Umbilical cord blood-derived neutrophils possess higher viability than peripheral blood derived neutrophils.

Neutrophils, a primary type of immune cell, play critical roles in numerous biological processes. Both umbilical cord blood (UCB) and peripheral blood are rich in neutrophils. UCB is more abundant than peripheral blood, with cells generally at a more immature stage. However, comparative data between these two cell sources is lacking. This study aims to elucidate differences between UCB-derived neutrophils (UCBN) and peripheral blood-derived neutrophils (PBN). UCBN and PBN were isolated from fresh human umbilical cord blood and peripheral blood, respectively. Transcriptomic profiling was performed and compared against neutrophil RNA from three different donors. Bioinformatics analysis was employed to compare cell phenotypes. A cytokine cocktail (IFN-ß, IFN-γ, and LPS) was used to activate UCBN and PBN in vitro. A united multi-omic approach, combining transcriptomic and proteomic analysis, was followed by experimental validation through flow cytometry, cell killing assays, and proteome profiler array to verify cell functions. Transcriptomic analysis revealed that the most upregulated genes in freshly isolated umbilical cord blood neutrophils (UCBN) compared to peripheral blood neutrophils (PBN) predominantly involve neutrophil activation and cell-killing functions. Validation through flow cytometry and cell-killing experiments demonstrated that highly viable UCBN exhibited significantly stronger ovarian tumor cell-killing activity in vitro compared to PBN. Both transcriptomic and proteomic analyses indicated that the primary upregulated genes in activated UCBN are chiefly involved in biological processes related to the regulation of cytokine secretion. Integrative multi-omic analysis, including a proteome profiler array, confirmed that UCBN indeed secrete elevated levels of cytokines. In conclusion: UCBN shows higher viability and cellular activity compared with PBN, particularly in tumor cell-killing and cytokine secretion.

Glutamine Mitigates Oxidative Stress-Induced Matrix Degradation, Ferroptosis, and Pyroptosis in Nucleus Pulposus Cells via Deubiquitinating and Stabilizing Nrf2.

Aims: Intervertebral disc degeneration (IDD) is closely related to low back pain, which is a prevalent age-related problem worldwide; however, the mechanism underlying IDD is unknown. Glutamine, a free amino acid prevalent in plasma, is recognized for its anti-inflammatory and antioxidant properties in various diseases, and the current study aims to clarify the effect and mechanism of glutamine in IDD. Results: A synergistic interplay was observed between pyroptosis and ferroptosis within degenerated human disc specimens. Glutamine significantly mitigated IDD in both ex vivo and in vivo experimental models. Moreover, glutamine protected nucleus pulposus (NP) cells after tert-butyl hydroperoxide (TBHP)-induced pyroptosis, ferroptosis, and extracellular matrix (ECM) degradation in vitro. Glutamine protected NP cells from TBHP-induced ferroptosis by promoting the nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation by inhibiting its ubiquitin-proteasome degradation and inhibiting lipid oxidation. Innovation and Conclusions: A direct correlation is evident in the progression of IDD between the processes of pyroptosis and ferroptosis. Glutamine suppressed oxidative stress-induced cellular processes, including pyroptosis, ferroptosis, and ECM degradation through deubiquitinating Nrf2 and inhibiting lipid oxidation in NP cells. Glutamine is a promising novel therapeutic target for the management of IDD.

Purification and biochemical characterization of the G4 resolvase and DNA helicase FANCJ.

G-quadruplex (G4) DNA or RNA poses a unique nucleic acid structure in genomic transactions. Because of the unique topology presented by G4, cells have exquisite mechanisms and pathways to metabolize G4 that arise in guanine-rich regions of the genome such as telomeres, promoter regions, ribosomal DNA, and other chromosomal elements. G4 resolvases are often represented by a class of molecular motors known as helicases that disrupt the Hoogsteen hydrogen bonds in G4 by harnessing the chemical energy of nucleoside triphosphate hydrolysis. Of special interest to researchers in the field, including us, is the human FANCJ DNA helicase that efficiently resolves G4 DNA structures. Notably, FANCJ mutations are linked to Fanconi Anemia and are prominent in breast and ovarian cancer. Since our discovery that FANCJ efficiently resolves G4 DNA structures 15 years ago, we and other labs have characterized mechanistic aspects of FANCJ-catalyzed G4 resolution and its biological importance in genomic integrity and cellular DNA replication. In addition to its G4 resolvase function, FANCJ is also a classic DNA helicase that acts on conventional duplex DNA structures, which are relevant to the enzyme's role in interstrand cross link repair, double-strand break repair via homologous recombination, and response to replication stress. Here, we describe detailed procedures for the purification of recombinant FANCJ protein and characterization of its G4 resolvase and duplex DNA helicase activity.

Novel Risk Factors for Cervical Facet Joint Degeneration in the Subaxial Cervical Spine: Correlation with Cervical Sagittal Alignment and Bone Mineral Density.

OBJECTIVE: The impact of cervical sagittal alignment on cervical facet joint degeneration (CFD) and the risk factors for CFD in patients with degenerative cervical myelopathy (DCM) were investigated in the current study. METHODS: A total of 250 surgical patients with DCM were recruited. The clinical data and radiographical characteristics, including CFD, cervical sagittal balance parameters, Hounsfield unit (HU) values, disc degeneration (DD), and modic change, were collected. The detailed correlation between these characteristics and CFD was analyzed. Characteristics, including CFD, were compared among the various cervical alignment types and different CFD groups. Finally, the risk factors for CFD were revealed via logistic regression. RESULTS: CFD was prevalent in DCM patients. Age, cervical sagittal vertical axis (cSVA), range of motion, T1 slope, thoracic inlet angle, DD, HU value, and modic change correlated with CFD segmentally and globally (P < 0.05). The lordosis and sigmoid types had a significantly higher CFD prevalence (P < 0.05). Furthermore, the average CFD threshold for the severe CFD group was 1.625 (area under the curve, 0.958). Additionally, 167 patients with average CFD <1.625 and 83 patients with CFD of ≥1.625 were classified into the mild CFD group and severe CFD group, respectively. Finally, multivariate analysis was performed, and age, cSVA, HU value, modic change, and DD were determined to be independent risk factors for CFD. CONCLUSIONS: The load distribution tends to shift to a more shear-like pattern in the sigmoid and kyphosis types and in those with a higher cSVA, thereby promoting CFD. Aging, cervical malalignment, low bone mineral density, DD, and modic change were revealed to result in high risks of CFD.

DDX41: exploring the roles of a versatile helicase.

DDX41 is a DEAD-box helicase and is conserved across species. Mutations in DDX41 have been associated with myeloid neoplasms, including myelodysplastic syndrome and acute myeloid leukemia. Though its pathogenesis is not completely known, DDX41 has been shown to have many cellular roles, including in pre-mRNA splicing, innate immune sensing, ribosome biogenesis, translational regulation, and R-loop metabolism. In this review, we will summarize the latest understandings regarding the various roles of DDX41, as well as highlight challenges associated with drug development to target DDX41. Overall, understanding the molecular and cellular mechanisms of DDX41 could help develop novel therapeutic options for DDX41 mutation-related hematologic malignancies.

Structural distortion-induced monoclinic sodium iron hexacyanoferrate as a high-performance electrode for rocking-chair desalination batteries.

Sodium iron hexacyanoferrate (NaFeHCF) has been recognized as a promising Prussian blue analogue (PBA)-based electrode for electrochemical desalination; however, its application potential is limited by its unsatisfactory desalination capacity and cycling stability. Herein, the structurally distorted high-quality monoclinic NaFeHCF with fewer defects in the framework was synthesized by a crystal-controlled coprecipitation method via tuning the crystallization reaction conditions and applied to seawater desalination. Physicochemical characterization and desalination experiments show that the NFHFC-2 with minimized defects possesses enhanced electrochemical activity of Fe2+ and electrochemical kinetics, thus achieving higher desalination performance (specific capacity of 75.0 mA h g-1 and capacity retention of 85.3% after 50 cycles). Furthermore, a symmetrical NFHCF-2 RCDB is assembled, and the operation parameters (including various salinities and electrode spacing) are optimized to achieve a remarkable salt removal capacity (SRC) of 108.9 mg g-1 and a salt removal rate (SRR) of 2.22 mg g-1 min-1 with low energy consumption (0.056 kW h kg-1-NaCl) and outstanding cycling stability (almost no capacity attenuation in 150 cycles). Impressively, the RCDB further exhibits favorable technical feasibility in the simultaneous removal of univalent/bivalent ions from the natural seawater. This study inspires the design of high-quality PBA-based electrodes with optimized crystal structures for electrochemical desalination.

Improving gut functions and egg nutrition with stevia residue in laying hens.

This study aimed to investigate the effect of stevia residue (STER) on the production performance, egg quality and nutrition, antioxidant ability, immune responses, gut morphology and microbiota of laying hens during the peak laying period. A total of 270 Yikoujingfen NO. 8 laying hens (35 wk of age) were randomly divided into 5 treatments. The control group fed a basal diet and groups supplemented with 2, 4, 6, and 8% STER. The results showed that STER significantly increased egg production, the content of amino acids (alanine, proline, valine, ornithine, asparagine, aspartic acid, and cysteine) in egg whites, and decreased the yolk color (P < 0.05). Additionally, STER significantly increased acetate, HOMOγ linolenic acid and cis-13, 16-docosadienoic acid levels in egg yolk (P < 0.05). IL-2, IL-4, and IL-10 levels in serum significantly increased by STER (P < 0.05), while IL-1ß significantly decreased (P < 0.05). STER also increased total antioxidant activity (T-AOC) in the liver and estradiol level in the oviduct (P < 0.05), but decreased the cortisol level in the oviduct (P < 0.05). For the intestinal morphology, the jejunal villus height and crypt-to-villus (V:C) significantly increased by STER (P < 0.05). STER increased the relative abundance of Actinobacteriota (P < 0.05), while deceased Proteobacteria, Desulfobacterota, and Synergistota (P < 0.05). In conclusion, STER improved egg production, quality and nutrition, improved the immune responses, antioxidant capabilities, estrogen level, gut morphology, and increased the relative abundance of beneficial bacteria while decreased the harmful bacteria. Among all treatments, 4 and 6% STER supplementation yielded the most favorable results in terms of enhancing production performance, egg nutrition, gut health, and immune capabilities in laying hens.

Helicases in R-loop Formation and Resolution.

With the development and wide usage of CRISPR technology, the presence of R-loop structures, which consist of an RNA-DNA hybrid and a displaced single-strand (ss) DNA, has become well accepted. R-loop structures have been implicated in a variety of circumstances and play critical roles in the metabolism of nucleic acid and relevant biological processes, including transcription, DNA repair, and telomere maintenance. Helicases are enzymes that use an ATP-driven motor force to unwind double-strand (ds) DNA, dsRNA, or RNA-DNA hybrids. Additionally, certain helicases have strand-annealing activity. Thus, helicases possess unique positions for R-loop biogenesis: they utilize their strand-annealing activity to promote the hybridization of RNA to DNA, leading to the formation of R-loops; conversely, they utilize their unwinding activity to separate RNA-DNA hybrids and resolve R-loops. Indeed, numerous helicases such as senataxin (SETX), Aquarius (AQR), WRN, BLM, RTEL1, PIF1, FANCM, ATRX (alpha-thalassemia/mental retardation, X-linked), CasDinG, and several DEAD/H-box proteins are reported to resolve R-loops; while other helicases, such as Cas3 and UPF1, are reported to stimulate R-loop formation. Moreover, helicases like DDX1, DDX17, and DHX9 have been identified in both R-loop formation and resolution. In this review, we will summarize the latest understandings regarding the roles of helicases in R-loop metabolism. Additionally, we will highlight challenges associated with drug discovery in the context of targeting these R-loop helicases.

An Accurate Estimate of the Amino Acid Content of Human Milk Collected from Chinese Women Adjusted for Differences in Amino Acid Digestibility.

BACKGROUND: The amino acid (AA) composition of human milk is used to define the AA requirements of the infant. Thus, it is important that estimates of composition be as complete and accurate as possible. When determining AA composition using standard hydrolysis methods, some AAs are progressively destroyed while others are incompletely released. For accuracy, AA composition needs to be determined using multiple hydrolysis times. The true ileal digestibility of AAs also needs to be taken into consideration. OBJECTIVE: The objective was to bring together AA compositional (determined using multiple hydrolysis intervals) and digestibility data determined using the piglet to give an estimate of the absorbed AA profile of human milk with reference in particular to Asian females. METHODS: Mature milk was collected from Chinese females. AA analysis using multiple hydrolysis intervals and a nonlinear regression model was used to accurately estimate AA composition. Human milk, as well as a protein-free diet, were fed to piglets (n = 6), and ileal digesta were collected (piglet age, 21 d) to determine the true ileal AA digestibility of AAs in human milk. RESULTS: True ileal AA digestibility coefficients ranged from (mean ± standard error of the mean) 0.61 ± 0.081 for tyrosine to 1.01 ± 0.030 for tryptophan, with a digestibility for total nitrogen of 0.90 ± 0.013. Convergence criteria were met for the modeling for each AA, and the model had a level of significance of P < 0.0001 for each AA. The amount of available AAs (total AA content as per the model prediction multiplied by the true ileal AA digestibility coefficient determined in the piglet) are reported. CONCLUSIONS: An estimate of the absorbed AA profile of mature milk collected from Chinese females is provided. For the first time, data is presented for cysteine.

Carbazole-Decorated Organoboron Emitters with Low-Lying HOMO Levels for Solution-Processed Narrowband Blue Hyperfluorescence OLED Devices.

The hyperfluorescence has drawn great attention in achieving efficient narrowband emitting devices based on multiple resonance thermally activated delayed fluorescence (MR-TADF) emitters. However, achieving efficient solution-processed pure blue hyperfluorescence devices is still a challenge, due to the unbalanced charge transport and serious exciton quenching caused by that the holes are easily trapped on the high-lying HOMO (the highest occupied molecular orbital) level of traditional diphenylamine-decorated emitters. Here, we developed two narrowband blue organoboron emitters with low-lying HOMO levels by decorating the MR-TADF core with weakly electron-donating carbazoles, which could suppress the hole trapping effect by reducing the hole traps between host and MR-TADF emitter from deep (0.40 eV) to shallow (0.14/0.20 eV) ones for facilitating hole transport and exciton formation, as well as avoiding exciton quenching. And the large dihedral angle between the carbazole and MR-TADF core makes the carbazole act as a steric hindrance to inhibit molecular aggregation. Accordingly, the optimized solution-processed pure blue hyperfluorescence devices simultaneously realize record external quantum efficiency of 29.2 %, narrowband emission with a full-width at half-maximum of 16.6 nm, and pure blue color with CIE coordinates of (0.139, 0.189), which is the best result for the solution-processed organic light-emitting diodes based on MR-TADF emitters.

MUC16 stimulates neutrophils to an inflammatory and immunosuppressive phenotype in ovarian cancer.

BACKGROUND: MUC16 (CA125) is a commonly used tumor marker for ovarian cancer screening and reported to be an immunosuppressive factor by acting on the sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) on the surface of natural killer cells (NK cells), B cells, and monocytes. However, the role of MUC16 on neutrophils in the tumor microenvironment remains to be further explored. METHODS: The correlation between the proportion and count of peripheral blood cells, serum inflammatory-related factors and serum MUC16 (CA125) level in patients was constructed based on clinical samples. RNAseq data was obtained from TCGA and sequencing of ovarian cancer tissues, followed by TIMER immune cell infiltration and correlation analysis. Ovarian cancer organoid was constructed to stimulate neutrophils with immunophenotype identification by qPCR and flow cytometry. MUC16 protein stimulation to neutrophils validated the role of MUC16 under the analysis of RNA sequencing and inhibition of NK cytotoxicity in vitro. RESULTS: The serum MUC16 level was positively correlated with the proportion and count of peripheral blood neutrophils, neutrophil-to-lymphocyte ratio (NLR) and inflammatory factors IL-6, IL-8, IL-10 and IL-2R. Siglec-9, the receptor of MUC16, was expressed on neutrophils and was positively correlated to neutrophil infiltration in ovarian cancer. After the stimulation of ovarian cancer organoids and MUC16 respectively, the proportions of CD11b+, CD66b+, and ICAM-1+ neutrophils were significantly increased, while the proportion of CXCR4+ neutrophils was slightly decreased, with increasing of of inflammatory factors MMP9, IL-8, OSM, IL-1ß, TNF-α, CXCL3, and ROS. RNA-sequencing analysis revealed that inflammatory response, TNFA signaling pathway, and IL6-related pathway were upregulated in MUC16-stimulated neutrophils, accompanied by high expression of immunosuppression-related factors HHLA2, IL-6, TNFRSF9, ADORA2A, CD274 (PD-L1), and IDO1. NK cytotoxicity was decreased when treated by supernanant of MUC16-stimulated neutrophils in vitro. CONCLUSION: MUC16 acted on neutrophils by Siglec-9 leading to an inflammatory and immunosuppressive phenotype in ovarian cancer.

Identification of TRPM2 as a prognostic factor correlated with immune infiltration in ovarian cancer.

INTRODUCTION: Ovarian cancer (OC) is one of the most common gynecologic malignant cancers with the current survival rate remaining low. TRPM2 has been reported as a survival predictor in various cancers but not in OC. The aim of this study is to explore the role and its underlying mechanism of TRPM2 in OC. METHODS: The transcriptome data and clinical data were obtained from TCGA, GTEx, and GEO (GSE17260). DriverDBv3 and PrognoScan were used to analyze survival correlations. GSEA analysis was performed to uncover the underlying mechanism. The correlations between TRPM2 and immune score, immune cell infiltration were analyzed by TIMER2.0. RESULTS: TRPM2 was highly expressed in OC and high TRPM2 expression was related to the poor prognosis based on the Kaplan-Meier curves, univariate and multivariate analysis. The enrichment analysis suggested that TRPM2 was involved in immune-related pathways. Positive correlations were also observed between TRPM2 expression and immune score and immune cells covering B cells, T cells, macrophage, neutrophil, and myeloid dendritic cells. We also found that TRPM2 was positively related to immune checkpoints including ICOSLG, CD40, CD86, etc. TRPM2 expression had a positive correlation with M2 macrophage, but not with M1 macrophage. Besides, TRPM2 showed a strong positive correlation with pyroptosis-related genes including NLRP3, NLRC4, NOD2, NOD1, IL1B, GSDMD. CONCLUSION: Our study demonstrated that TRPM2 is a poor prognostic prediction factor in ovarian cancer and is correlated to the immune microenvironment and pyroptosis. TRPM2 may act as a new immunotherapy target, which promoted the survival rate of OC patients.

A multimodal imaging-based classification for pediatric diffuse intrinsic pontine gliomas.

OBJECT: Pediatric diffuse intrinsic pontine glioma (DIPG) is a radiologically heterogeneous disease entity, here we aim to establish a multimodal imaging-based radiological classification and evaluate the outcome of different treatment strategies under this classification frame. METHODS: This retrospective study included 103 children diagnosed with DIPGs between January 2015 and August 2018 in Beijing Tiantan Hospital (Beijing, China). Multimodal radiological characteristics, including conventional magnetic resonance imaging (MRI), diffuse tensor imaging/diffuse tensor tractography (DTI/DTT), and positron emission tomography (PET) were reviewed to construct the classification. The outcome of different treatment strategies was compared in each DIPG subgroup using Kaplan-Meier method (log-rank test) to determine the optimal treatment for specific DIPGs. RESULTS: Four radiological DIPG types were identified: Type A ("homocentric", n=13), Type B ("ventral", n=41), Type C ("eccentric", n=37), and Type D ("dorsal", n=12). Their treatment modalities were grouped as observation (43.7%), cytoreductive surgery (CRS) plus radiotherapy (RT) (24.3%), RT alone (11.7%), and CRS alone (20.4%). CRS+RT mainly fell into type C (29.7%), followed by type B1 (21.9%) and type D (50%). Overall, CRS+RT exhibited a potential survival advantage compared to RT alone, which was more pronounced in specific type, but this did not reach statistical significance, due to limited sample size and unbalanced distribution. CONCLUSION: We proposed a multimodality imaging-based radiological classification for pediatric DIPG, which was useful for selecting optimal treatment strategies, especially for identifying candidates who may benefit from CRS plus RT. This classification opened a window into image-guided integrated treatment for pediatric DIPG.

Topological and random spread models with frozen symbols.

When a symbol or a type has been "frozen" (namely, a type of which an individual only produces one individual of the same type), its spread pattern will be changed and this change will affect the long-term behavior of the whole system. However, in a frozen system, the ξ-matrix and the offspring mean matrix are no longer primitive so that the Perron-Frobenius theorem cannot be applied directly when predicting the spread rates. In this paper, our goal is to characterize these key matrices and analyze the spread rate under more general settings both in the topological and random spread models with frozen symbols. More specifically, we propose an algorithm for explicitly computing the spread rate and relate the rate with the eigenvectors of the ξ-matrix or offspring mean matrix. In addition, we reveal that the growth of the population is exponential and that the composition of the population is asymptotically periodic. Furthermore, numerical experiments are provided as supporting evidence for the theory.

Pan-cancer integrated bioinformatics analysis reveals cuproptosis related gene FDX1 is a potential prognostic and immunotherapeutic biomarker for lower-grade gliomas.

FDX1 participates in cuproptosis, a copper-dependent cell death mode, which might influence tumor progressions like ferroptosis and pyroptosis. However, the role of FDX1 in tumors remains to be explored. This study investigated FDX1 expression features, and correlations to prognosis, tumor stages, immune microenvironment, and cuproptosis from a pan-cancer perspective based on integrated bioinformatics. FDX1 mRNA and clinical data were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Broad Institute Cancer Cell Line Encyclopedia (CCLE) databases. Differential expression of FDX1 in tumor stages was performed on GEPIA2.0. Cox proportional hazard regression and survival curve were used to analyze the prognostic value of FDX1. The relationships between FDX1 expression and immune infiltration, immune cells, immune checkpoints, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methyltransferase (DNMT) were explored. GSEA was utilized to find the biological function of FDX1 in LGG. Results showed that FDX1 was abnormally expressed in multiple tumor types and demonstrated variability in various tumor stages. Survival analysis revealed FDX1 predicted poor prognosis in glioma (GBMLGG), brain lower-grade glioma (LGG), and good prognosis in the pan-kidney cohort (KIPAN), and kidney renal clear cell carcinoma (KIRC). Immune correlation analysis suggested FDX1 showed positive correlations to StromalScore, ImmuneScore, ESTIMATEScore in LGG and negative correlation in KIRC. Additionally, positive correlations were observed between FDX1 and immune cells infiltration, immune checkpoints, tumor stemness, homologous recombination deficiency (HRD), and TMB in LGG in the pan-cancer analysis. Validation with CGGA suggested prognostic value and immune correlation of FDX1 in LGG. Specifically, high expression of FDX1 was accompanied by high expression of immune checkpoints such as CD276 (B7-H3), CD274 (PD-L1), PDCD1LG2 (PD-L2), CTLA4, and HAVCR2. These findings illustrated that FDX1 might be considered a potential poor prognosis biomarker and immunotherapy predictor in LGG.

Mathematical analysis of topological and random m-order spread models.

This paper focuses on the analysis of two particular models, from deterministic and random perspective respectively, for spreading processes. With a proper encoding of propagation patterns, the spread rate of each pattern is discussed for both models by virtue of the substitution dynamical systems and branching process. In view of this, we are empowered to draw a comparison between two spreading processes according to their spreading models, based on which explanations are proposed on a higher frequency of a pattern in one model than the other. These results are then supported by the numerical evidence later in the article.

A high-contrast polymorphic difluoroboron luminogen with efficient RTP and TADF emissions.

A simple N,S-chelated four-coordinated difluoroboron-based emitter is reported with three polymorphs, which emit high contrast green (G), yellow (Y) and red (R) light. Interestingly, the G and R-Crystals show different thermally activated delayed fluorescence (TADF) at 530 nm and 630 nm with a remarkable emission spectral shift of up to 100 nm, while the Y-Crystal exhibits room temperature phosphorescence (RTP) at around 570 nm with a high solid-state quantum yield of 77%. Single crystal analysis and theoretical calculations reveal that different molecular conformations and packing modes lead to distinct triplet exciton conversion channels.

The Effect of an Essential Oil Blend on Growth Performance, Intestinal Health, and Microbiota in Early-Weaned Piglets.

Essential oils (EO) are promising feed additives for their antibacterial, antioxidant, and immune-enhancing abilities with low toxicity. Carvacrol, thymol, and cinnamaldehyde are commonly used to synthesize EO. However, few studies focus on combining these three EO in early-weaned piglets. In the present study, 24 piglets weaned at 21 d of age were randomly divided into 2 groups (6 replicate pens per group, 2 piglets per pen). The piglets were fed a basal diet (the control group) and a basal diet supplemented with 400 mg/kg EO (a blend consisting of carvacrol, thymol, and cinnamaldehyde, the EO group) for 28 days. At the end of the experiment, one piglet per pen was randomly chosen to be sacrificed. Growth performance, hematology, plasma biochemical indices, antioxidant capacity, intestinal epithelial development and immunity, colonic volatile fatty acids (VFA), and microbiota were determined. The results indicated that the diet supplemented with EO significantly improved average daily feed intake (ADFI, p < 0.01) and average daily gain (ADG, p < 0.05) in the day 0 to 28 period. EO supplementation led to a significant decrease in plasma lysozyme (p < 0.05) and cortisol levels (p < 0.01). Additionally, EO significantly promoted jejunal goblet cells in the villus, jejunal mucosa ZO-1 mRNA expression, ileal villus height, and ileal villus height/crypt depth ratio in piglets (p < 0.05). The ileal mucosal TLR4 and NFκB p-p65/p65 protein expression were significantly inhibited in the EO group (p < 0.05). Colonic digesta microbiota analysis revealed that bacteria involving the Erysipelotrichaceae family, Holdemanella genus, Phascolarctobacterium genus, and Vibrio genus were enriched in the EO group. In conclusion, these findings indicate that the EO blend improves ADG and ADFI in the day 0 to 28 period, as well as intestinal epithelial development and intestinal immunity in early-weaned piglets, which provides a theoretical basis for the combined use of EO in weaned piglets.

11C-methionine PET imaging characteristics in children with diffuse intrinsic pontine gliomas and relationship to survival and H3 K27M mutation status.

PURPOSE: This study aimed to describe 11C-methionine (11C-MET) PET imaging characteristics in patients with paediatric diffuse intrinsic pontine glioma (DIPG) and correlate them with survival and H3 K27M mutation status. METHODS: We retrospectively analysed 98 children newly diagnosed with DIPG who underwent 11C-MET PET. PET imaging characteristics evaluated included uptake intensity, uniformity, metabolic tumour volume (MTV), and total lesion methionine uptake (TLMU). The maximum, mean, and peak of the tumour-to-background ratio (TBR), calculated as the corresponding standardised uptake values (SUV) divided by the mean reference value, were also recorded. The associations between the PET imaging characteristics and clinical outcomes in terms of progression-free survival (PFS) and overall survival (OS) and H3 K27M mutation status were assessed, respectively. RESULTS: In univariate analysis, imaging characteristics significantly associated with shorter PFS and OS included a higher uniformity grade, higher TBRs, larger MTV, and higher TLMU. In multivariate analysis, larger MTV at diagnosis, shorter symptom duration, and no treatment were significantly correlated with shorter PFS and OS. The PET imaging features were not correlated with H3 K27M mutation status. CONCLUSION: Although several imaging features were significantly associated with PFS and OS, only MTV, indicating the size of the active tumour, was identified as a strong independent prognostic factor.

Facile synthesis of direct Z-scheme UiO-66-NH2/PhC2Cu heterojunction with ultrahigh redox potential for enhanced photocatalytic Cr(VI) reduction and NOR degradation.

Z-scheme heterojunction-based photocatalysts typically have robust removal efficiencies for water contaminants. Herein, we employed p-type PhC2Cu and n-type UiO-66-NH2 to develop a direct Z-scheme UiO-66-NH2/PhC2Cu photocatalyst with an ultrahigh redox potential for Cr(VI) photoreduction and norfloxacin (NOR) photodegradation. Moreover, UV-vis diffuse reflectance, photoelectrochemical measurements, photoluminescence (PL) spectra and electron spin resonance (ESR) technique revealed that the UiO-66-NH2/PhC2Cu composite boosted light capturing capacities to promote photocatalytic efficiencies. Strikingly, the optimized UiO-66-NH2/PhC2Cu50 wt% rapidly reduced Cr(VI) (96.2%, 15 min) and degraded NOR (97.9%, 60 min) under low-power blue LED light. In addition, the UiO-66-NH2/PhC2Cu photocatalyst also exhibited favorable mineralization capacity (78.4%, 120 min). Benefitting from the enhanced interfacial electron transfer and ultrahigh redox potential of the Z-scheme heterojunction, the UiO-66-NH2/PhC2Cu photocatalyst greatly enhanced the separation efficacies of photogenerated carriers. This resulting abundance of active species (e.g., e-, h+, O2•-, and •OH) were generated to photo-reduce Cr(VI) and photo-oxidize NOR. Base on the identified intermediates, four degradation pathways of NOR were proposed. Finally, the Z-scheme mechanism were systematically confirmed through X-ray photoelectron spectroscopy (XPS), ESR, cyclic voltammetry (CV) tests, and photodeposition techniques.