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We performed a comprehensive angle-resolved photoemission spectroscopy study of the electronic band structure of LaOFeAs single crystals. We found that samples cleaved at low temperature show an unstable and highly complicated band structure, whereas samples cleaved at high temperature exhibit a stable and clearer electronic structure. Using in situ surface doping with K and supported by first-principles calculations, we identify both surface and bulk bands. Our assignments are confirmed by the difference in the temperature dependence of the bulk and surface states.

Epigenetic mechanisms play a critical role in the pathogenesis of human diseases including kidney disorders. As the erasers of DNA methylation, Ten-eleven translocation (TET) family proteins can oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), thus leading to passive or active DNA demethylation. Similarly, TET family proteins can also catalyze the same reaction on RNA. In addition, TET family proteins can also regulate chromatin structure and gene expression in a catalytic activity-independent manner through recruiting the SIN3A/HDAC co-repressor complex. In 2012, we reported for the first time that the genomic 5-hydroxymethylcytosine level and the mRNA levels of Tet1 and Tet2 were significantly downregulated in murine kidneys upon ischemia and reperfusion injury. Since then, accumulating evidences have eventually established an indispensable role of TET family proteins in not only acute kidney injury but also chronic kidney disease. In this review, we summarize the upstream regulatory mechanisms and the pathophysiological role of TET family proteins in major types of kidney diseases and discuss their potential values in clinical diagnosis and treatment., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Butyric acid, a pivotal short-chain fatty acid in rumen digestion, profoundly influences animal digestive and locomotor systems. Extensive research indicates its direct or indirect involvement in the growth and development of muscle and fat cells. However, the impact of butyric acid on the proliferation and differentiation of bovine skeletal muscle satellite cells (SMSCs) remains unclear. This study aimed to elucidate the effects of butyrate on SMSCs proliferation and differentiation. After isolating, SMSCs were subjected to varying concentrations of sodium butyrate (NaB) during the proliferation and differentiation stages. Optimal treatment conditions (1 mM NaB for 2 days) were determined based on proliferative force, cell viability, and mRNA expression of proliferation and differentiation marker genes. Transcriptome sequencing was employed to screen for differential gene expression between 1 mM NaB-treated and untreated groups during SMSCs differentiation. Results indicated that lower NaB concentrations (≤1.0 mM) inhibited proliferation while promoting differentiation and apoptosis after a 2-day treatment. Conversely, higher NaB concentrations (≥2.0 mM) suppressed proliferation and differentiation and induced apoptosis. Transcriptome sequencing revealed differential expression of genes(ND1, ND3, CYTB, COX2, ATP6, MYOZ2, MYOZ3, MYBPC1 and ATP6V0A4,etc.) were associated with SMSCs differentiation and energy metabolism, enriching pathways such as Oxidative phosphorylation, MAPK, and Wnt signaling. These findings offer valuable insights into the molecular mechanisms underlying butyrate regulation of bovine SMSCs proliferation and differentiation, as well as muscle fiber type conversion in the future study., Competing Interests: Declaration of competing interest The authors confirm that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Single-cell technology depicts integrated tumor profiles including both tumor cells and tumor microenvironments, which theoretically enables more robust diagnosis than traditional diagnostic standards based on only pathology. However, the inherent challenges of single-cell RNA sequencing (scRNA-seq) data, such as high dimensionality, low signal-to-noise ratio (SNR), sparse and non-Euclidean nature, pose significant obstacles for traditional diagnostic approaches. The diagnostic value of single-cell technology has been largely unexplored despite the potential advantages. Here, we present a graph neural network-based framework tailored for molecular diagnosis of primary liver tumors using scRNA-seq data. Our approach capitalizes on the biological plausibility inherent in the intercellular communication networks within tumor samples. By integrating pathway activation features within cell clusters and modeling unidirectional inter-cellular communication, we achieve robust discrimination between malignant tumors (including hepatocellular carcinoma, HCC, and intrahepatic cholangiocarcinoma, iCCA) and benign tumors (focal nodular hyperplasia, FNH) by scRNA data of all tissue cells and immunocytes only. The efficacy to distinguish iCCA from HCC was further validated on public datasets. Through extending the application of high-throughput scRNA-seq data into diagnosis approaches focusing on integrated tumor microenvironment profiles rather than a few tumor markers, this framework also sheds light on minimal-invasive diagnostic methods based on migrating/circulating immunocytes., (© 2024. The Author(s).)

Background: Gluten-free bread (GFB) has technical bottlenecks such as hard texture, rough taste and low nutrition in practical production. In order to solve these problems, this study used germinated brown rice starch as the main raw material, and investigated the effects of soybean isolate protein (SPI) on the multiscale structure of germinated brown rice starch and bread quality., Results: A gluten-free rice bread process simulation system was established, and the interaction between SPI and starch in the simulation system was characterized. The result shows that the interaction forces between SPI and germinated brown rice starch were mainly represented by hydrogen bonds, and with the addition of SPI, the crystallinity of starch showed a downward trend. At the same time, when the amount of SPI was 3%, the appearance quality was the best and the specific volume of bread was 1.08 mL g -1 . When the amount of SPI was 6%, the texture quality was the best. Compared with the bread without SPI, the hardness of the bread with 6% SPI was reduced by 0.13 times, the springiness was increased by 0.03 times, the color was the most vibrant, the L* value being 1.02 times the original, and the baking loss was reduced to 0.98 times the original., Conclusions: The interaction force between SPI and germinated brown rice starch and its effect on bread quality were clarified, and these results inform choices about providing a theoretical basis for the subsequent development of higher-quality GFB. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: This study explored the denaturation of 11S globulin, a protein known for its diverse functional properties in soy protein applications, at pH 3.0 and pH 10.0, followed by a gradual return to pH 7.0 to facilitate renaturation. It investigated the structural and functional changes during renaturation induced by a change in pH, revealing the stabilization mechanism of 11S globulin., Results: The findings revealed that during pH adjustment to neutral, the denatured soybean 11S globulin - resulting from alkaline (pH 10.0) or acidic (pH 3.0) treatments - experienced a refolding of its extended tertiary structure to varying extents. The particle size and the proportions of α-helix and β-sheet in the secondary structure aligned progressively with those of the natural-state protein. However, for the alkali-denatured 11S, the β-sheet content decreased upon adjustment to neutral, whereas an increase was observed for the acid-denatured 11S. In terms of functional properties, after alkaline denaturation, the foaming capacity (FC) and emulsifying activity index (EAI) of 11S increased by 1.4 and 1.2 times, respectively, in comparison with its native state. The solubility, foamability, and emulsifiability of the alkali-denatured 11S gradually diminished during renaturation but remained superior to those of the native state. Conversely, these properties showed an initial decline, followed by an increase during renaturation triggered by pH neutralization., Conclusions: This research contributes to the enhancement of protein functionality, offering a theoretical foundation for the development of functional soy protein products and expanding their potential applications. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

This study reported for the first time that Ascorbic acid (AA) could appreciably boost the efficiency of Octyl gallate (OG)-mediated photodynamic inactivation (PDI) on Escherichia coli and Staphylococcus aureus in planktonic and biofilm states. The combination of OG (0.075 mM) and AA (200 mM) with 420 nm blue light (212 mW/cm 2 ) led to a >6 Log killing within only 5 min for E. coli and S. aureus and rapid eradication of biofilms. The mechanism of action appears to be the generation of highly toxic hydroxyl radicals (•OH) via photochemical pathways. OG was exposed to BL irradiation to generate various reactive oxygen radicals (ROS) and the addition of AA could transform singlet oxygen ( 1 O 2 ) into hydrogen peroxide (H 2 O 2 ), which could further react with AA to generate enormous •OH. These ROS jeopardized bacteria and biofilms by nonspecifically attacking various biomacromolecules. Overall, this PDI strategy provides a powerful microbiological decontamination modality to guarantee safe food products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The substantial nonlinear optical response observed in numerous topological materials renders them well-suited for optic and photonic applications, underscoring the critical need to devise effective strategies for manipulating their nonlinearity to enhance their versatility across different applications. In this Letter, we focus on the second-harmonic generation (SHG) response of the topological material PtBi 2 under intense terahertz (THz) pulses and unveil the transient nonlinearity manipulated by a THz electric field. Our findings demonstrate that upon excitation of an intense THz pulse, there emerges a substantial enhancement in the SHG signal of PtBi 2 , which is predominantly attributed to the linear term involving the THz field, i.e., χ (2) χ (3) E THz . We also clearly observe the transient change in the nonlinear coefficients, which could arise from the excitation of the bands with linear dispersion via the intense THz pulse. These findings bear significant implications for achieving ultrafast modulation of nonlinearity in topological materials, thereby opening avenues for advanced applications in this field.

We report on (resonant) x-ray diffraction experiments on the normal state properties of kagome-lattice superconductors KV 3 Sb 5 and RbV 3 Sb 5 . We have confirmed previous reports indicating that the charge density wave (CDW) phase is characterized by a doubling of the unit cell in all three crystallographic directions. By monitoring the temperature dependence of Bragg peaks associated with the CDW phase, we ascertained that it develops gradually over several degrees, as opposed to CsV 3 Sb 5 , where the CDW peak intensity saturates promptly just below the CDW transition temperature. Analysis of symmetry modes indicates that this behavior arises due to lattice distortions linked to the formation of CDWs. These distortions occur abruptly in CsV 3 Sb 5 , while they progress more gradually in RbV 3 Sb 5 and KV 3 Sb 5 . In contrast, the amplitude of the mode leading to the crystallographic symmetry breaking fromP6/mmmto Fmmm appears to develop more gradually in CsV 3 Sb 5 as well. Diffraction measurements close to the V K edge and the Sb L 1 edge show no sensitivity to inversion- or time-symmetry breaking, which are claimed to be associated with the onset of the CDW phase. The azimuthal angle dependence of the resonant diffraction intensity observed at the Sb L 1 edge is associated with the difference in the population of unoccupied states and the anisotropy of the electron density of certain Sb ions., (Creative Commons Attribution license.)

While photodynamic inactivation (PDI) has emerged as a novel sterilization strategy for drinking water treatment that recently attracted tremendous attention, its efficiency needs to be further improved. In this study, we aimed to clarify the ultraefficient mechanism by which potassium iodide (KI) potentiates octyl gallate (OG)-mediated PDI against bacteria and biofilms in water. When OG (0.15 mM) and bacteria were exposed to blue light (BL, 420 nm, 210 mW/cm 2 ), complete sterilization (>7.5 Log cfu/mL of killing) was achieved by the addition of KI (250 mM) within only 5 min (63.9 J/cm 2 ). In addition, at lower doses of OG (0.1 mM) with KI (100 mM), the biofilm was completely eradicated within 10 min (127.8 J/cm 2 ). The KI-potentiated mechanism involves in situ rapid photogeneration of a multitude of reactive oxygen species, especially hydroxyl radicals ( • OH), reactive iodine species, and new photocytocidal substances (quinone) by multiple photochemical pathways, which led to the destruction of cell membranes and membrane proteins, the cleavage of genomic DNA and extracellular DNA within biofilms, and the degradation of QS signaling molecules. This multitarget synergistic strategy provided new insights into the development of an environmentally friendly, safe, and ultraefficient photodynamic drinking water sterilization technology.

Postmenopausal osteoporosis is one of the most common metabolic diseases in old women, and supplementing estrogen through bioactive substances is one of the important ways to improve menopausal syndrome. Some studies have confirmed that soybean isoflavone has estrogenic activity, and the main active component of soybean isoflavones is isoflavone aglycones. However, few studies have investigated the improvement effect of high-purity soy isoflavone aglycones on postmenopausal osteoporosis. Thus, the effect of different doses of high-purity soybeans isoflavone aglycone on the ovariectomized female osteoporosis rat model was evaluated by oral gavage. The rats were divided into seven experimental groups including SHAM, OVX, EE, SIHP, AFDP-L, AFDP-M, and AFDP-H, which was administered for 60 days from 30 days after ovariectomy. We collected blood from the abdominal aorta of rats on the 30th, 60th, and 90th days respectively, analyzed its serum biochemistry, and took out the femur for micro-CT imaging and bone microstructure parameter analysis. Results showed that the intervention effect of AFDP-H group on osteoporosis rats at 60 and 90 days was similar to that of EE group, and superior to the OVX group, SIHP group, AFDP-L group, AFDP-M group. The AFDP-H group inhibited the decrease in serum bone markers, bone density, trabeculae quantity, trabeculae thickness, and bone volume fraction, and increased the trabecular separation caused by ovariectomy, thereby significantly improving bone microstructure. It also prevented continuous weight gain and increased cholesterol levels in female rats. This study provided theoretical to application of soybean isoflavone aglycone in the intervention of osteoporosis. and confirmed that could replace chemical synthetic estrogen drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Yang, Ma, Li, Bian, Fu, Ren, Wang, Shi and Zhang.)

Multidrug resistance is a major challenge in treating advanced hepatocellular carcinoma (HCC). Although recent studies have reported that the multidrug resistance phenotype is associated with abnormal DNA methylation in cancer cells, the epigenetic mechanism underlying multidrug resistance remains unknown. Here, we reported that the level of 5-hydroxymethylcytosine (5-hmC) in human HCC tissues was significantly lower than that in adjacent liver tissues, and reduced 5-hmC significantly correlated with malignant phenotypes, including poor differentiation and microvascular invasion; additionally, loss of 5-hmC was related to chemotherapy resistance in post-transplantation HCC patients. Further, the 5-hmC level was regulated by ten-eleven translocation 2 (TET2), and the reduction of TET2 in HCC contributes to chemotherapy resistance through histone acetyltransferase P300/CBP-associated factor (PCAF) inhibition and AKT signaling hyperactivation. In conclusion, loss of 5-hmC induces chemotherapy resistance through PCAF/AKT axis and is a promising chemosensitivity prediction biomarker and therapeutic target for HCC patients., (© 2023. The Author(s).)

Lysine-specific demethylase 1 (LSD1) was the first histone demethylase discovered and the founding member of the flavin-dependent lysine demethylase family (KDM1). The human KDM1 family includes KDM1A and KDM1B, which primarily catalyze demethylation of histone H3K4me1/2. The KDM1 family is involved in epigenetic gene regulation and plays important roles in various biological and disease pathogenesis processes, including cell differentiation, embryonic development, hormone signaling, and carcinogenesis. Malfunction of many epigenetic regulators results in complex human diseases, including cancers. Regulators such as KDM1 have become potential therapeutic targets because of the reversibility of epigenetic control of genome function. Indeed, several classes of KDM1-selective small molecule inhibitors have been developed, some of which are currently in clinical trials to treat various cancers. In this chapter, we review the discovery, biochemical, and molecular mechanisms, atomic structure, genetics, biology, and pathology of the KDM1 family of lysine demethylases. Focusing on cancer, we also provide a comprehensive summary of recently developed KDM1 inhibitors and related preclinical and clinical studies to provide a better understanding of the mechanisms of action and applications of these KDM1-specific inhibitors in therapeutic treatment., (© 2023. Springer Nature Switzerland AG.)

Single crystals and polycrystalline samples of Ho 5 Pd 4 Sn 12 have been synthesized using flux and arc-melting methods, respectively. Single-crystal X-ray diffraction studies indicate that Ho 5 Pd 4 Sn 12 crystallizes in a tetragonal structure ( I 4/ m ) at room temperature and transforms into a monoclinic structure ( C 2/ m ) below ∼194 K. This structural transition is further supported by a transmission electron microscopy study and an anomaly at ∼194 K in the specific heat data. Temperature-dependent resistivity data also show a kink around the structural transition temperature. Ho 5 Pd 4 Sn 12 is antiferromagnetically ordered below 7 K. Ho 5 Pd 4 Sn 12 shows magnetic anisotropy, and the isothermal magnetization curve ( H ⊥ c ) at 2 K exhibits a field-induced magnetic phase transition around 22.8 kOe.

This study aimed to investigate the synergistic bactericidal activity and mechanism of dual-stage light-guided membrane and DNA-targeted photodynamic inactivation (PDI) by the combination of blue light (BL, 420 nm) and the food additive octyl gallate (OG) against Vibrio parahaemolyticus in planktonic and biofilm growth modes. While OG serves as an outstanding exogenous photosensitizer, the planktonic cells were not visibly detectable after the OG-mediated PDI treatment with 0.2 mM OG within 15 min (191.7 J/cm 2 ), and its biofilm was nearly eradicated within 60 min (383.4 J/cm 2 ). Gram-positive Staphylococcus aureus was more susceptible to the PDI than Gram-negative V. parahaemolyticus . The cellular wall and proteins, as well as DNA, were the vulnerable targets for PDI. The membrane integrity could be initially disrupted by OG bearing a hydrophilic head and a hydrophobic tail via transmembrane insertion. The enhancement of OG uptake due to the first-stage light-assisted photochemical internalization (PCI) promoted the accumulation of OG in cells. It further boosted the second-stage light irradiation of the photosensitizer-inducing massive cell death. Upon the second-stage BL irradiation, reactive oxygen species (ROS) generated through the OG-mediated PDI in situ could extensively deconstruct membranes, proteins, and DNA, as well as biofilms, while OG could be activated by BL to carry out photochemical reactions involving the formation of OG-bacterial membrane protein (BMP) covalent conjugates and the interactions with DNA. This dual-stage light-guided subcellular dual-targeted PDI strategy exhibits encouraging effects on the eradication of planktonic bacteria and sessile biofilms, which provides a new insight into the development of an ultraeffective antimicrobial and biofilm removing/reducing technique to improve microbiological safety in the food industry.

Pseudomonas fluorescens is a Gram-negative spoilage bacterium and dense biofilm producer, causing food spoilage and persistent contamination. Here, we report an ultra-efficient photodynamic inactivation (PDI) system based on blue light (BL) and octyl gallate (OG) to eradicate bacteria and biofilms of P. fluorescens. OG-mediated PDI could lead to a > 5-Log reduction of viable cell counts within 15 min for P. fluorescens. The activity is exerted through rapid penetration of OG towards the cells with the generation of a high-level toxic reactive oxygen species triggered by BL irradiation. Moreover, OG plus BL irradiation can efficiently not only prevent the formation of biofilms but also scavenge the existing biofilms. Additionally, it was shown that the combination of OG/poly(lactic acid) electrospun nanofibers and BL have great potential as antimicrobial packagings for maintaining the freshness of the salamander storge. These prove that OG-mediated PDI can provide a superior platform for eradicating bacteria and biofilm., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

N 6 -methyladenosine (m 6 A) methylation is co-transcriptionally deposited on mRNA, but a possible role of m 6 A on transcription remains poorly understood. Here, we demonstrate that the METTL3/METTL14/WTAP m 6 A methyltransferase complex (MTC) is localized to many promoters and enhancers and deposits the m 6 A modification on nascent transcripts, including pre-mRNAs, promoter upstream transcripts (PROMPTs), and enhancer RNAs. PRO-seq analyses demonstrate that nascent RNAs originating from both promoters and enhancers are significantly decreased in the METTL3-depleted cells. Furthermore, genes targeted by the Integrator complex for premature termination are depleted of METTL3, suggesting a potential antagonistic relationship between METTL3 and Integrator. Consistently, we found the Integrator complex component INTS11 elevated at promoters and enhancers upon loss of MTC or nuclear m 6 A binders. Taken together, our findings suggest that MTC-mediated m 6 A modification protects nascent RNAs from Integrator-mediated termination and promotes productive transcription, thus unraveling an unexpected layer of gene regulation imposed by RNA m 6 A modification., Competing Interests: Declaration of interests Y.S. is a co-founder of and holds equity in K36 Therapeutics. Y.S. is a consultant for Active Motif, a member of the Scientific Advisory Board of the College of Life Sciences, West Lake University, and a member of the MD Anderson External Advisory Board. K.A. received research funding from Novartis not related to this work, is a consultant for Syros Pharmaceuticals, is on the SAB of CAMP4 Therapeutics, and is a member of the Advisory Board of Molecular Cell. All other authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Excitonic insulators are usually considered to form via the condensation of a soft charge mode of bound electron-hole pairs. This, however, presumes that the soft exciton is of spin-singlet character. Early theoretical considerations have also predicted a very distinct scenario, in which the condensation of magnetic excitons results in an antiferromagnetic excitonic insulator state. Here we report resonant inelastic x-ray scattering (RIXS) measurements of Sr 3 Ir 2 O 7 . By isolating the longitudinal component of the spectra, we identify a magnetic mode that is well-defined at the magnetic and structural Brillouin zone centers, but which merges with the electronic continuum in between these high symmetry points and which decays upon heating concurrent with a decrease in the material's resistivity. We show that a bilayer Hubbard model, in which electron-hole pairs are bound by exchange interactions, consistently explains all the electronic and magnetic properties of Sr 3 Ir 2 O 7 indicating that this material is a realization of the long-predicted antiferromagnetic excitonic insulator phase., (© 2022. The Author(s).)

A series of alkyl gallates were evaluated for the antibacterial activity against two common Gram-negative foodborne bacteria (Pseudomonas fluorescens and Vibrio parahaemolyticus) associated with seafood. The length of the alkyl chain plays a pivotal role in eliciting their antibacterial activities and octyl gallate (OG) exerted an excellent inhibitory efficacy. To extend the aqueous solubility, stability, and bactericidal properties of octyl gallate (OG), an inclusion complex between OG and β-cyclodextrin (βCD), OG/βCD, was prepared and identified with various methods including X-ray diffraction (XRD), differential scanning calorimeter (DSC) and Fourier transform infrared spectroscopy (FTIR). Furthermore, the enhanced inhibitory effect and potential antibacterial mechanism of OG/βCD against two Gram-negative and Gram-positive foodborne bacteria were comprehensively investigated. The results show that OG/βCD could function against bacteria through effectively damaging the membrane, permeating into cells, and then disturbing the activity of the respiratory electron transport chain to cause the production of high-level intracellular hydroxyl radicals. Moreover, the reinforced OG/βCD-incorporated polylactic acid (PLA) nanofibers were fabricated using the electrospinning technique as food packaging to extend the Chinese giant salamander fillet's shelf life at 4 °C. This research highlights the antibacterial effectiveness of OG/βCD in aqueous media, which can be used as a safe multi-functionalized food additive combined with the benefits of electrospun nanofibers to extend the Chinese giant salamander fillets shelf life by 15 d at 4 °C., (Copyright © 2021 Elsevier B.V. All rights reserved.)

An excellent bactericidal effect of octyl gallate (OG)-mediated photodynamic inactivation (PDI) against foodborne pathogens ( Escherichia coli and Staphylococcus aureus ) was evaluated in relation to the mode of action. UV-A irradiation (wavelength, 365 nm; irradiance, 8.254 ± 0.18 mW/cm 2 ) of the bacterial suspension containing 0.15 mM OG could lead to a >5-log reduction of viable cell counts within 30 min for E. coli and only 5 min for S. aureus . Reactive oxygen species (ROS) formation was considered the main reason for the bactericidal effect of OG + UV-A light treatment because toxic ROS induced by OG-mediated PDI could attack the cellular wall, proteins, and DNA of microbes. Moreover, the bactericidal effect, as well as the yields of ROS, depended on OG concentrations, irradiation time, and laser output power. Furthermore, we prepared an edible photodynamic antimicrobial membrane comprising electrospun cyclodextrin nanofibers (NFs) by embedding OG. The resultant OG/HPβCD NFs (273.6 μg/mL) under UV-A irradiation for 30 min (14.58 J/cm) could cause a great reduction (>5-log) of viable bacterial counts of E. coli . The in situ photodynamic antibacterial activity of OG/HPβCD NF-based packaging was evaluated during the Chinese giant salamander storage. Overall, this research highlights the dual functionalities (antibacterial and photodynamic properties) of OG as both an antibacterial agent and photosensitizer and the effectiveness of electrospun NFs containing OG as an active antibacterial packaging material for food preservation upon UV light illumination.

The intestinal microecological environment is critical to an infant's growth. For those infants consuming milk power, it is very important to improve the intestinal microecological environment to promote the healthy growth of infants. In this paper, Milk protein hydrolysate (MPH), consisting of different proportions of proteins and small molecule peptides (5:5, 4:6, 3:7, 2:8, 1:9) were added to infant formula powder (IFP). The effects of MFP-enriched IFP addition on proliferation and metabolism of Bifidobacterium L80 were studied. Compared with MPH-free IFP, MFP-enriched IFP with 1:9 of proteins to small molecule peptides significantly enhanced the proliferation of Bifidobacterium L80, resulting in higher cell density, greater viable counts and higher titratable acidity. MFP-enriched IFP increased the content of seven organic acids and H 2 O 2 in the system, and improved the antibacterial activity to E. coli BL21. This study suggested that MPH could be an effective addition to infant formula powder to promote the growth of Bifidobacterium, so to improve the intestinal health of infants., (© 2021. The Author(s).)

The objective of this study was to investigate antibacterial activities and action mode of alkyl gallates against three food-related bacteria. Results show that the length of the alkyl chain plays a critical role in eliciting their antibacterial activities and octyl gallate (GAC8) exhibited an outstanding bactericidal effect against these strains. A possible bactericidal mechanism of GAC8 against E. coli was fully elucidated by analyzing associated changes in cellular functions of E. coli, including assessments of membrane modification and intracellular oxidation state. Our data strongly suggested that GAC8 functions outside and inside the bacterial membrane and causes increased intracellular reactive oxygen species (hydroxyl radicals) and subsequent oxidative damage. We demonstrated that the hydroxyl radical formation induced by GAC8 is the end product of an oxidative damage cellular death pathway involving a transient depletion of NADH, the tricarboxylic acid cycle, intrinsic redox cycling activities, and stimulation of the Fenton reaction. Also, chitosan-based edible films containing GAC8 have unique superiorities for icefish preservation at 4 °C. This research highlights the effectiveness of GAC8 as an attractive antibacterial, which possesses both antioxidant and antibacterial activities and can be used as a multifunctional food additive combined with the benefit of active packaging for food preservations., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Precision medicine (PM) aims to revolutionise healthcare, but little is known about the role religion and spirituality might play in the ethical discourse about PM. This Perspective reports the outcomes of a knowledge exchange fora with religious authorities in Singapore about data sharing for PM. While the exchange did not identify any foundational religious objections to PM, ethical concerns were raised about the possibility for private industry to profiteer from social resources and the potential for genetic discrimination by private health insurers. According to religious authorities in Singapore, sharing PM data with private industry will require a clear public benefit and robust data governance that incorporates principles of transparency, accountability and oversight., Supplementary Information: The online version contains supplementary material available at 10.1007/s41649-021-00180-4., (© The Author(s) 2021.)

The variations in flavor substances across the different stages of fermented soybean whey tofu (FSWT) production were analyzed by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) combined with principal component analysis (PCA). The results revealed 24 representative flavor compounds in the samples across all production stages. After heating, the signal intensity of hexanal, 1-octen-3-ol, heptanal, and (E)-2-hexenol, which are unpleasant flavor substances found in raw soymilk, weakened, whereas those of some aroma substances increased. Furthermore, fermented flavor compounds, namely, 2-heptanone, 2-pentylfuran, pentanal, and 2,3-butanedione, were produced after the addition of fermented soybean whey as a coagulant. A PCA based on the signal intensity of the detected volatile compounds revealed effective differentiation of samples from different stages into comparatively independent spaces. These results showed that the flavor fingerprints of the samples from different stages of FSWT production can be successfully built using HS-GC-IMS and PCA based on the detected volatile compounds., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The objective of this study was to investigate the antibacterial activity and potential mechanism of alkyl gallates against Escherichia coli and Staphylococcus aureus. Results show that the length of the alkyl chain plays a pivotal role in eliciting the activity and octyl gallate (OG) exerted excellent bactericidal activity through a multiple bactericidal mechanism. OG functions against both bacteria through damaging bacterial cell wall integrity, permeating into cells and then interacting with DNA, as well as disturbing the activity of the respiratory electron transport chain to induce a high-level toxic ROS (hydroxyl radicals) generation and up-regulation of the ROS genes. Also, electrospun nanofibers with OG have unique superiorities for maintaining the freshness of the icefish (4 °C). This research not only provides a more in-depth understanding of the interaction between OG and microorganisms but also highlights the great promise of using OG as a safe multi-functionalized food additive for food preservations., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Activation of PD-1/PD-L1 checkpoint is a critical step for the immune evasion of malignant tumors including breast cancer. However, the epigenetic mechanism underlying the aberrant expression of PD-L1 in breast cancer cells remains poorly understood. To investigate the role of TET2 in the regulation of PD-L1 gene expression, quantitative reverse transcription PCR (RT-qPCR), Western blotting, chromatin immunoprecipitation (ChIP) assay and MeDIP/hMeDIP-qPCR were performed on MCF7 and MDA-MB-231 human breast cancer cells. Here, we reported that TET2 depletion upregulated PD-L1 gene expression in MCF7 cells. Conversely, ectopic expression of TET2 inhibited PD-L1 gene expression in MDA-MB-231 cells. Mechanistically, TET2 protein recruits histone deacetylases (HDACs) to PD-L1 gene promoter and orchestrates a repressive chromatin structure to suppress PD-L1 gene transcription, which is likely independent of DNA demethylation. Consistently, treatment with HDAC inhibitors upregulated PD-L1 gene expression in wild-type (WT) but not TET2 KO MCF7 cells. Furthermore, analysis of the CCLE and TCGA data showed a negative correlation between TET2 and PD-L1 expression in breast cancer. Taken together, our results identify a new epigenetic regulatory mechanism of PD-L1 gene transcription, linking the catalytic activity-independent role of TET2 to the anti-tumor immunity in breast cancer.

Since Pseudomonas fluorescens is the main microorganism causing severe spoilage in refrigerated aquatic products, the searching for non-antibiotic antibacterial agents effective against it continues to receive increasing interest. This study aimed to investigate the antibacterial effects and mechanisms of alkyl gallic esters against P. fluorescens isolated from the Russian sturgeon (Acipenser gueldenstaedti), as well as the effectiveness in combination with chitosan films on the preservation of sturgeon meats at 4 °C. Our data shows that the alkyl chain length plays a significant role in eliciting their antibacterial activities and octyl gallate (GAC8) exhibited an outstanding inhibitory efficacy. GAC8 can rapidly enter into the membrane lipid bilayer portion to disorder the membrane, and further inhibit the growth of the P. fluorescens through interfering both tricarboxylic acid cycle related to energy supply and amino acid metabolism associated with cell membranes, suppressing oxygen consumption and disturbing the respiration chain. Moreover, the alteration in membrane fatty acids indicated that GAC8 could disrupt the composition of cell membrane fatty acids, rendering the bacteria more sensitive to the antibacterial. The SEM results also substantiate the damage of the structure of the bacterial membrane caused by GAC8. Additionally, the edible chitosan-based films incorporated with GAC8 showed the enhanced antibacterial efficacy to remarkably extend the shelf life of Russian sturgeon. Overall, our findings not only provide new insight into the mode of action of GAC8 against P. fluorescens but also demonstrate composite films containing GAC8, as a kind of safe and antibacterial material, have a great promise for application in food preservations., (Copyright © 2021 Elsevier B.V. All rights reserved.)

METTL3 (methyltransferase-like 3) mediates the N 6 -methyladenosine (m 6 A) methylation of mRNA, which affects the stability of mRNA and its translation into protein 1 . METTL3 also binds chromatin 2-4 , but the role of METTL3 and m 6 A methylation in chromatin is not fully understood. Here we show that METTL3 regulates mouse embryonic stem-cell heterochromatin, the integrity of which is critical for silencing retroviral elements and for mammalian development 5 . METTL3 predominantly localizes to the intracisternal A particle (IAP)-type family of endogenous retroviruses. Knockout of Mettl3 impairs the deposition of multiple heterochromatin marks onto METTL3-targeted IAPs, and upregulates IAP transcription, suggesting that METTL3 is important for the integrity of IAP heterochromatin. We provide further evidence that RNA transcripts derived from METTL3-bound IAPs are associated with chromatin and are m 6 A-methylated. These m 6 A-marked transcripts are bound by the m 6 A reader YTHDC1, which interacts with METTL3 and in turn promotes the association of METTL3 with chromatin. METTL3 also interacts physically with the histone 3 lysine 9 (H3K9) tri-methyltransferase SETDB1 and its cofactor TRIM28, and is important for their localization to IAPs. Our findings demonstrate that METTL3-catalysed m 6 A modification of RNA is important for the integrity of IAP heterochromatin in mouse embryonic stem cells, revealing a mechanism of heterochromatin regulation in mammals.

Nowadays, more and more infants are getting allergic to cow's milk protein, so it is urgent to search for infant formula powder with milk protein alternatives. In the present work, soy protein hydrolysate (SPH) was added to protein-free infant formula powder and the effects of SPH addition on proliferation and metabolism of Streptococcus thermophilus were studied. Compared with commercially available infant formula powder (CK) and protein-free milk powder (BK), the infant formula powder with 20% SPH significantly enhanced the proliferation of S. thermophilus in MRS medium, resulting in a higher cell density and greater viable counts. Moreover, the influence of SPH on the metabolism of S. thermophilus was investigated by analyzing the content of seven organic acids and H 2 O 2 in the medium . The higher content of organic acids and H 2 O 2 is consistent with the stronger antibacterial activity to Escherichia coli. As a consequence, the addition of SPH to infant formula powder can effectively promote the growth of probiotics and SPH may be a promising protein alternative in the infant formula powder., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

As exemplified by the growing interest in the quantum anomalous Hall effect, the research on topology as an organizing principle of quantum matter is greatly enriched from the interplay with magnetism. In this vein, we present a combined electrical and thermoelectrical transport study on the magnetic Weyl semimetal EuCd_{2}As_{2}. Unconventional contribution to the anomalous Hall and anomalous Nernst effects were observed both above and below the magnetic transition temperature of EuCd_{2}As_{2}, indicating the existence of significant Berry curvature. EuCd_{2}As_{2} represents a rare case in which this unconventional transverse transport emerges both above and below the magnetic transition temperature in the same material. The transport properties evolve with temperature and field in the antiferromagnetic phase in a different manner than in the paramagnetic phase, suggesting different mechanisms to their origin. Our results indicate EuCd_{2}As_{2} is a fertile playground for investigating the interplay between magnetism and topology, and potentially a plethora of topologically nontrivial phases rooted in this interplay.

Monocytic myeloid-derived suppressor cells (M-MDSCs), granulocytic MDSC (G-MDSCs) and regulatory T cells (Tregs) inhibit adaptive anti-tumor immunity and undermine the efficacy of anti-PD-1 therapy. However, the impact of anti-PD-1 treatment on these immunosuppressive cells has not been clearly defined in non-small cell lung cancer (NSCLC). In this retrospective study, 27 advanced NSCLC patients were divided into partial response (PR), stable disease (SD), and progressive disease (PD) groups. The impact of anti-PD-1 therapy on circulating Tregs, G-MDSCs, and M-MDSCs was assessed by flow cytometer. Here, we found that anti-PD-1 treatment boosted circulating Tregs levels, which presented the most remarkable augment during the first two therapeutic cycles, in NSCLC patients. In contrast, anti-PD-1 therapy did not overall change G-MDSCs and M-MDSCs levels. However, the PR group had a higher baseline level of M-MDSCs, which exhibited a significant decrease after the first cycle of anti-PD-1 treatment. Besides, M-MDSCs levels in the PR group were maintained at a low level in the following therapeutic cycles. Consistently, Tregs levels robustly increased in the syngeneic tumor model after anti-mouse PD-1 Ab treatment. Accordingly, M-MDSCs neutralization by anti-mouse ly6c Ab enhanced the anti-tumor efficacy of anti-PD-1 therapy in mice. Finally, the decreased M-MDSCs levels were associated with the enhanced effector CD8 + T cells expansion in the PR group and mice. In conclusion, anti-PD-1 therapy upregulates Tregs levels in NSCLC patients, and the M-MDSC levels are associated with the anti-tumor efficacy of anti-PD-1 treatment. Neutralization of M-MDSCs may be a promising option to augment anti-PD-1 therapy efficacy in NSCLC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Soy protein isolate hydrolysates (SPIH) were prepared from soy protein isolate (SPI). Effects of SPIH on a satiety signal cholecystokinin (CCK) and feeding behavior in rats were investigated. SPIH induced more CCK release (164.66 ± 2.40 pg/mL) by rat intestinal mucosal cells than SPI (143.33 ± 3.71 pg/mL). Meal size (MS), intermeal interval (IMI), and satiety ratio (SR = MS/IMI) of rats received different daily doses of SPIH or dietary fiber were detected for 40 days. A 100 mg/kg dose of SPIH resulted in a greater SR than an identical dose of dietary fiber, while a 300 mg/kg dose resulted in a less MS and IMI. A 500 mg/kg dose of SPIH had similar effects to the same dose of dietary fiber on reducing MS, extending IMI, and increasing SR, but resulted in a significantly less body weight at the end of the experiment (318.15 ± 17.83 g) than the dietary fiber group (340.28 ± 6.15 g)., Competing Interests: Conflict of interestThe authors declare that they have non-financial interests., (© Association of Food Scientists & Technologists (India) 2020.)

Russian sturgeon is a high-quality cultured fish and traditional heating methods may lead to deterioration of its food quality. This study aimed to evaluate the food quality and microbial composition of sturgeon fillets by low temperature vacuum heating (LTVH) and storage at 4 °C. The treatments varied in temperature (50, 60, and 70 °C) and duration (15 and 30 min); samples treated by traditional heating (100 °C, 15 min) methods were included as controls. We found that LTVH could reduce the values of lightness (L*), yellowness (b*), and pH and increase the values of redness (a*), chewiness, and hardness, to promote food quality. The biogenic amine content declined with the increase in heating temperature and time, the histamine of most concern was low at the end of storage, the values of LTVH70-30 and TC was 33.12 ± 1.25 and 30.39 ± 0.86 mg/kg. The total viable count (TVC) and biogenic amines showed the same trend, and the finial TVC values of LTVH60-30, LTVH70-15, LTVH70-30 and TC were 6.72 ± 0.17, 6.33 ± 0.18, 6.18 ± 0.08 and 5.93 ± 0.16 log CFU/g, which did not exceed the limit value (7 log CFU/g), indicating that the biosafety risk was reduced. According to the high-throughput sequencing results, the microbial composition of LTVH samples showed a lesser abundance pseudomonads than that found in the control. Thus, LTVH technology could be used as an alternative to traditional heating treatment., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A new aromatic glycoside ( 1 ) and a new natural product, neolignan ( 2 ), along with twenty-three known compounds ( 3-25 ), were isolated from the thorns of Gleditsia sinensis . According to the spectroscopic analyses (IR, UV, HRESIMS, NMR and ECD), the structures of isolates were elucidated. Herein, compounds 4 , 6-8 , 10-13 , 15 , 16 , 18 , 20 , 23 were isolated from the plant of G. sinensis for the first time. Moreover, compounds 4, 6 , 15 and 24 showed cytotoxic effects on human ovarian cancer (SKOV-3) cells with IC 50 values of 24.83 ± 4.90, 48.86 ± 9.11, 80.13 ± 5.62, 15.38 ± 2.21 μM, respectively. [Formula: see text].

The host immune response is a fundamental mechanism for attenuating cancer progression. Here we report a role for the DNA demethylase and tumor suppressor TET2 in host anti-tumor immunity. Deletion of Tet2 in mice elevates IL-6 levels upon tumor challenge. Elevated IL-6 stimulates immunosuppressive granulocytic myeloid-derived suppressor cells (G-MDSCs), which in turn reduce CD8 + T cells upon tumor challenge. Consequently, systematic knockout of Tet2 in mice leads to accelerated syngeneic tumor growth, which is constrained by anti-PD-1 blockade. Removal of G-MDSCs by the anti-mouse Ly6g antibodies restores CD8 + T-cell numbers in Tet2 -/- mice and reboots their anti-tumor activity. Importantly, anti-IL-6 antibody treatment blocks the expansion of G-MDSCs and inhibits syngeneic tumor growth. Collectively, these findings reveal a TET2-mediated IL-6/G-MDSCs/CD8 + T-cell immune response cascade that safeguards host adaptive anti-tumor immunity, offering a cell non-autonomous mechanism of TET2 for tumor suppression., (© 2020 The Authors.)

Background: Sturgeon is popular for its nutritious value and its taste. However, sturgeon fillets are traditionally heated in 100 °C boiling water, resulting in unfavorable taste and with a negative effect on the quality. This study considered the effect of combinations of vacuum and low-temperature treatments (LTVH groups) on sturgeon fillets compared with the traditional heat treatment (TC groups)., Results: The results show that the LTVH groups had lower cooking-loss rates. All LTVH fillets were changed to a white color, and appeared 'done', as did the TC fillets. The LTVH and TC methods gave rise to significant differences in texture: the springiness of the LTVH groups decreased with heating time, and decreased rapidly in the TC groups (P < 0.05); hardness and chewiness increased with time and temperature in the LTVH groups, but decreased in the TC groups. More compact and denser gaps were observed in LTVH70 groups and TC groups. Less protein and lipid oxidation was evident in LTVH groups, including more myofibril protein solubility; there was less protein aggregation, fewer thiobarbituric acid reactive substance, and Schiff base., Conclusion: Vacuum and low-temperature treated sturgeon fillets can be served as a good alternative. This treatment caused slight tissue damage and less proteolysis and lipid oxidation, which is beneficial for the quality of aquatic products., (© 2020 Society of Chemical Industry.)

Background: Alzheimer's disease (AD) is the most common type of dementia, and patients with advanced AD frequently lose the ability to identify family members. The fusiform gyrus (FUS) of the brain is critical in facial recognition. However, AD etiology in the FUS of AD patients is poorly understood. New analytical strategies are needed to reveal the genetic and epigenetic basis of AD in FUS., Results: A complex of new analytical paradigms that integrates an array of transcriptomes and methylomes of normal controls, AD patients, and "AD-in-dish" models were used to identify genetic and epigenetic signatures of AD in FUS. Here we identified changes in gene expression that are specific to the FUS in brains of AD patients. These changes are closely linked to key genes in the AD network. Profiling of the methylome (5mC/5hmC/5fC/5caC) at base resolution identified 5 signature genes (COL2A1, CAPN3, COL14A1, STAT5A, SPOCK3) that exhibit perturbed expression, specifically in the FUS and display altered DNA methylome profiles that are common across AD-associated brain regions. Moreover, we demonstrate proof-of-principle that AD-associated methylome changes in these genes effectively predict the disease prognosis with enhanced sensitivity compared to presently used clinical criteria., Conclusions: This study identified a set of previously unexplored FUS-specific AD genes and their epigenetic characteristics, which may provide new insights into the molecular pathology of AD, attributing the genetic and epigenetic basis of FUS to AD development.

Histone H3 point mutations have been identified in incurable pediatric brain cancers, but the mechanisms through which these mutations drive tumorigenesis are incompletely understood. Here, we provide evidence that RACK7 (ZMYND8) recognizes the histone H3.3 patient mutation (H3.3G34R) in vitro and in vivo. We show that RACK7 binding to H3.3G34R suppresses transcription of CIITA , which is the master regulator of MHC (major histocompatibility complex) class II molecules and genes involved in vesicular transport of MHC class II molecules to the cell surface, resulting in suppression of MHC class II molecule expression and transport. CRISPR-based knock-in correction of the H3.3G34R mutation in human pediatric glioblastoma (pGBM) cells significantly reduces overall RACK7 chromatin binding and derepresses the same set of genes as does knocking out RACK7 in the H3.3G34R pGBM cells. By demonstrating that H3.3G34R and RACK7 work together, our findings suggest a potential molecular mechanism by which H3.3G34R promotes cancer., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

In this study, a pot experiment was carried out to examine the effects of high CO 2 concentration, drought and interaction on seedling growth traits, biomass accumulation and physiological characteristics of different stay-green wheat seedlings, with a stay-green wheat variety Yannong 19 and a non stay-green wheat variety Hanxuan 3 as test materials. There were four treatments in the Open Top Chamber with factorial of CO 2 concentration (370 μmol·mol -1 vs 550 μmol·mol -1 ) and drought (45%-55% vs. 75%-85% of field water-holding capacity). Drought significantly inhibited the growth and development of wheat seedlings, while CO 2 concentration significantly increased the number of tillers and promoted the growth and development of wheat seedlings. Under drought condition, high CO 2 concentration increased the number of tillers of Hanxuan 3 and Yannong 19 by 61.0% and 42.3%, respectively. Under both water conditions, high CO 2 concentration significantly increased the biomass of wheat seedlings, and decreased the content of peroxidase and proline in leaves. Under drought condition, high CO 2 concentration showed stronger "fertilizer effect". Furthermore, different varieties had different responses to high CO 2 concentration, with higher sensitivity of Hanxuan 3 to enhancement of CO 2 concentration. Under the scenario of increasing CO 2 concentration, the amount of irrigation water applied to a field can be appropriately reduced for efficient use of water resources. Meanwhile, it is necessary to pay attention to the selection of suitable wheat varieties.