Heteropolyacid-Catalyzed Phosphorylation of Secondary Aromatic Alcohols with H-Phosphine Oxides in DMC: A Simple Protocol for C-P Bond Formation.

We successfully achieved the phosphorylation of secondary aromatic alcohols with H-phosphine oxides (less developed system) using phosphotungstic acid as a catalyst in dimethyl carbonate. The system was simple and environmentally friendly and showed better activity than traditional Lewis or Brønsted acids such as FeCl3, p-TsOH·H2O, etc., generating up to a 97% isolated yield. Control experiments indicated that the reaction did not occur through the radical pathway, and ethers and carbocation were the key intermediates in the pathway.

Interaction between a Commercial Mannoprotein and Cyanidin-3-O-glucoside-4-vinylphenol and Its Stability and Antioxidative Properties as a Novel Functional Pigment.

Hydroxyphenyl-pyranoanthocyanins, which are derived from anthocyanins and phenolic acids during the fermentation and aging of red wine, are prone to polymerization and precipitation, which largely limits their application and bioactivity research. In the present study, cyanidin-3-O-glucoside-4-vinylphenol (C3GVP), a hydroxyphenyl-pyranoanthocaynin, was prepared from C3G and p-coumaric acid, and mannoprotein (MP) was employed to improve its stability in various complex solvents by forming a stable anthocyanin-MP complex. We used scanning electron microscopy, ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, and circular dichroism spectroscopy to observe structural changes in C3GVP and MP. The results demonstrated that the intermolecular polymerization of C3GVP was mitigated and the secondary conformation of MP was changed slightly. Fluorescence spectroscopy and molecular docking indicated that C3GVP and MP interacted via hydrogen bonds and hydrophobic interactions. Importantly, the C3GVP-MP complex exhibited better thermal stability and antioxidant capacity than C3G.

Study on the mechanism of interaction between mulberry anthocyanins and yeast mannoprotein.

To solve the problem of mulberry juice colour instability caused by ultraviolet radiation, we proposed the addition of mannoprotein (MP) to improve the stabilization of mulberry juice colour. First, the purified mulberry anthocyanins extracted (MAE) were identified by UFLC-MS, and their purity was determined by liquid-phase peak area normalization. The interaction mechanism between MP and MAE at different pH values was systematically investigated by Fourier transform infrared (FTIR) spectroscopy, circular dichroism (CD) spectroscopy, fluorescence spectroscopy, and molecular docking. After conjugation with MAE, the secondary structure of MP changed slightly. The fluorescence quenching of MP by MAE was dose dependent. Thermodynamic analysis showed that the main interaction forces at pH 3.2 were hydrogen bonding and van der Waals forces, while the main force at pH 7.4 was hydrophobic forces. The molecular docking results verified the good binding properties of MP with cyanidin-3-O-glucoside (C3G) and cyanidin-3-O-rutinoside (C3R).

COVID-19 vaccination boosts the potency and breadth of the immune response against SARS-CoV-2 among recovered patients in Wuhan.

The immunity of patients who recover from coronavirus disease 2019 (COVID-19) could be long lasting but persist at a lower level. Thus, recovered patients still need to be vaccinated to prevent reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or its mutated variants. Here, we report that the inactivated COVID-19 vaccine can stimulate immunity in recovered patients to maintain high levels of anti-receptor-binding domain (RBD) and anti-nucleocapsid protein (NP) antibody titers within 9 months, and high neutralizing activity against the prototype, Delta, and Omicron strains was observed. Nevertheless, the antibody response decreased over time, and the Omicron variant exhibited more pronounced resistance to neutralization than the prototype and Delta strains. Moreover, the intensity of the SARS-CoV-2-specific CD4+ T cell response was also increased in recovered patients who received COVID-19 vaccines. Overall, the repeated antigen exposure provided by inactivated COVID-19 vaccination greatly boosted both the potency and breadth of the humoral and cellular immune responses against SARS-CoV-2, effectively protecting recovered individuals from reinfection by circulating SARS-CoV-2 and its variants.

Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine.

In influenza vaccine development, Madin-Darby canine kidney (MDCK) cells provide multiple advantages, including large-scale production and egg independence. Several cell-based influenza vaccines have been approved worldwide. We cultured H5N1 virus in a serum-free MDCK cell suspension. The harvested virus was manufactured into vaccines after inactivation and purification. The vaccine effectiveness was assessed in the Wuhan Institute of Biological Products BSL2 facility. The pre- and postvaccination mouse serum titers were determined using the microneutralization and hemagglutination inhibition tests. The immunological responses induced by vaccine were investigated using immunological cell classification, cytokine expression quantification, and immunoglobulin G (IgG) subtype classification. The protective effect of the vaccine in mice was evaluated using challenge test. Antibodies against H5N1 in rats lasted up to 8 months after the first dose. Compared with those of the placebo group, the serum titer of vaccinated mice increased significantly, Th1 and Th2 cells were activated, and CD8+ T cells were activated in two dose groups. Furthermore, the challenge test showed that vaccination reduced the clinical symptoms and virus titer in the lungs of mice after challenge, indicating a superior immunological response. Notably, early after vaccination, considerably increased interferon-inducible protein-10 (IP-10) levels were found, indicating improved vaccine-induced innate immunity. However, IP-10 is an adverse event marker, which is a cause for concern. Overall, in the case of an outbreak, the whole-virion H5N1 vaccine should provide protection.

RNF186/EPHB2 Axis Is Essential in Regulating TNF Signaling for Colorectal Tumorigenesis in Colorectal Epithelial Cells.

The receptor tyrosine kinase EPHB2 (EPH receptor B2) is highly expressed in many human cancer types, especially in gastrointestinal cancers, such as colorectal cancer. Several coding mutations of the EPHB2 gene have been identified in many cancer types, suggesting that EPHB2 plays a critical role in carcinogenesis. However, the exact functional mechanism of EPHB2 in carcinogenesis remains unknown. In this study, we find that EPHB2 is required for TNF-induced signaling activation and proinflammatory cytokine production in colorectal epithelial cells. Mechanistically, after TNF stimulation, EPHB2 is ubiquitinated by its E3 ligase RNF186. Then, ubiquitinated EPHB2 recruits and further phosphorylates TAB2 at nine tyrosine sites, which is a critical step for the binding between TAB2 and TAK1. Due to defects in TNF signaling in RNF186-knockout colorectal epithelial cells, the phenotype of colitis-propelled colorectal cancer model in RNF186-knockout mice is significantly reduced compared with that in wild-type control mice. Moreover, we find that a genetic mutation in EPHB2 identified in a family with colorectal cancer is a gain-of-function mutation that promoted TNF signaling activation compared with wild-type EPHB2. We provide evidence that the EPHB2-RNF186-TAB2-TAK1 signaling cascade plays an essential role in TNF-mediated signal transduction in colorectal epithelial cells and the carcinogenesis of colorectal cancer, which may provide potential targets for the treatment of colorectal cancer.

A Comparative Analysis of Lipid Digestion in Human Milk and Infant Formulas Based on Simulated In Vitro Infant Gastrointestinal Digestion.

To investigate the lipid digestive behaviors of human and infant formulas and analyze the differences between them, we investigated the fat globule particle size distribution, lipolysis rate, and fatty acid release of infant formulas with different fat sources and human milk using an in vitro infant digestion model. The results suggested that the particle size in infant formula increased rapidly during gastric digestion and decreased significantly after intestinal digestion, whereas the particle size in human milk increased slowly during gastric digestion but increased rapidly during intestinal digestion (p < 0.05). Despite having a larger droplet size, human milk demonstrated a very high lipolysis rate due to the presence of MFGM. In terms of the distribution of fatty acids in digestion products, the proportion of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) in vegetable oil-based infant formulas was close to that of human milk. The amount of SFAs in milk fat-based infant formulas was significantly higher than that in human milk, and the content of MUFAs in all infant formulas was significantly lower than that in human milk (p < 0.05). After digestion, the most abundant fatty acid released by human milk was C18:2n6c, while the fatty acids released by infant formulas were SFAs, such as C14:0, C16:0, and C18:0.

Batch study for Pb2+ removal by polyvinyl alcohol-biochar macroporous hydrogel bead.

In this paper, a novel adsorbent which used polyvinyl alcohol, alginate and biochar was successfully made and been used to remove lead from aqueous solutions. Batch experiments were carried out to evaluate the adsorption capacities of Pb (II) on this bead. Experimental data were analysed by the model equations like Langmuir and Freundlich and adsorption kinetic constants were determined using pseudo-first-order (PFO) and pseudo-second-order (PSO). In this study, the adsorption characteristics of Pb (II) were well fitted by the Langmuir isotherm model and pseudo-second-order (PSO) kinetic model. The adsorption of Pb (II) onto PVA-biochar beads are spontaneous and exothermic at 303-333 K by the evidence of the changes in standard Gibbs free energy, standard enthalpy and standard entropy. The maximum adsorption capacity for Pb (II) was estimated to be 176.40 mg/g, which is comparable with other adsorbents. While the maximum adsorption increased varying the pH of initial solution from 2 to 6, the effect on the adsorption amount by the sodium ion concentration is not very large. The results of EDS spectra indicated that the existence of lead in polyvinyl alcohol (PVA)-biochar bead after adsorption, which proving the adsorption of lead. In XPS spectrum, the observed Pb elements also demonstrated that the lead was adsorbed by PVA-biochar bead.

Polymer Lasing in a Periodic-Random Compound Cavity.

Simultaneous distributed feedback (DFB) lasing and linear polarized random lasing are observed in a compound cavity, which consists of a grating cavity and a random cavity. The grating cavity is fabricated by interference lithography. A light-emitting polymer doped with silver nanoparticles is spin-coated on the grating, forming a random cavity. DFB lasing and random lasing occur when the periodic-random compound cavity is optically pumped. The directionality and polarization of the random laser are modified by the grating structure. These results can potentially be used to design integrated laser sources.

A polyethylenimine-modified carboxyl-poly(styrene/acrylamide) copolymer nanosphere for co-delivering of CpG and TGF-ß receptor I inhibitor with remarkable additive tumor regression effect against liver cancer in mice.

Cancer immunotherapy based on nanodelivery systems has shown potential for treatment of various malignancies, owing to the benefits of tumor targeting of nanoparticles. However, induction of a potent T-cell immune response against tumors still remains a challenge. In this study, polyethylenimine-modified carboxyl-styrene/acrylamide (PS) copolymer nano-spheres were developed as a delivery system of unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides and transforming growth factor-beta (TGF-ß) receptor I inhibitors for cancer immunotherapy. TGF-ß receptor I inhibitors (LY2157299, LY) were encapsulated to the PS via hydrophobic interaction, while CpG oligodeoxynucleotides were loaded onto the PS through electrostatic interaction. Compared to the control group, tumor inhibition in the PS-LY/CpG group was up to 99.7% without noticeable toxicity. The tumor regression may be attributed to T-cell activation and amplification in mouse models. The results highlight the additive effect of CpG and TGF-ß receptor I inhibitors co-delivered in cancer immunotherapy.

A cross-stacked plasmonic nanowire network for high-contrast femtosecond optical switching.

We report an ultrafast optical switching device constructed by stacking two layers of gold nanowires into a perpendicularly crossed network, which works at a speed faster than 280 fs with an on/off modulation depth of about 22.4%. The two stacks play different roles in enhancing consistently the optical switching performance due to their different dependence on the polarization of optical electric fields. The cross-plasmon resonance based on the interaction between the perpendicularly stacked gold nanowires and its Fano-coupling with Rayleigh anomaly is the dominant mechanism for such a high-contrast optical switching device.

Water-soluble L-cysteine-coated FePt nanoparticles as dual MRI/CT imaging contrast agent for glioma.

Nanoparticles (NPs) are advantageous for the delivery of diagnosis agents to brain tumors. In this study, we attempted to develop an L-cysteine coated FePt (FePt-Cys) NP as MRI/CT imaging contrast agent for the diagnosis of malignant gliomas. FePt-Cys NPs were synthesized through a co-reduction route, which was characterized by transmission electron microscopy, high-resolution transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy, and dynamic light scattering. The MRI and CT imaging ability of FePt-Cys NPs was evaluated using different gliomas cells (C6, SGH44, U251) as the model. Furthermore, the biocompatibility of the as-synthesized FePt-Cys NPs was evaluated using three different cell lines (ECV304, L929, and HEK293) as the model. The results showed that FePt-Cys NPs displayed excellent biocompatibility and good MRI/CT imaging ability, thereby indicating promising potential as a dual MRI/CT contrast agent for the diagnosis of brain malignant gliomas.

Glioma-targeting micelles for optical/magnetic resonance dual-mode imaging.

Surgical resection is the primary mode for glioma treatment, while gross total resection is difficult to achieve, due to the invasiveness of the gliomas. Meanwhile, the tumor-resection region is closely related to survival rate and life quality. Therefore, we developed optical/magnetic resonance imaging (MRI) bifunctional targeted micelles for glioma so as to delineate the glioma location before and during operation. The micelles were constructed through encapsulation of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) with polyethylene glycol-block-polycaprolactone (PEG-b-PCL) by using a solvent-evaporation method, and modified with a near-infrared fluorescent probe, Cy5.5, in addition to the glioma-targeting ligand lactoferrin (Lf). Being encapsulated by PEG-b-PCL, the hydrophobic SPIONs dispersed well in phosphate-buffered saline over 4 weeks, and the relaxivity (r 2) of micelles was 215.4 mM(-1)·s(-1), with sustained satisfactory fluorescent imaging ability, which might have been due to the interval formed by PEG-b-PCL for avoiding the fluorescence quenching caused by SPIONs. The in vivo results indicated that the nanoparticles with Lf accumulated efficiently in glioma cells and prolonged the duration of hypointensity at the tumor site over 48 hours in the MR image compared to the nontarget group. Corresponding with the MRI results, the margin of the glioma was clearly demarcated in the fluorescence image, wherein the average fluorescence intensity of the tumor was about fourfold higher than that of normal brain tissue. Furthermore, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay results showed that the micelles were biocompatible at Fe concentrations of 0-100 µg/mL. In general, these optical/MRI bifunctional micelles can specifically target the glioma and provide guidance for surgical resection of the glioma before and during operation.

Transferrin-targeted magnetic/fluorescence micelles as a specific bi-functional nanoprobe for imaging liver tumor.

In order to delineate the location of the tumor both before and during operation, we developed targeted bi-functional polymeric micelles for magnetic resonance (MR) and fluorescence imaging in liver tumors. Hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) were loaded into the polymeric micelles through self-assembly of an amphiphilic block copolymer poly(ethylene glycol)-poly(ϵ-caprolactone). After, transferrin (Tf) and near-infrared fluorescence molecule Cy5.5 were conjugated onto the surface of the polymeric micelles to obtain the nanosized probe SPIO@PEG-b-PCL-Tf/Cy5.5 (SPPTC). Imaging capabilities of this nanoprobe were evaluated both in vitro and in vivo. The accumulation of SPPTC in HepG2 cells increased over SPIO@PEG-b-PCL-Cy5.5 (SPPC) by confocal microscopy. The targeted nanoprobe SPPTC possessed favorable properties on the MR and fluorescence imaging both in vitro and in vivo. The MTT results showed that the nanoprobes were well tolerated. SPPTC had the potential for pre-operation evaluation and intra-operation navigation of tumors in clinic.

Hyperosmotic stress in murine hybridoma cells: effects on antibody transcription, translation, posttranslational processing, and the cell cycle.

Mechanisms for increased antibody production in batch cultures of murine hybridoma cells in response to hyperosmotic stress were investigated. The rates of immunoglobulin transcription and protein translation and posttranslational processing were determined in control and hyperosmotic cultures. Changes in immunoglobulin transcription played a minor role in the increase in antibody production in response to hyperosmotic stress. In contrast, protein translation increased substantially in response to osmotic stress. However, the antibody translation rate remained relatively constant after correcting for the overall increase in protein translation. Cell size and intracellular antibody pool also increased in response to hyperosmolarity. The intracellular antibody pool increased proportionately with the increase in cell size, indicating that hyperosmotic cultures do not selectively increase their intracellular antibody population. Changes in cell cycle distribution in response to osmotic stress and the relationship between the cell cycle and antibody production were also evaluated. Hyperosmotic stress altered the cell cycle distribution, increasing the fraction of the cells in S-phase. However, this change was uncorrelated with the increase in antibody production rate. Immunoglobulin degradation was relatively low ( approximately 15%) and remained largely unchanged in response to hyperosmotic stress. There was no apparent increase in immunoglobulin stability as a result of osmotic stress. Antibody secretion rates increased approximately 50% in response to osmotic stress, with a commensurate increase in the antibody assembly rate. The rate of transit through the entire posttranslational processing apparatus increased, particularly for immunoglobulin light chains. The levels of endoplasmic reticulum chaperones did not increase as a fraction of the total cellular protein but were increased on a per cell basis as the result of an increase in total cellular protein. A difference in the interactions between the immunoglobulin heavy chains and BiP/GRP78 was observed in response to hyperosmotic conditions. This change in interaction may be correlated with the decrease in transit time through the posttranslational pathways. The increase in the posttranslational processing rate appears to be commensurate with the increase in antibody production in response to hyperosmotic stress.