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Catalytic hydrogenation of carbon dioxide to methanol offers a promising avenue for recycling CO2, enhancing environmental sustainability. Cu/ZnO has long been identified as one of the most effective heterogeneous catalysts for this reaction, yet the detailed understanding of its reaction mechanism and active sites remains incomplete. Recent advances have highlighted the critical role of defects, such as ZnCu steps and stacking faults on Cu surfaces, in enhancing catalyst performance. Here this concept is explored through first‐principles surface simulations of six models, featuring diverse Cu–Zn combinations and specific coordination environments under realistic conditions. It is revealed that Cu/ZnO catalysts with kink defects, rather than surface ZnCu alloys, exhibit optimal activity for methanol synthesis. Specifically, the findings demonstrate how intermediate configurations and rate‐determining steps vary with changes in surface structure and reveal the role of the kink in promoting CO2 reduction to methanol through electronic structure calculation. Moreover, it is found that the predominant synthetic pathway for CH3OH from CO2 involves the reverse water gas shift and CO hydrogenation, rather than the formate route, on Cu/ZnO surfaces with kinks.

Abstract In this paper, we selected representative electric buses (EBs) and diesel buses as research cases, aiming to explore a localized method suitable for various vehicle types that can be implemented in any region to measure the carbon emissions of urban buses throughout the lifecycle. We take into account the influence of seasonal factors over the lifecycle. We fully consider the production, assembly, and recycling stages of vehicle systems. We construct a model for estimating CO2 emissions during the fuel cycle. We analyze and compare the impacts of the optimized power grid structure on the lifecycle CO2 emissions of the two types of buses. The results indicate that seasonal factors affect both bus types' energy consumption, with EBs being more sensitive. Carbon emissions primarily stem from manufacturing the body, chassis, and notably, the lithium‐ion batteries, with the latter having a pronounced impact on EBs. A decrease in coal power generation from 71% to 21% in the grid reduced EB fuel‐cycle emissions by 70.7%. Although EBs are sensitive to seasonal factors, they still have the greatest potential for carbon reduction, depending on the proportion of clean energy in the power grid and the production processes of vehicle components.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulators may attenuate PCSK9-induced low-density lipoprotein receptor (LDLR) degradation in lysosome and promote the clearance of circulating low-density lipoprotein cholesterol (LDL-C). A novel series of tetrahydroprotoberberine derivatives (THPBs) were designed, synthesized, and evaluated as PCSK9 modulators for the treatment of hyperlipidemia. Among them, eight compounds exhibited excellent activities in downregulating hepatic PCSK9 expression better than berberine in HepG2 cells. In addition, five compounds 15, 18, 22, (R)-22, and (S)-22 showed better performance in the low-density lipoprotein, labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl-indocarbocyanine perchlorate (DiI-LDL) uptake assay, compared with berberine at the same concentration. Compound 22, selected for in vivo evaluation, demonstrated significant reductions of total cholesterol (TC) and LDL-C in hyperlipidemic hamsters with a good pharmacokinetic profile. Further exploring of the lipid-lowering mechanism showed that compound 22 promoted hepatic LDLR expression in a dose-dependent manner in HepG2 cells. Additional results of human ether-à-go-go related gene (hERG) inhibition assay indicated the potential druggability for compound 22, which is a promising lead compound for the development of PCSK9 modulator for the treatment of hyperlipidemia. Key words: PCSK9, Tetrahydroprotoberberine derivatives, Low-density lipoprotein cholesterol, Lipid-lowering, PCSK9 expression, Low-density lipoprotein receptor, Total cholesterol, Hyperlipidemia hamster

Metabolomics has great potential to process accessible biofluids through high-throughput and quantitative analysis for radiation biomarker screening. This study focused on the potential radiation responsive metabolites in rat plasma and the dose-response relationships. In the discovery stage, 20 male Sprague–Dawley rats were exposed to 0, 1, 3 and 5 Gy of cobalt-60 gamma rays at a dose rate of 1 Gy/min. Plasma samples were collected at 72 h after exposure and analyzed using liquid chromatography mass spectrometry based on non-targeted metabolomics. In the verification stage, 50 additional rats were exposed to 0, 1, 2, 3, 5 and 8 Gy of gamma rays. The concentrations of candidate metabolites were then analyzed using targeted metabolomics methods. Fifteen candidate radiation responsive metabolites were identified as potential radiation metabolite biomarkers. Metabolic pathways, such as linoleic acid metabolism and glycerophospholipid metabolism pathways, were changed after irradiation. Six radiation responsive metabolites, including LysoPC(20:2), LysoPC(20:3), PC(18:0/22:5), L-palmitoylcarnitine, N-acetylornithine and butyrylcarnitine, had good dose-response relationships ( R 2 > 0.80). The area under the curve of the panel of the 6 radiation responsive metabolites was 0.923. The radiation exposure metabolomics biomarkers and dose-response curves may have potential for rapid dose assessment and triage in nuclear and radiation accidents.

Due to the increased frequency and magnitude of changes in urban road traffic demand, temporal resource optimization alone is no longer effective in alleviating congestion at intersections. A spatial resource optimization mode based on variable guiding lanes has caused some confusion to drivers, making it difficult to fully improve spatial resource optimization efficiency. This paper proposes a multiobjective optimal spatial and temporal resource assignment model based on the intelligent vehicle infrastructure cooperative system (I-VICS) and variable guidance lane (VGL). The model constrains the number of lanes, signal timing, traffic demand, evaluation indicators, communication conditions, and type of variables, aiming to maximize green signal utilization and minimize lane occupancy ratio. Through the introduction of a speed guidance strategy and a signal-coordinated optimization model, demand-responsive control coordinated with signals is achieved. The assignment model is solved by combining a fuzzy inference system and the nondominated sorting genetic algorithm with the elite strategy (NSGA-II). Finally, the model is integrated with the solving method into an intelligent control process for practical application. The interaction of information between the onboard units and roadside units eliminates information barriers for drivers. Simulation results demonstrate that the proposed solution can significantly reduce the average vehicle delay by 25.34% and average traveling time by 38.59%. Furthermore, under oversaturated conditions during peak hours, both green signal utilization and lane occupancy rates are increased to different extents, with maximum benefit increments of 17.23% and 18.74%, respectively. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Chondroblastoma is a rare bone tumor that originates from the epiphysis, constitutes around 1% of all primary bone tumors and is recognized for its tendency to exhibit local invasiveness, as well as the possibility of metastasis and recurrence in nearby areas. Currently, the main surgical treatment for chondroblastoma is open surgery, involving excision of the lesion. There are relatively few reports on arthroscopic surgery for the treatment of chondroblastoma. However, open surgical curettage is associated with operation‐related trauma and potential for damage to the osteoepiphysis resulting in growth disturbances. Case Presentation This case study presents the application of an arthroscopic technique in a 14‐year‐old male patient with chondroblastoma affecting the proximal tibia and tibial eminence. The procedure involved thorough removal of the lesion using direct visualization with the management of the cavity utilizing a substitute for autologous bone graft. After 1 year of follow‐up, the patient remains free from symptoms, exhibits normal knee functionality, and radiographic analysis reveals a good autologous bone graft fusion without any signs of recurrence. Conclusions Based on the existing cases of arthroscopic treatment for chondroblastoma and the report of this case, arthroscopic treatment for chondroblastoma can be considered as a specific treatment option for certain patients. In some cases, this technique could be an effective alternative to open surgery.

Abstract High-performance gas separation membranes have potential in industrial separation applications, while overcoming the permeability-selectivity trade-off via regulable aperture distribution remains challenging. Here, we report a strategy to fabricate Polyolefin Reweaved Ultra-micropore Membrane (PRUM) to acquire regulable microporous channel. Specifically, olefin monomers are dispersed uniformly into a pristine membrane (e.g., PIM-1) via solution diffusion method. Upon controlled electron beam irradiation, the olefin undergoes a free radical polymerization, resulting in the formation of olefin polymer in-situ reweaved in the membrane. The deliberately regulated and contracted pore-aperture size of the membrane can be accomplished by varying the olefin polymer loading to achieve efficient gas separation. For instance, PIM-1 PRUM containing 27 wt% poly-glycidyl methacrylate demonstrate CO2 permeability of 1976 Barrer, combined with CO2/CH4 and CO2/N2 selectivities of 58.4 and 48.3 respectively, transcending the performance upper bounds. This controllable and high efficiency-design strategy provides a general approach to create sub-nanometre-sized pore-apertures of gas separation membranes with wide universality.

Abstract Aiming at the crucial engineering challenge of the ambiguous excavation deformation mechanism of hard and brittle surrounding rock under high geos-tress conditions, with the right bank diversion tunnel at the dam site of the hydropower station as the research object, the deformation and failure characteristics of the surrounding rock and their formation mechanisms during the layered excavation of the diversion tunnel were investigated. The research findings show: (1) The main factors influencing the deformation of the diversion tunnel’s surrounding rock are the high ground stress environment, the degree of fracture development in the rock mass, and the effectiveness of the support system. (2) Following the excavation of the first layer, extensive shallow damage predominates, with damaged blocks primarily exhibiting sheet-like and plate-like forms. After excavating the second and third layers, there is a significant reduction in confining pressure in this region, leading to a rapid deterioration in the extent of damage. (3) Layered excavation induces ‘time-dependent’ variations in the yield characteristics of the surrounding rock, while simultaneously being influenced by the location and extent of fracture development. The study results are expected to provide a theoretical basis for the excavation of underground caverns under high ground stress.

In this study, the bond-slip behavior between textile reinforced concrete (TRC)-confined concrete and rebars both at ambient temperature and after ISO 834 standard fire was investigated experimentally through pull-out tests. The failure modes, ultimate load, average ultimate bonding stress and energy consumption were obtained and discussed. Effects of rebar diameters (12 mm, 14 mm and 16 mm), bonding lengths (2.5d, 5d and 7.5d) and high-temperature exposure durations (30 min and 60 min) on the bonding behavior between TRC-confined concrete and rebars were examined emphatically. It was observed that the damage modes of specimens changed from pull-out failure at ambient temperature into splitting failure for both TRC-confined specimens and companion unconfined specimens exposed to high temperatures. The results obtained demonstrated that both the ultimate load and the average ultimate bonding stress can be significantly improved by the utilization of TRC jackets after 30 min exposure, and the increment of the average ultimate bonding stress can reach up to 90% as compared to those unconfined specimens. However, the enhancement of TRC jackets became unobvious after 60 min. Finally, based on test results and Prigogine's dissipative structure theory, the energy analysis of bond-slip curves was evaluated to verify the enhancement of TRC jackets quantitatively. [ABSTRACT FROM AUTHOR]

In order to investigate the impact of ozone pretreatment and lipid modification on the structure and properties of starch, ozone-pretreated banana starch-lauric acid complexes were prepared and their physicochemical properties and digestibility were evaluated. Results showed that in comparison with the native starch, the complexation index (CI) of the pretreated starch with lauric acid increased by 12.67%; the resulting complexes exhibited a significant increase in water solubility, swelling power and syneresis, an elevation in gelatinization temperature from 104.24–135.23 ℃ to 155.60–161.68 ℃, and a 6.71% increase in resistant starch, but a decrease in iodine binding capacity. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) demonstrated that lauric acid was bound to the surface of starch granules to form a complex, thereby increasing the surface height of starch granules. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) revealed that banana starch and lauric acid formed non-V-type and V-type complexes through hydrogen bonding and hydrophobic interactions. The results of contact angle and thermogravimetric (TG) analysis demonstrated that the hydrophobic properties and thermal stability of the complexes were improved. Consequently, the combination of ozone pretreatment and lauric acid modification could enhance the water solubility, swelling capacity, and thermal stability of banana starch, further improving its digestibility resistance. These findings will expand the application potential of starch in the food field.

Abstract Objective It has been shown that the CYFIP2 (Cytoplasmic FMR1-interacting protein 2) gene is apoptosis p53-dependent and is associated with poor prognosis in malignant tumors such as gastric cancer and other and cervical cancer. However, the prognostic potential of CYFIP2 in pancreatic cancer remains unclear. In this work, we first explain the great potential of CYFIP2 malignant progression from a broader perspective (pan-cancer) and confirm its oncogenic value in pancreatic cancer. Methods The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) database, CELL and GEO databases were utilized to explore the distribution of the CYFIP2 gene in human cancers. Data were analyzed using a variety of web-based platforms and software such as R (4.3.2), UCSC, MethSurv, Cytoscape (v3.10.2), UALAND, STRING, TISIDB, Harmonizome 3.0, TIMER 2.0, TCIA and TIDE. The R packages R packages “limma” and “ggplot2” were used to compare and visualize CYFIP2 mRNA expression. The R packages “survminer” and “survival” were used to statistically analyze the relationship between CYFIP2 expression and the survival and prognosis of tumor patients. the R package “ss GSEA” was used to assess the correlation between CYFIP2 expression and immune infiltration. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Variation Analysis (GSVA) were used to explore the multiple biological functions and regulatory pathways in which CYFIP2 co-expressed genes co-engage in pancreatic cancer. The R package “maftool” was used to explore somatic mutation information in pancreatic cancer, and the TIDE database and the R package “oncoPredic” were used to explore immunotherapeutic responses and sensitive drugs. Pancreatic cancer cell lines were constructed with the specific expression of CYFIP2 mRNA, and their invasive and metastatic abilities were analysed using scratch and transwell assays. Results Bioinformatics analysis and in vitro experiments confirmed that CYFIP2 was differentially expressed in a variety of tumors and correlated with clinical stage, and could be used as a potential marker for evaluating the prognosis and immunotherapy of a variety of tumors, including KIRC (Kidney renal clear cell carcinoma), PAAD (Pancreatic adenocarcinoma), PAAD (Pancreatic adenocarcinoma), SKCM (Skin Cutaneous Melanoma), and UCEC (Uterine Corpus Endometrial Carcinoma).Mutations in the CYFIP2 gene and methylation indices can affect the prognosis of tumor patients. In addition, we found that CYFIP2 expression values in pancreatic cancer were positively correlated with the expression of most immune cells, especially CD8 + T Cells, and significantly negatively correlated with macrophages M0, and negatively correlated with the metastatic and invasive ability of pancreatic cancer cells, which may provide new strategies and ideas for pancreatic cancer immunotherapy.

Abstract This study investigated whether transcranial direct current stimulation (tDCS) targeting the inferior frontal gyrus (IFG) can alter the thinking process and neural basis of creativity. Participants’ performance on the compound remote associates (CRA) task was analyzed considering the semantic features of each trial after receiving different tDCS protocols (left cathodal and right anodal, L + R−; right cathodal and left anodal, L−R+; and Sham). Moreover, we constructed and compared 80 prediction models of CRA performance for each group based on task-related functional connectivity. Results showed that L + R− stimulation improved performance in semantically bundled CRA trials, while L−R+ stimulation enhanced performance in trials with greater semantic distance. Furthermore, alpha-band task connectivity models for the L + R− group showed inferior performance and greater left frontal lateralization than other two groups. These findings suggest that tDCS targeting the bilateral IFG alters cognitive processes during creative ideation rather than enhancing or impairing an established thinking process.

Abstract Idiopathic pulmonary fibrosis (IPF) is a high-mortality lung disease with unclear pathogenesis. Convincing evidence suggests that an imbalance in mitochondrial homeostasis resulting from repeated injury to alveolar epithelial type 2 cells (AEC2) underlies IPF. Non-receptor protein tyrosine phosphatase 21 (PTPN21) performs various functions in cancer; however, its role in IPF has not been studied. This study aimed to investigate the role of PTPN21 in lung fibrosis. The experimental results showed that loss of PTPN21 exacerbated lung fibrosis by increasing cell numbers in bronchoalveolar lavage fluid, lung hydroxyproline content, and extracellular matrix protein expression of fibronectin and α-smooth muscle actin (α-SMA) in bleomycin-challenged mouse lungs. In A549 cells (AEC2), knockdown of PTPN21 suppressed focal adhesion and migration, reduced mitochondrial fission and increased fusion, increased the level of mitochondrial superoxide, decreased mitochondrial membrane potential and ATP levels. Simultaneously, knockdown of PTPN21 impaired autophagy, and increased intracellular reactive oxygen species levels. Treatment of fibroblasts (MRC-5) and primary human lung fibroblasts (PHLF)) with the supernatant from PTPN21-knockdown A549 cells increased the expression of fibronectin, collagen 1 and α-SMA. Conversely, overexpression of PTPN21 in A549 cells produced opposite effects. However, treatment of MRC-5 and PHLF with the supernatant from PTPN21-overexpressing A549 cells only slightly reduced the expression of fibronectin, collagen 1 in MRC-5 cells, but did not change the expression of α-SMA. In summary, this study revealed that the loss of PTPN21 in epithelial cells disrupted mitochondrial metabolic homeostasis, leading to epithelial cell inactivation and increased the deposition of extracellular matrix proteins in fibroblasts, thereby exacerbating experimental pulmonary fibrosis.

Abstract Background Huashi Baidu Formula (HBF) is a clinical formula known for its efficacy against coronavirus disease 2019 (COVID-19). HBF may reduce the number of patients with abnormal serum creatinine while improving respiratory symptoms, suggesting that this formula may have potential for treating acute kidney injury (AKI). However, the protective effect of HBF on AKI has not been definitively confirmed, and the mechanism remains unclear. Therefore, the present study explored the renoprotective effects and molecular mechanisms of HBF and screened for its active ingredients to identify new potential applications of renoprotection by HBF. Methods The present study first assessed the protective effects of HBF on AKI in a DOX-induced mouse model. Then, RNA-seq and bioinformatics analyses were used to explore the related pathological processes and potential molecular mechanisms, which were subsequently validated using qRT-PCR and Western blotting. Furthermore, candidate compounds with potential binding affinity to two pivotal targets, sphingosine kinase 1 (SphK1) and plasminogen activator inhibitor-1 (PAI-1), were screened from the 29 constituents present in the blood using Microscale Thermophoresis (MST). Finally, to identify the active ingredients, the candidate components were re-screened using the SphK1 kinase activity detection system or the uPA/PAI-1 substrate colorimetric assay system. Results In the DOX-induced AKI mouse model, therapeutic administration of HBF significantly reduced the levels of CRE, BUN, TNF-α, IL-1β, IL-6, and UA in plasma and the levels of MDA, T-CHO, and TG in kidney tissue. Additionally, the levels of TP and Alb in plasma and SOD and CAT in the kidney tissue were significantly increased. Histopathological assessment revealed that HBF reduced tubular vacuolation, renal interstitial inflammatory cell infiltration, tubular atrophy, and positive staining of renal interstitial collagen. RNA-seq and bioinformatics analyses showed that oxidative stress, the immune-inflammatory response, and extracellular matrix (ECM) formation could be the pathological processes that HBF targets to exerts its renoprotective effects. Furthermore, HBF regulated the APJ/SPHK1/NF-κB and APJ/PAI-1/TGFβ signaling axes and reduced the phosphorylation levels of NF-κB p65 and SMAD2 and the expression of cytokines and the ECM downstream of the axis. Finally, six SphK1 inhibitors (paeoniflorin, astragalin, emodin, glycyrrhisoflavone, quercetin, and liquiritigenin) and three PAI-1 inhibitors (glycyrrhisoflavone, licochalcone B, and isoliquiritigenin) were identified as potentially active ingredients in HBF. Conclusion In brief, our investigation underscores the renoprotective effect of HBF in a DOX-induced AKI model mice, elucidating its mechanisms through distinct pathological processes and identifying key bioactive compounds. These findings offer new insights for broadening the clinical applications of HBF and unravelling its molecular mode of action.

Abstract Background Osteogenesis imperfecta (OI) is a genetic disorder characterized by low bone mass, bone fragility and short stature. There is a significant gap in knowledge regarding the growth patterns across different types of OI, and the prediction of height in individuals with OI was not adequately addressed. In this study, we described the growth patterns and predicted the height of individuals with OI employing multiple machine learning (ML) models. Accurate height prediction enables effective monitoring and facilitates the development of personalized intervention plans for managing OI. Method This study included cross-sectional data for 323 participants with OI, and the median height Z-score for OI types I, III and IV were − 0.62 (-5.93 ~ 3.24), -3.97 (-10.44 ~ -0.02) and − 1.64 (-6.67 ~ 2.44), respectively. Based on the cross-sectional data of participants, the height curves across different gender and OI types were plotted and compared. Subsequently, feature selection techniques, specifically the filter and wrapper methods, were employed to identify predictive factors for the height of participants. Finally, multiple machine learning (ML) models were constructed for height prediction, and the performance of each model was systematically evaluated. Results The analysis of height curves revealed that male with OI are significantly taller than female with OI from the age of 14 (p = 0.045), individuals with OI type III are statistically shorter than those with OI types I and IV starting from 3 years old (p = 0.006), and those with OI type IV are statistically shorter than those with OI type I from the age of 10 (p = 0.028). The application of filter and wrapper methods identified gender (p = 0.001), age (p

Abstract Aberrant repair underlies the pathogenesis of pulmonary fibrosis while effective strategies to convert fibrosis to normal regeneration are scarce. Here, we found that thyroid hormone is decreased in multiple models of lung injury but is essential for lung regeneration. Moreover, thyroid hormone receptor α (TRα) promotes cell proliferation, while TRβ fuels cell maturation in lung regeneration. Using a specific TRβ agonist, sobetirome, we demonstrate that the anti-fibrotic effects of thyroid hormone mainly rely on TRβ in mice. Cellularly, TRβ activation enhances alveolar type-2 (AT2) cell differentiation into AT1 cell and constrains AT2 cell hyperplasia. Molecularly, TRβ activation directly regulates the expression of KLF2 and CEBPA, both of which further synergistically drive the differentiation program of AT1 cells and benefit regeneration and anti-fibrosis. Our findings elucidate the modulation function of the TRβ-KLF2/CEBPA axis on AT2 cell fate and provide a potential treatment strategy to facilitate lung regeneration and anti-fibrosis.

The microchannel plate (MCP) is an electron multiplier with millions of micro through-holes that must withstand strong vibrations and enormous shocks in spaceborne detectors. To ensure the reliability and robustness of the MCP in space applications, we proposed an equivalent mechanical model of the MCP to investigate its mechanical properties, since the direct creation of the finite element model using the finite element method (FEM) is not feasible. Then, we developed a test system to verify the effectiveness of the equivalent mechanical model. The results show that the error of harmonic response analysis and the test result is less than 10 %, which is acceptable. Finally, we conducted parametric studies of the MCPs and obtained the equivalent mechanical model of the MCPs with different geometric parameters. This study will help researchers to optimize the MCP for aerospace-grade detectors.

Abstract We discover an intrinsic dipole Hall effect in a variety of magnetic insulating states at integer fillings of twisted MoTe2 moiré superlattice, including topologically trivial and nontrivial ferro-, antiferro-, and ferri-magnetic configurations. The dipole Hall current, in linear response to in-plane electric field, generates an in-plane orbital magnetization M ∥ along the field, through which an AC field can drive magnetization oscillation up to THz range. Upon the continuous topological phase transitions from trivial to quantum anomalous Hall states in both ferromagnetic and antiferromagnetic configurations, the dipole Hall current and M ∥ have an abrupt sign change, enabling contact-free detection of the transitions through the magnetic stray field. In configurations where the linear response is forbidden by symmetry, the dipole Hall current and M ∥ appear as a crossed nonlinear response to both in-plane and out-of-plane electric fields. These magnetoelectric phenomena showcase fascinating functionalities of insulators from the interplay between magnetism, topology, and electrical polarization.

Abstract Ovarian cancer, the second most leading cause of gynecologic cancer mortality worldwide, is challenged by chemotherapy resistance, presenting a significant hurdle. Pyroptosis, an inflammation-linked programmed cell death mediated by gasdermins, has been shown to impact chemoresistance when dysregulated. However, the mechanisms connecting pyroptosis to chemotherapy resistance in ovarian cancer are unclear. We found that cytokine receptor-like factor 1 (CRLF1) is a novel component of mTORC2, enhancing AKT Ser473 phosphorylation through strengthening the interaction between AKT and stress-activated protein kinase interacting protein 1 (SIN1), which in turn inhibits the mitogen-activated protein kinase kinase kinase 5 (ASK1)-JNK-caspase-3-gasdermin E pyroptotic pathway and ultimately confers chemoresistance. High CRLF1-expressing tumors showed sensitivity to AKT inhibition but tolerance to cisplatin. Remarkably, overexpression of binding-defective CRLF1 variants impaired AKT-SIN1 interaction, promoting pyroptosis and chemosensitization. Thus, CRLF1 critically regulates chemoresistance in ovarian cancer by modulating AKT/SIN1-dependent pyroptosis. Binding-defective CRLF1 variants could be developed as tumor-specific polypeptide drugs to enhance chemotherapy for ovarian cancer.

Abstract PANoptosis is engaged in the program of immune response and carcinogenicity. Nonetheless, the actual impacts of PANoptosis on clinical management and oncology immunity in hepatocellular carcinoma (HCC) are not fully grasped. RNA-seq-derived computations were conducted to sort out the molecular subtypes and elucidate the disparities based on PANoptosis molecules. Single-cell sequencing (scRNA-seq) tools including Cytotrace and Addmodulescore were extracted to characterize diversification potency and quantify the PANoptosis motion. Transcriptional factors were inferred by the pySCENIC package and Cellchat program scrutinized the intercellular exchange across cell compartments. The PANoptosis score system originated by incorporating 10 machine learning algorithms and 101 compositions to project clinical results and deteriorate tendencies. Circulatory PANoptosis-associated protein HSP90AA1 was determined by enzyme-linked immunosorbent assay (ELISA). HCC individuals could be categorized into low- and high-PANoptosis groups with diverse biogenic and pharmacotherapy heterogeneity. Individuals in the elevated PANoptosis subtype were characterized as “hot tumor” conveying the increased presence of immunogenicity while reiterating an explicit negative connection with tumor stemness. Compared to immune and stromal cells, cancerous cells showcased decreased PANoptosis and heightened PANoptosis malignant cell subgroups might be tied to a substantial level of genomic expression of SREBF2, JUND, GATAD1, ZBTB20, SMAD5 and implied a more aggressive potential. The PANoptosis index, derived from machine learning, has been established to provide succinct frameworks for predicting outcomes and clarified the noteworthy utility of conventional regimens, as the differentiated power of HCC occurred together with vascular invasion and hepatocellular adenoma (HCA). The experiment confirmed that the circulating HSP90AA1 was aberrantly augmented in HCC patients, thus demonstrating its potential as a discriminatory biomarker. We systematically deciphered the molecular and immune ecosystem traits of PANoptosis in bulk and scRNA-seq degrees, which may deliver advantageous insights for customized treatment, awareness of the pathological process and prognosis scrutiny for HCC patients.

Oleanolic acid (OA) is a five-ring triterpenoid compound, which is widely present in plants. Due to a wide range of pharmacological activities, oleanolic acid has attracted more and more attention. However, oleanolic acid is insoluble in water and has low bioavailability, which limits its clinical application. In this review, we focus on summarizing the anti-cancer activity and mechanism of the A ring or C-28 carboxyl modified derivatives of OA since 2015, to determine the strength of its anti-cancer effectiveness and evaluate whether it could be used as a clinical anti-cancer drug. [ABSTRACT FROM AUTHOR]

The prevailing trend in industrial equipment development is integration, with pipelines as the lifeline connecting system components. Given the often harsh conditions of these industrial equipment pipelines, leakage is a common occurrence that can disrupt normal operations and, in severe cases, lead to safety accidents. Early detection of even minor drips at the onset of leakage can enable timely maintenance measures, preventing more significant leaks and halting the escalation of pipeline failures. In light of this, our study investigates a method for monitoring pipe drips in industrial equipment using machine vision technology. We propose a machine vision model specifically designed for pipe drip detection, aiming to facilitate monitoring of pipe system drips. The system designed to collect the image of the droplet side cross-section with a Charge charge-coupled device (CCD) industrial camera, is aided by the computer image processing system used to analyze and process the collected images. Image enhancement technology is applied to improve the visibility of the image and image filtering technology is applied to remove the noise of the image. With the help of image segmentation technology, target droplet identification and division are achieved. Morphological reconstruction and region-filling techniques are used to remove the noise caused by shooting in the side cross-section image, such as hollow, reflection, and irregular droplet edge, to upgrade the quality of the solution droplet edge. The mathematical model is established for boundary position points extracted from the droplet side cross-section image. Then, the fitting droplet image is drawn. The droplet volume is obtained by calculating the volume of the rotating body. The two-dimensional image of the target droplet is obtained dynamically through the camera capture technology. The droplet boundary extraction algorithm is proposed, and the three-dimensional model of the target droplet is established, so the volume calculation problem of the droplet is solved, which provides a way of thinking for drip leakage detection of the pipeline.

lncRNAs (long non-coding RNAs) are heterogeneous RNA molecules that modulate various cellular processes, such as proliferation, differentiation, migration, invasion, and apoptosis, via different mechanisms. An increasing amount of research indicates that abnormal expression of lncRNA influences the development of drug resistance as well as the genesis and advancement of cancer, including melanoma. Furthermore, they are attractive biomarkers for non-invasive cancer diagnostics due to their strongly modulated expression and improved tissue and disease specificity. This review offers a succinct overview of the present understanding concerning the potential diagnostic biomarker potential of lncRNAs in melanoma. Cell death occurs frequently during growth and throughout life and is an active, organized, and genetically determined process. It is essential for the regulation of homeostasis. Controlled cell death and non-programmed cell death are both forms of cell death. The most prevalent forms of regulatory cell death are pyroptosis, ferroptosis, autophagy, necroptosis, necrosis, and apoptosis. Ferroptosis, pyroptosis, and autophagy are less common forms of cell death compared to necrosis, apoptosis, and necroptosis. ncRNAs are regulatory RNA molecules that are not involved in encoding proteins. They primarily consist of circular RNAs (circ RNAs), lncRNAs, and microRNAs (miRNAs). Moreover, non-coding RNAs have the ability to modulate tumor cell autophagy, pyroptosis, and ferroptosis at the transcriptional or post-transcriptional stage, as well as function as oncogenes and tumor suppressor genes, which can have considerable effects on the incidence and growth of tumors. This review concentrated on the recent advancements in the research of the diagnostic and therapeutic functions of ncRNAs in the regulation of programmed cell death in melanoma.

BackgroundMyocardial infarction(MI) is one of the most serious health threats. Despite the increasing number of clinical methods used to predict the onset of MI, the prediction of MI is still unsatisfactory and necessitates new methods.ObjectiveTo systematically review observational studies from the past two decades on the association between waist-to-hip ratio (WHR) and MI risk.MethodsOriginal literature on the correlation between WHR and MI was searched in PubMed, Embase, Web of Science, Cochrane Library, Science Direct, CNKI, and Wanfang up to January 31, 2024. Two researchers independently screened, extracted data, and assessed quality using the Newcastle-Ottawa Scale (NOS) and Revman5.3. Meta-analysis with Stata 16.0 calculated the combined Odd ratio (OR) for WHR and MI risk. Heterogeneity was assessed with the I2 statistic to select the appropriate effects model. Subgroup analysis, meta-regression, sensitivity analysis, and funnel plots tested for heterogeneity and publication bias.ResultsA total of 22 observational studies were included, involving 709,093 participants. The meta-analysis showed that an elevated WHR was significantly associated with an increased risk of MI, with a pooled odds ratio (OR) of 1.98 [95% Confidence interval (CI): 1.75–2.24] and high heterogeneity (I2 = 91.5%, P

Background The relapse rate in myasthenia gravis (MG) is high, and promising therapies have emerged; however, identifying potential predictive factors for relapse remains a challenge. This study aimed to explore the association between circulating natural killer (NK) cell levels and the risk of recurrence in MG. Methods This retrospective cohort study included 265 patients with MG whose data were included in the Neurology Department of the Affiliated Hospital of Guizhou Medical University database between March 2015 and March 2022. Data from electronic medical records were collected, which included the patients’ circulating NK cell count (exposure variable) and demographic/clinical characteristics (covariates). The primary outcome was the 1-year MG recurrence rate. Results The study revealed a non-linear relationship between peripheral NK cell count and MG recurrence, with an inflection point at 5.38. Below this threshold, the risk of recurrence was low with higher NK cell counts (relative risk (RR): 0.23, 95% confidence interval (CI) [0.11–0.490]); above this threshold, no significant association was observed (RR: 1.43, 95% CI [0.62–3.34]). Furthermore, the NK cell proportion showed no significant linear or non-linear association with MG recurrence risk (RR: 0.84, 95% CI [0.57–1.2]). Conclusion This study provides epidemiological evidence of a potential association between peripheral NK cell count and MG recurrence risk, suggesting an immunoregulatory protective effect within a specific NK cell count range. These findings may inform more personalized MG treatment strategies, warranting further validation in larger and more diverse cohorts.

Cholestatic liver injury results from the accumulation of toxic bile acids in the liver, presenting a therapeutic challenge with no effective treatment available to date. Andrographolide (AP) has exhibited potential as a treatment for cholestatic liver disease. However, its limited oral bioavailability poses a significant obstacle to harnessing its potent therapeutic properties and restricts its clinical utility. This limitation is potentially attributed to the involvement of gut microbiota in AP metabolism. In our study, employing pseudo-germ-free, germ-free and strain colonization animal models, along with 16S rRNA and shotgun metagenomic sequencing analysis, we elucidate the pivotal role played by gut microbiota in the C-sulfonate metabolism of AP, a process profoundly affecting its bioavailability and anti-cholestatic efficacy. Subsequent investigations pinpoint a specific enzyme, adenosine-5’-phosphosulfate (APS) reductase, predominantly produced by Desulfovibrio piger, which catalyzes the reduction of SO42- to HSO3−. HSO3− subsequently interacts with AP, targeting its C=C unsaturated double bond, resulting in the formation of the C-sulfonate metabolite, 14-deoxy-12(R)-sulfo andrographolide (APM). Inhibition of APS reductase leads to a notable enhancement in AP bioavailability and anti-cholestatic efficacy. Furthermore, employing RNA sequencing analysis and farnesoid X receptor (FXR) knockout mice, our findings suggest that AP may exert its anti-cholestatic effects by activating the FXR pathway to promote bile acid efflux. In summary, our study unveils the significant involvement of gut microbiota in the C-sulfonate metabolism of AP and highlights the potential benefits of inhibiting APS reductase to enhance its therapeutic effects. These discoveries provide valuable insights into enhancing the clinical applicability of AP as a promising treatment for cholestatic liver injury.