miR-373-3p promotes aerobic glycolysis in colon cancer cells by targeting MFN2.

MicroRNAs (miRNAs) are implicated in the development of cancers and may serve as potential targets for therapy. However, the functions and underlying mechanisms of miRNAs in cancers are not well understood. This work aims to study the role of miR-373-3p in colon cancer cells. We find that the expression of miR-373-3p mimics promotes and the miR-373-3p inhibitor suppresses aerobic glycolysis and proliferation of colon cancer cells. Mechanistically, miR-373-3p inhibits the expression of MFN2, a gene that is known to suppress glycolysis, which leads to the activation of glycolysis and eventually the proliferation of cells. In a nude mouse tumor model, the expression of miR-373-3p in colon cancer cells promotes tumor growth by enhancing lactate formation, which is inhibited by the co-expression of MFN2 in the cells. Administration of the miR-373-3p antagomir blunts in vivo tumor growth by decreasing lactate production. In addition, in human colon cancers, the expression levels of miR-373-3p are increased, while those of MFN2 mRNA are decreased, and the increase of miR-373-3p is associated with the decrease of MFN2 mRNA. Our results reveal a previously unknown function and underlying mechanism of miR-373-3p in the regulation of glycolysis and proliferation in cancer cells and underscore the potential of targeting miR-373-3p for colon cancer treatment.

Potential mechanisms and effects of ultrasound treatment combined with pre- and post-addition of κ-carrageenan on the gelling properties and rheological behavior of myofibrillar proteins under low-salt condition.

This study investigated the effect of ultrasound (US) combined with pre- and post-addition of κ-carrageenan (KC) on the gelling properties, structural characteristics and rheological behavior of myofibrillar proteins (MP) under low-salt conditions. The results showed that US combined with either pre- or post-addition of KC rendered higher gel strength and water holding capacity (WHC) of MP gels than those treated with US alone and added with KC alone (P < 0.05). US combined with pre-addition of KC facilitated the binding between MP and KC, which enhanced the gel strength and WHC of the mixed MP gels and significantly improved the rheological behavior of MP. This was also confirmed by the highest surface hydrophobicity, disulfide bonds and ß-sheet content of the MP gels with US combined with pre-addition of KC. Moreover, microstructural results reflected a denser structure for the pre-addition of KC in combination with US. However, US combined with post-addition of KC resulted in limited MP unfolding and relatively weak hydrophobic interactions in the composite gels, which were less effective in improving the gel properties of the MP gels. This study provides potential strategies for enhancing the gelling properties of low-salt meat products via application of US and KC.

Epileptic seizures as an initial symptom for Sturge­Weber syndrome type III: A report of two cases.

Sturge-Weber syndrome (SWS) type III, a rare neurocutaneous disorder, presents diagnostic challenges due to its variable clinical manifestations. The present study focuses on enhancing the understanding of this syndrome by conducting a detailed analysis of two pediatric cases and providing a comprehensive review of the existing literature. The cases, managed at the Children's Hospital Affiliated to Shandong University (Jinan, China), highlight the diverse clinical presentations and successful management strategies for SWS type III. In the first case, a 4-year-old male patient exhibited paroxysmal hemiplegia, epileptic seizures and cerebral angiographic findings indicative of left pia mater and venous malformation. The second case involved a 2.5-year-old male patient presenting with recurrent seizures and angiographic findings on the right side. Both cases underscore the importance of considering epileptic seizures, acquired and transient hemiplegia and cognitive impairments in the diagnosis of SWS type III. The present study provides insights into the effective use of both pharmacological and surgical interventions, drawing from the positive outcomes observed in these cases. The findings emphasize the need for heightened awareness and a meticulous approach in diagnosing and treating SWS type III, contributing to the better management and prognosis of this condition.

Unveiling the therapeutic potential of IHMT-337 in glioma treatment: targeting the EZH2-SLC12A5 axis.

Glioma is the most common malignant tumor of the central nervous system, with EZH2 playing a crucial regulatory role. This study further explores the abnormal expression of EZH2 and its mechanisms in regulating glioma progression. Additionally, it was found that IHMT-337 can potentially be a therapeutic agent for glioma. The prognosis, expression, and localization of EZH2 were determined using bioinformatics, IHC staining, Western blot (WB) analysis, and immunofluorescence (IF) localization. The effects of EZH2 on cell function were assessed using CCK-8 assays, Transwell assays, and wound healing assays. Public databases and RT-qPCR were utilized to identify downstream targets. The mechanisms regulating these downstream targets were elucidated using MS-PCR and WB analysis. The efficacy of IHMT-337 was demonstrated through IC50 measurements, WB analysis, and RT-qPCR. The effects of IHMT-337 on glioma cells in vitro were evaluated using Transwell assays, EdU incorporation assays, and flow cytometry. The potential of IHMT-337 as a treatment for glioma was assessed using a blood-brain barrier (BBB) model and an orthotopic glioma model. Our research confirms significantly elevated EZH2 expression in gliomas, correlating with patient prognosis. EZH2 facilitates glioma proliferation, migration, and invasion alongside promoting SLC12A5 DNA methylation. By regulating SLC12A5 expression, EZH2 activates the WNK1-OSR1-NKCC1 pathway, enhancing its interaction with ERM to promote glioma migration. IHMT-337 targets EZH2 in vitro to inhibit WNK1 activation, thereby suppressing glioma cell migration. Additionally, it inhibits cell proliferation and arrests the cell cycle. IHMT-337 has the potential to cross the BBB and has successfully inhibited glioma progression in vivo. This study expands our understanding of the EZH2-SLC12A5 axis in gliomas, laying a new foundation for the clinical translation of IHMT-337 and offering new insights for precision glioma therapy.

Study of multifunctional anti-AD ligands: design, synthesis, X-ray crystal structure and biological evaluation of diosmetin derivatives.

The development of anti-AD drugs has attracted much attention as the number of AD patients is increasing year by year. Five diosmetin derivatives (1-5) were designed and synthesized by introducing carbamate groups. The crystal structure of 1 was analyzed by X-ray diffraction, which showed a large conjugated coplanar structure and might be favorable for the insertion into the Aß folding. Meanwhile, in vitro experiments were carried out to investigate the anticholinesterase activity, metal chelating property, antioxidant activity, and anti-Aß aggregation ability of 1-5. The results showed that 1-5 had good cholinesterase inhibitory activities. Compound 4 showed the highest inhibitory activities against butyrylcholinesterase (IC50 = 0.0760 µM). Further kinetic experiments and molecular docking studies showed that 4 could bind well to butyrylcholinesterase. The molecular dynamics simulations also signified that compared with diosmetin, 4 could reduce the flexibility of the butyrylcholinesterase protein skeleton to a greater extent, and thus had a better inhibitory effect. In addition, 1-5 could selectively chelate copper ions and all of them had good antioxidant activity as well as anti-Aß aggregation ability. Among them, 4 had the strongest activity to inhibit Cu2+-induced Aß aggregation (51.09%) and had low cytotoxicity. In addition, in vivo ROS activity assay (Caenorhabditis elegans) showed that 4 had the ability to scavenge ROS. Besides, the in vivo Aß aggregation assay showed that 4 could reduce Aß aggregation. In conclusion, 4 has the potential to be developed into a multifunctional anti-AD drug.

5,7,4'-Trimethoxyflavone triggers cancer cell PD-L1 ubiquitin-proteasome degradation and facilitates antitumor immunity by targeting HRD1.

Targeting the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway has been identified as a successful approach for tumor immunotherapy. Here, we identified that the small molecule 5,7,4'-trimethoxyflavone (TF) from Kaempferia parviflora Wall reduces PD-L1 expression in colorectal cancer cells and enhances the killing of tumor cells by T cells. Mechanistically, TF targets and stabilizes the ubiquitin ligase HMG-CoA reductase degradation protein 1 (HRD1), thereby increasing the ubiquitination of PD-L1 and promoting its degradation through the proteasome pathway. In mouse MC38 xenograft tumors, TF can activate tumor-infiltrating T-cell immunity and reduce the immunosuppressive infiltration of myeloid-derived suppressor cells and regulatory T cells, thus exerting antitumor effects. Moreover, TF synergistically exerts antitumor immunity with CTLA-4 antibody. This study provides new insights into the antitumor mechanism of TF and suggests that it may be a promising small molecule immune checkpoint modulator for cancer therapy.

Genome-wide expression quantitative trait locus analysis reveals silk-preferential gene regulatory network in maize.

Silk of maize (Zea mays L.) contains diverse metabolites with complicated structures and functions, making it a great challenge to explore the mechanisms of metabolic regulation. Genome-wide identification of silk-preferential genes and investigation of their expression regulation provide an opportunity to reveal the regulatory networks of metabolism. Here, we applied the expression quantitative trait locus (eQTL) mapping on a maize natural population to explore the regulation of gene expression in unpollinated silk of maize. We obtained 3,985 silk-preferential genes that were specifically or preferentially expressed in silk using our population. Silk-preferential genes showed more obvious expression variations compared with broadly expressed genes that were ubiquitously expressed in most tissues. We found that trans-eQTL regulation played a more important role for silk-preferential genes compared to the broadly expressed genes. The relationship between 38 transcription factors and 85 target genes, including silk-preferential genes, were detected. Finally, we constructed a transcriptional regulatory network around the silk-preferential gene Bx10, which was proposed to be associated with response to abiotic stress and biotic stress. Taken together, this study deepened our understanding of transcriptome variation in maize silk and the expression regulation of silk-preferential genes, enhancing the investigation of regulatory networks on metabolic pathways.

Mechanism of heterochromatin remodeling revealed by the DDM1 bound nucleosome structures.

The SWI/SNF2 chromatin remodeling factor decreased DNA methylation 1 (DDM1) is essential for the silencing of transposable elements (TEs) in both euchromatic and heterochromatic regions. Here, we determined the cryo-EM structures of DDM1-nucleosomeH2A and DDM1-nucleosomeH2A.W complexes at near-atomic resolution in the presence of the ATP analog ADP-BeFx. The structures show that nucleosomal DNA is unwrapped more on the surface of the histone octamer containing histone H2A than that containing histone H2A.W. DDM1 embraces one DNA gyre of the nucleosome and interacts with the N-terminal tails of histone H4. Although we did not observe DDM1-H2A.W interactions in our structures, the results of the pull-down experiments suggest a direct interaction between DDM1 and the core region of histone H2A.W. Our work provides mechanistic insights into the heterochromatin remodeling process driven by DDM1 in plants.

[Analysis of 28 day-mortality risk factors in sepsis patients and construction and validation of predictive model].

OBJECTIVE: To construct and validate a nomogram model for predicting the risk of 28-day mortality in sepsis patients. METHODS: A retrospective cohort study was conducted. 281 sepsis patients admitted to the department of intensive care unit (ICU) of the 940th Hospital of the Joint Logistics Support Force of PLA from January 2017 to December 2022 were selected as the research subjects. The patients were divided into a training set (197 cases) and a validation set (84 cases) according to a 7 : 3 ratio. The general information, clinical treatment measures and laboratory examination results within 24 hours after admission to ICU were collected. Patients were divided into survival group and death group based on 28-day outcomes. The differences in various data were compared between the two groups. The optimal predictive variables were selected using Lasso regression, and univariate and multivariate Logistic regression analyses were performed to identify factors influencing the mortality of sepsis patients and to establish a nomogram model. Receiver operator characteristic curve (ROC curve), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to evaluate the nomogram model. RESULTS: Out of 281 cases of sepsis, 82 cases died with a mortality of 29.18%. The number of patients who died in the training and validation sets was 54 and 28, with a mortality of 27.41% and 33.33% respectively. Lasso regression, univariate and multivariate Logistic regression analysis screened for 5 independent predictors associated with 28-day mortality. There were use of vasoactive drugs [odds ratio (OR) = 5.924, 95% confidence interval (95%CI) was 1.244-44.571, P = 0.043], acute physiology and chronic health evaluation II (APACHE II: OR = 1.051, 95%CI was 1.000-1.107, P = 0.050), combined with multiple organ dysfunction syndrome (MODS: OR = 17.298, 95%CI was 5.517-76.985, P < 0.001), neutrophil count (NEU: OR = 0.934, 95%CI was 0.879-0.988, P = 0.022) and oxygenation index (PaO2/FiO2: OR = 0.994, 95%CI was 0.988-0.998, P = 0.017). A nomogram model was constructed using the independent predictive factors mentioned above, ROC curve analysis showed that the AUC of the nomogram model was 0.899 (95%CI was 0.856-0.943) and 0.909 (95%CI was 0.845-0.972) for the training and validation sets respectively. The C-index was 0.900 and 0.920 for the training and validation sets respectively, with good discrimination. The Hosmer-Lemeshoe tests both showed P > 0.05, indicating good calibration. Both DCA and CIC plots demonstrate the model's good clinical utility. CONCLUSIONS: The use of vasoactive, APACHE II score, comorbid MODS, NEU and PaO2/FiO2 are independent risk factors for 28-day mortality in patients with sepsis. The nomogram model based on these 5 indicators has a good predictive ability for the occurrence of mortality in sepsis patients.

Insect herbivory on woody broadleaf seedlings along a subtropical elevational gradient supports the resource concentration hypothesis.

PREMISE: Theories of plant-herbivore interactions hold that seedlings are more vulnerable to herbivory in warmer and more stable climates at lower elevations. Hypotheses of plant apparency, resource concentration, and resource availability have been proposed to explain variability in leaf herbivory. However, seasonal differences in the effects of these hypotheses on leaf herbivory on seedlings remain unclear. METHODS: We evaluated the three herbivory hypotheses by comparing the percentage and frequency of leaf herbivory in understory broadleaf seedlings in a subtropical forest in May (spring) and October (autumn) along an elevational gradient (290-1370 m a.s.l.). In total, we measured 2890 leaves across 696 seedlings belonging to 95 species and used beta regressions to test the effects of plant apparency (e.g., leaf area, seedling height), resource concentration (e.g., plant species diversity), and resource availability (e.g., canopy openness, soil available N and P) on leaf herbivory. RESULTS: Seedlings exhibited unimodal patterns of leaf herbivory along elevation, with drivers of leaf herbivory varying by the month. Variation in the frequency of leaf herbivory was best explained by the resource concentration hypothesis (e.g., plant species diversity) in both months, and herbivory was lower on seedlings in sites with higher plant diversity. Plant apparency hypothesis (e.g., leaf area, seedling height) was weakly supported only in spring, and the evidence for resource availability hypothesis (e.g., canopy openness, soil nutrients) was mixed. CONCLUSIONS: This study supports the resource concentration hypothesis and reveals the importance of seasonal difference on understanding leaf herbivory patterns and the drivers of plant diversity in subtropical forests.

Progress and application of lung-on-a-chip for lung cancer.

Lung cancer is a malignant tumour with the highest incidence and mortality worldwide. Clinically effective therapy strategies are underutilized owing to the lack of efficient models for evaluating drug response. One of the main reasons for failure of anticancer drug therapy is development of drug resistance. Anticancer drugs face severe challenges such as poor biodistribution, restricted solubility, inadequate absorption, and drug accumulation. In recent years, "organ-on-a-chip" platforms, which can directly regulate the microenvironment of biomechanics, biochemistry and pathophysiology, have been developed rapidly and have shown great potential in clinical drug research. Lung-on-a-chip (LOC) is a new 3D model of bionic lungs with physiological functions created by micromachining technology on microfluidic chips. This approach may be able to partially replace animal and 2D cell culture models. To overcome drug resistance, LOC realizes personalized prediction of drug response by simulating the lung-related microenvironment in vitro, significantly enhancing therapeutic effectiveness, bioavailability, and pharmacokinetics while minimizing side effects. In this review, we present an overview of recent advances in the preparation of LOC and contrast it with earlier in vitro models. Finally, we describe recent advances in LOC. The combination of this technology with nanomedicine will provide an accurate and reliable treatment for preclinical evaluation.

Constraint-Aware Learning for Fractional Flow Reserve Pullback Curve Estimation from Invasive Coronary Imaging.

Estimation of the fractional flow reserve (FFR) pullback curve from invasive coronary imaging is important for the intraoperative guidance of coronary intervention. Machine/deep learning has been proven effective in FFR pullback curve estimation. However, the existing methods suffer from inadequate incorporation of intrinsic geometry associations and physics knowledge. In this paper, we propose a constraint-aware learning framework to improve the estimation of the FFR pullback curve from invasive coronary imaging. It incorporates both geometrical and physical constraints to approximate the relationships between the geometric structure and FFR values along the coronary artery centerline. Our method also leverages the power of synthetic data in model training to reduce the collection costs of clinical data. Moreover, to bridge the domain gap between synthetic and real data distributions when testing on real-world imaging data, we also employ a diffusion-driven test-time data adaptation method that preserves the knowledge learned in synthetic data. Specifically, this method learns a diffusion model of the synthetic data distribution and then projects real data to the synthetic data distribution at test time. Extensive experimental studies on a synthetic dataset and a real-world dataset of 382 patients covering three imaging modalities have shown the better performance of our method for FFR estimation of stenotic coronary arteries, compared with other machine/deep learning-based FFR estimation models and computational fluid dynamics-based model. The results also provide high agreement and correlation between the FFR predictions of our method and the invasively measured FFR values. The plausibility of FFR predictions along the coronary artery centerline is also validated.

Equivalent consumption minimization strategy based on global optimization of equivalent factor for hybrid tractor.

Due to the increase in emission requirements for non-road vehicles in many countries and the reduction of agricultural personnel, tractors are developing towards high horsepower and electrification. According to the working conditions of high-horsepower tractors, a hydromechanical continuously variable transmission (HMCVT) is designed for hybrid tractors. Taking a tractor equipped with this transmission as the research object, an equivalent factor global optimization model was established and a genetic algorithm was used to optimize the equivalent factor S offline to obtain the optimal equivalent factor of the tractor under different operating mileage and the initial state of charge (SOC) of battery. By using the optimized equivalent factor, the tractor can be in the charge depleting (CD) mode for a longer time on the premise of making full use of the energy in the battery, so as to improve the auxiliary ability of the motor in the whole operation cycle to reduce the fuel consumption of the tractor. The effectiveness of the control strategy is verified by MATLAB/Simulink and hardware in the loop (HIL) tests, and the fuel economy of tractors is improved by 2.939% and 3.909% respectively in the two tests.

Ozone enhances the efficacy of radiation therapy in esophageal cancer.

Radioresistance is increasingly developed in esophageal cancer. Increasing radiation sensitivity can reduce the mortality of esophageal cancer. To investigate the effect and mechanism of ozone on the radiotherapy sensitization of esophageal carcinoma. KYSE150 cells were xenografted subcutaneously into nude mice and irradiated with 8 Gy radiation according to different subgroups (sham, radiation, ozone and radiation+ozone group (n = 10 per group)). Half of the mice were used to determine the body weight, tumor size and tumor weight. Half of the mice were used to collect peripheral blood. The serum was centrifuged to detect circulating cell-free DNA (cf-DNA), interleukin-6 (IL-6), interferon-γ (IFN-γ), myeloperoxidase (MPO)-DNA complexes, tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9) and hypoxia-inducible factor-1α (HIF-1α) using commercial kits. The levels of phosphorylation AMP-activated protein kinase (p-AMPK) and scavenger receptor-A (SR-A) were measured by immunocytochemistry and Western blotting in the tumor tissues of mice. Ozone alone or combined with radiation therapy significantly reduced the body weight, tumor volume and tumor weight of esophageal cancer compared to the sham group. The ELISA results showed that the levels of cf-DNA, IFN-γ, MPO-DNA complexes, TNF-α, IL-6, HIF-1α and MMP-9 in the peripheral blood of mice treated with ozone combined with radiation were significantly lower compared with the radiation group. Ozone, synergistically with radiation, significantly increased the protein expression of p-AMPK and SR-A. Ozone may increase the radiosensitivity of esophageal cancer by inhibiting neutrophil extracellular traps.

Pioneering nanomedicine in orthopedic treatment care: a review of current research and practices.

A developing use of nanotechnology in medicine involves using nanoparticles to administer drugs, genes, biologicals, or other materials to targeted cell types, such as cancer cells. In healthcare, nanotechnology has brought about revolutionary changes in the treatment of various medical and surgical conditions, including in orthopedic. Its clinical applications in surgery range from developing surgical instruments and suture materials to enhancing imaging techniques, targeted drug delivery, visualization methods, and wound healing procedures. Notably, nanotechnology plays a significant role in preventing, diagnosing, and treating orthopedic disorders, which is crucial for patients' functional rehabilitation. The integration of nanotechnology improves standards of patient care, fuels research endeavors, facilitates clinical trials, and eventually improves the patient's quality of life. Looking ahead, nanotechnology holds promise for achieving sustained success in numerous surgical disciplines, including orthopedic surgery, in the years to come. This review aims to focus on the application of nanotechnology in orthopedic surgery, highlighting the recent development and future perspective to bridge the bridge for clinical translation.

The sublethal concentration of acetamiprid suppresses the population growth of 2 species of wheat aphids, Sitobion miscanthi and Schizaphis graminum (Hemiptera: Aphididae).

Sitobion miscanthi and Schizaphis graminum (Rondani) are the 2 main aphid species that occur simultaneously, causing significant loss to wheat production. Acetamiprid has been used to control a variety of pests, including aphids. In this study, the sublethal effect of acetamiprid on S. miscanthi and S. graminum was evaluated using life-table analyses. The results showed that acetamiprid has a high toxicity to S. miscanthi and S. graminum with a LC50 of 1.90 and 3.58 mg/L at 24 h, respectively. The adult longevity and fecundity of S. miscanthi and S. graminum F0 generation were significantly reduced after being exposed to a sublethal concentration of acetamiprid. Additionally, the sublethal concentration of acetamiprid had negative transgenerational effects on S. miscanthi and S. graminum, which showed a significant decrease in fecundity and population life-table parameters involving age-stage-specific survival rate (sxj), age-specific survival rate (lx), and intrinsic rate of increase (r). Furthermore, the population projections showed that the total population size of S. miscanthi and S. graminum was significantly lower in the aphid group exposed to sublethal concentration of acetamiprid compared to the control group. These results suggest that sublethal concentration of acetamiprid suppresses the population growth of S. miscanthi and S. graminum. This finding is beneficial to the control of wheat aphids, and is important to fully understand the role of acetamiprid in integrated pest management.

Effect of microwave vacuum drying time on the quality profiles, microstructures and in vitro digestibility of pork chip snacks.

In present study, the quality profiles, microstructures and in vitro digestibility of pork chip snacks (PCS) prepared by microwave vacuum drying (MVD) under different drying times (20, 21, 22, 23, and 24 min) were investigated. The results revealed significant decreases in the moisture content and L*-value of PCS, while the protein/ash contents, a*-value, and b*-value of PCS markedly increased with prolonged MVD time (P < 0.05). Additionally, as MVD time extended from 20 to 24 min, the textural characteristics of PCS, particularly brittleness and crunchiness, initially increased and then gradually decreased (P < 0.05). Scanning electron microscopy (SEM) images showed that a moderate MVD time (22 min) resulted in the formation of larger pores in PCS, enhancing brittleness and crunchiness. However, excessive MVD time (24 min) led to the melting of these pores, subsequently reducing the brittleness and crunchiness of PCS. Furthermore, in vitro protein digestibility of PCS gradually decreased with increasing MVD time, primarily attributed to increased protein aggregation, as indicated by changes in sulfhydryl contents. In summary, our findings highlight that PCS subjected to 22 min of MVD exhibited the highest overall acceptability. This study provides a novel strategy for the application of MVD in the processing of meat snacks.

Cerium oxide nanoparticles in wound care: a review of mechanisms and therapeutic applications.

Skin wound healing is a complex and tightly regulated process. The frequent occurrence and reoccurrence of acute and chronic wounds cause significant skin damage to patients and impose socioeconomic burdens. Therefore, there is an urgent requirement to promote interdisciplinary development in the fields of material science and medicine to investigate novel mechanisms for wound healing. Cerium oxide nanoparticles (CeO2 NPs) are a type of nanomaterials that possess distinct properties and have broad application prospects. They are recognized for their capabilities in enhancing wound closure, minimizing scarring, mitigating inflammation, and exerting antibacterial effects, which has led to their prominence in wound care research. In this paper, the distinctive physicochemical properties of CeO2 NPs and their most recent synthesis approaches are discussed. It further investigates the therapeutic mechanisms of CeO2 NPs in the process of wound healing. Following that, this review critically examines previous studies focusing on the effects of CeO2 NPs on wound healing. Finally, it suggests the potential application of cerium oxide as an innovative nanomaterial in diverse fields and discusses its prospects for future advancements.