Modulating Electronic Metal-Support Interactions to Boost Visible-Light-Driven Hydrolysis of Ammonia Borane: Nickel-Platinum Nanoparticles Supported on Phosphorus-Doped Titania.

Ammonia borane (AB) is a promising material for chemical H2 storage owing to its high H2 density (up to 19.6 wt %). However, the development of an efficient catalyst for driving H2 evolution through AB hydrolysis remains challenging. Therefore, a visible-light-driven strategy for generating H2 through AB hydrolysis was implemented in this study using Ni-Pt nanoparticles supported on phosphorus-doped TiO2 (Ni-Pt/P-TiO2 ) as photocatalysts. Through surface engineering, P-TiO2 was prepared by phytic-acid-assisted phosphorization and then employed as an ideal support for immobilizing Ni-Pt nanoparticles via a facile co-reduction strategy. Under visible-light irradiation at 283 K, Ni40 Pt60 /P-TiO2 exhibited improved recyclability and a high turnover frequency of 967.8 mol H 2 ${{_{{\rm H}{_{2}}}}}$ molPt -1 min-1 . Characterization experiments and density functional theory calculations indicated that the enhanced performance of Ni40 Pt60 /P-TiO2 originated from a combination of the Ni-Pt alloying effect, the Mott-Schottky junction at the metal-semiconductor interface, and strong metal-support interactions. These findings not only underscore the benefits of utilizing multipronged effects to construct highly active AB-hydrolyzing catalysts, but also pave a path toward designing high-performance catalysts by surface engineering to modulate the electronic metal-support interactions for other visible-light-induced reactions.

Characterization of Modification Patterns, Biological Function, Clinical Implication, and Immune Microenvironment Association of m6A Regulators in Pancreatic Cancer.

Objective: N6-methyladenosine (m6A) modification may modulate various biological processes. Nonetheless, clinical implications of m6A modification in pancreatic cancer are undefined. Herein, this study comprehensively characterized the m6A modification patterns in pancreatic cancer based on m6A regulators. Methods: Genetic mutation and expression pattern of 21 m6A regulators and their correlations were assessed in pancreatic cancer from TCGA dataset. m6A modification patterns were clustered using unsupervised clustering analysis in TCGA and ICGC datasets. Differences in survival, biological functions and immune cell infiltrations were assessed between modification patterns. A m6A scoring system was developed by principal component analysis. Genetic mutations and TIDE scores were compared between high and low m6A score groups. Results: ZC3H13 (11%), RBM15B (9%), YTHDF1 (8%), and YTHDC1 (6%) frequently occurred mutations among m6A regulators. Also, most of regulators were distinctly dysregulated in pancreatic cancer. There were tight crosslinks between regulators. Two m6A modification patterns were constructed, with distinct prognoses, immune cell infiltration and biological functions. Furthermore, we quantified m6A score in each sample. High m6A scores indicated undesirable clinical outcomes. There were more frequent mutations in high m6A score samples. Lower TIDE score was found in high m6A score group, with AUC = 0.61, indicating that m6A scores might be used for predicting the response to immunotherapy. Conclusion: Collectively, these data demonstrated that m6A modification participates pancreatic cancer progress and ornaments immune microenvironment, providing an insight into pancreatic cancer pathogenesis and facilitating precision medicine development.

Highly-Dispersed Submicrometer Single-Crystal Nickel-Rich Layered Cathode: Spray Synthesis and Accelerated Lithium-Ion Transport.

For conventional polycrystalline Ni-rich cathode material consisting of numerous primary particles in disordered orientation, the crystal anisotropy in charge/discharge process results in the poor rate capability and rapid capacity degradation. In this work, highly-dispersed submicron single-crystal LiNi0.8 Co0.15 Al0.05 O2 (SC-NCA) cathode is efficiently prepared by spray pyrolysis (SP) technique followed by a simple solid-state lithiation reaction. Porous Ni0.8 Co0.15 Al0.05 Ox precursor prepared via SP exhibits high chemical activity for lithiation reaction, enabling the fabrication of single-crystal cathode at a relatively low temperature. In this way, the contradiction between high crystallinity and cation disordering is well balanced. The resulted optimized SC-NCA shows polyhedral single-crystal morphology with moderate grain size (≈1 µm), which are beneficial to shortening the Li+ diffusion path and improving the structural stability. As cathode for lithium ion batteries, SC-NCA delivers a high discharge capacity of 202 and 140 mAh g-1 at 0.1 and 10 C, respectively, and maintains superior capacity retention of 161 mAh g-1 after 200 cycles at 1C. No micro-crack is observed in the cycled SC-NCA particles, indicating such single-crystal morphology can greatly relieve the anisotropic micro-strain. This effective, continuous and adaptable strategy for preparing single-crystal Ni-rich cathode without any additive may accelerate their practical application.

Histone acetyltransferase 1 is a succinyltransferase for histones and non-histones and promotes tumorigenesis.

Lysine succinylation (Ksucc) is an evolutionarily conserved and widespread post-translational modification. Histone acetyltransferase 1 (HAT1) is a type B histone acetyltransferase, regulating the acetylation of both histone and non-histone proteins. However, the role of HAT1 in succinylation modulation remains unclear. Here, we employ a quantitative proteomics approach to study succinylation in HepG2 cancer cells and find that HAT1 modulates lysine succinylation on various proteins including histones and non-histones. HAT1 succinylates histone H3 on K122, contributing to epigenetic regulation and gene expression in cancer cells. Moreover, HAT1 catalyzes the succinylation of PGAM1 on K99, resulting in its increased enzymatic activity and the stimulation of glycolytic flux in cancer cells. Clinically, HAT1 is significantly elevated in liver cancer, pancreatic cancer, and cholangiocarcinoma tissues. Functionally, HAT1 succinyltransferase activity and the succinylation of PGAM1 by HAT1 play critical roles in promoting tumor progression in vitro and in vivo. Thus, we conclude that HAT1 is a succinyltransferase for histones and non-histones in tumorigenesis.

Chronic ethanol consumption and HBV induce abnormal lipid metabolism through HBx/SWELL1/arachidonic acid signaling and activate Tregs in HBV-Tg mice.

Rationale: Chronic ethanol consumption as a public health problem worldwide boosts the development of chronic liver diseases in hepatitis B virus (HBV)-infected patients. Arachidonic acid metabolite prostaglandin E2 (PGE2) activates regulatory T cells (Tregs) function. Here, we aim to investigate the underlying mechanism by which chronic ethanol consumption enriches the HBV-induced abnormal lipid metabolism and Tregs. Methods: The si-RNAs were used to weaken the expression of SWELL1 in HepG2, HepG2.2.15 and K180 cancer cell lines, followed by RNA sequencing from HepG2 cells. Arachidonic acid metabolite PGE2 and LTD4 were measured by ELISA assay in vivo and in vitro. Western blot analysis and RT-qPCR were used to examine HBx and SWELL1 and transcriptional factor Sp1 in clinical HCC samples and cell lines. The effect of chronic ethanol consumption on Tregs was tested by flow cytometry in HBV-Tg mice. The splenic Tregs were collected and analyzed by RNA sequencing. Results: The cooperative effect of ethanol and HBV in abnormal lipid metabolism was observed in vivo and in vitro. The depression of SWELL1 (or HBx) resulted in the reduction of lipid content and arachidonic acid metabolite, correlating with suppression of relative gene atlas. Ethanol and SWELL1 elevated the levels of PGE2 or LTD4 in the liver of mice and cell lines. Interestingly, the ethanol modulated abnormal lipid metabolism through activating HBx/Sp1/SWELL1/arachidonic acid signaling. Chronic ethanol consumption remarkably increased the population of PBL Tregs and splenic Tregs in HBV-Tg mice, consistently with the enhanced expression of PD-L1 in vivo and in vitro. Mechanically, RNA-seq data showed that multiple genes were altered in the transcriptomic atlas of Tregs sorting from ethanol-fed mice or HBV-Tg mice. Conclusion: The chronic ethanol intake enriches the HBV-enhanced abnormal lipid metabolism through HBx/SWELL1/arachidonic acid signaling and activates Tregs in mice.

IFN-α2b inhibits the ethanol enriched-HBV cccDNA through blocking a positive feedback loop of HBx/MSL2/cccDNA/HBV/HBx in liver.

Hepatitis B virus (HBV) is a major risk factor for liver diseases, in which HBV covalently closed circular DNA (cccDNA), as the genomic form that templates viral transcription, plays crucial roles in sustaining viral persistence. Clinically, the excessive ethanol intake accelerates the progression of liver diseases with HBV infection. Here, we supposed that ethanol might trigger HBV cccDNA in the liver. Interestingly, we observed that the ethanol remarkably elevated the levels of HBeAg, HBsAg, HBV DNA and cccDNA in HBV-expressing hepatoma cells. Mechanically, the ethanol increased the levels of HBx and MSL2 in vivo and in HBV-expressing HepG2 cells, but not in HBV-free HepG2 cells. Moreover, the down-regulation of MSL2 by small interference RNA could block the ethanol-promoted HBV cccDNA in HepG2.2.15 cells. As a commonly administered treatment for HBV, the effect of IFNα on ethanol-triggered HBV cccDNA remains poorly understood. Strikingly, we showed that the treatment with IFN-α2b inhibited the ethanol-promoted cccDNA through depressing MSL2 in the cells. Thus, we conclude that IFN-α2b inhibits the ethanol-enriched HBV cccDNA through blocking a positive feedback loop of HBx/MSL2/cccDNA/HBV/HBx. Our finding provides new insights into the mechanism by which IFN-α2b inhibits ethanol-enhanced HBV cccDNA. Therapeutically, IFNα may contribute to the cccDNA induced by ethanol in liver.

SPIN1 triggers abnormal lipid metabolism and enhances tumor growth in liver cancer.

Abnormal lipid metabolism plays crucial roles in the development of cancer. Spindlin 1 (SPIN1) involving the process of spindle organization and chromosomal stability serves as an important player in the carcinogenesis. In this study, we try to identify the new function of SPIN1 in lipid metabolism of liver cancer. Tissue microarray showed that 75% (60/80) of hepatocellular carcinoma (HCC) tissues were positive for SPIN1, which was highly expressed in clinical HCC samples and positively associated with malignancy of HCC. Strikingly, SPIN1 could modulate abnormal lipid metabolism by increasing intracellular triglycerides, cholesterols, and lipid droplets in hepatoma cells, which could remarkably enhance the proliferation of hepatoma cells. Mechanistically, SPIN1 up-regulated FASN in hepatoma cells. SPIN1 co-activated transcriptional factor SREBP1c in the promoter of FASN through interaction with SREBP1c. Moreover, SPIN1 promoted the growth of liver cancer in vitro and in vivo and the levels of intracellular triglycerides, cholesterols and lipid droplets were increased in the tumor tissues from mice. In conclusion, SPIN1 modulates abnormal lipid metabolism and enhances growth of liver cancer through SREBP1c-triggered FASN signaling. Therapeutically, SPIN1 may serve as a novel target for HCC.

Identification and Characterization of Gastrointestinal-Resistant Angiotensin-Converting Enzyme Inhibitory Peptides from Egg White Proteins.

Egg proteins are recognized as excellent sources of bioactive peptides, such as angiotensin-converting enzyme inhibitory (ACEi) peptides. Oral administration of a thermolysin-digested egg white hydrolysate (T-EWH) caused a significant blood pressure reduction in spontaneously hypertensive rats; a further ACEi assay implied that its ACEi activity was enhanced after in vitro gastrointestinal (GI) digestion. These results indicated that T-EWH contained ACEi peptides resisting GI digestion and/or being further released during GI digestion. Therefore, the objective of this study was to identify these responsible ACEi peptides from T-EWH. The conventionally activity-guided fractionation was applied, coupled with a synchronized GI digestion throughout, during which both peptide yield and ACEi activity before and after the GI digestion were measured. Finally, six ACEi peptides (LAPYK, LKISQ, LKYAT, INKVVR, LFLIKH, and LGHWVY) with good GI resistance were identified with IC50 values <20 µM, especially LKYAT (0.09 µM). The structure-activity relationship of these peptides was discussed. The discovery of GI-resistant ACEi peptides could further support the application of egg white proteins as functional food ingredients.

Purification and characterization of antioxidant peptides from cooked eggs using a dynamic in vitro gastrointestinal model in vascular smooth muscle A7r5 cells.

Antioxidant peptides derived from food sources are considered as safer alternatives to commercially available antioxidant drugs. As one of the most abundant protein sources, hen's egg proteins were extensively used to produce antioxidant peptides by enzymatic hydrolysis. Our previous work indicated that gastrointestinal digestion of cooked eggs significantly increased the antioxidant activity due to hydrolysis of egg proteins. To characterize the responsible antioxidant peptides, cooked eggs were digested in a simulated in vitro model of human gastro-intestinal digestion. Prepared digests were fractionated with FPLC (Fast Protein Liquid Chromatography) and RP-HPLC (Reverse-Phase High-Performance Liquid Chromatography) and the antioxidant activity was determined in A7r5 cells (vascular smooth muscle cell line). Further identification of peptides from peptide fractions with the highest antioxidant activity was carried out using LC-MS/MS. Four peptides derived from ovalbumin, DSTRTQ (48-53), DKLPG (61-65), DVYSF (96-100), and ESKPV (205-209), were identified; of which DKLPG did not show antioxidant activity in cells. Enzyme cleave analysis suggested that these four peptides were likely released from ovalbumin only by pepsin non-specific cleaves. It is postulated that egg consumption may exert protection against oxidative stress on human health due to release of antioxidant peptides during digestion.

Elevated Interleukin 1ß and Interleukin 6 Levels in the Serum of Children With Hyperuricemia.

PURPOSES: The aim of this study was to investigate the serum levels and clinical significance of interleukin 1ß (IL-1ß) and IL-6 in children with hyperuricemia (HUA). METHODS: We included 71 children with HUA and 71 children with no HUA as control subjects. Children with HUA were divided into groups I and II according to whether they had a history of acute gout-like attacks (including sudden monoarthritis of rapid onset with intense pain and swelling). Group I was examined twice (A, in the acute phase; B, in the remission phase). Serum IL-1ß and IL-6 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum IL-1ß and IL-6 levels were increased in children with HUA and were overall statistically different from the control group (P < 0.05, respectively). Serum IL-1ß and IL-6 were significantly higher in group IA in comparison with group IB, group II, and control subjects (P < 0.05, respectively), as well as in groups IB and II compared with control subjects (P < 0.05, respectively). In group IB, the serum IL-1ß and IL-6 concentrations were higher than those in group II, but there were no statistical differences (P > 0.05). In addition, in children with HUA, serum IL-1ß and IL-6 levels were positively associated with white blood cell count, neutrophil count, monocyte count, uric acid levels, erythrocyte sedimentation rate, C-reactive protein, blood urea nitrogen, and serum creatinine levels (all P < 0.05), but were not associated with triglycerides, total cholesterol, low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol levels (all P > 0.05). CONCLUSION: IL-1ß and IL-6 levels are increased in children with hyperuricemia, even if they have not had acute gout. Further studies are necessary to fully characterize the significance of IL-1ß and IL-6 found in HUA children, and whether they could be correlated with long-term prognosis.

[Values of fat saturation sequence in MRI for juvenile arthritis].

OBJECTIVE: To explore the values of fat saturation sequence in MRI for juvenile arthritis.
 Methods: A total of 1 131 cases with juvenile arthritis and 1 601 with symptomatic arthritis were examined by MRI normal T1 weighted imaging (T1WI) and T2 weighted imaging (T2WI) sequence and spectral presaturation attenuatedinversion recovery (SPAIR) T2 fat saturation sequence. All the images were independently evaluated by two senior doctors from the Department of Radiology and the Department of Pediatric Rheumatology and Immunology respectively to confirm the types and degree of pathological changes of joint tissues.
 Results: Among the subjects, 847 patients demonstrated positive in MRI, accounting for 52.9%; 409 patients showed positive in normal sequence, accounting for 48.3%; 816 patients showed positive in fat saturation sequence, accounting for 96.3%. Joint hydrops accounted for 59.5%. Bone marrow edema accounted for 39.7%. The relevant ratio of bone marrow edema, joint hydrops, thickening of synovium and cartilage injuries in fat saturation sequence were higher than that in normal sequence (P<0.05). The relevant ratio of bone erosion in normal sequence was higher than that in fat saturation sequence (P<0.05). However, no significant difference of joint cysts was found between the fat saturation sequence and normal sequence (P<0.05).
 Conclusion: Application of fat saturation sequence by MRI to check juvenile arthritis could obviously improve the positive MRI relevant ratio. In addition, the relevant ratio of the early pathological changes of juvenile arthritis (such as bone marrow edema and joint hydrops) was high, which might provide references for the early diagnosis of juvenile arthritis.

An improved method to extract and purify cystatin from hen egg white.

Hen egg white cystatin, an inhibitor of cysteine proteinase, may have wide applications for improving human health. However, its pricy cost associated with extraction and preparation has hurdled its further utilization. The objective was to develop an improved method to extract and purify cystatin from egg white. After removal of ovomucin, a fraction containing cystatin was obtained by cation exchange chromatography, and further purified by affinity chromatography using a cm-papain-Sepharose column. The prepared cystatin was then characterized by SDS-PAGE, Western-Blot, and LC-MS/MS, and its purity was determined by HPLC method instead of the conventional immunodiffusion method. The protein content of cystatin extract was 66.4 ± 2.3%. In comparison with the conventional method, the purity of cystatin was improved from 56.6 ± 1.7% to 93.3 ± 4.0%, and its yield was improved from 21.3 ± 1.2% to 33.6 ± 1.5%. Relative activities of cystatin to inhibit papain prepared by our method and the conventional method were determined to be 88 ± 7% and 91 ± 4% respectively, against a cystatin standard from Sigma. This suggested no significant loss of activity during the separation process.

Stabilization of peptide-based vesicles via in situ oxygen-mediated cross-linking.

Reversible vesicles from poly(L-glutamic acid)(65) -block-poly[(L-lysine)-ran-(L-3,4-dihydroxyphenylalanine)](75) [PLGA(65)-b-P(LL-r-DOPA)(75)] block copolypeptide adopt different configurations depending on the surrounding pH. At pH = 3, AFM and TEM images show ellipsoidal morphologies, whereas at pH = 12 both TEM and AFM reveal the formation of hollow vesicles. At pH = 12, the P(LL-r-DOPA) block forms the internal layer of the vesicle shell and the subsequent oxygen-mediated oxidation of the phenolic groups of the DOPA lead to the formation of quinonic intermediates, which undergo intermolecular dimerization to stabilize the vesicles via in situ cross-linking. Consequently, the vesicles maintain their shape even when the pH is reversed back to 3, as confirmed by AFM and TEM.

Proteomics analysis of egg white proteins from different egg varieties.

The market of specialty eggs, such as omega-3-enriched eggs, organic eggs, and free-range eggs, is continuously growing. The nutritional composition of egg yolk can be manipulated by feed diet; however, it is not known if there is any difference in the composition of egg white proteins among different egg varieties. The purpose of the study was to compare the egg white proteins among six different egg varieties using proteomics analysis. Egg white proteins were analyzed using two-dimensional gel electrophoresis (2-DE), and 89 protein spots were subjected to LC-MS/MS. A total of 23 proteins, belonging to Gallus gallus , were identified from 72 detected protein spots. A quiescence-specific protein precursor in egg white was identified for the first time in this study. Significant differences in the abundant levels of 19 proteins (from 65 protein spots) were observed among six egg varieties. Four proteins, ovalbumin-related protein Y, cystatin, avidin, and albumin precursor, were not different among these six egg varieties. These findings suggest that the abundance, but not the composition, of egg white proteins varied among the egg varieties.

Ovomucin - a glycoprotein with promising potential.

Ovomucin, accounting for ∼3.5% of total egg white protein, is responsible for the thick gel characteristics of liquid egg white. Besides its excellent foaming and emulsion capacities, it possesses anti-viral, anti-bacterial, anti-tumor and other bioactivities. This paper reviews compositional, structural, physicochemical, functional and biological properties of ovomucin, as well as development of methods of extraction. As one of the least defined proteins in egg white, further study is required to characterize the structure and to explore its full potential in new applications as functional foods and nutraceuticals.