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The objective of this study was to evaluate the impacts of different drying technologies including microwave drying (MD), vacuum microwave drying (VMD), sun drying (SD), vacuum drying (VD), hot air drying (HAD), and vacuum freeze drying (VFD) on the physical characteristics, nutritional properties and antioxidant capacities of kiwifruit pomace in order to realize by-product utilization and improve energy efficiency. Results showed that both MD and VMD significantly reduced drying time by >94.6%, compared to traditional thermal drying which took 14–48 h. MD exhibited the highest content of soluble dietary fiber (9.5%) and the lowest energy consumption. Furthermore, VMD resulted in the highest content of vitamin C (198.78 mg/100 g) and reducing sugar (73.78%), and the antioxidant capacities ranked only second to VFD. Given the financial advantages and product quality, VMD was suggested to be advantageous technology in actual industrial production. [Display omitted] • Quality of kiwifruit pomace was influenced by different drying technologies. • Vacuum microwave drying (VMD) dramatically reduced drying time of kiwifruit pomace. • Microwave drying (MD) exhibited low energy consumption for kiwifruit pomace drying. • MD possessed high content of soluble dietary fiber in kiwifruit pomace. • VMD maintained high antioxidant capacities compared to conventional thermal drying. [ABSTRACT FROM AUTHOR]

Plant-derived extracellular vesicles (PLEVs), as a type of naturally occurring lipid bilayer membrane structure, represent an emerging delivery vehicle with immense potential due to their ability to encapsulate hydrophobic and hydrophilic compounds, shield them from external environmental stresses, control release, exhibit biocompatibility, and demonstrate biodegradability. This comprehensive review analyzes engineering preparation strategies for natural vesicles, focusing on PLEVs and their purification and surface engineering. Furthermore, it encompasses the latest advancements in utilizing PLEVs to transport active components, serving as a nanotherapeutic system. The prospects and potential development of PLEVs are also discussed. It is anticipated that this work will not only address existing knowledge gaps concerning PLEVs but also provide valuable guidance for researchers in the fields of food science and biomedical studies, stimulating novel breakthroughs in plant-based therapeutic options. • Plant-derived extracellular vesicles (PLEVs) are important for disease treatment. • Advances of PLEVs purification and surface modification engineering. • Latest progress in transporting bioactive substances as nano-therapeutic system. [ABSTRACT FROM AUTHOR]

Soybean meal (SBM), a high-protein animal feed, contains several anti-nutritional factors, which limit its utilization. Poly-γ-glutamic acid (γ-PGA), a biological macromolecule, can significantly improve the health and growth benefits of animal feed. However, there are rare reports about SBM fermentation with γ-PGA-producing bacteria to improve its nutritional quality. In this study, we isolated a glutamic acid-independent poly γ-glutamic acid (γ-PGA) producing Bacillus velezensis SCP024–S-4 bacterial strain and used it for solid fermentation of SBM. The results showed that the maximum γ-PGA yield in fermented soybean meal (FSBM) reached up to 89.64 g/kg without adding glutamic acid. Meanwhile, the content of proteins, free amino acids and small peptides increased by 12.83%, 347.96 μg/g and 108.11 mg/g, respectively. Soy globulin, β-conglutinin and trypsin inhibitor all decreased below 3 mg/g. Mice were fed with CK (control diet), SBM and FSBM respectively. The average daily food intake in the FSBM, SBM, and CK groups were 7.68, 5.25, and 6.36 g, respectively. Compared with the CK group, the mice weight growth rate was significantly higher in the FSBM group. Mice blood and spleen tests showed no negative effect of FSBM. The high-throughput sequencing of mice intestinal microflora indicated that FSBM increased the richness of intestinal microbiota ; especially, the types and quantities of Lactobacillus were significantly increased. This study provides a feasible strategy to improve the nutritional quality of SBM as an animal feed. [Display omitted] • A novel glutamic acid-independent γ-PGA producing Bacillus velezensis was newly isolated. • Nutritional quality and palatability were improved through degrading nutritional inhibitors and producing γ-PGA. • FSBM improved the growth and intestinal microbial community indicators of mice. [ABSTRACT FROM AUTHOR]

Objective The cortico–thalamo–cortical network plays a key role in childhood absence epilepsy (CAE). However, the exact interaction between the cortex and the thalamus remains incompletely understood. This study aimed to investigate the dynamic changes of frequency-dependent neural networks during the initialization of absence seizures. Methods Magnetoencephalography data from 14 patients with CAE were recorded during and between seizures at a sampling rate of 6000 Hz and analyzed in seven frequency bands. Neuromagnetic sources were volumetrically scanned with accumulated source imaging. Effective connectivity networks of the entire brain, including the cortico–thalamo–cortical network, were evaluated at the source level through Granger causality analysis. Results The low-frequency (1–80 Hz) activities showed significant frontal cortical and parieto–occipito–temporal junction source localization around seizures. The high-frequency (80–250 Hz) oscillations showed predominant activities consistently localized in deep brain areas and medial frontal cortex. The increased cortico–thalamic effective connectivity was observed around seizures in both low- and high-frequency ranges. The direction was predominantly from the cortex to the thalamus at the early time, although the cortex that drove connectivity varied among subjects. Conclusions The cerebral cortex plays a key role in driving the cortico–thalamic connections at the early portion of the initialization of absence seizures. The oscillatory activities in the thalamus could be triggered by networks from various regions in the cortex. Significance The dynamic changes of neural network provide evidences that absence seizures are probably resulted from cortical initialized cortico–thalamic network. [ABSTRACT FROM AUTHOR]

Lager beer with high content of cyclic adenosine monophosphate (c-AMP) and strong antioxidant activity was produced by supplementing six jujube cultivars (Ziziphus Jujuba cv. Hetian , Muzao , Huizao , Goutou , Jinsixiaozao , and Banzao) as adjuncts. Jujube supplementation significantly increased total phenolic and flavonoids contents of final beers, and therefore improved antioxidant activities based on DPPH, ABTS and FRAP methods, especially for Banzao supplementation, exhibiting the highest antioxidant activities, increasing by 31.00%, 20.81% and 43.66%, respectively, which were positively correlated with protocatechuic acid, p-coumaric acid and rutin levels. Furthermore, hierarchical cluster analysis revealed that jujube supplementation significantly influenced flavor formation in final beers. There were 17 new volatile compounds formation after jujube supplementation, including one alcohol, 11 esters, two acids and three aldehydes, suggesting the improved complexity of beer flavor. In addition, high contents of c-AMP ranging from 4.02 to 15.14 μg/mL were observed in final beers fermented by jujube supplementation, endowing beer with a new health function. [Display omitted] • Jujube was suggested as a promising adjunct for beer brewing. • Beer fermented by jujube supplementation exhibited stronger antioxidant capacity. • Jujube adjunct improved protocatechuic acid, p-comaric acid, and rutin contents. • Beer fermented by jujube supplementation exhibited high c-AMP level. • Jujube supplementation improved the aroma complexity of beer. [ABSTRACT FROM AUTHOR]

[Display omitted] • New A56 -based PROTACs target-degrading PD-L1 have been designed and synthesized. • Compounds 9i and 9j induce the internalization and degradation of PD-L1 in HCC-827 cells. • Compounds 9i and 9j degrade of PD-L1 through dual means of lysosome and proteasome. • The compounds have good anti-tumor activity by activating immunity in vivo. Currently, antibody drugs targeting programmed cell death ligand 1 (PD-L1) have achieved promising results in cancer treatment, while the development of small-molecule drugs lags behind. In this study, we designed and synthesized a series of PD-L1-degrading agents based on the PROTAC design principle, utilizing the PD-L1 inhibitor A56. Through systematic screening of ligands and linkers and investigating the structure–activity relationship of the degraders, we identified two highly active compounds, 9i and 9j. These compounds enhance levels of CD4+, CD8+, granzyme B, and perforin, demonstrating significant in vivo antitumor effects with a tumor growth inhibition (TGI) of up to 57.35 %. Both compounds facilitate the internalization of PD-L1 from the cell surface and promote its degradation through proteasomal and lysosomal pathways, while also maintaining inhibition of the PD-1/PD-L1 interaction. In summary, our findings provide a novel strategy and mechanism for developing biphenyl-based PROTAC antitumor drugs targeting and degrading PD-L1. [ABSTRACT FROM AUTHOR]

In this work, nickel cobalt bimetallic sulfide with typical multi-shell hollow sphere structure behaved superior electrocatalytic activity towards hydrogen evolution reaction (HER), which have been prepared through a easy method included solvothermal step, calcination step and in-situ sulfurization step. The composition and structure of the obtained nickel cobalt bimetallic sulfide are controlled through adjusting the sulfurization temperature and dosage of sulfur source. The as-prepared Ni–Co-S multi-shell hollow microspheres (abbreviated as Ni-Co-S) behaves superb HER properties in alkaline medium and Ni-Co-S-340(60) performs the most superior property, in which reflected the lowest overpotential (129 mV vs. RHE) at the current density of 10 mA cm−2 and the smallest Tafel slope (96.1 mV dec−1) among all the synthesized samples. The superior electrocatalytic performance of the obtained Ni-Co-S-340(60) for HER is owing to the unique multi-shell hollow structure derived from the intrinsic porous character of Ni-Co-BTC MOF precursor in one hand. And in the other hand, introducing highly active NiCo 2 S 4 into NiS 2 would enhance its elctrocatalytic activity because of the strong interfacial effect between NiS 2 and NiCo 2 S 4. Image 1 [ABSTRACT FROM AUTHOR]

[Display omitted] • Electron beam irradiation inactivated Lactobacillus plantarum thoroughly. • High pressure processing increased extractable phenolics and carotenoids contents. • High pressure processing improved antioxidant capacity of fermented cabbage sauce. • Non-thermal processing was more beneficial to flavor formation than thermal. To extend shelf life of fermented spicy Chinese cabbage sauce at room temperature, the effects of electron beam irradiation (EBI), high pressure processing (HPP), pasteurization (PT) and autoclave sterilization (AS) treatments on the colony counts of Lactobacillus plantarum , phytochemicals, antioxidant activities and volatile compounds were investigated. Results showed that thermal and non-thermal treatments could significantly decrease the colony counts of Lactobacillus plantarum , in which EBI and AS treatments inactivated Lactobacillus plantarum thoroughly. EBI and HPP treatments were superior to PT and AS treatments in terms of volatile compounds, bioactive compounds and antioxidant activities. The total contents of volatile compounds in sauces treated by EBI and HPP were significantly increased by 43.92%–61.87% and 71.53%–84.46%, respectively, and the new formed substance 2,3-butanedione endowed sauces with sweet and creamy aroma. In addition, HPP treatment improved the extractable contents of total phenolics and carotenoids, retained capsicum red pigment content, and significantly enhanced antioxidant capacities of sauces. Sauce treated by HPP at 200 MPa exhibited the highest total carotenoid content, DPPH radical scavenging activity and FRAP, increasing by 9.27%, 2.24% and 16.13%, respectively, compared with CK. EBI treatment exhibited higher total phenolic content and FRAP, which positively depended on the dose. Therefore, HPP and EBI treatments were suggested as potential technologies to improve shelf-life stability and volatile compounds of fermented spicy Chinese cabbage sauce. [ABSTRACT FROM AUTHOR]

This study investigated the effects of ultrasound-assisted phosphorylation on gelling properties of fish gelatin (FG). Ultrasound-assisted phosphorylation (UP) for 60, 90, and 120 min resulted in >6.54% increase of phosphorylation degree and decreased zeta potential of FG. Atomic force microscopy revealed that UP-FGs showed larger aggregates than P-FGs (normal phosphorylation FGs). Low frequent-NMR and microstructure analysis revealed that phosphorylation enhanced water-binding capability of FG and improved the gel networks. However, UP60 had the highest gel strength (340 g), gelling (17.96 °C) and melting (26.54 °C) temperature while UP90 and UP120 showed slightly lower of them. FTIR analysis indicated thatβ-sheet and triple helix content increased but random coil content decreased in phosphorylated FGs. Mass spectrometry demonstrated phosphate groups mainly bound to serine, threonine and tyrosine residues of FG and UP-FG exhibited more phosphorylation sites. The study showed that mild phosphorylation (UP60) could be applied to improve FG gel properties. [Display omitted] • Ultrasound assistance increased the phosphorylation degree and sites of FG. • Phosphate group mainly bound to serine, threonine and tyrosine residues of FG. • Moderate phosphorylation increased water binding ability, GS, GT and MT of FG. • Over phosphorylation led to poor gel network and gel properties of FG. [ABSTRACT FROM AUTHOR]

A series of novel 2-arylmethoxy-4-(2-fluoromethyl-biphenyl-3-ylmethoxy) benzylamine derivatives was designed, synthesized, and evaluated for their antitumor effects as PD-1/PD-L1 inhibitors both in vitro and in vivo. Firstly, the ability of these compounds to block the PD-1/PD-L1 immune checkpoint was assessed using the homogeneous time-resolved fluorescence (HTRF) assay. Two of the compounds can strongly block the PD-1/PD-L1 interaction, with IC 50 values of less than 10 nM, notably, compound HD10 exhibited significant clinical potential by inhibiting the PD-1/PD-L1 interaction with an IC 50 value of 3.1 nM. Further microscale thermophoresis (MST) analysis demonstrated that HD10 had strong interaction with PD-L1 protein. Co-crystal structure (2.7 Å) analysis of HD10 in complex with the PD-L1 protein revealed a strong affinity between the compound and the target PD-L1 dimer. This provides a solid theoretical basis for further in vitro and in vivo studies. Next, a typical cell-based experiment demonstrated that HD10 could remarkably prevent the interaction of hPD-1 293 T cells from human recombinant PD-L1 protein, effectively restoring T cell function, and promoting IFN-γ secretion in a dose-dependent manner. Moreover, HD10 was effective in suppressing tumor growth (TGI = 57.31 %) in a PD-1/PD-L1 humanized mouse model without obvious toxicity. Flow cytometry, qPCR, and immunohistochemistry data suggested that HD10 inhibits tumor growth by activating the immune system in vivo. Based on these results, it seems likely that HD10 is a promising clinical candidate that should be further investigated. [Display omitted] • Novel 2-fluoromethyl-biphenyl containing benzylamine derivatives were synthesized. • HD10 exhibited significant clinical potential as a PD-1/PD-L1 inhibitor. • Co-crystal structure (2.7 Å) of HD10 with the PD-L1 protein revealed their strong interaction. • HD10 showed tumor growth inhibition (TGI = 57.31 %) in a humanized mouse model without obvious toxicity. [ABSTRACT FROM AUTHOR]

Bisphenol M (BPM), an alternative to bisphenol A (BPA), is commonly utilized in various industrial applications. However, BPM does not represent a safe substitute for BPA due to its detrimental effects on living beings. This research aimed to assess the influence of BPM exposure on the in vitro maturation of mouse oocytes. The findings revealed that BPM exposure had a notable impact on the germinal vesicle breakdown (GVBD) rate and polar body extrusion (PBE) rate throughout the meiotic progression of mouse oocytes, ultimately resulting in meiotic arrest. Investigations demonstrated that oocytes exposure to BPM led to continued activation of spindle assembly checkpoint. Further studies revealed that securin and cyclin B1 could not be degraded in BPM-exposed oocytes, and meiosis could not realize the transition from the MI to the AI stage. Mechanistically, BPM exposure resulted in abnormal spindle assembly and disrupted chromosome alignment of oocytes. Additionally, abnormal positioning of microtubule organizing center-associated proteins implied that MTOC may be dysfunctional. Furthermore, an elevation in the acetylation level of α-tubulin in oocytes was observed after BPM treatment, leading to decreased microtubule stability. In addition to its impact on microtubules, BPM exposure led to a reduction in the expression of the actin, signifying the disruption of actin assembly. Further research indicated a heightened incidence of DNA damage in oocytes following BPM exposure. Besides, BPM exposure induced alterations in histone modifications. The outcomes of this experiment demonstrate that BPM exposure impairs oocyte quality and inhibits meiotic maturation of mouse oocytes. • BPM inhibits meiotic maturation of oocytes. • BPM causes abnormal spindle morphology and disorganized chromosome arrangement in oocytes. • BPM affects cytoskeleton architecture and cell cycle processess in mouse oocytes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Microfluidic electrospinning for synthesizing fucoxanthin-loaded core–shell nanofibers. • GZ12/ZFx nanofibers significantly enhance hydrophobicity and stability of fucoxanthin. • Fucoxanthin-loaded nanofibers alleviate lipid accumulation and oxidative stress in oleic acid-incubated HepG2 cells. Fucoxanthin is a xanthophyll carotenoid that possesses potent antioxidant, anti-obesity, and anti-tumor properties. However, its limited solubility in water and susceptibility to degradation create challenges for its application. In this study, a microfluidic coaxial electrospinning technique was used to produce core–shell zein-gelatin nanofibers for encapsulating fucoxanthin, enhancing its bioavailability, and improving its stability. In comparison to uniaxially-loaded fucoxanthin nanofibers, the encapsulation efficiency of fucoxanthin reached 98.58 % at a core–shell flow rate ratio of 0.26:1, representing a 14.29 % improvement. The photostability of the nanofibers increased by 74.59 % after three days, UV stability increased by 38.82 % after 2 h, and temperature stability also significantly improved, demonstrating a protective effect under harsh environmental conditions (P < 0.05). Additionally, nanofibers effectively alleviated oleic acid-induced reactive oxygen species production and reduced fluorescence intensity by 54.76 %. MTT experiments indicated great biocompatibility of the nanofibers, effectively mitigating mitochondrial membrane potential polarization and lipid accumulation in HepG2 cells. Overall, the microfluidic coaxial electrospinning technique enables promising applications of fucoxanthin delivery in the food industry. [ABSTRACT FROM AUTHOR]

Triphenyltin chloride (TPTCL) is widely used in various industrial and agricultural applications. This study aimed to elucidate the mechanisms underlying the toxicological effects of TPTCL on oocytes. The obtained findings revealed that TPTCL exposure reduced polar body extrusion (PBE) and induced meiotic arrest. Mechanistically, TPTCL disrupted meiotic spindle assembly and chromosome alignment. Further analysis indicated a significant decrease in p-MAPK expression, and disturbances in the localization of Pericentrin and p-Aurora A in TPTCL exposed oocytes, which suggesting impaired microtubule organizing center (MTOC)function. Moreover, TPTCL exposure enhance microtubule acetylation and microtubule instability. Therefore, the spindle assembly checkpoint (SAC) remained activated, and the activity of the anaphase-promoting complex (APC) was inhibited, thereby preventing oocytes from progressing into the entering anaphase I (AI) stage. TPTCL exposure also augmented the actin filaments in the cytoplasm. Notably, mitochondrial function appeared unaffected by TPTCL, as evidenced indicated by stable mitochondrial membrane potential and ATP content. Furthermore, TPTCL treatment altered H3K27me2, H3K27me3 and H3K9me3 levels, suggesting changes in epigenetic modifications in oocytes. Taken together, our results suggest that TPTCL disrupts cytoskeleton assembly, continuously activates SAC, inhibits APC activity, and blocks meiotic progression, ultimately impair oocyte maturation. • TPTCL exposure compromises the meiotic maturation of mouse oocytes. • TPTCL exposure affects spindle assembly in mouse oocytes. • TPTCL exposure affects the localization of MTOC-associated proteins and reduces P-Mapk expression in mouse oocytes. • TPTCL exposure continuously activates of spindle assembly checkpoint in mouse oocytes. [ABSTRACT FROM AUTHOR]

The molecular mechanisms governing skin fibrosis in murine sclerodermatous graft-versus-host disease (Scl GVHD) are not known. We used Affymetrix DNA microarrays representing >14,000 mouse genes to characterize global gene expression in skin during development of Scl GVHD in lethally irradiated BALB/c (H-2d) mice transplanted with B10.D2 (H-2d) bone marrow and spleen cells. These mice develop skin thickening, whereas control mice transplanted with syngeneic BALB/c (H-2d) bone marrow and spleen cells do not develop disease. We found consistent differences between mice with Scl GVHD and controls in cytokine messenger RNAs (mRNAs) for both Th1-like (IFN-γ) and Th2-like (IL-6, Il-10, and IL-13) inflammatory patterns. mRNAs for chemokines CCL2, CCL5, CCL17, IFN-γ inducible chemokines (CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC), and for growth factors such as platelet-derived growth factor-c, connective tissue growth factor, fibroblast growth factor 1, epidermal growth factor, nerve growth factor-β, vascular endothelial growth factor (VEGF)-α, and VEGF-β were elevated, similar to human scleroderma. mRNAs for cell adhesion molecules, such as L-selectin (selectin lymphocyte), P-selectin (selectin platelet), E-selectin (selectin endothelium), and vascular cell adhesion molecule 1, were also upregulated. In separate experiments, we confirmed the increased synthesis of IFN-γ and IL-2, unchanged IL-10, and absence of tumor necrosis factor-α, and IL-4 proteins by flow cytometry of isolated skin T cells. These constellations of immunologic changes provide a “fingerprint” for fibrosing autoimmune disease. They are useful to understand the pathogenesis of Scl GVHD, to identify markers for early diagnosis of disease, and to devise more effective strategies for intervention in early scleroderma and Scl GVHD.Journal of Investigative Dermatology (2007) 127, 281–292. doi:10.1038/sj.jid.5700517; published online 17 August 2006 [ABSTRACT FROM AUTHOR]

PD-L1 is an important immune checkpoint protein that can bind to T cells' PD-1 receptor, thereby promoting immune escape from tumors. In recent years, many researchers have developed strategies to degrade PD-L1 to improve the effect of immunotherapy. The study of degrading PD-L1 provides new opportunities for immunotherapy. Here, we mainly summarize and review the current active molecules and mechanisms that mediate the degradation of immature and mature PD-L1 during the post-translational modification stages, involving PD-L1 phosphorylation, glycosylation, palmitoylation, ubiquitination, and the autophagy-lysosomal process. This review expects that by degrading PD-L1 protein, we will not only gain a better understanding of oncogenic mechanisms involving tumor PD-L1 protein but also provide a new way to improve immunotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

The cytochrome P450 monooxygenases of insects play crucial roles in the metabolic detoxification of insecticides. Our previous finding showed that two cytochrome P450 genes, both CYP301B1 and CYP6AX1v2 , in the BPH underwent overexpression due to β-asarone. In this study, we investigated the molecular characteristics, expression patterns and functions of these two cytochrome P450 genes. The results showed that CYP301B1 had the highest expression level in the eggs, while CYP6AX1v2 was expressed in macropterous female adults. Moreover, the expression level of CYP301B1 in the head was higher than that in the integument, fat body and gut. The expression level of CYP6AX1v2 in the fat body and gut was higher than that in head and integument. Importantly, silencing CYP301B1 and CYP6AX1v2 separately could increase the sensitivity, resulting in significant higher mortality of BPH following treatment with β-asarone. Our findings indicated that CYP301B1 and CYP6AX1v2 could contribute to the resistance of BPH to β-asarone, and these two genes may be involved in the detoxification metabolism of β-asarone in BPH. • CYP301B1 is mainly expressed in the eggs, head and integument. • CYP6AX1v2 is mainly expressed in macropterous female adults and the fat body and gut. • Silencing CYP301B1 and CYP6AX1v2 could increase the sensitivity of BPH to β-asarone. [ABSTRACT FROM AUTHOR]

The investigation and development of bimetallic phosphosulphide electrocatalyst with low cost and abundant reserves is extremely significant for the improvement of the efficiency of hydrogen evolution reaction (HER), while it remains a challenge. Herein, we explored a feasible method to prepare three-dimensional (3D) self-supported FeNiP-S/NF-5 nanosheet arrays on Ni foil (NF) by hydrothermal method and in situ phosphorization and following sulfurization treatment. The as-obtained FeNiP-S/NF-5 only needs a potential of 183 mV vs. RHE to reach 20 mA cm−2, which is smaller than that of FeNiP/NF (187 mV vs. RHE) and FeNiS/NF-5 (239 mV vs. RHE), presenting excellent electrocatalytic stability. Such outstanding performance of the FeNiP-S/NF-5 can be attributed to following several reasons: (i) bi-metallic phosphide and sulphide have the high intrinsic activity because of its synergistic effect; (ii) the 3D nanosheet arrays structure of FeNiP-S/NF-5 is conducive to expose plentiful active sites and facilitate the electrolyte penetration along with electron transportation; (iii) the sulfurization process followed phosphorization treatment could further optimize their electronic structure and inhibited the surface oxidation of catalyst in the catalytic process. Image 1 • NiS modified FeNiP nanosheet electrocatalyst have been synthesized. • The best condition of sulfurization treatment has also been investigated. • The 3D structure and the introduction of NiS can boost activity. [ABSTRACT FROM AUTHOR]

Bimetallic phosphides have been widely investigated as electrocatalysts for oxygen evolution reaction (OER) due to their efficient activity and environmental friendliness. While the reasonable design and controllable synthesis of bimetallic phosphide with typical nanostructure is still a great challenge. Hence, we put forward a novel and straightforward way for constructing FeP nanoparticles coated Ni 2 P ultrathin nanotube arrays on the surface of Ni foil (FeP@Ni 2 P/NF), which is synthesized through two steps of electrodeposition and subsequent in-situ phosphorization process. The obtained FeP@Ni 2 P/NF shows excellent electrochemical activity for OER, and it only needs potential of 1.52 V vs. RHE to reach the current density of 50 mA cm−2 in an alkaline media. The excellent electrocatalytic activity of FeP@Ni 2 P/NF mainly benefits from: (i) the synergistic effect between FeP and Ni 2 P promoting electron transfer; (ii) the formation of the unique 3D ultrathin nanotube arrays increasing the quantity of active sites and avoiding the agglomeration of catalysts during testing. In addition, the influence of reaction condition on the electrochemical activity for OER has also been investigated through altering the phosphorization temperature of precursor. Image 1 • The bimetallic phosphide was obtained through electrodeposition and phosphorization process. • The typical nanoparticle coated nanotube structure could expose more active sites. • Temperature of phosphorization treatment is a crucial factor to the enhanced activity. • The synergistic effective between FeP and Ni 2 P contributes to the excellent performance. [ABSTRACT FROM AUTHOR]

Obesity is associated with an increased risk of primary graft dysfunction (PGD) after lung transplantation. The contribution of specific adipose tissue depots is unknown. We performed a prospective cohort study of adult lung transplant recipients at 4 U.S. transplant centers. We measured cross-sectional areas of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on chest and abdominal computed tomography (CT) scans and indexed each measurement to height.2 We used logistic regression to examine the associations of adipose indices and adipose classes with grade 3 PGD at 48 or 72 hours, and Cox proportional hazards models to examine survival. We used latent class analyses to identify the patterns of adipose distribution. We examined the associations of adipose indices with plasma biomarkers of obesity and PGD. A total of 262 and 117 subjects had available chest CT scans and underwent protocol abdominal CT scans, respectively. In the adjusted models, a greater abdominal SAT index was associated with an increased risk of PGD (odds ratio 1.9, 95% CI 1.02–3.4, p = 0.04) but not with survival time. VAT indices were not associated with PGD risk or survival time. A greater abdominal SAT index correlated with greater pre- and post-transplant leptin (r = 0.61, p < 0.001, and r = 0.44, p < 0.001), pre-transplant IL-1RA (r = 0.25, p = 0.04), and post-transplant ICAM-1 (r = 0.25, p = 0.04). We identified 3 latent patterns of adiposity. The class defined by high thoracic and abdominal SAT had the greatest risk of PGD. Subcutaneous, but not visceral, adiposity is associated with an increased risk of PGD after lung transplantation. [ABSTRACT FROM AUTHOR]

Abstract Stable, earth-abundant and efficient electrocatalysts for overall water splitting are urgently needed. In this work, we have reported the synthesis of FeNiP/NC hollow microboxes (FeNiP/NC) based bifunctional electrocatalyst via the phosphorization process using rationally designed cube-type metal-organic framework (FeNi-MOF) as both the template and carbon source. The FeNiP/NC, which were obtained by assembling the uniform FeNiP nanoparticals together through N-doped carbon, manifests outstanding catalytic performances for both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in KOH solution. Notably, FeNiP/NC displays exceptional activity when it was utilized as both anode and cathode toward overall water splitting with potential of 1.54 V at a current density of 10 mA cm−2 in alkaline electrolyte, which is much better than FeP/NC and Ni 2 P/NC electrocatalyst. More importantly, the improvement of the catalytic activities of FeNiP/NC mainly benefits from the well dispersion of FeNiP nanoparticles on the surface of carbon support, the large active surface area and the doping of N and C derived from organic ligands. In addition, the enhanced electrocatalytic performance of FeNiP/NC for OER is closely related with the in-situ formed surficial MOOH (M = Fe, Ni) active sites, which has been confirmed by X-ray photoelectron spectroscopy (XPS) analysis. Graphical abstract Image 1 Highlights • Uniform FeNiP nanoparticles assembled together through N-doped carbon based hollow microboxs have been synthesized. • FeNiP/NC was obtained using FeNi-MOF as precursor. • Hollow FeNiP/NC is a bifunctional electrocatalyst for HER and OER in alkaline media. • The MOOH (M = Fe, Ni) with high activity for OER have in-situ formed on the surface of FeNiP/NC. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are very attractive as carriers of active components due to their good immunological and their ability to penetrate the physiological barrier that synthetic delivery carriers cannot penetrate. However, the low secretion capacity of EVs limited its widespread adoption, let alone the lower yield of EVs loaded with active components. Here, we report a large-scale engineering preparation strategy of synthetic probiotic membrane vesicles for encapsulating fucoxanthin (FX-MVs), an intervention for colitis. Compared with the EVs naturally secreted by probiotics, the engineering membrane vesicles showed a 150-fold yield and richer protein. Moreover, FX-MVs improved the gastrointestinal stability of fucoxanthin and inhibited H 2 O 2 -induced oxidative damage by scavenging free radicals effectively (p < 0.05). The in vivo results showed that FX-MVs could promote the polarization of macrophages to M2 type, prevent the injury and shortening of colon tissue (p < 0.05), and improve the colonic inflammatory response. Consistently, proinflammatory cytokines were effectively suppressed after FX-MVs treatment (p < 0.05). Unexpectedly, such engineering FX-MVs could also reshape the gut microbiota communities and improve the abundance of short-chain fatty acids in the colon. This study lays a foundation for developing dietary interventions using natural foods to treat intestinal-related diseases. [ABSTRACT FROM AUTHOR]

• The proposed method constitutes a novel automatic strategy for computationally inferring respiratory phases via free-breathing MRI. No need for manual labeling or assistance. • The optical-flux idea as the respiration surrogate is robust as seen from the results. It offers a quantum improvement in performance compared to existing techniques. • Strategies for detecting abnormal cycles and aligning to one normal respiratory model are novel and natural. • The results have been fully evaluated with the 4 proposed evaluation methods for both spatial and temporal continuity of the constructed 4D image. Since real-time 4D dynamic magnetic resonance imaging (dMRI) methods with adequate spatial and temporal resolution for imaging the pediatric thorax are currently not available, free-breathing slice acquisitions followed by appropriate 4D construction methods are currently employed. Self-gating methods, which extract breathing signals only from image information without any external gating technology, have much potential for this purpose, such as for use in studying pediatric thoracic insufficiency syndrome (TIS). Patients with TIS frequently suffer from extreme malformations of the chest wall, diaphragm, and spine, leading to breathing that is very complex, including deep or shallow respiratory cycles. Existing 4D construction methods cannot perform satisfactorily in this scenario, and most are not fully automatic, requiring manual interactive operations. In this paper, we propose a novel fully automatic 4D image construction method based on an image-derived concept called flux to address these challenges. We utilized 25 dMRI data sets from 25 pediatric subjects with no known thoracic anomalies and 58 dMRI data sets from 29 patients with TIS where each patient had a dMRI scan before and after surgery. A time sequence of 80 slices are acquired at each sagittal location continuously at a rate of ~480 ms per slice under free-breathing conditions, with 30–40 sagittal locations across the chest for each subject depending on the thoracic size. In our approach, we first extract the breathing signal for each sagittal location based on the flux of the optical flow vector field of the body region from the image time series. Here, for each time point of respiratory phase, the net flux of the body region can be regarded as the flux going into or out of the body region, which we term Optical Flux (OFx). OFx provides a very robust representation of the real breathing motion of the thorax. OFx allows us to perform a full analysis of all respiratory cycles, extract only normal cycles in a robust manner, and map all extracted normal cycles on to one cosine respiration model for each sagittal location. Subsequently, we re-sample one normal cycle from the respiration model for each location independently. The normal cycle models associated with the different sagittal locations are finally composited to form the final constructed 4D image. We employ several metrics to evaluate the quality of the 4D construction results: E ie – error in locating time instants corresponding to end inspiration and end expiration; E to – deviation from correct temporal order in each detected normal cycle; E ss – deviation in spatial smoothness; and E sc – deviation from spatial continuity as scored by a reader. The means and standard deviations of these metrics for normal subjects and TIS patients are found to be, respectively: E ie : 0.25 ± 0.05 and 0.38 ± 0.16 in units of time instance (ideal value = 0); E to : 2.7% ± 2.3% and 1.8% ± 2% (ideal value = 0%); E ss : 0.5 ± 0.17 and 0.54 ± 0.25 in pixel units (ideal value = 0); E sc : 4.6 ± 0.48 and 4.56 ± 0.98 (score range: best = 5, worst = 1). The results show that the OFx method achieves excellent spatial and temporal continuity and its yield was 100% meaning that it successfully performed 4D construction on every data set tested. Compared to a recently published method, OFx is fully automatic requiring about 5 min of computational time per study starting from acquired dMRI scans. The method achieves high temporal and spatial continuity even on complex TIS data sets that include many abnormal respiratory cycles. A new 4D dMRI construction method based on the concept of optical flux is presented which is fully automatic and very robust in deriving respiratory signals purely from dynamic image sequences even when presented with complex breathing patterns due to severe disease conditions like TIS. Evaluations show that its accuracy is comparable to the variations found in manual annotations. An important characteristic of the method is that it is independent of the number of sagittal locations used in the construction process, which suggests that it is applicable to imaging techniques where data are acquired at only a few sagittal locations instead of the full width of the thorax. The method is not tied to any specific imaging modality, as demonstrated in this paper on not just dMRI but dynamic computed tomography (CT) as well. [Display omitted] [ABSTRACT FROM AUTHOR]

• Jujube juices were excellent food matrices for select lactic acid bacteria. • Total phenolic content of jujube juice was increased by lactic acid fermentation. • Antioxidant capacities of jujube juice were improved by lactic acid fermentation. • Lactic acid fermentation led the increase of caffeic acid and rutin. • Lactic acid fermentation improved the aroma complexity of jujube juice. The objective of this study was to investigate the effects of four commercial lactic acid bacteria (LAB), namely L. acidophilus , L. casei , L. helveticus and L. plantarum , on the phenolic profiles, antioxidant capacities and flavor profiles of jujube juices prepared from two crop varieties (Ziziphus Jujuba cv. Muzao and Hetian). Results showed that both jujube juices were excellent matrices for LAB growth with more than 11 log CFU/mL of viable counts at the end of fermentation. LAB fermentation dramatically increased total phenolic content, while decreased total flavonoid content of jujube juices. However, antioxidant capacities based on DPPH and FRAP methods were significantly improved by LAB fermentation and positively correlated with caffeic acid and rutin contents. Furthermore, a total of 74 volatile compounds were identified and increased in total content by LAB fermentation, which resulted in 22 and 19 new flavor volatiles formation in Muzao juice and Hetian juice, respectively. [ABSTRACT FROM AUTHOR]

In response to the ongoing shift of the regulatory cardiac safety paradigm, a recent White Paper proposed general principles for developing and implementing proarrhythmia risk prediction models. These principles included development strategies to validate models, and implementation strategies to ensure a model developed by one lab can be used by other labs in a consistent manner in the presence of lab-to-lab experimental variability. While the development strategies were illustrated through the validation of the model under the Comprehensive In vitro Proarrhythmia Assay (CiPA), the implementation strategies have not been adopted yet. The proposed implementation strategies were applied to the CiPA model by performing a sensitivity analysis to identify a subset of calibration drugs that were most critical in determining the classification thresholds for proarrhythmia risk prediction. The selected calibration drugs were able to recapitulate classification thresholds close to those calculated from the full list of CiPA drugs. Using an illustrative dataset it was shown that a new lab could use these calibration drugs to establish its own classification thresholds (lab-specific calibration), and verify that the model prediction accuracy in the new lab is comparable to that in the original lab where the model was developed (lab-specific validation). This work used the CiPA model as an example to illustrate how to adopt the proposed model implementation strategies to select calibration drugs and perform lab-specific calibration and lab-specific validation. Generic in nature, these strategies could be generally applied to different proarrhythmia risk prediction models using various experimental systems under the new paradigm. [ABSTRACT FROM AUTHOR]