Effect of excitation voltage in a magnetically induced electric field on the physicochemical, structural and functional properties of citrus pectin.

Treatment with a magnetic induced electric field (MIEF) under acidic conditions has proven to be an effective method for modifying pectin, enhancing its functional attributes. In this study, the effects of varying excitation voltages of MIEF under acidic conditions on the physicochemical, structural, and functional properties of citrus pectin (CP) were explored. The results demonstrated that compared to CP without MIEF treatment, MIEF-treated CP exhibited enhanced thermal stability, rheological behavior, emulsifying and gel-forming abilities, and antioxidant capacity. These improvements were attributed to higher degrees of esterification, reduced molecular weights, and increased levels of galacturonic acid and homogalacturonan in the structural backbone of the treated CP. Additionally, MIEF treatment under acidic conditions altered the surface morphology and crystalline structure of CP. Therefore, our findings suggest that applying moderate excitation voltages (150-200 V) during MIEF treatment can enhance the functional properties of CP, leading to the production of high-quality modified pectin.

Evaluating the relationship between standing height, body mass index, body fat percentage with risk of inguinal hernia: a Mendelian randomization study.

Observational studies have suggested links between standing height, BMI, body fat percentage, and inguinal hernia risk, but with inconsistent results. We conducted Mendelian randomization (MR) method to investigate their causal relationships. Independent SNPs associated with standing height, BMI, and body fat percentage were extracted from GWAS data as instrumental variables (IVs). Two-sample MR initially explored causal relationships between these factors and inguinal hernia risk. Multivariable Mendelian randomization (MVMR) assessed the direct causal effects of exposures on inguinal hernia. Positive findings from the MVMR analysis were independently validated. The inverse-variance weighted Methods (IVW), weighted median(WM), and MR-Egger were used for the MR estimates. Sensitivity analyses were used to examine the stability and reliability of the results. Two-sample MR analysis revealed a suggestive causal association between height and inguinal hernia (OR = 1.091, 95% CI = 1.003-1.186, P = 0.042). BMI (OR = 0.846, 95% CI = 0.774-0.924, P < 0.001) and body fat percentage (OR = 0.793, 95% CI = 0.690-0.911, P = 0.001) were significantly protective factors. After MVMR adjustment, BMI (OR = 0.746,95%CI = 0.638-0.872, P < 0.001) remained protective. Independent validation yielded consistent result. Genetically predicted BMI is a significant protective factor for inguinal hernia, providing valuable guidance for individualized prevention strategies.

The Ku70-SIX1-GPT2 axis regulates alpha-ketoglutarate metabolism to drive progression of prostate cancer.

Sine oculis homeobox homolog 1 (SIX1) is a new identified cancer driver in the development of prostate cancer (PC). However, the upstream regulatory mechanisms for SIX1 reactivation in cancer remains elusive. Here, we found that Ku70 robustly interacts with SIX1 in the nucleus of PC cells. The HD domain of SIX1 and the DBD domain of Ku70 are required for formation of Ku70-SIX1 complex. 20 groups of hydrogen bonds were identified in this complex by molecular dynamics simulation. Depletion of Ku70/SIX1 notably abrogates the proliferation and migration of PC. Further studies revealed that SIX1 is recruited to the promoter region on glutamate-pyruvate transaminase 2 (GPT2). Ku70 enhances the SIX1-mediated transcriptional activation on GPT2, thereby facilitating the generation of alpha-ketoglutarate (α-KG). In addition, formation of the Ku70-SIX1 complex promotes GPT2-dependent cell proliferation and migration in PC. Moreover, the expression of GPT2 is upregulated and strongly correlated with the expression of Ku70/SIX1 in PC tissues. In summary, our findings not only provide insight into the mechanistic interactions between Ku70 and SIX1, but also highlight the significance of the Ku70-SIX1-GPT2 axis for α-KG metabolism and PC carcinogenesis.

Transforming tire-derived char into powerful arsenic adsorbents by mild modification.

A large amount of arsenic-containing wastewater discharged by the non-ferrous metal industry will cause serious environmental problems if it is not properly treated. Pyrolysis char of waste tire is a kind of solid waste. Since the surface properties of tire derived char (TC) are affected by tar/ash adhesion during pyrolysis, it is necessary to modify TC to treat wastewater containing As(V) effectively as an adsorbent. At present, most studies on the modification of TC are prepared into activated carbon by high temperature activation in N2 atmosphere. In this study, TC was modified at room temperature and air atmosphere, and Fe(OH)3-TCNaOH adsorbent with particle size of 61-75 µm was obtained under the premise of the removal rate of As(V) and the settling performance of the adsorbent. When the initial concentration of As(V) was 5 mg/L, the removal rate of As(V) by Fe(OH)3-TCNaOH with a particle size of 61-75 µm could reach 90% within 30 min under a wide pH range (3-9). The adsorption of As(V) by Fe(OH)3-TCNaOH was most affected by the coexistence of PO43-, which resulted in the removal rate of As(V) decreased by about 20%. The adsorption mechanism shows that the significant increase in the number of 3-5 nm mesoporous pores of Fe(OH)3-TCNaOH and the formation of H bonds are beneficial to the adsorption of Fe(OH)3-TCNaOH to As(V), and improve the stability of Fe-As complex.

Loss-of-function in testis-specific serine/threonine protein kinase triggers male infertility in an invasive moth.

Genetic biocontrol technologies present promising and eco-friendly strategies for the management of pest and insect-transmitted diseases. Although considerable advancements achieve in gene drive applications targeting mosquitoes, endeavors to combat agricultural pests have been somewhat restricted. Here, we identify that the testis-specific serine/threonine kinases (TSSKs) family is uniquely expressed in the testes of Cydia pomonella, a prominent global invasive species. We further generated male moths with disrupted the expression of TSSKs and those with TSSKs disrupted using RNA interference and CRISPR/Cas9 genetic editing techniques, resulting in significant disruptions in spermiogenesis, decreased sperm motility, and hindered development of eggs. Further explorations into the underlying post-transcriptional regulatory mechanisms reveales the involvement of lnc117962 as a competing endogenous RNA (ceRNA) for miR-3960, thereby regulating TSSKs. Notably, orchard trials demonstrates that the release of male strains can effectively suppress population growth. Our findings indicate that targeting TSSKs could serve as a feasible avenue for managing C. pomonella populations, offering significant insights and potential strategies for controlling invasive pests through genetic sterile insect technique (gSIT) technology.

Rare-Earth Metal-Based Materials for Hydrogen Storage: Progress, Challenges, and Future Perspectives.

Rare-earth-metal-based materials have emerged as frontrunners in the quest for high-performance hydrogen storage solutions, offering a paradigm shift in clean energy technologies. This comprehensive review delves into the cutting-edge advancements, challenges, and future prospects of these materials, providing a roadmap for their development and implementation. By elucidating the fundamental principles, synthesis methods, characterization techniques, and performance enhancement strategies, we unveil the immense potential of rare-earth metals in revolutionizing hydrogen storage. The unique electronic structure and hydrogen affinity of these elements enable diverse storage mechanisms, including chemisorption, physisorption, and hydride formation. Through rational design, nanostructuring, surface modification, and catalytic doping, the hydrogen storage capacity, kinetics, and thermodynamics of rare-earth-metal-based materials can be significantly enhanced. However, challenges such as cost, scalability, and long-term stability need to be addressed for their widespread adoption. This review not only presents a critical analysis of the state-of-the-art but also highlights the opportunities for multidisciplinary research and innovation. By harnessing the synergies between materials science, nanotechnology, and computational modeling, rare-earth-metal-based hydrogen storage materials are poised to accelerate the transition towards a sustainable hydrogen economy, ushering in a new era of clean energy solutions.

Development and validation of a nomogram for predicting 28-day mortality in critically ill patients with acute gastrointestinal injury: prospective observational study.

Objective: Developing and validating a clinical prediction nomogram of 28-day mortality in critically ill patients with acute gastrointestinal injury (AGI). Methods: Firstly, the construction of a clinical prediction model was developed using data obtained from a prospective observational study from May 2023 to April 2024. Then, data from a prospective multicenter observational study conducted in the intensive care units of 12 teaching hospitals in 2014 were utilized to independently and externally validate the clinical prediction model developed in the first part. We first screened the covariates of the development cohort by univariate cox regression, and then carried out cox regression analysis on the development cohort by backward stepwise regression to determine the optimal fitting model. Subsequently, a nomogram was derived from this model. Results: A total of 1102 and 379 patients, 28-day mortality occurred in 20.3% and 15.8% of patients respectively, were included in the development and validation cohort, respectively. We developed a nomogram in critically ill patients with AGI and the AGI grade, APACHE II score, Mechanical ventilation (MV), Feeding intolerance (FI) and daily calorie intake (DCI) in 72 h, were independent predictors of 28-day mortality, with the OR of the AGI grade was 1.910 (95% CI, 1.588-2.298; P < 0.001), the OR of APACHE II score was 1.099 (95% CI, 1.069-1.130; P < 0.001), the OR of MV was 1.880 (95% CI, 1.215-2.911; P = 0.005), the OR of FI was 3.453 (95% CI, 2.414-4.939; P < 0.001) and the DCI > 0.7 or < 0.5 of calorie target is associated with increased 28-day mortality, with OR of 1.566 (95% CI, 1.024-2.395; P = 0.039) and 1.769 (95% CI, 1.170-2.674; P = 0.007), respectively. Independent external validation of the prediction model was performed. This model has good discrimination and calibration. The DCA and CIC also validated the good clinical utility of the nomogram. Conclusion: The prediction of 28-day mortality can be conveniently facilitated by the nomogram that integrates AGI grade, APACHE II score, MV, FI and DCI in 72 h in critically ill patients with AGI.

Stability, Inheritance, Cross-Resistance, and Fitness Cost of Resistance to λ-Cyhalothrin in Cydia pomonella.

Insecticides are commonly utilized in agriculture and forestry for pest control, but their dispersal can pose hazards to humans and environment. Understanding resistance, inheritance patterns, and fitness costs can help manage resistance. A λ-cyhalothrin-resistant population (LCR) of Cydia pomonella, a global pest of pome fruits and walnuts, was obtained through selective insecticide breeding for 15 generations, showing stable moderate resistance (23.85-fold). This population was cross-resistant to deltamethrin (4.26-fold) but not to ß-cypermethrin, chlorantraniliprole, chlorpyrifos, and avermectin. Genetic analysis revealed the resistance was autosomal, incompletely dominant, and controlled by multiple genes. Increased activity of glutathione S-transferases and cytochrome P450 monooxygenases (P450s) played a primary role in resistance, with specific genes up-regulated in LCR, and exhibited significant expression in midgut. LCR also exhibited fitness costs, including delays in development, reduced fecundity, and slower population growth. These findings contribute to understanding λ-cyhalothrin resistance in C. pomonella and can guide resistance management strategies.

Response Surface Methodology Optimization of Exosome-like Nanovesicles Extraction from Lycium ruthenicum Murray and Their Inhibitory Effects on Aß-Induced Apoptosis and Oxidative Stress in HT22 Cells.

Exosome-like nanovesicles (ELNs) derived from plants are nanoscale vesicles isolated from edible plant sources. Lycium ruthenicum Murray (LRM) has garnered growing attention for its dietary value and therapeutic benefits. In this study, a PEG6000-based method was developed to isolate LRM-ELNs. Response surface methodology (RSM) was used to optimize the extraction conditions to obtain the optimal extraction efficiency. When PEG6000 concentration was at 11.93%, relative centrifugal force was 9720 g, and incubation time was 21.12 h, the maximum LRM-ELN yield was 4.24 g/kg. This optimization process yielded LRM-ELNs with a particle size of 114.1 nm and a surface charge of -6.36 mV. Additionally, LRM-ELNs mitigated Aß-induced apoptosis in HT22 cells by enhancing mitochondrial membrane potential (MMP), lowering the Bax/Bcl-2 ratio, and reducing Cleaved Caspase-3 expression. Furthermore, LRM-ELNs alleviated Aß-induced oxidative stress in HT22 cells by promoting the nuclear translocation of Nrf2 and upregulating the expression of HO-1 and NQO1. These findings indicate that LRM-ELNs exert protective effects against Aß-induced damage in HT22 cells and may be considered as a potential dietary supplement for Alzheimer's disease prevention.

Transcranial Doppler ultrasound in evaluating cerebral blood flow abnormalities in major depressive disorder.

Previous research has shown that blood flow abnormalities affect major depressive disorder (MDD) from multiple perspectives. Therefore, this study aims to investigate the relationship between middle cerebral artery (MCA) blood flow velocity parameters and clinical symptom scores (Hamilton Depression Rating Scale [HAMD] and Montgomery-Åsberg Depression Rating Scale [MADRS]) in patients with MDD. We compared the MCA blood flow velocity parameters, including peak systolic velocity (MCA-PSV), end-diastolic velocity (MCA-EDV), and mean velocity (MCA-MV), between 50 MDD patients and 50 control subjects. Additionally, we analyzed the correlation between these parameters and HAMD and MADRS scores. Hemodynamic parameters such as pulsatility index and resistance index were also compared between the 2 groups. MCA-PSV, MCA-EDV, and MCA-MV were significantly lower in MDD patients compared to the control group, while pulsatility index and resistance index were significantly higher. Correlation analysis revealed that MCA-PSV, MCA-EDV, and MCA-MV were significantly negatively correlated with HAMD and MADRS scores in MDD patients, indicating that cerebral blood flow velocity decreases as depressive symptoms worsen. Furthermore, regression analysis confirmed the negative relationship between blood flow velocity parameters and clinical symptom scores. The results of this study suggest that the reduction in cerebral blood flow velocity in MDD patients may be associated with the severity of depressive symptoms. This finding provides new insights into the pathophysiological mechanisms of MDD and offers a potential theoretical basis for developing depression treatment strategies based on cerebral blood flow velocity parameters.

Interpreting the biological effects of protons as a function of physical quantity: linear energy transfer or microdosimetric lineal energy spectrum?

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The primary advantage of using the "dose and LET" physical system is its relative simplicity, especially for presenting and recording results. Inclusion of additional information such as the energy spectrum of charged particles renders this approach adequate to describe the biological effects of large dose levels from homogeneous sources. The primary disadvantage of this system is that it does not provide a unique description of the stochastic nature of radiation interactions. We and others have used dose-averaged LET (LETd) as a correlative physical quantity to the relative biological effectiveness (RBE) of proton beams. This approach is based on established experimental findings that proton RBE increases with LETd. However, this approach might not be applicable to intensity-modulated proton therapy or other applications in which the proton energy spectrum is highly heterogeneous. In the current study, we irradiated cancer cells with scanning proton beams with identical LETd (3.4 keV/µm) but arising from two different proton energy/LET spectra (a narrow spectrum in group 1 and a widespread heterogeneous spectrum in group 2). Clonogenic survival after irradiation revealed significant differences in RBE at any cell surviving fraction: e.g., at a surviving fraction of 0.1, the RBE was 0.97 ± 0.03 in group 1 and 1.16 ± 0.04 in group 2 (p≤0.01), validating our hypothesis that LETd alone may not adequately indicate proton RBE. Further analysis showed that microdosimetric spectrum (the probability density function of the stochastic physical quantity lineal energy y) was helpful for interpreting observed differences in biological effects. However, more accurate use of microdosimetric spectrum to quantify RBE requires a cell line-specific mechanistic model.

Genetical effects of sleep traits on postpartum depression: a bidirectional two-sample Mendelian randomization study.

BACKGROUND: Postpartum depression (PPD) is widely recognized as the most prevalent mental health crisis following childbirth and has been linked to sleep disturbances. However, the potential causal relationships between various sleep traits and PPD remain unclear. This study employs a bidirectional two-sample Mendelian randomization (MR) approach to investigate these associations. METHODS: The inverse-variance-weighted method was used to evaluate the causally linked sleep traits on postpartum depression. The weighted median, weighted mode, and MR-Egger were used to estimate the robustness of the inverse-variance-weighted method. The leave-one-out method estimated the sensitivity of the result. Cochran's Q method was used for the heterogeneous test. The MR-Egger intercept and MR-PRESSO methods detected the horizontal pleiotropy. RESULTS: We examined the genetic causal relationships between nine sleep traits and postpartum depression. Sleep apnea syndrome (OR: 1.122; 95%CI: 1.063-1.185; p = 0.000), sleeplessness/insomnia (OR: 1.465; 95%CI: 1.104-1.943; p = 0.008), and frequency of tiredness/lethargy in last 2 weeks (OR: 1.725; 95%CI: 1.345-2.213; p = 0.000) genetically predicted the increased risk of postpartum depression. The reverse Mendelian randomization analysis showed PPD caused sleeplessness/insomnia (ß: 0.006; 95%CI: 0.001-0.010; p = 0.016) and frequency of tiredness/lethargy in last 2 weeks (ß: 0.007; 95%CI: 0.002-0.011; p = 0.004). The remaining six sleep traits showed no significant association with PPD. There was no heterogeneity or horizontal pleiotropy. CONCLUSIONS: Genetic evidence reveals causal relationships between specific sleep traits and PPD, including sleep apnea syndrome, sleeplessness/insomnia, and tiredness. Whether certain sleep health indicators suggest a risk of postpartum depression or sleep issues that are caused by PPD, both may offer insights into the prevention and treatment of PPD.

Multimodal apparent diffusion MRI model in noninvasive evaluation of breast cancer and Ki-67 expression.

BACKGROUND: To assess the capability of multimodal apparent diffusion (MAD) weighted magnetic resonance imaging (MRI) to distinguish between malignant and benign breast lesions, and to predict Ki-67 expression level in breast cancer. METHODS: This retrospective study was conducted with 93 patients who had postoperative pathology-confirmed breast cancer or benign breast lesions. MAD images were acquired using a 3.0 T MRI scanner with 16 b values. The MAD parameters, as flow (fF, DF), unimpeded (fluid) (fUI), hindered (fH, DH, and αH), and restricted (fR, DR), were calculated. The differences of the parameters were compared by Mann-Whitney U test between the benign/malignant lesions and high/low Ki-67 expression level. The diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: The fR in the malignant lesions was significantly higher than in the benign lesions (P = 0.001), whereas the fUI and DH were found to be significantly lower (P = 0.007 and P < 0.001, respectively). Compared with individual parameter in differentiating malignant from benign breast lesions, the combination parameters of MAD (fR, DH, and fUI) provided the highest AUC (0.851). Of the 73 malignant lesions, 42 (57.5%) were assessed as Ki-67 low expression and 31 (42.5%) were Ki-67 high expression. The Ki-67 high status showed lower DH, higher DF and higher αH (P < 0.05). The combination parameters of DH, DF, and αH provided the highest AUC (0.691) for evaluating Ki-67 expression level. CONCLUSIONS: MAD weighted MRI is a useful method for the breast lesions diagnostics and the preoperative prediction of Ki-67 expression level.

Rapid detection of mutations in the suspected piperaquine resistance gene E415G-exo in Plasmodium falciparum exonuclease via AS‒PCR and RAA with CRISPR/Cas12a.

Malaria remains a major public health concern. The rapid spread of resistance to antimalarial drugs is a major challenge for malaria eradication. Timely and accurate molecular monitoring based on practical detection methods is a critical step toward malaria control and elimination. In this study, two rapid detection techniques, allele-specific PCR (AS‒PCR) and recombinase-aided amplification (RAA) combined with CRISPR/Cas12a, were established, optimized and assessed to detect single nucleotide polymorphisms in the Plasmodium falciparum exonuclease (Pfexo) gene related to suspected piperaquine resistance. Moreover, phosphorothioate and artificial mismatches were introduced into the allele-specific primers for AS‒PCR, and crRNA-mismatched bases were introduced into the RAA‒CRISPR/Cas12a assay because crRNAs designed according to conventional rules fail to discriminate genotypes. As a result, the detection limits of the AS‒PCR and RAA‒CRISPR/Cas12a assays were 104 copies/µL and 103 copies/µL, respectively. The detection threshold for dried blood spots was 100‒150 parasites/µL, with no cross-reactivity against other genotypes. The average cost of AS‒PCR is approximately $1 per test and takes 2-3 h, whereas that of the RAA‒CRISPR/Cas12a system is approximately $7 per test and takes 1 h or less. Therefore, we provide more options for testing single nucleotide polymorphisms in the Pfexo gene, considering economic conditions and the availability of instruments, equipment, and reagents, which can contribute to the molecular monitoring of antimalarial resistance.

Large-scale conformal synthesis of one-dimensional MAX phases.

MAX phases, a unique class of layered ternary compounds, along with their two-dimensional derivatives, MXenes, have drawn considerable attention in many fields. Notably, their one-dimensional (1D) counterpart exhibits more distinct properties and enhanced assemblability for broader applications. We propose a conformal synthetic route for 1D-MAX phases fabrication by integrating additional atoms into nanofibers template within a molten salt environment, enabling in-situ crystalline transformation. Several 1D-MAX phases are successfully synthesized on a large scale. Demonstrating its potential, a copper-based layer-by-layer composites containing 1% by volume of 1D-Ti2AlC reinforced phase achieves an impressive 98 IACS% conductivity and a friction coefficient of 0.08, while maintaining mechanical properties comparable to other Cu-MAX phase composites, making it suitable for advanced industrial areas. This strategy may promise opportunities for the fabrication of various 1D-MAX phases.

Puerarin ameliorates high glucose-induced MIN6 cell injury by activating PINK1/Parkin-mediated mitochondrial autophagy.

The dysfunction of pancreatic ß-cells plays a pivotal role in the pathogenesis of type 2 diabetes mellitus (T2DM). Despite numerous studies demonstrating the anti-inflammatory and antioxidant properties of puerarin, the protective effects of puerarin on ß-cells remain poorly understood. Hence, this study aimed to explore the effects of puerarin on ß-cell dysfunction in a hyperglycemic environment via the PINK/Parkin-mediated mitochondrial autophagy pathway. The alterations in cell viability of MIN6 cells exposed to glucose concentrations of 5 mM, 10 mM, 20 mM, and 30 mM for 24 h, 48 h, and 72 h, respectively, were assessed using the CCK-8 assay to optimize the modeling conditions. Subsequently, cellular insulin secretion was measured using enzyme-linked immunosorbent assay (ELISA), apoptosis rate by flow cytometry, mitochondrial membrane potential alteration by JC-1, cellular ROS production by the DCFH-DA fluorescent probe, and fusion of cellular autophagosomes and lysosomes through adenoviral infection analysis. Furthermore, gene and protein expression levels of the PINK/Parkin-mediated mitochondrial autophagy pathway and mitochondrial apoptosis pathway were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. Results indicated a significant decrease in MIN6 cell viability following 48 h of exposure to 30 mM glucose concentration. Puerarin intervention markedly attenuated ROS production, restored mitochondrial membrane potential, induced PINK/Parkin-mediated mitochondrial autophagy, suppressed activation of the mitochondrial apoptotic pathway, mitigated apoptosis, and enhanced insulin secretion in a high glucose (HG) environment. The findings of this investigation contribute to a deeper understanding of the precise mechanism underlying the protective effects of puerarin on ß-cells and offer a theoretical foundation for advancing puerarin-based therapeutics aimed at ameliorating T2DM.

A gain-of-function mutation at the C-terminus of FT-D1 promotes heading by interacting with 14-3-3A and FDL6 in wheat.

Vernalization and photoperiod pathways converging at FT1 control the transition to flowering in wheat. Here, we identified a gain-of-function mutation in FT-D1 that results in earlier heading date (HD), and shorter plant height and spike length in the gamma ray-induced eh1 wheat mutant. Knockout of the wild-type and overexpression of the mutated FT-D1 indicate that both alleles are functional to affect HD and plant height. Protein interaction assays demonstrated that the frameshift mutation in FT-D1eh1 exon 3 led to gain-of-function interactions with 14-3-3A and FDL6, thereby enabling the formation of florigen activation complex (FAC) and consequently activating a flowering-related transcriptomic programme. This mutation did not affect FT-D1eh1 interactions with TaNaKR5 or TaFTIP7, both of which could modulate HD, potentially via mediating FT-D1 translocation to the shoot apical meristem. Furthermore, the 'Segment B' external loop is essential for FT-D1 interaction with FDL6, while residue Y85 is required for interactions with TaNaKR5 and TaFTIP7. Finally, the flowering regulatory hub gene, ELF5, was identified as the FT-D1 regulatory target. This study illustrates FT-D1 function in determining wheat HD with a suite of interaction partners and provides genetic resources for tuning HD in elite wheat lines.

[Daidzein attenuates high glucose-induced inflammatory injury in macrophages by regulating NLRP3 inflammasome signaling pathway].

This study aims to explore the inhibitory effect of daidzein on macrophage inflammation induced by high glucose via regulating the NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. The cell counting kit-8(CCK-8) assay was employed to detect the effects of daidzein at different concentrations on the viability of RAW264.7 cells. Western blot was employed to determine the protein level of tumor necrosis factor(TNF)-α in macrophages exposed to different concentrations of glucose for different time periods as well as the expression levels of proteins involved in the polarization and Toll-like receptor 4(TLR4)-myeloid differentiation factor(MyD88)-NLRP3 inflammasome pathway of the macrophages exposed to high glucose. Enzyme-linked immunosorbent assay was employed to measure the levels of TNF-α, interleukin(IL)-18, and IL-1ß secreted by macrophages. The expression level of nuclear factor-kappa B(NF-κB) p65 in macrophages exposed to high glucose was detected by immunofluorescence, and the level of intracellular reactive oxygen species(ROS) was detected by the DCFH-DA fluorescent probe. The mRNA levels of NLRP3, TNF-α, and IL-18 in macrophages were determined by qRT-PCR. The results showed that treatment with 30 mmol·L~(-1) glucose for 48 h was the best condition for the modeling of macrophage injury. Compared with the blank group, the model group showed improved polarization of macrophages, increased secretion of TNF-α, IL-18, and IL-1ß, elevated ROS level, and up-regulated expression of NF-κB p65. In addition, the modeling up-regulated the mRNA levels of NLRP3, TNF-α, and IL-18 and the protein levels of TLR4, MyD88, NLRP3, NF-κB p65, p-NF-κB p65, I-κB, p-I-κB, ASC, pro-caspase-1, pro-IL-1ß, cleaved IL-1ß, and pro-IL-18. Compared with the model group, daidzein(10, 20, and 40 µmol·L~(-1)) lowered the levels of inflammatory cytokines and down-regulated the mRNA levels of NLRP3, TNF-α, and IL-18 as well as the protein levels of TLR4, MyD88, NLRP3, NF-κB p65, p-NF-κB p65, I-κB, p-I-κB, ASC, pro-caspase-1, pro-IL-1ß, cleaved IL-1ß, and pro-IL-18. In addition, daidzein reduced intracellular ROS. According to the available reports and the experimental results, high glucose can induce the polarization of macrophages and promote the secretion of inflammatory cytokines. Daidzein can inhibit the expression of ROS in macrophages by regulating the NLRP3 inflammasome signaling pathway, thereby reducing the inflammation of macrophages exposed to high glucose.

Hormonally and chemically defined expansion conditions for organoids of biliary tree Stem Cells.

Wholly defined ex vivo expansion conditions for biliary tree stem cell (BTSC) organoids were established, consisting of a defined proliferative medium (DPM) used in combination with soft hyaluronan hydrogels. The DPM consisted of commercially available Kubota's Medium (KM), to which a set of small molecules, particular paracrine signals, and heparan sulfate (HS) were added. The small molecules used were DNA methyltransferase inhibitor (RG108), TGF- ß Type I receptor inhibitor (A83-01), adenylate cyclase activator (Forskolin), and L-type Ca2+ channel agonist (Bay K8644). A key paracrine signal proved to be R-spondin 1 (RSPO1), a secreted protein that activates Wnts. Soluble hyaluronans, 0.05 % sodium hyaluronate, were used with DPM to expand monolayer cultures. Expansion of organoids was achieved by using DPM in combination with embedding organoids in Matrigel that was replaced with a defined thiol-hyaluronan triggered with PEGDA to form a hydrogel with a rheology [G*] of less than 100 Pa. The combination is called the BTSC-Expansion-Glycogel-System (BEX-gel system) for expanding BTSCs as a monolayer or as organoids. The BTSC organoids were expanded more than 3000-fold ex vivo in the BEX-gel system within 70 days while maintaining phenotypic traits indicative of stem/progenitors. Stem-cell-patch grafting of expanded BTSC organoids was performed on the livers of Fah-/- mice with tyrosinemia and resulted in the rescue of the mice and restoration of their normal liver functions. The BEX-gel system for BTSC organoid expansion provides a strategy to generate sufficient numbers of organoids for the therapeutic treatments of liver diseases.

Mimicking large spot-scanning radiation fields for proton FLASH preclinical studies with a robotic motion platform.

Previously, a synchrotron-based horizontal proton beamline (87.2 MeV) was successfully commissioned to deliver radiation doses in FLASH and conventional dose rate modes to small fields and volumes. In this study, we developed a strategy to increase the effective radiation field size using a custom robotic motion platform to automatically shift the positions of biological samples. The beam was first broadened with a thin tungsten scatterer and shaped by customized brass collimators for irradiating cell/organoid cultures in 96-well plates (a 7-mm-diameter circle) or for irradiating mice (1-cm2 square). Motion patterns of the robotic platform were written in G-code, with 9-mm spot spacing used for the 96-well plates and 10.6-mm spacing for the mice. The accuracy of target positioning was verified with a self-leveling laser system. The dose delivered in the experimental conditions was validated with EBT-XD film attached to the 96-well plate or the back of the mouse. Our film-measured dose profiles matched Monte Carlo calculations well (1D gamma pass rate >95%). The FLASH dose rates were 113.7 Gy/s for cell/organoid irradiation and 191.3 Gy/s for mouse irradiation. These promising results indicate that this robotic platform can be used to effectively increase the field size for preclinical experiments with proton FLASH.