Search

Drawing on ethnographic data, this article chronicles a Japanese queer immigrant's English learning experiences in a metropolitan area in western Canada. Informed by sociocultural theories and identity-centred approaches to Second Language Acquisition (SLA) research, I highlight the significance and interconnection between social identity, ideology, and language learner agency in second language (L2) learning, teaching, and education. Over a seven-month span, I investigated two research questions targeting the ideological constraints and potential coping strategies in the key participant's English learning. Nexus analysis is applied as the methodological framework. Following a three-step procedure, I first illustrate my positionality as a researcher and the rationale of the project. I then conduct critical discourse analysis delving into two featured social actions selected from the database generated through ethnographic observations, semi-structured interviews, and participant's reflective journals. I conclude with a discussion of how SLA researchers and educational practitioners can better support marginalized immigrants' L2 learning. Building on this case, I propose an allyship-centred approach in L2 teaching and researching and a model of collaborative working between researchers and educational practitioners to provoke more equitable nexuses of practice in immigrants' L2 education.

Abstract Chronic gastritis (CG) is a common inflammatory disease of chronic inflammatory lesion of gastric mucosa and in the diagnosis of gastritis in traditional Chinese medicine (TCM), CG can be classified into Cold ZHENG (syndrome in TCM) and Hot ZHENG. However, the molecular features of Cold/Hot ZHENG in CG and the mechanism of Cold/Hot herbs in formulae for CG remained unclear. In this study, we collected a transcriptomics data including 35 patients of Cold/Hot ZHENG CG and 3 scRNA-seq CG samples. And 25 formulae for CG and 89 herbs recorded in these formulae were also collected. We conduct a comprehensive analysis based on the combination of transcriptomics datasets and machine learning algorithms, to discover biomarkers for Cold/Hot ZHENG CG. Then the target profiles of the collected formulae and Cold/Hot herbs were predicted to uncover the features and biomarkers of them against Cold/Hot ZHENG CG. These biomarkers suggest that Hot ZHENG CG might be characterized by over-inflammation and exuberant metabolism, and Cold ZHENG CG showed a trend of suppression in immune regulation and energy metabolism. Biomarkers and specific pathways of Hot herbs tend to regulate immune responses and energy metabolism, while those of Cold herbs are more likely to participate in anti-inflammatory effects. Finally, the findings were verified based on public transcriptomics datasets, as well as transcriptomics and ELISA detection, taking Jin Hong tablets as a case study. Biomarkers like leptin and IL-6 together with proportions of immune cells showed significant changes after the intervention. These findings might reflect the mechanism and build a bridge between macro and micro views of Cold/Hot ZHENG as well as Cold/Hot herbs. Graphical abstract

Renal cell carcinoma (RCC) is a type of tumor with high morbidity and recurrence rates. The application of circulating tumor cells (CTCs) in RCC remains controversial. Hence, we performed a meta-analysis to elucidate the diagnostic and prognostic value of CTCs in RCC. To obtain a precise conclusion, a systematic search was conducted in Pubmed, Cochrane Database, Embase and Web of Science up to Dec 01, 2022. We also further identified the references in relevant studies. The diagnostic accuracy variables (sensitivity, specificity) and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to access precise of CTCs and relationship between CTCs and disease stages, respectively. Heterogeneity test, sensitivity analysis, meta-regression and publishing bias were also applied. A total of 12 studies involving 767 patients were considered to be included in the final meta-analysis. The results revealed that the overall sensitivity, specificity of CTC detection in RCC were 45% (95%CI, 32-60%) and 99% (95%CI, 97-100%), respectively. In subgroup analysis, diagnostic sensitivity of CTCs in clear cell renal cell carcinoma (ccRCC) (69%, 95%CI; 50-88%) was significantly higher than other RCC subtypes (34%, 95%CI; 21-48%) (p

Abstract Background Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. Methods A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg− 1), curcumin (Cur, 40 mg·kg− 1) and metformin (Met, 50 mg·kg− 1) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml− 1, 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. Results The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. Conclusion NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.

Abstract Chinese rose (Rosa chinensis) is an important ornamental plant, with economic, cultural, and symbolic significance. During the application of outdoor greening, adverse environments such as high temperature and drought are often encountered, which affect its application scope and ornamental quality. The starch phosphorylase (Pho) gene family participate in the synthesis and decomposition of starch, not only related to plant energy metabolism, but also plays an important role in plant stress resistance. The role of Pho in combating salinity and high temperature stress in R. chinensis remains unknown. In this work, 4 Phos from R. chinensis were detected with Pfam number of Pho (PF00343.23) and predicted by homolog-based prediction (HBP). The Phos are characterized by sequence lengths of 821 to 997 bp, and the proteins are predicted to subcellularly located in the plastid and cytoplasm. The regulatory regions of the Phos contain abundant stress and phytohormone-responsive cis-acting elements. Based on transcriptome analysis, the Phos were found to respond to abiotic stress factors such as drought, salinity, high temperature, and plant phytohormone of jasmonic acid and salicylic acid. The response of Phos to abiotic stress factors such as salinity and high temperature was confirmed by qRT-PCR analysis. To evaluate the genetic characteristics of Phos, a total of 69 Phos from 17 species were analyzed and then classified into 3 groups in phylogenetic tree. The collinearity analysis of Phos in R. chinensis and other species was conducted for the first time. This work provides a view of evolution for the Pho gene family and indicates that Phos play an important role in abiotic stress response of R. chinensis.

Abstract Objectives The purpose of our study is to further understanding of the depression symptoms of HIV/AIDS patients in Guilin, Guangxi via exploring whether there is a mediating effect of sleep quality on medical-social support and depression symptoms and therefore provide a theoretical basis for application of medical-social support to alleviate depression symptoms of HIV/AIDS patients. Methods A convenience sampling method was used to select 200 HIV/AIDS patients for the study. Depression symptoms, sleep quality, and medical-social support of the study participants were investigated using The Center for Epidemiological Studies Depression Scale (CES-D), The Pittsburg Sleep Quality Index (PSQI), and The Medical Outcomes Study Social Support Survey (MOS-SSS), respectively. Predictors of depression symptoms were explored by multiple linear regression, and Pearson correlation was used to analyze the relationship between sleep quality, medical-social support, and depression symptoms. Mediating effect analysis was performed by nonparametric Bootstrap test. Results In this study, the incidence of depression symptoms was 54.4%. Multiple linear regression analysis showed that leanness (β = 0.161, P = 0.008), obesity (β = 0.186, P = 0.002), sleep quality score > 7 (β = 0.331, P 56 (β = -0.247, P

In recent years, the application of textile reinforced mortar (TRM) as an overlay has become an important method for repairing and strengthening old masonry structures. However, the quantitative analysis and design of TRM-strengthened reinforced concrete (RC) beams are still limited. To address this gap, a nonlinear finite element (FE) model is proposed in this study to simulate the flexural behavior of TRM-strengthened RC beams. The developed model is validated using experimental results and subsequently utilized for the design of TRM-strengthened RC beams. Various TRM design parameters, including the number of textile layers, textile longitudinal length, and textile mesh size, are parametrically investigated. The modelling results reveal that increasing the number of textile layers and longitudinal length while decreasing the textile mesh size can enhance the bending strength of TRM-strengthened RC beams. Furthermore, an analytical model is proposed to predict the flexural strength of TRM-strengthened RC beams, facilitating rapid strength estimation of TRM-strengthened RC beams. The predicted results demonstrate good agreement with the numerical simulation results. The established FE models can predict the bending performance of TRM-strengthened RC beams under different reinforcement conditions, and the simulation outcomes can provide valuable guidance for their design.

Abstract While the monolayer sheet is well-established as a Mott-insulator with a finite energy gap, the insulating nature of bulk 1T-TaS2 crystals remains ambiguous due to their varying dimensionalities and alterable interlayer coupling. In this study, we present a unique approach to unlock the intertwined two-dimensional Mott-insulator and three-dimensional band-insulator states in bulk 1T-TaS2 crystals by structuring a laddering stack along the out-of-plane direction. Through modulating the interlayer coupling, the insulating nature can be switched between band-insulator and Mott-insulator mechanisms. Our findings demonstrate the duality of insulating nature in 1T-TaS2 crystals. By manipulating the translational degree of freedom in layered crystals, our discovery presents a promising strategy for exploring fascinating physics, independent of their dimensionality, thereby offering a “three-dimensional” control for the era of slidetronics.

Abstract Objectives This study aims to gather and analyze the anatomical characteristics of the posterior gastric artery (PGA), investigate the presence and metastasis of lymph nodes around the PGA in patients with gastric cancer. Additionally, the study aims to analyze the relationship between the PGA and its surrounding lymph nodes and the clinicopathological features of patients with gastric cancer. Methods This study consisted of a cross-sectional analysis of data from 52 patients with gastric cancer who underwent total or proximal gastrectomy at the Department of Gastrointestinal Surgery, First Affiliated Hospital of Dalian Medical University, between January 2020 and November 2022. Intraoperative exploration was performed to determine the presence of the PGA, and patients with the PGA were assessed for relevant anatomical characteristics, including the length of the PGA and the distance from the root of the PGA to the celiac trunk. Dissection of lymph nodes around the PGA was also performed. Statistical methods were employed to describe and analyze the data regarding the presence of the PGA, as well as the presence and metastasis of the lymph nodes around the PGA. Additionally, the study identified clinicopathological factors associated with these conditions. Results The PGA was identified in 39 (75.0%) out of 52 patients with gastric cancer, exhibiting a mean PGA length of 3.5 ± 0.8 cm and a mean distance from the root of the PGA to the celiac trunk of 6.7 ± 1.7 cm. Among the 39 patients who underwent dissection of lymph nodes around the PGA, 36 lymph nodes around the PGA were detected in 20 patients. Analysis of factors associated with the presence of lymph nodes around the PGA revealed a significant correlation with the macroscopic type of the tumor and the total number of dissected lymph nodes (P = 0.007 and P = 0.022, respectively), with a larger number of total dissected lymph nodes being an independent factor (OR = 1.105, 95%CI: 1.019–1.199, P = 0.016). Furthermore, analysis of risk factors for metastasis of the lymph nodes around the PGA demonstrated that the total number of metastatic lymph nodes, No.3 lymph node metastasis, and No.11 lymph node metastasis were associated with metastasis of the lymph nodes around the PGA (P = 0.043, P = 0.028, and P = 0.020, respectively). Conclusion The PGA exhibits a high incidence. It is essential to carefully identify the PGA during procedures involving the PGA and consider appropriate preservation or disconnection of this vessel. The presence of lymph nodes around the PGA is not an isolated occurrence. Gastric cancer can result in metastasis of the lymph nodes around the PGA. Although the overall risk of metastasis of the lymph nodes around the PGA is low in patients with gastric cancer, it increases in the presence of conditions such as No.3 lymph node metastasis, No.11 lymph node metastasis, advanced tumor stage, and extensive metastases in other regional lymph nodes.

Abstract Background To investigate the short-term and long-term outcomes of preserving the celiac branch of the vagus nerve during laparoscopic distal gastrectomy. Methods A total of 149 patients with prospective diagnosis of gastric cancer who underwent laparoscopic-assisted distal gastrectomy (LADG) combined with Billroth-II anastomosis and D2 lymph node dissection between 2017 and 2018 were retrospectively analyzed. The patients were divided into the preserved LADG group (P-LADG, n = 56) and the resected LADG group (R-LADG, n = 93) according to whether the vagus nerve celiac branch was preserved. We selected 56 patients (P-LADG, n = 56) with preservation of the celiac branch of the vagus nerve and 56 patients (R-LADG, n = 56) with removal of the celiac branch of the vagus nerve by propensity-matched score method. Postoperative nutritional status, weight change, short-term and long-term postoperative complications, and gallstone formation were evaluated in both groups at 5 years of postoperative follow-up. The status of residual gastritis and bile reflux was assessed endoscopically at 12 months postoperatively. Results The incidence of diarrhea at 5 years postoperatively was lower in the P-LADG group than in the R-LADG group (p

Jasmonic acid is a crucial phytohormone that plays a pivotal role, serving as a regulator to balancing plant development and resistance. However, there are analogous and distinctive characteristics exhibited in JA biosynthesis, perception, and signal transduction pathways in both herbaceous and woody plants. Moreover, the majority of research subjects have predominantly focused on the function of JA in model or herbaceous plants. Consequently, there is a significant paucity of studies investigating JA regulation networks in woody plants, particularly concerning post-transcriptional regulatory events such as alternative splicing (AS). This review article aims to conduct a comprehensive summary of advancements that JA signals regulate plant development across various woody species, comparing the analogous features and regulatory differences to herbaceous counterparts. In addition, we summarized the involvement of AS events including splicing factor (SF) and transcripts in the JA regulatory network, highlighting the effectiveness of high-throughput proteogenomic methods. A better understanding of the JA signaling pathway in woody plants has pivotal implications for forestry production, including optimizing plant management and enhancing secondary metabolite production.

Abstract Continuous cropping has a negative effect on soybean yield. In this study, a positioning experiment was conducted starting in 2015, with three treatments: maize–soybean rotation (SMR), 2-year maize, 2-year soybean rotation cropping (SC2), and 8-year soybean continuous cropping (SC8). We determined soybean yields (2015–2022) and analyzed soil microbial communities, functions, and metabolites composition in the 0–20 cm tillage layer using metagenomics technology and GC–MS technology during soybean flowering in 2022. Results indicated that continuous cropping (SC8) significantly reduced soybean yield compared to crop rotation (SMR) during the experimental period, while SC8 showed higher yield than SC2 in 2022. Compared to SMR, SC8 significantly increased soil N content and significantly decreased pH and TP, AP, and AK content. However, the pH and AK contents of SC8 were significantly higher than those of SC2. LeFSe analysis showed that Friedmanniella, Microlunatus, Nitrososphaera, Rubrobacter, Geodermatophilus, Nitriliruptor were enriched in SC8. Gaiella, Sphaerobacter, Methyloceanibacter were enriched in SC2. Sphingomonas, Cryobacterium, Marmoricola, Haliangium, Arthrobacter, Ramlibacter, Rhizobacter, Pseudolabrys, Methylibium, Variovorax were enriched in SMR. And the relative abundance of Cryobacterium, Marmoricola, Haliangium, Arthrobacter, Ramlibacter, Rhizobacter, Methylibium, Variovorax was significantly positively correlated with yield, while the relative abundance of Gaiella and Sphaerobacter was significantly negatively correlated with yield. SC8 significantly increased the abundance of genes in nitrogen metabolism and significantly decreased the abundance of genes related to phosphorus and potassium metabolism compared with SMR. However, the abundance of genes in potassium metabolism was significantly higher in SC8 than in SC2. Metabolomic analysis showed that compared to SMR, SC8 decreased the abundance of carbohydrates, ketones, and lipid. However, the abundance of carbohydrates, ketones, and lipid was significantly higher in SC8 than in SC2. Mantel test showed that soil pH and AK significantly affected soil microbial community, function, and metabolite composition. Correlation analysis showed significant correlation between soil metabolites and microorganisms, metabolic functions. Graphical Abstract

Abstract Electrochemical reduction of carbon dioxide into ethylene, as opposed to traditional industrial methods, represents a more environmentally friendly and promising technical approach. However, achieving high activity of ethylene remains a huge challenge due to the numerous possible reaction pathways. Here, we construct a hierarchical nanoelectrode composed of CuO treated with dodecanethiol to achieve elevated ethylene activity with a Faradaic efficiency reaching 79.5%. Through on in situ investigations, it is observed that dodecanethiol modification not only facilitates CO2 transfer and enhances *CO coverage on the catalyst surfaces, but also stabilizes Cu(100) facet. Density functional theory calculations of activation energy barriers of the asymmetrical C–C coupling between *CO and *CHO further support that the greatly increased selectivity of ethylene is attributed to the thiol-stabilized Cu(100). Our findings not only provide an effective strategy to design and construct Cu-based catalysts for highly selective CO2 to ethylene, but also offer deep insights into the mechanism of CO2 to ethylene.

Objective Thermal ablation (TA) is a safe and effective treatment for benign thyroid nodules (BTNs). However, there has been no consensus on the optimal maximum diameter (MD) of BTNs for TA. This study aimed to identify the optimal MD of BTNs for TA based on complete disappearance rate after TA.Materials and methods This retrospective study included 639 BTNs treated with TA from June 2014 to January 2022. The complete disappearance rate of BTNs after TA was summarized, related influencing factors were explored, and the optimal MD of BTNs for TA was identified.Results At the final follow-up (median: 40 months, range: 24–95 months), the overall volume reduction rate was 95.4 ± 9.0%, and 50.5% of the BTNs (323/639) completely disappeared. The MD was significantly negatively correlated with complete disappearance (odds ratio 0.89, 95% confidence interval 0.87–0.92; p 25.0 mm had a greater complication rate (6.5% vs. 2.4%, p = 0.012).Conclusions The MD of BTNs was negatively correlated with complete disappearance after TA; an MD > 25.0 mm indicated a reduced likelihood of complete disappearance compared with an MD ≤ 25.0 mm. An MD of 25.0 mm is an appropriate threshold of BTNs for TA on the basis of complete disappearance rate.

Objective To assess the feasibility, efficacy, and safety of microwave ablation in treating follicular thyroid neoplasms and suspicious follicular thyroid neoplasms.Methods In this retrospective study, the data of patients treated with microwave ablation for follicular neoplasms from December 2016 to January 2024 were summarized. The changes in nodule size, volume, technical success rate, disease progression, complete tumor resolution, thyroid function, and complications post-ablation were evaluated.Results Seventy-four patients (15 men, 59 women; mean age 46.3 ± 15.2 years) with follicular neoplasms were included. Over a median follow-up of 13 months, complete ablation was achieved, giving a 100% technical success rate. At the first month post-ablation, the maximum diameter of nodules showed no significant change (p = 0.287). From the third month, both maximum diameter and volume significantly decreased (p 0.05). The complication and side effect rates were 8.1% and 4.1%, respectively.Conclusions Initial findings suggest microwave ablation is an effective and safe treatment for follicular neoplasms, with low incidences of disease progression and complications, while maintaining thyroid function.

AbstractObjective To evaluate the complications associated with microwave ablation (MWA) in treating persistent/recurrent hyperparathyroidism (HPT) post-surgical or ablative treatments.Materials and methods From January 2015 to December 2022, 87 persistent/recurrent HPT patients (primary HPT [PHPT]: secondary HPT [SHPT] = 13:74) who underwent MWA after surgical or ablative treatment were studied. Grouping was based on ablation order (initial vs. re-MWA), prior treatment (parathyroidectomy [PTX] vs. MWA), and etiology (PHPT vs. SHPT). The study focused on documenting and comparing treatment complications and analyzing major complication risk factors.Result Among the 87 patients, the overall complication rate was 17.6% (15/87), with major complications at 13.8% (12/87) and minor complications at 3.4% (3/87). Major complications included recurrent laryngeal nerve (RLN) palsy (12.6%) and Horner syndrome (1.1%), while minor complications were limited to hematoma (3.4%). Severe hypocalcemia noted in 21.6% of SHPT patients. No significant differences in major complication rates were observed between initial and re-MWA groups (10.7% vs. 13.8%, p = 0.455), PTX and MWA groups (12.5% vs. 15.4%, p = 0.770), or PHPT and SHPT groups (15.4% vs. 13.5%, p > 0.999). Risk factors for RLN palsy included ablation of superior and large parathyroid glands (>1.7 cm). All patients recovered spontaneously except for one with permanent RLN palsy in the PTX group (2.1%).Conclusion Complication rates for MWA post-surgical or ablative treatments were comparable to initial MWA rates. Most complications were transient, indicating MWA as a viable and safe treatment option for persistent/recurrent HPT patients.

Canine circovirus (CanineCV) is a recently identified member of the Circoviridae family. Since its discovery in 2011, CanineCV has been detected in different countries worldwide, infecting both domestic and wild canids. The virus is potentially associated with gastrointestinal and respiratory illnesses. In 2016, CanineCV was reported in the southwestern region of Guangxi, China. However, its prevalence in other provinces in the Southwest region remained unknown. This study collected a total of 208 serum samples from domestic dogs in Sichuan, China in 2022 to investigate the prevalence of CanineCV. Among these samples, 26 tested positive for CanineCV, resulting in a positivity rate of 12.5%. Additionally, 12 strains were sequenced, 9 of which had a sequence length of 2,063 nucleotides (nt), 2 of the other threes had a length of 2,062 nts and another was 2,064 nt. Notably, a frameshift mutation was identified, resulting in a truncated ORF1 and the occurrence of a novel sequence comprised of 13 amino acids at the end of the replicate protein (Rep). This mutation could affect the replication cycle of the virus. Phylogenetic and evolutionary analyses revealed that the isolates belonged to the CanineCV-3 genotype and were prevalent in the Southeast and the Southwest regions of China, as well as in the neighboring countries alongside other strains of the same genotype. Collectively, this epidemiological investigation widens our understanding of the genetic diversity of CanineCV in Southwest China and provides insights into viral evolution.

Summary: Pyrrolidine (PyD) has an important impact on the environment and human health. However, there is currently no method for trace detection of PyD. Here, we successfully designed diaminomethylene-4H-pyran (1) as the first specific fluorescent probe for PyD. Only by adding PyD to probe 1, there is blue fluorescence at 455 nm, and the color of the solution changes from colorless to yellow. The detection limit is 1.12 × 10−6 M, and the response time is less than 5 min. Meanwhile, probe 1 can also sense the gaseous PyD and detect PyD in actual water samples. Moreover, due to the low biological toxicity, probe 1 can detect the exogenous PyD in zebrafish. The preliminary mechanism shows that probe 1 and PyD undergo a combination-type chemical reaction to generate a new substance 1-PyD. Therefore, the 100% atom utilization reaction enables probe 1 to exhibit specific adsorption and removal of PyD.

Non-alcoholic fatty liver disease (NAFLD), particularly advanced non-alcoholic steatohepatitis (NASH), leads to irreversible liver damage. This study investigated the therapeutic effects and potential mechanism of a novel extract from traditional Chinese medicine Alisma orientale (Sam.) Juzep (AE) on free fatty acid (FFA)-induced HepG2 cell model and high-fat diet (HFD) + carbon tetrachloride (CCl4)-induced mouse model of NASH. C57BL/6 J mice were fed a HFD for 10 weeks. Subsequently, the mice were injected with CCl4 to induce NASH and simultaneously treated with AE at daily doses of 50, 100, and 200 mg/kg for 4 weeks. At the end of the treatment, animals were fasted for 12 h and then sacrificed. Blood samples and liver tissues were collected for analysis. Lipid profiles, oxidative stress, and histopathology were examined. Additionally, a polymerase chain reaction (PCR) array was used to predict the molecular targets and potential mechanisms involved, which were further validated in vivo and in vitro. The results demonstrated that AE reversed liver damage (plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatocyte ballooning, hepatic steatosis, and NAS score), the accumulation of hepatic lipids (TG and TC), and oxidative stress (MDA and GSH). PCR array analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that AE protects against NASH by regulating the adipocytokine signaling pathway and influencing nuclear receptors such as PPARα. Furthermore, AE increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PPARGC1α) and reversed the decreased expression of PPARα in NASH mice. Moreover, in HepG2 cells, AE reduced FFA-induced lipid accumulation and oxidative stress, which was dependent on PPARα up-regulation. Overall, our findings suggest that AE may serve as a potential therapeutic approach for NASH by inhibiting lipid accumulation and reducing oxidative stress specifically through the PPARα pathway.

Over-expression of glutathione S-transferase (GST) can promote Cisplatin resistance in hepatocellular carcinoma (HCC) treatment. Hence, inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therapy. Although several synthesized GST inhibitors have been developed, the side effects and narrow spectrum for anticancer seriously limit their clinical application. Considering the abundance of natural compounds with anticancer activity, this study developed a rapid fluorescence technique to screen “green” natural GST inhibitors with high specificity. The fluorescence assay demonstrated that schisanlactone B (hereafter abbreviated as C1) isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo. Importantly, C1 can selectively kill HCC cells from normal liver cells, effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression. Considering the high GST levels in HCC patients, this compound demonstrated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.

IntroductionFine needle aspiration (FNA) biopsy is a widely accepted method for diagnosing thyroid nodules. However, the influence of maximum diameter (MD) of ACR TIRADS 5 (TR5) thyroid nodules on the FNA outcomes remains debated. This study examined the influence of MD on the FNA outcomes and investigated the optimal MD threshold for FNA in TR5 nodules.MethodsWe conducted a retrospective analysis of 280 TR5 thyroid nodules from 226 patients who underwent FNA from January to June 2022 in our department. Probably malignant (PM) group was defined as Bethesda V in cytopathology with confirmed BRAF V600E mutation or Bethesda VI, the other cytopathology outcomes were defined as probably benign (PB) group. We examined factors influencing malignant cytopathology outcomes and determined the optimal MD threshold for FNA in TR5 nodules using logistic regression and restricted cubic spline (RCS) analysis.ResultsAmong these nodules, 58.2% (163/280) had PM outcomes. The PM group had a significantly larger MD than the PB group [6.5mm (range 5.0-8.4) vs. 5.3mm (range 4.0-7.0), p < 0.001]. In multivariate logistic regression fully adjusted for confounders, MD was significantly associated with PM outcomes [odds ratio 1.16, 95%CI 1.05-1.31; p = 0.042]. The highest quartile of MD had a greater likelihood of PM outcomes compared to the lowest quartile [odds ratio 4.71, 95% CI 1.97-11.69, p = 0.001]. The RCS analysis identified 6.2 mm as the optimal MD threshold for FNA in TR5 nodules.ConclusionMD significantly affects the probability of malignant outcomes in FNA of TR5 thyroid nodules. A MD threshold of ≥6.2mm is suggested for FNA in these nodules.

BackgroundThe Chikungunya virus is an Alphavirus that belongs to the Togaviridae family and is primarily transmitted by mosquitoes. It causes acute infection characterized by fever, headache, and arthralgia. Some patients also experience persistent chronic osteoarthritis-like symptoms. Dedicated antiviral treatments are currently unavailable for CHIKV. This study aims to explore the potential anti-CHIKV effect of rosmarinic acid using network pharmacology.MethodsThis study employed network pharmacology to predict and verify the molecular targets and pathways associated with ROSA in the context of CHIKV. The analysis outcomes were further validated using molecular docking and in vitro experiments.ResultsThe analysis of CHIKV targets using the Kyoto Encyclopedia of Genes and Genomes and MCODE identified IL-17 as an important pathogenic pathway in CHIKV infection. Among the 30 targets of ROSA against CHIKV, nearly half were found to be involved in the IL-17 signaling pathway. This suggests that ROSA may help the host in resisting CHIKV invasion by modulating this pathway. Molecular docking validation results showed that ROSA can stably bind to 10 core targets out of the 30 identified targets. In an in vitro CHIKV infection model developed using 293T cells, treatment with 60 μM ROSA significantly improved the survival rate of infected cells, inhibited 50% CHIKV proliferation after CHIKV infection, and reduced the expression of TNF-α in the IL-17 signaling pathway.ConclusionThis study provides the first confirmation of the efficacy of ROSA in suppressing CHIKV infection through the IL-17 signaling pathway. The findings warrant further investigation to facilitate the development of ROSA as a potential treatment for CHIKV infection.

Abstract Objective This study aimed to explore the efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with ZiLongJin Tablet (ZLJT) in delaying acquired resistance in advanced EGFR-mutant lung adenocarcinoma (LUAD) patients. Furthermore, we employed network pharmacology and molecular docking techniques to investigate the underlying mechanisms. Methods A retrospective comparative study was conducted on stage IIIc/IV LUAD patients treated with EGFR-TKIs alone or in combination with ZLJT at the Second Affiliated Hospital of the Air Force Medical University between January 1, 2017, and May 1, 2023. The study evaluated the onset of TKI resistance, adverse reaction rates, safety indicators (such as aspartate aminotransferase, alanine aminotransferase, and creatinine), and inflammatory markers (neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio) to investigate the impact of EGFR-TKI combined with ZLJT on acquired resistance and prognostic indicators. Additionally, we utilized the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine, PubChem, UniProt, and Swiss Target Prediction databases to identify the active ingredients and targets of ZLJT. We obtained differentially expressed genes related to EGFR-TKI sensitivity and resistance from the Gene Expression Omnibus database using the GSE34228 dataset, which included sensitive (n = 26) and resistant (n = 26) PC9 cell lines. The "limma" package in R software was employed to detect DEGs. Based on this, we constructed a protein‒protein interaction network, performed gene ontology and KEGG enrichment analyses, and conducted pathway network analysis to elucidate the correlation between the active ingredients in ZLJT and signaling pathways. Finally, molecular docking was performed using AutoDockVina, PYMOL 2.2.0, and Discovery Studio Client v19.1.0 software to simulate spatial and energy matching during the recognition process between predicted targets and their corresponding compounds. Results (1) A total of 89 patients were included, with 40 patients in the EGFR-TKI combined with ZLJT group (combination group) and 49 patients in the EGFR-TKI alone group (monotherapy group). The baseline characteristics of the two groups were comparable. There was a significant difference in the onset of resistance between the combination group and the monotherapy group (P 0.05). There were no statistically significant differences in serum AST, ALT, CREA, TBIL, ALB and BUN levels between the two groups after medication (P > 0.05). (3) Regarding inflammatory markers, there were no statistically significant differences in the changes in neutrophil-to-lymphocyte Ratio(NLR) and Platelet-to-lymphocyte Ratio(PLR) values before and after treatment between the two groups (P > 0.05). (4) Network pharmacology analysis identified 112 active ingredients and 290 target genes for ZLJT. From the GEO database, 2035 differentially expressed genes related to resistant LUAD were selected, and 39 target genes were obtained by taking the intersection. A "ZLJT-compound-target-disease" network was successfully constructed using Cytoscape 3.7.0. GO enrichment analysis revealed that ZLJT mainly affected biological processes such as adenylate cyclase-modulating G protein-coupled receptor. In terms of cellular components, ZLJT was associated with the cell projection membrane. The molecular function primarily focused on protein heterodimerization activity. KEGG enrichment analysis indicated that ZLJT exerted its antitumor and anti-drug resistance effects through pathways such as the PI3K-Akt pathway. Molecular docking showed that luteolin had good binding activity with FOS (-9.8 kJ/mol), as did tanshinone IIA with FOS (-9.8 kJ/mol) and quercetin with FOS (-8.7 kJ/mol). Conclusion ZLJT has potential antitumor progression effects. For patients with EGFR gene-mutated non-small cell LUAD, combining ZLJT with EGFR-TKI treatment can delay the occurrence of acquired resistance. The underlying mechanisms may involve altering signal transduction pathways, blocking the tumor cell cycle, inhibiting tumor activity, enhancing cellular vitality, and improving the bioavailability of combination therapy. The combination of EGFR-TKI and ZLJT represents an effective approach for the treatment of tumors using both Chinese and Western medicine.

Abstract Glioblastoma (GBM) is an aggressive intracranial tumour, and current chemotherapy regimens have limited efficacy. Aloperine (ALO), a natural alkaline compound, has shown potential as an antitumor agent. However, the effect of ALO against GBM remains unclear. This study aimed to investigate the function of ALO in treating GBM. U87, A172, and GL261 cell lines were used for in vitro experiments, and GL261 was also used to establish in vivo models. The results showed that ALO inhibited the proliferation of GBM cells by cell cycle arrest and apoptosis. Furthermore, autophagy was found to play a critical role, suggested by observation of autophagosomes under the transmission electron microscopy. It was discovered for the first time that ALO targeted lysosomes directly in glioma cells, tested by fluo-rescence-labelled ALO and organelle-localizing probes. In addition, ALO inhibited late autophagy and induced paraptosis in GBM, verified by classical gene expression changes in qPCR and western blotting. Also, ALO inhibited tumour growth and acted synergistically with temozolomide in intracranial glioma mice models in vivo. Our findings suggest that ALO targets lysosomes to inhibit late autophagy in GBM, inducing cell cycle arrest, paraptosis, and apoptosis. ALO may therefore be a promising therapeutic agent for the treatment of GBM.

Using first-principles theory, this work purposes Ru-doped Janus WSSe (Ru-WSSe) monolayer as a potential gas sensor for detection of three typical gas species (CO, C2H2, and C2H4), in order to evaluate the operation status of the oil-immersed transformers. The Ru-doping behavior on the WSSe surface is analyzed, giving rise to the preferred doping site by the replacement of a Se atom with the formation energy of 0.01 eV. The gas adsorption of three gas species onto the Ru-WSSe monolayer is conducted, and chemisorption is identified for all three gas systems with the adsorption energy following the order: CO (−2.22 eV) > C2H2 (−2.01 eV) > C2H4 (−1.70 eV). Also, the modulated electronic properties and the frontier molecular orbital are investigated to uncover the sensing mechanism of Ru-WSSe monolayer upon three typical gases. Results reveal that the sensing responses of the Ru-WSSe monolayer, based on the variation of energy gap, to CO, C2H2, and C2H4 molecules are calculated to be 1.67 × 106, 2.10 × 105, and 9.61 × 103, respectively. Finally, the impact of the existence of O2 molecule for gas adsorption and sensing is also analyzed to uncover the potential of Ru-WSSe monolayer for practical application in the air atmosphere. The obtained high electrical responses manifest strong potential as a resistive sensor for detection of three gases. The findings hold practical implications for the development of novel gas sensing materials based on Janus WSSe monolayer. We anticipate that our results will inspire further research in this domain, particularly for applications in electrical engineering where the reliable detection of fault gases is paramount for maintaining the integrity and safety of power systems.

Moisture has been a crucial problem during the operation of cable systems. When we are faced with polypropylene (PP)-based insulation for the development of cable systems, there are few reports on the effects of water intrusion on the electrical performances of PP. In this study, the water absorption characteristics of isotactic PP (iPP) and atactic PP (aPP), as well as their effects on volume resistivity and relative permittivity, were investigated. The structure evolution during the water absorption process of the two PPs was also compared via infrared spectra and X-ray diffraction analyses. The results show that both of the two PPs show a saturation of water absorption at ~216 h, even though there are structural differences. And water intrusion into bulk could increase the interplanar spacing of iPP while decreasing the interplanar spacing of aPP. Moreover, with the increase in water absorption, the volume resistivity of the two PPs show a decreasing trend while the relative permittivity presents an increasing behavior, which shows an almost linear correlation.

The position error in an inertial navigation system (INS) for autonomous underwater vehicles (AUVs) increases over time. Terrain-aided navigation can assist in correcting these INS position errors. To enhance the matching accuracy under large initial position errors, an improved terrain matching algorithm comprising terrain contour matching (TERCOM), particle swarm optimization (PSO), and iterative closest contour point (ICCP), named TERCOM-PSO-ICCP, is proposed. Initially, an enhanced TERCOM with an increased rotation angle is utilized to minimize heading errors and reduce the initial position error. The similarity extremum approach evaluates the initial matching outcomes, leading to an enhanced accuracy in the initial results. Next, artificial bee colony (ABC)-optimized PSO is employed for secondary matching to further reduce the initial position error and narrow the matching area. Finally, the ICCP, using the Mahalanobis distance as the objective function, is applied for the third matching, leveraging the ICCP’s fine search capabilities. The effective combination of these three algorithms significantly improves the terrain-aided navigation matching effect. Two tests show that the improved TERCOM-PSO-ICCP effectively reduces the matching error and corrects the position of the INS.

With the increase in port throughput and the development of the trend of large-scale ships, selecting applicable anchor positions for ships and ensuring the rational and comprehensive utilization of anchorage areas have become a key issue in utilizing the rate of anchorage resources, ensuring the safety of ships anchoring operations and promoting the development of the shipping industry. Existing anchor position selection and detection algorithm studies are limited to a two-dimensional plane for ship anchor position selection, with few studies considering intelligent detection algorithms for safe ship anchoring water depths based on three-dimensional space, considering conditions such as wind and waves. By considering water depth conditions and the objectives of anchorage safety issues, this study proposes an intelligent detection method for ship anchor detection to find the ship’s ideal anchor location in the anchorages by applying the Monte Carlo algorithm. In the processing step, in combination with the Monte Carlo random plane anchor position detection algorithm and Monte Carlo random sampling water depth detection method, the anchor position circle radius model, safe spacing model, anchoring area detection model and safe water depth model are used for examining the anchorage area for awaiting the ship in three-dimensions. To verify the accuracy of the proposed model, based on the scale of common ship types and considering the most conservative parameters, a series of simulation experiments are conducted to check whether the water depth meets the requirements and fully ensure the safety of the experimental results. The research results indicate that the detection almost cover the whole anchorage area and obtain safe water depth restrictions. This method helps to improve the efficiency of ship anchoring and makes actual anchoring operations safer. Under the premise of ensuring sufficient safe spacing between ships, the anchorage ground can accommodate more ships and simulate multi-type ship anchor position detection operations concerning various ship-type parameters to further ensure the safety of ship anchoring.

Abstract Recurrent spontaneous abortion (RSA) is a pregnancy‐related condition with complex etiology. Trophoblast dysfunction and abnormal macrophage polarization and metabolism are associated with RSA; however, the underlying mechanisms remain unknown. Jupiter microtubule‐associated homolog 2 (JPT2) is essential for calcium mobilization; however, its role in RSA remains unclear. In this study, it is found that the expression levels of JPT2, a nicotinic acid adenine dinucleotide phosphate‐binding protein, are decreased in the villous tissues of patients with RSA and placental tissues of miscarried mice. Mechanistically, it is unexpectedly found that abnormal JPT2 expression regulates trophoblast function and thus involvement in RSA via c‐Jun N‐terminal kinase (JNK) signaling, but not via calcium mobilization. Specifically, on the one hand, JPT2 deficiency inhibits trophoblast adhesion, migration, and invasion by inhibiting the JNK/atypical chemokine receptor 3 axis. On the other hand, trophoblast JPT2 deficiency contributes to M1 macrophage polarization by promoting the accumulation of citrate and reactive oxygen species via inhibition of the JNK/interleukin‐6 axis. Self‐complementary adeno‐associated virus 9‐JPT2 treatment alleviates embryonic resorption in abortion‐prone mice. In summary, this study reveals that JPT2 mediates the remodeling of the immune microenvironment at the maternal–fetal interface, suggesting its potential as a therapeutic target for RSA.

BackgroundLMB-100 is a mesothelin (MSLN)-targeting recombinant immunotoxin (iTox) carrying a Pseudomonas exotoxin A payload that has shown promise against solid tumors, however, efficacy is limited by the development of neutralizing anti-drug antibodies (ADAs). Tofacitinib is an oral Janus Kinase (JAK) inhibitor that prevented ADA formation against iTox in preclinical studies.MethodsA phase 1 trial testing LMB-100 and tofacitinib in patients with MSLN-expressing cancers (pancreatic adenocarcinoma, n=13; cholangiocarcinoma, n=1; appendiceal carcinoma, n=1; cystadenocarcinoma, n=1) was performed to assess safety and to determine if tofacitinib impacted ADA formation. Participants were treated for up to 3 cycles with LMB-100 as a 30-minute infusion on days 4, 6, and 8 at two dose levels (100 and 140 µg/kg) while oral tofacitinib was administered for the first 10 days of the cycle (10 mg BID). Peripheral blood was collected for analysis of ADA levels, serum cytokines and circulating immune subsets.ResultsThe study was closed early due to occurrence of drug-induced pericarditis in 2 patients. Pericarditis with the combination was not reproducible in a transgenic murine model containing human MSLN. Two of 4 patients receiving all 3 cycles of treatment maintained effective LMB-100 levels, an unusual occurrence. Sustained increases in systemic IL-10 and TNF-α were seen, a phenomenon not observed in prior LMB-100 studies. A decrease in activated T cell subsets and an increase in circulating immunosuppressive myeloid populations occurred. No radiologic decreases in tumor volume were observed.DiscussionFurther testing of tofacitinib to prevent ADA formation is recommended in applicable non-malignant disease settings.Clinical trial registrationhttps://www.clinicaltrials.gov/study/NCT04034238.

Pseudoaneurysm is a rare but lethal complication of acute myocardial infarction. In this study, we present a unique case of a patient with left ventricular free wall rupture detected by cardiac magnetic resonance more than 1 year after a percutaneous transluminal coronary intervention.

Abstract The dual emission (DE) feature in materials holds great potential to revolutionize the development of one‐component system white organic light‐emitting diodes (WOLEDs). However, the reported DE materials remain scarce owing to the formidable challenge of breaking Kasha's rule and managing the intricate energy/charge transfer processes. Herein, we have introduced a groundbreaking DE AIEgen, 2CzAn‐TPE, which possesses a simple structure and undergoes Z‐to‐E isomerization and exhibits yellow and red fluorescence powders for pre‐ and post‐sublimation, respectively. With relatively lower potential energy, Z‐conformation ((Z)‐1,2‐diphenyl‐1,2‐bis(4‐(10‐(9‐phenyl‐9H‐carbazol‐3‐yl)anthracen‐9‐yl)phenyl)ethene) of 2CzAn‐TPE can be readily transformed into E‐conformation ((E)‐1,2‐diphenyl‐1,2‐bis(4‐(10‐(9‐phenyl‐9H‐carbazol‐3‐yl)anthracen‐9‐yl)phenyl)ethene) via vacuum sublimation. The utilization of X‐ray diffraction and grazing‐incidence‐wide‐angle X‐ray scattering techniques confirms the structural transformation, while the crystallographic analysis reveals the establishment of numerous intermolecular CH···π interactions between the tetraphenylethene (TPE) moiety and both the anthracene and carbazole units. This allows a densely packed molecular arrangement, thereby offering propitious conditions for excimer generation in the E‐conformation aggregated state. By utilizing the sublimated 2CzAn‐TPE as an emitter, a nondoped one‐component WOLED was prepared, exhibiting an exceptionally high external quantum efficiency (EQE) of 5.0%, which represents one of the highest performances among all one‐component WOLEDs. This research introduces a novel, simple, and efficient approach to realize highly efficient one‐molecule WOLEDs.

Abstract Soybean whey and soybean hydrolyzate can be used for the biotechnological production of high-value products. Herein, we isolate soybean whey (SW)-and soybean hydrolyzate (SH)-derived bacterial cellulose (BC, produced by kombucha) and characterize it by a range of instrumental techniques to reveal differences in micromorphology, crystallinity, and themal behavior. Studies have shown that the amounts of wet state BC produced from HS, SW and SH was 181 g/L, 47 g/L and 83 g/L, respectively. The instrumental analysis of BC, included SEM, AFM, FT-IR, XRD and TGA. It is shown that the FT-IR spectra of BC have a similar character, but we found differences in the micromorphology,crystallinity and thermal temperature of BC. The minimum average widths of the fibers produced from SH medium was 100 ± 29 nm. The CrI values of BC produced from SH medium was 61.8%. The maximum thermal degradation rate temperature of BC produced from SW medium was 355.73 °C. The combined results demonstrate that soybean industrial waste can be used as a cost-effective raw material for BC production.

This research focused on the rubber bushings of the rear sub-frame in an electric vehicle. A dynamic model was developed to represent the bushing, incorporating an elastic element, a frictional element, and a viscoelastic element arranged in series using a fractional-order Maxwell and a Kelvin–Voigt model. To identify the parameters of the bushing model, an improved adaptive chaotic particle swarm optimization algorithm was employed, in conjunction with dynamic stiffness test data obtained at an amplitude of 0.2 mm. The test data obtained at different amplitudes (0.2 mm, 0.3 mm, 0.5 mm, and 1 mm) were fitted to the model, resulting in fitting errors of 1.13%, 4.07%, 4.42%, and 28.82%, respectively, when compared to the corresponding test data in order to enhance the accuracy of the model fitting; the Sobol sensitivity analysis method was utilized to analyze the parameter sensitivity of the model. Following the analysis, the parameters α, β, and k2, which exhibited high sensitivity, were re-identified. This re-identification process led to a reduction in the fitting error at the 1 mm amplitude to 7.45%. The improved accuracy of the model plays a crucial role in enhancing the simulation accuracy of design of experiments (DOE) analysis and verifying the vehicle’s performance under various conditions, taking into account the influence of the bushing.

Abstract This paper develops an adaptive neural fault‐tolerant control for an unknown two‐degree of freedom helicopter nonlinear system with output error constraints, actuator fault, and unknown external disturbances. A neural network disturbance observer is used to estimate system uncertainties and actuator gain failures. The tan‐type barrier Lyapunov equation is used to solve the system's output error constraint. To compensate for actuator bias failures and unknown external disturbances in the system, an adaptive auxiliary parameter is established. Furthermore, rigorously analyzing the chosen Lyapunov function, the system's stability is ensured. Finally, the numerical simulation results prove the rationality and effectiveness of the proposed control strategy.

In this article, a new intelligent fault-tolerant control (FTC) is designed to control a flexible-link manipulator with uncertain dead-zone and intermittent actuator faults. Initially, a smooth dead-zone inverse model using a hyperbolic tangent function is introduced to handle dead-zone nonlinearity and suppress input chattering. An adaptive law is proposed to estimate an unknown coupling item, combining the upper bounds of compensation error and floating bias faults, achieving robust adaptive control of the system. A new FTC strategy is subsequently developed to address intermittent actuator faults. Finally, the bounded convergence of system state errors is proven using direct Lyapunov methods, and the effectiveness and superiority of the proposed controller are demonstrated through numerical simulation and experiment.