Effect of fat replacement in high internal phase emulsions constructed by high temperature saccharification of grafted proteins on gel properties and flavor profiles of sausages.

In order to mitigate the risk of cardiovascular diseases associated with excessive saturated fatty acid intake, utilizing high internal phase emulsions (HIPEs) as a substitute for animal fat in producing high-quality fat-substituted meat products is an ideal approach. This study involves the preparation of glycosylation products of egg white protein (EWP) through saccharification at high temperatures in the presence of fructooligosaccharides (FO). The resulting glycation products of EWP were employed to create colloidal particles, forming HIPEs, which were further utilized to induce the formation of HIPEs gels (HIPEs-Gs). The study investigated the effects of substituting different ratios (25%, 50%, 75%, and 100%) of animal fat with HIPEs and HIPEs-Gs on the gel properties and flavor characteristics of sausages. Results showed that, compared to the control group, substituting fat with HIPEs significantly improved the gel properties, cooking yield, and G' of sausages, while excessive HIPEs-Gs substitution yielded negative effects. Low-field nuclear magnetic resonance results also demonstrated that adding HIPEs improved water and oil distribution in the sausage batter, enhancing protein's binding capacity with water. Scanning electron microscope revealed that HIPEs substitution led to a denser gel network with smaller pores, effectively "locking in" more water. Analysis of volatile compounds indicated accelerated release of aromatic compounds, alkanes, sulfides, and lipids when fat was substituted with HIPEs and HIPEs-Gs. Electronic tongue analysis suggested that HIPEs-Gs substitution reduced response values for umami and saltiness. In conclusion, compared to HIPEs-Gs, using HIPEs as a fat substitute improves the quality of sausages.

Synergistic effect of concurrent high molecular risk mutations and lower JAK2 mutant variant allele frequencies on prognosis in patients with myelofibrosis-insights from a multicenter study.

In addition to high-molecular risk (HMR) mutations (ASXL1, EZH2, SRSF2, IDH, and U2AF1Q157), lower JAK2V617F variant allele frequencies (VAF) have been demonstrated to be associated with poor prognosis of myelofibrosis (MF) patients. Nevertheless, the relationship between JAK2V617F VAF and HMR mutations remains inconclusive. To address this, we analyzed the mutation status of 54 myeloid neoplasm-relevant genes using targeted next-generation sequencing in 124 MF patients. Three cohorts from multiple international centers were analyzed for external validation. Among JAK2-mutated patients, the presence of HMR mutations drove poor prognosis in patients with lower JAK2V617F VAF but not in those with higher JAK2V617F VAF. Survival analyses showed consistent results across validation cohorts. In multivariable analysis, concurrent HMR and a lower JAK2V617F VAF was identified as an independent adverse prognostic factor for survival, irrespective of age, MIPSS70, MIPSS70 + v2, and GIPSS risk groups. Mutation co-occurrence tests revealed no shared mutational pattern over different cohorts, excluding potential confounding effect from other concurrent mutations. Importantly, the integration of HMR/JAK2V617F VAF (≤50%) status significantly enhanced existing prognostic models, as evidenced by higher c-indexes and time-dependent ROC analyses. Single-cell studies with sequential follow-ups are warranted to decipher the clonal evolution of MF and how it relates to JAK2V617F VAF dynamics.

Oxidative stability of chelated Sn(II)(aq) at neutral pH: The critical role of NO3- ions.

Tin(II) compounds are versatile materials with applications across fields such as catalysis, diagnostic imaging, and therapeutic drugs. However, oxidative stabilization of Sn(II) has remained an unresolved challenge as its reactivity with water and dioxygen results in loss of functionality, limiting technological advancement. Approaches to slow Sn(II) oxidation with chelating ligands or sacrificial electron donors have yielded only moderate improvements. We demonstrate here that the addition of nitrate to pyrophosphate-chelated Sn(II)(aq) suppresses Sn(II) oxidation in water across a broad pH range. Evidence of hydroxyl radical concentration reduction and detection of a radical nitrogen species that only forms in the presence of chelated Sn(II) point to a radical-based reaction mechanism. While this chemistry can be broadly applied, we present that this approach maintains Sn(II)'s antibacterial and anti-inflammatory efficacies as an example of sustained oral chemotherapeutic functionality.

Effects of pasteurization temperature and amino acids on the gelation behavior of liquid egg yolk: Emphasizing rheology, gel properties, intermolecular forces and microstructure.

Pipeline blockage caused by liquid egg yolk (LEY) in the pasteurization process has become an urgent problem for egg industry. This study investigated the effects of amino acids (betaine/proline) on rheology of LEY and gel property of egg yolk gel (EYG) at various pasteurization temperatures (68, 72, and 76 °C). Rheological results revealed that 72 °C was the key transition point for increase in LEY thermal aggregation rate. Average particle size of EYG, BEYG and PEYG increased by 63.9 %, 27.3 % and 17.3 % with increasing pasteurization temperature. Amino acids promoted increase in disulfide bonding content and facilitated retention of free and bound water within gels. Moreover, amino acids enhanced crystallinity and order of gel structures. Amino acids can effectively mitigate thermal aggregation of LEY at mild temperatures and promote cross-linking of gel network at high temperatures. This study provides a theoretical foundation for heat resistance of LEY and application of EYG.

Mechanistic study on the decline of foaming characteristics of egg white under heat stress: Emphasizing apparent phenomena, structure, and intermolecular interactions.

Heat stress is a critical step in the processing of liquid egg white; however, this treatment can severely affect its foaming properties. This study aims to elucidate the mechanisms underlying the decline in foaming properties of liquid egg white during heat stress. The research begins by examining the adverse effects of heat stress on the foaming properties of liquid egg whites, where an increase in apparent viscosity, turbidity, and particle size is initially observed, indicating the formation of aggregates. After heat stress, the binding water capacity of the liquid egg white increases, intermolecular forces strengthen, and the secondary structure transforms towards ß-sheet and ß-turn configurations, while surface hydrophobicity decreases. Heat stress promotes the transition of liquid egg white into a more stable gel state. Additionally, electrophoresis results show the disappearance of bands for ovomucin subunit, ovotransferrin, and lysozyme, while microscopic observations reveal a rougher surface texture of the samples. In summary, this study provides insights and theoretical basis for understanding the mechanisms behind the decline in foaming properties of liquid egg whites under heat stress.

Biological soil crusts significantly improve soil fertility and change soil microbiomes in Qinghai-Tibetan alpine grasslands.

Biological soil crusts (BSCs), a vital component of ecosystems, are pivotal in carbon sequestration, nutrient enrichment, and microbial diversity conservation. However, their impact on soil microbiomes in alpine regions remains largely unexplored. Therefore, this study aimed to determine the influence of BSCs on alpine grassland soil microbiomes, by collecting 24 pairs of soils covered by biological and physical crusts along a transect on the Qinghai-Tibetan Plateau. We found that BSCs significantly increased the contents of soil moisture, organic carbon, total nitrogen, and many available nutrients. They also substantially altered the soil microbiomes. Specifically, BSCs significantly increased the relative abundance of Cyanobacteria, Verrucomicrobiota, and Ascomycota, while decreasing the proportions of Gemmatimonadota, Firmicutes, Nitrospirae, Mortierellomycota, and Glomeromycota. By contrast, microbial abundance and α-diversity demonstrated low sensitivity to BSCs across most study sites. Under the BSCs, the assembly of prokaryotic communities was more affected by homogeneous selection and drift, but less affected by dispersal limitation. Conversely, soil fungal community assembly mechanisms showed an inverse trend. Overall, this study provides a comprehensive understanding of the effects of BSCs on soil properties and microbial communities, offering vital insights into the ecological roles of BSCs.

Fine particulate matter manipulates immune response to exacerbate microbial pathogenesis in the respiratory tract.

Particulate matter with a diameter ≤2.5 µm (PM2.5) poses a substantial global challenge, with a growing recognition of pathogens contributing to diseases associated with exposure to PM2.5 Recent studies have focused on PM2.5, which impairs the immune cells in response to microbial infections and potentially contributes to the development of severe diseases in the respiratory tract. Accordingly, changes in the respiratory immune function and microecology mediated by PM2.5 are important factors that enhance the risk of microbial pathogenesis. These factors have garnered significant interest. In this review, we summarise recent studies on the potential mechanisms involved in PM2.5-mediated immune system disruption and exacerbation of microbial pathogenesis in the respiratory tract. We also discuss crucial areas for future research to address the gaps in our understanding and develop effective strategies to combat the adverse health effects of PM2.5.

A comprehensive review on freeze-induced deterioration of frozen egg yolks: Freezing behaviors, gelation mechanisms, and control techniques.

Over the years, the production of eggs has increased tremendously, with an estimated global egg production of 9.7 billion by 2050. Further processing of shell eggs to egg products has gained growing popularity. Liquid egg yolks, an innovative form of egg replacement, still suffer from short shelf-life issues, and freezing has been applied to maintain freshness. An undesirable phenomenon called "gelation" was found during the production of frozen egg yolks, which has attracted numerous scholars to study its mechanism and quality control methods. Therefore, we comprehensively reviewed the history of the studies on frozen egg yolks, including the production procedure, the fundamentals of freezing, the gelation mechanism, the factors affecting gelation behaviors, and the techniques to control the gelation behaviors of frozen egg yolks. Reporting the production procedure and freezing fundamentals of frozen egg yolks will give readers a better understanding of the science and technological aspects of frozen egg yolks. Furthermore, a comprehensive summary of the mechanism of egg yolk gel formation induced by freeze-thawing and relevant control techniques will provide insights to researchers and manufacturers in the field of frozen egg processing.

Exploring plant growth promoting traits and biocontrol potential of new isolated Bacillus subtilis BS-2301 strain in suppressing Sclerotinia sclerotiorum through various mechanisms.

Sclerotinia sclerotiorum (Lib.) de Bary is the causative agent of stem white mold disease which severely reduces major crop productivity including soybean and rapeseed worldwide. The current study aimed to explore plant growth-promoting traits and biocontrol of new isolated Bacillus subtilis BS-2301 to suppress S. sclerotiorum through various mechanisms. The results indicated that the BS-2301 exhibited strong biocontrol potential against S. sclerotiorum up to 74% both in dual culture and partition plate experiments. The BS-2301 and its crude extract significantly suppressed S. sclerotiorum growth involving excessive reactive oxygen species (ROS) production in mycelia for rapid death. Furthermore, the treated hyphae produced low oxalic acid (OA), a crucial pathogenicity factor of S. sclerotiorum. The SEM and TEM microscopy of S. sclerotiorum showed severe damage in terms of cell wall, cell membrane breakage, cytoplasm displacement, and organelles disintegration compared to control. The pathogenicity of S. sclerotiorum exposed to BS-2301 had less disease progression potential on soybean leaves in the detached leaf assay experiment. Remarkably, the strain also demonstrated broad-range antagonistic activity with 70%, and 68% inhibition rates against Phytophthora sojae and Fusarium oxysporum, respectively. Furthermore, the strain exhibits multiple plant growth-promoting and disease-prevention traits, including the production of indole-3-acetic acid (IAA), siderophores, amylases, cellulases and proteases as well as harboring calcium phosphate decomposition activity. In comparison to the control, the BS-2301 also showed great potential for enhancing soybean seedlings growth for different parameters, including shoot length 31.23%, root length 29.87%, total fresh weight 33.45%, and total dry weight 27.56%. The antioxidant enzymes like CAT, POD, SOD and APX under BS-2301 treatment were up-regulated in S. sclerotiorum infected plants along with the positive regulation of defense-related genes (PR1-2, PR10, PAL1, AOS, CHS, and PDF1.2). These findings demonstrate that the BS-2301 strain possesses a notable broad-spectrum biocontrol potential against different phytopathogens and provides new insight in suppressing S. sclerotiorum through various mechanisms. Therefore, BS-2301 will be helpful in the development of biofertilizers for sustainable agricultural practices.

Synthetic routes and clinical application of new drugs approved by EMA during 2023.

In 2023, the European Medicines Agency (EMA) granted approval to 77 new molecular entities (NMEs), consisting of 45 new chemical entities (NCEs) and 32 new biological entities (NBEs). These pharmacological agents encompass a broad spectrum of therapeutic domains, including oncology, cardiology, dermatology, diagnostic medicine, endocrinology, gastroenterology and hepatology, metabolic disorders, and neurology. Among the 77 approved pharmaceuticals, three received accelerated review status, and 17 (22 %) were granted orphan drug designation for the treatment of rare diseases. This review provides an overview of the clinical applications and synthetic routes of 42 newly approved NCEs by the EMA in 2023. The objective is to offer a comprehensive understanding of the synthetic approaches used in the development of these drug molecules, thereby inspiring the creation of novel, efficient, and applicable synthetic methodologies.

Dynamic Electric Discharge Paths in Liquid Metal Marble Arrays.

Electric discharge occurs ubiquitously in both natural and engineered systems, where the discharge paths provide critical information. However, control and visualization of discharge patterns is a challenging task. Here arrays of liquid metal marbles, droplets of a gallium-indium eutectic alloy with a copper-doped ZnS luminescent coating, are designed for pixelated visualization of electric discharge paths at optical imaging length-scales. The ZnS particles embed themselves into the surface of liquid metal droplets and are anchored by a self-limiting gallium oxide layer. The operation is achieved by generating spark discharges at inter-marble air gaps and reduced voltage drop across highly conducting liquid metal droplets. By taking advantage of the malleability of soft liquid metal marbles, the dynamic visualization platforms allow the manipulation of discharge path selections in configurable marble arrays and the embedding of artificial defect features. The systems are further integrated for characterizing dynamic changes in granular and soft systems, and for enabling logic computing and information encoded display. This demonstration holds promises for creating new-generation electric discharge-based optoelectronics.

IDH2 mutation accelerates TPO-induced myelofibrosis with enhanced S100a8/a9 and NFκB signaling in vivo.

Introduction: IDH2 mutation is an unfavorable prognostic factor in patients with primary myelofibrosis (PMF) but its effect on myelofibrosis (MF) remains largely unclear. Methods: In this study, we aimed to elucidate the roles of IDH2 mutation in the development and progression of MF by transcriptomic and molecular techniques using the Idh2 R172K transgenic mice. Results: We found that thrombopoietin (TPO)-overexpressed Idh2 R172K (Idh2 R172K + TPO) mice had accelerated progression to MF, compared with TPO-overexpressed Idh2-wild (WT + TPO) mice, showing activation of multiple inflammatory pathways, among which nuclear factor κB (NFκB) was the most significantly enhanced. Single-cell transcriptomes of the marrow cells in early MF showed that S100a8/a9 expression was mainly confined to neutrophil progenitors in the WT + TPO mice, but highly expressed in several types of myeloid precursor cells, including the megakaryocyte progenitors in the Idh2 R172K + TPO group. Furthermore, Idh2 R172K mice at age of 18 months had larger spleens, increased S100a8/a9-Tlr4 expression, and elevated serum S100a8/a9 levels compared with WT mice. PMF patients with IDH2 mutations had higher bone marrow plasma S100A8/A9 levels than those without IDH2 mutations. Conclusion: Overall, our findings showed that IDH2 mutation induced proinflammatory effects, which further exacerbated MF, as evidenced by the increase in S100a8/a9 levels and NFκB hyperactivation in Idh2 R172K + TPO mice.

A Polymeric Two-in-One Electron Transport Layer and Transparent Electrode for Efficient Indoor All-Organic Solar Cells.

Transparent electrodes (TEs) are vital in optoelectronic devices, enabling the interaction of light and charges. While indium tin oxide (ITO) has traditionally served as a benchmark TE, its high cost prompts the exploration of alternatives to optimize electrode characteristics and improve device efficiencies. Conducting polymers, which combine polymer advantages with metal-like conductivity, emerge as a promising solution for TEs. This work introduces a two-in-one electron transport layer (ETL) and TE based on films of polyethylenimine ethoxylated (PEIE)-modified poly(benzodifurandione) (PBFDO). These PEIE-modified PBFDO layers exhibit a unique combination of properties, including low sheet resistance (130 Ω sq-1), low work function (4.2 eV), and high optical transparency (>85% in the UV-vis-NIR range). In contrast to commonly used poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), the doping level of PBFDO remains unaffected by the PEIE treatment, as verified through UV-vis-NIR absorption and X-ray photoelectron spectroscopy measurements. When employed as a two-in-one ETL/TE in organic solar cells, the PEIE-modified PBFDO electrode exhibits performance comparable to conventional ITO electrodes. Moreover, this work demonstrates all-organic solar cells with record-high power conversion efficiencies of >15.1% under indoor lighting conditions. These findings hold promise for the development of fully printed, all-organic optoelectronic devices.

Synthetic approaches and clinical application of representative small-molecule inhibitors of phosphodiesterase.

Phosphodiesterases (PDEs) constitute a family of enzymes that play a pivotal role in the regulation of intracellular levels of cyclic nucleotides, including cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Dysregulation of PDE activity has been implicated in diverse pathological conditions encompassing cardiovascular disorders, pulmonary diseases, and neurological disorders. Small-molecule inhibitors targeting PDEs have emerged as promising therapeutic agents for the treatment of these ailments, some of which have been approved for their clinical use. Despite their success, challenges such as resistance mechanisms and off-target effects persist, urging continuous research for the development of next-generation PDE inhibitors. The objective of this review is to provide an overview of the synthesis and clinical application of representative approved small-molecule PDE inhibitors, with the aim of offering guidance for further advancements in the development of novel PDE inhibitors.

Risk of new onset hyperuricemia and chronic kidney disease after living kidney donation through propensity score matching analysis.

Living kidney donors have been regarded as those people having earned the healthiest status level after having undergone scrutiny. Although one's post-donation GFR is expected to fall to 50% of their pre-donation value, it is well documented that there is a compensatory increase in GFR which subsequently reaches approximately 60-70% of the donor's pre-donation value. Data regarding gout/hyperuricemia in living kidney donors has remained scarce until now. This study involved kidney donors enrolled within the years 2000 to 2017, where those who were selected to be matched to those in group of case cohort by age, year of index date, gender and co-morbidity were considered as the control cohort. During the 17-year study period 2,716 participants were enrolled. Results revealed that kidney donors experienced a risk of new onset gout/ hyperuricemia (adjusted HR = 1.73; 95%CI = 1.27, 2.36), and new onset CKD (adjusted HR = 6.7; 95% CI = 4.4, 10.21) were found to be higher in kidney donors. Our findings suggest that people after kidney donation are significantly associated with a higher risk of new onset gout/hyperuricemia. Clinical professionals therefore need to be cautious of new onset gouy/hyperuricemia after donation surgery.

Clinical relevance of NFYA splice variants in patients with acute myeloid leukaemia undergoing intensive chemotherapy.

Aberrant alternative splicing (AS) contributes to leukemogenesis, but reports on the clinical and biological implications of aberrant AS in acute myeloid leukaemia (AML) remain limited. Here, we used RNA-seq to analyse AS in AML cells from 341 patients, comparing them to healthy CD34+ haematopoietic stem cells (HSCs). Our findings highlight distinct AS patterns in the nuclear transcription factor Y subunit alpha (NFYA) gene, with two main isoforms: NFYA-L (Long) and NFYA-S (Short), differing in exon 3 inclusion. Patients with lower NFYA-L but higher NFYA-S expression, termed NFYA-S predominance, displayed more favourable characteristics and better outcomes following intensive chemotherapy, regardless of age and European LeukemiaNet risk classification, compared to those with higher NFYA-L but lower NFYA-S expression, termed NFYA-L predominance. The prognostic effects were validated using The Cancer Genome Atlas cohort. Transcriptome analysis revealed upregulated cell cycle genes in NFYA-S predominant cases, resembling those of active HSCs, demonstrating relative chemosensitivity. Conversely, NFYA-L predominant cases, as observed in KMT2A-rearranged leukaemia, were associated with relative chemoresistance. NFYA-S overexpression in OCI-AML3 cells promoted cell proliferation, S-phase entry and increased cytarabine sensitivity, suggesting its clinical and therapeutic relevance in AML. Our study underscores NFYA AS as a potential prognostic biomarker in AML.

Structural Simplification of Podophyllotoxin: Discovery of γ-Butyrolactone Derivatives as Novel Antiviral Agents for Plant Protection.

Natural products are a valuable resource for the discovery of novel crop protection agents. A series of γ-butyrolactone derivatives, derived from the simplification of podophyllotoxin's structure, were synthesized and assessed for their efficacy against tobacco mosaic virus (TMV). Several derivatives exhibited notable antiviral properties, with compound 3g demonstrating the most potent in vivo anti-TMV activity. At 500 µg/mL, compound 3g achieved an inactivation effect of 87.8%, a protective effect of 71.7%, and a curative effect of 67.7%, surpassing the effectiveness of the commercial plant virucides ningnanmycin and ribavirin. Notably, the syn-diastereomer (syn-3g) exhibited superior antiviral activity compared to the anti-diastereomer (anti-3g). Mechanistic studies revealed that syn-3g could bind to the TMV coat protein and interfere with the self-assembly process of TMV particles. These findings indicate that compound 3g, with its simple chemical structure, could be a potential candidate for the development of novel antiviral agents for crop protection.

Using convolutional neural network denoising to reduce ambiguity in X-ray coherent diffraction imaging.

The inherent ambiguity in reconstructed images from coherent diffraction imaging (CDI) poses an intrinsic challenge, as images derived from the same dataset under varying initial conditions often display inconsistencies. This study introduces a method that employs the Noise2Noise approach combined with neural networks to effectively mitigate these ambiguities. We applied this methodology to hundreds of ambiguous reconstructed images retrieved from a single diffraction pattern using a conventional retrieval algorithm. Our results demonstrate that ambiguous features in these reconstructions are effectively treated as inter-reconstruction noise and are significantly reduced. The post-Noise2Noise treated images closely approximate the average and singular value decomposition analysis of various reconstructions, providing consistent and reliable reconstructions.

Biocontrol of plant parasitic nematodes by bacteria and fungi: a multi-omics approach for the exploration of novel nematicides in sustainable agriculture.

Plant parasitic nematodes (PPNs) pose a significant threat to global crop productivity, causing an estimated annual loss of US $157 billion in the agriculture industry. While synthetic chemical nematicides can effectively control PPNs, their overuse has detrimental effects on human health and the environment. Biocontrol agents (BCAs), such as bacteria and fungi in the rhizosphere, are safe and promising alternatives for PPNs control. These BCAs interact with plant roots and produce extracellular enzymes, secondary metabolites, toxins, and volatile organic compounds (VOCs) to suppress nematodes. Plant root exudates also play a crucial role in attracting beneficial microbes toward infested roots. The complex interaction between plants and microbes in the rhizosphere against PPNs is mostly untapped which opens new avenues for discovering novel nematicides through multi-omics techniques. Advanced omics approaches, including metagenomics, transcriptomics, proteomics, and metabolomics, have led to the discovery of nematicidal compounds. This review summarizes the status of bacterial and fungal biocontrol strategies and their mechanisms for PPNs control. The importance of omics-based approaches for the exploration of novel nematicides and future directions in the biocontrol of PPNs are also addressed. The review highlighted the potential significance of multi-omics techniques in biocontrol of PPNs to ensure sustainable agriculture.