The investigation on sialic acid-modified pectin nanoparticles loaded with oxymatrine for orally targeting and inhibiting the of ulcerative colitis.

The aim of the study was to develop an oral targeting drug delivery system (OTDDS) of oxymatrine (OMT) to effectively treat ulcerative colitis (UC). The OTDDS of OMT (OMT/SA-NPs) was constructed with OMT, pectin, Ca2+, chitosan (CS) and sialic acid (SA). The obtained particles were characterized in terms of particle size, zeta potential, morphology, drug loading, encapsulation efficiency, drug release and stability. The average size of OMT/SA-NPs was 255.0 nm with a zeta potential of -12.4 mV. The loading content and encapsulation efficiency of OMT/SA-NPs were 14.65% and 84.83%, respectively. The particle size of OMT/SA-NPs changed slightly in the gastrointestinal tract. The nanoparticles can delivery most of the drug to the colon region. In vitro cell experiments showed that the SA-NPs had excellent biocompatibility and anti-inflammation, and the uptake of SA-NPs by RAW 264.7 cells was time and concentration-dependent. The conjugated SA can help the internalization of NPs into target cells. In vivo experiments showed that OMT/SA-NPs had a superior anti-inflammation effect and the effect of reducing UC, which was attributed to the delivery most of OMT to the colonic lumen, the specific targeting and retention in colitis site and the combined anti-inflammation of OMT and NPs.

Ultrasonic treatment enhanced the binding capacity of volatile aldehydes and pearl mussel (Hyriopsis cumingii) muscle: Investigation of underlying mechanisms.

This study was aim to investigate the influencing mechanism of ultrasonic treatment on the interaction between volatile aldehydes and myosin. The results showed that when the mass concentration ratio of myosin to heptanal/hexanal was 1:0.3, ultrasonic treatment could enhance the binding capacity of myosin to heptanal/hexanal, especially the binding of myosin to hexanal. The entropy and enthalpy values of their interaction were negative, indicating that the interaction was mainly driven by hydrogen bond and van der Waals force. After ultrasonic treatment, the fluorescence wavelength of myosin-heptanal/hexanal complex was redshifted, the α-helix content was increased, while its roughness values, particle size and the polydispersity index were decreased. These demonstrated that ultrasonic treatment was conducive to myosin binding to heptanal/hexanal, thereby restraining the release of volatile flavor compounds from myosin, which could provide new insights for the regulation of volatile flavor compounds.

Amyloid-like nanofibrous network confined and aligned ultrafine bimetallic nanozymes for smart antibacterial therapy.

Nanozyme-based antibacterial therapy (NABT) has emerged as a promising strategy to combat bacterial antimicrobial resistance. Engineering the noble metal nanozymes with strong bacterial capture and high catalytic activity for enhanced NABT is highly anticipated but still challenged. Herein, we developed hybrid nanozymes by engineering ultrafine bimetallic Au/Cu nanoparticles confined on the lysozyme amyloid-like nanofibrous networks (LNF). The introduction of copper in the nanozymes facilitates the H2O2 adsorption and reduces the energy barrier for activating the H2O2 decomposition to form •OH, meanwhile displaying the significantly enhanced POD-like activity under NIR irradiation. Taking advantage of the inherent supramolecular networks inspired from human defensin 6-trapping bacteria mechanism, the hybrid nanozymes effectively capture the bacteria and allow the catalytic attack around the bacterial surfaces to improve the antibacterial efficiency. Finally, the as-prepared nanozymes exhibit the preeminent bactericidal efficacy against bacteria, especially for drug-resistant bacteria both in vitro and in vivo, and the effect on wound healing.

Comprehensive analysis of the key amino acid substitutions in the polymerase and NP of avian influenza virus that enhance polymerase activity and affect adaptation to mammalian hosts.

Accumulation of adaptive mutations in the polymerase and NP genes is crucial for the adaptation of avian influenza A viruses (IAV) to a new host. Here, we identified residues in the polymerase and NP proteins for which the percentages were substantially different between avian and human influenza viruses, to screen for key mammalian adaptive markers. The top 10 human virus-like residues in each gene segment were then selected for analysis of polymerase activity. Our research revealed that the PA-M311I and PA-A343S mutations increased the polymerase activity among the 40 individual mutations that augmented viral transcription and genomic replication, leading to increased virus yields, pro-inflammatory cytokine/chemokine levels and pathogenicity in mice. We also investigated the accumulative mutations in multiple polymerase genes and discovered that a combination of PB2-E120D/V227I, PB1-K52R/L212V/R486K/V709I, PA-R204K/M311I, and NP-E18D/R65K (hereafter referred to as the ten-sites joint mutations) has been identified to generate the highest polymerase activity, which can to some extent make up for the highest polymerase activity caused by the PB2-627 K mutation. When the ten-sites joint mutations co-occur with 627 K, the polymerase activity was further enhanced, potentially resulting in a virus with an improved phenotype that can infect a broader range of hosts, including mammals. This could lead to a greater public health concern than the current epidemic, highlighting that continuous surveillance of the variations of these sites is utmost important.

Novel silk protein/hyaluronic acid hydrogel loaded with azithromycin as an immunomodulatory barrier to prevent postoperative adhesions.

Peritoneal adhesions, a common postoperative complication of laparotomy, are still treated with physical barriers, but their efficacy and ease of use are controversial. In this paper, we developed a wound microenvironment-responsive hydrogel composed of Antheraea pernyi silk protein (ASF) from wild cocoons and tyramine-modified hyaluronic acid (HA-Ph) loaded with azithromycin (AZI), glucose oxidase (GOX), and horseradish peroxidase (HRP). In addition, GOX-catalyzed oxygen production enhanced the antibacterial ability of the hydrogel. Moreover, the drug-loaded hydrogel increased macrophage CD206 expression while decreasing IL-6 and TNF-α expression. More importantly, the retarding effect of this novel hydrogel system on AZI almost eliminated the appearance of postoperative adhesions in rats. It was also found that the novel hydrogel enhanced the modulation of the TLR-4/Myd88/NF-κB pathway and TGF-ß/Smad2/3 pathway by azithromycin in the locally damaged peritoneum of rats, which accelerated the remodeling of damaged tissues and dramatically reduced the deposition of collagen. Therefore, spraying the novel drug-loaded hydrogel on postoperative abdominal wounds can effectively inhibit the formation of postoperative adhesions.

Adsorptive removal of Cr(III)-EDTA chelate from an aqueous solution by magnetic mesoporous silica microspheres.

The 3-aminopropyltrimethoxysilane-modified magnetic mesoporous adsorbent (FNMs/APTES) was synthesized and applied to remove Cr(III)-EDTA chelates from water. The characterization of FNMs/APTES showed that the prepared adsorbent with a magnetic mesoporous structure was successfully grafted by APTES, which has good stability under acid conditions. The maximum capacities of FNMs/APTES for Cr(III)-EDTA adsorption at 15, 25 and 35 °C and pH 4.0 were 12.58, 13.13 and 14.00 mg·g-1, respectively. The adsorption isotherm of FNMs/APTES for Cr(III)-EDTA conforms to the Freundlich model, and the adsorption kinetic model accords with the pseudo-second-order kinetic model. Adsorption of Cr(III)-EDTA on the adsorbent was not affected in the presence of Na+, K+ and Ca2+ even at 100 mmol·L-1. Cr(III)-EDTA was anchored on FNMs/APTES through electrostatic interaction between protonated amino groups of adsorbents and Cr(III)-EDTA anions, and Cr(III)-EDTA chelates were adsorbed as a whole on the adsorbent. The Cr(III)-EDTA-saturated adsorbent can be readily regenerated in HCl solution and 83.03% of the initial Cr(III)-EDTA adsorption capacity remains after four adsorption-regeneration experiment cycles. The results highlighted that the FNMs/APTES as a potential adsorbent can be applied for the minimization of Cr(III)-EDTA chelates from water.

Evaluation of aroma characteristics in grass carp mince as affected by different washing processes using an E-nose, HS-SPME-GC-MS, HS-GC-IMS, and sensory analysis.

The aroma characteristics of grass carp mince washed in four processes were analyzed via electronic nose (E-nose), headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS), headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS), and sensory analysis techniques. Significant differences were revealed in the E-nose and sensory analysis results of the aroma characteristics of grass carp mince samples washed via different washing processes, while fifty-seven volatile compounds (thirteen aldehydes, eighteen alcohols, two ketones, eighteen hydrocarbons, two aromatic compounds, one furan, and two other compounds) and twenty volatile compounds (five aldehydes, four ketones, six alcohols, four esters, and one acid) were identified via HS-SPME-GC-MS and HS-GC-IMS of the Raw and washed grass carp mince samples, respectively. All these techniques revealed that the types and relative contents of volatile compounds in the grass carp mince decreased significantly and differently after each of the four washing processes. Moreover, compared with the water and saline solution washing processes, washing with weak alkaline solution processes exhibited the most significant removal effect on the volatile compounds of grass carp mince. Besides, the sensory analysis results also showed that weak alkaline solution washing processes (washing twice with pure water and once with 0.3% sodium bicarbonate solution) may be most effective in removing fishy off-odor compounds and contributing to a better overall aroma profile in grass carp mince. The findings of this study may provide some basic knowledge for the rational screening of washing methods in the production of high-quality grass carp surimi.

Cofactors-like peptide self-assembly exhibiting the enhanced catalytic activity in the peptide-metal nanocatalysts.

The peptide self-assembly would be expected to be as the assistance of metallic nanocatalysts to promote the catalytic reaction, attracting limited attention, but being highly anticipated. Herein, we proposed and verified an alternative strategy for enhancing the catalytic activity of the 4-nitrophenol reduction as a model reaction, by optimizing and constructing "cofactors" inspired amyloid peptide self-assembly applied in the peptide-metal nanocatalysts as the template due to the potential superiority of substrate binding. Amyloid peptide self-assembled membrane exhibited better enhanced catalytic activity, compared to peptide nanofibers as the template in the peptide-gold nanocatalysts. The optimized amyloid peptide was designated by molecular dynamic simulation to display the relative strongest interaction with specific substrate and the relative good template effect on the enhanced catalytic activity was also proved accordingly. This work may shed light on the future design and construction of novel enzyme mimics with dramatic enhanced catalytic activity by peptide assembly-metal nanocatalysts.

Evolution of the PB1 gene of human influenza A (H3N2) viruses circulating between 1968 and 2019.

One avian H3N2 influenza virus, providing its PB1 and HA segments, reassorted with one human H2N2 virus and caused a pandemic outbreak in 1968, killing over 1 million people. After its introduction to humanity, the pandemic H3N2 virus continued adapting to humans and has resulted in epidemic outbreaks every influenza season. To understand the functional roles of the originally avian PB1 gene in the circulating strains of human H3N2 influenza viruses, we analyzed the evolution of the PB1 gene in all human H3N2 isolates from 1968 to 2019. We found several specific residues dramatically changed around 2002-2009 and remained stable through to 2019. Then, we verified the functions of these PB1 mutations in the genetic background of the early pandemic virus, A/Hong Kong/1/1968(HK/68), as well as a recent seasonal strain, A/Jiangsu/34/2016 (JS/16). The PB1 V709I or PB1 V113A/K586R/D619N/V709I induced higher polymerase activity of HK/68 in human cells. And the four mutations acted cooperatively that had an increased replication capacity in vitro and in vivo at an early stage of infection. In contrast, the backward mutant, A113V/R586K/N619D/I709V, reduced polymerase activity in human cells. The PB1 I709V decreased viral replication in vitro, but this mutant only showed less effect on mice infection experiment, which suggested influenza A virus evolved in human host was not always consisted with highly replication efficiency and pathogenicity in other mammalian host. Overall, our results demonstrated that the identified PB1 mutations contributed to the viral evolution of human influenza A (H3N2) viruses.

Low-dose decitabine plus venetoclax is safe and effective as post-transplant maintenance therapy for high-risk acute myeloid leukemia and myelodysplastic syndrome.

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are usually associated with poor outcomes, especially in high-risk AML/MDS. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for patients suffering from high-risk AML/MDS. However, many patients relapse after allo-HSCT. Novel therapy to prevent relapse is urgently needed. Both the BCL-2 inhibitor venetoclax (VEN) and the hypomethylating agent decitabine (DEC) possess significant antitumor activity effects against AML/MDS. Administration of DEC has been shown to ameliorate graft-versus-host disease (GVHD) and boost the graft-versus-leukemia (GVL) effect post-transplantation. We therefore conducted a prospective study (ChiCTR1900025374) to examine the tolerability and efficacy of a maintenance therapy of low-dose decitabine (LDEC) plus VEN to prevent relapse after allo-HSCT for high-risk AML/MDS patients. Twenty patients with high-risk AML (n = 17) or high-risk MDS (n = 3) post-transplantation were recruited. Approximately day 100 post-transplantation, all patients received LDEC (15 mg/m2 for 3 d) followed by VEN (200 mg) on d 1-21. The cycle interval was 2 mo, and there was 10 cycles. The primary end points of this study were rates of overall survival (OS) and event-free survival (EFS). The secondary endpoints included adverse events (AEs), cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), incidences of acute GVHD (aGVHD) and chronic GVHD (cGVHD), and incidences of viral infection after allo-HSCT. Survival outcomes were assessed using Kaplan-Meier analysis. The median follow-up was 598 (149-1072) d. Two patients relapsed, 1 died, and 1 is still alive after the second transplant. The 2-y OS and EFS rates were 85.2% and 84.7%, respectively. The median 2-y EFS time was 525 (149-1072) d, and 17 patients still had EFS and were alive at the time of this writing. The most common AEs were neutropenia, anemia, thrombocytopenia, neutropenic fever, and fatigue. Grade 2 or 3 AEs were observed in 35% (7/20) and 20% (4/20) of the patients, respectively. No grade >3 AEs were observed. aGVHD (any grade) and cGVHD (limited or extensive) occurred in 55% and 20% of patients, respectively. We conclude that LDEC + VEN can be administered safely after allo-HSCT with no evidence of an increased incidence of GVHD, and this combination decreases the relapse rate in high-risk AML/MDS patients. This novel maintenance therapy may be a promising way to prevent relapse in high-risk AML/MDS patients.

Enhanced removal of Cr(III)-EDTA chelates from high-salinity water by ternary complex formation on DETA functionalized magnetic carbon-based adsorbents.

A novel amino-functionalized magnetic adsorbent (Fe3O4@C@DETA) was developed for adsorption of Cr(III) and Cr(III)-EDTA from wastewater. Fe3O4@C@DETA were successfully prepared by modification of Fe3O4@C with diethylenediamine (DETA), which exhibits a core-shell structure and sufficient saturation magnetization. Fe3O4@C@DETA exhibits much better adsorption performance for Cr(III) and its chelates than the Fe3O4@C because of newly introduced amino active sites. The enhanced adsorption capacity of Fe3O4@C@DETA for Cr(III) is 44.74 mg g-1 (at 25 °C and pH 3.0), which is due to the surface coordination with the newly introduced amino functional sites. The Cr(III)-EDTA anions as a whole was adsorbed through the electrostatic interaction with protonated amino species of the Fe3O4@C@DETA and have maximum adsorption capacity of 47.27 mg g-1 (at 25 °C and pH 3.0). The adsorption data of free and EDTA coordinated Cr(III) were followed the Langmuir equation, while the adsorption dynamics was well explained by pseudo second order model indicating the chemical nature of adsorption process. The higher concentration of Ca2+ ions in the wastewater compete for adsorption sites and inhibit the Cr(III) removal, while on other hand Ca2+ ions promotes the adsorption of Cr(III)-EDTA, because of electrostatic interaction with adsorbent active sits. Furthermore, the adsorbent can be easily separated by external magnetic field and regenerated in acidic solution. The adsorbent is stable, recyclable and have more than 75% regeneration efficiency and can be repeatedly used in the adsorption process.

Alterations of Brain Networks in Alzheimer's Disease and Mild Cognitive Impairment: A Resting State fMRI Study Based on a Population-specific Brain Template.

This study aimed to investigate the alterations in brain networks in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) based on a population-specific brain template. Previous studies on AD brain networks using graph theory rarely adopted brain templates specific for certain ethnicities. In this study, patients were divided into 3 groups: AD (n = 24), MCI (n = 27), and healthy controls (HCs, n = 33), and all of the subjects are Chinese. Functional brain networks were constructed for each group based on a Chinese brain template using resting-state functional magnetic resonance imaging (rs-fMRI) data; several graph metrics were calculated. Graph metrics with significant differences after false discovery rate (FDR) correction were analyzed with respect to correlations with four neuropsychological test scores: Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL), and Clinical Dementia Rating (CDR), which assessed the subjects' cognitive functions and ability to engage in ADL. Graph metrics including assortativity coefficient, nodal degree centrality, nodal clustering coefficient, nodal efficiency, and nodal local efficiency of the frontal gyrus and cerebellum were significantly altered in AD and MCI compared with HC. Several graph metrics were significantly correlated with cognitive function and the ability to engage in daily activities. The findings suggest that altered graph metrics in the frontal gyrus may reflect brain plasticity, and that patients with MCI may have unique graph metric alterations in the cerebellum. Future graph analysis studies on functional brain networks in AD and MCI based on population-specific brain atlases for particular ethnicities may prove valuable.

[Enhanced Membrane Anti-fouling Ability of Anaerobic Membrane Bioreactor Equipped with Bio-electrochemical System Using Nano-zero-valent Iron and Its Regulation Mechanism].

Membrane fouling is the biggest challenge of membrane bioreactor industrialization. In this study, a bio-electrochemical system (BES)-anaerobic membrane bioreactor (AnMBR) system was constructed, and the effect of nano-zero-valent iron (nZVI) on membrane anti-fouling ability and methane production was investigated. The results showed that the BES-AnMBR system was stable and the chemical oxygen demand (COD) removal rate was maintained at approximately 95%. The optimum condition was observed to be nZVI 0.1 g·g-1(VS). Under this condition, transmembrane pressure (TMP) was reduced by 28.1%, the membrane flux had a slight improvement, and methane production was up to 81.3 mL·g-1(CODremoved). This was 12.1% higher than that of the control. In addition, a further analysis of extracellular polymeric substances (EPS) fraction and membrane resistance showed that nZVI enhanced EPS decomposition, promoted the formation of an iron-rich layer of inorganic and organic matters on the membrane surface, and changed the distribution of organics and inorganics, thereby significantly alleviating membrane fouling. This study will enrich basic theory of conventional AnMBR and provide a new solution for efficient sludge treatment and resource utilization.

Integrated Analysis of microRNA-mRNA Expression in Mouse Lungs Infected With H7N9 Influenza Virus: A Direct Comparison of Host-Adapting PB2 Mutants.

MicroRNAs (miRNAs) are important regulators involved in the antiviral response to influenza virus infection, however, an analytical comparison of miRNA and mRNA expression changes induced by several H7N9 host-adapting PB2 mutants remains undone. Here, miRNA microarray and transcriptome sequencing of BALB/c mouse lungs infected with A/Anhui/1/2013 (H7N9) [hereafter referred to as H7N9/AH1-PB2-627K(WT)] and mutant variants with PB2 amino acid substitutions (avian-like H7N9/AH1-PB2-627E and mammalian-adapted H7N9/AH1-PB2-627E/701N) were directly compared. The results showed that influenza virus infection induced dysregulation of numerous host cell processes. In a miRNA-mRNA network associated with immunity, changes in the expression of 38 miRNAs and 58 mRNAs were detected following influenza virus infection. Notably, the miRNAs of mmu-miR-188-5p, mmu-miR-511-5p, mmu-miR-483-5p, and mmu-miR-690 were specifically associated with the replication of the avian-like virus H7N9/AH1-PB2-627E. Likewise, the miRNAs of mmu-miR-691, mmu-miR-329-3p, and mmu-miR-144-3p were specifically associated with the mammalian-adapted virus H7N9/AH1-PB2-627E/701N. Finally, the miRNAs of mmu-miR-98-5p, mmu-miR-103-3p, mmu-miR-199a-5p, and mmu-miR-378a-3p were specifically associated with H7N9/AH1-PB2-627K(WT) virus replication. This is the first report of comparative integration analysis of miRNA-mRNA expression of these three H7N9 influenza viruses with different host-adapting PB2 mutations. Our results highlight potential miRNAs of importance in influenza virus pathogenesis.

BmSUC1 is essential for glycometabolism modulation in the silkworm, Bombyx mori.

Sucrose is the most commonly transported sugar in plants and is easily assimilated by insects to fulfill the requirement of physiological metabolism. BmSuc1 is a novel animal ß-fructofuranosidase (ß-FFase, EC 3.2.1.26)-encoding gene that was firstly cloned and identified in silkworm, Bombyx mori. BmSUC1 was presumed to play an important role in the silkworm-mulberry enzymatic adaptation system by effectively hydrolyzing sucrose absorbed from mulberry leaves. However, this has not been proved with direct evidence thus far. In this study, we investigated sucrose hydrolysis activity in the larval midgut of B. mori by inhibition tests and found that sucrase activity mainly stemmed from ß-FFase, not α-glucosidase. Next, we performed shRNA-mediated transgenic RNAi to analyze the growth characteristics of silkworm larvae and variations in glycometabolism in vivo in transgenic silkworms. The results showed that in the RNAi-BmSuc1 transgenic line, larval development was delayed, and their body size was markedly reduced. Finally, the activity of several disaccharidases alone in the midgut and the sugar distribution, total sugar and glycogen in the midgut, hemolymph and fat body were then determined and compared. Our results demonstrated that silencing BmSuc1 significantly reduced glucose and apparently activated maltase and trehalase in the midgut. Together with a clear decrease in both glycogen and trehalose in the fat body, we conclude that BmSUC1 acts as an essential sucrase by directly modulating the degree of sucrose hydrolysis in the silkworm larval midgut, and insufficient sugar storage in the fat body may be responsible for larval malnutrition and abnormal petite phenotypes.

Vitamin C and vitamin E supplementation alleviates oxidative stress induced by dexamethasone and improves fertility of breeder roosters.

This study was conducted to determine the effect of supplemental dietary vitamin C (VC) and vitamin E (VE) on improving semen quality and antioxidative status in breeder roosters challenged with dexamethasone (DEX). 120 45-week-old Lveyang black-boned breeder roosters were divided into 5 experimental treatments, including negative group, positive group, and three trial groups, which were fed basal diet supplemented with 300mg/kg VC, 200mg/kg VE, or 300mg/kg VC and 200mg/kg VE (VC+VE). At 49 weeks of age, the positive control and trial groups were subcutaneously injected 3 times every other day with DEX 4 mg/kg body weight, the negative control group was sham injected with saline. At 50 weeks of age, average daily feed intake of birds challenged with DEX significantly increased (P<0.05), however, serum testosterone significantly decreased (P<0.05). Dietary supplementation of VC+VE enhanced serum testosterone and sperm motility remarkably (P<0.05). There were no differences in sperm viability between the DEX-treated groups. During the post-stress recovery period (52 weeks of age), dietary supplementation of VE and VC+VE significantly increased the body weight of birds under oxidative stress (P<0.01). VC, VE, and VC+VE groups had greater sperm viability than control group (P<0.01). Additionally, there was a decrease in the semen plasma malondialdehyde content (P<0.05) of the VC and VC+VE groups, and in the testicular malondialdehyde content (P<0.01) of the VE and VC+VE groups. In summary, VC, VE, especially their combination alleviate the oxidative stress induced by DEX and are favorable for the fertility of breeder roosters.