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Vaccines against SARS-CoV-2 that induce mucosal immunity capable of preventing infection and disease remain urgently needed. In this study, we demonstrate the efficacy of Bordetella colonization factor A (BcfA), a novel bacteria-derived protein adjuvant, in SARS-CoV-2 spike-based prime-pull immunizations. We show that i.m. priming of mice with an aluminum hydroxide– and BcfA-adjuvanted spike subunit vaccine, followed by a BcfA-adjuvanted mucosal booster, generated Th17-polarized CD4+ tissue-resident memory T cells and neutralizing Abs. Immunization with this heterologous vaccine prevented weight loss following challenge with mouse-adapted SARS-CoV-2 (MA10) and reduced viral replication in the respiratory tract. Histopathology showed a strong leukocyte and polymorphonuclear cell infiltrate without epithelial damage in mice immunized with BcfA-containing vaccines. Importantly, neutralizing Abs and tissue-resident memory T cells were maintained until 3 mo postbooster. Viral load in the nose of mice challenged with the MA10 virus at this time point was significantly reduced compared with naive challenged mice and mice immunized with an aluminum hydroxide–adjuvanted vaccine. We show that vaccines adjuvanted with alum and BcfA, delivered through a heterologous prime-pull regimen, provide sustained protection against SARS-CoV-2 infection.

Extinction limits and flame microstructures of CH4 versus air (N2/O2) counterflow diffusion flames with additional CO2 to oxidizer stream under various pressure conditions were numerically investigated by a proposed decoupled strategy. The chemical and thermal effects of CO2 addition were isolated from the synergistic effect on extinction limits and flame microstructures. The results show that the extinction limits were decreased due to the CO2 addition and extended caused by the enhanced pressure, respectively. The changes of flame microstructures from far away from extinction to near extinction mainly are reflected in a narrower combustion zone and thinner flame thickness, while there is no visible displacement of the flame front location. Quantitative analyses manifest the thermal effect of CO2 addition on extinction limit is greater than chemical effect, and elevated pressure can enhance both thermal and chemical effects. An interesting phenomenon occurred between the thermal and chemical effects resulting from increasing CO2 mole fraction in an oxidizer on extinction limit; the former monotonically increase along with CO2 mole fraction, while the latter represents a kind of approximate quadratic-parabola tend along with CO2 mole fraction. The distributions of the production and consumption rate of hydroxyl (OH) radicals were presented to clarify the contribution of the kinetic term in the asymptotic solution to the extinction limits with increasing CO2 molar fraction and various pressures.

We identified novel antioxidant peptides from Pacific saury (Cololabis saira).

Umami peptides have currently become the research focus in the food umami science field and the key direction for umami agent development.

The

The denaturation of proteins (particularly myosin) due to freezing can lead to the deterioration of Penaeus vannamei. The purpose of this study was to verify the antifreeze protective effects of polyphenols screened by a molecular docking technique, and to explore their interactions with myosin after freezing treatment. It was found that the screened polyphenols could significantly increase the freezing rate and unfreezable water content of shrimp paste. The results of fluorescence spectra indicated that the hesperetin to myosin quenching process included both dynamic and static quenching, and it was primarily bound to myosin through hydrophobic interactions; The quenching of myosin by both dihydroquercetin and mangiferin was static quenching, and they were bound to myosin mainly by hydrogen bonds and van der Waals forces; All three of these polyphenols had only one binding site on myosin. Surface hydrophobicity indicated that all four polyphenols were engaged in non-covalent binding (hydrophobic interactions) with myosin. Infrared spectra demonstrated that the addition of these four polyphenols significantly increased the α-helix content of myosin. They also reduced the myosin particle size, zeta potential, and protein degeneration degree. Scanning electron microscopy revealed that the four polyphenols reduced the degree of aggregation, while more uniformly distributing the myosin particles. These observations provide a basis for the screening of polyphenols and further research into the protective mechanism of polyphenols on frozen myosin.

The study of pathogenic mechanisms in adult asthma is often marred by a lack of precise information about the natural history of the disease. Children who have persistent wheezing (PW) during the first 6 years of life and whose symptoms start before age 3 years (PWOur aim was to determine whether nasal epithelial cells from PWAir-liquid interface cultures derived from nasal epithelial cells of 36-year old participants with active asthma with and without a history of PW in childhood (10 PWA total of 35 differentially expressed genes involved in extracellular remodeling and angiogenesis distinguished the PWAsthmatic adults with a history of persistent wheeze in the first 6 years of life have specific biomolecular alterations in response to RV-A that are not present in patients without such a history. Targeting these mechanisms may slow the progression of asthma in these patients.

Drug-resistant bacteria are caused by antibiotic abuse and/or biofilm formation and have become a threat to the food industry. Carbon dot (CD)-based nanomaterials are a very promising tools for combating pathogenic and spoilage bacteria, and they possess exceptional and adjustable photoelectric and chemical properties. In view of the rapid development of CD-based nanomaterials and their increasing popularity in the food industry, a comprehensive and updated review is needed to summarize their antimicrobial mechanisms and applications in foods. This review discusses the synthesis of CDs, antimicrobial mechanisms, and their applications for extending the shelf life of food. It includes the synthesis of CDs using small molecules, polymers, and biomass. It also discusses the different antimicrobial mechanisms of CDs and their use as antibacterial agents and carriers/ligands. CD-based materials have proven effective against pathogenic and spoilage bacteria in food by inhibiting planktonic bacteria and biofilms. Optimization of the production parameters of CDs can help them achieve a full-spectral response, but degradability still requires further research.

Determination of the orientation of microfibrils within ultra-high molecular weight polyethylene (UHMWPE) fibers is considered to be an important method in evaluating the mechanical properties of the fibers. Four commonly used orientation evaluation methods are summarized and used to evaluate UHMWPE fibers at different drawing stages in the industrial line, and the results exhibit certain limitations. To overcome these limitations, a new evaluation method for quantitive characterization of UHMWPE fiber properties is proposed. Meanwhile, in situ small-angle X-ray scattering data of an UHMWPE fiber drawn at 100°C were used to perform a Pearson correlation coefficient test, and the results show a very strong correlation between the strain ratio and the evaluated coefficient.

In the present study, egg white protein (EWP) and myofibrillar protein (MP) were mixed in different ratios (0/100, 10/90, 20/80, 30/70, 40/60, 50/50, 100/0 for EWP/MP) and subjected to unheated, preheated (40°C/30 min), two-step heated (40°C/30 min, 90°C/20 min), and one-step heated (90°C/20 min) treatments to study the thermal aggregation of the two proteins. Their aggregation behavior was characterized by turbidity, active sulfhydryl, degree of protein cross-linking, protein characteristic spectra, and microscopic morphology. The results indicated that for the mixed protein system composed of EWP and MP, the mixed protein aggregation volume was larger and regular at an EWP/MP of 30/70, when the degree of cross-linking was best. When the ratio of EWP/MP was 50/50, the aggregate-protein interaction was dominant, and the excess EWP acted as a barrier to cross-linking and wrapped around the surface of the aggregates to form larger aggregates. Comparing the two-step heated and one-step heated conditions, the former is superior. PRACTICAL APPLICATION: The combination of egg white protein and myofibrillar protein can provide a theoretical reference for the protein content in surimi products, and moderate addition has an enhancing effect on surimi protein cross-linking and promotes gel formation. Excessive addition will form aggregates outside the egg white protein wrapping phenomenon, and the quality of surimi gel products will be affected.

Lithium-sulfur (Li-S) batteries hold great promise for new-generation energy storage technologies owing to their overwhelming energy density. However, the poor conductivity of active sulfur and the shuttle effect limit their widespread use. Herein, a carbon cloth decorated with thiol-containing UiO-66 nanoparticles (CC@UiO-66(SH)

Multiple sclerosis (MS) is the most prevalent demyelinating disease of the central nervous system, characterized by myelin destruction, axonal degeneration, and progressive loss of neurological functions. Remyelination is considered an axonal protection strategy and may enable functional recovery, but the mechanisms of myelin repair, especially after chronic demyelination, remain poorly understood. Here, we used the cuprizone demyelination mouse model to investigate spatiotemporal characteristics of acute and chronic de- and remyelination and motor functional recovery following chronic demyelination. Extensive remyelination occurred after both the acute and chronic insults, but with less robust glial responses and slower myelin recovery in the chronic phase. Axonal damage was found at the ultrastructural level in the chronically demyelinated corpus callosum and in remyelinated axons in the somatosensory cortex. Unexpectedly, we observed the development of functional motor deficits after chronic remyelination. RNA sequencing of isolated brain regions revealed significantly altered transcripts across the corpus callosum, cortex and hippocampus. Pathway analysis identified selective upregulation of extracellular matrix/collagen pathways and synaptic signaling in the chronically de/remyelinating white matter. Our study demonstrates regional differences of intrinsic reparative mechanisms after a chronic demyelinating insult and suggests a potential link between long-term motor function alterations and continued axonal damage during chronic remyelination. Moreover, the transcriptome dataset of three brain regions and over an extended de/remyelination period provides a valuable platform for a better understanding of the mechanisms of myelin repair as well as the identification of potential targets for effective remyelination and neuroprotection for progressive MS.

5-methylcytosine (m

PDF file, 315KB, Supplemental Figure 1: Validation of differential Meis1 and Meis2 expression between Prostate and Seminal Vesicle Epithelial Cells. Supplemental Figure 2: Gene expression profiles from 181 prostatectomy specimens of patients (Taylor dataset) using the PAM (Prediction Analysis for Microarrays) algorithm to stratify patients into two groups based on changes in expression of Meis1, Meis2, Pbx1, HoxA9, HoxB7. Supplemental Figure 3: Meis biomodule network analysis. Supplemental Methods: qPCR Analyses of Meis1 and Meis2. Supplemental Table 1: Historical datasets used in the analyses. Supplemental Table 2: Prostate epithelial cell (PrEC) versus seminal epithelial cell (SVEC) culture differentially expressed genes. Supplemental Table 3: Functional Annotation of the Prostate versus Seminal Vesicle Epithelium Signature. Supplementary Table 4: Univariate and Multivariate Cox Regression.

Purpose: The aberrant activity of developmental pathways in prostate cancer may provide significant insight into predicting tumor initiation and progression, as well as identifying novel therapeutic targets. To this end, despite shared androgen-dependence and functional similarities to the prostate gland, seminal vesicle cancer is exceptionally rare.Experimental Design: We conducted genomic pathway analyses comparing patient-matched normal prostate and seminal vesicle epithelial cells to identify novel pathways for tumor initiation and progression. Derived gene expression profiles were grouped into cancer biomodules using a protein–protein network algorithm to analyze their relationship to known oncogenes. Each resultant biomodule was assayed for its prognostic ability against publically available prostate cancer patient gene array datasets.Results: Analyses show that the embryonic developmental biomodule containing four homeobox gene family members (Meis1, Meis2, Pbx1, and HoxA9) detects a survival difference in a set of watchful-waiting patients (n = 172, P = 0.05), identify men who are more likely to recur biochemically postprostatectomy (n = 78, P = 0.02), correlate with Gleason score (r = 0.98, P = 0.02), and distinguish between normal prostate, primary tumor, and metastatic disease. In contrast to other cancer types, Meis1, Meis2, and Pbx1 expression is decreased in poor-prognosis tumors, implying that they function as tumor suppressor genes for prostate cancer. Immunohistochemical staining documents nuclear basal-epithelial and stromal Meis2 staining, with loss of Meis2 expression in prostate tumors.Conclusion: These data implicate deregulation of the Hox protein cofactors Meis1, Meis2, and Pbx1 as serving a critical function to suppress prostate cancer initiation and progression. Clin Cancer Res; 18(16); 4291–302. ©2012 AACR.

As one of the malignant tumors with high mortality, the initial symptoms of liver cancer are not obvious. In addition, the liver is the largest internal organ of the human body, and its structure and distribution are relatively complex. Therefore, in order to help doctors judge liver cancer more accurately, this paper proposes a variant model based on Unet network. Before segmentation, the image is preprocessed, and Pulse Coupled Neural Network(PCNN) algorithm is used to filterthe image adaptively to make the image clearer. For the segmentation model, the SE module is used as the input of the residual network, and then its output is connected to the Unet model through bilinear interpolation to perform the down-sampling and up-sampling operations. The Lits and collected liver cancer images are combined into a new data set for training. The results show that this method has better segmentation performance and accuracy than the original Unet method, and the dice coefficient, mIou and other evaluation indicators have increased by at least 2.1%, which is a method that can be applied to cancer segmentation.

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the main target for neutralizing antibodies (NAbs). The S protein trimer is anchored in the virion membrane in its prefusion (preS) but metastable form. The preS protein has been stabilized by introducing two or six proline substitutions, to generate stabilized, soluble 2P or HexaPro (6P) preS proteins. Currently, it is not known which form is the most immunogenic. Here, we generated recombinant vesicular stomatitis virus (rVSV) expressing preS-2P, preS-HexaPro, and native full-length S, and compared their immunogenicity in mice and hamsters. The rVSV-preS-HexaPro produced and secreted significantly more preS protein compared to rVSV-preS-2P. Importantly, rVSV-preS-HexaPro triggered significantly more preS-specific serum IgG antibody than rVSV-preS-2P in both mice and hamsters. Antibodies induced by preS-HexaPro neutralized the B.1.1.7, B.1.351, P.1, B.1.427, and B.1.617.2 variants approximately two to four times better than those induced by preS-2P. Furthermore, preS-HexaPro induced a more robust Th1-biased cellular immune response than preS-2P. A single dose (10 4 pfu) immunization with rVSV-preS-HexaPro and rVSV-preS-2P provided complete protection against challenge with mouse-adapted SARS-CoV-2 and B.1.617.2 variant, whereas rVSV-S only conferred partial protection. When the immunization dose was lowered to 10 3 pfu, rVSV-preS-HexaPro induced two- to sixfold higher antibody responses than rVSV-preS-2P in hamsters. In addition, rVSV-preS-HexaPro conferred 70% protection against lung infection whereas only 30% protection was observed in the rVSV-preS-2P. Collectively, our data demonstrate that both preS-2P and preS-HexaPro are highly efficacious but preS-HexaPro is more immunogenic and protective, highlighting the advantages of using preS-HexaPro in the next generation of SARS-CoV-2 vaccines.

Background Systemic sclerosis (SSc; also known as “scleroderma”) is an autoimmune disorder characterized by extensive fibrosis, vascular changes, and immunologic dysregulation. Baicalein (phenolic flavonoid derived from Scutellaria baicalensis Georgi) has been used to treat the pathological processes of various fibrotic and inflammatory diseases. In this study, we investigated the effect of baicalein on the major pathologic characteristics of SSc: fibrosis, B-cell abnormalities, and inflammation. Methods The effect of baicalein on collagen accumulation and expression of fibrogenic markers in human dermal fibroblasts were analyzed. SSc mice were produced by injecting bleomycin and treated with baicalein (25, 50, or 100 mg/kg). The antifibrotic features of baicalein and its mechanisms were investigated by histologic examination, hydroxyproline assay, enzyme-linked immunosorbent assay, western blotting and flow cytometry. Results Baicalein (5–120 μM) significantly inhibited the accumulation of the extracellular matrix and fibroblast activation in transforming growth factor (TGF)-β1- and platelet derived growth factor (PDGF)-induced human dermal fibroblasts, as evidenced by abrogated deposition of total collagen, decreased secretion of soluble collagen, reduced collagen contraction capability and downregulation of various fibrogenesis molecules. In a bleomycin-induced model of dermal fibrosis in mice, baicalein (25–100 mg/kg) restored dermal architecture, ameliorated inflammatory infiltrates, and attenuated dermal thickness and collagen accumulation in a dose-dependent manner. According to flow cytometry, baicalein reduced the proportion of B cells (B220+ lymphocytes) and increased the proportion of memory B cells (B220+CD27+ lymphocytes) in the spleens of bleomycin-induced mice. Baicalein treatment potently attenuated serum levels of cytokines (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor-α), chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1 beta) and autoantibodies (anti-scleroderma 70 (Scl-70), anti-polymyositis-scleroderma (PM-Scl), anti-centromeres, anti-double stranded DNA (dsDNA). In addition, baicalein treatment can significantly inhibit the activation of TGF-β1 signaling in dermal fibroblasts and bleomycin-induce mice of SSc, evidenced by reducing the expression of TGF-β1 and IL-11, as well as inhibiting both small mother against decapentaplegic homolog 3 (SMAD3) and extracellular signal-related kinase (ERK) activation. Conclusions These findings suggest that baicalein has therapeutic potential against SSc, exerting modulating B-cell abnormalities, anti-inflammatory effects, and antifibrosis.

The magnetic nanoparticles plus microwave thawing (MNPMT), a new rewarming technology entitled 'nanowarming', can serve as an effective method to achieve rapid and uniform thawing, thus reducing drip loss. The purpose of this study was to decipher the drip loss inhibitory mechanism of MNPMT in jumbo squid (Dosidicus gigas) from the perspectives of protein structure and ice crystal recrystallization. A number of different techniques such as dynamic rheology, Raman spectra, intrinsic fluorescence measurement, and ultraviolet (UV) absorption spectra were conducted to analyze myofibrillar protein conformation and stability of jumbo squid. Scanning electron microscopy (SEM) and myofibrillar fragmentation index (MFI) were used to observe the growth of ice crystals. The interaction between magnetic nanoparticles (MNPs) and ice crystals was studied by using molecular dynamic (MD) simulation.MNPMT exhibited the highest storage modulus (G') value at 90 °C, suggesting the protein conformation was more stable. The increase in α-helices, fluorescence intensity and characteristic absorption peak of MNPMT illustrated that MNPMT can effectively maintain the secondary and tertiary structure of the protein. Compared with cold storage thawing (CST) and microwave thawing (MT), the MFI value of MNPMT was significantly decreased (P 0.01). The result of MD simulation showed that MNPs displayed a tendency to gradually approach the surface of ice crystals, and induced a certain degree of damage to the ice crystal surface, thereby markedly inhibiting ice crystal recrystallization.MNPMT can reduce the drip loss by keeping the protein conformation stable and inhibiting the recrystallization of ice crystals during the thawing process. © 2022 Society of Chemical Industry.

This study improved the bioaccessibility of puerarin, a bioactive flavonoid, through incorporating co-encapsulated puerarin and β-carotene into a food-grade high internal-phase Pickering emulsion (HIPPE) system stabilised with meat proteins.

Glycoproteins are present in all living beings, and have many biological functions. The characterisation of glycan structures of plant glycoproteins has become increasingly important in biotechnology and agricultural applications. In the present work, the antioxidant activities of the okra glycoprotein were assessed. The glycan structures of the okra glycoprotein were analysed using lectin microarray combined with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. The okra glycoprotein showed relatively strong 2,2-diphenyl-1-picrylhydrazyl-scavenging ability and reducing power. In addition, the glycan structures of the okra glycoprotein mainly contained N-acetylglucosamine, mannose, and galactose. Furthermore, complex-type N-glycans were the major type of glycan structures from the okra glycoprotein. Most of the complex N-glycans of the okra glycoprotein had terminal GalNAc and Gal N-glycan structures; the glycoprotein showed a high level of fucosylated complex-type glycans. Therefore, the okra glycoprotein is a promising antioxidant. Results of the present work might serve as a reference for a better understanding of the structural information and bioactivity of okra glycoprotein.

In this study, halibut bone, a byproduct of Greenland halibut processing, was prepared into a thick soup through a non-frying process. The formation of colloidal micro-nano particles and flavor characteristics in halibut bone soup was explored. The results showed that the nutrients in halibut bones migrated to the soup continuously with the cooking process and reached the highest concentration (total sugars, 38.16 mg/100 ml; water-soluble proteins, 25.71 mg/ml; fatty acids, 2.15 g/100 ml; solids, 1.14 g/100 ml) at 150 min. Taste substances such as organic acids, 5'-nucleotides and total free amino acids (TFAAs) content in halibut bone soup also reached maximum at 150 min. At this time, results for particle size showed that MNPs with uniform size (725.62 nm) were formed, which made the bone soup milky white, stable, and had good tasting. Headspace-gas chromatography-ion mobility spectrometry results showed that a total of 59 volatile substances were detected from the halibut bone soup. The content of volatile flavor substances in the 150 min group was lower than that in the 90-120 min group. Meanwhile, aldehydes and ketones gradually became esters. PRACTICAL APPLICATION: Soup is an indispensable part of the world food culture. In order to increase the added value of Greenland halibut, halibut bone soup was studied in this paper. This study found that halibut bone soup that had not been fried, formed the MNPs and has a more harmonious and pleasant flavor. Thus, non-fried halibut bone soup is a good processing method and can improve economic efficiency.

Respiratory syncytial virus (RSV) is one of the most important causes of respiratory disease in infants, immunocompromised individuals, and the elderly. Natural infection does not result in long-term immunity, and there is no licensed vaccine. Vesicular stomatitis virus (VSV) is a commonly used vaccine vector platform against infectious diseases, and has been used as a vector for a licensed Ebola vaccine. In this study, we expressed the RSV fusion (F) protein, the RSV F protein stabilized in either a pre-fusion or a post-fusion configuration, the attachment glycoprotein (G), or the G and F proteins of RSV in combination in a VSV vector. Cotton rats were immunized with these recombinants intranasally or subcutaneously to test immunogenicity. RSV F stabilized in either a pre-fusion or a post-fusion configuration proved to be poorly immunogenic and protective when compared to unmodified F. RSV G provided partial protection and moderate levels of neutralizing antibody production, both of which improved with intranasal administration compared to subcutaneous inoculation. The most successful vaccine vector was VSV expressing both the G and F proteins after intranasal inoculation. Immunization with this recombinant induced neutralizing antibodies and provided protection from RSV challenge in the upper and lower respiratory tract for at least 80 days. Our results demonstrate that co-expression of F and G proteins in a VSV vector provides synergistic effects in inducing RSV-specific neutralizing antibodies and protection against RSV infection.