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Phenolic acids, essential compounds in whole grains, are renowned for their health-enhancing antioxidant and anti-inflammatory properties. Variations in concentration, particularly of hydroxybenzoic and hydroxycinnamic acids, are observed among grain types. Their antiobesity and antidiabetes effects are linked to their modulation of key signaling pathways like AMPK and PI3K, crucial for metabolic regulation and the body’s response to inflammation and oxidative stress. Processing methods significantly influence phenolic acid content and bioavailability in whole grains. Thermal techniques like boiling, baking, or roasting can degrade these compounds, with loss influenced by processing conditions. Nonthermal methods such as germination, fermentation, or their combination, can protect or enhance phenolic acid content under ideal conditions. Novel nonthermal approaches like ultrahigh pressure (UHP), irradiation, and pulsed electric fields (PEF) show promise in preserving these compounds. Further research is needed to fully comprehend the impact mechanisms of these innovative methods on the nutritional and sensory attributes of cereals.

In the fields of wind power, and other industries, the Al2O3/TiO2coating is prepared and ground on the bearing ring, in order to obtain the insulation resisting the electrical erosion for the motors at high voltage. A novel wet chemical mechanical grinding (WCMG) method is proposed to finish this hard-brittle composite material, utilizing the structured diamond abrasives pad and the NaOH solution. The softened workpiece's surface under the chemical reaction was demonstrated by means of Raman spectrum, indentation and scratching tests. The analytical model of surface roughness and fracture cracks is established based on the synthesis of geometry and kinematics, contact mechanics, material removal and indentation fracture mechanics. The surface roughness of coating was reduced from initial Sa3.293 μm down to final Sa0.049 μm in the WCMG process with grain size 3 μm and pH 12.01, mostly attributed to the ductile removal of chemically softened coating surface.

A series of activators of GCN2 (general control nonderepressible 2) kinase have been developed, leading to HC-7366, which has entered the clinic as an antitumor therapy. Optimization resulted in improved permeability compared to that of the original indazole hinge binding scaffold, while maintaining potency at GCN2 and selectivity over PERK (protein kinase RNA-like endoplasmic reticulum kinase). The improved ADME properties of this series led to robust in vivocompound exposure in both rats and mice, allowing HC-7366 to be dosed in xenograft models, demonstrating that activation of the GCN2 pathway by this compound leads to tumor growth inhibition.

The protein kinase A (PKA) signaling pathway, which mediates protein phosphorylation, is important for sperm motility and male fertility. This process relies on A-kinase anchoring proteins that organize PKA and its signalosomes within specific subcellular compartments. Previously, it was found that the absence of A-kinase anchoring protein 3 (AKAP3) leads to multiple morphological abnormalities in mouse sperm. But how AKAP3 regulates sperm motility is yet to be elucidated. AKAP3 has two amphipathic domains, here named dual and RI, in its N-terminus. These domains are responsible for binding regulatory subunits I alpha (RIα) and II alpha (RIIα) of PKA and for RIα only, respectively. Here, we generated mutant mice lacking the dual and RI domains of AKAP3. It was found that the deletion of these domains caused male mouse infertile, accompanied by mild defects in the fibrous sheath of sperm tails. Additionally, the levels of serine/threonine phosphorylation of PKA substrates and tyrosine phosphorylation decreased in the mutant sperm, which exhibited a defect in hyperactivation under capacitation conditions. The protein levels of PKA subunits remained unchanged. But, interestingly, the regulatory subunit RIα was mis-localized from principal piece to midpiece of sperm tail, whereas this was not observed for RIIα. Further protein–protein interaction assays revealed a preference for AKAP3 to bind RIα over RIIα. Collectively, our findings suggest that AKAP3 is important for sperm hyperactivity by regulating type-I PKA signaling pathway mediated protein phosphorylation via its dual and RI domains.Ablation of dual and RI domains of A-kinase anchoring proteins disrupts its interaction with type-I protein kinase A, which causes defects in mouse sperm fibrous sheath formation, protein phosphorylation, hyperactivation, and fertility.Graphical Abstract

Several systematic reviews (SRs) have investigated the association between ultra-processed foods (UPFs) and the risk of hypertension in various populations. However, the quality of the evidence remains unclear. This umbrella review was thus conducted to fill this gap.

Tumor cell-derived cancer nanovaccines introduce tumor cell-derived components as functional units that endow the nanovaccine systems with some advantages, especially providing all potential tumor antigens. However, cumbersome assembly steps, potential risks of exogenous adjuvants, as well as insufficient lymph node (LN) targeting and dendritic cell (DC) internalization limit the efficacy and clinical translation of existing tumor cell-derived cancer nanovaccines. Herein, we introduced an endoplasmic reticulum (ER) stress inducer α-mangostin (αM) into tumor cells through poly(d, l-lactide-co-glycolide) nanoparticles and harvested biologically self-assembled tumor cell-derived cancer nanovaccines (αM-Exos) based on the biological process of tumor cell exocytosing nanoparticles through tumor-derived exosomes (TEXs). Besides presenting multiple potential antigens, αM-Exos inherited abundant 70 kDa heat shock proteins (Hsp70s) upregulated by ER stress, which can not only act as endogenous adjuvants but also improve LN targeting and DC internalization. Following subcutaneous injection, αM-Exos efficiently migrated to LNs and was expeditiously endocytosed by DCs, delivering tumor antigens and adjuvants to DCs synchronously, which then powerfully triggered antitumor immune responses and established long-term immune memory. Our study exhibited an all-in-one biologically self-assembled tumor cell-derived cancer nanovaccine platform, and the fully featured cancer nanovaccines assembled efficiently through this platform are promising for desirable cancer immunotherapy.

Safety issues related to flammable electrolytes in lithium-ion batteries (LIBs) remain a major challenge for their extended applications. The use of non-flammable phosphate-based electrolytes has proved the validity in inhibiting the combustion of LIBs. However, the strong interaction between Li+and phosphate leads to a dominant solid electrolyte interphase (SEI) with limited electronic shielding, resulting in the poor Li+intercalation at the graphite (Gr) anode when using high-phosphate-content electrolytes. To mitigate this issue and improve Li+insertion, we propose an “In-N-Out” strategy to render phosphates “non-coordinative”. By employing a combination of strongly polar solvents for a “block effect” and weakly polar solvents for a “drag effect”, we reduce the Li+-phosphate interaction. As a result, phosphates remain in the electrolyte phase (“In”), minimizing their impact on the incompatibility with the Gr electrode (“Out”). We have developed a non-flammable electrolyte with high triethyl phosphate (TEP) content (>60 wt.%), demonstrating the excellent ion conductivity (5.94 mS cm −1at 30 °C) and reversible Li+intercalation at a standard concentration (~1 mol L −1). This approach enables the manipulation of multiple electrolyte functions and holds the promise for the development of safe electrochemical energy storage systems using non flammable electrolytes.

Weaning piglets usually suffer from severe diarrhea (commonly known as postweaning diarrhea, PWD) along with intestinal motility disorder. Intestinal peristalsis is mainly regulated by the longitudinal muscle-myenteric plexus (LM-MP). To understand the relationship between intestinal LM-MP function and the development of PWD, we compared the intestinal electrical activity, and the transcriptional profile of the LM-MP between 21-day-old piglets (just weaned, n=7) and 24-day-old piglets (suffered the most severe weaning stress, n=7). The results showed that 24-day-old piglets exhibited different degrees of diarrhea. A significant increase in the slow-wave frequency in the ileum and colon was observed in 24-day-old piglets, while c-kit expression in the intestinal LM-MPs was significantly decreased, indicating that PWD caused by elevated slow-wave frequency may be associated with loss of c-kit. The real-time quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) showed that intestinal LM-MPs in 24-day-old piglets may undergo inflammation and oxidative stress. Significant increases in 8-hydroxy-2’-deoxyguanosine and decreases in thioredoxin suggest that weaning may lead to DNA damage in the LM-MP of 24-day-old piglets. In addition, activating transcription factor 3 was significantly upregulated, indicating nerve damage in the LM-MP of 24-day-old piglets. The transcriptomic results showed that most of the differentially expressed genes in the ileal LM-MP after weaning were downregulated and closely related to the cell cycle process. Subsequent RT-qPCR analysis showed that the relative expression of p21was upregulated, while the expression of cyclin A2, cyclin B1, and proliferating cell nuclear antigenwas downregulated in the ileal and colonic LM-MP of 24-day-old piglets, suggesting that weaning may inhibit cell proliferation and cause G1/S cell cycle arrest in ileal and colonic LM-MP. In conclusion, weaning may lead to cell cycle arrest by causing DNA damage in the LM-MP, impairing intestinal motility regulation, and ultimately leading to diarrhea in piglets.

Accurately and rapidly acquiring the microscopic properties of a material is crucial for catalysis and electrochemistry. Characterization tools, such as spectroscopy, can be a valuable tool to infer these properties, and when combined with machine learning tools, they can theoretically achieve fast and accurate prediction results. However, on the path to practical applications, training a reliable machine learning model is faced with the challenge of uneven data distribution in a vast array of non-negligible solvent types. Herein, we employ a combination of the first-principles-based approach and data-driven model. Specifically, we utilize density functional theory (DFT) to calculate theoretical spectral data of CO–Ag adsorption in 23 different solvent systems as a data source. Subsequently, we propose a hierarchical knowledge extraction multiexpert neural network (HMNN) to bridge the knowledge gaps among different solvent systems. HMNN undergoes two training tiers: in tier I, it learns fundamental quantitative spectra–property relationships (QSPRs), and in tier II, it inherits the fundamental QSPR knowledge from previous steps through a dynamic integration of expert modules and subsequently captures the solvent differences. The results demonstrate HMNN’s superiority in estimating a range of molecular adsorbate properties, with an error range of less than 0.008 eV for zero-shot predictions on unseen solvents. The findings underscore the usability, reliability, and convenience of HMNN and could pave the way for real-time access to microscopic properties by exploiting QSPR.

ObjectiveSqualene epoxidase (SQLE) promotes metabolic dysfunction-associated steatohepatitis-associated hepatocellular carcinoma (MASH-HCC), but its role in modulating the tumour immune microenvironment in MASH-HCC remains unclear.DesignWe established hepatocyte-specific Sqletransgenic (tg) and knockout mice, which were subjected to a choline-deficient high-fat diet plus diethylnitrosamine to induce MASH-HCC. SQLE function was also determined in orthotopic and humanised mice. Immune landscape alterations of MASH-HCC mediated by SQLE were profiled by single-cell RNA sequencing and flow cytometry.ResultsHepatocyte-specific Sqletg mice exhibited a marked increase in MASH-HCC burden compared with wild-type littermates, together with decreased tumour-infiltrating functional IFN-γ+and Granzyme B+CD8+T cells while enriching Arg-1+myeloid-derived suppressor cells (MDSCs). Conversely, hepatocyte-specific Sqleknockout suppressed tumour growth with increased cytotoxic CD8+T cells and reduced Arg-1+MDSCs, inferring that SQLE promotes immunosuppression in MASH-HCC. Mechanistically, SQLE-driven cholesterol accumulation in tumour microenvironment underlies its effect on CD8+T cells and MDSCs. SQLE and its metabolite, cholesterol, impaired CD8+T cell activity by inducing mitochondrial dysfunction. Cholesterol depletion in vitro abolished the effect of SQLE-overexpressing MASH-HCC cell supernatant on CD8+T cell suppression and MDSC activation, whereas cholesterol supplementation had contrasting functions on CD8+T cells and MDSCs treated with SQLE-knockout supernatant. Targeting SQLE with genetic ablation or pharmacological inhibitor, terbinafine, rescued the efficacy of anti-PD-1 treatment in MASH-HCC models.ConclusionSQLE induces an impaired antitumour response in MASH-HCC via attenuating CD8+T cell function and augmenting immunosuppressive MDSCs. SQLE is a promising target in boosting anti-PD-1 immunotherapy for MASH-HCC.

To elucidate the mechanism of modified biochar in inhibiting soybean root rot and improving its quality. The effects of 0 t·ha−1(CK), 15 t·ha−1(15BC; 15KBC), 30 t·ha−1(30BC; 30KBC) and 45 t·ha−1(45BC; 45KBC) of raw biochar (BC) and modified biochar (KBC) on the incidence of root rot, rhizosphere soil ecological environment and quality were studied. The improvement of soybean root rot by BC was very weak, and the application of 45 t·ha−1BC could reduce soybean root rot by about 7% only. Compared with the BC treatment, the disease index of 30KBC and 45KBC was 22.17% and 19.82% less than CK, respectively. High application rates of BC and KBC increased the aeration, bacterial abundance and diversity of soybean rhizosphere soil, and improved the proportion of soil nutrients. The 30KBC and 45KBC significantly increased the relative abundance of beneficial bacteria (Acidobacteria, Mortierellomycota, Pseudomonas, Chryseolinea, Lysobacter and Mortierella) and decreased that of pathogenic bacteria (Bacteroidetes, Ascomycota and Fusarium) in soil. Soybean quality indicators including oil content, K, P and protein content correspond to 30KBC. The biochar can improve soil physicochemical properties, reduce the relative abundance of pathogenic bacteria, and increase that of beneficial bacteria, thereby reducing root rot incidence and improving soybean quality. Under the condition of water saving and nitrogen reduction, 30KBC is the optimum. This study is significant for alleviating soybean continuous cropping obstacles, disease prevention and control, and improving soybean quality.

Rapid, high-precision pickup of microseismic P- and S-waves is an important basis for microseismic monitoring and early warning. However, it is difficult to provide fast and highly accurate pickup of micro-seismic P- and S-waves arrival-time. To address this, the study proposes a lightweight and high-precision micro-seismic P- and S-waves arrival times picking model, lightweight adversarial U-shaped network (LAU-Net), based on the framework of the generative adversarial network, and successfully deployed in low-power devices. The pickup network constructs a lightweight feature extraction layer (GHRA) that focuses on extracting pertinent feature information, reducing model complexity and computation, and speeding up pickup. We propose a new adversarial learning strategy called application-aware loss function. By introducing the distribution difference between the predicted results and the artificial labels during the training process, we improve the training stability and further improve the pickup accuracy while ensuring the pickup speed. Finally, 8986 and 473 sets of micro-seismic events are used as training and testing sets to train and test the LAU-Net model, and compared with the STA/LTA algorithm, CNNDET+CGANet algorithm, and UNet++ algorithm, the speed of each pickup is faster than that of the other algorithms by 11.59ms, 15.19ms, and 7.79ms, respectively. The accuracy of the P-wave pickup is improved by 0.221, 0.01, and 0.029, respectively, and the S-wave pickup accuracy is improved by 0.233, 0.135, and 0.102, respectively. It is further applied in the actual project of the Shengli oilfield in Sichuan. The LAU-Net model can meet the needs of practical micro-seismic monitoring and early warning and provides a new way of thinking for accurate and fast on-time picking of micro-seismic P- and S-waves.

ObjectivePrevious studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair.DesignEosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf).ResultWe observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury.ConclusionTogether, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis.

Marine dissolved organic matter (DOM) is one of the largest dynamic pools of organic carbon in the global carbon cycle, yet DOM is still chemically poorly characterized. To better understand the origin, composition, and cycling of DOM in the China marginal sea, dissolved humic substances (DHS) were isolated from seawaters in two locations in the Southern Yellow Sea. The DHS were subdivided into fulvic acids (FAs), humic acids (HAs) and the XAD-4 fractions. Complementary analytical approaches were used to characterize the isolated DHS samples including stable carbon isotopic composition, Fourier transform infrared spectroscopy (FTIR), 13C cross polarization magic angle spinning (CP/MAS) nuclear magnetic resonance (NMR), and pyrolysis gas chromatography-mass spectrometry (Py-GC/MS). The results demonstrated that both DHS samples encountered the influences from marine source, indicating that algal and microbial-derived materials are the predominant precursors for the studied samples. The three fractions of DHS showed different properties. FAs presented more aromatic features, whereas HAs contained more aliphatic lipids and proteinaceous materials. The XAD-4 fractions were enriched in 13C and contained more carbohydrates but less aromatic compounds. The lower molecular weight and higher heteroatom content and number of carboxyl groups for the XAD-4 fractions may give them considerable geochemical significance for aspects of trace metal species, bioavailability of pollutants, mineral weathering and water acidification in marine environments.

Collaborative innovation within platform-based innovation ecosystems (PIEs) relies upon the creation of effective partnerships between platform owners and complementors. Despite this, limited research examines the mechanisms that drive collaborative innovation performance within them. To address this important gap, this study performs a fuzzy set qualitative comparative analysis (fsQCA) on 203 Chinese technological firms with the aim of uncovering the distinct configurations of relational elements that drive collaborative innovation within PIEs. The findings reveal three strategies that are equally effective at delivering collaborative innovation: super-modular complementarity in relational operation dependence, unique complementarity in relational operation dependence, and coherence in relational norms dependence. Theoretically, the study contributes to the literature on interorganizational relationships in PIEs and collaborative innovation, by delineating essential relational structures and linking these relational elements to collaborative innovation performance. From a practical standpoint, both platform owners and complementors can use these findings to strengthen their collaborative innovation performance within PIEs.

Background: Both behavioral therapies and pharmacotherapy are effective in smoking treatment. Combining both treatment approaches is recommended in clinical practice. Objective: We conducted a network meta-analysis to assess the comparative impact of various combined behavioral and pharmacological interventions on smoking cessation. Methods: We searched four electronic databases to identify randomized controlled trials evaluating combined interventions on smoking cessation. The risk of bias of the included studies was evaluated according to the Cochrane tool. Network meta-analysis was performed to calculate the relative risk (RR) and 95% confidence interval (CI) through R-3.4.0. The certainty of evidence was assessed using the grading of recommendation, assessment, development, and evaluation approach. Results: A total of 103 studies with 38118 participants were included. The results demonstrated that Varenicline + Cognitive behavioral therapy (CBT) is significantly more effective for smoking cessation than Bupropion + Counselling (RR = 0.39, 95%CI [0.22, 0.70]), Nicotine replacement therapy (NRT) + Counselling (RR = 0.37, 95% CI [0.22, 0.62]), NRT + Tailoring (RR = 0.49, 95% CI [0.29, 0.83]), and Varenicline + Counselling. Bupropion + CBT is more likely to achieve success relative to Bupropion + Counselling and NRT + Counselling. NRT + CBT is more likely to achieve success relative to Bupropion + Counselling, NRT + Counselling, and NRT + Tailoring. Conclusions: Among combined interventions for smoking cessation, Varenicline + CBT, NRT + CBT + Financial incentive, and Bupropion + CBT demonstrate the highest levels of success. CBT, FI, and Varenicline are potential intervention components that may possess greater effectiveness.

It is significant to develop novel difluoromethylation methods because of the important roles of difluoromethyl groups in the medicinal chemistry and material industries. Here, we developed a novel difluoromethylation–carboxylation and difluoromethylation–deuteration method triggered by a difluoromethyl radical generated by electroreduction of stable and easily available difluoromethyltriphenylphosphonium bromide. Various molecules containing difluoromethyl and carboxyl or deuterium groups can be synthesized through this method. The establishment of this method will provide an alternative to radical difluoromethylation reactions.

Combining targeting ability, imaging function, and photothermal/photodynamic therapy into a single agent is highly desired for cancer theranostics. Herein, we developed a one-for-all nanoplatform with N/P/S-codoped fluorescent carbon nanodots (CNDs) for tumor-specific phototheranostics. The CNDs were prepared via a one-pot hydrothermal process using cancer cells as sources of carbon, nitrogen, phosphorus, and sulfur. The obtained N/P/S-codoped CNDs exhibit wide light absorption in the range of 200–900 nm and excitation-dependent emission with high photostability. Importantly, the cancer cell-derived N/P/S-codoped CNDs have outstanding biocompatibility and naturally intrinsic targeted ability for cancer cells as well as dual photothermal/photodynamic effects under 795 nm laser irradiation. Moreover, the photothermal conversion efficiency and singlet oxygen (1O2) generation efficiency were calculated to be 52 and 34%, respectively. These exceptional properties enable CNDs to act as fine theranostic agents for targeted imaging and photothermal–photodynamic synergistic therapy within the NIR therapeutic window. The CNDs prepared in this work are promising for construction as a universal tumor phototheranostic platform.

Magnesium-mediated reductive carboxylation of p-QMs with CO2via an Umpolung strategy has been developed, which can be used for the preparation of various aryl acetic acids. This protocol featured high atom economy, mild conditions, and operational simplicity. The creation of this Umpolung carboxylation of p-QMs will unprecedentedly extend the application of p-QMs to nucleophilic reagents.

Reversibly interlocked polymer networks (RILNs) were recently developed via topological rearrangement of two cross-linked polymers containing orthogonal reversible covalent bonds. Glass transition temperature measurement and microscopic observation indicated that an interlocked structure throughout the entire material can suppress phase separation between subnetworks regardless of their miscibility, but there is no in-depth study yet about the localized distribution of the subnetworks in the RILNs. In the present work, solid-state nuclear magnetic resonance spectroscopy was employed to investigate the microstructures of specially designed but representative RILNs. It was found that the macromolecular chains from different subnetworks interlaced with each other on the molecular level, while the composition fluctuation still existed and the sample with equal contents of the two subnetworks proved to be the most uniform. The outcomes will not only help to further reveal authentic microstructures of RILNs, but also benefit in the designing of new RILNs.