Induction Stage Research Articles

Evaluation of the Compatibility Between Formation and Injection Water in Ultra-Low Permeability Reservoirs

This study focuses on the reservoir scaling and the under-injection issues of the water injection well during the water injection development of an ultra-low permeability reservoir in Xinjiang due to the complex composition of injected water. Microfluidic experiments were applied to visualize the flow channel changes during water flooding, indoor core flooding experiments were employed to analyze the permeability and ion concentration, and nuclear magnetic resonance (NMR) was used to evaluate the pore structure damage. Together, these experiments were used to clarify the scaling and precipitation characteristics as the injected water met the formation water in porous media and the effects on reservoir damage. The research results showed that the poor compatibility of the injected water with the formation water could easily produce calcium carbonate scaling. The scaling products exhibited a unique network structure of blocks and a radial distribution, mainly composed of calcium carbonate and aluminosilicate. The scaling in the porous media exhibited the characteristics of unstable crystal precipitation, migration, and repeated scaling following water mixing, while the scale crystal growth occurred in the pores and the throats. According to the scaling characteristics, the damage to the reservoir permeability by scaling can be divided into the induction, damage, and stabilization stages. The filling and clogging of the scale crystals enhanced the pore structure heterogeneity, with the median pore radius reduced by 21.61% and the permeability reduced by 50%.

Identification and expression profiling of neuropeptides and neuropeptide receptor genes in a natural enemy, Coccinella septempunctata.

Neuropeptides and their receptors constitute diverse and abundant signal molecules in insects, primarily synthesized and released primarily from neurosecretory cells within the central nervous system Neuropeptides act as neurohormones and euromodulators, regulating insect behavior, lifecycle, and physiology by binding to receptors on cell surface. As a typical natural predator of agricultural pests, the lady beetle, Coccinella septempunctata, has been commercially mass-cultured and widely employed in pest management. Insect diapause is a physiological and ecological adaptative strategy acquired in adverse environments. In biological control programs, knowledge about diapause regulation in natural enemy insects provides important insight for improving long-term storage, transportation, and field adoption of these biological control agents. However, little is known about the function of neuropeptides and their receptors in controlling reproductive diapause of C. septempunctata. It is unclear which neuropeptides affect diapause of C. septempunctata. In this study, RNA-seq technology and bioinformatics were utilized to investigate genes encoding neuropeptides and their receptors in female adults of C. septempunctata. Quantitative real-time PCR (qRT-PCR) analysis was employed to examine gene expression across different development/diapause stages. A total of 17 neuropeptide precursor genes and 9 neuropeptide receptor genes were identified, implicated in regulating various behaviors such as feeding, reproduction, and diapause. Prediction of partial mature neuropeptides from precursor sequences was also performed using available information about these peptides from other species, conserved domains and motifs. During diapause induction, the mRNA abundance of AKH was notably higher on the 10th day compared to non-diapause females, but decreased by the 20th day. In contrast, GPHA showed lower expression levels on the 5th day of diapause induction compared to non-diapause females, but increased significantly by the 15th and 20th days. NPF was higher expressed in head and midgut while DH showed higher expression in the fat body and midgut. Additionally, NPF expression remained consistently lower throughout all stages of diapause induction compared to non-diapause conditions in females. This study represents the first sequencing, identification, and expression analysis of neuropeptides and neuropeptide receptor genes in C. septempunctata. Our results could provide a foundational framework for further investigations into the presence, functions, and potential targets of neuropeptides and their receptors, particularly in devising novel strategies for diapause regulation in C. septempunctata.

An unexpected role of IL10 in mesoderm induction and differentiation from pluripotent stem cells: Implications in zebrafish angiogenic sprouting, vascular organoid development, and therapeutic angiogenesis

Mesoderm induction is a crucial step for vascular cell specification, vascular development and vasculogenesis. However, the cellular and molecular mechanisms underlying mesoderm induction remain elusive. In the present study, a chemically-defined differentiation protocol was used to induce mesoderm formation and generate functional vascular cells including smooth muscle cells (SMCs) and endothelial cells (ECs) from human induced pluripotent stem cells (hiPSCs). Zebrafish larvae were used to detect an in vivo function of interleukin 10 (IL10) in mesoderm formation and vascular development. A three dimensional approach was used to create hiPSC-derived blood vessel organoid (BVO) and explore a potential impact of IL10 on BVO formation. A murine model hind limb ischemia was applied to investigate a therapeutic potential of hiPSC-derived cells treated with or without IL10 during differentiation. We found that IL10 was significantly and specifically up-regulated during mesoderm stage of vascular differentiation. IL10 addition in mesoderm induction media dramatically increased mesoderm induction and vascular cell generation from hiPSCs, whereas an opposite effect was observed with IL10 inhibition. Mechanistic studies revealed that IL10 promotes mesoderm formation and vascular cell differentiation by activating signal transducer and activator of transcription 3 signal pathway. Functional studies with an in vivo model system confirmed that knockdown of IL10 using morpholino antisense oligonucleotides in zebrafish larvae caused defective mesoderm formation, angiogenic sprouting and vascular development. Additionally, our data also show IL10 promotes blood vessel organoid development and enhances vasculogenesis and angiogenesis. Importantly, we demonstrate that IL10 treatment during mesoderm induction stage enhances blood flow perfusion recovery and increases vasculogenesis and therapeutic angiogenesis after hind limb ischemia. Our data, therefore, demonstrate a regulatory role for IL10 in mesoderm formation from hiPSCs and during zebrafish vascular development, providing novel insights into mesoderm induction and vascular cell specifications.

Features of cellular selection of tomato plants, resistance against salining

Aim. For selection at the cellular level, nutrient media are offered, which, although not completely, would partially correspond to natural stress conditions. Methods. As explants, immature embryos, cotyledon nodes with meristematic activity, and hypocotyls of tomato plants of the Lagidnyi, Khoryv, Borivskyi. Results. An agar medium of general mineral composition with different concentrations of growth regulators was used for the cultivation of isolated tissues the generally accepted method. Conclusions. When creating in vitro new forms of tomato plants with increased resistance to chloride salinization of the soil, it is necessary to select resistant cell lines using the stepwise selection method according to the scheme, which includes several consecutive actions of a selective agent in different concentrations at the stages of induction – proliferation, morphogenesis of callus cultures. An increase in the content of hydrogen peroxide in callus structures and stimulation of the activity of antioxidant enzymes superoxide dismutase and peroxidase were also found.

Multi-angle research on the performance of self-foaming filling materials and analysis of engineering applications

Utilizing self-foaming filling material to fill the hollow area is an effective way to settle the issues of low rate and poor effect of filling and roofing in the large stope. There are fewer studies related to the expansion rate, hydration exotherm and strength properties of self-foaming fillers in mines. Based on this, this paper investigates the expansion characteristics, hydration exothermic characteristics and compressive strength characteristics of the self-foaming filler under different cement-tailings ratios (1:4, 1:6, 1:8), reveals the hydration reaction mechanism of the material and its microscopic characteristics through XRD, TG and SEM tests, and evaluates the application effect and economy of the self-foaming filler in practical engineering with the background of Mashong Iron Ore Mine. The main findings are as follows: (1) The volumetric expansion of self-foaming filling material can be divided into the initial stage Ⅰ (0–1.5 h), the rapid reaction stage Ⅱ (1.5–8 h) and the stabilization stage, and as the cement-tailings ratio grows, the expansion rate of the filling body increases, and the expansion rate of the filling material with 1:4 ratio is as high as 20.4 %. (2) The hydration process of a self-foaming filled body does not contain induction and acceleration stages; under the same conditions, the self-foaming filled body has more exothermic heat of hydration than that of a self-foaming filled body by about 50 J/g, and the bigger the cement-tailings ratio, the bigger the hydration exothermic rate and exothermic quantity. (3) The compressive strength of self-foaming filler is inferior to the strength of conventional filler, the higher the cement-tailings ratio, the greater the degree of hydration, the more hydration products are produced, and the greater the compressive strength. (4) The bigger the ratio of gray sand, the greater the proportion of macropores and the actual engineering of self-foaming filling materials to catch the top rate of up to 98 %, directly saving the total cost of 11.6 %. The above research results can offer theoretical support and scientific guidance for the utilization of spontaneous foam materials to fill the goaf and control the roof rate, temperature, and strength of the stope.

Influence of Early Hydration Process on the Hydrostatic Pressure Change of Cement Pastes at Different Temperatures.

In cementing operations, a rapid decrease in the hydrostatic pressure of cement paste is one of the main causes of early gas channeling. In response to this issue, tests were conducted on the variation in the hydrostatic pressure of cement paste over time at different temperatures (30 °C-180 °C), and it was found that the curve of its rapid decrease time point with temperature change conforms to the Boltzmann function. The relationship between the early hydration process and the microstructure of paste at 90 and 150 °C, as well as the changes in hydrostatic pressure, was studied using X-ray powder diffraction, thermogravimetry, and scanning electron microscopy. The results show that the hydrostatic pressure curve of the paste shows a trend of first stabilization and then rapidly decreasing at medium and low temperatures (30 and 90 °C). At high temperatures (150 °C), the pressure curve initially increases until stabilization, enters a stable period, and finally rapidly decreases. In the early stage of hydration induction, there is a large amount of free water between hydration products, and the hydrostatic pressure of the paste remains stable. In the process of hydrostatic pressure reduction, the microstructure of the paste develops from the particle hydration products to a "gel framework", which isolates the pressure transfer of part of the free water. During the acceleration period of hydration, the hydration products enhance the "framework" and reduce the porosity of the paste, completely cutting off the transmission of water pressure, resulting in a rapid decrease in the hydrostatic pressure of the paste. A method for predicting the rapid decrease in hydrostatic pressure of the paste was proposed using the hydration reaction process.

Endogenous phytohormone analysis during sequential stages of somatic embryogenesis in Musa AAA cv. Grand Naine (subgroup Cavendish)

Abstract This is the first initiative study to provide quantified levels of four endogenous phytohormones during the induction, regeneration, maturation and germination stages of somatic embryogenesis (SE) in banana, using immature male bud explants, in the popular commercial triploid cultivar Grand Naine (AAA). Phytohormones are known to play a major role in the regulation of SE and most protocols have been developed for various cultivars of banana following empirical approaches. Although, several reports are available with regard to the impact of growth regulators exogenously supplemented to the media, the vital role of endogenous growth hormones in various developmental stages of SE remain unclear in banana. Reverse Phase High Performance Liquid Chromatography (RP-HPLC) was used to analyze endogenous status of indole acetic acid (IAA), zeatin, gibberellic acid (GA) and abscisic acid (ABA). Results from this study revealed that endogenous IAA and GA along with exogenous auxin play a major role in the induction of embryogenic competence of male bud explants. The levels of endogenous IAA and zeatin were found to be higher in embryogenic calli than non-embryogenic calli, although three different types of exogenous auxins were supplemented in callogenesis medium, but not cytokinin. Higher level of ABA and GA was observed in early and late developmental stages of somatic embryo, respectively. GA also played a predominant role in germination of somatic embryos. These findings will be applied for improvement of SE protocol in recalcitrant banana cultivars by suitably altering or supplementing exogenous growth hormones.

Analysis of changes in intestinal microbiota in female Wistar rats at the stage of breast cancer induction by N-methyl-N-nitrosourea

The intestinal microbiota, having enormous metabolic potential, makes a significant contribution to the physiological and pathological processes of humans and animals and is currently considered as an important factor in the pathogenesis of cancer. The aim of this study is to determine changes in the quantitative and qualitative composition of the intestinal microbiota in Wistar rats during chemical induction of breast cancer (BC). Material and methods. The work was performed on female Wistar rats (n = 40) aged 3 months, weighing 200–210 g, using cultural methods for studying fecal microbiota in intact rats (1 group) on the 1st, 14th, 35th days and in rats with induction of breast cancer and and in rats, whereby N-methyl-N-nitrosourea was administered to induce breast cancer (2 group) on the 1st (before injection of N-methyl-N-nitrosourea), 14th, 35th days after injection of N-methyl-N-nitrosourea. Results and discussion. In all experimental animals, representatives characteristic of the intestinal normobiota of warm-blooded animals predominated, namely: Bifidobacterium spp., Lactobacillus spp., Escherichia coli with pronounced enzymatic properties, Enterococcus spp., Clostridium spp. In addition, Staphylococcus spp., yeast-like fungi of the genus Candida and mold. Escherichia coli with reduced enzymatic activity was also detected. It was established that the isolated bacteria belonged to 3 types, 4 classes, 5 orders, 6 families, 6 genera of the bacterial domain. Also, 2 genera of fungi belonging to the order Saccharomycetales were isolated. The most significant changes in the composition of the intestinal microbiota were noted in rats with chemically induced breast cancer on the 35th day tumor induction: the appearance of pathogenic microflora in the intestine was revealed.

Successful treatment of acute promyelocytic leukemia with initial hyperleukocytosis, differentiated syndrome and massive intracranial hemorrhage in a child

Introduction. The development of hemorrhagic syndrome at the onset of the disease in patients with acute promyelocytic leukemia (APL) is one of the main causes of therapy failures and the most common cause of death in the early stages of remission induction. The risk of severe hemorrhagic complications increases in patients with the microgranular APL variant, often accompanied with hyperleukocytosis.Aim — to present a clinical case of successful diagnosis and treatment of primary APL with initial hyperleukocytosis in a patient with massive intracranial hemorrhage and differentiated syndrome.Main findings. A clinical observation of the diagnosis and treatment of APL in a 13-year-old patient with initial hyperleukocytosis, massive intracranial hemorrhage and differentiation syndrome is presented. Data on the variable manifestations of hemorrhagic syndrome in patients with APL and its effect on survival outcomes are also given. Diagnostic criteria and approaches in the treatment of differentiation syndrome are presented on the example of a clinical observation, when early clinical diagnosis and timely initiation of special antitumor treatment in the intensive care unit made it possible to achieve clinical, hematological and molecular remission, avoiding the fatal consequences of massive intracranial hemorrhage.

Comprehensive network modeling approaches unravel dynamic enhancer-promoter interactions across neural differentiation

BackgroundIncreasing evidence suggests that a substantial proportion of disease-associated mutations occur in enhancers, regions of non-coding DNA essential to gene regulation. Understanding the structures and mechanisms of the regulatory programs this variation affects can shed light on the apparatuses of human diseases.ResultsWe collect epigenetic and gene expression datasets from seven early time points during neural differentiation. Focusing on this model system, we construct networks of enhancer-promoter interactions, each at an individual stage of neural induction. These networks serve as the base for a rich series of analyses, through which we demonstrate their temporal dynamics and enrichment for various disease-associated variants. We apply the Girvan-Newman clustering algorithm to these networks to reveal biologically relevant substructures of regulation. Additionally, we demonstrate methods to validate predicted enhancer-promoter interactions using transcription factor overexpression and massively parallel reporter assays.ConclusionsOur findings suggest a generalizable framework for exploring gene regulatory programs and their dynamics across developmental processes; this includes a comprehensive approach to studying the effects of disease-associated variation on transcriptional networks. The techniques applied to our networks have been published alongside our findings as a computational tool, E-P-INAnalyzer. Our procedure can be utilized across different cellular contexts and disorders.

Induction chemoimmunotherapy followed by radiotherapy in locally advanced head and neck squamous cell carcinoma: A real-world study.

131 Background: Patients with locally advanced head and neck squamous cell cancers (LAHNSCC) present poor prognosis despite multi-disciplinary comprehensive treatment, and novel treatment strategies are urgently needed. Recently, several phase II clinical trials reported encouraging pathological complete response rate of induction chemoimmunotherapy (IC+ICI) in LAHNSCC, suggesting potentially long-term survival benefits. Therefore, we conducted this real-world study to compare the efficacy of IC+ICI followed by radiotherapy (RT) versus induction chemotherapy (IC) followed by RT in LAHNSCC. Methods: We retrospectively included patients with LAHNSCC from Sun Yat-sen University Cancer center database treated with IC+ICI followed by RT or IC followed by RT between 1/2018-12/2021. Survival outcomes and adverse effects (AEs) were compared between the two groups. Results: A total of 262 patients were included: 128 (48.9%) in the IC+ICI group, and 134 (51.1%) in the IC group. Median age for the whole cohort was 60 (53–66) years, and the male-to-female ratio is 8.9:1. Most patients (84.4%) had stage IV disease. The median follow-up time was 26.7 (IQR 25.8-29.6) months. Marginally significant higher objective response rate (ORR) was observed in the IC+ICI group than that in the IC group (81.25% vs 72.39%, P=0.09). Patients in the IC+ICI group had significantly better results than those in the IC group in 2-year overall survival (OS; 88.9% vs. 71.5%, P<0.001), disease-free survival (DFS; 77.5% vs. 58.3%, P=0.005), locoregional relapse-free survival (LRRFS; 78.4% vs. 59.7%, P=0.009) and distant metastasis-free survival (DMFS; 87.5% vs. 64.6%, P<0.001). Multivariate analysis confirmed that combining immunotherapy in the induction stage was an independent prognostic factor for OS (HR 0.40, 95%CI 0.19-0.84), DFS (HR 0.45, 95%CI 0.28-0.72), LRRFS (HR 0.56, 95%CI 0.31-0.99), and DMFS (HR 0.37, 95%CI 0.19-0.73). The incidences of G3/4 AEs between the IC+ICI group and the IC group were comparable during the induction stage (6.25% vs 12.69%, P = 0.076) as well as the radiotherapy stage (14.06% vs 14.18%, P = 0.978). Conclusions: This study firstly reported that IC+ICI followed by RT was superior to IC followed by RT in long-term survival outcome in LAHNSCC.

Abstract Tu095: Cycloastragenol Alleviates Cardiac Fibrosis through Inhibiting Pyroptosis Activated by NLRP3 Inflammasome

Cardiac fibrosis is cardiac interstitial remodeling characterized by an enhanced extracellular matrix deposition. Acute sympathetic stress causes cardiac cells to immediately undergo pyroptosis, which induces cardiac inflammation and damage, and ultimately results in cardiac fibrosis. Our previous study has demonstrated the inhibitory effects of cycloastragenol (CAG), an active form of astragaloside IV isolated from Astragalus membranaceus, on isoproterenol (ISO)-induced cardiac fibrosis through blocking the NLRP3 signaling pathway. It is yet unknown how CAG affects pyroptosis of cardiac cells and whether its ability to prevent cardiac fibrosis coincides with this process. In this study, 5 mg/kg ISO was subcutaneously injected into wild-type (WT), NLRP3 knockout (KO), and GSDMD KO mice for 7 days to induce cardiac fibrosis. CAG (125 mg/kg/d) was administrated to the mice intragastrically at the start of the ISO injection. Primary cardiomyocytes and cardiac fibroblasts were isolated from neonatal rat hearts and treated with 10 μM ISO either with or without CAG. The results show that CAG alleviates cardiac fibrosis in WT mice, while lost this efficacy in NLRP3 KO mice. GSDMD KO mice do not develop ISO-induced cardiac fibrosis, indicating the key role of pyroptosis in cardiac fibrosis. Pyroptosis mainly occurs in mouse hearts during the initial stages of ISO induction (1 and 24 hours after ISO injection), and CAG significantly reduces pyroptosis of heart cells in WT mice, while CAG is unable to prevent pyroptosis in NLRP3 KO mouse hearts. The TGF-/Smads signaling pathway is also inhibited by CAG in WT mice but not in NLRP3 KO mice. Additionally, CAG prevents the in vitro pyroptosis of cardiomyocytes induced by ISO directly and cardiac fibroblasts caused by LPS+ATP. These results suggest that the principal mechanism of the anti-cardiac fibrosis effect of CAG mainly depends on its inhibition of pyroptosis mediated by NLRP3 inflammasome.

Experimental study on small molecule combinations inducing reprogramming of rat fibroblasts into functional neurons.

To establish a methodological system for reprogramming rat embryonic fibroblasts (REF) into chemically induced neurons (ciNCs) via small molecule compounds to provide safe and effective donor cells for treatment of neurodegenerative diseases. Based on the method established by PEI Gang's research group to directly reprogram human fibroblasts into neurons, the induction medium and maturation medium was optimized by replacing the coating solution, mitigating oxidative stress injury, adding neurogenic protective factors, adjusting the concentration of trichothecenes, performing small-molecule removal experiments, and carrying out immunofluorescence and Western blotting on cells at different stages of induction to validate the effect of induction. When the original protocol was used for induction, the cell survival rate was (34.24±2.77)%. After replacing the coating solution gelatin with matrigel, the cell survival rate increased to (45.41±4.27)%; after adding melatonin, the cell survival rate increased to (67.95±5.61)% and (23.43±1.42)% were transformed into neural-like cells; after adding the small molecule P7C3-A20, the cell survival rate was further increased to (76.27±1.41)%, and (39.72±4.75)% of the cells were transformed into neural-like cells. When the concentration of trichothecene was increased to 30 μmol/L, the proportion of neural-like cells reached (55.79±1.90)%; after the removal of SP600125, (86.96±2.15)% of the cells survived, and the rate of neural-like cell production increased to (63.43±1.60)%. With the optimized protocol, REF could be successfully induced into ciNC through the neural precursor cell stage, in which the neural precursor cells were able to highly express the neural precursor cell markers SRY-related HMG-box gene 2 (Sox2) and paired box 6 (Pax6) as well as neuron-specific marker tubulin 1 (Tuj1), while the expression of fiber-associated protein vimentin was reduced. After two weeks of induction of neural precursor cells in a maturation medium, most cells displayed neuronal-like cell morphology. The induced ciNCs were able to highly express the mature neuronal surface markers Tuj1 and microtubule-associated protein 2 (MAP2), while the expression of vimentin was reduced. The small molecule combinations optimized in this study can reprogram REF to ciNCs under normoxic conditions.

Numerical Investigation of Hydrogen Role on Detonation of CH4/H2/air Mixtures

ABSTRACT Steady one-dimensional Zeldovich-von Neumann-Dӧring (ZND) calculation and thermo-chemical analysis are performed to investigate the hydrogen role on ZND detonation of CH4/H2/air mixtures. Different hydrogen blend ratios (i.e. Hbr) ranging from 0% to 100% are selected in this paper. The results show that hydrogen blend ratio has a significant impact on the ZND detonation reaction pathway of stoichiometric CH4-air mixtures. When Hbr ≤ 20%, CH4 is converted to CO2 by route 1: CH4 => CH3 => C2H6 => … => CO2 and route 2: CH4 => CH3 => CH3O => CH2O => HCO => CO => CO2. When Hbr ≥ 50%, CH3 in route 2 is directly converted to CH2O through R97 (CH3 + O <=> CH2O + H). This causes different ZND detonation structures. The induction length decreases with hydrogen addition. This is because R0 (H + O2 <=> O + OH) governs the heat release during the induction stage, enhancing the energy absorption in induction stage and the molecular thermal decomposition after leading shock wave. Finally, the effect of hydrogen blend ratio on the detonation cell size is explored, and a prediction model of detonation cell size incorporated with detonation stability parameter and induction length is developed for CH4/H2/air mixtures.

Fault Characterization for AC/DC Distribution Networks Considering the Control Strategy of Photovoltaic and Energy Storage Battery

In order to cope with the failure of existing fault analysis schemes for AC/DC distribution networks with a high proportion of distributed generations, this paper proposes a fault characteristic analysis method for AC/DC distribution networks that considers the influence of distributed generation control strategies. Firstly, a transient model for the AC/DC distribution network connected to distributed generations is built. Then, the fault characteristics of the AC/DC distribution network in different stages, such as the capacitor discharge stage, inductive renewal stage, and steady state stage, is analyzed. Finally, detailed simulation analysis is conducted using PSCAD/EMTDC to validate the effectiveness of the developed scheme by the superior approximation performance between simulated curves and calculated curves.

Huangqin tang alleviates colitis-associated colorectal cancer via amino acids homeostasisand PI3K/AKT/mtor pathway modulation

Ethnopharmacological relevanceHuangqin Tang (HQT), a traditional Chinese medicine formula, is commonly used in clinical practice for the treatment of inflammatory bowel diseases. It has been reported that HQT exerts antitumor effects on colitis-associated colorectal cancer (CAC). However, the mechanism by which HQT interferes with the inflammation-to-cancer transformation remains unclear. Aims of the studyThe purpose of this study was to dynamically evaluate the efficacy of HQT in alleviating or delaying CAC and to reveal the underlying mechanism. MethodsWe established a mouse model of CAC using azoxymethane combined with 1.5% dextran sodium sulphate. The efficacy of HQT was evaluated based on pathological sections and serum biochemical indices. Subsequently, amino acids (AAs) metabolism analyses were performed using ultra-performance liquid chromatography-tandem mass spectrometry, and the phosphatidylinositol 3 kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway was detected by western blotting. ResultsThe data demonstrated that HQT could alleviate the development of CAC in the animal model. HQT effectively reduced the inflammatory response, particularly interleukin-6 (IL-6), in the inflammation induction stage, as well as in the stages of proliferation initiation and tumorigenesis. During the proliferation initiation and tumorigenesis stages, immunohistochemistry staining showed that the expression of the proliferation marker Ki67 was reduced, while apoptosis was increased in the HQT group. Accordingly, HQT substantially decreased the levels of specific AAs in the colon with CAC, including glutamic acid, glutamine, arginine, and isoleucine. Furthermore, HQT significantly inhibited the activated PI3K/AKT/mTOR pathway, which may contribute to suppression of cell proliferation and enhancement of apoptosis. ConclusionHQT is effective in alleviating and delaying the colon “inflammation-to-cancer”. The mechanism of action may involve HQT maintained AAs metabolism homeostasis and regulated PI3K/AKT/mTOR pathway, so as to maintain the balance between proliferation and apoptosis, and then interfere in the occurrence and development of CAC.

Chicken PRMT3 facilitates IBDV replication

Protein arginine methyltransferases (PRMTs) in mammals play a role in various signaling pathways, such as virus infection, inflammasome responses, and cancer growth. While some PRMTs have been found to regulate interferon production in mammals, the mechanism in chickens remains to be fully understood. This study focused on investigating the function of chicken PRMTs. Our findings indicate that chicken PRMTs act as inhibitors of interferon production in response to dsRNA or MDA5 stimulation. Each PRMT is involved in different stages of interferon induction through the MDA5-MAVS-TBK1 pathway. Furthermore, we observed the colocalization of multiple PRMTs with the viral protein VP3 of infectious bursal disease virus (IBDV). Among the chicken PRMTs studied, PRMT3 was found to be widely expressed in various organs and its expression was upregulated during IBDV infection. Notably, PRMT3 supported IBDV replication, as demonstrated by ectopic expression and inhibition studies using SGC-707. Silencing of PRMT3 led to enhanced interferon production and inhibition of IBDV replication. This study provides novel insights into the role of chicken PRMTs, particularly PRMT3, in promoting IBDV replication by suppressing interferon signaling.

Hydration kinetics and apparent activation energy of cement pastes containing high silica fume content at lower curing temperature

To promote the application of silica fume (SF) in civil engineering in cold regions, relative influences from SF content and low temperature environment on the early hydration kinetics of composite cement pastes were evaluated based on the isothermal calorimetric method. The effect of high SF content on the apparent activation energy (Ea) of Portland cement and the filler effect (via the index of area multiplier) of SF on the hydration parameters was also analyzed. The results showed that the intensity of the shoulder peak (Al peak) of the hydration kinetic curve (heat flow curve) gradually grew as the SF content increased, and the double-peak phenomenon was gradually clear. The heat flow peak is delayed and lowered with the decreasing curing temperature, while the final time of the induction stage and the duration of the acceleration stage are delayed. Moreover, the duration of the acceleration stage was slightly extended with the increase of SF content. The full-width at half-maximum (FWHM) value of the heat flow curves dropped as the SF content and curing temperature increased. The low temperature environment and the inclusion of SF inhibited the growth in early hydration degree. The higher SF content mitigated the impact of low temperature on the hydration time parameter τ. The apparent Ea results also indicated that the SF reduced the temperature sensitivity of the hydration process of the composite cement pastes, which might contribute to the development of the hydration reaction at low temperatures. The AM (Area Multiplier) factor increased approximately linearly with increasing SF replacement levels. Apparent Ea decreased linearly with increasing AM, which may be attributed to a further reduction in the diffusion-controlled hydration rate of composite cement pastes with larger AM.

Multifunctional fluorescence/photoacoustic bimodal imaging of γ-glutamyltranspeptidase in liver disorders under different triggering conditions

Hepatocellular carcinoma (HCC) seriously threatens the human health. Previous investigations revealed that γ-glutamyltranspeptidase (GGT) was tightly associated with the chronic injury, hepatic fibrosis, and the development of HCC, therefore might act as a potential indicator for monitoring the HCC-related processes. Herein, with the contribution of a structurally optimized probe ETYZE-GGT, the bimodal imaging in both far red fluorescence (FL) and photoacoustic (PA) modes has been achieved in multiple HCC-related models. To our knowledge, this work covered the most comprehensive models including the fibrosis and developed HCC processes as well as the premonitory induction stages (autoimmune hepatitis, drug-induced liver injury, non-alcoholic fatty liver disease). ETYZE-GGT exhibited steady and practical monitoring performances on reporting the HCC stages via visualizing the GGT dynamics. The two modes exhibited working consistency and complementarity with high spatial resolution, precise apparatus and desirable biocompatibility. In cooperation with the existing techniques including testing serum indexes and conducting pathological staining, ETYZE-GGT basically realized the universal application for the accurate pre-clinical diagnosis of as many HCC stages as possible. By deeply exploring the mechanically correlation between GGT and the HCC process, especially during the premonitory induction stages, we may further raise the efficacy for the early diagnosis and treatment of HCC.

#2581 Cryptococcosis in kidney transplant recipients: a nationwide multicenter retrospective cohort study—CRITERE study

Abstract Background and Aims Cryptococcosis stands as the third most common invasive fungal infection in solid organ transplant recipients. Clinical management and prognosis of the disease remains largely unexplored in the context of kidney transplant recipients. Our main objective was to describe the natural history of cryptococcosis after kidney transplantation from the graft patterns of kidney injury to the long term outcomes. Method We established a nationwide cohort of adult kidney transplant recipients diagnosed with cryptococcosis between 2002 and 2019 in France. All data were gathered starting from the transplantation date and encompassed up to the latest follow-up consultation. All putative causes of AKI as claimed by the attending clinicians were recorded. Cases were matched (ratio 1:6) with kidney transplant recipients from the French prospective multicenter cohort DIVAT with parameters at time of transplant including immunosuppression and known risk factors of cryptococcosis such as age, history of smoke, history of cancer and HIV status. Transplant outcomes (graft failure and patient death) were then compared between matched patients. Results 88 patients were included. Patients were predominantly male (n = 61, 69.3%), with a mean age of 57.0 years [SD ±13.3]. The majority of patients were primary kidney transplants (n = 71, 80.7%) with a median time from ESRD to transplantation of 2.8 years [IQ 1.25-5]. The majority of patients received ATG as induction therapy for their transplant (n = 50, 69.4%)Acute kidney injury (AKI) at diagnosis involved 37.3% of the patients with 13.3% requiring renal replacement therapy. AKI staging was distributed as follows, AKI grade 1 in 12.5% of patients, grade 2 in 13.3% of patients, and grade 3 in 11.5% of patients. During the induction stage, 39% of patients developed amphotericin B-related AKI. AKI resulting from tacrolimus overdose subsequent to tacrolimus/fluconazole interaction occurred in 25.7% of patients during the consolidation stage. Among the patients alive at 3 months following the diagnosis of cryptococcosis, 33.7% of patients exhibited graft dysfunction. Following cryptococcosis, 5 patients displayed T cell rejection and 4 patients developed antibody-mediated rejection. A total of 41 patients with cryptococcosis were matched to 246 controls (ratio 1:6), after a median follow-up of 52.3 [28.1-90.2] months, patients with cryptococcosis exhibited a higher risk of mortality with 35.9% compared with 9.8% (p &amp;lt; 0.001) and graft failure with 33.3% compared with 15.0% (p = 0.0005). Conclusion This study has shown that kidney injury manifests itself through a sequential, multi-step process that initially includes pre-renal impairment, ATN and iatrogenic mechanisms. Amphotericin B-related AKI, followed by tacrolimus overdose represent common causes of AKI.