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Laminated glass has been widely used as safety glass for decades owing to its remarkable post-breakage load-bearing capacity. The post-breakage behaviour of laminated glass is mainly affected by several key factors such as the interlayer property, the adhesion property of the glass-interlayer interface, and the size of glass fragments. In this study, the adhesion properties of polyvinyl butyral (PVB) laminated glass under high-speed uniaxial tension were studied by through-cracked tensile (TCT) tests. Two adhesion grades (i.e., BG-R15 medium adhesion grade and BG-R20 high adhesion grade) PVB-laminated glass and three loading rates (i.e., 0.1m/s, 0.5m/s, and 5m/s) were considered in the tests. The delamination behaviour of PVB-laminated glass was modelled using a numerical cohesive zone model (CZM) to accurately calibrate the interfacial adhesion properties. It was found that BG-R15 PVB-laminated glass exhibits a progressive delamination behaviour under high-speed loading, which results in a stable but low post-cracking force, whereas the delamination was significantly constrained for BG-R20 PVB-laminated glass, which leads to a higher post-cracking force but very poor deformability. The deformability of high adhesion grade laminated glass increases with the crack number since more PVB participates into the stretching of cracked laminated glass. The interfacial adhesion property shows a significant rate effect, with the bonding strength and energy release rate of BG-R15 PVB-laminated glass increase by nearly 25% and 50%, respectively, as the loading rate increases from 0.1m/s to 5m/s. In general, the energy dissipation capacity of the BG-R15 PVB-laminated glass is much higher than that of the BG-R20 PVB-laminated glass. This study can provide a valuable reference for the design of laminated glass under blast or impact loads.

Architectural glass has been widely used in modern buildings due to its aesthetics and functionality. The growing use of glass in load-bearing structures raises concerns about its long-term strength due to the existence of the flaws and subcritical crack propagation. Better understanding of flaw characteristics is crucial for evaluating the mechanical properties. However, existing knowledge on flaw characteristics is limited, and the load duration factor 𝑘𝑚𝑜𝑑 specified by standards doesn't consider different stress histories. This paper aims to fill these gaps by observing and analysing the flaw and statistical characteristics in glass, especially the edge defects, proposing a Monte-Carlo based model to simulate the long-term mechanical behaviour of glass specimen with distributed edge defects and modifying the 𝑘𝑚𝑜𝑑. 3D laser confocal microscope was utilized to observe the defects. The Monte-Carlo based model is able to generate edge defects and conduct numerical experiments to expand the data pool. Based on stress corrosion theory, the crack resistances under two load conditions (constant stress and constant stress rate) were derived respectively. By analysing and quantifying the influences of temperature, humidity and stress rate on crack growth parameters, the crack resistances under two load conditions are compared, and a modified 𝑘𝑚𝑜𝑑 is then proposed. The Monte-Carlo based model is verified by lifetime test from literature. The modified 𝑘𝑚𝑜𝑑 is validated with substantial dataset across various load durations and is compared with international standards, demonstrating the accuracy in predicting glass long-term strength.

Anticlastic glass surfaces play a significant role in free-form glass facades. For realizing anticlastic surface, cold bending by loading at the corner of the plate is more adaptive and more economic than traditional hot bending method. Previous research on anticlastic cold bending mainly focuses on the description of instability phenomenon and qualitative analysis of parameters. However, the failure mechanisms of glass plates during cold bending and the influence of lamination remains unclear. In this paper, the anticlastic cold bending test was conducted to explore the influence of various factors, including aspect ratio, scale and composition of the plates. Subsequently, an effective finite element model was established and validated by test results, which is used for further explore the cold bending controlling condition for better engineering practice. The failure modes are considered as instability and strength failure. For laminated glass, maximum stresses can be derived from monolithic glass based on equivalent thickness method. The instability is induced by the compression area in the middle surface of glass plate which is significantly influenced by the composition of the laminates. Consequently, thin glass laminates exhibit enhanced stability because a reduced glass to PVB thickness ratio changes the compression area from bi-directional to uni-directional.

Atherosclerosis is now widely considered to be a chronic inflammatory disease, with increasing evidence suggesting that lipid alone is not the main factor contributing to its development. Rather, atherosclerotic plaques contain a significant amount of inflammatory cells, characterized by the accumulation of monocytes and lymphocytes on the vessel wall. This suggests that inflammation may play a crucial role in the occurrence and progression of atherosclerosis. As research deepens, other pathological factors have also been found to influence the development of the disease. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is a recently discovered target of inflammation that has gained attention in recent years. Numerous studies have provided evidence for the causal role of this pathway in atherosclerosis, and its downstream signaling factors play a significant role in this process. This brief review aims to explore the crucial role of the JAK/STAT pathway and its representative downstream signaling factors in the development of atherosclerosis. It provides a new theoretical basis for clinically affecting the development of atherosclerosis by interfering with the JAK/STAT signaling pathway.

ObjectiveSome previous studies have suggested a potential link between stroke and gastroesophageal reflux disease (GERD). We used a two-sample bidirectional Mendelian randomization (MR) method to explore the causal relationship between stroke and GERD.DesignSummary-level data derived from the published genome-wide association studies (GWAS) were employed for analyses. Single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for stroke (n = 446,696) and its common subtypes ischemic stroke (IS) (n = 440,328), large vessel stroke (LVS) (n = 410,484), small vessel stroke (SVS) (n = 198,048), and cardioembolic stroke (CES) (n = 413,304) were obtained from the MEGASTROKE consortium. The data on intracerebral hemorrhage (ICH) (n = 721,135) come from the UK Biobank. Instrumental variables (IVs) for lacunar stroke (LS) (n = 474,348) and GERD (n = 602,604) were screened from publicly available genetic summary data. The inverse variance weighted (IVW) method was used as the main MR method. Pleiotropy was detected by the MR-Egger intercept test, MR pleiotropy residual sum and outlier, and leave-one-out analysis. Cochran Q statistics were used as supplements to detect pleiotropy.ResultsWe found that GERD can causally increase the risk of stroke [IVW odds ratio (OR): 1.22, 95% confidence interval (CI): 1.13–1.32, p = 1.16 × 10−6] and its common subtypes IS (OR: 1.19, 95% CI: 1.10–1.30, p = 3.22 × 10−5), LVS (OR: 1.49, 95% CI: 1.21–1.84, p = 1.47 × 10−4), and LS (OR: 1.20, 95% CI: 1.001–1.44, p = 0.048). Several important risk factors for stroke have also been implicated in the above causal relationship, including type 2 diabetes, sleep apnea syndrome, high body mass index, high waist-to-hip ratio, and elevated serum triglyceride levels. In reverse MR analysis, we found that overall stroke (OR: 1.09, 95% CI: 1.004–1.19, p = 0.039) and IS (OR: 1.10, 95% CI: 1.03–1.17, p = 0.007) have the causal potential to enhance GERD risk.ConclusionThis MR study provides evidence supporting a causal relationship between GERD and stroke and some of its common subtypes. We need to further explore the interconnected mechanisms between these two common diseases to better prevent and treat them.

Abstract Expounding the heterogeneity for ovarian cancer (OC) with the cognition in developmental biology might be helpful to search for robust prognostic markers and effective treatments. In the present study, we employed single-cell RNA-seq with ovarian cancers, normal ovary, and embryo tissue to explore their heterogeneity. Then the differentiation process of clusters was explored; the pivotal cluster and markers were identified. Furthermore, the consensus clustering algorithm was used to explore the different clinical phenotypes in OC. At last, a prognostic model was construct and used to assess the prognosis for OCs. As a result, eight diverse clusters were identified, and the similarity existed in some clusters between embryo and tumours based on their gene expression. Meaningfully, a subtype of malignant epithelial cluster, PEG10+ EME, was associated with poor survival and was an intermediate stage of embryo to tumour. PEG10 was a CSC marker and might influence CSC self-renewal and promote cisplatin resistance via NOTCH pathway. Utilising specific gene profiles of PEG10+ EME based on public data sets, four phenotypes with different survival and clinical response to anti-PD-1/PD-L1 immunotherapy were identified. These insights allowed for the investigation of single-cell transcriptome of OCs and embryo, which advanced our current understanding of OC pathogenesis and resulted in promising therapeutic strategies.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Our previous studies have found that Shuangyu Tiaozhi Decoction (SYTZD) could produce an improvement in NAFLD-related indicators, but the underlying mechanism associated with this improvement remains unclear. The study aimed to investigate the potential mechanism of SYTZD against NAFLD through network pharmacology and experimental verification. The components of SYTZD and SYTZD drug containing serum were analyzed using ultra-performance liquid chromatography to quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). Active components and targets of SYTZD were screened by the traditional Chinese medical systems pharmacology (TCMSP) and encyclopedia of traditional Chinese medicine (ETCM) databases. NAFLD-related targets were collected from the GeneCards and DisGeNET databases. The component-disease targets were mapped to identify the common targets of SYTZD against NAFLD. Protein–protein interaction (PPI) network of the common targets was constructed for selecting the core targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the core targets was performed using the database for annotation, visualization, and integrated discovery (DAVID) database. Furthermore, animal and cell models were constructed for validating the predictions of network pharmacology. Lipid accumulation, liver histopathology, insulin resistance, and core gene expression were measured by oil red O staining, hematoxylin and eosin staining, insulin tolerance test, real-time quantitative polymerase chain reaction, and Western blotting, respectively. Two components and 22 targets of SYTZD against NAFLD were identified by UPLC-Q/TOF-MS and relevant databases. PPI analysis found that ESR1, FASN, mTOR, HIF-1α, VEGFA, and GSK-3β might be the core targets of SYTZD against NAFLD, which were mainly enriched in the thyroid hormone pathway, insulin resistance pathway, HIF-1 pathway, mTOR pathway, and AMPK pathway. Experimental results revealed that SYTZD might exert multiple anti-NAFLD mechanisms, including improvements in lipid deposition, inflammation, and insulin resistance. SYTZD treatment led to decreases in the lipid profiles, hepatic enzyme levels, inflammatory cytokines, and homeostatic model assessment for insulin resistance (HOMA-IR). SYTZD treatment affected relative mRNA and protein levels associated with various pathways. Our findings reveal that SYTZD could alleviate NAFLD through a multi-component, multi-target, and multi-pathway mechanism of action.

Abstract Tumor‐derived extracellular vesicles (EVs) function as critical mediators in selective modulation of the microenvironment of distant organs to generate a pre‐metastatic niche that facilitates organotropic metastasis. Identifying the organ‐specific molecular determinants of EVs can develop potential anti‐metastatic therapeutic targets. In the current study, large oncosomes (LOs), atypically large cancer‐derived EVs, are found to play a crucial role in facilitating bone‐tropic metastasis of hepatocellular carcinoma (HCC) cells by engineering an osteoclastic pre‐metastatic niche and establishing a vicious cycle between the osteoclasts and HCC cells. Transmembrane protein, VAMP‐associated protein A (VAPA), is significantly enriched on LOs surface via direct interaction with LOs marker αV‐integrin. VAPA‐enriched LOs‐induced pre‐metastatic education transforms the bone into a fertile milieu, which supports the growth of metastatic HCC cells. Mechanically, LOs‐delivered VAPA integrates to plasma membrane of osteoclasts and directly interacts with and activates neural Wiskott–Aldrich syndrome protein (N‐WASP) via dual mechanisms, consequently resulting in ARP2/3 complex‐mediated reorganization of actin cytoskeleton in osteoclasts and osteoclastogenesis. Importantly, treatment with N‐WASP inhibitor 187‐1‐packaged LOs (LOs/187‐1) dramatically abolishes the inductive effect of VAPA‐enriched LOs on pre‐metastatic niche formation and precludes HCC bone metastasis. These findings reveal a plausible mechanism for bone‐tropism of HCC and can represent a potential strategy to prevent HCC bone metastasis.

Abstract Backgrounds Pregnancy termination during the second trimester in patients with placenta previa and placenta accreta spectrum (PAS) is a complex and challenging clinical problem. Based on our literature review, there has been a relative increase in the number of such cases being treated by hysterotomy and/or local uterine lesion resection and repair. In the present study, a retrospective analysis was conducted to compare the clinical outcomes when different management strategies were used to terminate pregnancy in the patients with placenta previa and PAS. Methods A total of 51 patients who underwent pregnancy termination in the second trimester in Beijing Obstetrics and Gynecology Hospital between June 2013 and December 2018 were retrospectively analyzed in this study. All patients having previous caesarean delivery (CD) were diagnosed with placenta previa status and PAS. Results ① Among the 51 patients, 16 cases received mifepristone and misoprostol medical termination, 15 cases received mifepristone and Rivanol medical termination, but 1 of them was transferred to hysterotomy due to failed labor induction, another 20 cases were performed planned hysterotomy. There was no placenta percreta cases and uterine artery embolization (UAE) was all performed before surgery.② There were 31 cases who underwent medical termination and 30 cases were vaginal delivery. Dilation and evacuation (D&E) were used in 20 cases of medical abortion failure and in all 30 cases of difficult manual removal of placental tissue. ③ A statistically significant difference was found among the three different strategies in terms of gestational weeks, the type of placenta previa status, main operative success rate and β-HCG regression time (P

Abstract Background Breast cancer (BC) has a marked tendency to spread to the bone, resulting in significant skeletal complications and mortality. Recently, circular RNAs (circRNAs) have been reported to contribute to cancer initiation and progression. However, the function and mechanism of circRNAs in BC bone metastasis (BC-BM) remain largely unknown. Methods Bone-metastatic circRNAs were screened using circRNAs deep sequencing and validated using in situ hybridization in BC tissues with or without bone metastasis. The role of circIKBKB in inducing bone pre-metastatic niche formation and bone metastasis was determined using osteoclastogenesis, immunofluorescence and bone resorption pit assays. The mechanism underlying circIKBKB-mediated activation of NF-κB/bone remodeling factors signaling and EIF4A3-induced circIKBKB were investigated using RNA pull-down, luciferase reporter, chromatin isolation by RNA purification and enzyme-linked immunosorbent assays. Results We identified that a novel circRNA, circIKBKB, was upregulated significantly in bone-metastatic BC tissues. Overexpressing circIKBKB enhanced the capability of BC cells to induce formation of bone pre-metastatic niche dramatically by promoting osteoclastogenesis in vivo and in vitro. Mechanically, circIKBKB activated NF-κB pathway via promoting IKKβ-mediated IκBα phosphorylation, inhibiting IκBα feedback loop and facilitating NF-κB to the promoters of multiple bone remodeling factors. Moreover, EIF4A3, acted acting as a pre-mRNA splicing factor, promoted cyclization of circIKBKB by directly binding to the circIKBKB flanking region. Importantly, treatment with inhibitor eIF4A3-IN-2 reduced circIKBKB expression and inhibited breast cancer bone metastasis effectively. Conclusion We revealed a plausible mechanism for circIKBKB-mediated NF-κB hyperactivation in bone-metastatic BC, which might represent a potential strategy to treat breast cancer bone metastasis.

Metabolic enzyme-genes (MEs) play critical roles in various types of cancers. However, MEs have not been systematically and thoroughly studied in pancreatic cancer (PC). Global analysis of MEs in PC will help us to understand PC progressing and provide new insights into PC therapy. In this study, we systematically analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) (n = 180 + 4) and GSE15471 (n = 36 + 36) and discovered that metabolic pathways are disordered in PC. Co-expression network modules of MEs were constructed using weighted gene co-expression network analysis (WGCNA), which identified two key modules. Both modules revealed that the glutathione signaling pathway is disordered in PC and correlated with PC stages. Notably, glutathione peroxidase 2 (GPX2), an important gene involved in glutathione signaling pathway, is a hub gene of the key modules. Analysis of immune microenvironment components reveals that PC stage is associated with M2 macrophages, the marker gene of which is significantly correlated with GPX2. The results indicated that GPX2 is associated with PC progression, providing new insights for future targeted therapy.

Bone metastasis is one of the most common distant metastasis of breast cancer, which could cause serious skeletal disease and increased cancer-related death. Therefore, identification of novel target(s) to develop therapeutics would improve patient outcomes. The role of NKX2-8 in modulation of bone remodeling was determined using osteoclastogenesis and micro-CT assays. The expression of NKX2-8 was examined via immunohistochemistry analysis in 344 breast cancer tissues. The mechanism underlying NKX2-8-mediated PTHrP downregulation was investigated using biotinylated deactivated Cas9 capture analysis, chromatin immunoprecipitation, co-immunoprecipitation assays. A bone-metastatic mouse model was used to examine the effect of NKX2-8 dysregulation on breast cancer bone metastasis and the impact of three PTHrP inhibitor on prevention of breast cancer bone metastasis. The downregulated expression of NKX2-8 was significantly correlated with breast cancer bone metastasis. In vivo bone-metastatic mouse model indicated that silencing NKX2-8 promoted, but overexpressing NKX2-8 inhibited, breast cancer osteolytic bone metastasis and osteoclastogenesis. Mechanistically, NKX2-8 directly interacted with HDAC1 on the PTHrP promoter, which resulted in a reduction of histone H3K27 acetylation, consequently transcriptionally downregulated PTHrP expression in breast cancer cells. Furthermore, targeting PTHrP effectively inhibited NKX2-8-downregulation-mediated breast cancer bone metastasis. Taken together, our results uncover a novel mechanism underlying NKX2-8 downregulation-mediated breast cancer bone metastasis and represent that the targeting PTHrP might be a tailored treatment for NKX2-8 silencing-induced breast cancer bone metastasis.

Brown adipose tissue (BAT), a unique tissue, plays a key role in metabolism and energy expenditure through adaptive nonshivering thermogenesis. It has recently become a therapeutic target in the treatment of obesity and metabolic diseases. The thermogenic effect of BAT occurs through uncoupling protein-1 by uncoupling adenosine triphosphate (ATP) synthesis from energy substrate oxidation. The review discusses the recent developments and progress associated with the biology, function, and activation of BAT, with a focus on its therapeutic potential for the treatment of polycystic ovary syndrome (PCOS). The endocrine activity of brown adipocytes affects the energy balance and homeostasis of glucose and lipids, thereby affecting the association of BAT activity and the metabolic profile. PCOS is a complex reproductive and metabolic disorder of reproductive-age women. Functional abnormalities of adipose tissue (AT) have been reported in patients with PCOS. Numerous studies have shown that BAT could regulate the features of PCOS and that increases in BAT mass or activity were effective in the treatment of PCOS through approaches including cold stimulation, BAT transplantation and compound activation in various animal models. Therefore, BAT may be used as a novel management strategy for the patients with PCOS to improve women’s health clinically. It is highly important to identify key brown adipokines for the discovery and development of novel candidates to establish an efficacious therapeutic strategy for patients with PCOS in the future.

Sipunculus nudus is an important intertidal aquaculture species that can ingest organic matter from the surface sediment and shows a high transportation capacity in sediment. However, little is known about the influence of intertidal aquaculture species on the sediment microbial community and the exchange of microbiota between the intestine and the surrounding sediment. In this study, the microbial communities in the intestine of S. nudus and three kinds of surrounding sediments were analyzed using high-throughput sequencing of the 16S rRNA gene amplicon, and the relationships between different communities were examined. Principal coordinate analysis and ANOSIM/Adonis analysis showed that the microbial communities of worm intestine samples were significantly different from those of surrounding sediments (p < 0.05). Meanwhile, compared with the sediment samples, the microbial α-diversity was significantly lower in the intestinal samples. Although the relative abundances of Proteobacteria and Cyanobacteria were high in all samples, three phyla (Bacteroidetes, Gemmatimonadetes, and Latescibacteria) showed a great difference between the four groups, as the abundances of the three phyla were significantly lower in the intestinal samples. Moreover, several microbial interactions were found between the worm intestine and surrounding sediments. BugBase functional prediction analysis indicated that the oxygen status of the sediment and the intestine was changed by bioturbation by the worm. Therefore, the microenvironment and microbial community in sediment were affected by the activity of S. nudus in the intertidal aquaculture zone.

Abstract Purpose To study the quality of our human ovarian tissue cryopreservation technique as performed in the first official "International Fertility Protection Centre" in China in patients with certain cancer types using a mouse model, and to find the best site for tissue transplantation in the mouse. Methods Thirty-six BALB/C female nude mice were randomly divided into 3 groups, group 1: control group; group 2: ovariectomized group; group 3: ovarian tissue transplantation group. Seventy-two pieces obtained from six ovarian tissue samples from each of three cancer patients were transplanted into the ovarian bursa cavity (OBC), the subcutaneous thigh (TS) and the subcutaneous neck (NS) and removed after 1.5 and 2.5 months, respectively. Follicular growth rate (FGR), total follicle surviving rate (TFSR), tissue recovery rate (TRR), antral follicles (AF), follicle stimulating hormone (FSH), estradiol (E2) and anti-Mullerian hormone (AMH) levels were measured. Results No significant differences in FGR, OBC, NS (p > 0.05); TFSR was 100% in OBC, NS and TS. No significant differences in TRR (p > 0.05); AF were found only in OBC; TFSR was 100% after transplantation; significantly higher FGR in the 2.5 months compared to the 1.5 months-group (p

Objective: The purpose of this study was to evaluate the rehabilitation effects of four common interventions (BA: body acupuncture, SA: scalp acupuncture, TA: tongue acupuncture, SLT: speech and language training) used singly or in combination with language function in patients with post-stroke aphasia (PSA). Design: We systematically searched PubMed, EMBASE, Cochrane Library, Ovid, Web of Science, CNKI, VIP, and Wanfang from inception to 4 April 2022. Only randomized controlled trials that met the eligibility criteria were included. The risk of bias of studies included was assessed using the RoB-2 tool. The effects of different interventions for PSA patients were analyzed and ranked according to the surface under the cumulative ranking (SUCRA) analysis. Results: A total of 69 RCTs were included, including 5097 total participants. According to the results of the SUCRA curves, TA ranked highest in improving overall efficacy (SUCRA = 86%) and oral expression score (SUCRA = 86%). BA + TA ranked highest in increasing the comprehension score (SUCRA = 74.9%). BA + SA ranked highest in improving aphasia patients’ repetition (SUCRA = 89.2%) and denomination scores (SUCRA = 93%). Conclusions: Results of our network meta-analysis and SUCRA ranking showed that tongue acupuncture, body acupuncture + tongue acupuncture, and body acupuncture + scalp acupuncture seem to offer better advantages than other interventions for improving the language function in PSA patients. Moreover, it is noteworthy that our results are limited to the Chinese population, since all eligible studies are from China. Future well-designed studies with larger sample sizes and more ethnic groups are required to further verify these findings.

This paper presents an experimental study into the global behavior of glass columns with square hollow cross-section under axial compression. In the research, totally 6 specimens were tested. All specimens were of the same geometry (length 750 mm, width 150 mm and 10 mm) but had different composition. Half of them were made of monolithic glass, with the other half made of laminated glass. The adopted interlayer material is PVB which is widely used in practice. During the test, vertical displacement, lateral deflection and normal stresses at mid-span were measured. For all specimens, local failure mechanism at the top or bottom due to progressive cracking was found, without any damage occurred at the glued joint. However, there is significant difference between the specimens made of monolithic glass and those made of laminated glass. Laminated glass columns had a sufficient residual capacity, able to carry compressive load in the post-crack stage, while monolithic glass columns collapsed quickly after the appearance of the first crack. Subsequently, the influence of the initial geometrical imperfection was studied in detail. Based on the results of experiment, the current findings could be further extended to various glass columns typologies (e.g. different cross-sections) in order to build appropriate practical design rules.

Background Aberrant activation of the NLRP3 (nucleotide‐binding oligomerization domain, leucine‐rich repeat–containing receptor family pyrin domain‐containing 3) inflammasome is thought to play a causative role in atherosclerosis. NLRP3 is kept in an inactive ubiquitinated state to avoid unwanted NLRP3 inflammasome activation. This study aimed to test the hypothesis that pharmacologic manipulating of NLRP3 ubiquitination blunts the assembly and activation of the NLRP3 inflammasome and protects against vascular inflammation and atherosclerosis. Since genetic studies yielded mixed results about the role for this inflammasome in atherosclerosis in low‐density lipoprotein receptor– or apolipoprotein E–deficient mice, this study attempted to clarify the discrepancy with the pharmacologic approach using both models. Methods and Results We provided the first evidence demonstrating that tranilast facilitates NLRP3 ubiquitination. We showed that tranilast restricted NLRP3 oligomerization and inhibited NLRP3 inflammasome assembly. Tranilast markedly suppressed NLRP3 inflammasome activation in low‐density lipoprotein receptor– and apolipoprotein E–deficient macrophages. Through reconstitution of the NLRP3 inflammasome in human embryonic kidney 293T cells, we found that tranilast directly limited NLRP3 inflammasome activation. By adopting different regimens for tranilast treatment of low‐density lipoprotein receptor– and apolipoprotein E–deficient mice, we demonstrated that tranilast blunted the initiation and progression of atherosclerosis. Mice receiving tranilast displayed a significant reduction in atherosclerotic lesion size, concomitant with a pronounced decline in macrophage content and expression of inflammatory molecules in the plaques compared with the control group. Moreover, tranilast treatment of mice substantially hindered the expression and activation of the NLRP3 inflammasome in the atherosclerotic lesions. Conclusions Tranilast potently enhances NLRP3 ubiquitination, blunts the assembly and activation of the NLRP3 inflammasome, and ameliorates vascular inflammation and atherosclerosis in both low‐density lipoprotein receptor– and apolipoprotein E–deficient mice.

Abstract To understand the impacts of peanut worms Sipunculus nudus on the prokaryotic community composition in a tidal flat, an onsite investigation was conducted in Suixi in the Beibu Gulf (109.82E, 21.35N) in the burrow sediments, non‐burrow sediments and the sediments without peanut worm disturbance (control). The16S rRNA gene Illumina MiSeq sequencing was used to investigate the microbial communities and their response to bioturbation by S. nudus in a sandy tidal flat. A total of 18 bacteria phyla were detected, and Proteobacteria and Cyanobacteria constituted the majority of the prokaryotic community in the samples. The distribution of the relative abundances of genera showed that approximately 6.99%–17% of the reads in the samples were classified into 25 known genera. Sulfate‐reducing bacteria (Desulfococcus and Desulfosarcina) were the most abundant taxa, followed by Thermodesulfovibrionaceae LCP‐6, indicating that sulfate reduction is the main process in the sandy tidal flat. The abundances of Desulfococcus, LCP‐6 and Cyanobacterium in the non‐burrow sediment were greater than in the burrow sediment, suggesting that the anoxic condition is more suitable for Desulfococcus and LCP‐6 when the activity of S. nudus is absent. The biomass of Cyanobacterium was decreased by the feeding bioturbation of S. nudus. Meanwhile, the relative abundance of the Bacteroidetes Luteimonas in the burrow sediments was significantly greater than in the non‐burrow sediment, and there was a strong relationship between S. nudus bioturbation and increased in oxygen contents and oxidation‐reduction potentials in the burrow sediment. The abundances of Desulfococcus and LCP‐6 were greater in the middle layer (20–30 cm) than in the top layer in the non‐burrow sediment. However, the middle and bottom layers (20–30, 30–40 cm) had higher abundances of these genera than did the upper layers (0–10, 10–20 cm) in the burrow sediments. The abundances of the Fusobacteria Propionigenium and the Spirochaetes Spirochaeta were greater in the middle and bottom layers (20–30 cm, 30–40 cm) than in the top layers (0–10, 10–20 cm) in the burrow sediment, but this phenomenon was not found in the non‐burrow sediment. This study demonstrates that bioturbation by S. nudus plays an important role in reshaping the bacterial community composition in intertidal regions.

An analytical model for large-cylinder asymmetrical rolling is proposed based on an improved slab method, which can predict the rolling force more quickly. In this method, uneven normal and shear stresses acting on the vertical side are supposed. In the solution, the upper and lower contact lengths are different, and the roll gap is divided into four slabs. Moreover, the effects of the rolling parameters such as roll speed ratio, roll radius, exit thickness, and radius of cylinder on the rolling force and cross-shear zone ratio are investigated. The cross-shear zone ratio, which means the shear effect, is a key parameter in reducing rolling force and microstructure refinement. This method is conducted with the experimental and finite element verification, and good agreement has been found. It should be noted that the calculation result can be obtained rapidly and easily by this proposed model. Therefore, the present model is suitable for online application.

The cation transport behavior of thermally treated reduced graphene oxide membranes (GOMs) is reported. The GOMs were reduced by heat treatment at 25, 80, and 120 °C and then characterized by Fourier transform infrared spectroscopy, X-ray powder diffraction, and X-ray photoelectron spectroscopy to determine oxygen group content, C/O ratio, and layer spacing. The permeation rates of various cations with different sizes and charge numbers through these membranes were measured to understand the effect of the cations on transport behavior. The results indicated that the cation transport through the membranes depended on the layer spacing of the membrane and ion size and charge. Cations of the same valence permeating through the same GOM could be differentiated by their hydration radius, whereas the same type of cation passing through different GOMs could be determined by the spacing of the GOM layers. The cation valence strongly affected permeation behavior. The GOM that was prepared at 120 °C exhibited a narrow layer spacing and high separation factors for Mg/Ca, Mg/Sr, K/Ca, and K/Fe. The cations moving through the membrane could insert into the membrane lamellas, which neutralized the negative charge of the membrane, enlarged the layer spacing of the GOMs, and affected cation permeation.