Effects of Ultra-High-Pressure Treatment on Chemical Composition and Biological Activities of Free, Esterified and Bound Phenolics from Phyllanthus emblica L. Fruits.

Phyllanthus emblica L. fruits (PEFs) were processed by ultra-pressure (UHP) treatment and then extracted by the ultrasonic-assisted extraction method. The influence of UHP on the phenolic composition, enzyme inhibitory activity and antioxidant activity of the free, esterified, and bound phenolic fractions from PEFs were compared. UHP pretreatment of PEFs significantly increased the total phenolic and flavonoid contents (p < 0.05). A total of 24 chemical compositions were characterized in normal and UHP-treated PEFs by UHPLC-ESI-HRMS/MS. Compared with normal PEFs, these three different phenolic fractions had stronger antioxidant activities and inhibitory effects on the intracellular reactive oxygen species (ROS) production in H2O2-induced HepG2 cells (p < 0.05). The ROS inhibition might be due to an up-regulation of the expressions of superoxide dismutase (SOD) and glutathione (GSH) activities. In addition, these three different phenolic fractions also significantly inhibited the activities of metabolic enzymes, including α-glucosidase, α-amylase and pancreatic lipase. This work may provide some insights into the potential economics and applications of PEFs in food and nutraceutical industries.

Influence of Ultra-High-Pressure Pretreatment Method on Chemical Constituents, Antioxidant and Cytoprotective Activities of Free, Esterified, and Bound Phenolics from Anneslea Fragrans Wall. Leaves.

Anneslea fragrans Wall., an edible and medicinal plant, is traditionally used to treat liver and gastrointestinal diseases. This paper aimed to investigate the influence of ultra-high pressure (UHP) pretreatment on the phenolics profiling, antioxidant, and cytoprotective activities of free (FP), esterified (EP), and bound (BP) phenolics from A. fragrans leaves. A total of 32 compounds were characterized and quantified. The davidigenin (44.46 and 113.37 mg/g extract) was the highest in A. fragrans leaves. The vitexin (9), afzelin (10), coreopsin (15), and davidigenin (28) were analyzed with MS2 fragment pathways. Results showed that UHP treated A. fragrans leaves had higher total phenolic (TPC) and total flavonoid (TFC) contents of FP, EP, and BP fractions than those in the raw leaves. Moreover, UHP pretreated A. fragrans leaves had higher scavenging activities on DPPH+• and ABTS+•, and inhibitory effects on the intracellular ROS generation in H2O2-induced HepG2 cells. UFP showed the highest inhibition of ROS production among the samples. Therefore, UHP pretreatment method might be used as an effective strategy for elevating the availabilities of A. fragrans leaves to develop functional foods.

Investigating the Marginal and Herd Effects of COVID-19 Vaccination for Reducing Case Fatality Rate: Evidence from the United States between March 2021 to January 2022.

Vaccination campaigns have been rolled out in most countries to increase vaccination coverage and protect against case mortality during the ongoing pandemic. To evaluate the effectiveness of COVID-19 vaccination, it is vital to disentangle the herd effect from the marginal effect and parameterize them separately in a model. To demonstrate this, we study the relationship between the COVID-19 vaccination coverage and case fatality rate (CFR) based on U.S. vaccination coverage at county level, with daily records from 11 March 2021 to 26 January 2022 for 3109 U.S. counties. Using segmented regression, we discovered three breakpoints of the vaccination coverage, at which herd effects could potentially exist. Controlling for county heterogeneity, we found the size of the marginal effect was not constant but actually increased as the vaccination coverage increased, and only the herd effect at the first breakpoint to be statistically significant, which implied an indirect benefit of vaccination may exist at the early stage of a vaccination campaign. Our results demonstrated that public-health researchers should carefully differentiate and quantify the herd and marginal effects when analyzing vaccination data, to better inform vaccination-campaign strategies as well as evaluate vaccination effectiveness.

Sediment-water distribution and potential sources of polyhalogenated carbazoles in a coastal river locating at a north metropolis, China.

The fate and transformation of PHCZs in the coastal river environment are not yet comprehensively understood. Paired river water and surface sediment were collected, and 12 PHCZs were analyzed to find out their potential sources and investigate the distribution of PHCZs between river water and sediment. The concentration of ∑PHCZs varied from 8.66 to 42.97 ng/g (mean 22.46 ng/g) in sediment and 17.91 to 81.82 ng/L (mean 39.07 ng/L) in river water. 18-B-36-CCZ was the dominant PHCZ congener in sediment, while 36-CCZ was in water. Meanwhile, the logKoc values for CZ and PHCZs were among the first calculated in the estuary and the mean logKoc varied from 4.12 for 1-B-36-CCZ to 5.63 for 3-CCZ. The logKoc values of CCZs were higher than those of BCZs, this may suggest that sediments have a higher capacity for accumulation and storage of CCZs than highly mobile environmental media.

Identification of heptapeptides targeting a lethal bacterial strain in septic mice through an integrative approach.

Effectively killing pathogenic bacteria is key for the treatment of sepsis. Although various anti-infective drugs have been used for the treatment of sepsis, the therapeutic effect is largely limited by the lack of a specific bacterium-targeting delivery system. This study aimed to develop antibacterial peptides that specifically target pathogenic bacteria for the treatment of sepsis. The lethal bacterial strain Escherichia coli MSI001 was isolated from mice of a cecal ligation and puncture (CLP) model and was used as a target to screen bacterial binding heptapeptides through an integrative bioinformatics approach based on phage display technology and high-throughput sequencing (HTS). Heptapeptides binding to E. coli MSI001 with high affinity were acquired after normalization by the heptapeptide frequency of the library. A representative heptapeptide VTKLGSL (VTK) was selected for fusion with the antibacterial peptide LL-37 to construct the specific-targeting antibacterial peptide VTK-LL37. We found that, in comparison with LL37, VTK-LL37 showed prominent bacteriostatic activity and an inhibitive effect on biofilm formation in vitro. In vivo experiments demonstrated that VTK-LL37 significantly inhibited bacterial growth, reduced HMGB1 expression, alleviated lesions of vital organs and improved the survival of mice subjected to CLP modeling. Furthermore, membrane DEGP and DEGQ were identified as VTK-binding proteins by proteomic methods. This study provides a novel strategy for targeted pathogen killing, which is helpful for the treatment of sepsis in the era of precise medicine.

The multiomics landscape of serum exosomes during the development of sepsis.

INTRODUCTION: Sepsis is an infection-induced severe inflammatory disorder leading to multiple organ dysfunction. It remains a highly lethal condition for which early diagnosis and therapy achieve unsatisfactory results. Circulating exosomes containing biomarkers and mediators of sepsis have recently received attention, but the progress has been far from optimal. OBJECTIVES: The present study focuses on the profiles of molecular dynamics in serum exosomes and explores the potential molecular mechanisms on serum exosomes during the process of sepsis. METHODS: We used high-performance liquid chromatography-tandem mass spectrometry and RNA-seq to detect the dynamic profiles of exosome proteins and RNAs (including mRNAs, lncRNAs and miRNAs) in serum exosomes from 3 healthy individuals and 9 septic patients at the different stages. Then integrative multiomics analyses were performed and the results were validated by qRT-PCR, LiquiChip assay and metabolomics analysis on mice subjected to cecal ligation and puncture (CLP) modeling. RESULTS: A total of 354 proteins, 195 mRNAs, 82 lncRNAs and 55 miRNAs were identified as differentially expressed molecules in serum exosomes from septic patients. Integrative multiomics analysis showed that exosome components were associated with cytokine storm, complement and clotting cascades, the endothelial barrier, 20S proteasome-dependent protein degradation and vitamin metabolism. Importantly, pretreatment with serum exosomes derived from mice subjected to CLP significantly restrained proinflammatory cytokine expression and alleviated tissue injury in septic mice. Further metabolomics analysis demonstrated that pretreatment with septic serum exosomes significantly affected the metabolites associated with vitamin digestion and absorption in CLP mice. CONCLUSION: Our study for the first time describes the landscape of the molecular dynamics of serum exosomes during the development of sepsis and proposes some hypothetical molecular mechanisms by integrative multiomics analysis, which may provide helpful diagnostic and therapeutic insights for the ongoing battle against sepsis.

Cantilevered adaptive fiber-optics collimator based on piezoelectric bimorph actuators.

A novel, to the best of our knowledge, cantilever construction design of an adaptive fiber-optics collimator (AFOC) based on piezoelectric bimorph actuators for tip/tilt control is introduced. With this new cantilever structure, an AFOC with a diameter of only 6 mm was developed, and the output laser beam deviation angle and resonance frequency of the device were measured. The experimental results show that this new AFOC can provide more than 1 mrad deflection angle at a 20 V driving voltage, and the first resonance frequency is about 500 Hz. Further, in order to verify whether the cantilever structure can be used in a high-power fiber collimator, a high-power X-Y positioner with an 8 mm diameter fiber end cap was developed. The experimental results show that the high-power X-Y positioner can output more than 2 kW laser power and provide about 330 µm displacement of the fiber end cap in the X direction and about 770 µm in the Y direction at a 150 V driving voltage.

Au-on-Ag nanostructure forin-situSERS monitoring of catalytic reactions.

Dual-functionality Au-on-Ag nanostructures (AOA) were fabricated on a silicon substrate by first immobilizing citrate-reduced Ag nanoparticles (Ag NPs, ∼43 nm in diameter), followed by depositing ∼7 nm Au nanofilms (Au NFs) via thermal evaporation. Au NFs were introduced for their catalytic activity in concave-convex nano-configuration. Ag NPs underneath were used for their significant enhancement factor (EF) in surface-enhanced Raman scattering (SERS)-based measurements of analytes of interest. Rhodamine 6G (R6G) was utilized as the Raman-probe to evaluate the SERS sensitivity of AOA. The SERS EF of AOA is ∼37 times than that of Au NPs. Using reduction of 4-nitrothiophenol (4-NTP) by sodium borohydride (NaBH4) as a model reaction, we demonstrated the robust catalytic activity of AOA as well as its capacity to continuously monitor via SERS the disappearance of reactant 4-NTP, emergence and disappearance of intermediate 4,4'-DMAB, and the appearance of product 4-ATP throughout the reduction process in real-time andin situ.

Activity Guided Isolation of Phenolic Compositions from Anneslea fragrans Wall. and Their Cytoprotective Effect against Hydrogen Peroxide Induced Oxidative Stress in HepG2 Cells.

Anneslea fragrans Wall., commonly known as "Pangpo Tea", is traditionally used as a folk medicine and healthy tea for the treatment of liver and intestine diseases. The aim of this study was to purify the antioxidative and cytoprotective polyphenols from A. fragrans leaves. After fractionation with polar and nonpolar organic solvents, the fractions of aqueous ethanol extract were evaluated for their total phenolic (TPC) and flavonoid contents (TFC) and antioxidant activities (DPPH, ABTS, and FRAP assays). The n-butanol fraction (BF) showed the highest TPC and TFC with the strongest antioxidant activity. The bio-guided chromatography of BF led to the purification of six flavonoids (1-6) and one benzoquinolethanoid (7). The structures of these compounds were determined by NMR and MS techniques. Compound 6 had the strongest antioxidant capacity, which was followed by 5 and 2. The protective effect of the isolated compounds on hydrogen peroxide (H2O2)-induced oxidative stress in HepG2 cells revealed that the compounds 5 and 6 exhibited better protective effects by inhibiting ROS productions, having no significant difference with vitamin C (p > 0.05), whereas 6 showed the best anti-apoptosis activity. The results suggest that A. fragrans could serve as a valuable antioxidant phytochemical source for developing functional food and health nutraceutical products.

Screening silica-confined single-atom catalysts for nonoxidative conversion of methane.

The development of a single-atom iron catalyst (Fe©SiO2) for the direct conversion of methane to olefins, aromatics, and hydrogen is a breakthrough in the field of nonoxidative conversion of methane (NCM). However, the optimization of the catalyst remains desirable for industrial applications. Herein, 25 transition metals, including Sc, Ti, V, Cr, Mn, Co, Ni, Cu, Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Ag, Hf, Ta, W, Re, Os, Ir, Pt, and Au, are selected to replace the central Fe atom for screening out better single-atom catalysts for the NCM. Using the performance on the activation of methane, such as the adsorption energy of methane, the dissociation energy, and the barrier of methane as the screening descriptors, Mn©SiO2, Fe©SiO2, W©SiO2, and Re©SiO2 are first screened out. The remarkable performance of the four catalysts on methane activation is attributed to the unique geometric structure and the dz 2 orbitals of the central metal crossing over the Fermi level, which can benefit the interaction between methane and the catalysts. By considering the catalytic performance on the whole pathway of methane to ethylene, W©SiO2 is finally selected as the most active catalyst for the NCM, which has the lowest rate-determining barrier of 1.62 eV and the smallest free energy span (1.06 eV) of the overall catalytic cycle.

Anneslea fragrans Wall. ameliorates ulcerative colitis via inhibiting NF-κB and MAPK activation and mediating intestinal barrier integrity.

ETHNOPHARMACOLOGICAL RELEVANCE: Anneslea fragrans Wall. is traditionally used as a folk medicine in treating indigestion, fever, dysentery, diarrhea, and liver inflammation in China, Vietnam and Cambodia. However, its anti-inflammatory activity and mechanism under a safety therapeutic dose as well as the main chemical components have not yet been fully investigated. AIM OF THE STUDY: This study aimed to explore the therapeutic effect and possible molecular mechanisms of aqueous-methanol extract (AFE) of A. fragrans leaves on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) mice and illustrate its potent anti-inflammatory chemical compounds. MATERIALS AND METHODS: The AFE was obtained and then analyzed by high performance liquid chromatography (HPLC). Phytochemical investigation on the AFE was carried out to isolate and characterize its major components. The acute toxicity test was performed to provide the safety information of AFE. Subsequently, the protective effect of AFE on DSS-induced UC was evaluated by physiological changes, histopathological and immunohistochemical analysis, and the expressions of antioxidant enzyme, pro-inflammatory cytokines and anti-inflammatory cytokines. The expressions of target proteins in nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) were determined by western blot analysis. The tight junction (TJ) proteins in colon tissue were performed by immunohistochemical technique for evaluating the intestinal barrier integrity. RESULTS: HPLC guided isolation of AFE resulted into two dihydrochalcones, which were elucidated as vacciniifolin (1) and confusoside (2). Acute toxicity evaluation revealed that median lethal dose (LD50) of AFE was greater than 5000 mg/kg. Furthermore, AFE significantly attenuated ulcerative colitis symptoms, suppressed myeloperoxidase activity, and increased the expression of superoxide dismutase and glutathione. AFE treatment could also reduce the levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 and increase the levels of interleukin-4 and interleukin-10 in colon tissues and serum of DSS-induced UC mice. In addition, AFE significantly increased the expression of zonula occludens-1, occludin and claudin-1, and inhibited the phosphorylation of target protein of the NF-κB and MAPK signaling pathways in colon tissue. CONCLUSION: Dihydrochalcone glycosides are the major chemical constituents in AFE. AFE ameliorated DSS-induced UC in mice by inhibiting the inflammatory response via modulation of NF-κB and MAPK pathways and maintaining the intestinal barrier function, indicating that the plant A. fragrans could be used as a therapeutic candidate for ulcerative colitis.

Spectroscopically clean Au nanoparticles for catalytic decomposition of hydrogen peroxide.

Au nanoparticles synthesized from colloidal techniques have the capability in many applications such as catalysis and sensing. Au nanoparticles function as both catalyst and highly sensitive SERS probe can be employed for sustainable and green catalytic process. However, capping ligands that are necessary to stabilize nanoparticles during synthesis are negative for catalytic activity. In this work, a simple effective mild thermal treatment to remove capping ligands meanwhile preserving the high SERS sensitivity of Au nanoparticles is reported. We show that under the optimal treatment conditions (250 °C for 2 h), 50 nm Au nanoparticles surfaces are free from any capping molecules. The catalytic activity of treated Au nanoparticles is studied through H2O2 decomposition, which proves that the treatment is favorable for catalytic performance improvement. A reaction intermediate during H2O2 decomposition is observed and identified.

Observation and Identification of an Atomic Oxygen Structure on Catalytic Gold Nanoparticles.

Interactions between oxygen and gold surfaces are fundamentally important in diverse areas of science and technology. In this work, an oxygen dimer structure was observed and identified on gold nanoparticles in catalytic decomposition of hydrogen peroxide to oxygen and water. This structure, which is different from isolated atomic or molecular oxygen surface structures, was observed with in situ surface-enhanced Raman spectroscopic measurements and identified with density functional theory calculations. The experimental measurements were performed using monodisperse 5, 50 and 400 nm gold particles supported on silica with liquid-phase hydrogen and deuterium peroxides at multiple pH values. The calculations show that on surfaces with coordinatively unsaturated gold atoms, two oxygen atoms preferentially share a gold atom with a bond distance of 0.194-0.196 nm and additionally bind to two other surface gold atoms with a larger bond distance of 0.203-0.213 nm, forming an Au-O-Au-O-Au structure. The formation of this structure depends on reaction rates and conditions.