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This study systematically investigated the electrochemical corrosion and static immersion corrosion behavior of the novel Ti6422 (Ti–6Al–4V–2Mo–2Fe) alloy with equiaxed (EM) and lamellar structure (LM) in HCl solution. The differences in corrosion performance between EM and LM samples were analyzed based on the characteristics of the passive film and substrate microstructure. Results indicated that the LM sample contained higher contents of TiO₂, Al₂O₃, and MoO₃ with higher stability compared with the EM sample, and the thickness of passive film was approximately twice that of the EM sample. Additionally, the donor density of LM sample was lower than EM sample. These findings indicate that the passive film on LM samples is thicker, with fewer defects and higher density. Electrochemical corrosion results revealed that the corrosion current of LM samples was lower and the polarization resistance was higher than these of EM samples, both suggesting superior corrosion resistance of LM samples. Immersion corrosion further confirmed that the LM sample had a lower corrosion rate. The enhanced corrosion resistance in LM samples was primarily due to higher content of corrosion-resistant β phase. Conversely, the numerous micro-galvanic cells between αs precipitates and adjacent β phase in EM samples weakened the corrosion resistance. Overall, these results demonstrated that regulating microstructure through heat treatment is an effective strategy for improving corrosion resistance of titanium alloys.

Abstract Objective The release of adipose tissue-derived miRNAs is increased under conditions of obesity, but the exact molecular mechanisms involved have not been elucidated. This study investigated whether obesity-induced increases in palmitic acid (PA) content could activate the NF-κB/endoplasmic reticulum stress (ER stress) pathway and promote the expression and release of exosomal miRNAs in adipocytes. Methods Abdominal adipose tissue and serum samples were collected from normal weight individuals and people with obesity to clarify the correlation of serum PA content with NF-κB/ER stress and the release of exosomal miRNAs. NF-κB and ER stress were blocked in obese mice and in vitro cultured adipocytes to demonstrate the molecular mechanisms by which PA promotes the release of exosomal miRNAs.The morphology, particle size and distribution of the exosomes were observed via transmission electron microscopy and NTA. Results Accompanied by increased serum PA levels, the NF-κB/ER stress pathway was activated in the adipose tissue of people with obesity and in high-fat diet (HFD)-induced obese mice; moreover, the levels of miRNAs in both adipose tissue and serum were increased. P-p65 (Bay11-7082) and ER stress (TUDCA) blockers significantly reduced the levels of miRNAs in abdominal adipose tissue and serum, decreased blood glucose levels, and improved glucose tolerance and insulin sensitivity in obese mice. In 3T3-L1 adipocytes, high concentrations of PA activated the NF-κB/ER stress pathway and increased the expression and release of miRNAs in exosomes. P-p65 (Bay11-7082) and ER stress (TUDCA) blockers significantly reversed the increased release exosomal miRNAs cause by PA. Conclusions Obesity-induced increases in PA content increase the expression and release of miRNAs in adipocyte exosomes by activating the NF-κB/ER stress pathway.

CM247LC, a Ni-based superalloy widely used in the aerospace industry due to its exceptional high-temperature performance, faces severe cracking issues in laser powder bed fusion (L-PBF) processing. This study investigates the effects of removing Hf and reducing Al content on the cracking and mechanical behaviors of LPBF-processed CM247LC. Microstructure characterization and thermodynamic calculation reveal that removing Hf narrows the solidification interval, reduces the fraction and size of inter-dendritic MC carbides, and thereby lowers its susceptibility to hot cracking. Decreasing Al content reduces the fraction and size of the γ'/γ eutectic phase and γ′ phase, alleviates local stress concentration, and enhances resistance to solid-state cracking. After chemical modification, the alloy exhibits a remarkable 96% reduction in crack density, a 75% reduction in crack length, and an 86% reduction in porosity, but displays comparable or even higher mechanical properties compared to LPBF-processed CM247LC. The effects of composition modification on the distribution of other elements, the precipitation of MC carbides and γ′ phase, the formation of annealed twins, the room and high temperature strength and ductility, are analyzed in detail. This study demonstrates that conventionally designed alloys can be adapted to the L-PBF process through compositional modification, achieving reduced defects and retained mechanical properties. The findings in this work are also instructive for alloy design tailored for the L-PBF process.

Abstract Background Obesity-induced abnormal bone marrow microenvironment is one of the important risk element for bone metastasis in prostate cancer (PCa). The present study aimed to determine whether obesity-induced elevation in palmitic acid (PA), which is the most abundant of the free fatty acids (FFAs), increased CCL2 via the GPRs/KLF7 pathway in bone marrow adipocytes (BMA) to facilitate PCa growth and metastasis. Methods We constructed a bone-tumor bearing mouse model with obesity through high-fat diet, and observed the tumor formation ability of PCa cells. In vitro, observe the effect of PA on the expression level of CCL2 in BMA through GPRs/KLF7 signaling pathway. After co-culture of BMA and PCa cells, CCK8 assay and transwell experiment were used to detect the changes in biological behavior of PCa cells stimulated by BMA. Results The BMA distribution in the bone marrow cavity of BALB/c nude mice fed with the high-fat diet (HFD) was evidently higher than that in the mice fed with the normal diet (ND). Moreover, HFD-induced obesity promoted KLF7/CCL2 expression in BMA and PCa cell growth in the bone marrow cavity of the mice. In the vitro experiment, a conditioned medium with increased CCL2 obtained from the BMA cultured with PA (CM-BMA-PA) was used for culturing the PCa cell lines, which evidently enhanced the proliferation, invasion, and migration ability. KLF7 significantly increased the CCL2 expression and secretion levels in BMA by targeting the promoter region of the CCL2 gene. In addition, GPR40/120 engaged in the PA-induced high KLF7/CCL2 levels in BMA to facilitate the malignant progression of PC-3 cells. Conclusions PA-activated GPRs/KLF7/CCL2 pathway in BMA facilitates prostate cancer growth and metastasis.

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia, which is clinically identified with irregular and rapid heartbeat rhythm. AF puts a patient at risk of forming blood clots, which can eventually lead to heart failure, stroke, or even sudden death. Electrocardiography (ECG), which involves acquiring bioelectrical signals from the body surface to reflect heart activity, is a standard procedure for detecting AF. However, the occurrence of AF is often intermittent, costing a significant amount of time and effort from medical doctors to identify AF episodes. Moreover, human error is inevitable, as even experienced medical professionals can overlook or misinterpret subtle signs of AF. As such, it is of critical importance to develop an advanced analytical model that can automatically interpret ECG signals and provide decision support for AF diagnostics.Methods: In this paper, we propose an innovative deep-learning method for automated AF identification using single-lead ECGs. We first extract time-frequency features from ECG signals using continuous wavelet transform (CWT). Second, the convolutional neural networks enhanced with residual learning (ReNet) are employed as the functional approximator to interpret the time-frequency features extracted by CWT. Third, we propose to incorporate a multi-branching structure into the ResNet to address the issue of class imbalance, where normal ECGs significantly outnumber instances of AF in ECG datasets.Results and Discussion: We evaluate the proposed Multi-branching Resnet with CWT (CWT-MB-Resnet) with two ECG datasets, i.e., PhysioNet/CinC challenge 2017 and ECGs obtained from the University of Oklahoma Health Sciences Center (OUHSC). The proposed CWT-MB-Resnet demonstrates robust prediction performance, achieving an F1 score of 0.8865 for the PhysioNet dataset and 0.7369 for the OUHSC dataset. The experimental results signify the model’s superior capability in balancing precision and recall, which is a desired attribute for ensuring reliable medical diagnoses.

Abstract Alloy synthesis and processing determine the design of alloys with desired microstructure and properties. However, using data science to identify optimal synthesis-design routes from a specified set of starting materials has been limited by large-scale data acquisition. Text mining has made it possible to convert scientific text into structured data collections. Still, the complexity, diversity, and flexibility of synthesis and processing expressions, and the lack of annotated corpora with a gold standard severely hinder accurate and efficient extraction. Here we introduce a semi-supervised text mining method to extract the parameters corresponding to the sequence of actions of synthesis and processing. We automatically extract a total of 9853 superalloy synthesis and processing actions with chemical compositions from a corpus of 16,604 superalloy articles published up to 2022. These have then been used to capture an explicitly expressed synthesis factor for predicting γ′ phase coarsening. The synthesis factor derived from text mining significantly improves the performance of the data-driven γ′ size prediction model. The method thus complements the use of data-driven approaches in the search for relationships between synthesis and structures.

Abstract Background We compared the clinical efficacy of mini-open reduction and autologous bone grafting (G M) and closed reduction (G C) using intramedullary nailing for the treatment of tibial shaft fractures. Methods This retrospective study included 70 tibial shaft fractures treated with G M or G C between January 2018 and December 2021. The demographic characteristics and clinical outcomes were compared between the two treatment methods. Results This study included 70 patients who were followed-up for 12.4 months. In total, 31 and 39 patients were treated with G M and G C, respectively. The operative duration was significantly shorter for G M (95.2 ± 19.3 min) than for G C (105.5 ± 22.2 min, p = 0.0454). The number of radiation times was significantly lower for G M (14.7 ± 6.3) than for G C (22.2 ± 9.2, p

Metallic plastic deformation involves complex microstructural changes and defect evolution, posing challenges in predicting and controlling the quality and performance of formed parts. Therefore, a pressing demand exists for a proficient online defect‐sensing system to monitor defects evolution continuously within components during plastic deformation in real time. This article proposes an intelligent online sensing approach for detecting defects in metallic plastic forming based on acoustic emission (AE) and machine learning. A comparative analysis is conducted on AE amplitude signals, stress–strain curves, and defect evolution during the tensile process of TA15 titanium alloy specimens under different stress states. It is found that the defect formation process can be divided into four stages based on the AE amplitude signals. A convolutional neural network model for intelligent defect sensing is established. It leverages transfer learning and is grounded in the relationship between AE signals and the evolution of internal defects. The prediction accuracy using different pretrained models is investigated and compared. It is discerned that utilizing GoogleNet as the pretrained model offers the swiftest training pace with a prediction accuracy of 97.57%. This approach enables intelligent online sensing of internal defect evolution in metal plastic deformation processes.

Abstract Background In previous study, we found that the content of medium-chain fatty acid Caprylic Acid (FFA C8:0) may be an important risk factor of obesity induced prostate cancer (PCa). However, the relationship between FFA C8:0 and PCa has not been reported. In this study, we explored whether the FFA C8:0 can promotes the progression of PCa by up-regulating Krüppel-like factor 7 (KLF7). Methods We collected tissues from PCa patients and Benign Prostate Hyperplasia (BPH), constructed a primary-tumor bearing mouse model with obesity through high-fat diet, and observed the tumor formation ability of PCa cells. In vitro, CCK8 assay, plate cloning, Transwell and scratch experiment were used to detect the changes in biological behavior of PCa cells stimulated by FFA C8:0. Results First, we found that the expression level of KLF7 is higher in PCa tissues of patients, and the expression of KLF7 is positively correlated with tumour-promoting gene IL-6, while it is negative correlated with another tumour-suppressor gene p21. Then, this study found that PCa cells were more likely to form tumors in diet induced obese mice. Compared with the normal diet group (ND), the expression levels of KLF7 in tumor tissues in high-fat diet group (HFD) were higher. Futhermore, we verified that high concentrations of FFA C8:0 can promote the biological behavior of PCa cells by activating KLF7/IL-6/p21 signaling pathway, which is mediated by the GPR84. Conclusions Our research may provide a potential target for clinical prevention and treatment of PCa which induced by obesity.

Abstract Materials genome engineering represents the new frontier of materials research, and is disrupting the conventional “trial and error” paradigm for materials innovation. In the present perspective, the author reflects on the major achievements already made in five sub‐domains, including high‐efficiency materials computation and design, revolutionary experimental technologies, materials big data technologies, research and development of advanced materials, and industrial applications. Furthermore, the author lays out five crucial directions of future efforts for maturing the relevant technologies. These directions include cross‐scale modeling and computational design, artificial intelligence for materials science, automatic and intelligent experimentation, digital twin, and data resource management and sharing.

Abstract One of the challenges in material design is to rapidly develop new materials or improve the performance of materials by utilizing the data and knowledge of existing materials. Here, a rapid and effective method of alloy material design via data transfer learning is proposed to efficiently design new alloys using existing data. A new type of aluminum alloy (E2 alloy) with ultra strength and high toughness previously developed by the authors is used as an example. An optimal three-stage solution-aging treatment process (T66R) was efficiently designed transferring 1053 pieces of process-property relationship data of existing AA7xxx commercial aluminum alloys. It realizes the substantial improvement of strength and plasticity of E2 alloy simultaneously, which is of great significance for lightweight of high-end equipment. Meanwhile, the microstructure analysis clarifies the mechanism of alloy performance improvement. This study shows that transferring the existing alloy data is an effective method to design new alloys.

Transcription factors (TFs) play critical roles in specifying many aspects of neuronal cell fate including dendritic morphology. How TFs are accurately regulated during neuronal morphogenesis is not fully understood. Here, we show that LIM homeodomain protein MEC-3, the key TF for C. elegans PVD dendrite morphogenesis, is regulated by both alternative splicing and an E3 ubiquitin ligase. The mec-3 gene generates several transcripts by alternative splicing. We find that mbl-1, the orthologue of the muscular dystrophy disease gene muscleblind-like (MBNL), is required for PVD dendrite arbor formation. Our data suggest mbl-1 regulates the alternative splicing of mec-3 to produce its long isoform. Deleting the long isoform of mec-3(deExon2) causes reduction of dendrite complexity. Through a genetic modifier screen, we find that mutation in the E3 ubiquitin ligase EEL-1 suppresses mbl-1 phenotype. eel-1 mutants also suppress mec-3(deExon2) mutant but not the mec-3 null phenotype. Loss of EEL-1 alone leads to excessive dendrite branches. Together, these results indicate that MEC-3 is fine-tuned by alternative splicing and the ubiquitin system to produce the optimal level of dendrite branches.

Metal additive manufacturing (AM) has been extensively studied in recent decades. Despite the significant progress achieved in manufacturing complex shapes and structures, challenges such as severe cracking when using existing alloys for laser powder bed fusion (L-PBF) AM have persisted. These challenges arise because commercial alloys are primarily designed for conventional casting or forging processes, overlooking the fast cooling rates, steep temperature gradients and multiple thermal cycles of L-PBF. To address this, there is an urgent need to develop novel alloys specifically tailored for L-PBF technologies. This review provides a comprehensive summary of the strategies employed in alloy design for L-PBF. It aims to guide future research on designing novel alloys dedicated to L-PBF instead of adapting existing alloys. The review begins by discussing the features of the L-PBF processes, focusing on rapid solidification and intrinsic heat treatment. Next, the printability of the four main existing alloys (Fe-, Ni-, Al- and Ti-based alloys) is critically assessed, with a comparison of their conventional weldability. It was found that the weldability criteria are not always applicable in estimating printability. Furthermore, the review presents recent advances in alloy development and associated strategies, categorizing them into crack mitigation-oriented, microstructure manipulation-oriented and machine learning-assisted approaches. Lastly, an outlook and suggestions are given to highlight the issues that need to be addressed in future work.

Stress-inducible interleukin 6 (IL-6) is generated in brown adipocytes via beta-3 adrenergic receptor (ADRB3) signaling, which is necessary in stress hyperglycemia, the kind of metabolic adaptation enabling “fight or flight” response by means of liver gluconeogenesis. Nevertheless, the mechanism of ADRB3 signaling mediates IL-6 in brown adipocytes remains unclear. As a result, it is critical to understand how brown adipocytes produce IL-6 via ADRB3 signaling. We found that the ADRB3 agonist and cold stimulation promoted the expression of KLF7 and IL-6 in brown adipocytes of mice. In parallel to these results in vivo, treatment with ADRB3 agonist promoted the expression of KLF7 and the release of IL-6 in primary brown adipocytes of mice. Notably, we discovered that KLF7 positively controls the expression of IL-6 and downregulated KLF7 largely blunted ADRB3 agonist induced IL-6 expressions in brown adipocytes. Our findings suggest that KLF7 is required for the generation of IL-6 when ADRB3 signaling is activated in brown adipocytes.

Abstract Objective Our previous results have shown that obesity-induced excessive palmitic acid (PA) can promote the expression of KLF7, which plays a vital role in regulation of inflammation, glucose metabolism. But the exact mechanism of PA up-regulating the expression of KLF7 is not clear yet. This study is intend to explore whether PA promoting KLF7 expression through GPRs/NF-κB signaling pathway, causing inflammation and glucose metabolism disorders. Methods Cells were blocked GPRs/NF-κB under PA stimulation in vitro to demonstrate the molecular mechanism of PA up-regulates KLF7 expression. The regulatory effect of p65 on KLF7 was detected by luciferase reporter gene assay. Blocking GPRs/NF-κB in diet-induced obesity mice to detect the expression of KLF7, inflammatory cytokines and glucose metabolism related factors, clarifying the effects of GPRs/NF-κB on KLF7 in vivo. Results In 3T3-L1 adipocytes and HepG2 cells, PA could up-regulate the expression of KLF7 by promoting the GPR40/120-NF-κB signaling pathway, leading to inflammation and reduced glucose consumption (p

Abstract Data provides a foundation for machine learning, which has accelerated data-driven materials design. The scientific literature contains a large amount of high-quality, reliable data, and automatically extracting data from the literature continues to be a challenge. We propose a natural language processing pipeline to capture both chemical composition and property data that allows analysis and prediction of superalloys. Within 3 h, 2531 records with both composition and property are extracted from 14,425 articles, covering γ′ solvus temperature, density, solidus, and liquidus temperatures. A data-driven model for γ′ solvus temperature is built to predict unexplored Co-based superalloys with high γ′ solvus temperatures within a relative error of 0.81%. We test the predictions via synthesis and characterization of three alloys. A web-based toolkit as an online open-source platform is provided and expected to serve as the basis for a general method to search for targeted materials using data extracted from the literature.

Abstract Background Obesity-induced elevated serum free fatty acids (FFAs) levels result in the occurrence of type 2 diabetes mellitus (T2DM). However, the molecular mechanism remains largely enigmatic. This study was to explore the effect and mechanism of KLF15 on FFAs-induced abnormal glucose metabolism. Methods Levels of TG, TC, HDL-C, LDL-C, and glucose were measured by different assay kits. qRT-PCR and Western Blot were used to detect the levels of GPR120, GPR40, phosphorylation of p38 MAPK, KLF15, and downstream factors. Results KLF15 was decreased in visceral adipose tissue of obesity subjects and high-fat diet (HFD) mice. In HFD mice, GPR120 antagonist significantly promoted KLF15 protein expression level and phosphorylation of p38 MAPK, meanwhile reduced the blood glucose levels. While, blocking GPR40 inhibited the KLF15 expression. In 3T3-L1 adipocytes, 1500 μM PA inhibited KLF15 through a GPR120/P-p38 MAPK signal pathway, and 750 μM OA inhibited KLF15 mainly through GPR120 while not dependent on P-p38 MAPK, ultimately resulting in abnormal glucose metabolism. Unfortunately, GPR40 didn’t contribute to PA or OA-induced KLF15 reduction. Conclusions Both PA and OA inhibit KLF15 expression through GPR120, leading to abnormal glucose metabolism in adipocytes. Notably, the inhibition of KLF15 expression by PA depends on phosphorylation of p38 MAPK.

An in-depth and integral understanding of the microstructural evolution during thermomechanical process (TMP) is of great significance to optimize the manufactural process for high-quality components via additive manufacturing. The solidified microstructure model of Inconel 718 alloy fabricated via laser powder bed fusion (L-PBF) is established by multiphase field model firstly. Furthermore, the microstructural evolution during homogenization process is simulated and optimized in this study. Phase field simulation results show that the concentration gradient of Nb along the radius of the cellular substructure decreases from the initial 1.217 wt% to 0.001 wt%, and 67% area fraction of the Laves phase dissolves at the homogenization time of 0.5 h, which have achieved the homogenization purpose. The experimental results show that the average grain size decreases from 9.4 μm to 5.9 μm at the homogenization time from 1.5 h (the standard AMS 5383) to 0.5 h, which resulted in the increase of yield strength and tensile strength of the aged alloy by 14% and 6%, respectively. This research can provide guidance and reference for the microstructural control as well as the TMP parameters design of the additive manufactured alloys.

Abstract Aims/Introduction Microribonucleic acid‐155 (microRNA155) and microRNA29 are reported to inhibit glucose metabolism in some cell and animal models, but no evidence from susceptible populations that examines the relationship between microRNA155 or microRNA29 and type 2 diabetes mellitus currently exists. Furthermore, target genes regulated by microRNA155 and microRNA29 that affect glucose and lipid metabolism remain unknown. Materials and Methods Human participants were divided into normal weight (n = 72), obesity (n = 120) and type 2 diabetes (n = 59) groups. The contents of microRNA155 and microRNA29 abundance in serum were measured, and candidate genes potentially related to glucose and lipid metabolism targeted by either microRNA155 or microRNA29 were screened. Overexpression of microRNA155 and microRNA29 in HepG2 cells was used to verify candidate gene expression, and measure the effects on glucose and lipid metabolism. Results Serum levels of microRNA155 and microRNA29 show a significant increase in individuals with obesity and type 2 diabetes compared with normal weight individuals. Identified target genes for microRNA155 were MAPK14, MAP3K10, DUSP14 and PRKAR2B. Identified target genes for microRNA29 were PEX11A and FADS1. Overexpression of microRNA155 or microRNA29 in HepG2 cells was found to downregulate the expression of identified target genes, and result in inhibition of triglyceride synthesis and glucose incorporation. Conclusions MicroRNA155 and microRNA29 were significantly higher in type 2 diabetes patients compared with the control patients, their levels were also positively correlated with fasting plasma glucose levels, and over‐expression of microRNA155 or microRNA29 were found to downregulate glucose and lipid metabolism target genes, and reduce lipid synthesis and glucose incorporation in HepG2 cells.

Abstract Background Han and Uygur are the two main nationalities living in Xinjiang, China. There are significant differences in the incidence of metabolic diseases for two nationalities, but the specific reasons are not clear. Obesity is an important risk factor for the development of metabolic syndrome, which may be closely related to the increase of serum free fatty acids (FFAs) content. This study aims to use metabolomics to compare the changes of serum FFAs profiles between normal weight (NW) and obese (OB) individuals of two nationalities, screening out the differential FFAs, predicting and evaluating their relationship with diseases. Methods Thirty-four kinds of FFAs in serum were detected by ultra-high-pressure liquid chromatography–mass spectrometry (UHPLC-MS) and distinctions in FFAs profiles were evaluated using a metabolomics method while Receiver operating characteristics (ROC) and logistic regression models were used to explore FFAs significant for diagnosing obesity and obesity-associated comorbidities. Results In the Han nationality, ten kinds of FFAs (C7:0, C8:0, C9:0, C10:0, C11:0, C14:0, C18:2, C20:3, C20:4 and C22:6) showed significant differences between NW and OB individuals. These differential FFAs may be related to hypertension and gestational diabetes mellitus. In the Uygur nationality, C20:3 and C20:5 showed significant differences between NW and OB individuals. C9:0 and C19:0, which were screened out among the female subjects, showed a good ability to predict obesity status in Uygur females (AUC = 0.950). Conclusion In both the Han and Uygur nationalities, the FFAs profiles of NW individuals differed from those of OB individuals. The significantly differential FFAs are closely related to obesity and may be important risk factors for obesity and related metabolic diseases.

Memory consolidation theory suggests that memory is maintained at a stable strength after formation. The authors show that memory is dynamically maintained at an intermediate level allowing a bidirectional regulation which is mediated by a balance between activated Rac1 and expressed α2-chimaerin.

The corrosion resistance of zirconium alloys is closely related to the size of precipitates. β-phase quenching is the key process for controlling the precipitate size of zirconium alloy. In this study, the microstructure and the precipitates size of nuclear graded Zircaloy-4 (hereinafter called as Zr-4) alloy treated by the quenching in different cooling mediums were studied, and the critical quenching diameter of the Zr-4 alloy rod was determined by finite element method. The results showed that, the cooling rate of the β-phase quenching had small effect on the grain size of the alloy, however the size of the needle α grains increased with a decrease of cooling rate. The thickness of α grains quenched in water, quenched in oil, quenched at room temperature and quenched at 440 °C were about 1 μm, 5 μm, 9 μm, and 15 μm, respectively. When the cooling rate was high (water-quenching and oil-quenching), the precipitates formed only along the grain boundary, and with the length of less than 100 nm. When the cooling rate was low (air quenching), precipitates formed not only at the grain boundaries but also inside the grains, and the precipitates length was about 150–200 nm. When the Zr-4 alloy rod was quenched in water or oil, the maximum diameter of the specimen with suitable precipitate size (about 100–200 nm) was 140 and 97 mm, respectively. Keywords: Zr-4 alloy, βphase quenching, Cooling rate, Microstructure, Critical quenching diameter

Summary: To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, translation, CD28, and Akt and not involving increased glucose uptake or activity of glycolytic enzymes. Rather, TCR signaling promotes activation of pyruvate dehydrogenase kinase 1 (PDHK1), inhibiting mitochondrial import of pyruvate and facilitating breakdown into lactate. Inhibition of PDHK1 reveals this switch is required acutely for cytokine synthesis but dispensable for cytotoxicity. Functionally, cytokine synthesis is modulated via lactate dehydrogenase, which represses cytokine mRNA translation when aerobic glycolysis is disengaged. Our data provide mechanistic insight to metabolic contribution to effector T cell function and suggest that T cell function may be finely tuned through modulation of glycolytic activity.

Esophageal squamous cell carcinoma is the most common type of squamous cell carcinoma. Grape seed proanthocyanidin extract (GSPE) is considered to exhibit anticancer activity against several different types of cancer. We aimed to determine whether GSPE inhibited esophageal squamous cancerous cells and the possible involvement of NF-κB in this process. The human esophageal squamous cancer cell line ECA109 was treated with GSPE (0–80 μg/mL) and BAY11-7082 (10 μmol/L) for 12, 24, and 48 h. The MTT assay was used to determine cell proliferation; alterations in cell apoptosis were detected by flow cytometry; levels of inflammatory factors interleukin-6 and cyclooxygenase-2 and apoptotic proteins Bax/Bcl-2 were measured by ELISA; qRT-PCR and western blots were used to examine the activation of caspase-3 and NF-κB signaling. GSPE inhibited the proliferation of ECA109 cells and induced cellular apoptosis in a time- and dose-dependent manner. ELISA results showed that GSPE and BAY11-7082 reduced the secretion of inflammatory cytokines interleukin-6 and cyclooxygenase-2. The results of PCR and western blotting indicated that GSPE and BAY11-7082 activated caspase-3 and attenuated the activation of the NF-κB signaling pathway. GSPE induced apoptosis in ECA109 cells and inhibited ECA109 cell proliferation via a reduction in the secretion of inflammatory cytokines. This mechanism may be related to the attenuation of NF-κB activity and the sensitization of caspase-3.

Objective. Current research has reported that obesity is a chronic inflammatory state, which is closely related with excessive accumulation of free fatty acid, while the specific mechanism that high level of FFA causes inflammation is not very clear. Thus, our research intended to observe the high FFA effects on TLR9/KLF4 expression and the downstream inflammatory factors, to explore the mechanism of inflammatory response suppressed by TLR9/KLF4. Methods. qRT-PCR and Western blot were used to detect the mRNA and protein expression levels of TLR9, KLF4, and key inflammation-related factors. ELISA was used to detect the release level of inflammatory cytokines. The triglyceride (TG) and glucose (GLU) testing cassettes were used to detect the TG and GLU levels in culture medium. Results. In the omental tissue of obese individuals (OB), we found that TLR9, KLF4, mRNA, and the protein expression levels were lower than those of the normal weight control (NC) group. Similarly, in the omental tissue of high-fat diet (HFD) rats, we found that the mRNA expression levels of TLR9 and KLF4 were lower than those of the normal diet control group. In mature adipocytes, we found that KLF4 played an important anti-inflammatory role; moreover, PA can promote the development of inflammation by inhibiting KLF4 expression; TLR9 has a positive regulation function on KLF4 expression, but unrelated to PA. Conclusions. TLR9/KLF4 is involved in regulating FFA-induced adipocyte inflammation.

Objective. To investigate the role and possible molecular mechanism of Krüppel-like factor 7 (KLF7) in the TLR4/NF-κB/IL-6 inflammatory signaling pathway activated by free fatty acids (FFA). Methods. The mRNA and protein expression levels of KLF7 and the factors of TLR4/NF-κB/IL-6 inflammatory signal pathways were detected by qRT-PCR and Western blotting after cell culture with different concentrations of palmitic acid (PA). The expression of KLF7 or TLR4 in adipocytes was upregulated or downregulated; after that, the mRNA and protein expression levels of these key factors were detected. KLF7 expression was downregulated while PA stimulated adipocytes, and then the mRNA and protein expressions of KLF7/p65 and downstream inflammatory cytokine IL-6 were detected. The luciferase reporter assay was used to determine whether KLF7 had a transcriptional activation effect on IL-6. Results. (1) High concentration of PA can promote the expression of TLR4, KLF7, and IL-6 in adipocytes. (2) TLR4 positively regulates KLF7 expression in adipocytes. (3) KLF7 positively regulates IL-6 expression in adipocytes. (4) PA promotes IL-6 expression via KLF7 in adipocytes. (5) KLF7 has a transcriptional activation on IL-6. Conclusion. PA promotes the expression of the inflammatory cytokine IL-6 by activating the TLR4/KLF7/NF-κB inflammatory signaling pathway. In addition, KLF7 may directly bind to the IL-6 promoter region and thus activate IL-6.

The evolution of microstructure and residual stress during the tempering of 700 L low-carbon micro-alloyed steel was studied using a crack compliance method for measuring residual stress. Additionally, a non-isothermal tempering dilatation test, Vickers micro-hardness test, and transmission electron microscopy were used. The evolution of residual stress during tempering consists of two stages. The first stage coincided with cementite precipitation. Under the initial residual stress, the transformation plasticity due to cementite precipitation leads to partial relaxation of the micro-stress evoked by the austenite-to-ferrite transformation during quenching. It also caused the material surface and the core to exhibit different residual stress evolution trends. After tempering at 300 ∘ C for 30 min, the residual stress was reduced from 487 MPa to 200 MPa; however, the elastic strain energy remained unchanged. The second stage coincided with alloy carbide precipitation and Mn partitioning, but the precipitation of the alloy carbide only reduced the elastic strain energy by 8.7%. Thus, the change in activation energy was the main reason for the relaxation of residual stress at this stage. After tempering at 600 ∘ C for 30 min, the residual stress was reduced to 174 MPa, the elastic strain energy was reduced by 72.72%, and the residual stress was controlled.

Transformation plasticity and kinetics play an essential role in the prediction of residual stresses resulting from transformation. This paper is devoted to the investigation of the influence of stress on the kinetics and transformation plasticity of ferrite for H420LA steel. It has been shown that under small external stresses, lower than the yield stress of the weaker phase, the ferrite transformation is inhibited at the beginning of the transformation in the continuous cooling process and the mechanical stabilization of austenite is observed, due to transformation hysteresis effects. This phenomenon affects the metallurgical and mechanical behaviors of the transformation progress. However, most existing models ignore these effects, leading to deviations in the description of transformation plasticity during the transformation progress. Considering the hysteresis effects, the micromechanical model for kinetics and transformation plasticity is reexamined. A general formulation of austenite decomposition kinetics accounting for these effects is developed to better describe the phase transformation under a continuous cooling process. In addition, the influence of hysteresis effects on the evolution of transformation plasticity is analyzed. Consideration of the hysteresis effects decreases the discrepancy between the calculated and experimental values. This will allow better prediction of residual stresses in the thermomechanically controlled processes.

The elastocaloric effect in a columnar-grained Cu71.5Al17.5Mn11 shape memory alloy fabricated by directional solidification was investigated. A large entropy change of 25.0 J/kg K generated by the reversible martensitic transformation was demonstrated. The adiabatic temperature change of 12-13 K was directly measured, covering a wide temperature range of more than 100 K. The low applied stress with a specific elastocaloric ability of 100.8 K/GPa was identified and the potentially attainable operational temperature window as wide as more than 215 K was also discussed. The outstanding elastocaloric refrigeration capability, together with the low applying stress and uniform phase transformation, makes the columnar-grained Cu–Al–Mn shape memory alloy a promising material for solid-state refrigeration.

In this paper, the researchers collected visceral adipose tissue from the Uygur population, which were divided into two groups: the normal control group (NC, n=50, 18.0 kg/m2 ≤ BMI ≤ 23.9 kg/m2) and the obese group (OB, n=45, BMI ≥ 28 kg/m2), and then use real-time PCR to detect the mRNA expression level of key genes involved in inflammation signaling pathway. The findings suggest that, in obese status, the lower expression level of A2bAR, KLF4, and KLF15 of visceral adipose tissue may correlate with obese-dyslipidemia induced inflammation in Uygur population.

Our results showed that, at the same BMI level, Uygurs have greater WHR values, abdominal visceral fat content, and diabetes risks than Kazaks. In addition, values of HDL-C in Uygur subjects were lower than those in Kazak subjects, and values of creatinine, uric acid, diastolic blood pressure, blood glucose, and fructosamine in Uygur male subjects were lower than those in Kazak male subjects. In contrast, systolic blood pressure values in Uygur subjects were greater than those in Kazak subjects, and blood glucose values were greater in Uygur female subjects than in Kazak female subjects. Additionally, in Uygurs, visceral adipose tissue expression levels of TBX1 and TCF21 were greater in obesity group than in normal and T2DM groups and lower in T2DM group than in normal group (P

Solid-state refrigeration technology based on elastocaloric effects (eCEs) is attracting more and more attention from scientists and engineers. The response speed of the elastocaloric materials, which relates to the sensitivity to the strain rate and measuring temperature, is a significant parameter to evaluate the development of the elastocaloric material in device applications. Because the Cu-Al-Mn shape memory alloy (SMA) possesses a good eCE and a wide temperature window, it has been reported to be the most promising elastocaloric cooling material. In the present paper, the temperature changes (ΔT) induced by reversible martensitic transformation in a columnar-grained Cu71Al17.5Mn11.5 SMA fabricated by directional solidification were directly measured over the strain rate range of 0.005–0.19 s−1 and the measuring temperature range of 291–420 K. The maximum adiabatic ΔT of 16.5 K and a lower strain-rate sensitivity compared to TiNi-based SMAs were observed. With increasing strain rate, the ΔT value and the corresponding coefficient of performance (COP) of the alloy first increased, then achieved saturation when the strain rate reached 0.05 s−1. When the measuring temperature rose, the ΔT value increased linearly while the COP decreased linearly. The results of our work provide theoretical reference for the design of elastocaloric cooling devices made of this alloy.

Invasion and metastasis are the major causes of death in patients with esophageal squamous cell carcinoma (ESCC). Epithelial-mesenchymal transition (EMT) is a critical step in tumor progression and transforming growth factor-β1 (TGF-β1) signaling has been shown to play an important role in EMT. In this study, we investigated how TGF-β1 signaling pathways contributed to EMT in three ESCC cell lines as well as 100 patients of nomadic ethnic Kazakhs residing in northwest Xinjiang Province of China. In vitro analyses included Western blotting to detect the expression of TGF-β1/Smad and EMT-associated proteins in Eca109, EC9706 and KYSE150 cell lines following stimulation with recombinant TGF-β1 and SB431542, a potent inhibitor of ALK5 that also inhibits TGF-β type II receptor. TGF-β-activated Smad2/3 signaling in EMT was significantly upregulated as indicated by mesenchymal markers of N-cadherin and Vimentin, and in the meantime, epithelial marker, E-cadherin, was markedly downregulated. In contrast, SB431542 addition downregulated the expression of N-cadherin and Vimentin, but upregulated the expression of E-cadherin. Moreover, the TGF-β1-induced EMT promoted invasion capability of Eca109 cells. Tumor cells undergoing EMT acquire fibroblastoid-like phenotype. Expressed levels of TGF-β1/Smad signaling molecules and EMT-associated proteins were examined using immunohistochemical analyses in 100 ESCC tissues of Kazakh patients and 58 matched noncancerous adjacent tissues. The results showed that ESCC tissues exhibited upregulated expression of TGF-β1/Smad. We also analyzed the relationship between the above proteins and the patients' clinicopathological characteristics. The TGF-β1/Smad signaling pathway in human Eca109 ESCC cells may carry similar features as in Kazakh ESCC patients, suggesting that TGF-β1/Smad signaling pathway may be involved in the regulation of EMT in ethnic Kazakh patients with ESCC from Xinjiang, China.