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Abstract. Background:. We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse hearts. Herein, we sought to identify the effect of magnesium lithospermate B (MLB) on hiPSC-CMs during myocardial repair using a myocardial infarction (MI) mouse model. Methods:. In C57BL/6 mice, MI was surgically induced by ligating the left anterior descending coronary artery. The mice were randomly divided into five groups (n = 10 per group); a MI group (treated with phosphate-buffered saline only), a hiPSC-CMs group, a MLB group, a hiPSC-CMs + MLB group, and a Sham operation group. Cardiac function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after surgery. To identify the associated mechanism, nuclear factor (NF)-κB p65 and intercellular cell adhesion molecule-1 (ICAM1) signals, cell adhesion ability, generation of reactive oxygen species, and rates of apoptosis were detected in human umbilical vein endothelial cells (HUVECs) and hiPSC-CMs. Results:. After 4 weeks of transplantation, the number of cells that engrafted in the hiPSC-CMs + MLB group was about five times higher than those in the hiPSC-CMs group. Additionally, MLB treatment significantly reduced tohoku hospital pediatrics-1 (THP-1) cell adhesion, ICAM1 expression, NF-κB nuclear translocation, reactive oxygen species production, NF-κB p65 phosphorylation, and cell apoptosis in HUVECs cultured under hypoxia. Similarly, treatment with MLB significantly inhibited the apoptosis of hiPSC-CMs via enhancing signal transducer and activator of transcription 3 (STAT3) phosphorylation and B-cell lymphoma-2 (BCL2) expression, promoting STAT3 nuclear translocation, and downregulating BCL2-Associated X, dual specificity phosphatase 2 (DUSP2), and cleaved-caspase-3 expression under hypoxia. Furthermore, MLB significantly suppressed the production of malondialdehyde and lactate dehydrogenase and the reduction in glutathione content induced by hypoxia in both HUVECs and hiPSC-CMs in vitro. Conclusions:. MLB significantly enhanced the potential of hiPSC-CMs in repairing injured myocardium by improving endothelial cell function via the NF-κB/ICAM1 pathway and inhibiting hiPSC-CMs apoptosis via the DUSP2/STAT3 pathway.

The influence of thermal damage on macroscopic and microscopic characteristics of different rocks has received much attention in the field of rock engineering. When the rocks are subjected to thermal treatment, the change of macroscopic characteristics and evolution of micro-structure would be induced, ultimately resulting in different degrees of thermal damage in rocks. To better understand the thermal damage mechanism of different rocks and its effect on the rock performance, this study reviews a large number of test results of rock specimens experiencing heating and cooling treatment in the laboratory. Firstly, the variations of macroscopic behaviors, including physical parameters, mechanical parameters, thermal conductivity and permeability, are examined. The variations of mechanical parameters with thermal treatment variables (i.e. temperature or the number of thermal cycles) are divided into four types. Secondly, several measuring methods for microstructure, such as polarizing microscopy, fluorescent method, scanning electron microscopy (SEM), X-ray computerized tomography (CT), acoustic emission (AE) and ultrasonic technique, are introduced. Furthermore, the effect of thermal damage on the mechanical parameters of rocks in response to different thermal treatments, involving temperature magnitude, cooling method and thermal cycle, are discussed. Finally, the limitations and prospects for the research of rock thermal damage are proposed.

Abstract Background Long-chain acyl-coenzyme A synthetase (LACS) is a type of acylating enzyme with AMP-binding, playing an important role in the growth, development, and stress response processes of plants. Results The research team identified different numbers of LACS in four cotton species (Gossypium hirsutum, Gossypium barbadense, Gossypium raimondii, and Gossypium arboreum). By analyzing the structure and evolutionary characteristics of the LACS, the GhLACS were divided into six subgroups, and a chromosome distribution map of the family members was drawn, providing a basis for further research classification and positioning. Promoter cis-acting element analysis showed that most GhLACS contain plant hormones (GA, MeJA) or non-biological stress-related cis-elements. The expression patterns of GhLACS under salt stress treatment were analyzed, and the results showed that GhLACS may significantly participate in salt stress response through different mechanisms. The research team selected 12 GhLACSs responsive to salt stress for tissue expression analysis and found that these genes are expressed in different tissues. Conclusions There is a certain diversity of LACS among different cotton species. Analysis of promoter cis-acting elements suggests that GhLACS may be involved in regulating plant growth, development and stress response processes. GhLACS25 was selected for in-depth study, which confirmed its significant role in salt stress response through virus-induced gene silencing (VIGS) and induced expression in yeast cells.

Abstract Background Vasculopathy is the most common complication of diabetes. Endothelial cells located in the innermost layer of blood vessels are constantly affected by blood flow or vascular components; thus, their mechanosensitivity plays an important role in mediating vascular regulation. Endothelial damage, one of the main causes of hyperglycemic vascular complications, has been extensively studied. However, the role of mechanosensitive signaling in hyperglycemic endothelial damage remains unclear. Methods Vascular endothelial-specific Piezo1 knockout mice were generated to investigate the effects of Piezo1 on Streptozotocin-induced hyperglycemia and vascular endothelial injury. In vitro activation or knockdown of Piezo1 was performed to evaluate the effects on the proliferation, migration, and tubular function of human umbilical vein endothelial cells in high glucose. Reactive oxygen species production, mitochondrial membrane potential alternations, and oxidative stress-related products were used to assess the extent of oxidative stress damage caused by Piezo1 activation. Results Our study found that in VECreERT2;Piezo1flox/flox mice with Piezo1 conditional knockout in vascular endothelial cells, Piezo1 deficiency alleviated streptozotocin-induced hyperglycemia with reduced apoptosis and abscission of thoracic aortic endothelial cells, and decreased the inflammatory response of aortic tissue caused by high glucose. Moreover, the knockout of Piezo1 showed a thinner thoracic aortic wall, reduced tunica media damage, and increased endothelial nitric oxide synthase expression in transgenic mice, indicating the relief of endothelial damage caused by hyperglycemia. We also showed that Piezo1 activation aggravated oxidative stress injury and resulted in severe dysfunction through the Ca2+-induced CaMKII-Nrf2 axis in human umbilical vein endothelial cells. In Piezo1 conditional knockout mice, Piezo1 deficiency partially restored superoxide dismutase activity and reduced malondialdehyde content in the thoracic aorta. Mechanistically, Piezo1 deficiency decreased CaMKII phosphorylation and restored the expression of Nrf2 and its downstream molecules HO-1 and NQO1. Conclusion In summary, our study revealed that Piezo1 is involved in high glucose-induced oxidative stress injury and aggravated endothelial dysfunction, which have great significance for alleviating endothelial damage caused by hyperglycemia.

20CrMnTi steel is widely used in the gear manufacturing field of engineering machinery. The addition of Ti element to steel can effectively improve its low-temperature impact toughness and enhance its mechanical properties. However, during the smelting process of 20CrMnTi, large-sized TiN inclusions are inevitably formed in the steel, which affects its service performance improvement. This paper focuses on the directional modification behaviors of TiN inclusions in 20CrMnTi gear steel by rare earth Ce under deoxygenation conditions of Si–Ca–Ba alloy. The results show that under the deoxygenation conditions of Si–Ca–Ba alone, there are composite inclusions in 20CrMnTi steel with CaAl12O19 as the core and TiN wrapped around the periphery, all of which have sizes greater than 2 μm. This type of inclusion is square or diamond shaped, and the addition of Si–Ca–Ba deoxygenation alone has poor TiN modification effect on gear steel 20CrMnTi. Adding Ce element can effectively improve the nucleation core of inclusions. The CeAlO3–TiN and (CaAl12O19–Ba–Ce)–TiN composite inclusions are formed, and the TiN inclusions are modified in terms of morphology and size. The average size of inclusions decreases from 4.1 to 3.0 μm, which prevented the excessive growth of pure TiN inclusions to some extent.

Abstract Metallurgical dust and sludge are solid waste resources with recycling value. In recent years, rotary hearth furnace has become the most important means to treat metallurgical dust and sludge because of its wide range of raw materials and strong treatment capacity. In this study blast furnace ash and converter sludge were selected as the research objects, and high-quality metallized pellets were prepared based on the rotary hearth furnace process. The strength changed of pellets, the reduction process of iron oxides and the removal process of zinc during the roasting of pellets in rotary hearth furnace were studied. To explore the reasonable roasting condition for preparing metallized pellets in rotary hearth furnace. The optimum roasting temperature of the pellets was 1250℃ and the roasting time was 25 min. The compressive strength, metallization rate and dezincification rate of metallized pellets reached 1361N, 97.44% and 95.67%, respectively. The efficient resource utilization of various metallurgical dust and sludge is realized.

20CrMnTi gear steel has high low-temperature impact toughness and is widely used in the manufacturing of engineering machinery such as automotive transmission gears. The sizes and distributions of TiN inclusions have a significant impact on the service performances of 20CrMnTi gear steel. Controlling the growth behaviors and size distributions of TiN inclusions are the foundation for stable, high-quality, and efficient production of 20CrMnTi gear steel. This paper uses experimental and computational methods to study the effects of different ratios of Al–Ce composite deoxidizers on the modification behaviors of TiN inclusions in 20CrMnTi steel. The results show that the TiN inclusions in 20CrMnTi steel without Al–Ce composite deoxidizer are square in shape, with a size of approximately 4 μm. After Al–Ce composite deoxidation, a composite phase inclusion is formed in the steel, which has contracted edges and corners. The center is the nucleation core composed of elements such as Ce, Al, O, etc. The elements of Ti and N are wrapped around the periphery of the composite inclusion, reducing its size to 2 μm. When the ratio of Al and Ce in the Al–Ce composite deoxidizer is 7:3, the number of TiN inclusions in steel is the highest, accounting for 51.7% of the total amount of titanium inclusions. The average diameter of inclusions in the modified steel decreases to 2.4 μm. When the ratio of Al and Ce elements is 8:2 and 7:3, the final deoxygenation product is CeAlO3, which is more conducive to the modification of TiN inclusions in 20CrMnTi steel.

Precise positioning is a never‐ending goal in both fundamental science and technology. Recent decades of advancements in high‐precision position detection have predominantly relied on photoelectric effects for light detection in semiconductors. Herein, a different approach is proposed: The thermoelectric‐based position‐sensitive detector (T‐PSD) concept is designed to detect single heat spots arising from various energy sources, including electromagnetic radiation, electrons, and macroscopic mechanical heat. The T‐PSD concept is initially derived mathematically from the fundamental principles of heat conduction and the Seebeck effect. Subsequently, it is proved by finite element simulation in both 1D and 2D configurations. Following this theoretical groundwork, T‐PSD prototypes are fabricated and subjected to positional detection using various stimuli such as CO2 laser beam, hot soldering tip, and electron beam. In the prototypes, structured aluminum‐doped zinc oxide thermoelectric thin films, prepared via atomic layer deposition, are outfitted with voltage probes, enabling the measurement of thermoelectric voltages as a function of position and the intensity or temperature of the heat spot. Furthermore, practical decoding strategies are introduced to infer the position from the measured signals. The T‐PSD in this article showcases considerable promise in high‐precision position detection such as (quasi‐)particle tracking and precision machinery, offering an alternative concept in PSD design.

The world has been experiencing huge upheavals since the COVID-19 crises. Conflicts caused by opposing ideologies, economic-political agendas and realities are rampant within or across borders. Such unsteady circumstances contribute to shifting how Transnational Education (TNE) occurs worldwide, as well as the scientific, epistemic and educational discourses that go with it. Anchored within critical interculturality, this paper explores the concept of ‘inter-ideologicality’. The study looks at short-term online international student mobility to demonstrate how students from China and Finland navigate and negotiate ideologies around the concept of culture in intercultural research and education. The study also employs Wang Chong’s perspectives on criticality to identify emerging ideologies in the co-construction of criticality in students’ online cooperation. Findings reveal that (1) two ideological orientations, nation-oriented and society-oriented, developed during discussions about culture; (2) Finnish students used a specific form of reasoning to contradict Chinese students’ thoughts about Finland by means of criticality towards the nation-oriented ideology; (3) Chinese and Finnish students employed questioning and challenging to help each other be aware of something left unsaid about the status of women in their societies within the society-oriented ideology. The study represents an important meta-approach to intercultural communication education within internationalization of Higher Education, aimed at supporting mobile students to reflect critically on the scientific and educational notion of interculturality rather than providing them with ready-made recipes as to how to communicate and behave interculturally.

Abstract Mollisols are highly fertile soils and function as significant carbon reservoirs. However, determining their ages and formation processes is challenging due to extensive pedoturbation, which undermines conventional dating methods. Here, we employed luminescence, a light‐sensitive property of minerals widely used in geological dating, to investigate and quantify soil mixing. We analyzed over 2,400 luminescence ages of individual K‐feldspar grains from a Mollisol profile in Northeast China, and for the first time, we were able to determine the intensity of pedoturbation in the Mollisol profile over the past 50,000 years. The results showed that the current pedoturbation can penetrate to a depth of approximately 80 cm, with the intensity decreasing with depth. By identifying a significant intensification in historical pedoturbation, we inferred that the paleoenvironment might be suitable for the formation of Mollisols 16,400 years before present.

Summary: Previous studies have indicated the neuroprotective effect of olfactory mucosa mesenchymal stem cells (OM-MSCs) on brain injury. Intracerebral hemorrhage (ICH) models were established in rats by injecting autologous blood. SENP1 expression was enhanced in neurons but decreased in astrocytes compared to that in OM-MSCs. Overexpression of SENP1 promoted the proliferation and neuronal differentiation, while inhibiting the astrocytic differentiation of OM-MSCs. Conversely, its knockdown had the opposite effect. Moreover, OM-MSCs reduced neurological dysfunction in rats after ICH, and the neuroprotective effect of OM-MSCs could be further enhanced by SENP1 overexpression. In addition, SENP1 promoted mitophagy, which might be related to SENP1-mediated OPTN deSUMOylation. Furthermore, SENP1 promoted neuronal differentiation of OM-MSCs through mitophagy mediated by OPTN. Similar to SENP1, OPTN transfection further enhanced the remission effect of OM-MSC on ICH rats. SENP1 promoted neuronal differentiation of OM-MSCs through OPTN-mediated mitophagy to improve neurological deficits in ICH rats.

Abstract Purpose This study was aimed to identify the risk factors that influence the mortality risk in patients with acute aortic dissection (AAD) within one year after discharge, and aimed to construct a predictive model for assessing mortality risk. Methods The study involved 320 adult patients obtained from the Medical Information Mart for Intensive Care (MIMIC) database. Logistic regression analysis was conducted to identify potential risk factors associated with mortality in AAD patients within one year after discharge and to develop a predictive model. The performance of the predictive model was assessed using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). To further validate the findings, patient data from the First Affiliated Hospital of Guangxi Medical University (157 patients) were analyzed. Results Univariate and multivariate logistic regression analyses revealed that gender, length of hospital stay, highest blood urea nitrogen (BUN_max), use of adrenaline, and use of amiodarone were significant risk factors for mortality within one year after discharge (p

Objective: The aim of this study was to explore the effects of Babao dan (BBD), a traditional Chinese medicine, on gastric cancer (GC) progression in vivo. Materials and Methods: A subcutaneous xenograft mouse model of GC was established using MGC80-3 cells. The terminal deoxynucleotidyl transferase-mediated dUTP: 2'-deoxyuridine 5'-triphosphate -biotin nick-end labeling method was adopted to detect cell apoptosis in vivo. The expression levels of proteins associated with proliferation, apoptosis, and angiogenesis were measured by immunohistochemical staining or western blotting (WB). The activation and protein levels of p-c-Jun N-terminal kinase (JNK), p-p38, p-extracellular-regulated kinase 1/2, p-nuclear factor-κB (NF-κB), and p-STAT3 were examined by Bio-plex and WB. Results: BBD significantly inhibited tumor growth in GC mouse models with no adverse effect on body weight or organ function. It was also found that BBD significantly suppressed the proliferation of GC tumor cells, induced the apoptosis of tumor cells, and inhibited angiogenesis through inactivating with mitogen-activated protein kinase, NF-κB, and STAT3 pathways. Conclusions: BBD exerts suppressive effects on GC tumor growth by regulating multiple pathways in vivo, which may provide a novel treatment option for GC therapy.

Chlorophyll-a is an important parameter that is used to measure the water quality, and its concentrations indicate the degree of eutrophication. Taking the waters of Chaohu Lake as the research area, four remote sensing inversion models of the chlorophyll-a concentrations were constructed based on GF-1 WFV images using empirical and semiempirical/semianalytical methods. The optimal model was selected by evaluating the model validation accuracies, and this model was used to invert the spatial distributions of the chlorophyll-a concentrations in the waters of Chaohu Lake from May to July 2017. The results show that the NDCI model is the most suitable for inverting chlorophyll-a concentrations in the waters of Chaohu Lake based on GF-1 WFV images. This model has the highest validation accuracy, with a determination coefficient of 0.933, a Root mean square error of $2.85 ~\mu \text{g}$ /L and a mean absolute percentage error of 19.69%. The spatial distributions of the chlorophyll-a concentrations in the waters of Chaohu Lake from May to July 2017 all showed decreasing trends from Western Half Lake to Eastern Half Lake, the areas of higher chlorophyll-a concentrations in May and June were mainly concentrated in the northern waters of Western Half Lake, and the area with the highest chlorophyll-a concentrations in July was located in the northwestern waters of Middle Half Lake. The mean chlorophyll-a concentration in the waters of Chaohu Lake from May to July 2017 was $12.5 ~\mu \text{g}$ /L, which indicated slight eutrophication.

In light of the steel industry's rapid advancements, the availability of high-quality mineral resources is diminishing. Therefore, the recovery of iron from BOF slag is of great significance to the sustainability development. Considering the compositional characteristics of BOF slag, the transformation of the iron-containing phase into (Mn,Mg)yFe3-yO4 is the key step. Thus, a novel process for recovering iron resources by synergistic treatment of blast furnace slag (BFS) and BOF slag was proposed. This research employed FactSage thermodynamic simulation, XRD, SEM-EDS, XPS, and EPMA to analysis the impact of BFS addition (10–50 %), cooling methods (from water-cooling to furnace-cooling), and temperature (1400–1600 °C) on phase transformation and the RO oxidation mechanism, and the conditions of (Mn,Mg)yFe3-yO4 generation and enrichment was obtained. The results show that at BFS addition of 30 %, reaction temperature 1400 °C and furnace-cooling, the iron-containing phase (Ca2Fe2O5 and RO) was almost completely transformed into (Mn,Mg)yFe3-yO4. The oxidation mechanism of RO was formation of (Mn,Mg)yFe3-yO4 by cation diffusion. Under optimal conditions, the iron recovery rate and the grade reached 65.74 % and 32.07 %, respectively, which can be used as raw material for ironmaking. Meanwhile, the main phase of the tailing slag was β-Ca2SiO4, without f-CaO, which has the potential to be used in the cement and concrete industries with the advantages of both low cost and eco-friendly. Therefore, the process with green, efficient and low cost was provided, which is a feasible idea for the comprehensive utilization of industrial solid waste.

AbstractContext Gastrodin has been used as antihypertension therapy in China; however, the mechanisms underlying the effects of gastrodin have yet to be fully elucidated.Objective To explore the therapeutic efficiency of gastrodin as an antihypertensive and determine the mechanisms underlying this effect.Materials and methods C57BL/6 mice were continuously administered angiotensin II (Ang II) (500 ng/kg/min) to induce hypertension. Mice were randomly divided into control, Ang II and Ang II + gastrodin groups. Mice received intragastric administration of gastrodin (5 mg/kg) or double distilled water once a day for 4 weeks. Blood pressure, pulse wave velocity (PWV), thickness of the abdominal aorta, pathological morphology and differential expression transcripts (DETs) were assessed. Abdominal aorta rings and primary isolated vascular smooth muscle cells were subjected to Ang II stimulation to induce hypertension as ex vivo and in vitro models, respectively. Vascular ring tension, release of Ca2+ and levels of proteins involved in the myosin light chain kinase (MLCK)/phospho-myosin light chain 2 (p-MLC2) pathway were determined.Results Gastrodin treatment attenuated increases in blood pressure, PWV and thickness of the abdominal aorta. Treatment with gastrodin resulted in 2785 DETs and the enrichment of vascular contraction and calcium signalling pathways. Gastrodin treatment attenuated Ang II-induced vasoconstriction, produced a norepinephrine-precontracted vasodilation effect (attenuated by verapamil), and reduced intracellular Ca2+ release. Furthermore, gastrodin suppressed activation of the MLCK/p-MLC2 pathway in vivo and in vitro.Conclusions Gastrodin treatment lowers blood pressure, suppresses Ang II-induced vascular contraction and MLCK/p-MLC2 pathway activation, thereby demonstrating the mechanisms underlying the therapeutic efficacy of gastrodin as an antihypertensive.

The cultivation of largemouth bass (Micropterus salmoides), a species of significant economic value in aquaculture, has experienced notable growth recently. However, the deterioration of water quality seriously affects the metabolic responses of M. salmoides. While compound microbial agent (CMA) is widely utilized for ecological rehabilitation and water filtration, its application in M. salmoides has not been reported. Here, based on physio-biochemical tests and 16S rRNA sequencing, we investigated the effects of CMA (yeast, Bacillus subtilis, and lactic acid bacteria) on the water quality within the recirculating aquaculture system, along with physiological indices and gut microbiota of M. salmoides. Compared to the control and single microbial agent (yeast), CMA treatment improved the water quality by improving the dissolved oxygen and delaying the increase of pH, total nitrogen, total phosphorus, ammonia nitrogen, and nitrite. The 16s rRNA gene sequencing revealed that the water treated with CMA exhibited elevated levels of chao1, Shannon, Pd, and a larger population of dominant bacterial. Besides, higher values of ACE, chao1, Shannon, and OTU level, and lower Simpson index were found in CMA treated M. salmoides samples, suggesting that CMA treatment enhanced the species richness and diversity of gut microbiota of M. salmoides. Furthermore, CMA treatment hindered the generation and proliferation of harmful bacteria, such as the Mycoplasma mobile 163K species and the Erysipelotrichaceae family, which was associated with enhanced antioxidant enzymatic activity and decreased MDA level in both the serum and liver. These findings shed light on the essential roles of CMA in M. salmoides culturing and introduce an innovative approach to enhance the aquatic environment.

Background: Hypertension, a highly prevalent chronic disease, is known to inflict severe damage upon blood vessels. In our previous study, isoliensinine, a kind of bibenzyl isoquinoline alkaloid which isolated from a TCM named Lotus Plumule (Nelumbo nucifera Gaertn), exhibits antihypertensive and vascular smooth muscle proliferation-inhibiting effects, but its application is limited due to poor water solubility and low bioavailability. In this study, we proposed to prepare isoliensinine loaded by PEG-PLGA polymer nanoparticles to increase its efficacy Method: We synthesized and thoroughly characterized PEG-PLGA nanoparticles loaded with isoliensinine using a nanoprecipitation method, denoted as, PEG-PLGA@Isoliensinine. Additionally, we conducted comprehensive investigations into the stability of PEG-PLGA@Isoliensinine, in vitro drug release profiles, and in vivo pharmacokinetics. Furthermore, we assessed the antihypertensive efficacy of this nano-system through in vitro experiments on A7R5 cells and in vivo studies using AngII-induced mice. Result: The findings reveal that PEG-PLGA@Isoliensinine significantly improves isoliensinine absorption by A7R5 cells and enhances targeted in vivo distribution. This translates to a more effective reduction of AngII-induced hypertension and vascular smooth muscle proliferation. Conclusion: In this study, we successfully prepared PEG-PLGA@Isoliensinine by nano-precipitation, and we confirmed that PEG-PLGA@Isoliensinine surpasses free isoliensinine in its effectiveness for the treatment of hypertension, as demonstrated through both in vivo and in vitro experiments. Significance: This study lays the foundation for isoliensinine's clinical use in hypertension treatment and vascular lesion protection, offering new insights for enhancing the bioavailability of traditional Chinese medicine components. Importantly, no toxicity was observed, affirming the successful implementation of this innovative drug delivery system in vivo and offers a promising strategy for enhancing the effectiveness of Isoliensinine and propose an innovative avenue for developing novel formulations of traditional Chinese medicine monomers.

Background: Increasing global overweight and obesity rates not only increase the prevalence of myocardial infarction (MI), but also exacerbate ischemic injury and result in worsened prognosis. Currently, there are no drugs that can reverse myocardial damage once MI has occurred, therefore discovering drugs that can potentially limit the extent of ischemic damage to the myocardium is critical. Resveratrol is a polyphenol known for its antioxidant properties, however whether prolonged daily intake of resveratrol during obesity can protect against MI-induced damage remains unexplored. Methods: We established murine models of obesity via high-fat/high-fructose diet, along with daily administrations of resveratrol or vehicle, then performed surgical MI to examine the effects and mechanisms of resveratrol in protecting against myocardial ischemic injury. Results: Daily administration of resveratrol in obese mice robustly protected against myocardial ischemic injury and improved post-MI cardiac function. Resveratrol strongly inhibited oxidative and DNA damage via activating SIRT3/FOXO3a-dependent antioxidant enzymes following MI, which were completely prevented upon administration of 3-TYP, a selective SIRT3 inhibitor. Hence, the cardioprotective effects of prolonged resveratrol intake in protecting obese mice against myocardial ischemic injury was due to reestablishment of intracellular redox homeostasis through activation of SIRT3/FOXO3a signaling pathway. Conclusion: Our findings provide important new evidence that supports the daily intake of resveratrol, especially in those overweight or obese, which can robustly decrease the extent of ischemic damage following MI. Our study therefore provides new mechanistic insight and suggests the therapeutic potential of resveratrol as an invaluable drug in the treatment of ischemic heart diseases.

IntroductionEarly detection of the virus in the environment or in infected pigs is a critical step to stop African swine fever virus (ASFV) transmission. The p22 protein encoded by ASFV KP177R gene has been shown to have no effect on viral replication and virulence and can serve as a molecular marker for distinguishing field virus strains from future candidate KP177R deletion vaccine strains.MethodsThis study established an ASFV detection assay specific for the highly conserved ASFV KP177R gene based on recombinase polymerase amplification (RPA) and the CRISPR/Cas12 reaction system. The KP177R gene served as the initial template for the RPA reaction to generate amplicons, which were recognized by guide RNA to activate the trans-cleavage activity of Cas12a protein, thereby leading to non-specific cleavage of single-stranded DNA as well as corresponding color reaction. The viral detection in this assay could be determined by visualizing the results of fluorescence or lateral flow dipstick (LFD) biotin blotting for color development, and was respectively referred to as fluorescein-labeled RPA-CRISPR/Cas12a and biotin-labeled LFD RPA-CRISPR/Cas12a. The clinical samples were simultaneously subjected to the aforementioned assay, while real-time quantitative PCR (RT-qPCR) was employed as a control for determining the diagnostic concordance rate between both assays.ResultsThe results showed that fluorescein- and biotin-labeled LFD KP177R RPA-CRISPR/Cas12a assays specifically detected ASFV, did not cross-react with other swine pathogens including PCV2, PEDV, PDCoV, and PRV. The detection assay established in this study had a limit of detection (LOD) of 6.8 copies/μL, and both assays were completed in 30 min. The KP177R RPA-CRISPR/Cas12a assay demonstrated a diagnostic coincidence rate of 100% and a kappa value of 1.000 (p < 0.001), with six out of ten clinical samples testing positive for ASFV using both KP177R RPA-CRISPR/Cas12a and RT-qPCR, while four samples tested negative in both assays.DiscussionThe rapid, sensitive and visual detection assay for ASFV developed in this study is suitable for field application in swine farms, particularly for future differentiation of field virus strains from candidate KP177R gene-deleted ASFV vaccines, which may be a valuable screening tool for ASF eradication.

Abstract Background This meta-analysis was conducted to evaluate the efficacy of the treat-repair-treat (TRT) strategy in the treatment of severe pulmonary arterial hypertension with congenital heart disease (PAH-CHD). Methods PubMed, EMBASE, Cochrane and Web of Science online databases were searched by two independent investigators for studies that used the TRT strategy for PAH-CHD, and the retrieved studies were reviewed by a third investigator. The main outcomes were pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), 6-minute walk distance (6MWD), and transcutaneous oxygen saturation (SpO2). The changes were compared between follow-up and baseline. Stata version 14.0 was used for data analysis. A random-effects model was selected for meta-analysis. Subgroup analysis and meta-regression were used to find the source of heterogeneity. Results A total of 335 patients from 9 single-arm studies were included. Meta-analysis showed significant reductions in PAP and PVR and improvements in 6MWD and SpO2 (PAP: SMD -2.73 95% CI -2.97, − 2.50 p =

Abstract Braking control of urban rail vehicles with multiple carriages is critical to ensure the safe operation of urban rails. However, existing decentralized braking control methods lead to the inconsistent speed and excessive coupler force among carriages, which compromises the operation safety of urban rails. To address this issue, a cooperative braking strategy is proposed for urban rail vehicles based on Koopman model predictive control method. First, a cyber‐physical model is established, where the physical layer characterizes the dynamic model of multiple carriages using the Koopman operator. The cyber layer represents the communication topology of carriages with graph theory. Second, a cooperative braking controller is designed with the distributed model predictive control method. An optimisation problem is formulated to minimize the speed inconsistency and relative displacement difference among carriages. Third, extensive simulations under various scenarios, including normal and extreme operating conditions, are conducted to verify the effectiveness of the proposed method. Simulation results show that, compared with the classical decentralized method, the proposed braking method reduces the average relative displacement by 78% while reducing the speed error by 29%.

Objective: To explore whether Lycium barbarum polysaccharide (LBP) can reduce the apoptosis of retinal photoreceptor cells in retinitis pigmentosa (RP) mice by inhibiting nuclear factor-kappa B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) signaling pathway. Methods: (i) In vitro experiments, mouse retinal ganglion cells (661W cells) were divided into normal, model, LBP low-dose (LBP-L, 40 mg/L), LBP middle-dose (LBP-M, 80 mg/L), LBP high-dose (LBP-H, 160 mg/L), and positive drug control (NLRP3 inhibitor, 160 mg/L) groups. And the 661W cells were exposed to varying concentrations of H2O2 ranging from 50 to 400 μmol/L to determine the optimal concentration for inducing apoptosis (200 μmol/L). Then the cell viability was assessed using Cell Counting Kit-8 (CCK-8), while the apoptosis rate was detected by flow cytometry; the expression of NLRP3 was detected by immunofluorescence; and the expression of apoptosis markers was detected by enzyme-linked immunosorbent assay (ELISA) and Western blot (WB). (ii) In vivo assays were carried out with the use of C57/BL6 and Rd10 mice. The animal experimental groups were divided into normal, model, LBP-L, LBP-M, LBP-H, and NLRP3 inhibitor groups, in which the normal group was C57/BL6 mice and the other groups were Rd10 mice. Ten mice were included in each group, and the corresponding drugs were administered intragastrically for a duration of four weeks. NF-κB/NLRP3 pathway and the expression of apoptosis markers were observed by electroretinogram, histopathological examination, and WB to assess the effects of LBP on retinal photoreceptor cell apoptosis. Results: (i) In vitro experiments, compared with the normal group, the apoptosis rate of 661W cells in model group was significantly increased (P < 0.01), and the expression levels of key proteins of NF-κB/NLRP pathway, such as NLRP3, NF-κB, p-NF-κB, and pro-apoptotic protein caspase-3, were up-regulated (P < 0.01). The rate of Bax/Bcl-2 was increased (P < 0.01), and the concentrations of interleukin (IL)-1β and tumor necrosis factor (TNF)-α were significantly increased (P < 0.01). Compared with the model group, high dose of LBP decreased the apoptosis rate of 661W cells (P < 0.01), and down-regulated the expression levels of the key proteins of NF-κB/NLRP3 pathway, including NF-κB, NLRP3, p-NF-κB, and caspase-3 (P < 0.01). The rate of Bax/Bcl-2 was decreased (P < 0.01), and the concentrations of IL-1β and TNF-α were decreased (P < 0.01). (ii) In vivo experiments, high dose of LBP significantly increased morphological changes in the outer nuclear layer (ONL) thickness of Rd10 mice, as well as functional changes in the amplitudes of the a-wave and b-wave (P < 0.01), which also down-regulated the expression levels of NF-κB (P < 0.05), NLRP3, p-NF-κB, and caspase-3 (P < 0.01), reduced the Bax/Bcl-2 rate (P < 0.01), and decreased the concentrations of IL-1β (P < 0.01) and TNF-α (P < 0.05). Conclusion: LBP could improve both retinal morphology and function, providing protection to photoreceptors from apoptosis through the inhibition of the NF-κB/NLRP3 pathway.

Abstract In this paper, we investigate the Blandford–Znajek (BZ) process within the framework of Einsteinian cubic gravity (ECG). To analytically study the BZ process using the split monopole configuration, we construct a slowly rotating black hole in ECG up to cubic order in small spin, considering the leading order in small coupling constant of higher curvature terms. By deriving the magnetosphere solution around the black hole, we determine the BZ power up to the second relative order in spin. The BZ power is modified by the coupling constant compared to Kerr black hole case. Although the general nature of the BZ process in ECG remains unchanged at the leading order in spin, the coupling constant introduces modification at the second relative order in spin. Therefore, we anticipate that it is feasible to discern general relativity from higher derivative gravities by examining the BZ power in rapidly rotating black holes.

In this study, we conducted a 16-week feeding trial to investigate the effects of a high-cassava starch diet on growth performance, liver function, and metabolism in largemouth bass (Micropterus salmoides). We formulated five diets containing varying levels of cassava starch: 12%, 9%, 6%, 3%, and 0% (termed M12, M9, M6, M3, and M0, respectively). We distributed these diets among largemouth bass with the initial body weight of 83.33 ± 0.55 g via an in-pond “raceway” aquaculture system. Our findings suggest that high level (12%) of cassava starch dietary inclusion adversely affected growth performance metrics such as weight gain rate and specific growth rate, along with feed utilization efficiency indicators, including protein efficiency, protein deposition rate, and the apparent digestibility of dry matter and protein. This negative impact was accompanied by a decrease in intestinal amylase activity. Through further transcriptomic analysis, we identified several key genes associated with carbohydrate metabolism, which underwent changes influencing liver function. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the involvement of these differentially expressed genes (DEGs) in the tricarboxylic acid cycle (TCA cycle). Comparative metabolomics analysis further indicated that the M9 group showed significant enrichment in pathways related to amino acid metabolism and alterations in the levels of metabolites involved in carbohydrate metabolism. In conclusion, our study demonstrates that incorporating up to 9% cassava starch in the diet can enhance growth performance in largemouth bass by stimulating digestive enzyme activities and promoting glucose utilization.

In this study, the rotating welding process of Chinese fir (Keteleeriafortunei) in Guizhou, China, was systematically analyzed. The effects of rotating welding conditions, including the dowel-to-guide hole diameter ratio, welding time, depth, base surface, angle, and dowel type, on the performance of welded Chinese fir were explored. Moreover, the physical and chemical changes oftheChinese fir interface during welding were revealed by Fourier-Transform Infrared Spectroscopy (FT-IR), X-ray Photoelectron Spectroscopy (XPS), X-ray Diffraction (XRD), and Scanning Electron Microscopy (SEM). The results indicated the following: (1) The rotating welding technology can quickly achieve a strong connection between wood through friction heat without chemical adhesives and compared with traditional wood connection technology such as gluing or mechanical fixing;it has the advantages of simple operation, high production efficiency; and environmental friendliness. (2) Aftertherotating welding, the wood underwent significant pyrolysis, especially the degradation of hemicellulose. The heat generated in the welding process caused good melting and mechanical interlocking between the dowel and the wall of the guide hole, but it was also accompanied by afriction loss of the dowel and the substrate. (3) The welding parameters affected the wood’s connection strength and stability by altering heat production, distribution, transfer, and frictional losses. The impact of the dowel-to-guide hole diameter ratio had a great influence on the connection strength. When the diameter ratio was 1:0.7, the tensile strength was the highest, reaching 2.27 MPa. (4) The analyses of XPS, FTIR, XRD, and SEM proved thatthechemical composition changes at the interface, leading to a more structured crystalline bond and enhanced connection strength due to fiber entanglement and interlocking. This research providesatheoretical and experimental basis forthefurther innovation and development of wood processing technology and provides a new technical path forthegreen manufacturing of wood structure buildings.

MiRNAs are edited or modified in multiple ways during their biogenesis pathways. It was reported that miRNA editing was deregulated in tumors, suggesting the potential value of miRNA editing in cancer classification. Here we extracted three types of miRNA features from 395 LUAD and control samples, including the abundances of original miRNAs, the abundances of edited miRNAs, and the editing levels of miRNA editing sites. Our results show that eight classification algorithms selected generally had better performances on combined features than on the abundances of miRNAs or editing features of miRNAs alone. One feature selection algorithm, i.e., the DFL algorithm, selected only three features, i.e., the frequencies of hsa-miR-135b-5p, hsa-miR-210-3p and hsa-mir-182_48u (an edited miRNA), from 316 training samples. Seven classification algorithms achieved 100% accuracies on these three features for 79 independent testing samples. These results indicate that the additional information of miRNA editing is useful in improving the classification of LUAD samples.

Background: The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain. Methods: In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks. Results: Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to −1.59/−0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and −1.66/−1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05). Conclusion: QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG. Trial registration: ChiCTR2000033890.

A single-row plasma tube array (PTA) experimental system is established to improve the backscattering attenuation of a metal plate covered by a plasma tube array. The backscattering test system is utilized in a microwave anechoic chamber to examine the effects of gas composition, pressure, tube diameter, and discharge power on the backscattering attenuation of a metal plate using a plasma tube array. The electron density is obtained via microwave diagnosis. The backscattering attenuation mechanism in different frequency bands is revealed via numerical simulation. The results show that the reasonable selection of PTA parameters achieves strong attenuation in different frequency bands. The strong attenuation frequency bands of Ar–Hg PTA are in low frequency (1.5–3.5 GHz) and high frequency (13–17 GHz), while that of Ne–Hg discharge is in medium frequency (6.4–11.7 GHz). When the pressure is 0.5 and 1 Torr, the PTA shows a low, medium, and high multi-band distribution for the backscattering strong attenuation region. The backscattering strong attenuation region shows a low and high dual-band distribution, while the pressure is 2–4 Torr. As the tube diameter increases, the strong attenuation region maintains the dual-band, but it changes from low and high frequency bands to medium frequency (6-12 GHz), where the backscattering attenuation mechanism is collisional absorption when the frequency of plasma electron oscillation is close to that of electro-magnetic waves. The backscattering attenuation mechanism in the low frequency band involves the periodic structure of PTA generating local surface plasmon to absorb electromagnetic waves.

Out-of-face gradient sandwich structures have been widely studied for their excellent impact resistance. One uniform and two out-of-plane gradient cores are proposed based on the bionic structure of Royal Water Lily, and the midspan deflection of the back panel and the energy absorption of the out-of-plane gradient sandwich structures under various blast loads are studied. Two frequently adopted methods of explosive loading are applied to the sandwich panels, and the responses are contrasted for the loads applied as a time-dependent pressure history versus imposition of the initial velocity. The effect of the fluid–structure interaction is considered in the blast impulsion, and the dynamic responses of the sandwich structures with different out-of-plane density arrangements are analyzed under two loading approaches. Results show that the energy absorption of the core layer under the prescribed velocity approach is approximately 3–5 times that of the applied pressure approach, while the back panel deflections of different out-of-plane gradient sandwiches are similar. There are significant differences in the deformation mechanisms of structures under these two types of impact loads. Under the same type of impact load, the core compression process of the out-of-plane positive gradient sandwich panel is decoupled from the whole tensile bending deformation process of the structure, whereas the core compression process of the out-of-plane negative gradient sandwich panel is strongly coupled with the whole tensile bending deformation process of the structure. The related research will lay the foundation for an in-depth understanding of the theoretical study of the impact of out-of-face gradient sandwich structures.

Although virtual exchange has been widely discussed during the (post-)pandemic era, how students do (self-)reflexivity in this context has yet to be fully explored. This study examines interviews with Chinese and Finnish university students about how they reflect on their virtual exchanges by presenting them with videoclips of their encounters. Grounded in Foucault’s (1988) technologies of the self and Clark & Author 2’s (20xx) multidimensions of (self-)reflexivity, the study examines how (self-)reflexivity is co-constructed by individuals, the media and researchers (e.g., ways of doing (self-)reflexivity adopted by students). Further, we investigate how they conceptualize interculturality based on their own (self-)reflexivity. Recommendations for (online) intercultural education are given based on the findings, inviting scholars and researchers to rethink and unthink the notion of (self-)reflexivity in intercultural education.

Abstract The responses of atmospheric kinetic energy (KE) spectra to three convective parameterizations (CPs) in global high‐resolution simulations are revealed. The results show that the KE spectra exhibit high sensitivity to the CPs, mainly at mesoscales in the middle and upper troposphere. The New Tiedtke scheme produces the steepest mesoscale slope, followed by the Kain‐Fritsch scheme and then the Grell‐Freitas scheme. In general, there is a compensating relationship between latent heat released by the CP and microphysics parameterization (MP). The less latent heat released by the CP is compensated by the more latent heat released by the MP. The shallowest mesoscale spectra for the Grell‐Freitas scheme are related to the strongest downscale cascade dominated by the rotational component of the flow, and this is attributed to more latent heat released from MP enhancing the intensity of vorticity in the troposphere and producing more gravity wave activities in the lower stratosphere.

Objective: Sialic acid is a terminal monosaccharide of glycans in glycoproteins and glycolipids, and its derivation from glucose is regulated by the rate-limiting enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE). Although the glycans on key endogenous hepatic proteins governing glucose metabolism are sialylated, how sialic acid synthesis and sialylation in the liver influence glucose homeostasis is unknown. Studies were designed to fill this knowledge gap. Methods: To decrease the production of sialic acid and sialylation in hepatocytes, a hepatocyte-specific GNE knockdown mouse model was generated, and systemic glucose metabolism, hepatic insulin signaling and glucagon signaling were evaluated in vivo or in primary hepatocytes. Peripheral insulin sensitivity was also assessed. Furthermore, the mechanisms by which sialylation in the liver influences hepatic insulin signaling and glucagon signaling and peripheral insulin sensitivity were identified. Results: Liver GNE deletion in mice caused an impairment of insulin suppression of hepatic glucose production. This was due to a decrease in the sialylation of hepatic insulin receptors (IR) and a decline in IR abundance due to exaggerated degradation through the Eph receptor B4. Hepatic GNE deficiency also caused a blunting of hepatic glucagon receptor (GCGR) function which was related to a decline in its sialylation and affinity for glucagon. An accompanying upregulation of hepatic FGF21 production caused an enhancement of skeletal muscle glucose disposal that led to an overall increase in glucose tolerance and insulin sensitivity. Conclusion: These collective observations reveal that hepatic sialic acid synthesis and sialylation modulate glucose homeostasis in both the liver and skeletal muscle. By interrogating how hepatic sialic acid synthesis influences glucose control mechanisms in the liver, a new metabolic cycle has been identified in which a key constituent of glycans generated from glucose modulates the systemic control of its precursor.

Abstract The estrogen receptor (ER) designated ERα has actions in many cell and tissue types that impact glucose homeostasis. It is unknown if these include mechanisms in endothelial cells, which have the potential to influence relative obesity, and processes in adipose tissue and skeletal muscle that impact glucose control. Here we show that independent of impact on events in adipose tissue, endothelial ERα promotes glucose tolerance by enhancing endothelial insulin transport to skeletal muscle. Endothelial ERα-deficient male mice are glucose intolerant and insulin resistant, and in females the antidiabetogenic actions of estradiol (E2) are absent. The glucose dysregulation is due to impaired skeletal muscle glucose disposal that results from attenuated muscle insulin delivery. Endothelial ERα activation stimulates insulin transcytosis by skeletal muscle microvascular endothelial cells. Mechanistically this involves nuclear ERα-dependent upregulation of vesicular trafficking regulator sorting nexin 5 (SNX5) expression, and PI3 kinase activation that drives plasma membrane recruitment of SNX5. Thus, coupled nuclear and non-nuclear actions of ERα promote endothelial insulin transport to skeletal muscle to foster normal glucose homeostasis.

Abstract Hypercholesterolemia and vascular inflammation are key interconnected contributors to the pathogenesis of atherosclerosis. How hypercholesterolemia initiates vascular inflammation is poorly understood. Here we show in male mice that hypercholesterolemia-driven endothelial activation, monocyte recruitment and atherosclerotic lesion formation are promoted by a crosstalk between macrophages and endothelial cells mediated by the cholesterol metabolite 27-hydroxycholesterol (27HC). The pro-atherogenic actions of macrophage-derived 27HC require endothelial estrogen receptor alpha (ERα) and disassociation of the cytoplasmic scaffolding protein septin 11 from ERα, leading to extranuclear ERα- and septin 11-dependent activation of NF-κB. Furthermore, pharmacologic inhibition of cyp27a1, which generates 27HC, affords atheroprotection by reducing endothelial activation and monocyte recruitment. These findings demonstrate cell-to-cell communication by 27HC, and identify a major causal linkage between the hypercholesterolemia and vascular inflammation that partner to promote atherosclerosis. Interventions interrupting this linkage may provide the means to blunt vascular inflammation without impairing host defense to combat the risk of atherosclerotic cardiovascular disease that remains despite lipid-lowering therapies.

Abstract The effects and underlying mechanisms of gastrodin treatment on hypertensive vascular dysfunction and proliferation of vascular smooth muscle cells (VSMCs) were determined in vitro and in vivo. Using a pharmacological target network interaction analysis, 151 common targets and a PPI network were identified containing the top 10 hub genes. Kyoto encyclopedia of genes and genomes (KEGG) analysis identified the PI3K/AKT pathway as a significantly enriched pathway. Both spontaneous hypertensive rats (SHRs) and Wistar Kyoto rats were used to assess the therapeutic effects of gastrodin on hypertension. Gastrodin treatment of the SHRs resulted in a marked attenuation of elevated blood pressure, pulse wave velocity, and pathological changes in the abdominal aorta. Moreover, gastrodin treatment significantly inhibited cell growth and downregulated the expression of PCNA as well as the p-PI3K/PI3K and p-AKT/AKT levels in angiotensin II-stimulated VSMCs. Taken together, gastrodin treatment attenuates blood pressure elevation, vascular dysfunction, and proliferation of VSMCs and inhibits the activation of the PI3K/AKT pathway.

With rapid urbanization, the contradiction between traffic and the environmental pollution caused by it is becoming increasingly prominent. To preserve ground buildings, an increasing number of tunnel schemes are adopted. Urban Karst exploration is based on drilling, supplemented by traditional geophysical methods such as high-density electrical method and shallow seismic reflection method, which are inefficient and difficult to implement owing to site conditions. As a geophysical exploration technology developed in recent years, electromagnetic wave technology has the advantages of high resolution and convenient field operation, which can better reveal the development scale and characteristics of underground Karst. Based on traditional data processing, setting the minimum value, choosing the reflection projection result as the initial model, using the low-pass filtering and angle-limiting technology, and adopting the structure program of continuous survey mode to carry out normalized calculation processing can greatly improve the accuracy of electromagnetic wave CT data interpretation. The findings of this study show that the electromagnetic wave detection technology can be applied effectively in Karst exploration, and its detection results have great guiding significance in urban tunnel engineering.

Abstract Background Diabetic retinopathy (DR) is a common cause of visual impairment. Apigenin has been shown to have antiangiogenic effects in various diseases. Our study aimed to investigate the role of apigenin in DR and elucidate the underlying mechanism. Methods Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to establish a DR model. HRMECs were treated with apigenin. Then we knocked down or overexpressed miR-140-5p and HDAC3, and added PI3K/AKT inhibitor LY294002. The expression levels of miR-140-5p, HDAC3, and PTEN were measured using qRT-PCR. Western blot analysis was performed to assess the expression of HDAC3, PTEN, and PI3K/AKT pathway-related proteins. Finally, cell proliferation and migration were evaluated using MTT, wound-healing assay, and transwell assay, while angiogenesis was examined using the tube formation assay. Results HG treatment resulted in reduced miR-140-5p expression and overexpression of miR-140-5p suppressed proliferation, migration, and angiogenesis of the HG-induced HRMECs. Apigenin treatment significantly restored the decreased level of miR-140-5p caused by HG treatment and inhibited proliferation, migration, and angiogenesis of the HG-induced HRMECs by upregulating miR-140-5p. Moreover, miR-140-5p targeted HDAC3, and overexpression of miR-140-5p reversed the HG-inducted upregulation of HDAC3 expression. HDAC3 was found to bind to the promoter region of PTEN, inhibiting its expression. Knockdown of HDAC3 suppressed the PI3K/AKT pathway by elevating PTEN expression. Furthermore, apigenin inhibited angiogenesis in DR cell models through the regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Conclusions Apigenin effectively suppressed angiogenesis in HG-induced HRMECs by modulating the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Our study may contribute to the development of novel therapeutic approaches and identification of potential targets for the treatment of DR.

Context Ulcerative colitis has been clinically treated with Qing Hua Chang Yin (QHCY), a traditional Chinese medicine formula. However, its precise mechanisms in mitigating chronic colitis are largely uncharted.Objective To elucidate the therapeutic efficiency of QHCY on chronic colitis and explore its underlying molecular mechanisms.Materials and methods A total ion chromatogram fingerprint of QHCY was analysed. Chronic colitis was induced in male C57BL/6 mice using 2% dextran sodium sulphate (DSS) over 49 days. Mice were divided into control, DSS, DSS + QHCY (0.8, 1.6 and 3.2 g/kg/d dose, respectively) and DSS + mesalazine (0.2 g/kg/d) groups (n = 6). Mice were intragastrically administered QHCY or mesalazine for 49 days. The changes of disease activity index (DAI), colon length, colon histomorphology and serum pro-inflammatory factors in mice were observed. RNA sequencing was utilized to identify the differentially expressed transcripts (DETs) in colonic tissues and the associated signalling pathways. The expression of endoplasmic reticulum (ER) stress-related protein and NF-κB signalling pathway-related proteins in colonic tissues was detected by immunohistochemistry staining.Results Forty-seven compounds were identified in QHCY. Compared with the DSS group, QHCY significantly improved symptoms of chronic colitis like DAI increase, weight loss, colon shortening and histological damage. It notably reduced serum levels of IL-6, IL-1β and TNF-α. QHCY suppressed the activation of PERK–ATF4–CHOP pathway of ER stress and NF-κB signalling pathways in colonic tissues.Discussion and conclusions The findings in this study provide novel insights into the potential of QHCY in treating chronic colitis patients.

Terahertz (THz) sensors have attracted great attention in the biological field due to their nondestructive and contact-free biochemical samples. Recently, the concept of a quasi-bound state in the continuum (QBIC) has gained significant attention in designing biosensors with ultrahigh sensitivity. QBIC-based metasurfaces (MSs) achieve excellent performance in various applications, including sensing, optical switching, and laser, providing a reliable platform for biomaterial sensors with terahertz radiation. In this study, a structure-engineered THz MS consisting of a “double C” array has been designed, in which an asymmetry parameter α is introduced into the structure by changing the length of one subunit; the Q-factor of the QBIC device can be optimized by engineering the asymmetry parameter α. Theoretical calculation with coupling equations can well reproduce the THz transmission spectra of the designed THz QBIC MS obtained from the numerical simulation. Experimentally, we adopt an MS with α = 0.44 for testing arginine molecules. The experimental results show that different concentrations of arginine molecules lead to significant transmission changes near QBIC resonant frequencies, and the amplitude change is shown to be 16 times higher than that of the classical dipole resonance. The direct limit of detection for arginine molecules on the QBIC MS reaches 0.36 ng/mL. This work provides a new way to realize rapid, accurate, and nondestructive sensing of trace molecules and has potential application in biomaterial detection.

The task of aspect-based sentiment analysis (ASBA) is to identify all the sentiment analyses expressed by specific aspect words in the text. How to identify specific objects (i.e., aspect words), describe the modifiers of the specific objects (i.e., opinion words), and judge the sentiment analysis expressed by opinion words (sentimental classification) in one step has become a focus of research in ASBA. ASTE (Aspect Sentiment Triplet Extraction) based on DREN (Deep Relationship Enhancement Networks) has been proposed in this paper. It aims to extract the aspect words and opinion words in the review text in one-step. They can judge the sentiment analysis expressed by the opinion words. Therefore, the study defines ten kinds of word relations; then, the study uses the parts of the speech feature, syntactic feature, relative position feature and tree distance relative feature to enhance the word representation relationship, which enriches the table of information in the relational matrix. Secondly, based on the word representation of BERT and GCN, the structural information of the texts are extracted; then, further extraction of higher-level word semantic information and word relationship information through SWDA (Sliding Window Dilated Attention) occurs, as SWDA can capture the multi-granularity relationship in words. Finally, the experimental results show that the proposed method is effective.

Abstract In recent years, there have been several solutions to medical image segmentation, such as U-shaped structure, transformer-based network, and multi-scale feature learning method. However, their network parameters and real-time performance are often neglected and cannot segment boundary regions well. The main reason is that such networks have deep encoders, a large number of channels, and excessive attention to local information rather than global information, which is crucial to the accuracy of image segmentation. Therefore, we propose a novel multi-branch medical image segmentation network MBSNet. We first design two branches using a parallel residual mixer (PRM) module and dilate convolution block to capture the local and global information of the image. At the same time, a SE-Block and a new spatial attention module enhance the output features. Considering the different output features of the two branches, we adopt a cross-fusion method to effectively combine and complement the features between different layers. MBSNet was tested on five datasets ISIC2018, Kvasir, BUSI, COVID-19, and LGG. The combined results show that MBSNet is lighter, faster, and more accurate. Specifically, for a $$320 \times 320$$ 320 × 320 input, MBSNet’s FLOPs is 10.68G, with an F1-Score of $$85.29\%$$ 85.29 % on the Kvasir test dataset, well above $$78.73\%$$ 78.73 % for UNet++ with FLOPs of 216.55G. We also use the multi-criteria decision making method TOPSIS based on F1-Score, IOU and Geometric-Mean (G-mean) for overall analysis. The proposed MBSNet model performs better than other competitive methods. Code is available at https://github.com/YuLionel/MBSNet .

Background: Myocardial fibrosis (MF) is an advanced pathological manifestation of many cardiovascular diseases, which can induce heart failure and malignant arrhythmias. However, the current treatment of MF lacks specific drugs. Ginsenoside Re has anti-MF effect in rat, but its mechanism is still not clear. Therefore, we investigated the anti-MF effect of ginsenoside Re by constructing mouse acute myocardial infarction (AMI) model and AngⅡ induced cardiac fibroblasts (CFs) model. Methods: The anti-MF effect of miR-489 was investigated by transfection of miR-489 mimic and inhibitor in CFs. Effect of ginsenoside Re on MF and its related mechanisms were investigated by ultrasonographic, ELISA, histopathologic staining, transwell test, immunofluorescence, Western blot and qPCR in the mouse model of AMI and the AngⅡ-induced CFs model. Results: MiR-489 decreased the expression of α-SMA, collagenⅠ, collagen Ⅲ and myd88, and inhibited the phosphorylation of NF-κB p65 in normal CFs and CFs treated with AngⅡ. Ginsenoside Re could improve cardiac function, inhibit collagen deposition and CFs migration, promote the transcription of miR-489, and reduce the expression of myd88 and the phosphorylation of NF-κB p65. Conclusion: MiR-489 can effectively inhibit the pathological process of MF, and the mechanism is at least partly related to the regulation of myd88/NF-κB pathway. Ginsenoside Re can ameliorate AMI and AngⅡ induced MF, and the mechanism is at least partially related to the regulation of miR-489/myd88/NF-κB signaling pathway. Therefore, miR-489 may be a potential target of anti-MF and ginsenoside Re may be an effective drug for the treatment of MF.

Background With higher age, frailty escalates the risk of falls, unexpected physical dysfunction, hospitalization, and mortality. Polypharmacy in the older population is a major challenge that not only increases medical costs, but also may worsen the risk of hospitalization and death. More importantly, the properties of anti-cholinergic drugs contribute various negative effects. This study aimed to investigate the sex difference in the association of polypharmacy, anticholinergic burden, and frailty with mortality. Methods Participants older than 65 years who attended the geriatric outpatient clinic of the study center between January 2015 and July 2020 were invited to participate in this retrospective study. Comprehensive geriatric assessment data were collected and the phenotype of frailty was determined by Fried’s criteria. Cox regression and the Kaplan–Meier curve were used to identify risk factors of 5-year survival along with intergroup differences in the risks. Results Of the 2,077 participants, 47.5% were female. The prevalence of frailty and the rate of polypharmacy were 44.7% and 60.6%, respectively. Higher age, male sex, low body mass index, low Mini-Mental State Examination scores, low activities of daily living, frailty status, polypharmacy, and a high Charlson Comorbidity Index score, and greater anticholinergic burden were significant risk factors that were associated with the 5-year all-cause mortality. Male patients with frailty exhibited the highest risks of mortality compared with male patients without frailty and female patients with or without frailty. Polypharmacy was significantly associated with a higher 5-year mortality rate in the frail male group compared with the non-frail male. In frail female group, individuals with a higher anticholinergic burden (as indicated by the Anticholinergic Cognitive Burden Scale) from drug usage exhibited an elevated 5-year mortality rate. Conclusions Polypharmacy and greater anticholinergic burden, synergistically interacted with frailty and intensified the 5-year mortality risk in a gender-specific manner. To mitigate mortality risks, clinicians should prudently identify polypharmacy and anticholinergic burden in the older population.

This study presents a novel approach for converting cottonseed hulls (CSHs) into valuable proanthocyanidins (PAs) through deep eutectic solvent (DES)-based ultrasound-assisted extraction (UAE-DES). Response surface methodology (RSM) was applied to optimize and model this process, resulting in maximum yields of 78.58 mg/g. The ideal PA extraction conditions were determined to be a liquid-to-material ratio of 36.25 mL/g, a water content of 33.21%, and an extraction period of 7.4 min. Molecular dynamic simulations (MDS) were performed to study the interactions between the solvent and target chemicals. Increased van der Waals forces and stronger interactions between DES and the target chemical catechin (CA) compared to those observed with methanol or water were observed. Furthermore, the optimized extract exhibited a higher PA content than can be obtained with conventional extraction methods and demonstrated antioxidant activity in vitro. The cottonseed hulls residues (CSRs) remaining after the extraction process can be used to produce activated carbon (ACCSR), which has some capacity to adsorb methylene blue (MB) contaminants. This study offers a reference for the fruitful transformation of waste biomass into high-value products.

Aim of the study: To assess the impact of Fructus Lycii and Salvia miltiorrhiza Bunge extract (FSE) on retinitis pigmentosa (RP) and to explore the mechanisms by which FSE can prevent oxidative stress-induced photoreceptor ferroptosis in RP. Methods: Hydrogen peroxide(H2O2) was used to induce oxidative stress in 661 W cells, which were then examined using flow cytometry and enzyme linked immunosorbent assay (ELISA). Changes in mitochondria were observed by using an electron microscope to characterize the ferroptosis of the cells. The protective effect of FSE on the retina function and structure of rd10 mice was evaluated using histopathological examination, fundus photographs, and electroretinography (ERG). Protein expression levels of Tumor Protein p53 (P53), Solute Carrier Family 7 Member 11 (SLC7A11), Glutathione peroxidase 4 (GPX4), Arachidonate-12-Lipoxygenase (ALOX12), and Dipeptidyl peptidase 4 (DPP4) were evaluated by Western blot assays in Vivo and in Vitro. Results: H2O2-induced 661 W cells increased oxidative stress products and P53 and ALOX12, decreasing the expression of SLC7A11, GPX4, and DPP4. GPX4 activator does not reduce reactive oxygen species (ROS) generation and has little effect on ferroptosis. Fer-1 and FSE attenuate ROS generation and inhibit ferroptosis of photoreceptors in RP via inhibited P53 expression and increased SLC7A11 and GPX4 expression. Conclusion: FSE may be available in clinical therapeutics to alleviating RP and the mechanism by which inhibits ferroptosis of photoreceptors following oxidative stress via the P53/ SLC7A11 pathway.

IntroductionCopper metabolism encompasses all cellular metabolic processes involving copper ions and plays a significant role in the pathogenesis of diseases, including cancer. Furthermore, copper is intricately involved in various processes related to nucleotide metabolism. However, a comprehensive analysis of copper metabolism in gliomas remains lacking despite its importance.MethodsTo address this gap, glioma patients were stratified based on the expression levels of copper metabolism-related genes. By utilizing machine learning techniques, a novel copper metabolism-associated biomarker was developed. The potential of this biomarker in prognosis, mutation analysis, and predicting immunotherapy response efficiency in gliomas was systematically investigated.ResultsNotably, IGFBP2, identified as a glioma tumor promoter, was found to promote disease progression and influence immunotherapy response. Additionally, glioma-derived IGFBP2 was observed to enhance microglial migration. High IGFBP2 expression in GBM cells facilitated macrophage interactions through the EGFR, CD63, ITGB1, and CD44 signaling pathways. Discussion: Overall, the copper metabolism-associated biomarker shows promising potential to enhance the clinical management of gliomas, offering valuable insights into disease prognosis and treatment strategies.

Abstract Introduction This study aimed to investigate the treatment effect of G protein‐coupled receptor 30 (GPR30) agonist G1 combined with hypothermia (HT) on cognitive impairment and anxiety‐like behavior after subarachnoid hemorrhage (SAH) in rats. Methods Fifty male rats were randomly assigned to one of five groups: Sham group, SAH group, SAH + G1 group, SAH + HT group, and SAH + G1 + HT group. The SAH rat model was established by modified endovascular puncture in all groups except the Sham group. Neurological function after the operation was assessed by Garcia scoring. The degree of rat cerebral edema was determined using dry‐wet weighing method on the 28th day after operation. Moreover, the behavioral test was performed on rats on the 4th and 28th days after operation. Results Compared with Sham group, the Garcia score of each SAH rat model group decreased significantly on the first day and thereafter increased gradually. However, the recovery rate of each treatment group was higher than the SAH group (no treatment), and the Garcia score of SAH + G1 + HT group was much higher than the SAH group on the seventh day after operation. In addition, each treatment group could obviously reduce the cerebral edema degree of SAH rats, among which rats in SAH + G1 + HT group had lower cerebral edema degree than SAH + G1 group and SAH + HT group. Behavioral test results showed that the combination of GPR30 agonist G1 and HT markedly improved the learning and memory ability of SAH rats, alleviated their anxiety‐ and emotion‐related behavior, and enhanced their social interaction. Conclusion GPR30 agonist G1 combined with HT reduces cognitive impairment and anxiety‐like behavior in rats with SAH.