RESUMEN

Background: Patient-specific computer simulation of transcatheter aortic valve implantation (TAVI) predicts the interaction between an implanted device and the surrounding anatomy. In this study, we validated the predictive value of computer simulation for the frame deformation following a Venus-A TAVI implant in patients with pure aortic regurgitation (AR). Furthermore, we used the validated computational model to evaluate the anchoring mechanism within the same cohort. Methods: This was a retrospective study. FEops HEARTguide technology was used to simulate the virtual implantation of a Venus-A valve model in a patient-specific geometry. The predicted frame deformation was quantitatively compared to the postoperative device deformation at multiple levels. The outward forces acting on the frame were extracted for each patient and the total outward force acting around the aortic annular (AA) and sinotubular junction (STJ) planes were recorded. Results: Thirty patients were enrolled in the study with 10 in the migration group and 20 in the non-migration group. The dimensions of the simulated and observed frames had good correlations at Dmax (R2=0.88), Dmin (R2=0.91), perimeter (R2=0.92), and area (R2=0.92). The predicted outward force acting on the frame at the AA level was comparable between the migration and no-migration groups. The predicted outward force acting on the frame at the STJ level was always significantly higher in the migration group than the no migration group at different bandwidths: 3 mm (P=0.002), 5 mm (P=0.005), 10 mm (P=0.002). Conclusions: Patient-specific computer simulation of TAVI accurately predicted frame deformation in Chinese patients with pure AR. The forces at the STJ facilitated stabilization of the device within the aortic root, which might be used as a discriminator to identify patients at risk of device migration prior to intervention.

RESUMEN

Background: Lactate dehydrogenase A (LDHA) plays a crucial role in the final step of anaerobic glycolysis, converting L-lactate and NAD+ to pyruvate and nicotinamide adenine dinucleotide (NADH). Its high expression has been linked to tumorigenesis and patient survival in various human cancers. However, the full implications of LDHA's role and its correlation with clinicopathological features in pancreatic adenocarcinoma (PAAD) remain to be fully understood. This study was thus conducted to elucidate the specific functions of LDHA in PAAD, with the aim of providing more robust evidence for clinical diagnosis and treatment. Methods: In an extensive systems analysis, we searched through numerous databases, including The Cancer Genome Atlas (TCGA) and Oncomine. Our objective was to clarify the clinical implications and functional role of LDHA in PAAD. Bioinformatics was used to identify the biological function of LDHA expression and its correlation with tumor immune status. Results: Our analysis revealed that the LDHA gene is overexpressed in PAAD and that this upregulation was associated with a worse patient prognosis. Through gene set enrichment analysis, we found that LDHA's influence on PAAD is linked to signaling pathways involving Kirsten rat sarcoma viral oncogene homolog (K-Ras), transforming growth factor-ß (TGF-ß), and hypoxia inducible factor-1 (HIF-1). Mutation of K-Ras could upregulate its own expression and was positively correlated with LDHA expression. Moreover, our data demonstrated that LDHA expression was linked to immune infiltration and poor prognosis in PAAD, indicating its role in disease pathogenesis. Overexpression of LDHA may suppress tumor immunity, suggesting it as a potential target for the diagnosis and treatment of PAAD, thus providing new insights into managing this aggressive cancer. Conclusions: Overall, our results showed that LDHA as a prognostic biomarker could serve as a novel target for future PAAD immunotherapy.

RESUMEN

In the field of cancer therapy, inhibiting autophagy has emerged as a promising strategy. However, pharmacological disruption of autophagy can lead to the upregulation of programmed death-ligand 1 (PD-L1), enabling tumor immune evasion. To address this issue, we developed innovative ROS-responsive cationic poly(ethylene imine) (PEI) nanogels using selenol chemistry-mediated multicomponent reaction (MCR) technology. This procedure involved simple mixing of low-molecular-weight PEI (LMW PEI), γ-selenobutylacetone (γ-SBL), and poly(ethylene glycol) methacrylate (PEGMA). Through high-throughput screening, we constructed a library of AxSeyOz nanogels and identified the optimized A1.8Se3O0.5/siPD-L1 nanogels, which exhibited a size of approximately 200 nm, excellent colloidal stability, and the most effective PD-L1 silencing efficacy. These nanogels demonstrated enhanced uptake by tumor cells, excellent oxidative degradation ability, and inhibited autophagy by alkalinizing lysosomes. The A1.8Se3O0.5/siPD-L1 nanogels significantly downregulated PD-L1 expression and increased the expression of major histocompatibility complex class I (MHC-I), resulting in robust proliferation of specific CD8+ T cells and a decrease in MC38 tumor growth. As a result, the A1.8Se3O0.5/siPD-L1 nanogels inhibited tumor growth through self-inhibition of autophagy, upregulation of MHC-I, and downregulation of PD-L1. Designed with dynamic diselenide bonds, the A1.8Se3O0.5/siPD-L1 nanogels showed synergistic antitumor efficacy through self-inhibition of autophagy and prevention of immune escape.

RESUMEN

A chemoselective and regioselective copper-promoted defunctionalization procedure has been developed, enabling the rapid construction of various N-polyheterocycles. Initial mechanistic studies reveal that a single-electron transfer radical process is potentially involved.

RESUMEN

BACKGROUND: Recent studies have identified the presence of cancer-associated fibroblasts (CAFs) within glioblastoma (GBM), yet their biological roles and underlying mechanisms remain poorly understood. This study aimed to construct a CAF-related prognostic model to guide patient prognosis and treatment strategies. METHOD: We employed various bioinformatics methods, including enrichment analysis, Weighted Gene Co-expression Network Analysis (WGCNA), Lasso regression analysis, and machine learning techniques such as XGBoost and Random Forest, to develop a novel risk index termed CAFscore. Patients were stratified into high and low CAFscore groups for subsequent survival analysis. The area under the curve (AUC) and concordance index (C-index) for CAFscore were calculated and compared against other clinical characteristics and existing prognostic models. Drug sensitivity assessments were conducted using the Oncopredict package. Functional validation of key genes was performed through scratch and invasion assays in GBM cells. RESULTS: Our analyses revealed four core CAF-related genes, leading to the establishment of CAFscore. Notably, patients in the high CAFscore group exhibited significantly reduced survival and exhibited enrichment in epithelial-mesenchymal transition (EMT) and inflammation response pathways. Furthermore, CAFscore showed a significant negative correlation with the sensitivity to irinotecan and its analogs, while demonstrating a positive correlation with sensitivity to 505,124 (a TGFßRI inhibitor). LRP10 emerged as a central gene within the CAFscore, displaying markedly elevated expression in GBM and a strong association with CAF infiltration. Silencing LRP10 significantly inhibited the invasive capabilities of GBM cells. CONCLUSION: This study presented the first CAF related prognostic model (CAFscore) in GBM, and demonstrated that the model could effectively guide patient prognosis and potentially inform personalized treatment strategies. The core gene of CAFscore, LRP10, was significantly overexpressed in GBM and might play a pivotal role in regulating CAF infiltration as well as tumor invasion and metastasis, highlighting LRP10 as a promising therapeutic target for GBM management.

RESUMEN

Improving fattening efficiency is an important goal of breeding commercial pigs, especially for the large-scale pig farms. Fattening efficiency index (FEI) can be used to evaluate the fattening efficiency. The aim of this study was to identify the factors affecting the fattening efficiency of commercial pigs in large-scale pig farms and further study the impact of these factors on the production performance of commercial pig batches at different production levels. The data of 9,570 batches was mainly consisted of four parts (farm facilities, general information of piglets, production performance of nursery pigs and finishing pigs). A total of 28 variables were evaluated by the multi-variable linear regression models. The differences in production factors significantly correlated with FEI at piglets-finishing stage were compared among high-performing (HP), moderate-performing (MP), and low-performing (LP) batches of commercial pigs during the nursery and finishing stage. Among the 28 variables, 18 were significantly correlated with fattening efficiency (P < 0.05), including 11 continuous variables and seven discrete variables. The significant differences among the 11 consecutive variables in the HP, MP, and LP batches of commercial pigs mostly persisted from the piglets-nursery stage to the growing-finishing stage, ultimately affecting the FEI at piglets-finishing stage. For the seven significant discrete variables, the HP batches had a lower proportions in owned source of piglets, number of the purchasing piglets in spring and winter, number of batches in the East and North regions and five-way crossbred pigs, while a higher proportions in the use of closed circuit television video (CCTV) and wastes treatment system. The fattening efficiency of commercial pigs in large-scale pig farms was comprehensively affected by farm facilities, piglets, and production performance at nursery and finishing stage. The low fattening efficiency may have started at the end of nursery stage.

Asunto(s)

RESUMEN

Endothelial progenitor cells (EPCs) play a crucial role in maintaining vascular health and aiding in the repair of damaged blood vessels. However, the specific impact of EPCs-derived exosomes on vascular endothelial cell injury caused by lipopolysaccharide (LPS) remains inadequately understood. This study aims to explore the potential benefits of EPC-exosomes in mitigating LPS-induced vascular injury and to elucidate the underlying mechanism. Initially, EPCs were isolated from mouse peripheral blood, and their identity was confirmed through flow cytometry and immunocytochemistry. Subsequently, the exosomes derived from EPCs were identified using transmission electron microscopy (TEM) and western blot analysis. A sepsis model was induced by subjecting brain microvascular endothelial cells (BMECs) to LPS-induced injury. Both EPC and their exosomes demonstrated a significant increase in BMECs proliferation, reduced apoptosis, decreased levels of pro-inflammatory factors (TNF-α, IL-6, and caspase-3), and enhanced sprouting and angiogenesis of BMECs. Notable, the Exosomes demonstrated a more pronounced impact on these parameters. Furthermore, both EPCs and Exosomes exhibited significantly increased levels of miR-126a-5p, with the Exosomes showing a more substantial enhancement. These findings suggest that supplementing exosomal miR-126a-5p from EPCs can provide protective effects on BMECs, offering a potential therapeutic option for treating sepsis-induced microvascular endothelial cell injury.

Asunto(s)

RESUMEN

To improve the solubility of the fluoroquinolone drug fleroxacin (FL), based on the previous experience of our research group in synthesizing co-crystals/salts of quinolone drugs to improve the physicochemical properties of drugs, Fleroxacin-D-tartaric acid dihydrate salt (FL-D-TT, C17H19F3N3O3·C4H5O6·2(H2O)), was synthesized for the first time using fleroxacin and D/L-tartaric acid (D/L-TT). Structural characterization of FL-D-TT was carried out using single-crystal X-ray diffraction, infrared spectral analysis (FT-IR) and powder X-ray diffraction (PXRD). Molecular electrostatic potential analysis showed that D-tartaric acid interacted more readily with FL than L-tartaric acid. The solubility of FL-D-TT (9.71 mg/mL, 1.82 mg/mL) was significantly higher compared to FL (0.39 mg/mL, 0.71 mg/mL) in water and buffer solution at pH 7.4. This may be attributed to the formation of charge-assisted hydrogen bonds (CAHBs) between FL and D-TT that facilitates the dissociation of FL cations in the dissolution medium, leading to an increase in FL solubility. This also led to some improvement in the in vitro antimicrobial activity of FL-D-TT against E. coli, S. typhi, and S. aureus. In addition, the hygroscopic stability of FL has been improved. Surprisingly, FL-D-TT had better photostability than FL, which could be attributed to the introduction of D-TT to make the photosensitizing moiety of FL more stable, which led to the improvement of the photostability of FL.

Asunto(s)

RESUMEN

Introduction: Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D Ti3C2 structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. Ti3C2 nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with H2O2 in the tumor microenvironment. This new material can construct Ti3C2/TiO2 heterostructures in vivo. Methods: Photothermal (PTT), sonodynamic (SDT) effects, and photoacoustic (PA) image-guided synergy therapy can be achieved. Finally, anticancer immune responses occur with this nanozyme. In vivo experiments revealed that the Ti3C2/TiO2 heterostructure inhibited tumor growth. Results: Complementarily, our results showed that the Ti3C2/TiO2 heterostructure enhanced the immunogenic activity of tumors by recruiting cytotoxic T cells, thereby enhancing the tumor ablation effect. Mechanistic studies consistently indicated that Reactive Oxygen Species (ROS) regulates apoptosis of HCC cells by modulating NRF2/OSGIN1 signaling both in vitro and in vivo. As a result, Ti3C2 nanozyme effectively inhibited tumor through its synergistic ability to modulate ROS and enhance immune infiltration of cytotoxic T cells in the tumor microenvironment. Discussion: These findings open up new avenues for enhancing 2D Ti3C2 nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.

Asunto(s)

RESUMEN

The n-type semiconductor SnO2 with a wide band gap (3.6 eV) is massively used in gas-sensitive materials, but pure SnO2 still suffers from a high operating temperature, low response, and tardy responding speed. To solve these problems, we prepared small-sized pure SnO2 using hydrothermal and freeze-drying methods (SnO2-FD) and compared it with SnO2 prepared using a normal drying method (SnO2-AD). The sensor of SnO2-FD had an ultra-high sensitivity to NO2 at 100 °C with excellent selectivity and humidity stability. The outstanding gas sensing properties are attributed to the modulation of energy band structure and the increased carrier concentration, making it more accessible for electron exchange with NO2. The excellent gas sensing properties of SnO2-FD indicate its tremendous potential as a NO2 sensor.

RESUMEN

This paper investigates the impact of housing with both consumption and investment attributes on the risky financial asset allocation of households, constructs Probit and Tobit models using 2019 China Household Finance Survey (CHFS) data, and proceeds to the mediation effect test and heterogeneity analysis. Results indicate that owning only one house exhibits a crowding-out effect on the risky financial asset allocation of urban households, with the degree of risk preference as the mediating effect mechanism, while owning multiple houses exhibits an asset allocation effect. Housing borrowing other than bank loans inhibits urban households from making risky financial asset allocations. The effect of housing on risky financial asset allocation is heterogeneous by income, age, and region.

RESUMEN

Background: The correlation between metabolic syndrome (MetS) and hepatitis B surface antigen (HBsAg) loss remains to be further elucidated, particularly in patients receiving pegylated interferon-α (PEG-IFN) treatment. Methods: 758 patients with low HBsAg quantification who had received nucleos(t)ide analog (NUC) therapy for at least one year and subsequently switched to or add on PEG-IFN therapy over an unfixed course were enrolled. 412 patients were obtained with baseline data matched. A total of 206 patients achieved HBsAg loss (cured group) within 48 weeks. Demographic and biochemical data associated with MetS were gathered for analysis. HepG2.2.15 cell line was used in vitro experiments to validate the efficacy of interferon-α (IFN-α). Results: The proportion of patients with diabetes or hypertension in the uncured group was significantly higher than in the cured group. The levels of fasting blood glucose (FBG) and glycated albumin remained elevated in the uncured group over the 48 weeks. In contrast, the levels of blood lipids and uric acid remained higher in the cured group within 48 weeks. Triglycerides levels and liver steatosis of all patients increased after PEG-IFN therapy. Baseline elevated uric acid levels and hepatic steatosis may be beneficial for HBsAg loss. IFN-α could induce hepatic steatosis and indirectly promote HBsAg loss by increasing triglyceride level through upregulation of acyl-CoA synthetase long-chain family member 1(ACSL1). Conclusions: IFN-α could induce liver steatosis to promote HBsAg loss by increasing triglyceride level through upregulation of ACSL1. Comorbid diabetes may be detrimental to obtaining HBsAg loss with PEG-IFN therapy in CHB patients.

RESUMEN

Aerogel-based composites, renowned for their three-dimensional (3D) network architecture, are gaining increasing attention as lightweight electromagnetic (EM) wave absorbers. However, attaining high reflection loss, broad effective absorption bandwidth (EAB), and ultrathin thickness concurrently presents a formidable challenge, owing to the stringent demands for precise structural regulation and incorporation of magnetic/dielectric multicomponents with synergistic loss mechanisms within the 3D networks. In this study, we successfully synthesized a 3D hierarchical porous Fe3O4/MoS2/rGO/Ti3C2Tx MXene (FMGM) composite aerogel via directional freezing and subsequent heat treatment processes. Owing to their ingenious structure and multicomponent design, the FMGM aerogels, featured with abundant heterogeneous interface structure and magnetic/dielectric synergism, show exceptional impedance matching characteristics and diverse EM wave absorption mechanisms. After optimization, the prepared ultralight (6.4 mg cm-3) FMGM-2 aerogel exhibits outstanding EM wave absorption performance, achieving a minimal reflection loss of -66.92 dB at a thickness of 3.61 mm and an EAB of 6.08 GHz corresponding to the thickness of 2.3 mm, outperforming most of the previously reported aerogel-based absorbing materials. This research presents an effective strategy for fabricating lightweight, ultrathin, highly efficient, and broad band EM wave absorption materials.

RESUMEN

BACKGROUND: Bicaval dual lumen cannula (DLC) is gaining popularity in veno-venous extracorporeal membrane oxygenation (V-V ECMO) for having less recirculation and facilitating mobilization. It is usually inserted under fluoroscopic or transesophageal echocardiographic guidance to prevent potentially fatal complications. Thus, their utilization was limited during the COVID-19 outbreak due to stringent quarantine policy and manpower shortage, especially when emergency insertion was required. PURPOSE: To describe our experience on DLC insertion using transthoracic echocardiography alone during the pandemic, with a focus on safety considerations by using detail step-by-step procedural guide. OUTCOME: Four patients were performed V-V ECMO using the transthoracic echocardiographic-guided DLC cannulation technique during the fifth wave of the COVID-19 outbreak, with no cannulation-related complications. CONCLUSION: Transthoracic echocardiographic guidance for DLC insertion is feasible and probably safe with a detailed guide, which can be adopted as a supplementary tool during future endemic outbreaks.

RESUMEN

Empty sella syndrome (ESS) is characterized by the herniation of cerebrospinal fluid into the sella, which results in the enlargement of the sella and compression of the pituitary gland. ESS commonly accompanies pituitary dysfunction and abnormal secretion of one or more hormones, which manifests as symptoms like cold intolerance, fatigue, and memory impairment. However, the occurrence of sick sinus syndrome (SSS) in ESS has not been reported. A 66-year-old female patient was admitted to the hospital with complaints of dizziness and fatigue. Electrocardiogram (ECG) revealed sinus arrest, junctional escape rhythm, and a heart rate of 40 bpm. Then, the patient was diagnosed with SSS. Thyroid function test indicated decreased thyroxine levels and slightly elevated thyroid-stimulating hormone levels. Additionally, hyposecretion of cortisol and insulin-like growth factors was observed. Magnetic resonance imaging of the pituitary gland confirmed the diagnosis of ESS. The patient was treated with hydrocortisone and euthyrox, relieving the symptoms of dizziness and fatigue. Thyroid function tests during the follow-up period showed normal hormone levels, and ECG examination revealed no abnormalities.

Asunto(s)

RESUMEN

Mycoplasma capricolum subsp. capricolum (Mcc), a member of the Mycoplasma mycoides cluster, has a negative impact on the goat-breeding industry. However, little is known about the pathogenic mechanism of Mcc. This study infected mice using a previously isolated strain, Mcc HN-B. Hematoxylin and eosin staining, RNA sequencing, bioinformatic analyses, RT-qPCR, and immunohistochemistry were performed on mouse lung tissues. The results showed that 235 differentially expressed genes (DEGs) were identified. GO and KEGG enrichment analyses suggested that the DEGs were mainly associated with immune response, defensive response to bacteria, NF-kappa B signaling pathway, natural killer cell-mediated cytotoxicity, and T cell receptor signaling pathway. RT-qPCR verified the expression of Ccl5, Cd4, Cd28, Il2rb, Lck, Lat, Ptgs2, S100a8, S100a9, and Il-33. The up-regulation of S100A8 and S100A9 at the protein level was confirmed by immunohistochemistry. Moreover, RT-qPCR assays on Mcc HN-B-infected RAW264.7 cells also showed that the expression of S100a8 and S100a9 was elevated. S100A8 and S100A9 not only have diagnostic value in Mcc infection but also hold great significance in clarifying the pathogenic mechanism of Mcc. This study preliminarily elucidates the mechanism of Mcc HN-B-induced lung injury and provides a theoretical basis for further research on Mcc-host interactions.

RESUMEN

This study sequenced the complete chloroplast genomes of Stephania japonica var. timoriensis and Stephania japonica var. discolor using the Illumina NovaSeq and PacBio RSII platforms. Following sequencing, the genomes were assembled, annotated, comparatively analyzed, and used to construct a phylogenetic tree to explore their phylogenetic positions. Results indicated that the chloroplast genomes of S. japonica var. timoriensis and S. japonica var. discolor both displayed a typical double-stranded circular tetrameric structure, measuring 157,609 and 157,748 bp in length, respectively. Each genome contained 130 annotated genes, with similar total GC content and relative codon usage patterns, showing a distinct preference for A/U at the third codon position. Simple sequence repeat analysis identified 207 and 211 repeats in S. japonica var. timoriensis and S. japonica var. discolor, respectively, primarily the A/T type. Boundary condition analysis indicated no significant expansion or contraction in the inverted repeat regions with consistent gene types and locations across both varieties. Nucleotide polymorphism analysis highlighted greater variation in the intergenic regions than in the coding sequences of Stephania chloroplast genomes. Phylogenetic analyses demonstrated that the species Stephania clustered into a distinct, well-supported clade. Notably, Stephania japonica, along with S. japonica var. discolor and S. japonica var. timoriensis, established a monophyletic lineage. Within this lineage, S. japonica and S. japonica var. discolor were closely related, with S. japonica var. timoriensis serving as their sister taxon.

Asunto(s)

RESUMEN

OBJECTIVE: Metastases in the advanced stages of colorectal cancer (CRC) present a major challenge to its treatment. Epithelial-Mesenchymal Transition (EMT) plays a crucial role in enhancing the metastasis and invasion ability of cancer cells. However, the progress of E2F transcription factor 1 (E2F1) and Regulator of chromatin condensation 1 (RCCD1) in CRC on EMT has not been studied. METHODS: The CRC differential expression data from The Cancer Genome Atlas database were analyzed by Gene Set Enrichment Analysis to verify the difference in expression of E2F1 and RCCD1 in cancerous and para-cancerous tissues.DNA-pull down and dual luciferase experiments confirmed that E2F1 regulates RCCD1. Western-blot and q-PCR experiments confirmed that E2F1 regulates RCCD1 and participates in the EMT-related progress of CRC.EDU, Wound healing and Transwell experiments verified the effects of regulation of E2F1 and RCCD1 on the proliferation, migration and invasion of CRC cells. RESULTS: E2F1 and RCCD1 are highly expressed in cancer tissues and cancer cells. E2F1 binds to the upstream promoter of RCCD1 to regulate RCCD1 and affect the expression of EMT-related targets in CRC cells. It also affects the proliferation, migration and invasion of CRC cells. CONCLUSIONS: E2F1 regulates the involvement of RCCD1 in CRC EMT and affects the proliferation, migration and invasion ability of CRC cells.

Asunto(s)

RESUMEN

Deep-sea equipment usually operates under dwell-fatigue condition, which means the equipped energy storage devices must survive under the changing pressure. Special mechanical designs should be considered to maintain the electrochemical performance of electrodes under this extreme condition. In this work, an effective assembly strategy is proposed to accommodate the dwell-fatigue loading using Ag decorated reduced graphene oxide (rGO) foam (denoted as AGF) as a superelastic and robust Zn host. The wet-press assembly process enables the formation of highly porous and robust framework. The strong synergetic effect between rGO and Ag further guarantees AGF's superelasticity and ultrahigh mechanical strength. Meanwhile, the homogeneously distributed Ag species on the rGO sheets act as zincophilic sites to effectively facilitate Zn plating. Furthermore, AGF offers enough space to address the expansion during the charge and discharge cycles. As expected, the symmetrical cell using this AGF@Zn host demonstrates a long lifespan over 400 h at a depth-of-discharge of 50%. It is worth mentioning that the superelastic AGF host realizes stable Zn plating/stripping under varying pressures.