sequencing and comparative analysis were performed on specific positive phage clones, and the sequence of 12-peptide binding to H1-50 mAb was obtained. The binding epitopes of H1-50 mAb in influenza virus HA were determined by sequence analysis and experimental verification, and their distribution within the three-dimensional structure was assessed by PyMOL. The results showed that H1-50 mAb specifically binds to polypeptides (306-SLPFQNIHPITIGK-319) of influenza A virus HA, located in the stem of the HA protein. However, there is no specific binding sequence between H1-50 mAb and the PHB protein of islet ß-cells in the primary structure, and we speculate that the binding of H1-50 mAb to islet ß-cells may depend on the spatial conformation. The identification of the heterophilic epitopes of H1N1 influenza virus hemagglutinin provides a new perspective on type 1 diabetes that may be caused by influenza virus infection, which may contribute to the prevention and control of influenza.

Guanine nucleotide exchange factor T exerts the cancer-promoting function in cholangiocarcinoma by enhancing the Wnt-GSK-3ß-ß-catenin cascade via regulation of Rac1/Cdc42.

Guanine nucleotide exchange factor T (GEFT), which is frequently overexpressed in cancers, is closely related to tumorigenicity and metastasis. Up to now, little is known about the relationship between GEFT and cholangiocarcinoma (CCA). The work explored the expression and function of GEFT in CCA and revealed the underlying mechanisms. Both CCA clinical tissues and cell lines expressed higher levels of GEFT than normal controls. High GEFT levels were correlated with a low overall survival rate in CCA patients. A decrease in GEFT by RNA interference caused remarkable anticancer effects in CCA cells, including retarded proliferation, delayed cell cycle progression, subdued metastatic potential and enhanced chemosensitivity. Mechanistically, GEFT mediated the Wnt-GSK-3ß-ß-catenin cascade associated with the regulation of Rac1/Cdc42. The inhibition of Rac1/Cdc42 markedly diminished the enhancing effect of GEFT on the Wnt-GSK-3ß-ß-catenin and reversed GEFT-mediated cancer-promoting effects in CCA. Moreover, the reactivation of ß-catenin diminished GEFT-reduction-induced anticancer effects. Critically, CCA cells with decreasing GEFT had a weakened ability to form xenografts in mouse models. Collectively, this work illustrates that GEFT-mediated Wnt-GSK-3ß-ß-catenin cascade represents a novel mechanism underlying CCA progression and propose a decrease in GEFT as a potential path for treatment in CCA patients.

The effect of antioxidant dietary supplements and diet-derived circulating antioxidants on vitiligo outcome: evidence from genetic association and comprehensive Mendelian randomization.

Background: Previous studies have indicated that antioxidant diets may have a positive impact on vitiligo by interfering with oxidative stress mechanisms. However, there has been a lack of research utilizing the Mendelian randomization (MR) method to analyze the relationship between antioxidant diet intake and vitiligo. Methods: In this study, we employed both univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR) approaches. The specific antioxidant dietary supplements (such as coffee intake, green tea intake, herbal tea intake, standard tea intake, and average weekly red wine intake) as well as diet-derived circulating antioxidants, including Vit. C (ascorbate), Vit. E (α-tocopherol), Vit. E (γ-tocopherol), Carotene, Vit. A (retinol), Zinc, and Selenium (N = 2,603-428,860) were significantly associated with independent single-nucleotide polymorphisms (SNPs). We obtained pooled statistics on vitiligo from a meta-analysis of three genome-wide association studies (GWASs) of European ancestry, including 4,680 cases and 39,586 controls. Inverse variance weighted (IVW) was employed as the primary analytical method, and sensitivity analysis was conducted to assess the robustness of the main findings. Results: Genetically, coffee intake [odds ratio (OR) = 0.17, 95% confidence interval (CI) 0.07-0.37, p = 1.57 × 10-5], average weekly red wine intake (OR = 0.28, 95% CI 0.08-1.00, p = 0.049), and standard tea intake (OR = 0.99, 95% CI 0.98-0.99, p = 5.66 × 10-7) were identified as protective factors against vitiligo. However, no causal effect between the intake of other antioxidant diets and vitiligo was found. Moreover, no instances of pleiotropy or heterogeneity were observed in this study. Conclusion: Our study indicates that coffee, standard tea, and red wine consumption can potentially reduce the risk of vitiligo. However, there is insufficient evidence to support that other antioxidant diets have a significant effect on vitiligo.

Regulation of survivin and caspase/Bcl-2/Cyto-C signaling by TDB-6 induces apoptosis of colorectal carcinoma LoVo cells.

Background: Colorectal carcinoma (CRC) treatment remains severe. Survivin is aberrantly overexpressed in CRC tissues and might be a potential target for CRC treatment. TDB-6 is a new taspine derivative. The purpose of this study is to investigate the inhibitory effect of TDB-6 on CRC and its underlying mechanism. Methods: The MTT assay and xenograft model were utilized to investigate the inhibitory effect of TDB-6 on LoVo cells in vitro and in vivo. Hoechst staining and Annexin-V FITC/PI analysis were conducted to study the effect of TDB-6 on LoVo cell apoptosis. Mitochondrial membrane potential (Δψm) assay was conducted to demonstrated whether TDB-6 could induce mitochondrial-mediated apoptosis of LoVo cells. Western blotting was conducted to investigate the effect of TDB-6 on survivin protein and caspase/Bcl-2/Cyto-C signaling. Results: The results indicated that TDB-6 induced mitochondria-mediated apoptosis and inhibited the proliferation and growth of LoVo cells in vitro and in vivo. Mechanistic investigation utilizing western blotting indicated that TDB-6 inhibited survivin protein expression, and the inhibitory effect was augmented by TDB-6 and YM-155 co-administration, which revealed that TDB-6 might induce apoptosis of LoVo cells by targeted regulation of survivin. TDB-6 also regulated survivin downstream signaling. It significantly increased the protein level of cleaved caspase-3, cleaved caspase-7, cleaved caspase-9, cleaved-PARP, and Cyto-C, and decreased the protein level of Bcl-2. Conclusions: TDB-6 might be a promising survivin inhibitor with great potential for CRC treatment.

Identification and analysis of B cell epitopes of hemagglutinin of H1N1 influenza virus.

The frequent variation of influenza virus hemagglutinin (HA) antigen is the main cause of influenza pandemic. Therefore, the study of B cell epitopes of HA is of great significance in the prevention and control of influenza virus. In this study, the split vaccine of 2009 H1N1 influenza virus was used as immunogen, and the monoclonal antibodies (mAbs) were prepared by conventional hybridoma fusion and screening techniques. The characteristics of mAbs were identified by ELISA method, Western-blot test and hemagglutination inhibition test (HI). Using the obtained mAbs as a tool, the B cell epitopes of HA were predicted by ELISA blocking test, sandwich ELISA method and computer simulation method. Finally, four mAbs against HA antigen of H1N1 influenza virus were obtained. The results of ELISA and computer prediction showed that there were at least two types of epitopes on HA of influenza virus. The results of this study complemented the existing methods for predicting HA epitopes, and also provided a new method for predicting other pathogenic microorganisms.

Lipopolysaccharide reduces melanin synthesis in vitiligo melanocytes by regulating autophagy.

Vitiligo is an autoimmune-related disease with a complex aetiology that involves innate immunity. Toll-like receptors (TLRs) are important parts of innate immunity and are related to a variety of autoimmune diseases, including vitiligo, through an unknown mechanism. In this study, we found that the TLR4 gene expression was increased in blood samples of patients with advanced stage vitiligo, and then, we evaluated the effect of TLR4 ligand lipopolysaccharide (LPS) on melanin synthesis in a vitiligo melanocyte cell line PIG3V and along with its mechanism. LPS suppressed melanin synthesis, downregulated the expression of melanin synthesis-related proteins and activated autophagy in vitiligo melanocytes. Inhibiting autophagy with 3-methyladenine or chloroquine blocked these effects. This suggests that LPS inhibits skin pigmentation by modulating autophagy, thus providing novel insights into the pathogenesis of vitiligo.

Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3ß Pathway and Activating Autophagy in Gastric Cancer.

Objective: Costunolide (Cos) is a sesquiterpene lactone extracted from chicory. Although it possesses anti-tumor effects, the underlying molecular mechanism against gastric cancer cells remains unclear. This study aimed to explore the effect and potential mechanism of Cos on gastric cancer. Methods: The effect of Cos on HGC-27 and SNU-1 proliferation was detected by CCK-8 and clone formation assay. The changes in cell apoptosis were determined using Hoechst 33258 and tunel staining. The morphology of autophagy was analyzed by autophagosomes with the electron microscope and LC3-immunofluorescence with the confocal microscope. The related protein levels of the cell cycle, apoptosis, autophagy and AKT/GSK3ß pathway were determined by Western blot. The anti-tumor activity of Cos was evaluated by subcutaneously xenotransplanting HGC-27 into Balb/c nude mice. The Ki67 and P-AKT levels were examined by immunohistochemistry. Results: Cos significantly inhibited HGC-27 and SNU-1 growth and induced cell cycle arrest in the G2/M phase. Cos activated intrinsic apoptosis and autophagy through promoting cellular reactive oxygen species (ROS) levels and inhibiting the ROS-AKT/GSK3ß signaling pathway. Moreover, preincubating gastric carcinoma cells with 3-methyladenine (3-MA), a cell-autophagy inhibitor, significantly alleviated the effects of Cos in inducing cell apoptosis. Conclusion: Cos induced apoptosis of gastric carcinoma cells via promoting ROS and inhibiting AKT/GSK3ß pathway and activating pro-death cell autophagy, which may be an effective strategy to treat gastric cancer.

Theory of the exterior-interior relationship between the lungs and the large intestine to explore the mechanism of Eriobotrya japonica leaf water extract in the treatment of cough variant asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Eriobotrya japonica (Thunb.) Lindl leaf (EJL) is used as a traditional Chinese medicine. E. japonica is a member of the Rosaceae family. EJL suppresses cough and relieves asthma and is widely used to treat lung diseases. In the present study, guided by the traditional Chinese medicine theory of the exterior-interior relationship between the lungs and the large intestine, the pathogenesis of cough variant asthma (CVA) and the treatment mechanism of EJL on CVA were explored. AIM OF THE STUDY: This study aimed to explore the airway remodeling effects of EJL in CVA from the perspective of the intestinal flora and the matrix metallopeptidase 9/tissue inhibitor of metalloproteinases-1 (MMP-9/TIMP-1) pathway. MATERIALS AND METHODS: The oleanolic acid and ursolic acid contents in EJL were measured by high-performance liquid chromatography (HPLC) to ensure the quality of EJL. BALB/c mice were used to establish a CVA model through ovalbumin (OVA) sensitization and atomization. EJL (at 5, 10, or 20 g/kg/day) was intragastrically administered. The body weight, ratio of total bronchial wall area (WAt) to bronchial basement membrane perimeter (Pbm) (WAt/Pbm), the number of coughs, and cough latency were measured. The pathological changes of the lung tissue were analyzed by hematoxylin and eosin (HE) staining. The expression of α-smooth muscle actin (α-SMA) was measured by immunohistochemistry (IHC). The expressions of MMP-9 and TIMP-1 were detected in the lung tissue by reverse transcription quantitative polymerase chain reaction (RT-PCR) and Western blot analysis. Additionally, an Illumina Hiseq platform was used for 16S ribosomal DNA (16S rDNA) high-throughput sequencing to detect the intestinal flora in feces samples. RESULTS: The results confirmed the positive effects of EJL on CVA. After administration of EJL, the number of coughs and the WAt/Pbm ratio decreased, the cough latency was prolonged, body weight was increased, and the general status was better than that of the CVA model mice. HE staining revealed that EJL decreased inflammatory cell infiltration and improved the histopathological structure of the lung tissue. EJL also showed significant inhibitory effects on the expression of α-SMA, MMP-9, and TIMP-1 and normalized the intestinal flora to a certain extent. CONCLUSIONS: The results demonstrated that EJL alleviated airway remodeling of CVA mice, which might be related to the inhibition of the MMP-P/TIMP-1 pathway and the regulation of intestinal flora.

Thermosensitive and Conductive Hybrid Polymer for Real-Time Monitoring of Spheroid Growth and Drug Responses.

Three-dimensional (3D) cell culture based on polymer scaffold provides a promising tool to mimic a physiological microenvironment for drug testing; however, the next-generation cell activity monitoring technology for 3D cell culture is still challenging. Conventionally, drug efficacy evaluation and cell growth heavily rely on cell staining assays, using optical devices or flow cytometry. Here, we report a dual-function polymer scaffold (DFPS) composed of thermosensitive, silver flake- and gold nanoparticle-decorated polymers, enabling conductance change upon cell proliferation or death for in situ cell activity monitoring and drug screening. The cell activity can be quantitatively monitored via measuring the conductance change induced by polymeric network swelling or shrinkage. This novel dual-function system (1) provides a 3D microenvironment to enable the formation and growth of tumor spheroid in vitro and streamlines the harvesting of tumor spheroids through the thermosensitive scaffold and (2) offers a simple and direct quantitative method to monitor 3D cell culture in situ for drug responses. As a proof of concept, we demonstrated that a breast cancer stem cell line MDA-MB-436 was able to form cell spheroids in the scaffold, and the conductance change of the sensor exhibited a linear relationship with cell concentration. To examine its potential in drug screening, cancer spheroids in the cell sensor were treated with paclitaxel (PTX) and docetaxel (DTX), and predicted quantitative evaluation of the cytotoxic effect of drugs was established. Our results indicated that this cell sensing system may hold promising potential in expanding into an array device for high-throughput drug screening.

Amorphization mechanism of SrIrO3 electrocatalyst: How oxygen redox initiates ionic diffusion and structural reorganization.

The use of renewable electricity to prepare materials and fuels from abundant molecules offers a tantalizing opportunity to address concerns over energy and materials sustainability. The oxygen evolution reaction (OER) is integral to nearly all material and fuel electrosyntheses. However, very little is known about the structural evolution of the OER electrocatalyst, especially the amorphous layer that forms from the crystalline structure. Here, we investigate the interfacial transformation of the SrIrO3 OER electrocatalyst. The SrIrO3 amorphization is initiated by the lattice oxygen redox, a step that allows Sr2+ to diffuse and O2- to reorganize the SrIrO3 structure. This activation turns SrIrO3 into a highly disordered Ir octahedral network with Ir square-planar motif. The final Sr y IrO x exhibits a greater degree of disorder than IrO x made from other processing methods. Our results demonstrate that the structural reorganization facilitated by coupled ionic diffusions is essential to the disordered structure of the SrIrO3 electrocatalyst.

Neutralizing antibody PR8-23 targets the footprint of the sialoglycan receptor binding site of H1N1 hemagglutinin.

Influenza virus cause seasonal influenza epidemic and seriously sporadic influenza pandemic outbreaks. Hemagglutinin (HA) is an important target in the therapeutic treatment and diagnostic detection of the influenza virus. Variation in the sialic acid receptor binding site leads to strain-specific binding and results in different binding modes to the host receptors. Here, we evaluated the neutralizing activity and hemagglutination inhibition activity of a prepared murine anti-H1N1 monoclonal antibody PR8-23. Then we identified the epitope peptide of antibody PR8-23 by phage display technique from phage display peptide libraries. The identified epitope, 63-IAPLQLGKCNIA-74, containing two α-helix and two ß-fold located at the footprint of the sialoglycan receptor on the RBS in the globular head domain of HA. It broads the growing arsenal of motifs for the amino acids on the globular head domain of HA in sialic acid receptor binding site and neutralizing antibody production.

Syntenin regulates melanogenesis via the p38 MAPK pathway.

Melanogenesis is the synthesis of the skin pigment melanin, which serves a critical role in the study of pigmentary skin diseases. Syntenin has been identified as a melanosome protein, but its role in melanogenesis is not completely understood. The present study aimed to investigate the effects and mechanisms underlying syntenin on melanogenesis in immortalized human melanocytes. Depletion of syntenin expression increased both tyrosinase (Tyr) activity and melanin content. Syntenin silencing also increased the protein expression levels of Tyr, pre­melanosomal protein and microphthalmia­associated transcription factor. In addition, the results indicated that syntenin regulated melanogenesis by upregulating the phosphorylation of p38 mitogen­activated protein kinase (p38 MAPK). Taken together, these findings suggested that the regulation of melanogenesis by syntenin may be mediated by the activation of p38 MAPK and that syntenin might provide new insights into the pathogenesis of pigmented diseases.

The Improvement of Nanoemulsion Stability and Antioxidation via Protein-Chlorogenic Acid-Dextran Conjugates as Emulsifiers.

In this experiment, the peanut protein isolate (PPI), soybean protein isolate (SPI), rice bran protein isolate (RBPI), and whey protein isolate (WPI) were modified by linking chlorogenic acid covalently and linking dextran by Maillard reaction to prepare protein-chlorogenic acid-dextran (PCD) conjugates. As for structures, conformational changes of conjugates were determined by Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE), Fourier transform infrared (FT-IR), and fluorescence measurements. The molecular weights of PCD conjugates became larger, the structure became disorder, and the amino acid residues inside the protein were exposed to the polar environment when compared to protein-chlorogenic acid (PC) and native proteins (NPs). As for properties, the interfacial tension reduced and antioxidant activity of PCD conjugates enhanced in varying degrees. Based on this, PCD conjugates were used as emulsifiers in order to investigate the properties of nanoemulsions and compared with PC conjugates and NPs. The mean droplet diameters (MDD) results showed that the nanoemulsions that were stabilized by PCD conjugates had the smallest particle sizes and exhibited uniformly dispersed spherical shapes. The storage and oxidative stabilities of PCD conjugates were also significantly improved. In comparison, nanoemulsion that was stabilized by PPI-chlorogenic acid-dextran conjugate had the smallest particle size and optimal stability among four protein stabilized nanoemulsions.