A biosensor was fabricated by immobilizing glucose oxidase (GOD) into nanostructured graphene (GRA)-conducting polyaniline (PANI) nanocomposite, which was based on electrochemical polymerization of ...aniline in GRA synthesized by using electrochemical expansion of graphite in propylene carbonate electrolyte. Scanning electron spectroscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to characterize the morphology and performance of the as-prepared biosensor, respectively. Amperometric measurements were carried out to optimize test conditions (pH and applied potential) of the biosensor. Under the optimal conditions, the biosensor showed a linear range from 10.0μM to 1.48mM (R2=0.9988) with a sensitivity of 22.1μAmM−1cm−2, and a detection limit of 2.769μM (S/N=3). The apparent Michaelis–Menten constant (KMa) was estimated to be 3.26mM. The interference from glycine (Gly), D-galactose (D-Gal), urea (Urea), L-phenylalanine (L-Phe), ascorbic acid (AA), and L-tyrosine (L-Tyr) was also investigated. The results indicated that the biosensor exhibit high sensitivity and superior selectivity, providing a hopeful candidate for glucose biosensing.
•A novel glucose biosensor based on graphene–polyaniline nanocomposite was fabricated.•The graphene-polyaniline composite was synthesized by electrochemical polymerization.•Graphene prepared by electrochemical expansion showed superior electric conductivity.•Phase inversion was applied for fabrication of the biosensor.•The biosensor showed high sensitivity due to amplification of current response.•The biosensor exhibited excellent selectivity at a positive applied potential.
Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an ...attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.
Display omitted
•A dimeric form of MERS-CoV RBD is highly immunogenic and protective in mice•RBD-dimer structure guides further design of a homogeneous dimer by tandem repeat•The strategy is generalizable to design beta-CoV vaccines against COVID-19 and SARS•CoV RBD-dimer immunogens can be produced at high yields in pilot scale production
Gao et al. present the structure-guided design of a coronavirus immunogen comprised of two protein subunits each containing the virus spike receptor binding domain fused together via a disulfide link or tandem repeat. The immunogen elicits strong immunogenicity in mice and protects them against viral challenge. The vaccine design strategy can be universally applied to SARS, MERS, COVID-19, and other CoV vaccines to counter emerging threats.
This research uses difference-in-difference (DID) and other empirical methods to analyze firm-level real estate data to discover how heterogeneous firm characteristics affect managers’ ...decision-making about development expansion when a firm faces a temporary negative sales shock in the Chinese housing market. The manager’s decision is a utility maximization problem under uncertainty, determined by their risk aversion levels, which managers choose to optimize by considering other factors of interest, including career risk and personal wealth. Also, the advance payment rule encourages real estate developers to maintain high turnover, since new projects allow developers to collect cash first. The results show that state-owned enterprises (SOEs) are much more conservative than other types of developers. SOEs tend to focus on current developing projects. Firms with more concentrated management pursue expansion and seek to use new project sales to compensate for their slower growth. Larger developers with headquarters in large cities tend to slow their development speed when they observe negative signals, as they can quickly engage in new projects given these firms’ easy access to financial resources such as bank loans. This study makes a novel contribution to the literature since previous research has tended to focus on the macro market level rather than the firm level. The findings also have strong policy and regulation value. The results indicate that higher cashflow monitoring needs, especially to monitor family-owned developers, to prevent misuse and excessive project expansion.
Display omitted
•Tea polysaccharide (TPS) is an acid polysaccharide with various structural features.•TPS modulate gut microbiota composition and metabolites as a potential prebiotic.•The ...health-promoting effects of TPS by targeting gut microbiota are discussed.•Future perspective and challenges of TPS studies were proposed.
Tea has been used medicinally and dietarily for thousands of years. Tea polysaccharides (TPS), considered one of the main bioactive components of tea, show diverse health benefits. Yet it has received far less attention than tea polyphenols. During recent decades, considerable researches have been dedicated to TPS, including extraction, structural characteristics, and potential bioactivity. Recent studies suggested that the biological effects of dietary TPS are subjected to gut microbiota (GM) modulation. Thus, this review focuses on recent research advance on the structure characteristics of TPS, TPS degradation in the gut, TPS modulation on the diversity of GM and production of short chain fatty acids (SCFAs), and the health benefits of TPS through targeting GM. Furthermore, some future research directions were also proposed. The purpose of this review is to enhance our understanding the health-promoting properties of TPS and to promote further researches on the TPS.
Metabolic syndrome is a chronic metabolic disorder that has turned into a severe health problem worldwide. A previous study reported that large yellow tea exhibited better anti-diabetic and ...lipid-lowering effects than green tea. Nevertheless, the potential mechanisms are not yet understood. In this study, we examined the prevention effects and mechanisms of large yellow tea water extract (LWE) on metabolic syndrome using leptin receptor knockout (
) rats. Seven-week-old male
and wild type (WT) littermate rats were divided into
control group (KO) (n = 5),
with LWE-treated group (KL) (n = 5), WT control group (WT) (n = 6), and WT with LWE intervention group (WL) (n = 6). Then, the rats were administered water or LWE (700 mg/kg BW) daily by oral gavage for 24 weeks, respectively. The results showed that the administration of LWE significantly reduced the serum concentrations of random blood glucose, total cholesterol, triglyceride, and free fatty acids, and increased glucose tolerance in
rats. Moreover, LWE remarkably reduced hepatic lipid accumulation and alleviated fatty liver formation in
rats. A mechanistic study showed that LWE obviously activated SIRT6 and decreased the expression of key lipogenesis-related molecules SREBP1, FAS, and DGAT1 in the livers of
rats. Furthermore, LWE significantly improved microbiota dysbiosis via an increase in gut microbiota diversity and an abundance of the microbiota that produce short chain fatty acids (SCFAs), such as
,
,
and
. Finally, LWE supplementation increased the concentrations of SCFAs in the feces of
rats. These results revealed that LWE attenuated metabolic syndrome of
rats via the reduction of hepatic lipid synthesis through the SIRT6/SREBP1 pathway and the modulation of gut microbiota.
Genetic analysis of gene expression level is a promising approach for characterizing candidate genes that are involved in complex economic traits such as meat quality. In the present study, we ...conducted expression quantitative trait loci (eQTL) and allele-specific expression (ASE) analyses based on RNA-sequencing (RNAseq) data from the longissimus muscle of 189 Duroc × Luchuan crossed pigs in order to identify some candidate genes for meat quality traits.
Using a genome-wide association study based on a mixed linear model, we identified 7192 cis-eQTL corresponding to 2098 cis-genes (p ≤ 1.33e-3, FDR ≤ 0.05) and 6400 trans-eQTL corresponding to 863 trans-genes (p ≤ 1.13e-6, FDR ≤ 0.05). ASE analysis using RNAseq SNPs identified 9815 significant ASE-SNPs in 2253 unique genes. Integrative analysis between the cis-eQTL and ASE target genes identified 540 common genes, including 33 genes with expression levels that were correlated with at least one meat quality trait. Among these 540 common genes, 63 have been reported previously as candidate genes for meat quality traits, such as PHKG1 (q-value = 1.67e-6 for the leading SNP in the cis-eQTL analysis), NUDT7 (q-value = 5.67e-13), FADS2 (q-value = 8.44e-5), and DGAT2 (q-value = 1.24e-3).
The present study confirmed several previously published candidate genes and identified some novel candidate genes for meat quality traits via eQTL and ASE analyses, which will be useful to prioritize candidate genes in further studies.
A unique autothermal thermophilic aerobic digestion (ATAD) process has been used to convert human excreta to liquid fertilizer in Japan. This study investigated the changes in physicochemical and ...bacterial community characteristics during the full-scale ATAD process operated for approximately 3 weeks in 2 different years. After initiating simultaneous aeration and mixing using an air-inducing circulator (aerator), the temperature autothermally increased rapidly in the first 1 to 2 days with exhaustive oxygen consumption, leading to a drastic decrease and gradual increase in oxidation-reduction potential in the first 2 days, reached >50°C in the middle 4 to 6 days, and remained steady in the final phase. Volatile fatty acids were rapidly consumed and diminished in the first 2 days, whereas the ammonia nitrogen concentration was relatively stable during the process, despite a gradual pH increase to 9.3. Principal-coordinate analysis of 16S rRNA gene amplicons using next-generation sequencing divided the bacterial community structures into distinct clusters corresponding to three phases, and they were similar in the final phase in both years despite different transitions in the middle phase. The predominant phyla (closest species, dominancy) in the initial, middle, and final phases were
(
, 19 to 43%;
, 6.3 to 30%),
(
, 43 to 54%), and
(
, 11 to 28%;
, 2.1 to 16%), respectively. Two predominant operational taxonomic units (OTUs) in the final phase showed very low similarities to the closest species, indicating that the process is unique compared with previously published ones. This unique process with three distinctive phases would be caused by the aerator with complete aeration.
Although the autothermal thermophilic aerobic digestion (ATAD) process has several advantages, such as a high degradation capacity, a short treatment period, and inactivation of pathogens, one of the factors limiting its broad application is the high electric power consumption for aerators with a full-scale bioreactor. We elucidated the dynamics of the bacterial community structures, as well as the physicochemical characteristics, in the ATAD process with a full-scale bioreactor from human excreta for 3 weeks. Our results indicated that this unique process can be divided into three distinguishable phases by an aerator with complete aeration and showed a possibility of shortening the digestion period to approximately 10 days. This research not only helps to identify which bacteria play significant roles and how the process can be improved and controlled but also demonstrates an efficient ATAD process with less electric power consumption for worldwide application.
Autothermal thermophilic aerobic digestion (ATAD) is conducted for stabilization of sludge waste and is driven by the action of various microorganisms under aerobic conditions. However, the mechanism ...controlling bacterial community changes during ATAD via three (initial, middle and final) phases is currently unclear. To investigate this mechanism, activity analysis and a microcosm assay with shaking were performed on a bacterial community during the initial, middle, and final phases of incubation. Cell lysis activities toward gram-negative bacteria, but not gram-positive bacteria, were detected in the ATAD samples in the middle and final phases. During shaking incubation in initial-phase samples at 30 °C, major operational taxonomic units (OTUs) related to Acinetobacter indicus and Arcobacter cibarius dramatically increased along with decreases in several major OTUs. In middle-phase samples at 45 °C, we observed a major alteration of OTUs related to Caldicellulosiruptor bescii and Aciditerrimonas ferrireducens, together with distinct decreases in several other OTUs. Final-phase samples maintained a stable bacterial community with major OTUs showing limited similarities to Heliorestis baculata, Caldicellulosiruptor bescii, and Ornatilinea apprima. In conclusion, the changes in the bacterial community observed during ATAD could be partially attributed to the cell lysis activity toward gram-negative bacteria in the middle and final phases. The microcosm assay suggested that certain physical factors, such as a high oxygen supply and shearing forces, also might contribute to bacterial community changes in the initial and middle phases, and to the stable bacterial community in the final phase of ATAD.
Display omitted
•This study first detected cell lysis activities toward Escherichia coli (gram-negative bacteria) in the full-scale ATAD process.•Bacterial community changed dynamically in initial- and middle-phase samples during corresponding shaking incubation.•Bacterial community ultimately maintained stable in final-phase samples during shaking incubation.•Cell lysis activities, temperature increase, and shaking were first proposed to affect dynamic bacterial community in ATAD.
Yellow fever virus (YFV), a deadly human pathogen, is the prototype of the genus Flavivirus. Recently, YFV re-emerged in Africa and Brazil, leading to hundreds of deaths, with some cases imported to ...China. Prophylactic or therapeutic countermeasures are urgently needed. Previously, several human monoclonal antibodies against YFV were screened out by phage display. Here, we find that one of them, 5A, exhibits high neutralizing potency and good protection. Crystallographic analysis of the YFV envelope (E) protein in its pre- and post-fusion states shows conformations similar to those observed in other E proteins of flaviviruses. Furthermore, the structures of 5A in complex with the E protein in both states are resolved, revealing an invariant recognition site. Structural analysis and functional data suggest that 5A has high neutralization potency because it interferes with virus entry by preventing both virus attachment and fusion. These findings will be instrumental for immunogen or inhibitor design.
Display omitted
•The crystal structures of YFV-E in both pre- and post-fusion states are determined•A neutralizing monoclonal antibody engages YFV-E in both states as a double lock•This monoclonal antibody inhibits YFV infection at multiple steps of virus entry
Yellow fever virus (YFV) is a deadly flavivirus. Lu et al. report the structures of YFV envelope protein in its pre- and post-fusion states and a potent neutralizing monoclonal antibody bound to both states. Structural and functional analyses reveal the double lock of the antibody to neutralize YFV infection.
Display omitted
The circadian rhythm regulates the daily cycles of various physiological activities. Accumulating evidences revealed that circadian rhythm plays an important role in regulating ...metabolic homeostasis, and disruptions of circadian rhythms resulting in metabolic disorder. Peripheral clocks are not only controlled by the central clock but also entrained by external cues. Dietary pattern and compounds derived from food are found to play multiple roles in regulating metabolic processes through resetting peripheral clocks. Here we review the recent advance of effects and mechanisms of dietary pattern and compounds modulating peripheral clocks and regulating metabolic processes. Multiple molecular mechanisms linked dietary pattern and compounds with circadian rhythm and metabolism were summarized. Elaboration of crosstalk between diet and circadian rhythm may provide targets for the prevention of metabolic disorder. The exact mechanisms that feeding pattern and dietary compounds linked metabolic process and circadian rhythm need to be further investigated.
PDF
