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Purpose: Neovascular age-related macular degeneration (nAMD) is a prevalent cause of blindness in the elderly. Standard treatment includes anti-vascular endothelial growth factor (anti-VEGF) drugs, such as aflibercept. However, anti-VEGF drugs may have limited efficacy and cause drug resistance. This study explores whether Kavain, an anti-inflammatory molecule from Piper methysticum, can treat choroidal neovascularization (CNV). Methods: Various experiments were conducted to assess the Kavain’s toxicity. The impact of Kavain on in vitro cultured endothelial cells was examined through 5-ethynyl-20-deoxyuridine (EdU) assays, transwell migration assays, and tube formation assays. The therapeutic effects of Kavain on CNV were investigated using a laser-induced CNV mice model. To elucidate the mechanism of Kavain, network pharmacology analysis, molecular docking, and western blots were performed. Results: Kavain exhibited no apparent toxicity both in vitro and in vivo. Kavain significantly decreased endothelial cell viability, proliferation, migration, and tube formation ability in a dose-dependent manner compared to the hypoxia groups (P

Abstract Implantable neural probes, essential for brain electrophysiological research, have advanced with ultra-flexible designs to mitigate immune responses and postoperative complications. Strategies of shuttle-assisted implantation and temporary stiffening address issues in penetrating these probes into the target region, avoiding undesired bending. However, the risk of intraoperative bleeding remains due to these implants’ necessary rigidity during insertion. Here, we describe a neural probe with mechanical compliance accompanying self-implantation along the principal axis in the absence of bleeding. Crucial to the behavior is its anisotropic relaxation, which is dominated by the cross-sectional in-plane deformation inhibition due to interchain interactions between the parallel backbones in the globally aligned polymer system. We observed the ensured upright insertion of the probe into the brain while avoiding angiorrhexis with a two-photon microscope and a high-speed camera. The probes permit electrophysiological studies with minimal foreign body responses and imageological compatibility, underscoring their clinical potential.

Wastewater treatment plants (WWTPs) are important and energy-intensive municipal infrastructures. High energy consumption and relatively low operating performance are major challenges from the perspective of carbon neutrality. However, water–energy nexus analysis and models for WWTPs have rarely been reported to date. In this study, a cloud-model-based energy consumption analysis (CMECA) of a WWTP was conducted to explore the relationship between influent and energy consumption by clustering its influent’s parameters. The principal component analysis (PCA) and K-means clustering were applied to classify the influent condition using water quality and volume data. The energy consumption of the WWTP is divided into five standard evaluation levels, and its cloud digital characteristics (CDCs) were extracted according to bilateral constraints and golden ratio methods. Our results showed that the energy consumption distribution gradually dispersed and deviated from the Gaussian distribution with decreased water concentration and quantity. The days with high energy efficiency were extracted via the clustering method from the influent category of excessive energy consumption, represented by a compact-type energy consumption distribution curve to identify the influent conditions that affect the steady distribution of energy consumption. The local WWTP has high energy consumption with 0.3613 kW·h·m−3 despite low influent concentration and volumes, across four consumption levels from low (I) to relatively high (IV), showing an unsatisfactory operation and management level. The average oxygenation capacity, internal reflux ratio, and external reflux ratio during high energy efficiency days recognized by further clustering were obtained (0.2924–0.3703 kg O2·m−3, 1.9576–2.4787, and 0.6603–0.8361, respectively), which could be used as a guide for the days with low energy efficiency. Consequently, this study offers a water–energy nexus analysis method to identify influent conditions with operational management anomalies and can be used as an empirical reference for the optimized operation of WWTPs.

Green peas, with their high moisture content, require effective drying techniques to extend shelf life while preserving quality. Traditional drying methods face challenges due to the dense structure of the seed coat and wax layer, which limits moisture migration. This study investigates cold plasma (CP) pretreatment as a novel approach to enhance drying kinetics and maintain the quality attributes of green peas. The results showed that CP treatment significantly improves drying efficiency by modifying the pea epidermis microstructure, reducing drying time by up to 18.18%. The moisture effective diffusivity coefficients (Deff) for untreated and CP-pretreated green peas were calculated to range from 5.9629 to 9.9172 × 10−10 m2·s−1, with CP pretreatment increasing Deff by up to 66.31% compared to the untreated group. Optimal CP parameters (90 s, 750 Hz frequency, 70% duty cycle) were found to improve the rehydration ratio, preserve color, and increase total phenolic content (TPC) by 24.06%, while enhancing antioxidant activity by 29.64%. Microstructural changes, including pore formation and increased surface roughness, as observed through scanning electron microscopy (SEM), partially explain the enhanced moisture diffusion, improved rehydration, and alterations in nutrient content. These findings underscore the potential of CP technology as a non-thermal, eco-friendly pretreatment for drying agricultural products, with broad applications in food preservation and quality enhancement.

Abstract Purpose To explore the potential role of signal transducer and activator of transcription 5A (STAT5A) in the metastasis of breast cancer, and its mechanism of regulation underlying. Methods and results TCGA datasets were used to evaluate the expression of STAT5A in normal and different cancerous tissues through TIMER2.0, indicating that STAT5A level was decreased in breast cancer tissues compared with normal ones. Gene Set Enrichment Analysis predicted that STAT5A was associated with the activation of immune cells and cell cycle process. We further demonstrated that the infiltration of immune cells was positively associated with STAT5A level. Influorescence staining revealed the expression and distribution of F-actin was regulated by STAT5A, while colony formation assay, wound healing and transwell assays predicted the inhibitory role of STAT5A in the colony formation, migratory and invasive abilities in breast cancer cells. In addition, overexpression of the Notch3 intracellular domain (N3ICD), the active form of Notch3, resulted in the increased expression of STAT5A. Conversely, silencing of Notch3 expression by siNotch3 decreased STAT5A expression, supporting that STAT5A expression is positively associated with Notch3 in human breast cancer cell lines and breast cancer tissues. Mechanistically, chromatin immunoprecipitation showed that Notch3 was directly bound to the STAT5A promoter and induced the expression of STAT5A. Moreover, overexpressing STAT5A partially reversed the enhanced mobility of breast cancer cells following Notch3 silencing. Low expression of Notch3 and STAT5A predicted poorer prognosis of patients with breast cancer. Conclusion The present study demonstrates that Notch3 inhibits metastasis in breast cancer through inducing transcriptionally STAT5A, which was associated with tumor-infiltrating immune cells, providing a novel strategy to treat breast cancer.

Abstract Regulation of gut microbiota and its impact on human health is the theme of intensive research. The incidence and prevalence of atrial fibrillation (AF) are continuously escalating as the global population ages and chronic disease survival rates increase; however, the mechanisms are not entirely clarified. It is gaining awareness that alterations in the assembly, structure, and dynamics of gut microbiota are intimately engaged in the AF progression. Owing to advancements in next-generation sequencing technologies and computational strategies, researchers can explore novel linkages with the genomes, transcriptomes, proteomes, and metabolomes through parallel meta-omics approaches, rendering a panoramic view of the culture-independent microbial investigation. In this review, we summarized the evidence for a bidirectional correlation between AF and the gut microbiome. Furthermore, we proposed the concept of “gut-immune-heart” axis and addressed the direct and indirect causal roots between the gut microbiome and AF. The intricate relationship was unveiled to generate innovative microbiota-based preventive and therapeutic interventions, which shed light on a definite direction for future experiments.

Abstract Background Pathological neovascularization plays a pivotal role in the onset and progression of tumors and neovascular eye diseases. Despite notable advancements in the development of anti-angiogenic medications that target vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), the occurrence of adverse reactions and drug resistance has somewhat impeded the widespread application of these drugs. Therefore, additional investigations are warranted to explore alternative therapeutic targets. In recent years, owing to the swift advancement of high-throughput sequencing technology, pan-cancer analysis and single-cell sequencing analysis have emerged as pivotal methodologies and focal areas within the domain of omics research, which is of great significance for us to find potential targets related to the regulation of pathological neovascularization. Methods Pan-cancer analysis and scRNA-seq data analysis were employed to forecast the association between Actin filament-associated protein 1 like 1 (AFAP1L1) and the development of tumors and endothelial cells. Tumor xenograft model and ocular pathological neovascularization model were constructed as well as Isolectin B4 (IsoB4) staining and immunofluorescence staining were used to assess the effects of AFAP1L1 on the progression of neoplasms and neovascular eye diseases in vivo. Transwell assay, wound scratch assay, tube forming assay, three-dimensional germination assay, and rhodamine-phalloidin staining were used to evaluate the impact of AFAP1L1 on human umbilical vein endothelial cells (HUVECs) function in vitro; Dual luciferase reporting, qRT-PCR and western blot were used to investigate the upstream and downstream mechanisms of pathological neovascularization mediated by AFAP1L1. Results Our investigation revealed that AFAP1L1 plays a crucial role in promoting the development of various tumors and demonstrates a strong correlation with endothelial cells. Targeted suppression of AFAP1L1 specifically in endothelial cells in vivo proves effective in inhibiting tumor formation and ocular pathological neovascularization. Mechanistically, AFAP1L1 functions as a hypoxia-related regulatory protein that can be activated by HIF-1α. In vitro experiments demonstrated that reducing AFAP1L1 levels can reverse hypoxia-induced excessive angiogenic capacity in HUVECs. The principal mechanism of angiogenesis inhibition entails the regulation of tip cell behavior through the YAP-DLL4-NOTCH axis. Conclusion In conclusion, AFAP1L1, a newly identified hypoxia-related regulatory protein, can be activated by HIF-1α. Inhibiting AFAP1L1 results in the inhibition of angiogenesis by suppressing the germination of endothelial tip cells through the YAP-DLL4-NOTCH axis. This presents a promising therapeutic target to halt the progression of tumors and neovascular eye disease.

Despite growing evidence suggesting an important contribution of Tumor Protein P53 Inducible Protein 11 (TP53I11) in cancer progression, the role of TP53I11 remains unclear. Our first pan-cancer analysis of TP53I11 showed some tumor tissues displayed reduced TP53I11 expression compared to normal tissues, while others exhibited high TP53I11 expression. Meanwhile, TP53I11 expression carries a particular pan-cancer risk, as high TP53I11 expression levels are detrimental to survival for BRCA, KIRP, MESO, and UVM, but to beneficial survival for KIRC. We demonstrated that TP53I11 expression negatively correlates with DNA methylation in most cancers, and the S14 residue of TP53I11 is phosphorylated in several cancer types. Additionally, TP53I11 was found to be associated with endothelial cells in pan-cancer, and functional enrichment analysis provided strong evidence for its role in tumor angiogenesis. In vitro angiogenesis assays confirmed that TP53I11 can promote angiogenic function of human umbilical vein endothelial cells (HUVECs) in vitro. Mechanistic investigations reveal that TP53I11 is transcriptionally up-regulated by HIF2A under hypoxia.

Abstract Background Ocular neovascularization is a leading cause of blindness and visual impairment. While intravitreal anti-VEGF agents can be effective, they do have several drawbacks, such as endophthalmitis and drug resistance. Additional studies are necessary to explore alternative therapeutic targets. Methods Bioinformatics analysis and quantitative RT-PCR were used to detect and verify the FSCN1 expression levels in oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) mice model. Transwell, wound scratching, tube formation, three-dimensional bead sprouting assay, rhodamine-phalloidin staining, Isolectin B4 staining and immunofluorescent staining were conducted to detect the role of FSCN1 and its oral inhibitor NP-G2-044 in vivo and vitro. HPLC–MS/MS analysis, cell apoptosis assay, MTT assay, H&E and tunnel staining, visual electrophysiology testing, visual cliff test and light/dark transition test were conducted to assess the pharmacokinetic and security of NP-G2-044 in vivo and vitro. Co-Immunoprecipitation, qRT-PCR and western blot were conducted to reveal the mechanism of FSCN1 and NP-G2-044 mediated pathological ocular neovascularization. Results We discovered that Fascin homologue 1 (FSCN1) is vital for angiogenesis both in vitro and in vivo, and that it is highly expressed in oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV). We found that NP-G2-044, a small-molecule inhibitor of FSCN1 with oral activity, can impede the sprouting, migration, and filopodia formation of cultured endothelial cells. Oral NP-G2-044 can effectively and safely curb the development of OIR and CNV, and increase efficacy while overcoming anti-VEGF resistance in combination with intravitreal aflibercept (Eylea) injection. Conclusion Collectively, FSCN1 inhibition could serve as a promising therapeutic approach to block ocular neovascularization.

Permeation grouting is used to fill the voids in soils with particulates for the purpose of improving soil strength. The technique has been predominatly used for cohesionless soils, however due to nanotechnological advancements in colloidal silica, its application to other soil types has more recently gained attention. Given sands with high silt fractions are a common geotechnical deposit, permeation grouting using colloidal silica is potentially an attractive improvement technique, yet has received limited attention. Therefore, this paper seeks to investigate the transport properties of colloidal silica in low-permeability silty sand, in terms of the effective grouting penetration range and peak strength. To this end, permeation injection is applied on low-permeability silty sand in a laboratory setting and then direct shear tests are undertaken. The results indicate colloidal silica concentrations should be greater than 10% to meet water resistance and strength requirements, while lower than 30% to ensure a uniform distribution of grout and adequate penetration. A low injection pressure of between 45 and 55 kPa, and between 65 and 75 kPa, is found to be suitable for permeating 20% and 30% concentrations of colloidal silica, respectively. After 7 days of curing time, silty sand at natural moisture content and treated with a 20% concentration of colloidal silica shows an increase in peak strength of between 58.1% and 78.4%, which increases further with curing time. A 20% concentration of colloidal silica is recommended for treating silty sand with a coefficient of permeability in the range 10−6 m/s, based on both injection range and peak strength after treatment. These findings may guide the practice of permeation grouting for low-permeability soils.

Abstract Estrogen receptor α (ERα) serves as an essential therapeutic predictor for breast cancer (BC) patients and is regulated by epigenetic modification. Abnormal methylation of cytosine phosphoric acid guanine islands in the estrogen receptor 1 (ESR1) gene promoter could silence or decrease ERα expression. In ERα‐negative BC, we previously found snail family transcriptional repressor 2 (SNAI2), a zinc‐finger transcriptional factor, recruited lysine‐specific demethylase 1 to the promoter to transcriptionally suppress ERα expression by demethylating histone H3 lysine 4 dimethylation (H3K4me2). However, the role of SNAI2 in ERα‐positive BC remains elusive. In this study, we observed a positive correlation between SNAI2 and ESR1 methylation, and SNAI2 promoted ESR1 methylation by recruiting DNA methyltransferase 3 beta (DNMT3B) rather than DNA methyltransferase 1 (DNMT1) in ERα‐positive BC cells. Subsequent enrichment analysis illustrated that ESR1 methylation is strongly correlated with cell adhesion and junction. Knocking down DNMT3B could partially reverse SNAI2 overexpression‐induced cell proliferation, migration, and invasion. Moreover, high DNMT3B expression predicted poor relapse‐free survival and overall survival in ERα‐positive BC patients. In conclusion, this study demonstrated the novel mechanisms of the ESR1 methylation mediated with the SNAI2/DNMT3B complex and enhanced awareness of ESR1 methylation's role in promoting epithelial–mesenchymal transition in BC.

Abstract Hepatocellular carcinoma (HCC) is a symptomatic disease involed multi-stage program. Here, we elucidated the molecular mechanism of LncTUG1 in the regulation of HCC evolvement. And that may in all likelyhood supply a innovative latent target for HCC’s diagnoses and prognosis. LncRNA TUG1, miR-144-3p, RRAGD and mTOR signaling pathway were screened as target genes in the database, and their expression levels at the cytological level were verified utilized qRT-PCR, Western Blot and immunohistochemistry. Then, we adopted CCK-8, Transwell and flow cytometry assays to estimate cell proliferation, invasion and apoptosis. By use of luciferase reporter assay, the relationships of LncRNA TUG1, miR-144-3p and RRAGD was confirmed. In addition, the LncRNA TUG1-miR-144-3p-RRAGD-mTOR signaling pathway in HCC cells was verified adopted rescue experiment and confirmed by xenotransplantation animal experiment. LncTUG1 in HCC tissues from three databases were identified and further verified through qRT-PCR in HCC cells (Huh7, Hep3B). Knockdown the LncTUG1 could increase apoptosis and inhibite invasion and proliferation in HCC cells. Using inhibitors and activators of the mTOR/S6K pathway, LncTUG1 was confirmed to regulate HCC progression by the mTOR/S6K pathway. Luciferase reporter assay demonstrated that TUG1 negatively regulates miR-144-3p. Furthermore, miR-144-3p negativly regulates RRAGD by way of interacting with the 3′UTR of the RRAGD mRNA in HCC utilized luciferase reporter assay. In vivo, we also discovered that neoplasm weight and tumor volume reduced significantly in subcutaneous xenograft nude mouse models derived from sh-LncTUG1-expressing Huh7 cells. And the expressions of p-mTOR, p-S6K and RRAGD were decreased obviously while the miR144-3p increased in subcutaneous xenograft nude mouse models. In a word, the research suggests that LncTUG1 targets miR-144-3p while miR-144-3p binds to RRAGD mRNA, which induces mTOR/S6K pathway activation and promotes the progression of HCC.

Abstract Targeted anticancer drugs block cancer cell growth by interfering with specific signaling pathways vital to carcinogenesis and tumor growth rather than harming all rapidly dividing cells as in cytotoxic chemotherapy. The Response Evaluation Criteria in Solid Tumor (RECIST) system has been used to assess tumor response to therapy via changes in the size of target lesions as measured by calipers, conventional anatomically based imaging modalities such as computed tomography (CT), and magnetic resonance imaging (MRI), and other imaging methods. However, RECIST is sometimes inaccurate in assessing the efficacy of targeted therapy drugs because of the poor correlation between tumor size and treatment-induced tumor necrosis or shrinkage. This approach might also result in delayed identification of response when the therapy does confer a reduction in tumor size. Innovative molecular imaging techniques have rapidly gained importance in the dawning era of targeted therapy as they can visualize, characterize, and quantify biological processes at the cellular, subcellular, or even molecular level rather than at the anatomical level. This review summarizes different targeted cell signaling pathways, various molecular imaging techniques, and developed probes. Moreover, the application of molecular imaging for evaluating treatment response and related clinical outcome is also systematically outlined. In the future, more attention should be paid to promoting the clinical translation of molecular imaging in evaluating the sensitivity to targeted therapy with biocompatible probes. In particular, multimodal imaging technologies incorporating advanced artificial intelligence should be developed to comprehensively and accurately assess cancer-targeted therapy, in addition to RECIST-based methods.

Backgrounds: While not completely understood, the electrical, structural, and communication pathways that play a role in the onset and progression of atrial fibrillation (AF) seem to be connected to the intricate interplay between neurohormones and cellular mediators. Our study's objective was to examine how the expression profiles of the inflammatory cytokines interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor (TNF), and programmed death 1 (PD-1) changed in Cluster of Differentiation 4 (CD4) T cells depending on whether atrial fibrillation was paroxysmal or permanent. This analysis would provide new diagnostic markers for the detection and management of atrial fibrillation. Methods: In a cross-sectional study, 60 healthy controls, 49 patients with persistent atrial fibrillation, and 50 patients with paroxysmal atrial fibrillation were compared. Serum biomarker levels are found using the ELISA method, which uses enzyme-linked immunosorbent assay. Echocardiography was used to assess heart function. Results: Patients with atrial fibrillation had serum concentrations of IL-6, TNF-a, and IL-10 that were considerably higher than but PD-1 was lower those in the non-AF control group and those in patients with persistent atrial fibrillation. According to the diameter of LA and the serum level of NT-proB-type natriuretic peptide (NT-proBNP) is greater than that of patients with paroxysmal atrial fibrillation than control group. Patients with persistent atrial fibrillation had increased serum levels of low-density lipoprotein cholesterol (LDL-C) compared with those without atrial fibrillation. While PD-1 in patients with paroxysmal atrial fibrillation is closely related to C-reactive protein (CRP), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and very low density lipoprotein cholesterol. In addition, PD-1 in patients with persistent atrial fibrillation is closely related to IL-6, TNF-a, and IL-10. Conclusion: Higher blood concentrations of NT-proBNP, IL-6, IL-10, TNF-, and LDL-C but low level of PD-1 are associated with progression from paroxysmal or chronic AF.

Abstract Background The role of B cell subsets remained to be elucidated in a variety of immune diseases, though which was used as an effective biomarker for anti-inflammatory or antiviral response. This study aimed to evaluate the early changes of B cell subtypes distribution in elderly patients with community acquired pneumonia (CAP), as well as the association between B cell subtypes and prognosis. Methods This prospective study included elderly patients with CAP, severe CAP (sCAP) and healthy elderly subjects between April 2016 and March 2018. Flow cytometry was used to detect CD3, CD20, HLA-DR, CD24, CD27, CD38, IgM, and IgD. CD20+ B cells were further divided into naïve B cells (Bn), IgM/D+ memory B cells (IgM+ Bm), switched B cells (SwB), and transitional B cells (Btr). Results A total of 22 healthy controls, 87 patients with CAP and 58 patients with sCAP were included in the study. Compared to CAP, sCAP was characterized by significantly lower absolute number of B cells, Bn and Btr, significantly lower Btr and Bn subset percentage, while percentage of IgM+ Bm was significantly higher. Heat map showed Bn and Btr on day 3 and day 7 was negatively correlated with activated partial prothrombin time (APTT), international normalized ratio (INR), sequential organ failure assessment score (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II). After 28-day follow-up, Btr percentage in survival group was significantly higher. Receiver operator characteristic (ROC) curve analysis found that Btr count showed sensitivity of 48.6% and specificity of 87.0% for predicting the 28-day survival, with an area under the ROC curves of 0.689 (p = 0.019). Conclusions Severity and prognosis of CAP in elderly people is accompanied by changes in the B cell subsets. Btr subsets could play prognostic role for a short-term mortality of elderly CAP patients.

Abstract Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.

In the present research, the dynamic recrystallization (DRX) behavior of a newly-developed Mg–Al–Zn–RE alloy with abundant second-phase particles during hot extrusion is investigated by coupling finite element (FE) and cellular automaton (CA) models. A two-dimensional CA model is developed to quantitatively and topologically evaluate the DRX process during deformation with constant forming conditions. Considering the fact that second-phase particles with various sizes extensively exist in the studied Mg–Al–Zn–RE magnesium alloy, models of DRX nucleation and grain growth velocity are modified. The coefficients of the modified CA model are calibrated by isothermal compression experiments of the magnesium alloy. Subsequently, the CA model is coupled with FE analysis to investigate the DRX behavior during the hot extrusions of the Mg–Al–Zn–RE alloy. The DRX behavior of the magnesium alloy at different stages and positions of extruded plates is simulated by the established model. Finer grains near the edge than in the inner of the plates result from higher strain and strain rate. The influence of extrusion conditions on microstructural evolution is explored. Under the employed forming conditions, average grain size decreases 28–62 times from as-cast and solution-treated to as-extruded state due to grain refinement by DRX. With increasing initial billet temperature or extrusion speed, average grain size increases. The finest grains are obtained at the initial billet temperature of 623 K and the extrusion speed of 7.83 mm/s. Low initial billet temperature or high extrusion speed benefits homogeneous grain distribution. The simulated results are in good agreement with experimental ones.

An esophageal fistula can be caused by an esophageal tumor as well as the surgery, radiotherapy (RT), or chemoradiotherapy used to treat the tumor. The most dangerous complications are massive hemoptysis and asphyxia. This report describes a 58-year-old man with a >1-month history of dysphagia and hemoptysis. Contrast-enhanced computed tomography revealed a tumor in the upper esophagus and a tracheoesophageal fistula. Esophagography revealed a large lesion measuring approximately 8 cm in length. Esophagogastroduodenoscopy showed an ulcerated tumor with raised margins originating 22 cm from the incisors, and histologic examination of a biopsy specimen indicated squamous cell carcinoma. The tumor was finally classified as stage IVA (T4bN0M0) esophageal squamous cell carcinoma. Massive hemoptysis occurred after the patient was admitted to the hospital. Therefore, we applied staged dose-escalated RT in three stages (6.0 Gy in 5 fractions, 7.5 Gy in 5 fractions, and 46.8 Gy in 26 fractions) to decrease the rate of tumor shrinkage brought on by RT and give the normal tissue enough time to close the fistula. Finally, the hemoptysis resolved and the patient’s symptoms were significantly improved. Contrast-enhanced chest computed tomography revealed shrinkage of the tumor. In conclusion, staged dose-escalated RT can be applied for esophageal fistula closure.

Neuropathic pain (NP) is a frequent condition caused by a lesion in, or disease of, the central or peripheral somatosensory nervous system and is associated with excessive inflammation in the central and peripheral nervous systems. Repetitive transcranial magnetic stimulation (rTMS) is a supplementary treatment for NP. In clinical research, rTMS of 5–10 Hz is widely placed in the primary motor cortex (M1) area, mostly at 80%–90% RMT, and 5–10 treatment sessions could produce an optimal analgesic effect. The degree of pain relief increases greatly when stimulation duration is greater than 10 days. Analgesia induced by rTMS appears to be related to reestablishing the neuroinflammation system. This article discussed the influences of rTMS on the nervous system inflammatory responses, including the brain, spinal cord, dorsal root ganglia (DRG), and peripheral nerve involved in the maintenance and exacerbation of NP. rTMS has shown an anti-inflammation effect by decreasing pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, and increasing anti-inflammatory cytokines, including IL-10 and BDNF, in cortical and subcortical tissues. In addition, rTMS reduces the expression of glutamate receptors (mGluR5 and NMDAR2B) and microglia and astrocyte markers (Iba1 and GFAP). Furthermore, rTMS decreases nNOS expression in ipsilateral DRGs and peripheral nerve metabolism and regulates neuroinflammation.

The rapid development of computer science over the past few decades has led to unprecedented progress in the field of artificial intelligence (AI). Its wide application in ophthalmology, especially image processing and data analysis, is particularly extensive and its performance excellent. In recent years, AI has been increasingly applied in optometry with remarkable results. This review is a summary of the application progress of different AI models and algorithms used in optometry (for problems such as myopia, strabismus, amblyopia, keratoconus, and intraocular lens) and includes a discussion of the limitations and challenges associated with its application in this field.

Thermal power plants play a crucial role in the power system as critical lifeline infrastructure. In order to meet the production process requirements, the main building of a thermal power plant is often connected to a coal conveyor trestle. This study focuses on investigating the seismic interaction between the common three-row reinforced concrete frame-bent main building and the steel trestle in a circulating fluidized bed (CFB) unit. The objective is to assess the influence of the trestle on the main building and understand the failure mode of the trestle structure. The seismic interaction is analyzed through fragility analysis based on Incremental Dynamic Analysis (IDA). The results indicate that the trestle has minimal influence on the main building, except during the large deformation stage. The study identifies the failure mode of the coal conveyor trestle as excessive relative displacement along the longitudinal direction at the connection points, leading to collisions or falls. A seismic demand model based on longitudinal relative displacement is developed to obtain the fragility curve for the trestle structure. These findings offer valuable insights for assessing the seismic performance of thermal power plants.

An effective sponge city construction evaluation system plays a crucial role in evaluating sponge city construction schemes. The construction of a sponge city evaluation system still faces challenges related to incomplete index selection and unscientific weight division. Limited studies have focused on the comprehensive assessment of sponge city construction in the early stages. This study constructed a scientific assessment indicator system and a quantitative indicator weight at all levels by literature review and statistical analysis methods from an objective perspective. To demonstrate how to utilize our evaluation methods, three construction schemes randomly generated by MATLAB were evaluated under evaluation states of constant weight and variable weight, respectively. Scheme 3 had the highest score of 0.638 under the constant weight assessment, but it cannot practically be the final construction scheme due to the imbalance between indicators. Compared to the constant weight assessment, a variable weight assessment can effectively balance the states of the evaluation index with changes in the decision variable. Among the three schemes, Scheme 2 is the best choice with a value of 0.0355 under variable weight evaluation due to punishment and incentives in the variable weight method. The concept of “punishing” a disadvantageous indicator and “motivating” an advantageous indicator increases the relative advantages of the indices, ultimately affecting the assessment results of schemes and leading to a more balanced state. This study provides reasonable analysis and decision-making mechanisms to support decision-making and guide the scientific selection of a construction scheme.

Abstract Notch receptors (Notch1–4) play critical roles in tumorigenesis and metastasis of malignant tumors, including breast cancer. Although abnormal Notch activation is related to various tumors, the importance of single receptors and their mechanism of activation in distinct breast cancer subtypes are still unclear. Previous studies by our group demonstrated that Notch3 may inhibit the emergence and progression of breast cancer. PTEN is a potent tumor suppressor, and its loss of function is sufficient to promote the occurrence and progression of tumors. Intriguingly, numerous studies have revealed that Notch1 is involved in the regulation of PTEN through its binding to CBF-1, a Notch transcription factor, and the PTEN promoter. In this study, we found that Notch3 and PTEN levels correlated with the luminal phenotype in breast cancer cell lines. Furthermore, we demonstrated that Notch3 transactivated PTEN by binding CSL-binding elements in the PTEN promoter and, at least in part, inhibiting the PTEN downstream AKT-mTOR pathway. Notably, Notch3 knockdown downregulated PTEN and promoted cell proliferation and tumorigenesis. In contrast, overexpression of the Notch3 intracellular domain upregulated PTEN and inhibited cell proliferation and tumorigenesis in vitro and in vivo. Moreover, inhibition or overexpression of PTEN partially reversed the promotion or inhibition of cell proliferation induced by Notch3 alterations. In general, Notch3 expression positively correlated with elevated expression of PTEN, ER, lower Ki-67 index, and incidence of involved node status and predicted better recurrence-free survival in breast cancer patients. Therefore, our findings demonstrate that Notch3 inhibits breast cancer proliferation and suppresses tumorigenesis by transactivating PTEN expression.

The quality of traditional sMDT(single-centered multi-disciplinary treatment team) teaching model will be affected by the centerlocation, leve of heathcare service, performance habits, dominant disciplines, and superior technologies, which will directly affect the depth and breadth of students' knowledge learning. Based on the traditional sMDT teaching, the new multi-centered MDT (mMDT) teaching model establishes cooperative teaching relationships with multiple hospitals and disciplines, cocultivates undergraduate and graduate students, and regularly conducts mMDT teaching, which effectively avoids the defects of the traditional sMDT teaching model and meets the needs of students at different levels. Through the mMDT teaching mode, students can learn the advanced clinical reasoning and techniques in different disciplines or hospitals, have a deeper understanding of the concept of comprehensive diagnosis and treatment of tumors, and improve the comprehensive quality of clinical research.

To improve the topological stability of wireless sensor networks, an anti-destructive algorithm based on energy-aware weighting is proposed. The algorithm takes the Weighted Dynamic Topology Control (WDTC) algorithm as a reference, and calculates the weight of nodes by using the distance between nodes and the residual energy of nodes. Then chooses optimal weights and constructs a stable balanced topological network with multiple-connectivity paths using the K-connection idea. The simulation results show that the proposed algorithm improves the average connectivity of the topological network, enhances the robustness of the network, ensures the stable transmission of network information, and optimizes the betweenness centrality of the network nodes, making the network has a good invulnerability.

Abstract Background Anemia is one of severe complications in the perioperative period of total hip arthroplasty (THA). Erythropoietin (EPO) has been considered to improve patients’ anemia state, but its efficiency and safety remains controversial. Methods A total of 152 patients who underwent total hip arthroplasty from January 2017 to March 2019 were randomized to 2 groups. Recombinant human erythropoietin (rHu-EPO) group was treated with rHu-EPO subcutaneous injection 10000 IU after operation and once daily in the next week, while control group was treated with none extra treatment. Routine hematologic examination and thrombelastography (TEG) performed at different time point respectively. Doppler ultrasound for bilateral lower limbs was performed 1 day before surgery and 7 days after surgery. Auxiliary examination outcomes, blood transfusions outcomes, and postoperative complications were recorded as assessment indicators. Results The difference in the relevant indexes of traditional coagulation and TEG values between two groups were not significantly. No significant difference was observed in the incidence of thromboembolism events and other complications between two groups during postoperative period. The amount of intraoperative blood loss was similar between the two groups. However, the postoperative use and dosage of allogeneic blood in the rHu-EPO group were lower than those in the control group. The hemoglobin and hematocrit level in the rHu-EPO group were higher than that in the control group after surgery. Conclusion Postoperative subcutaneous injection of rHu-EPO can improve hematological anemia-related parameters, reduce the use and dosage of allogeneic blood transfusions (ABTs), and has no significant influence on the formation of thrombosis and other complications in patients undergoing total hip arthroplasty in short term.

This study investigated the effects of different drying methods on the drying characteristics, three-dimensional (3D) appearance, color, total polysaccharide content (TPC), antioxidant activity, and microstructure of Pleurotus eryngii slices. The drying methods included hot air drying (HAD), infrared drying (ID), and microwave drying (MD). The results showed that the drying method and conditions significantly influenced the drying time, with MD having a significant advantage in reducing the drying time. The 3D appearance of P. eryngii slices was evaluated based on shrinkage and roughness as quantitative indexes, and the best appearance was obtained by hot air drying at 55 and 65 °C. HAD and ID at lower drying temperatures obtained better color, TPC, and antioxidant activity, but MD significantly damaged the color and nutritional quality of P. eryngii. The microstructure of dried P. eryngii slices was observed using scanning electron microscopy, and the results showed that drying methods and conditions had an obvious effect on the microstructure of P. eryngii slices. Scattered mycelia were clearly observed in P. eryngii samples dried by HAD and ID at lower drying temperatures, while high drying temperatures led to the cross-linking and aggregation of mycelia. This study offers scientific and technical support for choosing appropriate drying methods to achieve a desirable appearance and quality of dried P. eryngii.

Accurately simulating the nonlinear response of reinforced concrete (RC) columns under cyclic loading is crucial in performance-based seismic design for building structures, especially regarding strength degradation. This paper presents the description, calibration and simulation of the hysteretic model for RC columns based on effective hysteretic energy dissipation with positive and negative directions. During the analysis of previous experimental data, the relationship between hysteresis energy dissipation, maximum displacement, and the effects of positive and negative loading directions on strength degradation has been summarized. The proposed method for determining the yield strength of the hysteresis loop is based on the farthest point method. Calibration of the hysteretic models’ existing RC columns’ experimental data demonstrates that the proposed model can simulate the main characteristics that influence deterioration.

Aims. In this report, it was investigated that hepatoma cells can cause downregulation of cytotoxic T lymphocyte (CTL) function and tea polyphenols (TPs) can reverse downregulation of CTL function. Methods. The expression of GRP78, PD-1, and TIM-3 was detected by western blotting in CTLL-2 cocultured with Hepa1-6 cells. Moreover, perforin (PRF1) and granzyme B (GzmB) protein levels and ER morphology were examined by ELISA and TEM, respectively. After 4-phenylbutyric acid (4-PBA) or tunicamycin (TM) treatment, programmed cell death protein 1 (PD-1), and mucin domain 3 (TIM-3), PRF1, and GzmB were measured by western blotting and ELISA. After sh-CHOP or GSK2656157 (PERK inhibitor) stimulation, the activation of the PERK-CHOP pathway was detected in CTLL-2 cells. Finally, changes in PD-1, TIM-3, PRF1, and GzmB levels were detected to verify the reversal of CTL depletion by TP. Results. The expression of GRP78, PD-1, and TIM-3 clearly increased, and swelling was observed for the endoplasmic reticulum (ER) in CTLL-2 cells cocultured with hepatoma cells. Concurrently, the levels of PRF1 and GzmB decreased. CTLL-2 depletion was induced after stimulation with TM and differed from 4-PBA stimulation. Treatment with sh-CHOP or GSK2656157 caused a decrease in PD-1 and TIM-3 expression, whereas the expression of PRF1 and GzmB clearly increased. After adding TP, the function of CTLs increased markedly. Conclusion. Hepatoma cells induced the depletion of CTLs through the ER stress PERK-CHOP pathway, and TP reversed this depletion by downregulating ER stress.

Buildings close to the ground treated by the resonance- free vibratory hammer method are often vulnerable to excessive vibrations. An in situ test of an urban soft site was carried out to investigate the resonance-free vibratory hammer induced vibration effects during construction. Vibration pickups were set at the positions with distances of 15 m, 30 m, 50 m, and 100 m away from the vibration source. On the basis of the results obtained from this investigation, vibration effects of the resonance-free vibratory hammer and safe construction distances were systematically analyzed. The testing results indicate that the vibration in the vertical direction is stronger than that in the other two horizontal directions. The vertical vibration should be the main reference quantity for the foundation treatment by using the resonance-free vibratory hammer method. The predominant frequency of each measuring point in the same direction decreased with an increase of the distance from the vibration source (DFTVS). In terms of the measuring point with a DFTVS of 30 m, the peak values of velocity in all directions were within 5 mm/s, which meet the requirements of the allowable limit of building vibration. According to the in situ testing results, a model for calculating the acceleration exponent of the vibration caused by the resonance-free vibratory hammer technology was established by comprehensively considering the amplitude of acceleration, the attenuation coefficient of THE DFTVS, and the vibration correction factor. Finally, the reliability of the calculation model was verified through the comparison between the calculated results and field vibration experimental results, in which all the correlation coefficients of validation example were above 0.9.