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Abstract Background Circular RNA (circRNAs) have been found to play major roles in the progression of colorectal cancer (CRC). However, the functions of circ_0008345 (transcribed by PTK2) in regulating CRC development remain undefined. In this study, we aimed to explore the roles and underlying mechanisms of circ_0008345 in CRC. Methods RNase R-treated total cellular RNA was used to verify the circular structure of circ_0008345, and a subcellular fractionation assay was performed to detect the subcellular localization of circ_0008345. RNA pull-down and dual-luciferase assays were used to verify the binding relation between microRNA (miR)-182-5p and circ_0008345 and/or CYP1A2. Colony formation assay, EdU, and Transwell assays were performed to detect the biological behavior of CRC cells in vitro, and CRC cells were injected into mice to observe the tumor formation. m6A immunoprecipitation was used to detect the m6A modification of circ_0008345 in CRC cells. Results Circ_0008345, upregulated in CRC tissues and cells, was mainly present in the cytoplasm. Circ_0008345 bound to miR-182-5p, and miR-182-5p targeted CYP1A2, an oncogene in CRC. The colony formation, mobility, EdU-positive cell rate in vitro, and tumor growth in mice were inhibited after the knockdown of circ_0008345. However, the suppressing effects of sh-circ_0008345 on CRC and CYP1A2 expression were significantly reversed after further knockdown of miR-182-5p. METTL3 was the m6A modifier mediating circ_0008345 expression, and the suppression of METTL3 reduced the expression of circ_0008345. Conclusions METTL3-dependent m6A methylation upregulated circ_0008345, which blocked the inhibitory effect of miR-182-5p on CYP1A2, thereby exacerbating the malignant phenotype of CRC cells.

Abstract Background Macrophages play a crucial role in the development of cardiac fibrosis (CF). Although our previous studies have shown that glycogen metabolism plays an important role in macrophage inflammatory phenotype, the role and mechanism of modifying macrophage phenotype by regulating glycogen metabolism and thereby improving CF have not been reported. Methods Here, we took glycogen synthetase kinase 3β (GSK3β) as the target and used its inhibitor NaW to enhance macrophage glycogen metabolism, transform M2 phenotype into anti-fibrotic M1 phenotype, inhibit fibroblast activation into myofibroblasts, and ultimately achieve the purpose of CF treatment. Results NaW increases the pH of macrophage lysosome through transmembrane protein 175 (TMEM175) and caused the release of Ca2+ through the lysosomal Ca2+ channel mucolipin-2 (Mcoln2). At the same time, the released Ca2+ activates TFEB, which promotes glucose uptake by M2 and further enhances glycogen metabolism. NaW transforms the M2 phenotype into the anti-fibrotic M1 phenotype, inhibits fibroblasts from activating myofibroblasts, and ultimately achieves the purpose of treating CF. Conclusion Our data indicate the possibility of modifying macrophage phenotype by regulating macrophage glycogen metabolism, suggesting a potential macrophage-based immunotherapy against CF. Graphical Abstract

Abstract Cancer is a complex disease composing systemic alterations in multiple scales. In this study, we develop the Tumor Multi-Omics pre-trained Network (TMO-Net) that integrates multi-omics pan-cancer datasets for model pre-training, facilitating cross-omics interactions and enabling joint representation learning and incomplete omics inference. This model enhances multi-omics sample representation and empowers various downstream oncology tasks with incomplete multi-omics datasets. By employing interpretable learning, we characterize the contributions of distinct omics features to clinical outcomes. The TMO-Net model serves as a versatile framework for cross-modal multi-omics learning in oncology, paving the way for tumor omics-specific foundation models.

Abstract Understanding the microstructure of materials and their impact on performance is crucial for new electronic devices design. The strong interaction between multiple degrees of freedom (spin, orbit, charge, and lattice) within perovskite type oxides can generate rich electron phase diagrams. The microscopic modulation of manganese ions electron states in rare earth manganate perovskites is the root of many novel macroscopic quantum behaviors, such as giant magnetoresistance phenomenon. For ABO3 type perovskites, the differences of radii and valence states of A‐site ions are used to regulate the coexistence of B site manganese multivalent states (Mn3+, Mn4+, Mn5+), and its ordered structure in the metastable state will create a new combination of electronic states. The ordered arrangement of the multi‐dimensional space of electronic states can induce unique transport properties. Therefore, the preparation of manganate perovskites will provide strong chemical support to construct new generation quantum devices. This review summarizes the challenges and difficulties on constructing trivalent coexisting metastable phase in manganate perovskites through disproportionation reactions, and discusses the status and potential of designing ideal rectified p‐n junctions taking advantage of this unique structure. Finally, the foregrounds of new quantum states driven by this chemical reaction are prospected.

Dilated cardiomyopathy (DCM) is one of the main causes of sudden cardiac death and heart failure and is the leading indication for cardiac transplantation worldwide. Mutations in dozens of cardiac genes have been connected to the development of DCM including the Troponin T2 gene (TNNT2). Here, we generated a human induced pluripotent stem cells (hiPSCs) from a DCM patient with a familial history that carries a missense mutation in TNNT2. The hiPSCs show typical morphology of pluripotent stem cells, expression of pluripotency markers, normal karyotype, and in vitro capacity to differentiate into all three germ layers.

The aim of this paper is to study the flexural behavior of reinforced concrete (RC) beams reinforced by engineered cementitious composite (ECC). The reinforcement effect of ECC on RC beam is studied by experiments, numerical simulation and theoretical analysis, considering the secondary load. Five beams were tested under static load, including two beams with ECC layers at the top and bottom (TBEB), two beams with ECC layers at the bottom (BEB) and one unreinforced beam. Different parameters in the test include reinforcement ratio, whether the top is equipped with ECC layer, and the thickness of the top ECC layer. The test data were used to validate the finite element model developed to simulate the bending response of the ECC layer reinforced beam. Then, a series of parameter studies were carried out to evaluate the effects of ECC layer thickness, reinforcement ratio and ECC elastic modulus on the reinforced beam. The experimental and numerical simulation results show that compared with other reinforced beams, TBEB equipped with 50 mm ECC layer at the top and bottom has better performance. Compared with the control beams, the ultimate bearing capacity is increased by 82.6 %, ductility and deformation capacity are increased by 2.38 times and 2.11 times, respectively. Finally, a calculation model for predicting the flexural capacity of TBEB is presented. The predicted flexural capacity is in good agreement with the experimental results.

Abstract Background Duplication of the bladder with duplication of the posterior urethra is a relatively rare congenital malformation. Cases of sagittal septum duplication of the bladder with duplication of the posterior urethra have rarely been reported. Furthermore, the combination thereof with congenital megacolon is rare. Case presentation A 21-year-old male was admitted to our hospital because of frequent urination for two months. He presented to another hospital first with frequent urination and underwent computed tomography (CT) and testicular biopsy. Anti-inflammatory therapy was administered by the doctor to the patient. For further diagnosis and treatment, the patient went to the outpatient department in our hospital on June 6, 2022. After admission, the patient underwent ultrasound, CT, MRI, cystoscopy, and other related examinations and tests. The examination results suggested that the patient had duplication of the bladder with duplication of the posterior urethra. In addition, the patient’s mother reported that he had suffered from long-term constipation with abdominal distension before the age of 5 years. At the time, he was admitted to the local hospital and was diagnosed with congenital megacolon based on the relevant examinations. After the patient was diagnosed with duplication of bladder and urethra, the doctor recommended surgical treatment to the patient. However, he considered that he only had frequent urination symptoms, and chose conservative treatment rather than to undergo surgical treatment. Thus, the doctor prescribed anti-inflammatory treatment. Four months later, the patient reported that frequent urination symptoms persisted, and was also considering fertility-related problems. The outpatient follow-up will be continued. Conclusions In this article, we summarize the imaging findings of duplication of the bladder with duplication of the posterior urethra and propose the advantages and disadvantages of each type of imaging examination. We also review the relevant literature on cases of bladders with duplication of the posterior urethra. The related differential diagnosis is summarized, and the significance of guiding clinical treatment and diagnosis is discussed.

Abstract The notorious woody plant-degrading pathogen Lasiodiplodia theobromae is a major causal agent of peach gummosis, one of the prevalent and devastating trunk diseases to peach production; however, its pathogenesis is largely unknown. Our previous study showed that L. theobromae LtGPX3, which encodes a glutathione peroxidase resembling yeast GPX3/HYR1-like, was constantly and dramatically upregulated at the infectious stages. Here, we functionally characterized LtGPX3 using the CRISPR-Cas9-aided split marker approach. The ΔLtgpx3 deletion mutants displayed increased sensitivity to the osmotic stress agent KCl and less sensitivity to the cell wall-damaging agent calcofluor white. Exogenous oxidants highly induced the expression of LtGPX3, and the ΔLtgpx3 mutants displayed increased sensitivity to ROS-generating oxidants. Pathogenicity assays revealed that ΔLtgpx3 mutants showed compromised virulence in peach shoots, which was partially restored when peach shoots were pretreated with an NADPH oxidase inhibitor before inoculation. Moreover, ROS levels were strongly boosted, and transcripts of plant defense-related genes were highly induced in the ΔLtgpx3 mutants-infected peach shoots compared with the wild-type-inoculated. Overall, our results showed the essential roles of LtGPX3 in the oxidative stress response and tolerance and pathological functions in L. theobromae. These findings deepen our understanding of the survival strategies of the woody plant-degrading pathogen L. theobromae and provide new insights into developing new strategies for peach gummosis disease control.

Abstract Background The objective of this study was to develop and validate a nomogram for the individualized prediction of adverse events in patients with Stanford type A aortic dissection (TAAD) undergoing hybrid total aortic arch repair. Methods From April 2019 to April 2022, we conducted a comprehensive review of the medical records of Stanford type A aortic dissection patients who underwent hybrid total aortic arch repair surgery at our hospital. Patients were separated into two groups based on whether or not a composite adverse event occurred following surgery. Using univariate and multivariate analyses of logistic regression, the prediction model was created. Construct risk prediction models utilizing nomograms and evaluate their precision, discrimination, and clinical utility. Results Age, platelets, serum blood urea nitrogen, and ascending aortic diameter were the variables included in the nomogram by univariate and multivariate analysis. The risk model performed well in internal validation, with an area under the curve (AUC) of 0.829. The calibration curve demonstrated good agreement between predicted and actual probabilities (Hosmer-Lemeshow test, P = 0.22). Clinical decision analysis curves demonstrate predictive nomograms’ clinical utility. Conclusion This study created and validated a nomogram for predicting the risk of composite endpoint events in TAAD patients undergoing hybrid total aortic arch repair. The nomogram can help determine the severity of a patient’s condition and provide a more personalized diagnosis and treatment.

BackgroundThe crucial role of inflammation in aortic aneurysm (AA) is gaining prominence, while there is still a lack of key cytokines or targets for effective clinical translation.MethodsMendelian randomization (MR) analysis was performed to identify the causal relationship between 91 circulating inflammatory proteins and AA and between 731 immune traits and AA. Bulk RNA sequencing data was utilized to demonstrate the expression profile of the paired ligand-receptor. Gene enrichment analysis, Immune infiltration, and correlation analysis were employed to deduce the potential role of CX3CR1. We used single-cell RNA sequencing data to pinpoint the localization of CX3CL1 and CX3CR1, which was further validated by multiplex immunofluorescence staining. Cellchat analysis was utilized to infer the CX3C signaling pathway. Trajectory analysis and the Cytosig database were exploited to determine the downstream effect of CX3CL1-CX3CR1.ResultsWe identified 4 candidates (FGF5, CX3CL1, IL20RA, and SCF) in multiple two-sample MR analyses. Subsequent analysis of the expression profile of the paired receptor revealed the significant upregulation of CX3CR1 in AA and its positive correlation with pro-inflammatory macrophages. Two sample MR between immune cell traits and AA demonstrated the potential causality between intermediate monocytes and AA. We finally deciphered in single-cell sequencing data that CX3CL1 sent by endothelial cells (ECs) acted on CX3CR1 of intermediated monocytes, leading to its recruitment and pro-inflammatory responses.ConclusionOur study presented a genetic insight into the pathogenetic role of CX3CL1-CX3CR1 in AA, and further deciphered the CX3C signaling pathway between ECs and intermediate monocytes.

Abstract The power conversion efficiency of organic photovoltaics (OPVs) has witnessed continuous breakthroughs in the past few years, mostly benefiting from the extensive use of a facile ternary blending strategy by blending the host polymer donor:small molecule acceptor mixture with a second small molecule acceptor. Nevertheless, this rather general strategy used in the well‐known PM6 systems fails in constructing high‐performance P3HT‐based ternary OPVs. As a result, the efficiencies of all resulting ternary blends based on a benchmark host P3HT:ZY‐4Cl and a second acceptor are no more than 8%. Employing the mutual miscibility of the binary blends as a guide to screen the second acceptor, here we were able to break the longstanding 10%‐efficiency barrier of ternary OPVs based on P3HT and dual nonfullerene acceptors. With this rational approach, we identified a multifunctional small molecule acceptor BTP‐2Br to simultaneously improve the photovoltaic performance in both P3HT and PM6‐based ternary OPVs. Attractively, the P3HT:ZY‐4Cl:BTP‐2Br ternary blend exhibited a record‐breaking efficiency of 11.41% for P3HT‐based OPVs. This is the first‐ever report that over 11% efficiency is achieved for P3HT‐based ternary OPVs. Importantly, the study helps the community to rely less on trial‐and‐error methods for constructing ternary solar cells.

Summary: Background: Currently, the diagnostic testing for the primary origin of liver metastases (LMs) can be laborious, complicating clinical decision-making. Directly classifying the primary origin of LMs at computed tomography (CT) images has proven to be challenging, despite its potential to streamline the entire diagnostic workflow. Methods: We developed ALMSS, an artificial intelligence (AI)-based LMs screening system, to provide automated liver contrast-enhanced CT analysis for distinguishing LMs from hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), as well as subtyping primary origin of LMs as six organ systems. We processed a CECT dataset between January 1, 2013 and June 30, 2022 (n = 3105: 840 HCC, 354 ICC, and 1911 LMs) for training and internally testing ALMSS, and two additional cohorts (n = 622) for external validation of its diagnostic performance. The performance of radiologists with and without the assistance of ALMSS in diagnosing and subtyping LMs was assessed. Findings: ALMSS achieved average area under the curve (AUC) of 0.917 (95% confidence interval [CI]: 0.899–0.931) and 0.923 (95% [CI]: 0.905–0.937) for differentiating LMs, HCC and ICC on both the internal testing set and external testing set, outperformed that of two radiologists. Moreover, ALMSS yielded average AUC of 0.815 (95% [CI]: 0.794–0.836) and 0.818 (95% [CI]: 0.790–0.842) for predicting six primary origins on both two testing sets. Interestingly, ALMSS assigned origin diagnoses for LMs with pathological phenotypes beyond the training categories with average AUC of 0.761 (95% [CI]: 0.657–0.842), which verify the model's diagnostic expandability. Interpretation: Our study established an AI-based diagnostic system that effectively identifies and characterizes LMs directly from multiphasic CT images. Funding: National Natural Science Foundation of China, Guangdong Provincial Key Laboratory of Medical Image Processing.

[Introduction] The application of UPFC (Unified Power Flow Controller) is to increase the transmission capacity of key sections, which mainly through the injection of a certain series voltage into the system and therefore divert the power flow of target line. [Method] Focusing on the key transmission sections, the regional power grid was divided into the transmission network, the interconnection network and the internal network based on their function, then the Gaussian elimination method was used to equalize the system network into a two-channel constant power exchange system. On this basis, based on the energy conservation principle, the phasor method was applied to provide phasor graph of the voltage, power angle, impedance, and active power relationship between the UPFC branch and the equivalent branch before and after the UPFC was put into operation, respectively, for the stand-alone infinity system and the constant power exchange system. The classical power transfer function was used to deduced the UPFC injection voltage and series converter capacity calculation formula. [Result] The calculation method is simple and practical, especially suitable for power system planning and design stage. [Conclusion] The above method is applied to the calculation of Shenzhen power grid example, and compared with the simulation results of PSCAD, the validity and practicability of the method are verified.

Based on undrained cyclic simple shear tests conducted on coastal tidal soft soil under various conditions of cyclic stress ratios and moisture contents, this study investigated the influence of these factors on the dynamic properties of the soil. The findings indicated that with increasing moisture content and stress cycle ratio, the stress–strain hysteresis loop gradually expanded, resulting in a higher strain difference and a transition from a dense to a sparse curve pattern. Moreover, the symmetry of the hysteresis loop was lost in the later stages of shearing. With an increase in the number of cycles, the cumulative shear strain gradually increased, and the increase in the cyclic ratio of water content to stress reduced the number of cyclic shear cycles required to achieve failure, thereby accelerating the soil’s failure rate. A predictive formula was developed based on the experimental results to estimate the failure cycles as a function of the cyclic stress ratio and moisture content. Furthermore, the softening index decreased gradually with an increasing number of cycles, and a higher moisture content and cyclic stress ratio accelerated the soil’s softening process. It was observed that under the conditions of optimal moisture content, the soil exhibited a slower softening rate during the initial stage of shearing.

In this study, the rolling process of the warm-rolled duplex-phase Mg–8.3Li–3.1Al–1.09Si alloy and the strengthening mechanism of as-rolled Mg–Li alloy were investigated. The highest ultimate tensile strength (UTS, 323.66 ± 19.89 MPa) could be obtained using a three-pass rolling process with a 30% thickness reduction for each pass at 553 K. The strength of the as-rolled LAS831 alloy is determined by a combination of second-phase strengthening, grain refinement strengthening, dislocation strengthening, and load-transfer reinforcement. Of these factors, dislocation strengthening, which is caused by strain hardening of the α-Mg phase, can produce a good strengthening effect but also cause a decrease in plasticity. The Mg2Si phase is broken up into particles or strips during the rolling process. After three passes, the AlLi particles were transformed into an AlLi phase, and the Mg2Si particles and nanosized AlLi particles strengthened the second phase to form a hard phase. The average size of the DRXed β-Li grains decreased with each successive rolling pass, and the average size of recrystallized grains in the three-pass-rolled LAS831 alloy became as low as 0.27 μm. The interface between the strip-like Mg2Si phase and the α-Mg phase is characterized by semicoherent bonding, which can promote the transfer of tensile and shear forces from the matrix to the strip-like Mg2Si phase, thereby improving the strength of the matrix and thus strengthening the LAS831 alloy.

Abstract Immune checkpoint blockade (ICB) treatment of hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) infection may activate viral-specific T cells to attack HBV infected hepatocytes and thus induce immune-related liver injury. Therefore, it is important to deeply understand the impacts of HBV infection on HCC immune microenvironment in order to better design effective immunotherapies for HBV+ (HBV infected) HCC patients. Here, We performed cytometry by time-of-flight (CyTOF) analyses to characterize the distinct immune compositions of HCC tumors, tumor borders, and their associations with HCC/HBV related clinical characteristics. We identified 31 distinct immune clusters and found significant associations between immune signatures with clinicopathological features of HCC. We further revealed the HBV infection had more effects on shaping immune compositions in tumor borders than in tumors, with the significant enrichment of HBV-specific PD-1+CD8+ tissue-resident memory T (TRM) cells in tumor borders of HBV+ patients. We confirmed this subset with a more exhausted phenotype and respond more actively under anti-PD-L1 treatment, suggesting its involvement in immune-related liver injury induced by ICB treatment to HBV+ HCC patients. Our study shows it may be necessary to consider antiviral prophylaxis for HBV+ HCC patients receiving ICB treatment.

Abstract Singe‐phase single‐stage AC–DC converters exhibit the advantages of lower cost, higher efficiency, and lower power semiconductor device count compared with traditional two‐stage topologies. However, most existing single‐stage AC–DC topologies encounter some or all the following drawbacks: hard‐switching operation, bulky bus or output capacitor, uncontrolled bus voltage, not actively shaped input current, a large amount of power semiconductor devices, etc. The bridgeless single‐stage full‐bridge AC–DC converter can be considered a promising solution for high power capacity and efficiency. However, this topology still suffers from most of the drawbacks. In this paper, a new asymmetric modulation method of bridgeless single‐stage full‐bridge AC–DC converter is proposed to achieve active power factor (PF) correction and zero‐voltage switching. Topology description, the proposed modulation and control methods, theoretical analysis progress, and reference design procedure are presented in detail. Finally, a 2‐kW laboratory prototype is implemented with experimental results presented to validate the principle and design.

The primary factors responsible for inducing landslide disasters are earthquakes and rainfall. Using the strength reduction method within the finite element analysis software Abaqus, a study was conducted to analyze the stability of coastal geotechnical slopes. This investigation considered the combined influence of rainfall and earthquakes, taking into account the geological conditions and characteristics specific to these coastal areas. The results indicate that, under the same seismic acceleration amplitude, the shear strength of the slope soil gradually decreases as the water content increases, resulting in a decrease in the stability coefficient. Similarly, with a constant water content in the slope, an increase in seismic acceleration amplitude leads to heightened soil shear stress, consequently decreasing the stability coefficient. Maintaining constant water content while increasing seismic acceleration results in elevated soil shear stress, reduced shear strength, and a subsequent decrease in the stability coefficient. The simultaneous occurrence of intense rainfall and a strong earthquake pushes the slope to its most precarious state, causing the most significant reduction in the stability coefficient. Incorporating anti-slip piles substantially enhances the slope’s stability coefficient, and an optimal arrangement of anti-slip piles for the most unfavorable conditions is proposed.

Introduction: Luteolin is a plant-derived flavonoid that exhibits a broad range of pharmacological activities. Studies on luteolin have mainly focused on its use for hyperlipidaemia prevention, whereas the capacity of the flavonoid to hinder hyperglycaemia development remains underexplored. Objectives: To probe the anti-hyperglycemic mechanism of 6,8-guanidyl luteolin quinone-chromium coordination (GLQ.Cr), and to assess its regulatory effect on intestinal microbiota in type 2 diabetes mellitus (T2DM) mice. Methods: High-sucrose/high-fat diet-induced and intraperitoneal injection of streptozotocin was used to develop a T2DM model. Glycometabolism related indicators, histopathology, and gut microbiota composition in caecum samples were evaluated, and RNA sequencing (RNA-seq) of liver samples was conducted. Faecal microbiota transplantation (FMT) was further used to verify the anti-hyperglycemic activity of intestinal microbiota. Results: The administration of GLQ.Cr alleviated hyperglycaemia symptoms by improving liver and pancreatic functions and modulating gut microbe communities (Lactobacillus, Alistipes, Parabacteroides, Lachnoclostridium, and Desulfovibrio). RNA-seq analysis showed that GLQ.Cr mainly affected the peroxisome proliferative activated receptor (PPAR) signalling pathway in order to regulate abnormal glucose metabolism. FMT significantly modulated the abundance of Lactobacillus, Alloprevotella, Alistipes, Bacteroides, Ruminiclostridium, Brevundimonas and Pseudomonas in the caecum to balance blood glucose levels and counteract T2DM mice inflammation. Conclusion: GLQ.Cr improved the abnormal glucose metabolism in T2DM mice by regulating the PPAR signalling pathway and modulating intestinal microbial composition. FMT can improve the intestinal microecology of the recipient and in turn ameliorate the symptoms of T2DM-induced hyperglycaemia.

Abstract Aims Diabetes mellitus is a common chronic disease of glucose metabolism. Endothelial dysfunction is an early event in diabetes complicated by cardiovascular disease. This study aimed to reveal the expression of BASP1 and its biological roles in endothelial cell dysfunction in diabetes complicated by cardiovascular disease. Materials and Methods By analyzing the databases related to diabetes complicated with coronary heart disease, BASP1 was screened out as an upregulated gene. Human umbilical vein endothelial cells (HUVECs) and primary mouse aortic endothelial cells were treated with high glucose to establish cell models of diabetes‐related endothelial dysfunction, and the expression changes of BASP1 were verified by RT‐qPCR, western blot, and immunofluorescence. BASP1 was silenced or overexpressed by siRNA or overexpression plasmid, and its effects on cell migration, apoptosis, tube formation, inflammatory response, and ROS were detected. The possible signaling pathway of BASP1 was found and the mechanism of BASP1 on promoting the progression of endothelial dysfunction was explored using the EGFR inhibitor, gefitinib. Results Bioinformatics analysis indicated that the expression of BASP1 in patients with diabetes mellitus and concomitant coronary heart disease was increased. High glucose induced the upregulation of BASP1 expression in endothelial cells, and showed a time‐dependent relationship. Silencing of BASP1 alleviated the damage of high glucose to endothelial cells. BASP1 regulated EGFR positively. The promoting effect of BASP1 on endothelial cell apoptosis may be achieved by regulating the EGFR pathway. Conclusion BASP1 promotes endothelial cell injury induced by high glucose in patients with diabetes, which may be activated by activating the EGFR pathway.

Nowadays, the use of new compound chemical stabilizers to treat marine clay has gained significant attention. However, the complex non-linear relationship between the influencing factors and the unconfined compressive strength of chemically treated marine clay is not clear. In order to study the influence of various factors (dosage, type of stabilizer, curing age) on the unconfined compressive strength of solidified soil during chemical treatment, experiments were performed to determine the unconfined compressive strength of soft marine clay modified with various types of stabilizers. Further, an artificial neural network (ANN) model was used to establish a prediction model based on the unconfined compressive strength test data and to verify the performance. Sensitivity and optimization analyses were further conducted to explore the relative significance of parameters as well as the optimal dosage amount. Research has found that when the content of aluminate cement is 89.5% and the content of curing agent is 30%, the unconfined compressive strength significantly increases after 28 days of solidification, and the change in quicklime content has the greatest effect on the improvement in the unconfined compressive strength. The influence of modifiers on the unconfined compressive strength is in the order: potassium hydroxide > kingsilica > quick lime > bassanite. The values of each factor were obtained when the unconfined compressive strength was the maximum, which provided support for the optimization of the treatment scheme. The analysis of chemical treatment is no longer limited to the linear relationship according to the test results, which proves the feasibility of non-linear relationship analysis based on the artificial neural network.

BackgroundType A aortic dissection (TAAD) is a cardiovascular emergency condition with high mortality rate. Hybrid total aortic arch replacement using endovascular graft for the descending aorta repair results in favorable outcomes and has been recommended as an alternative procedure for the higher-risk category patients. Our institution started applying the upper ministernotomy incision technique for the hybrid procedures back in 2018.MethodsWe collected patients who underwent hybrid total arch replacement (HTAR) via ministernotomy (96) and total arch replacement with frozen elephant trunk (TAR + FET) procedures (99), between 2018 and 2021. The baseline information, intraoperative and postoperative characteristics have been compared. Kaplan-Meier analysis was used for survival evaluation. Cox regression were applied to identify the independent predictor of mortality.ResultsThe baseline characteristics between the two patient groups were compared and found similar, except that RBC counts were higher (p = 0.038) and the ascending aorta diameter was smaller (P = 0.019) in the “HTAR” group relative to the “TAR + FET” group. The cardiopulmonary bypass time (P

Abstract Macrophages in tumors (tumor-associated macrophages, TAMs), a major population within most tumors, play key homeostatic functions by stimulating angiogenesis, enhancing tumor cell growth, and suppressing antitumor immunity. Resetting TAMs by simple, efficacious and safe approach(s) is highly desirable to enhance antitumor immunity and attenuate tumor cell malignancy. Previously, we used tumor cell-derived microparticles to package chemotherapeutic drugs (drug-MPs), which resulted in a significant treatment outcome in human malignant pleural effusions via neutrophil recruitments, implicating that drug-MPs might reset TAMs, considering the inhibitory effects of M2 macrophages on neutrophil recruitment and activation. Here, we show that drug-MPs can function as an antitumor immunomodulator by resetting TAMs with M1 phenotype and IFN-β release. Mechanistically, drug molecules in tumor MPs activate macrophage lysosomal P450 monooxygenases, resulting in superoxide anion formation, which further amplifies lysosomal ROS production and pH value by activating lysosomal NOX2. Consequently, lysosomal Ca2+ signaling is activated, thus polarizing macrophages towards M1. Meanwhile, the drug molecules are delivered from lysosomes into the nucleus where they activate DNA sensor hnRNPA2B1 for IFN-β production. This lysosomal-nuclear machinery fully arouses the antitumor activity of macrophages by targeting both lysosomal pH and the nuclear innate immunity. These findings highlight that drug-MPs can act as a new immunotherapeutic approach by revitalizing antitumor activity of macrophages. This mechanistic elucidation can be translated to treat malignant ascites by drug-MPs combined with PD-1 blockade.

Acute lung injury (ALI) is considered as a severe respiratory disease with aggravated inflammatory responses. Krüppel-like factor 9 (KLF9), a member of KLF family, has been reported to be involved in inflammatory disorders. However, the effect of KLF9 in ALI has not been elucidated. Here the present study was to clarify the role of KLF9 and its mechanism in ALI. The ALI in vitro model was established with lipopolysaccharide (LPS)-treated RAW264.7 cells. Mice were injected with LPS to conduct an ALI in vivo model. The expression of KLF9 and gasdermin D (GSDMD) was examined using quantitative reverse transcription-PCR, haematoxylin-eosin/immunohistochemistry staining and western blot assays. Enzyme-linked immunosorbent assay was employed to detect the levels of inflammatory cytokines. JASPAR database was used to predict the recognition motif of KLF9, and the relationship between KLF9 and GSDMD was determined by luciferase reporter assay and chromatin immunoprecipitation analysis. The number of neutrophils in bronchoalveolar lavage fluid as well as the wet/dry weight ratio was caculated. The results showed that The expression of KLF9 in lung was significantly increased in LPS-stimulated mice. Moreover, KLF9 knockout relieved the lung injury in ALI mice. GSDMD is one of targets genes of the transcription factor KLF9. KLF9 knockout induced a decreased expression of GSDMD in LPS-treated mice. Furthermore, in RAW264.7 cells after LPS administration, KLF9 knockdown reduced the levels of inflammatory factors and suppressed the expression of GSDMD. In summarise, these findings exhibited that KLF9 knockout could mitigate the lung injury and inflammatory responses in ALI mice by directly regulating GSDMD.

Abstract Background This study attempted to verify the potential of KCNJ14 as a biomarker in colorectal cancer (CRC). Methods Data on transcriptomics and DNA methylation and the clinical information of CRC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Biological information analysis methods were conducted to determine the role of KCNJ14 in the prognosis, diagnosis, immune cell infiltration, and regulation mechanism of CRC patients. The effect of KCNJ14 on the proliferation and migration of HCT116 and SW480 CRC cell lines was verified by in vitro experiments (MTT, colony-forming, wound healing, and transwell assays). Western blotting was performed to detect the effect of KCNJ14 on the levels of mTOR signalling pathway-related proteins. Results KCNJ14 expression was remarkably increased in CRC tissues and cell lines, which reduced the overall survival time of patients. KCNJ14 mRNA was negatively regulated by its methylation site cg17660703, which can also endanger the prognosis of patients with CRC. Functional enrichment analysis suggested that KCNJ14 is involved in the mTOR, NOD-like receptor, and VEGF signalling pathways. KCNJ14 expression was positively correlated with the number of CD4 + T cells and negatively correlated with that of CD8 + T cells in the immune microenvironment. KCNJ14 knockdown significantly reduced not only the proliferation and migration of CRC cell lines but also the levels of mTOR signalling pathway-related proteins. Conclusions This study not only increases the molecular understanding of KCNJ14 but also provides a potentially valuable biological target for the treatment of colorectal cancer.