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Background: Central pancreatectomy is a surgical procedure for benign and low-grade malignant tumors which located in the neck and proximal body of the pancreas that facilitates the preservation of pancreatic endocrine and exocrine functions but has a high morbidity rate, especially postoperative pancreatic fistula (POPF). The aim of this systematic review and meta-analysis was to evaluate the safety and effectiveness between minimally invasive central pancreatectomy (MICP) and open central pancreatectomy (OCP) basing on perioperative outcomes. Methods: An extensive literature search to compare MICP and OCP was conducted from October 2003 to October 2023 on PubMed, Medline, Embase, Web of Science, and the Cochrane Library. Fixed-effect models or random effects were selected based on heterogeneity, and pooled odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Results: A total of 10 studies with a total of 510 patients were included. There was no significant difference in POPF between MICP and OCP (OR = 0.95; 95% CI [0.64, 1.43]; P= 0.82), whereas intraoperative blood loss (MD = − 125.13; 95% CI [− 194.77, -55.49]; P< 0.001) and length of hospital stay (MD = − 2.86; 95% CI [− 5.00, − 0.72]; P= 0.009) were in favor of MICP compared to OCP, and there was a strong trend toward a lower intraoperative transfusion rate in MICP than in OCP (MD = 0.34; 95% CI [0.11, 1.00]; P= 0.05). There was no significant difference in other outcomes between the two groups. Conclusion: MICP was as safe and effective as OCP and had less intraoperative blood loss and a shorter length of hospital stay. However, further studies are needed to confirm the results.

Byline: Zhijin. Chen, Lin. Liu, Ziyin. Wang, Ju. Gong, Ning. Xia, Wei. Huang, Jian. Lu, Zhongmin. Wang Objective and Aims: To assess percutaneous vesselplasty's safety and efficacy in treating pathological [...]

The development of preparation methods for XOFs, as a new class of organic frameworks, plays a crucial role in shaping their structures, functions, and potential applications. In this study, we presented the construction of chiral supramolecular 2D halogen-bonded organic frameworks (XOFs) through a post-synthetic modification strategy. A linear halogen-bonded organic polymer (XOP), XOP-DPBA, decorated with aldehyde groups, was initially prepared to validate the feasibility of post-synthetic modification for XOF construction and functionalization. XOP-DPBAexhibited excellent reactivity with amines, forming imine bonds. By utilizing this reactivity, a series of cross-linked 2D XOFs were efficiently prepared through post-synthetic modified cross-linking reactions. Furthermore, we successfully introduced chiral α/β-cyclodextrins (α/β-CD) into the XOF skeletons viahost-guest interactions, resulting in the fabrication of chiral supramolecular 2D XOFs. These chiral XOFs displayed the induced circular dichroism (ICD) signals and assembled them into helical fibers. The post-synthetic modification strategy demonstrated its versatility and simplicity for the construction and functionalization of XOFs.

ABSTRACT The pronounced decrease of effective thermal conductivity (ETC) due to cracking behavior of concrete will change the temperature profile in concrete structures, indirectly inducing the redistribution of thermal stresses. [...]

Postoperative pancreatic fistula (POPF) is a severe complication after distal pancreatectomy (DP); however, it is unclear how to effectively reduce the incidence. The purpose of this meta-analysis is to determine whether reinforced stapling reduces POPF after DP. From February 2007 to April 2023, a comprehensive search of electronic data and references was conducted in PubMed/Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. In this study, the perioperative outcomes were evaluated for the reinforced stapler (RS) group and the standard stapler (SS) group in DP using Review Manager Software. Using fixed- or random-effects models, pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. In total, three randomized clinical trials (RCTs) with 425 patients and five observational clinical studies (OCS) with 318 patients were included. In pooled meta-analyses from RCTs, there was no difference between the two groups in the incidence of POPF (OR = 0.79; 95% CI [0.47,1.35]; P= 0.39), intraoperative blood loss (MD = 10.66; 95% CI [− 28.83,50.16]; P= 0.6), operative time (MD = 9.88; 95% CI [− 8.92,28.67]; P= 0.3), major morbidity (OR = 1.12; 95% CI [0.67,1.90]; P= 0.66), reoperation (OR = 0.97; 95% CI [0.41,2.32]; P= 0.95), readmission (OR = 0.99; 95% CI [0.57,1.72]; P= 0.97) or hospital stay (MD = − 0.95; 95% CI [− 5.22,3.31]; P= 0.66). However, the results of POPF and readmission were favorable for RS in the OCS group.

The structural diversity and the various applications of organic frameworks have attracted much attention in recent years. Recently, halogen-bonded organic frameworks (XOFs) became a novel member of these materials, thereby facilitating the exploration of the interesting structures as well as functions. Here we present two types of [N···I+···N] connected XOFs (XOF-TPyand XOF-TPEB) with two tridentate ligands as building blocks. XOF-TPyand XOF-TPEBwere characterized by 1H NMR, UV–vis, X-ray photoelectron spectroscopy (XPS), IR, SEM, and HR-TEM. Two-dimensional (2D) structural models were established based on powder X-ray diffraction (PXRD) data and theoretical simulations. Further experiment showed that these XOFs were excellent iodinating agents for the substituted arylboronic acids with either the electron-donating or electron-withdrawing groups upon heating without any catalyst. This research not only brings further understanding to the XOFs but also extends the applications of XOFs.

All currently available SARS-CoV-2 vaccines are administered by intramuscular injection. We aimed to evaluate the safety and immunogenicity of a live-attenuated influenza virus vector-based SARS-CoV-2 vaccine (dNS1-RBD) administered by intranasal spray in healthy adults.

ABSTRACTIntroductionTriple-negative breast cancer (TNBC) is a subtype of severely aggressive breast cancer that lacks the expression of oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 (HER2) and is highly metastatic and related to a poor prognosis. Current standard treatments are still limited to systemic chemotherapy, radiotherapy, and surgical resection. More effective treatments are urgently needed.Areas coveredThe immunogenicity of TNBC has provided opportunities for the development of targeted immunotherapy. In this review, we focus on the recent development in antibody-based drug modalities, including angiogenesis inhibitors, immune checkpoint inhibitors, antibody−drug conjugates, immunoconjugates, T cell-redirecting bispecific antibodies and CAR-T cells, and their mechanisms of action in TNBC.Expert opinionAt present, the treatment of TNBC is still a major challenge that needs to be addressed. Novel immunotherapies are promising opportunities for improving the management of this aggressive disease.

Passion fruit peel contained various phenolic compounds with α-glucosidase and α-amylase inhibitory activities in vitro. However, the bound state and glycosylated forms hindered their active expression. In this article, β-glucosidase-producing Lactobacilliwere inoculated into fermented peels for targeted metabolism. The results showed that the release of bound polyphenols and the increase of free polyphenols were significantly correlated with β-glucosidase activity. The strain G1 with high enzyme activity degraded 48.20% of the bound polyphenols after 24 h. The ability of extracts to inhibit α-glucosidase and α-amylase activities was significantly enhanced and closely related to the content of free polyphenols (r = −0.96 and −0.88, P < 0.001). Computer-assisted screening identified 38 phenolic compounds as potential dual inhibitors of α-glucosidase and α-amylase. Among them, 22 α-glucosidase inhibitors and 24 α-amylase inhibitors were identified for the first time. Various inhibitors, including phenolic acids, flavones, and flavonols, increased in content after fermentation. The total content of 14 glycosylated polyphenols decreased to 28.38% at 48 h, which was opposite to the aglycone. Molecular docking indicated that glycosylated polyphenols bind to β-glucosidase through hydrogen bonds and van der Waals forces. Different glycosylations at the C-3 position of quercetin bound at same sites to β-glucosidase. This study contributes to the theory of enhancing the functional activity of natural products through targeted fermentation transformation.

Recently, single-particle cryo-electron microscopy (cryo-EM) has become an indispensable method for determining macromolecular structures at high resolution to deeply explore the relevant molecular mechanism. Its recent breakthrough is mainly because of the rapid advances in hardware and image processing algorithms, especially machine learning. As an essential support of single-particle cryo-EM, machine learning has powered many aspects of structure determination and greatly promoted its development. In this article, we provide a systematic review of the applications of machine learning in this field. Our review begins with a brief introduction of single-particle cryo-EM, followed by the specific tasks and challenges of its image processing. Then, focusing on the workflow of structure determination, we describe relevant machine learning algorithms and applications at different steps, including particle picking, 2-D clustering, 3-D reconstruction, and other steps. As different tasks exhibit distinct characteristics, we introduce the evaluation metrics for each task and summarize their dynamics of technology development. Finally, we discuss the open issues and potential trends in this promising field.

Context Soybean cyst nematode is the most important pest of soybean (Glycine max (L.) Merr.) worldwide, causing serious yield losses. Lignin is a vital component of the cell wall that can provide resistance to cyst nematode. O -Methyltransferase (OMT) is a key enzyme involved in lignin metabolism in the phenylalanine pathway. Aims In this study, the soybean OMT gene family was systematically identified, and the expression response of GmOMT to abiotic and cyst nematode stresses was investigated. Methods In total, 67 OMT genes were obtained from the soybean genome through conserved structural domain alignment. GmOMT expression under abiotic stress of soybean was examined based on next-generation RNA sequencing (RNA-Seq). Comprehensive analysis of the genes was conducted, including gene structure, conserved structure, affinity, chromosomal localisation, functional prediction, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, promoter analysis, and expression pattern analysis. Key results The 67 GmOMT genes were identified and distributed among the 19 chromosomes. The GmOMT genes were classified into two categories: CCOMT subfamily and COMT subfamily. GmOMT genes from the same family shared similar gene structures and conserved structural domains, which have undergone strong purifying selection during evolution. The presence of multiple cis -responsive elements in the promoters of GmOMT genes suggested that members of the soybean OMT family may be involved in growth and developmental activities and resistance to stress in soybean. Conclusions GmOMT expression under abiotic stress showed that some of the genes may play a role in abiotic stress. Of them, GmCCOMT3 and GmCCOMT7 were closely associated with lignin synthesis based on both RNA-Seq and quantitative real-time PCR analysis. Implications These findings are valuable for elucidating the function of GmOMT in lignin metabolism and the relationship with SCN resistance.

Glioblastoma (GBM) is the deadliest brain malignancy without effective treatments. Here, we reported that epidermal growth factor receptor-targeted chimeric antigen receptor T cells (EGFR CAR-T) were effective in suppressing the growth of GBM cells in vitroand xenografts derived from GBM cell lines and patients in mice. However, mice soon acquired resistance to EGFR CAR-T cell treatment, limiting its potential use in the clinic. To find ways to improve the efficacy of EGFR CAR-T cells, we performed genomics and transcriptomics analysis for GBM cells incubated with EGFR CAR-T cells and found that a large cohort of genes, including immunosuppressive genes, as well as enhancers in vicinity are activated. BRD4, an epigenetic modulator functioning on both promoters and enhancers, was required for the activation of these immunosuppressive genes. Accordingly, inhibition of BRD4 by JQ1 blocked the activation of these immunosuppressive genes. Combination therapy with EGFR CAR-T cells and JQ1 suppressed the growth and metastasis of GBM cells and prolonged survival in mice. We demonstrated that transcriptional modulation by targeting epigenetic regulators could improve the efficacy of immunotherapy including CAR-T, providing a therapeutic avenue for treating GBM in the clinic.

Background and aimsDeletion of 15-nucleotide or 18-nucleotide (nt) covering preS1 ATG frequently arises during chronic infection with HBV genotypes B and C. Since the second ATG is 33nt downstream, they truncate large (L) envelope protein by 11 residues like wild-type genotype D. This study characterised their functional consequences.MethodsHBV genomes with or without deletion were amplified from a patient with advanced liver fibrosis and assembled into replication competent 1.1mer construct. Deletion, insertion or point mutation was introduced to additional clones of different genotypes. Viral particles concentrated from transfected HepG2 cells were inoculated to sodium taurocholate cotransporting polypeptide (NTCP)-reconstituted HepG2 (HepG2/NTCP) cells or differentiated HepaRG cells, and HBV RNA, DNA, proteins were monitored.ResultsFrom transfected HepG2 cells, the 15-nt and 18-nt deletions increased HBV RNA, replicative DNA and extracellular virions. When same number of viral particles was inoculated to HepG2/NTCP cells, the deletion mutants showed higher infectivity. Conversely, HBV infectivity was diminished by putting back the 18nt into naturally occurring genotype C deletion mutants and by adding 33nt to genotype D. Infectivity of full-length genotype C clones was also enhanced by mutating the first ATG codon of the preS1 region but diminished by mutating the second in-frame ATG. Removing N-terminal 11 residues from preS1 peptide 2–59 of genotype C potentiated inhibition of HBV infection and enhanced binding to HepG2/NTCP cells.ConclusionsThe 15-nt and 18-nt deletions somehow increase HBV RNA, replicative DNA and virion production. Shortened L protein is more efficient at mediating HBV infection.

Citrinin (CIT), a known nephrotoxic mycotoxin, is mainly produced by Penicillium, Aspergillus, and Monascusspecies. It is a natural contaminant in cereal grains, foods, and feedstuff. Liupao tea (or Liubao tea) is a typical Chinese dark tea obtained via indigenous tea fermentation facilitated by microorganisms. Certain fungi present in Liupao tea that may produce CIT are a potential threat to consumer health. In the present study, various potential toxigenic mycoflora and the natural occurrence of CIT in Liupao tea were surveyed via the culture-dependent method, high performance liquid chromatography–fluorescence detection (HPLC–FLD), and ultrahigh performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). Total mold counts ranged from 3.5 × 102CFU/g to 2.1 × 106CFU/g tea in 28 tea samples. A total of 218 fungal isolates belonging to five genera and 23 species were identified. Some of these strains, such as Aspergillus ochraceus, Aspergillus oryzae, Penicillium citrinum, and Penicillium chrysogenum, may potentially be a CIT-producing species. In addition, 32.7% of 113 Liupao tea samples were contaminated with CIT at concentrations ranging from 7.8 to 206.1 μg/kg. These CIT concentrations in Liupao tea are chiefly attributed to climatic conditions and water activity during storage that favor fungal proliferation and mycotoxin production. However, CIT could not be detected in Liupao tea stored for over 10 years. These results provide the first information about the potential toxigenic mycoflora and natural occurrence of CIT in Liupao tea. Therefore, storage conditions and fungal community must be monitored to ensure the quality of Liupao tea.

Abstract

Flavour is an essential quality characteristic of soymilk; however, it contains volatile compounds unacceptable to consumers. Hexanal is the most important flavour compound that gives a sensory beany, grassy flavour in the soymilk. An effective way to reduce hexanal content in soymilk is to screen for and utilise cultivars of soybean (Glycine max (L.) Merr.) with lower hexanal content. The objective of the present study was to dissect the genetic basis of hexanal content in soybean seed by using genome-wide association analysis (GWAS), thereby providing guidance for the selection and breeding of soybean varieties with low hexanal content. We used 24651 single-nucleotide polymorphisms (SNPs) and screened seeds from 111 cultivated soybean accessions to identify quantitative trait nucleotides (QTNs) affecting hexanal content. We discovered 14 novel QTNs located on five different chromosomes that are significantly associated with hexanal content in soybean seed. Among these, 11 QTNs co-localised with quantitative trait loci previously found in linkage or association mapping studies related to protein, oil and/or fatty acid content in soybean seed. We also identified some candidate genes involved in amino acid metabolism, protein content, lipid metabolism and hormone metabolism. Six cultivars with low hexanal content were identified by screening. This is the first GWAS study on hexanal content in soybean seed, and a number of QTNs and candidate genes were identified. Some of these may be useful to breeders for the improvement of marker-assisted breeding efficiency for low hexanal content and may be useful for exploring possible molecular mechanisms underlying hexanal content in soybean seed.

Association analysis is an alternative to conventional, family-based methods for detecting the location of gene(s) or quantitative trait loci (QTLs), and provides relatively high resolution in terms of defining the genome position of a gene or QTL. Flavour is an essential quality characteristic of soymilk; however, soymilk contains volatile compounds unacceptable to consumers. One of main constituents in the volatiles of normal soymilk is 2-heptenal, which is thought to be a degradative oxidation product of polyunsaturated acids. In this study, a genome-wide association study using 24651 single-nucleotide polymorphisms (SNPs) was performed to identify quantitative trait nucleotides (QTNs) controlling 2-heptenal content in soybean (Glycine max (L.) Merr.) seed from a natural population of 110 soybean germplasm accessions. We detected 62 significant QTNs located on 18 different chromosomes that are significantly associated with 2-heptenal content in soybean seed. Among these, 17 QTNs co-localised with QTLs previously found to be related to protein, oil and/or fatty acid content in soybean seed. We also identified some candidate genes involved in lipid metabolism. These findings further our understanding of the genetic basis of 2-heptenal content in soybean seed and the improvement of marker-assisted breeding efficiency, which will be important for breeding soybean cultivars with low 2-heptenal content.

ObjectiveThis study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models.MethodsA series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically.ResultsAmong the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance.ConclusionsThe novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.

The increase of polysaccharides in the dark tea pile process is thought to be connected to the cell wall polysaccharides’ breakdown. However, the relationship between tea polysaccharides (TPSs) and tea cell wall polysaccharides has not been further explored. In this study, the structural changes in the cell wall polysaccharides [e.g., cellulose, hemicellulose (HC), and pectin] in Liupao tea were characterized before and after traditional fermentation and tank fermentation. Additionally, the degradation mechanism of tea cell wall polysaccharides during fermentation was assessed. The results showed that cellulose crystallinity decreased by 11.9–49.6% after fermentation. The molar ratio of monosaccharides, such as arabinose, rhamnose, and glucose in HC, was significantly reduced, and the molecular weight decreased. The esterification degree and linearity of water-soluble pectin (WSP) were reduced. TPS content increases during pile fermentation, which may be due to HC degradation and the increase in WSP caused by cell wall structure damage. Microorganisms were shown to be closely associated with the degradation of cell wall polysaccharides during fermentation according to correlation analyses. Traditional fermentation had a greater effect on the cellulose structure, while tank fermentation had a more noticeable impact on HC and WSP.

Objective The superficial zone cells in articular cartilage (SFZCs) have been identified as stem/progenitor chondrocytes and promoted cell self-renewal in the osteoarthritis (OA). Several studies emphasized the involvement of senescence and autophagy in OA. Interleukin-1β (IL-1β) is one of the main inflammatory mediators of OA, and whether it induces senescence and autophagy in SFZCs remains unclear. The present study aimed to investigate autophagy flux, mitochondrial function, and intracellular reactive oxygen species (ROS) that resulted in senescence in SFZCs induced by IL-1β.Methods Using western blotting, reverse transcription-quantitative PCR, immunofluorescence, intracellular ROS detection, mitochondrial staining, and determination of mitochondrial membrane potential, we tested senescence and autophagy markers in SFZCs induced by IL-1β in vitro. The consequences of mitochondrial function and ROS were also studied with IL-1β-induced senescence.Results IL-1β treatment decreased SFZC proliferation, induced SFZC senescence, and reduced SFZCs’ chondrogenic differentiation capacity. Moreover, IL-1β impaired autophagy flux, and the autophagy activator, rapamycin, attenuated the senescence of SFZCs. IL-1β-induced autophagy defect resulted in mitochondrial dysfunction and overproduction of ROS, and autophagy activation notably protected against mitochondrial dysfunction and reduced the levels of ROS. Moreover, antioxidant N-acetylcysteine reversed the senescence of IL-1β in SFZCs.Conclusion IL-1β promotes autophagy impairment and subsequently results in dysfunctional mitochondria and overproduction of ROS, which finally causes SFZC senescence.

Cinnamonis widely used as a medicinal herb and a culinary spice. The major bioactive component of cinnamonis cinnamonessential oil (CEO). CEO has been reported to have anti-inflammatory and antioxidant effects, but its mechanism of action is not known. In this study, metabolomics was combined with “weighting coefficients” from network pharmacology to identify key pathways and targets, differential metabolites and key metabolic pathways for the therapeutic effects of CEO on Hyperuricemia (HUA), and to precisely investigate the molecular mechanisms of the therapeutic effects of CEO on HUA. Metabolomic analysis revealed that abnormal l-glutamate metabolism and dysregulation of Arachidonic acid (AA) metabolic pathways exacerbated inflammatory responses and oxidative stress, subsequently mediating pathological changes in HUA and exacerbating renal tissue damage. Pharmacodynamic validation showed that CEO alleviated the renal inflammatory response by inhibiting hepatic xanthine oxidase activity, upregulating superoxide dismutase and glutathione peroxidase levels, and downregulating malondialdehyde levels, synergistically inhibiting NLRP3 inflammasome activation, suppressing downstream inflammatory Interleukin-1 beta (IL-1β) and Interleukin-18 (IL-18) secretion, and enhancing antioxidant levels. Additionally, CEO exerted renal protective effects by upregulating the renal transporters OAT1 and ABCG2 and downregulating the GLUT9 and URAT1 levels, resulting in the downregulation of uric acid production and the alleviation of renal tubular lesions. This suggests that CEO could be considered as a potential functional food for kidney damage caused by hyperuricemia.

Hexanol is a major compound contributing to the off-flavors (the bean-like odor) of soybean derived soymilk. The most effective way to reduce the off-flavors of soymilk is the screening and utilization of soybean cultivars with improved hexanol content. However, no genome-wide genetic analysis for this particular trait has been conducted to date. The objective of the present study was to dissect the genetic basis of hexanol content in soybean seed through genome-wide association analysis (GWAS). A total of 105 soybean accessions were analyzed for hexanol content in a three-year experiments and genotyped by sequencing using the specific locus amplified fragment sequencing (SLAF-seq) approach. A total of 25 724 single nucleotide polymorphisms (SNPs) were obtained with minor allele frequencies (MAF)>5%. GWAS showed that 25 quantitative trait nucleotides (QTNs) were significantly associated with the hexanol concentration in soybean seed. These identified QTNs distributed on different genomic regions of the 15 chromosomes. A total of 91 genes were predicted as candidate genes underlying the seed hexanol level and six candidates were predicted possibly underlying the seed hexanol by gene based association. In this study, GWAS has been proven to be an effective way to dissect the genetic basis of the hexanol concentration in multiple genetic backgrounds. The identified beneficial alleles and candidate genes might be valuable for the improvement of marker-assisted breeding efficiency for low hexanol level and help to explore possible molecular mechanisms underlying hexanol content in soybean seed.

The ability of a strain to produce citrinin was analysed in the growth inhibition zone using HPLC and UHPLC–MS. A total of 12 Penicillium citrinumstrains isolated from Liupao tea were inoculated onto tea leaves and their capability for citrinin production were studied using different water content (15–45%) and temperatures (15–40 °C). The results provided a theoretical base for the safe manufacture of Liupao tea. Five strains of P. citrinumproduced a clear growth inhibition zone with diameters of 11–22 mm. The citrinin contents in the liquid cultures of the 12 strains of P. citrinumranged from 0.03 to 14.5 μg/mL. The citrinin contents of the teas with initial water content of 15 and 25% and those inoculated with P. citrinumwere below the limit of detection during the fermentation. The citrinin content of the teas with initial water contents of 35 and 45% at 25 °C increased rapidly at first and then decreased during the fermentation. Similarly, the citrinin contents of the teas at 15 and 25 °C rapidly increased and then decreased. Meanwhile, P. citrinumwas unable to produce citrinin at 35 and 40 °C. The optimum conditions were 45% water and 25 °C, generating the highest citrinin yield of 181 ng/g, which was higher than the limit of 50 ng/g citrinin in red yeast rice that can cause harm to human health. The highest citrinin yield in tea fermented for 50 days was 34.8 ng/g for stored teas with proper conditions. Therefore, storing teas with a low water content and temperature can reduce the content of citrinin.

Chemical compounds in soybean (Glycine max (L.) Merr.) seed have great effects on the flavour and taste of soymilk. The 1-octen-3-ol content in soybean seed could produce sensory off-flavours (mushrooms, lavender, rose and hay flavour) during the processing of soymilk. The most effective way to reduce off-flavours of soymilk is the screening and utilisation of soybean cultivars with reduced 1-octen-3-ol content. However, genomic study of 1-octen-3-ol in soybean has not previously been reported. In the present work, a natural population of 90 diverse soybean accessions was used to dissect the genetic basis of 1-octen-3-ol content in soybean seed through genome-wide association analysis by using 26822 single nucleotide polymorphisms (SNPs). Twenty-one novel quantitative trait nucleotides (QTNs) were thus identified to be associated with 1-octen-3-ol content in soybean seed. Among them, 13 QTNs overlapped with, or were located in, the linked regions of known QTNs for protein, oil and/or fatty acid content in soybean seed. The functional genes located in the 200-kb genomic region of each peak SNP were considered possible candidates related to 1-octen-3-ol, such as genes involved in amino acid metabolism, protein content, and hormone metabolism. The identified loci with beneficial alleles and the candidate genes may be valuable for improving the off-flavours of soymilk.

We present herein a novel ratiometric fluorescent probe (1) for benzoyl peroxide (BPO). Probe 1was obtained by coupling the recognition unit of arylboronate to a benzothiazole-derived fluorophore. The probe solution is colorless and displays weak blue fluorescence at 460 nm. Upon the addition of BPO, the arylboronate substituent can be removed viaoxidation and 1,4-elimination processes. The released fluorophore emits strong yellow-greenish fluorescence at 546 nm. The ratiometric response of the probe is highly selective and sensitive for BPO. The dynamic range was fitted over 1.0 - 75.0 μM with a detection limit of 0.26 μM. In addition, the probe was applied to quantitative detection of BPO in real samples of wheat flour and an antimicrobial agent. Cellular experiments further demonstrated that probe 1can be effectively utilized for imaging BPO in living cells.

A general peptide substrate for the specific detection of proteases is linked with a quencher/fluorophore pair. However, labeling of the substrate with a quencher/fluorophore pair may increase the complexity for the synthesis of peptides and affect the approach of protease to the cleavage site. A peptide with a specific sequence has been shown to bind Cu2+with high affinity. More intriguingly, Cu2+exhibits a high inherent quenching ability towards the fluorophore by complexation with the sequence-specific peptide. Based on this fact, this work reports a general single-labeled peptide substrate for the detection of protease activity, screening of potential inhibitors and evaluation of cell apoptosis. The feasibility and applications of the method were demonstrated by assays of caspase-3 and β-secretase with a signal-on and a signal-off format, respectively.

Oxidative stress and inflammation of the vessel wall contribute to prothrombotic states. The antioxidative protein paraoxonase-2 (PON2) shows reduced expression in human atherosclerotic plaques and endothelial cells in particular. Supporting a direct role for PON2 in cardiovascular diseases, Pon2 deficiency in mice promotes atherogenesis through incompletely understood mechanisms. Here, we show that deregulated redox regulation in Pon2 deficiency causes vascular inflammation and abnormalities in blood coagulation. In unchallenged Pon2−/− mice, we find increased oxidative stress and endothelial dysfunction. Bone marrow transplantation experiments and studies with endothelial cells provide evidence that increased inflammation, indicated by circulating interleukin-6 levels, originates from Pon2 deficiency in the vasculature. Isolated endothelial cells from Pon2−/− mice display increased tissue factor (TF) activity in vitro. Coagulation times were shortened and platelet procoagulant activity increased in Pon2−/− mice relative to wild-type controls. Coagulation abnormalities of Pon2−/− mice were normalized by anti-TF treatment, demonstrating directly that TF increases coagulation. PON2 reexpression in endothelial cells by conditional reversal of the knockout Pon2 cassette, restoration in the vessel wall using bone marrow chimeras, or treatment with the antioxidant N-acetylcysteine normalized the procoagulant state. These experiments delineate a PON2 redox-dependent mechanism that regulates endothelial cell TF activity and prevents systemic coagulation activation and inflammation.

ABSTRACTThe currently available drugs to treat hepatitis B virus (HBV) infection include interferons and nucleos(t)ide analogs, which can only induce disease remission and are inefficient for the functional cure of patients with chronic HBV infection (CHB). Since high titers of circulating hepatitis B surface antigen (HBsAg) may be essential to exhaust the host anti-HBV immune response and they cannot be significantly reduced by current drugs, new antiviral strategies aiming to suppress serum hepatitis B surface antigen (HBsAg) could help restore virus-specific immune responses and promote the eradication of the virus. As an alternative strategy, immunotherapy with HBsAg-specific antibodies has shown some direct HBsAg suppression effects in several preclinical and clinical trial studies. However, most described previously HBsAg-specific antibodies only had very short-term HBsAg suppression effects in CHB patients and animal models mimicking persistent HBV infection. More-potent antibodies with long-lasting HBsAg clearance effects are required for the development of the clinical application of antibody-mediated immunotherapy for CHB treatment. Our recent study described a novel mAb E6F6 that targets a unique epitope on HBsAg. It could durably suppress the levels of HBsAg and HBV DNA via Fcγ receptor-dependent phagocytosis in vivo. In this commentary, we summarize the current research progress, including the therapeutic roles and mechanisms of antibody-mediated HBV clearance as well as the epitope-determined therapeutic potency of the antibody. These insights may provide some clues and guidance to facilitate the development of therapeutic antibodies against persistent viral infection.

The uses and nutritional value of soybean (Glycine max (L.) Merrill) oil are largely influenced by the levels and relative proportions in the seed of the five major fatty acids: oleic (OA), palmitic (PA), stearic (SA), linoleic (LLA), linolenic (LNA). The present study was undertaken to identify quantitative trait loci (QTLs) that are associated with fatty acid content (particularly OA) and to determine the effects of epistasis and the environment. The mapping population included 134 recombinant inbred lines (RILs) derived from soybean varieties Suinong10 and L-9. Phenotypic data of the two parents and their RILs were obtained at Harbin in 2013, 2014 and 2015. Nineteen QTLs associated with individual fatty acid content (six for OA, four for LNA, three for PA, two for SA, four for LLA) were identified. Twelve of these QTLs (four for OA, three for LNA, two for PA, one for SA, two for LLA) were detected with an additive main effect and/or additive×environment interaction effect in certain environments. Epistatic QTLs were identified for contents of OA (two QTLs), LNA (one QTL) and LLA (one QTL) in different environments, and which exhibited significant epistatic effects. Our observation of these additive and epistatic QTLs suggested that soybean possesses a complex network for fatty acid accumulation, which is valuable for marker-assisted selection.

Poly (vinylidene fluoride) (PVDF) matrix hybrid nanocomposites, featuring ferroelectric barium titanate (BT) nanoparticles and multi-walled carbon nanotubes (MWCNT) embedded in the polymer, were fabricated by a miscible-immiscible coagulation method followed by hot pressing. SEM images showed good distribution of the ceramic nanoparticles with very little particle agglomeration. The conductive MWCNT increased the charge storage ability of the matrix polymer by serving as a polarized charge transport phase for the ferroelectric nanoparticles, while the small MWNT amounts used prevented the formation of conductive networks. The simple processing method utilized resulted in composites with high real permittivity and low dielectric loss over a wide range of frequency (10–1MHz). The dielectric properties of the polymer matrix nanocomposites with hybrid fillers (BT with and without MWNT) were improved by optimizing the synergistic effects between the charge storage behavior of the ferroelectric phase and the charge transport behavior of the conductive phase. The best combination of real permittivity and dielectric loss properties (71.7 and 0.045 respectively) were obtained for the nanocomposites containing 37.1vol% of BaTiO3and 3vol% of MWCNT. In addition to achieving reliable dielectric properties, the nanocomposites also displayed flexibility making these composites potentially useful for many flexible electronic devices and electrostatic energy storage devices.

A safe and highly efficacious Escherichia coli(E. coli)-produced HPV 16/18 bivalent vaccine has been prequalified by the World Health Organization. Here, we conducted a single-center, open-label, dose-escalation phase 1 clinical trial to evaluate the safety and immunogenicity of the second-generation nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine.

Polyphenols and isoflavones are the main bioactive components of soybean. During traditional processing, many active compounds are lost because of filtration and discard of okara. However, reports on changes in phenolic compounds, especially bound phenolic compounds (BPC), during the fermentation of whole soybean milk (WSM) are few. In this paper, three lactic acid bacterias (LABs) with different β-glucosidase activities were used to evaluate the effect of β-glucosidase and different okara contents in soybean milk on the conversion of extractable and non-extractable polyphenols during fermentation. The results showed that the action of β-glucosidase improved the release of BPC and isoflavones. During WSM fermentation, the β-glucosidase-producing capacity of LABs strongly correlated with both the decrease in conjugated phenolic compounds and isoflavone glycosides, and the increase in free phenolic compounds and isoflavone aglycones. With the increase of okara content, the acid tolerance of Lactobacillus delbrueckii b8was enhanced and the viability increased. During L. delbrueckii b8-mediated fermentation, the β-glucosidase activity of soy milk with high okara content (59.07 ± 1.48 U/mL) was 1.62 times that of soy milk with low okara content (36.43 ± 1.38 U/mL). As the okara concentration increased, the release of soybean polyphenols increased. Moreover, high okara content and high β-glucosidase activity mutually promote polyphenol conversion in soy yogurt. Therefore, WSM fermentation by β-glucosidase-producing LAB is a method for increasing the phenolic compound content in soymilk. This approach can offer a theoretical guide for efficiently utilizing soybean polyphenols and developing phenolic compound-rich soymilk.

Despite the success in decreasing varicella-related disease burden, live-attenuated Oka vaccine strain of varicella-zoster virus (vOka) remains neuro-virulence and may establish latency and reactivate, raising safety concerns. Here we aimed to evaluate the safety and immunogenicity of a skin- and neuro-attenuated varicella vaccine candidate (v7D).

ABSTRACTA dose-escalation, randomized, double-blind, placebo-controlled phase 1 clinical trial enrolled 145 eligible participants aged 18–55 years in March 2015 in Liuzhou, China. Stratified by age and sex, the participants were randomly assigned to receive either 30, 60, or 90 μg of the HPV-6/11 vaccine (n = 41/40/40) or the parallel placebo vaccine (n = 8/8/8) with a 0/1/6-month dose-escalation schedule. Participants were actively followed-up to record local and systemic AEs occurring within 30 days after each vaccination, and SAEs occurred in 7 months. Blood and urine samples of each participant were collected before and 2 days after the first and third vaccination to determine changes in routine blood, serum biochemical, and urine indexes. Serum HPV-6/11-specific IgG and neutralizing antibody levels at month 7 were analyzed. A total of 79 adverse events were reported, and no SAEs occurred. The incidences of total adverse reactions in the 30 μg, 60 μg, and 90 μg HPV vaccine groups and the control group were 31.7%, 50.0%, 42.5%, and 62.5%, respectively. All but one of the adverse reactions was mild or moderate with grade 1 or 2. No vaccine-related changes with clinical significance were found in paired blood and urine indexes before and after vaccinations. All the participants in the per-protocol set seroconverted at month 7 for both IgG and neutralizing antibodies. The candidate novel Escherichia-coli-produced bivalent HPV-6/11 vaccine has been preliminarily proven to be well tolerated and with robust immunogenicity in a phase 1 clinical study, supporting further trials with larger sample size. The study has been registered at ClinicalTrials.gov (NCT02405520)

Amyloid-β oligomers (AβOs) are the most important toxic species in the brain of Alzheimer’s disease (AD) patient. AβOs, therefore, are considered reliable molecular biomarkers for the diagnosis of AD. Herein, we reported a simple and sensitive electrochemical method for the selective detection of AβOs using silver nanoparticles (AgNPs) as the redox reporters and PrP(95–110), an AβOs-specific binding peptide, as the receptor. Specifically, adamantine (Ad)-labeled PrP(95–110), denoted as Ad-PrP(95–110), induced the aggregation and color change of AgNPs and the follow-up formation of a network of Ad-PrP(95–110)-AgNPs. Then, Ad-PrP(95–110)-AgNPs were anchored onto a β-cyclodextrin (β-CD)-covered electrode surface through the host–guest interaction between Ad and β-CD, thus producing an amplified electrochemical signal through the solid-state Ag/AgCl reaction by the AgNPs. In the presence of AβOs, Ad-PrP(95–110) interacted specifically with the AβOs, thus losing the capability to bind AgNPs and to induce the formation of an AgNPs-based network on the electrode surface. Consequently, the electrochemical signal decreased with an increase in the concentration of AβOs in the range of 20 pM to 100 nM. The biosensor had a detection limit of 8 pM and showed no response to amyloid-β monomers (AβMs) and fibrils (AβFs). On the basis of the well-defined and amplified electrochemical signal of the AgNPs-based network architecture, these results should be valuable for the design of novel electrochemical biosensors by marrying specific receptors.

Supplemental Digital Content is available in the text.

Hepatitis E virus (HEV) infection is one of the main causes of acute hepatitis worldwide. A recombinant hepatitis E vaccine, HEV 239, has been licensed in China for immunizing adults of 16 y old and above. The vaccine antigen contains pORF2 aa 368 - 606 of the HEV genotype 1 expressed in E. coli. The quality of the vaccine is controlled through a combination of biophysical, biochemical and immunochemical methods. The vaccine is well tolerated in adults. The efficacy of the HEV 239 vaccine against symptomatic and asymptomatic infection had been proven to be high during a Phase III clinical trial and long-term follow up. The safety and efficacy of HEV 239 vaccine in certain high-risk populations remains to be further investigated.

Amyloid-β oligomers (AβOs) have been regarded as reliable molecular biomarkers for Alzheimer's disease (AD) diagnosis and crucial targets for therapeutic intervention. In this work, we report a graphene oxide (GO)-based fluorescence method for the selective detection of AβOs based on the strong and specific interaction between AβOs and the PrP(95–110) peptide, a segment of the cellular prion protein. Specifically, fluorescein isothiocyanate (FITC)-labeled PrP(95–110), denoted as FITC-PrP(95–110), was adsorbed onto the surface of GO viaelectrostatic and π–π interactions, which resulted in effective fluorescence quenching. However, in the presence of AβOs, the competitive binding of AβOs with GO for the peptide probe blocked the interaction between GO and FITC-PrP(95–110), which resulted in the recovery of the fluorescence signal. As a result, a detection limit of 1 nM for AβOs (equivalent monomers) was achieved. The amenability of this method to AβO analysis in a biological matrix was demonstrated by assaying AβOs in artificial cerebrospinal fluid. In contrast to other reported methods for AβO detection, our method is simple, rapid, cost-effective, highly selective, and obviates the need for a less stable antibody. We believe that our approach offers a new method for clinical diagnosis of AD and routine laboratory investigation for understanding the dynamics and mechanism of the Aβ aggregation/fibrillation processes.

ABSTRACTHepatitis E virus (HEV) is a serious public health problem. The commonly used tests that are specific for current HEV infection diagnosis include the detection of anti-HEV IgM and HEV RNA. Here, we report an improved enzyme-linked immunosorbent assay (ELISA) method for HEV antigen detection with a linear range equivalent to 6.3 × 103to 9.2 × 105RNA copies per ml. The monoclonal antibody (MAb) 12F12, a high-ability MAb that binds HEV virus, was selected as the capture antibody from a panel of 95 MAbs. The positive period of HEV antigenemia in infected monkeys using this test was, on average, 3 weeks longer than previously reported and covered the majority of the acute phase. The positive detection rates of IgM, RNA, and new antigen from the first serum samples collected from 16 confirmed acute hepatitis E patients were 81% (13/16), 81% (13/16), and 100% (16/16), respectively. In three patients, the initial serum specimens that tested negative for IgM, despite the presence of symptoms of acute hepatitis and elevated alanine aminotransferase (ALT) levels, were positive for HEV antigen and HEV RNA. In contrast, the serum samples of the three RNA-negative patients were antigen positive (and IgM positive), possibly due to the degradation of HEV nucleic acids. Our results suggest that this new antigen detection method has acceptable concordance with RNA detection and could serve as an important tool for diagnosing acute hepatitis E.

Background: In recent years, many studies have reported the relationship between non-alcoholic fatty liver disease (NAFLD) and sex hormones, especially total testosterone (TT) and sex hormone–binding globulin (SHBG). However, the relationship between sex hormones and the severity of NAFLD is still unclear.Methods: PubMed, Embase, Cochrane Library, Web of Science, WanFang, China National Knowledge Infrastructure and VIP databases were searched for relevant studies from inception to 31 August 2021. Values of weighted mean differences (WMDs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were combined by Stata 12.0 software to evaluate the relationship between TT, SHBG and the severity of NAFLD in males.Results: A total of 2995 patients with NAFLD from 10 published cross-sectional studies were included for further analysis. The meta-analysis indicated that the moderate-severe group had a lower TT than the mild group in males with NAFLD (WMD: −0.35 ng/ml, 95% CI = −0.50 to −0.20). TT and SHBG were important risk factors of moderate-severe NAFLD in males (ORTT= 0.79, 95% CI = 0.73 to 0.86; ORSHBG= 0.22, 95% CI = 0.12 to 0.39; p< 0.001). Moreover, when the analysis was limited to men older than age 50, SHBG levels were lower in those with moderate-severe disease (WMD: −11.32 nmol/l, 95% CI = −14.23 to −8.40); while for men with body mass index (BMI) >27 kg/m2, moderate-severe NAFLD had higher SHBG levels than those with mild disease (WMD: 1.20 nmol/l, 95% CI = −2.01 to 4.42).Conclusion: The present meta-analysis shows that lower TT is associated with the severity of NAFLD in males, while the relationship between SHBG and severity of NAFLD is still to be further verified.

ABSTRACTHepatitis B surface antigen (HBsAg) quantification has garnered attention because of its high predictive value in determining treatment responses. The HBsAg quantification assays, such as Architect and Elecsys, are commercially available, and more assays are in development. We aimed to compare the results of the Architect and Elecsys assays with those of a new assay, WTultra. The WTultra HBsAg assay is a sandwich chemiluminescent microplate enzyme immunoassay and provides an alternative choice which is more cost-effective and potentially applicable in developing or resource-constrained countries and areas. A total of 411 serum samples were collected from patients during various phases of chronic hepatitis B (CHB) infection. The samples were assessed using the three assays, and the results were compared and analyzed. The results for the Architect, Elecsys, and WTultra assays were well correlated according to the overall results for the samples (correlation coefficients, rArchitect versus WTultra= 0.936, rArchitect versus Elecsys= 0.952, and rWTultra versus Elecsys= 0.981) and the various infection phases (rArchitect versus WTultraranging from 0.67 to 0.975, rArchitect versus Elecsysranging from 0.695 to 0.982, and rWTultra versus Elecsysranging from 0.877 to 0.99). Additionally, consistent results were observed according to genotype (genotype B: rArchitect versus WTultra= 0.976, rArchitect versus Elecsys= 0.978, and rWTultra versus Elecsys= 0.979; genotype C: rArchitect versus WTultra= 0.950, rArchitect versus Elecsys= 0.963, and rWTultra versus Elecsys= 0.981) and hepatitis B virus (HBV) DNA levels (rArchitect= 0.540, rWTultra= 0.553, and rElecsys= 0.580). In conclusion, the Elecsys and WTultra assays were well correlated with the Architect assay, irrespective of the CHB infection phase or genotype. All of these assays are reliable for HBsAg quantification.

Prophylactic vaccines against hepatitis B Virus (HBV) infection were produced in different expression systems under different processing conditions. Since the recombinant HBV surface antigen (HBsAg) in these vaccines is a cysteine-rich protein with 14 cysteines among a total of 226 amino acids, the epitopes are dependent on the formation of intra- and intermolecular disulfide bonds. A panel of 22 monoclonal antibodies (mAbs) were developed and evaluated with respect to their sensitivity to disulfide reduction treatment of recombinant HBsAg. Not surprisingly, different mAbs showed different degree of sensitivity to controlled HBsAg disulfide reduction. With a view to exploring the functionality of anti-HBsAg mAbs to be used in HBsAg quality analysis, in vitro neutralization activity for the mAbs was assessed. One of the mAbs tested, 5F11, which showed high sensitivity to the disulfide integrity in HBsAg, was shown also to be highly effective in neutralizing HBV in vitro. Conversely, 42B6, while exhibiting similar neutralization activity, showed comparable binding HBsAg with or without reduction treatment. Based on these mAb characteristics, a sandwich ELISA with 42B6 being the capture Ab and detection Ab was developed to quantify HBsAg (like a “mass” assay) during antigen bioprocessing or in vaccine products. In parallel, when 5F11 was used as the detection Ab (with the same capture Ab), the assay can be used to probe disulfide-dependent and virion-like epitopes in intermediates or final products of hepatitis B vaccine, serving as a surrogate marker for vaccine efficacy to elicit neutralizing antibodies. This approach enables the comparative epitope specific antigenicity analysis of HBsAg antigen preparations from different sources.

Alzheimer’s disease (AD) is characterized by the deposition of amyloid- (A) peptide in the brains of AD patients. Such a process is linked to the binding of metal ions (e.g., Cu, Fe and Zn) with A. As a result, metal chelation could be used as a rational therapeutic pathway for the treatment of AD. In this review, we address some noteworthy advances on the utilization of metal chelators, such as native metallothioneins and synthetic compounds, as potential therapeutic agents for AD. In addition, the future design and utility of metal chelating drugs as well as the strategy pursued to transport metal chelators into the brain are highlighted. We believe that this contribution will be valuable for the design of metal-chelating drugs for AD treatment.

A pseudovirion-based neutralisation assay (PBNA) has been considered the gold standard for measuring specific antibody responses against human papillomavirus (HPV). However, this assay is labor intensive and therefore very difficult to implement in large-scale studies. Previous studies have evaluated the agreement between virus-like particle (VLP)-based ELISA and PBNA for measuring HPV vaccine-induced antibodies. However, the concordance of these assays to detect antibodies induced by natural infection has not yet been fully elucidated. In this study, the results of an Escherichia coli (E. coli)-expressed VLP-based ELISA were found to be highly concordant with those of a baculovirus-expressed VLP-based ELISA (r = 0.96 and 0.97 for HPV-16 and HPV-18) when detecing HPV vaccine induced antibodies and the concordance was medium (r = 0.68 and 0.68 for HPV-16 and HPV-18) when assessing natural infection induced antibodies. The results of the E. coliexpressed VLP-based ELISA correlated well with those of the PBNA when testing 1020 post-vaccination human sera collected at one month after vaccination with the E. coliexpressed VLP-based bivalent HPV vaccine (r = 0.83 and 0.81 for HPV-16 and HPV-18). The agreement and correlation were moderate (kappa < 0.3 for both HPV types 16 and 18, r = 0.59 and 0.68 for HPV-16 and HPV-18, respectively) when assessing 1600 serum samples from unvaccinated women of age 18–25 years. In conclusion, the VLP-based ELISA is an acceptable surrogate for the neutralizing antibody assay in measuring vaccine responses. However, the use of the VLP-based ELISA in epidemiological studies should be carefully considered.

An Escherichia coli-expressed recombinant bivalent human papillomavirus (types 16 and 18) vaccine candidate has been shown to be safe and immunogenic in preclinical trials. The safety of this vaccine was analyzed in an open-label phase I clinical trial in Jiangsu province, China. Thirty-eight healthy women from 18 to 55 y of age were enrolled and vaccinated at 0, 1, and 6 mo. Adverse events that occurred within 30 d after each injection and serious adverse events that occurred throughout the study were recorded. In addition, blood parameters were tested before and after each injection. All but one woman received all 3 doses. Thirty-two (84.2%) of the participants reported adverse events, all adverse events of which were mild, of short duration and resolved spontaneously. No serious adverse events occurred during the study. Changes in blood parameters after each injection were random, mild, and not clinically significant. These preliminary results show that a new Escherichia coli-expressed recombinant HPV 16/18 bivalent vaccine is well tolerated in healthy women and support further immunogenicity and efficacy studies for this HPV vaccine candidate.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) possesses multiple protective properties in the vasculature, including anti-oxidative and anti-inflammatory effects and improvement of endothelial function. A substantial part of these effects is attributable to gene expression changes induced by the compound. Resveratrol can activate the NAD-dependent deacetylase sirtuin 1 (SIRT1), leading to deacetylation of SIRT1 target molecules such as NF-kB and forkhead box O (FOXO) transcription factors. The inhibition of NF-kB by resveratrol reduces the expression of inflammation mediators. FOXO factors are implicated in the upregulation of antioxidant enzymes and the endothelial-type nitric oxide synthase. In addition, resveratrol upregulates a number of antioxidant enzymes by activating nuclear factor-E2-related factor-2 (Nrf2) and downregulates NADPH oxidases through yet known mechanisms.