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Highlights: SERPINE1 mediates the transfer of cancer-derived exosomal let-7 g-5p to promote macrophage M2 polarization. Exosomal let-7 g-5p drives M2 polarization by downregulating SOCS7 and relieving its inhibition of STAT3 phosphorylation. SERPINE1 promotes the transcription of let-7 g-5p by activating the JAK2/STAT3 signaling pathway.Background: Tumor-associated macrophages (TAMs), particularly M2-polarized TAMs, are significant contributors to tumor progression, immune evasion, and therapy resistance in gastric cancer (GC). Despite efforts to target TAM recruitment or depletion, clinical efficacy remains limited. Consequently, the identification of targets that specifically inhibit or reprogram M2-polarized TAMs presents a promising therapeutic strategy. Objective: This study aims to identify a dual-function target in GC cells that drives both malignant phenotypes and M2 macrophage polarization, revealing its molecular mechanisms to provide novel therapeutic targets for selectivly targeting M2-polarized TAMs in GC. Methods: Transcriptomic and clinical data from GC and adjacent tissues were utilized to identify mRNAs associated with high M2 macrophage infiltration and poor prognosis. Single-cell sequencing elucidated cell types expressing the target gene. Transwell co-culture and exosome intervention experiments demonstrated its role in M2 polarization. Small RNA sequencing of exosomes, western blotting, and CoIP assays revealed the molecular mechanisms underlying exosome-mediated M2 polarization. Protein array, ChIP and dual-luciferase reporter assays clarified the molecular mechanisms by which the target gene regulated exosomal miRNA. In vivo validation was performed using xenograft tumor models. Results: SERPINE1 was identified as a highly expressed mRNA in GC tissues and cells, significantly associated with advanced clinical stages, worse prognosis, and higher M2 macrophage infiltration in patients with GC. SERPINE1 overexpression in GC cells promoted tumor growth and M2 macrophage polarization. SERPINE1 facilitated the transfer of let-7 g-5p to macrophages via cancer-derived exosomes, inducing M2 polarization. Exosomal let-7 g-5p internalized by macrophages downregulated SOCS7 protein levels, disrupting its interaction with STAT3 and relieving the inhibition of STAT3 phosphorylation, thereby leading to STAT3 hyperactivation, which consequently drove M2 polarization. Additionally, in GC cells, elevated SERPINE1 expression activated JAK2, enhancing STAT3 binding to the let-7 g-5p promoter and promoting its transcription, thereby increasing let-7 g-5p levels in exosomes. Conclusion: GC cell-derived SERPINE1, functioning as a primary driver of GC growth and TAM M2 polarization, promotes M2 polarization through the regulation of exosomal let-7 g-5p transfer via autocrine activation of the JAK2/STAT3 signaling pathway. These findings elucidate a novel mechanism of SERPINE1-induced M2 polarization and highlight SERPINE1 as a promising target for advancing immunotherapy and targeted treatments in GC. [ABSTRACT FROM AUTHOR]

Background/Aim. Cell proliferation and the regulation of protein expression play an important role in gastritis, but in chronic superficial gastritis (CSG), they are rarely reported. The aim of this study was to determine the relationship between the expression of nuclear factor kappa B (NF-κB) and regulatory proteins and the rat CSG. Methods. The CSG rat model was established artificially, by chemical agents and irregular diet. The expression of epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) in the gastric mucosa of CSG rats was measured by immunohistochemistry, while mRNA expression levels of NF-κB p65 were detected by in situ hybridization. Results. There was more obvious infiltration of inflammatory cells in the gastric mucosa of CSG rats than in that of control rats, and the inflammation score was significantly increased. The expression levels of PCNA, EGFR, and NF-κB p65 mRNA in the gastric mucosal cells of CSG model rats increased significantly. Correlation analysis showed that the inflammation score was positively correlated with the expression levels of NF-κB p65 mRNA and EGFR, while it presented no significant correlation with the expression level of PCNA. In addition, there was a significant positive correlation between NF-κB p65 mRNA and EGFR levels. Conclusion. High expression of NF-κB and EGFR plays an important role in the occurrence and progression of CSG, and it is significantly positively correlated with the degree of inflammation in the gastric mucosa. Therefore, changes in NF-κB and EGFR expression may be used as important indicators for the assessment of CSG; changes in their expression levels are helpful to assess the degree of gastric mucosal lesions and progression of CSG.

Pancreatic cancer (PC) is a highly aggressive and deadly malignancy with limited treatment options and poor prognosis. Identifying new therapeutic targets and developing effective strategies for PC treatment is of utmost importance. Here, we revealed that SHCBP1 is significantly overexpressed in PC and negatively correlated with patient prognosis. Knockout of SHCBP1 inhibits the proliferation and migration of PC cells in vitro, and suppresses the tumor growth in vivo. In addition, we identified AZD5582 as a novel inhibitor of SHCBP1, which efficiently restrains the growth of PC in cell lines, organoids, and patient‐derived xenografts. Mechanistically, we found that AZD5582 induced the apoptosis of PC cells by inhibiting the activity of PI3K/AKT signaling and preventing the degradation of TP53. Collectively, our study highlights SHCBP1 as a potential therapeutic target and its inhibitor AZD5582 as a viable agent for PC treatment strategies. [ABSTRACT FROM AUTHOR]

Polymer-derived ceramics (PDCs) have many advantages in ceramic molding and ceramic properties, but because of the obvious volume shrinkage in the process of precursor transformation into ceramics, it is easy for defects to appear in the forming process of bulk PDCs. Herein, theoretical analyses and experimental studies were carried out to improve the quality of sintered samples and realize the parametric design of raw materials. Firstly, based on the HPSO/D4Vi cross-linking system, the mathematical model of the free cross-linking ratio was established, and the theoretical value was calculated. After that, the samples with different free cross-linking rates were heated at 450 °C and 650 °C for different holding times. It was found that the free cross-linking ratio (α) had a significant impact on the weight loss of the samples. When the difference of the α value was 10%, the difference of the samples' weight loss ratio could reach 30%. Finally, the morphology of sintered products with different α values was analyzed, and it was found that obvious defects will occur when the free cross-linking ratio is too high or low; when this value is 40.8%, dense and crack-free bulk ceramics can be obtained. According to analysis of the chemical reaction and cross-linking network density during sintering, the appropriate value of the free cross-linking ratio and reasonable control of the cross-linking network are beneficial for reducing the loss of the main chain element and C element, alleviating the sintering stress, and thus obtaining qualified pressureless sintered bulk ceramic samples. [ABSTRACT FROM AUTHOR]

In numerical weather prediction (NWP) models, physical parameterization schemes are the most computationally expensive components, despite being greatly simplified. In the past few years, an increasing number of studies have demonstrated that machine learning (ML) parameterizations of subgrid physics have the potential to accelerate and even outperform conventional physics-based schemes. However, as the ML models are commonly implemented using the ML libraries written in Python, very few ML-based parameterizations have been successfully integrated with NWP models due to the difficulty of embedding Python functions into Fortran-based NWP models. To address this issue, we developed a coupler to allow the ML-based parameterizations to be coupled with a widely used NWP model, i.e., the Weather Research and Forecasting (WRF) model. Similar to the WRF I/O methodologies, the coupler provides the options to run the ML model inference with exclusive processors or the same processors for WRF calculations. In addition, to demonstrate the effectiveness of the coupler, the ML-based radiation emulators are trained and coupled with the WRF model successfully. [ABSTRACT FROM AUTHOR]

In numerical weather prediction (NWP) models, physical parameterization schemes are the most computationally expensive components, despite being greatly simplified. In the past few years, an increasing number of studies have demonstrated that deep learning (DL) parameterizations of subgrid physics have the potential to accelerate and even outperform conventional physic-based schemes. However, as the DL models are commonly implemented using the DL libraries written in Python, very few DL-based parameterizations have been successfully integrated with NWP models due to the difficulty of embedding Python functions into Fortran-based NWP models. To address this issue, we developed a coupler to allow the DL-based parameterizations to be coupled with a widely used NWP model, i.e., the Weather and Research Forecasting (WRF) model. Similar to the WRF I/O methodologies, the coupler provides the options to run the DL model inference with exclusive processors or the same processors for WRF calculations. In addition, to demonstrate the effectiveness of the coupler, the DL-based radiation emulators are trained and coupled with the WRF model successfully. [ABSTRACT FROM AUTHOR]

Operation stability is the main challenge that current existing saturable absorbers (SAs) are facing. In this paper, we report on two low chemical activity saturable absorbers, the tellurium dioxide and antimony trioxide thin film, for stable femtosecond pulse generation in 2 μm region. The nonlinear absorption of two oxides at 2 μm was firstly revealed and the extraordinary mode-locking performance based on two oxides was demonstrated. The phase noise and amplitude noise were also measured and analyzed, and the integrated RMS relative intensity noise was found to be 0.0196% and 0.0218% for TeO2 thin film and Sb2O3 thin film respectively. Great thermal stability and long-term stability were also confirmed. Heating the oxides coated area in atmosphere for hours and the lasers still could be mode-locked. Compared to low dimensional materials, the oxides proposed in this paper could be more suitable for robust mode locking in harsh environment. The broadened working conditions tolerance also enables new applications for optical modulators. [ABSTRACT FROM AUTHOR]

In order to explore the changes of intestinal flora and serum levels of relevant substances in patients with gastric cancer before and after surgery with carbon nanoparticle laparoscopy, a total of 180 patients with early distal gastric cancer who adopted laparoscopic radical gastrectomy for distal gastric cancer in the general surgery department of TCM Hospital of Shi Jia Zhuang City from January 2018 to January 2020 were selected and randomly divided into two groups: traditional laparoscopic operation (control group) and carbon nanoparticle laparoscopic operation (experimental group) were adopted for treatment for the two groups, respectively. Postoperative evaluation included the difference between the two groups in the operative time, the efficiency of intraoperative lymph node dissection, and the number of lymph node detection. The adverse reactions, changes of intestinal flora before and after surgery in the two groups, and the serum levels of epidermal growth factor receptor (EGFR), interleukin-32 (IL-32), and gastrin 17 were evaluated. In the experimental group, the success rate of carbon nanoparticle tracer black staining reached 100%, and the operation time of the experimental group was significantly shorter than that of the control group (P < 0.05). The lymph node detection rate of the experimental group was higher than that of the control group (P < 0.05), but there was no significant difference in the lymph node metastasis rate between the two groups (P > 0.05). The sentinel lymph node sensitivity of the experimental group reached 92.3%, and the specificity, accuracy, and positive and negative prediction rates reached 100%; the experimental group patients were with an obviously higher incidence of level I-II gastrointestinal reaction (P < 0.05). Postoperative increases in Bifidobacteria and Lactobacillus were observed in both groups, while decreases in Enterococcus and Escherichia coli were observed in both groups (P < 0.05). Moreover, the degree of increase and decrease in the experimental group was greater than that in the control group (P < 0.05). The serum levels of EGFR, IL-32, and gastrin 17 in the two groups were significantly lower than those in the control group on 3 d, 7 d, and 15 d after surgery (P < 0.05). In the radical gastrectomy for distal gastric cancer, carbon nanoparticle laparoscopy was not only helpful for the localization of small tumors but also for the thorough dissection of lymph nodes after the surgery, and the postoperative adverse reactions of carbon nanoparticle laparoscopy were also less, which was of great significance for the improvement of intestinal flora and the reduction of serum levels of EGFR, IL-32, and gastrin 17 in gastric cancer patients. [ABSTRACT FROM AUTHOR]

Slit1 is one of the known signaling factors of the slit family and can promote neurite growth by binding to its receptor, Robo2. Upregulation of Slit1 expression in dorsal root ganglia (DRG) after peripheral nerve injury plays an important role in nerve regeneration. Each sensory neuronal soma in the DRG is encapsulated by several surrounding satellite glial cells (SGCs) to form a neural structural unit. However, the temporal and spatial patterns of Slit1 upregulation in SGCs in DRG and its molecular mechanisms are not well understood. This study examined the spatial and temporal patterns of Slit1 expression in DRG after sciatic nerve crush by immunohistochemistry and western blotting. The effect of neuronal damage signaling on the expression of Slit1 in SGCs was studied in vivo by fluorescent gold retrograde tracing and double immunofluorescence staining. The relationship between the expression of Slit1 in SGCs and neuronal somas was also observed by culturing DRG cells and double immunofluorescence labeling. The molecular mechanism of Slit1 was further explored by immunohistochemistry and western blotting after intraperitoneal injection of Bright Blue G (BBG, P2X7R inhibitor). The results showed that after peripheral nerve injury, the expression of Slit1 in the neurons and SGCs of DRG increased. The expression of Slit1 was presented with a time lag in SGCs than in neurons. The expression of Slit1 in SGCs was induced by contact with surrounding neuronal somas. Through injured cell localization, it was found that the expression of Slit1 was stronger in SGCs surrounding injured neurons than in SGCs surrounding non-injured neurons. The expression of vesicular nucleotide transporter (VNUT) in DRG neurons was increased by injury signaling. After the inhibition of P2X7R, the expression of Slit1 in SGCs was downregulated, and the expression of VNUT in DRG neurons was upregulated. These results indicate that the ATP-P2X7R pathway is involved in signal transduction from peripheral nerve injury to SGCs, leading to the upregulation of Slit1 expression. [ABSTRACT FROM AUTHOR]

Background: Misplaced screw during the internal fixation of acetabular fractures may penetrate the hip joint which might cause chondrolysis and traumatic osteoarthritis in the future. This study aims to acquire the safe path for screw insertion along inferior border of the arcuate line fixation route at acetabular area.Methods: Computed tomography (CT) scans of 98 patients without pelvic trauma were rebuilt for three-dimensional models of pelvis. After depicting the fixation route curve, five cross-sections perpendicularly to the curve were established from the anterior of pelvis to the posterior along inferior border of the arcuate line. The safe screw lengths for section 1 and 5 were measured from the computer models. In section 2, 3 and 4, a line from the screw entry point tangent to the inferior edge of the acetabulum was depicted and the measurements of minimum safe direction of screw insertion were performed then marked with angle θ.Results: The safe screw lengths for section 1 and 5 were 22.29 ± 4.41 mm and 32.64 ± 4.70 mm (n = 98). The minimum safe angles of screw insertion for the middle three sections 2, 3, and 4 were 65.38 ± 10.23°, 74.20 ± 10.20°, and 57.88 ± 11.11°(n = 98), respectively. The results for the male group (n = 98) indicated smaller minimum safe angles in these three sections compared with the female (n = 98).Conclusions: Compared to male, the minimum safe angles of screw placement at acetabular area for female should be more away from inferior edge of acetabulum and tilt to the bottom of pelvis along inferior border fixation route in surgical management of acetabular fractures. [ABSTRACT FROM AUTHOR]

Ti/Ti–Al and SiCf-reinforced Ti/Ti–Al laminated composites were fabricated through vacuum hot-pressure using pure Ti foils, pure Al foils and SiC fibers as raw materials. The effects of SiC fiber and a laminated structure on the properties of Ti–Al laminated composites were studied. A novel method of fiber weaving was implemented to arrange the SiC fibers, which can guarantee the equal spacing of the fibers without introducing other elements. Results showed that with a higher exerted pressure, a more compact structure with fewer Kirkendall holes can be obtained in SiCf-reinforced Ti/Ti–Al laminated composites. The tensile strength along the longitudinal direction of fibers was about 400 ± 10 MPa, which was 60% higher compared with the fabricated Ti/Ti–Al laminated composites with the same volume fraction (60%) of the Ti layer. An in situ tensile test was adopted to observe the deformation behavior and fracture mechanisms of the SiCf-reinforced Ti/Ti–Al laminated composites. Results showed that microcracks first occurred in the Ti–Al intermetallic layer. [ABSTRACT FROM AUTHOR]