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Abdominal Aortic Aneurysm (AAA) is a life-threatening vascular disease characterized by the weakening and ballooning of the abdominal aorta, which has no effective therapeutic approaches due to unclear molecular mechanisms. Using single-cell RNA sequencing, we analyzed the molecular profile of individual cells within control and AAA abdominal aortas. We found cellular heterogeneity, with increased plasmacytoid dendritic cells and reduced endothelial cells and vascular smooth muscle cells (VSMCs) in AAA. Up-regulated genes in AAA were associated with muscle tissue development and apoptosis. Genes controlling VSMCs aberrant switch from contractile to synthetic phenotype were significantly enriched in AAA. Additionally, VSMCs in AAA exhibited cell senescence and impaired oxidative phosphorylation. Similar observations were made in a mouse model of AAA induced by Angiotensin II, further affirming the relevance of our findings to human AAA. The concurrence of gene expression changes between human and mouse highlighted the impairment of oxidative phosphorylation as a potential target for intervention. Nicotinamide phosphoribosyltransferase (NAMPT, also named VISFATIN) signaling emerged as a signature event in AAA. NAMPT was significantly downregulated in AAA. NAMPT-extracellular vesicles (EVs) derived from mesenchymal stem cells restored NAMPT levels, and offered protection against AAA. Furthermore, NAMPT-EVs not only repressed injuries, such as cell senescence and DNA damage, but also rescued impairments of oxidative phosphorylation in both mouse and human AAA models, suggesting NAMPT supplementation as a potential therapeutic approach for AAA treatment. These findings shed light on the cellular heterogeneity and injuries in AAA, and offered promising therapeutic intervention for AAA treatment.

Abstract The study investigates the optimization of life cycle carbon emissions in smart sustainable energy systems through power transformation and transmission project power load predictions. Firstly, a multi-task learning-based short-term user load forecasting technique is developed, where the power load curves of multiple residential customers are grouped and classified using the K-means clustering method. Additionally, the Bidirectional Long Short-Term Memory (BiLSTM) technique is introduced to anticipate the power load intelligently. Secondly, a life cycle carbon emission assessment model for the power transmission and transformation project (PTTP) is constructed based on the life cycle assessment (LCA) method, which divides the project's life cycle into four stages: production, installation and construction, operation and maintenance, and demolition. Finally, an experimental evaluation of this model is conducted. The results demonstrate that compared with the baseline model Long Short-Term Memory (LSTM), this model achieves a significantly lower average Mean Absolute Error (MAE) at 3.62% while achieving significantly higher accuracy in power load forecasting at 94.34%. A comprehensive examination of carbon emissions across all four phases reveals that overall carbon emissions are highest during the operation and maintenance stage followed by the equipment production stage and installation/construction stage, with the lowest overall carbon emissions observed. Hence, this study endeavors to forecast power load demand with precision and identify the principal determinants of carbon emissions in power engineering. By discerning and managing these key factors, an optimal, energy-efficient intelligent power load scheme can be derived.

Abstract Aurora-A kinase interacting protein 1 (AURKAIP1) has been proved to take an intermediary role in cancer by functioning as a negative regulator of Aurora-A kinase. However, it remains unclear whether and how AURKAIP1 itself would directly engage in regulating malignancies. The expression levels of AURKAIP1 were detected in triple negative breast cancer (TNBC) by immunohistochemistry and western blots. The CCK8, colony formation assays and nude mouse model were conducted to determine cell proliferation whereas transwell and wound healing assays were performed to observe cell migration. The interaction of AURKAIP1 and DEAD-box helicase 5 (DDX5) were verified through co-immunoprecipitation and successively western blots. From the results, we found that AURKAIP1 was explicitly upregulated in TNBC, which was positively associated with tumor size, lymph node metastases, pathological stage and unfavorable prognosis. AURKAIP1 silencing markedly inhibited TNBC cell proliferation and migration in vitro and in vivo. AURKAIP1 directly interacted with and stabilized DDX5 protein by preventing ubiquitination and degradation, and DDX5 overexpression successfully reversed proliferation inhibition induced by knockdown of AURKAIP1. Consequently, AURKAIP1 silencing suppressed the activity of Wnt/β-catenin signaling in a DDX5-dependent manner. Our study may primarily disclose the molecular mechanism by which AURKAIP1/DDX5/β-catenin axis modulated TNBC progression, indicating that AURKAIP1 might serve as a therapeutic target as well as a TNBC-specific biomarker for prognosis.

Abstract Background Adipose tissue, which is mainly composed of adipocytes, is a crucial component of the tumor microenvironment, particularly in breast cancer. Adipocytes surround breast cancer cells and may participate in cell‒cell interactions in the breast microenvironment. However, little is currently known about how adipocytes influence the biological behavior of the surrounding breast cancer cells. Hence, this study sought to investigate the role and underlying mechanisms of periostin in triple–negative breast cancer (TNBC) cells cocultured with adipogenic conditioned medium (ACM) and palmitic acid (PA). Methods Human TNBC cell lines (MDA‒MB‒231 and SUM159PT) were treated with ACM and PA, then the expression of periostin, matrix metalloproteinases (MMPs) and stemness–related molecules were assessed by Western blotting and RT‒qPCR. The cellular viability was assessed using CCK‒8 assay. Plasmid transfection, RNA sequencing, and pathway inhibitor were used to explore the specific mechanisms of periostin. Results ACM and PA elevated the expression of both MMPs and stemness–related molecules in TNBCs. MMPs can promote tumor cell infiltration and migration by degrading the extracellular matrix, and stemness expression increases the development of tumor chemoresistance. Additionally, ACM and PA increased periostin expression, while inhibiting periostin disrupted the involvement of ACM and PA in promoting extracellular matrix degradation, stemness, and chemoresistance in TNBCs. Furthermore, this study found that periostin promoted TNBC progression by activating the MAPK/ERK signaling pathway and that inhibition of MAPK/ERK signaling reduced the phenotype caused by periostin upregulation in TNBCs treated with ACM or PA. Finally, the present results showed that the high expression of POSTN, which encodes periostin, was substantially related to worse survival in TNBC patients. Conclusions The results of the study elucidated for the first time how periostin is the key protein secreted in TNBCs in response to the adipocyte–regulated tumor microenvironment, while periostin–neutralizing antibodies may serve as potential therapeutic agents in relation to TNBC progression.

The small GTPase ADP-ribosylation factor 6 (ARF6) mediates chemokine (C-C motif) ligand 18 (CCL18)-induced activation of breast cancer (BC) metastasis through its downstream effector AMAP1. However, the molecular mechanisms underlying CCL18 up-regulating ARF6 remain largely unclear. Here, microRNAs (miRNAs) that target ARF6 were predicted and selected in high metastatic BC cells treated with CCL18. Next, we assessed the role of exosomal miR-760 in vitro and in vivo. We further analyzed the expression of ARF6, AMAP1, and phosphorylated (p)-AMAP1 in tumor and adjacent normal tissues. We first observed that CCL18 increased the expression of ARF6 and p-AMAP1 and activated the Src/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. ARF6 knockdown significantly impaired CCL18-induced malignant cellular behaviors and the Src/PI3K/Akt signaling pathway. Next, ARF6 was confirmed as a target gene of miR-760 in exosomes derived from CCL18-stimulated high metastatic BC cells. Moreover, recipient MCF-7 cells could effectively uptake these miR-760-rich exosomes that significantly promoted proliferation, tumor growth in vivo, migration, invasion, and chemoresistance by activating ARF6-mediated Src/PI3K/Akt signaling and the epithelial-mesenchymal transition (EMT) pathway. Together, our results support that exosomal miR-760 secreted by CCL18-stimulated high metastatic BC cells promoted the malignant behaviors in low metastatic BC cells by up-regulating the ARF6-mediated Src/PI3K/Akt signaling pathway.

Objective Rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone, once every 3 weeks (R-CHOP21) is commonly used in non-Hodgkin’s lymphoma (NHL), but accompanied by Pneumocystis carinii pneumonia (PCP) as a fatal treatment complication. This study aims to estimate the specific effectiveness and cost-effectiveness of PCP prophylaxis in NHL undergoing R-CHOP21.Design A two-part decision analytical model was developed. Prevention effects were determined by systemic review of PubMed, Embase, Cochrane Library and Web of Science from inception to December 2022. Studies reporting results of PCP prophylaxis were included. Enrolled studies were quality assessed with Newcastle-Ottawa Scale. Costs were derived from the Chinese official websites, and clinical outcomes and utilities were obtained from published literature. Uncertainty was evaluated through deterministic and probabilistic sensitivity analyses (DSA and PSA). Willingness-to-pay (WTP) threshold was set as US$31 315.23/quality-adjusted life year (QALY) (threefold the 2021 per capita Chinese gross domestic product).Setting Chinese healthcare system perspective.Participants NHL receiving R-CHOP21.Interventions PCP prophylaxis versus no prophylaxis.Main outcome measures Prevention effects were pooled as relative risk (RR) with 95% CI. QALYs and incremental cost-effectiveness ratio (ICER) were calculated.Results A total of four retrospective cohort studies with 1796 participants were included. PCP risk was inversely associated with prophylaxis in NHL receiving R-CHOP21 (RR 0.17; 95% CI 0.04 to 0.67; p=0.01). Compared with no prophylaxis, PCP prophylaxis would incur an additional cost of US$527.61, and 0.57 QALYs gained, which yielded an ICER of US$929.25/QALY. DSA indicated that model results were most sensitive to the risk of PCP and preventive effectiveness. In PSA, the probability that prophylaxis was cost-effective at the WTP threshold was 100%.Conclusion Prophylaxis for PCP in NHL receiving R-CHOP21 is highly effective from retrospective studies, and routine chemoprophylaxis against PCP is overwhelmingly cost-effective from Chinese healthcare system perspective. Large sample size and prospective controlled studies are warranted.

Raphidiopsis raciborskii, which harms water supply and ecological security, may expand its range with climate warming. To explore the ecological management method of R. raciborskii blooms, the co-culture system of Eichhornia crassipes and R. raciborskii was established to study the inhibitory effect and inhibition mechanism of E. crassipes on R. raciborskii compared with the shaded culture of R. raciborskii alone. It was found that after co-cultured with E. crassipes (fresh weight, 5.10 ± 0.60 g·L−1) for seven days under initial high nutrient concentration, the algal cell density of co-culture groups with an initial cell density of 1.57 × 108 cells·L−1 and 1.57 × 109 cells·L−1 decreased by 63.19% and 14.87%, respectively. Meanwhile, the algal cell density in the co-culture group was significantly lower than that in the control group (p < 0.01). The algal cell density change showed that the growth of R. raciborskii was inhibited by co-cultured E. crassipes. In addition, E. crassipes could significantly reduce the nitrogen and phosphorus content in the water, but the growth state and photosynthesis of E. crassipes were not inhibited by R. raciborskii. These results suggested that E. crassipes has the potential to control R. raciborskii blooms. The study also found that when co-cultured, there was no significant difference in algal cell density between the groups supplemented with a certain amount of nutrients and the group without additional nutrients. Meanwhile, the inhibition rates of the co-culture groups were over 99% on day 4. These results showed that nutrient factors had no significant effect on the inhibitory effect of E. crassipes in the range of nutrients regulated by the experiment, and other factors played a leading role. In other words, under experimental conditions, nutrient competition was not the primary inhibitory mechanism of E. crassipes. This study also confirmed that E. crassipes had inhibitory allelopathy on R. raciborskii. The contribution and significance of allelopathy and other mechanisms could be studied in the future.

Analysis of heavy metals and their species in complex samples such as environment, biology and medicine is be of paramount importance due to their toxicity, persistence, and bioaccumulation. Considering the complexity of the sample matrix and the low concentration of heavy metals, sample preparation step should be exerted before analysis. Microextraction techniques have received extensive attention due to its miniaturization, quickness, low cost, environmental friendliness, and satisfactory extraction performance. So far, various formats based on microextraction techniques have been developed and applied to entrap heavy metals and related species. This review mainly concentrates on the recent development and applications of microextraction techniques including solvent-based liquid-phase microextraction and sorbent-based solid-phase microextraction for the detection and speciation of heavy metals in water, food, sediment, soil, hair, urine, and serum samples.

Air pollution forecasting plays a pivotal role in environmental governance, so a large number of scholars have devoted themselves to the study of air pollution forecasting models. Although numerous studies have focused on this field, they failed to consider fully the linear feature, non-linear feature, and fuzzy features contained in the original series. To fill this gap, a new combined system is built to consider features in the original series and accurately forecast PM2.5 concentration, which incorporates an efficient data decomposition strategy to extract the primary features of the PM2.5 concentration series and remove the noise component, and five forecasting models selected from three types of models to obtain the preliminary forecasting results, and a multi-objective optimization algorithm to combine the prediction results to produce the final prediction values. Empirical studies results indicated that in terms of RMSE the developed combined system achieves 0.652 6%, 0.810 1%, and 0.775 0% in three study cities, respectively. Compared to other prediction models, the RMSE improved by 60% on average in the study cities.

Helminth therapy or helminthic therapy is an experimental therapy in which people purposefully infect themselves with live parasites called helminth parasites. As helminths may affect a person's immune response, some people feel that helminthic therapy may one day help health practitioners cure some autoimmune and allergic illnesses.1 In United States, physicians cannot prescribe helminth therapy at this time. However, researchers on the other hand, can test specific varieties of worms on humans to see whether they can treat certain diseases. Helminths are a diverse group of worm-like parasites which includes flues, tapeworm, hookworm, whipworm and roundworm specifically.2 Helminths have developed over millions of years alongside their hosts, according to a 2018 report. As a result, they've mastered the art of suppressing and modifying the immunological response of their hosts. Partial immune suppression is caused by a parasite infection. Some modifications to the immune system, however, can benefit the host by lowering overall inflammation. Some scientists are interested in helminth treatment for this reason.3 A recent study found that the incidence of helminth infections has declined in high-income nations, where inflammatory and autoimmune disorders are most prevalent. However, helminth infections may assist to inhibit the development of some inflammatory diseases even if the cause-and-effect relationship is not established.1 Scientists are increasingly interested in using helminth treatment to treat several types of disorders such as inflammatory diseases, including Crohn's disease and ulcerative colitis, allergies, and parasitic infections.4 and also for respiratory diseases (asthma), skin diseases (multiple sclerosis, eczema). Some persons may benefit from the immunosuppressive effects of some helminths if they suffer from allergy illnesses or autoimmune diseases.5 The benefits of helminth infections on inflammatory diseases appear to be limited to those whose helminth infection preceded their inflammatory illness.6 Scientists examined animal data on the impact of helminths on inflammatory bowel illness, such as Crohn's disease and ulcerative colitis in a 2018, their outcomes were generally favorable, but it's unclear if they would have the same effect on humans. As a result, individuals who received the greatest dose of parasite eggs were somewhat more likely than those in the placebo group, whereas those who received the lowest amount of parasite eggs had lower chances of going into remission. Aside from that, laboratory testing revealed that the levels of inflammation in all of these groups were the same.4,5 Despite FDA approval, Helminth therapy is still an experimental treatment. Therefore, physicians in the United States are prohibited from prescribing the helminth treatment. Whether the helminth treatment is safe or not, it hasn't been studied long enough. However, helminth treatment still hasn't been mastered by medical science in a regulated and systematic method.1 In addition, there are several types of worms that have been awarded the designation “Investigational New Drug” by FDA, such as the pig whipworm and human hookworm. Researchers in the U.S. can now test the worms on people because of this designation.1,3 According to researchers, certain types of inflammation and autism spectrum disease have been correlated.7 As a result, some experts believe that helminth treatment might assist health practitioners to treat autism in the future. For a complete grasp of its potential advantages, scientists, on the other hand, advocate for additional research in this field.2

evil’s claw, a medicinal herb, derived its name from its hook-covered fruit appearance. The hook anchor animals to disperse its seeds. This plant has the scientific name Harpagophytum procumbens, which in Greek means “hook plant.” Some people utilize the plant's roots and tubers to treat a variety of ailments, such as rheumatoid arthritis, osteoarthritis and back discomfort. However, Devil's claw's efficacy for these purposes is currently unsupported by credible scientific data. Many active chemicals found in the plant's roots, which can be used as a herbal supplement. Iridoid glycosides, a chemical found in devil's claw, may have anti-inflammatory properties. Therefore, devil's claw supplements are being studied as a potential treatment for inflammatory diseases such as arthritis and gout.1 Scientists believe that the plant's anti-inflammatory and pain-relieving effects are the outcome of this animal study. Devil's claw is available in powder form, herbal tea, pills or concentrated extracts as a dietary supplement. In contrast to medicines, herbal and botanical products are not subject to the same level of scrutiny or quality control as pharmaceuticals.2 Since devil's claw is a natural substance, its efficacy and safety may vary depending on the product, and additional research is needed to determine its real efficacy and safety.1 It is believed that devil's claw, which contains iridoid glycosides like harpagoside, might be used to treat inflammation. Scientists have shown that harpagoside can reduce inflammation in animal and cell cultures.3 Some studies have shown that harpagoside has a substantial effect on cytokines. It is not known that how effective devil’s claw in humans but animal research proved it alternate therapy for inflammation.2,3 Devil's claw appear to decrease osteoarthritis related pain alone or in combination with nonsteroidal anti-inflammatory medications (NSAIDs).1 After 16 weeks of therapy, devil's claw may be as effective as a slow-acting osteoarthritis medication called diacerhein in relieving pain in the knees and hips. It has been shown that taking devil's claw by mouth tends to help relieve back discomfort. Devil's claw may be just as effective as some NSAIDs.4 While devil's claw has been touted for its efficacy, there is not enough data to assess how well it could function. Devil's claw's efficacy requires more research. Among them are: In flammatory conditions such as, gout, rheumatoid arthritis, fibromyalgia, menstrual cramps, indigestion, anxiety, migraine and tendinitis.5 Moreover, the possible side-effects of devil’s claw, need to be study further. We might get it as a very good player to address these disorders.1

BackgroundBreast cancer patients who achieve pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have favorable outcomes. Reliable predictors for pCR help to identify patients who will benefit most from NAC. The pretreatment serum albumin-to-alkaline phosphatase ratio (AAPR) has been shown to be a prognostic predictor in several malignancies, but its predictive value for pCR in breast cancer is still unknown. This study aims to investigate the predictive role of AAPR in breast cancer patients and develop an AAPR-based nomogram for pCR rate prediction.MethodsA total of 780 patients who received anthracycline and taxane-based NAC from January 2012 to March 2018 were retrospectively analyzed. Univariate and multivariate analyses were performed to assess the predictive value of AAPR and other clinicopathological factors. A nomogram was developed and calibrated based on multivariate logistic regression. A validation cohort of 234 patients was utilized to further validate the predictive performance of the model. The C-index, calibration plots and decision curve analysis (DCA) were used to evaluate the discrimination, calibration and clinical value of the model.ResultsPatients with a lower AAPR (

Abstract Background Increasing studies has found that circular RNAs (circRNAs) play vital roles in cancer progression. But the expression profile and function of circRNAs in triple-negative breast cancer (TNBC) are unclear. Methods We used a circRNA microarray to explore the circRNA expression profile of TNBC. The expression of the top upregulated circRNA, circKIF4A, was confirmed by qRT-PCR in breast cancer cell lines and tissues. Kaplan-Meier survival analysis was conducted to analyze the clinical impact of circKIF4A on TNBC. A series of experiments was performed to explore the functions of circKIF4A in TNBC progression, such as cell proliferation and migration. We investigated the regulatory effect of circKIF4A on miRNA and its target genes to explore the potential regulatory mechanisms of circKIF4A in TNBC. Results qRT-PCR analyses verified that circKIF4A was significantly upregulated and positively associated with poorer survival of TNBC. The inhibition of circKIF4A suppressed cell proliferation and migration in TNBC. Luciferase reporter assay and RNA immunoprecipitation assay revealed that circKIF4A and KIF4A could bind to miR-375 and that circKIF4A regulated the expression of KIF4A via sponging miR-375. Conclusions The circKIF4A-miR-375-KIF4A axis regulates TNBC progression via the competitive endogenous RNA (ceRNA) mechanism. circKIF4A may therefore serve as a prognostic biomarker and therapeutic target for TNBC.

Background: Numerous studies have showed that internal mammary lymph node (IMLN) metastasis is an important adverse prognostic factor in patients with breast cancer (BC), however, there are no available prediction model for the preoperative diagnosis of IMLN metastasis.Methods: Data from 102 breast cancer patients treated with IMLN operation were used to establish and calibrate a nomogram for IMLN status based on multivariate logistic regression. Prediction performance of this model was further validated with a second set of 50 patients with BC. Discrimination of the predict model was assessed by the C-index, and calibration assessed by calibration plots. Moreover, we conducted the decision curve analysis (DCA) to evaluate the clinical value of the nomogram. Finally, the survival status of patients in different risk groups based on nomogram were also compared.Results: The final multivariate regression model included tumor location, lymph vascular invasion (LVI), and pathological axillary lymph node stage (pALN stage). A nomogram was developed as a graphical representation of the model and had good calibration and discrimination in both sets (with C-index of 0.86 and 0.83 for the training and validation set, respectively). Moreover, the DCA showed the clinical usefulness of our constructed nomogram. False negative (FN) in low risk group classified by nomogram (FN-LR-nomogram) did not significantly impact adjuvant treatment decision making, and more importantly, patients with FN-LR-nomogram had recurrence-free survival equivalent to patients with pathologically ture negative in low risk group classified by nomogram (TN-LR-nomogram).Conclusions: As a non-invasive prediction tool, our nomogram shows favorable predictive accuracy for IMLN metastasis in patients with BC and can serve as a basis to integrate future molecular markers for its clinical application.

Enzymes with fructan exohydrolase (FEH) activity are present not only in fructan-synthesizing species but also in non-fructan plants. This has led to speculation about their functions in non-fructan species. Here, a cell wall invertase-related Zm-6&1-FEH2 with no “classical” invertase motif was identified in maize. Following heterologous expression in Pichia pastoris and in Nicotiana benthamiana leaves, the enzyme activity of recombinant Zm-6&1-FEH2 displays substrate specificity with respect to inulin and levan. Subcellular localization showed Zm-6&1-FEH2 exclusively localized in the apoplast, and its expression profile was strongly dependent on plant development and in response to drought and abscisic acid. Furthermore, formation of 1-kestotriose, an oligofructan, was detected in vivo and in vitro and could be hydrolyzed by Zm-6&1-FEH2. In summary, these results support that Zm-6&1-FEH2 enzyme from maize can degrade both inulin-type and levan-type fructans, and the implications of the co-existence of Zm-6&1-FEH2 and 1-kestotriose are discussed.

Abstract Backgroud The purpose of this study was to elucidate the regulation of programmed death ligand 1 (PDL1), lactate dehydrogenase A (LDHA) and miR-34a in triple negative breast cancer (TNBC) and to explore the function and mechanism of PDL1 and LDHA as competitive endogenous RNAs (ceRNAs) in TNBC via regulation of miR-34a. Methods Western blotting, quantitative RT-PCR (qRT-PCR) and immunohistochemistry (IHC) assays were conducted to explore the expression of PDL1, LDHA and miR-34a in TNBC and correlations between them. MTS cell viability, Transwell migration, glucose consumption and lactate production assays and flow cytometry were performed and mouse xenograft models were constructed to explore the functions and regulation of the PDL1 3’UTR and LDHA 3’UTR and miR-34a in TNBC. Results We found that PDL1 and LDHA were synchronously upregulated in TNBC cell lines and tissues. Co-expression of PDL1 and LDHA was correlated with poor outcome in TNBC. Both PDL1 and LDHA are targets of miR-34a, and the 3’UTRs of PDL1 and LDHA both have binding sites for miR-34a. The functions of PDL1 and LDHA were inhibited by miR-34a. In addition, PDL1 and LDHA acted as ceRNAs to promote the expression and function of each other through regulation of miR-34a in TNBC. Conclusions This study provides a new theoretical basis for a novel TNBC therapeutic strategy. Simultaneously targeting PDL1 and LDHA, which would combine immunotherapy and metabolically targeted treatments, might shed some light on the treatment of breast cancer, especially TNBC.

Abstract Background AHNAK, also known as desmoyokin, is a giant protein with the molecular size of approximately 700 kDa and exerts diverse functions in different types of cancer. Results In the present study, we demonstrated that AHNAK mRNA levels were down-regulated in 7 out of 8 human breast cancer cell lines, especially in triple - negative breast cancer (TNBC) cell lines. Moreover, in patients with TNBC, the expression of AHNAK gene was inversely correlated with the tumor status (P = 0.015), lymph node status (P

English medium instruction (EMI) has now become a ubiquitous education phenomenon due to the driving force of globalization and the prospective socioeconomic benefits associated with English proficiency. Although expanding rapidly in higher education, EMI in secondary education is a much less researched area. Specifically, EMI teachers' agency in the implementation of EMI has remained relatively less known. This study, informed by an extended framework on teacher agency, seeks to investigate how such agency has been manifested while the EMI teachers address various tensions and contradictions in the course of implementing EMI. Drawing on qualitative interviews and classroom observations in an international high school in Shenzhen, China, it reveals that the participants have exhibited moderately high levels of agency by constructing themselves as translanguagers who orchestrate different languages and meaning-making resources, jugglers of the roles of content teachers and L2 teachers, as well as duty-bond multicultural educators who negotiate the international curriculum to accommodate local educational and cultural mandates. The study calls for reconceptualizing EMI as a translanguaging space for the teachers to act as culturally responsive agents qua multilingual educators featuring multiple identities.

This study explored the expression, biological function and prognostic role of SOX2 in triple negative breast cancer (TNBC). Quantitative real-time PCR and immunohistochemistry were used to detect the expression of SOX2 in TNBC cell lines and clinical tissues. MTT assay, Transwell assay, flow cytometry and xenograft mouse model were used to assess the biological functions of SOX2. It was found that SOX2 was up-regulated in both TNBC cell lines and clinical tissues. High expression of SOX2 was associated with shorter overall survival and disease free survival. Moreover, inhibition of SOX2 suppressed cell proliferation and invasion, induced cell apoptosis in vitro, and suppressed tumorigenesis and metastasis in vivo. In addition, analysis of TNM stage and lymph nodes infiltration among the 237 TNBC patients by paired χ2 test showed that SOX2 was inversely correlated with tumor status, our findings provided evidence that SOX2 acts as a tumor promoter in TNBC and inhibition of SOX2 could be a potential therapeutic strategy for TNBC.

Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia respiratory failure, bilateral pulmonary infiltrates, and pulmonary edema of non-cardiac origin. Effective treatments for ARDS patients may arise from experimental studies with translational mouse models of this disease that aim to delineate the mechanisms underlying the disease pathogenesis. Mouse models of ARDS, however, can be limited by their rapid progression from injured to recovery state, which is in contrast to the course of ARDS in humans. Furthermore, current mouse models of ARDS do not recapitulate certain prominent aspects of the pathogenesis of ARDS in humans. In this study, we developed an improved endotoxemic mouse model of ARDS resembling many features of clinical ARDS including extended courses of injury and recovery as well as development of fibrosis following i.p. injection of lipopolysaccharide (LPS) to corn oil-preloaded mice. Compared with mice receiving LPS alone, those receiving corn oil and LPS exhibited extended course of lung injury and repair that occurred over a period of >2 weeks instead of 3-5days. Importantly, LPS challenge of corn oil-preloaded mice resulted in pulmonary fibrosis during the repair phase as often seen in ARDS patients. In summary, this simple novel mouse model of ARDS could represent a valuable experimental tool to elucidate mechanisms that regulate lung injury and repair in ARDS patients.

Glioblastoma multiforme (GBM), grade IV astrocytoma, is the most fatal malignant primary brain tumor. GBM contains functional subsets of cells called glioblastoma stem-like cells (GSCs), which are radioresistant and chemoresistant and eventually lead to tumor recurrence. Recent studies showed that GSCs reside in particular tumor niches that are necessary to support their behavior. To successfully eradicate GBM growth and recurrence, new strategies selectively targeting GSCs and/or their microenvironmental niche should be designed. In this regard, here we focus on elucidating the molecular mechanisms that govern these GSC properties and on understanding the mechanism of the microenvironmental signals within the tumor mass. Moreover, to overcome the blood–brain barrier, which represents a critical limitation of GBM treatments, a new drug delivery system should be developed. Nanoparticles can be easily modified by different methods to facilitate delivery efficiency of chemotherapeutics, to enhance the accumulation within the tumors, and to promote the capacity for targeting the GSCs. Therefore, nanotechnology has become the most promising approach to GSC-targeting therapy. Additionally, we discussed the future of nanotechnology-based targeted therapy and point out the disadvantages that should be overcome.

Invertases (INVs) play essential roles in plant growth in response to environmental cues. Previous work showed that plant invertases can be post-translationally regulated by small protein inhibitors (INVINHs). Here, this study characterizes a proteinaceous inhibitor of INVs in maize (Zm-INVINH4). A functional analysis of the recombinant Zm-INVINH4 protein revealed that it inhibited both cell wall and vacuolar invertase activities from maize leaves. A Zm-INVINH4::green fluorescent protein fusion experiment indicated that this protein localized in the apoplast. Transcript analysis showed that Zm-INVINH4 is specifically expressed in maize sink tissues, such as the base part of the leaves and young kernels. Moreover, drought stress perturbation significantly induced Zm-INVINH4 expression, which was accompanied with a decrease of cell wall invertase (CWI) activities and an increase of sucrose accumulation in both base parts of the leaves 2 to 7 days after pollinated kernels. In summary, the results support the hypothesis that INV-related sink growth in response to drought treatment is (partially) caused by a silencing of INV activity via drought-induced induction of Zm-INVINH4 protein.

Previous studies have indicated the prognostic value of various laboratory parameters in cancer patients. This study was to establish a prognostic index (PI) model for breast cancer patients based on the potential prognostic factors.A retrospective study of 1661 breast cancer patients who underwent surgical treatment between January 2002 and December 2008 at Sun Yat-sen University Cancer Center was conducted. Multivariate analysis (Cox regression model) was performed to determine the independent prognostic factors and a prognostic index (PI) model was devised based on these factors. Survival analyses were used to estimate the prognostic value of PI, and the discriminatory ability of PI was compared with Nottingham Prognostic Index (NPI) by evaluating the area under the receiver operating characteristics curves (AUC).The mean survival time of all participants was 123.6 months. The preoperative globulin >30.0g/L, triglyceride >1.10mmol/L and fibrinogen >2.83g/L were identified as risk factors for shorter cancer-specific survival. The novel prognostic index model was established and enrolled patients were classified as low- (1168 patients, 70.3%), moderate- (410 patients, 24.7%) and high-risk groups (83 patients, 5.0%), respectively. Compared with the low-risk group, higher risks of poor clinical outcome were indicated in the moderate-risk group [Hazard ratio (HR): 1.513, 95% confidence interval (CI): 1.169-1.959, p = 0.002] and high-risk group (HR: 2.481, 95%CI: 1.653-3.724, p< 0.001).The prognostic index based on three laboratory parameters was a novel and practicable prognostic tool. It may serve as complement to help predict postoperative survival in breast cancer patients.

Adult stem cell-based therapy is a promising novel approach for treatment of acute lung injury. Here we investigated the therapeutic potential of freshly isolated human umbilical cord blood CD34(+) progenitor cells (fCB-CD34(+) cells) in a mouse model of acute lung injury. At 3 h post-lipopolysaccharide (LPS) challenge, fCB-CD34(+) cells were transplanted i.v. to mice while CD34(-) cells or PBS were administered as controls in separate cohorts of mice. We observed that fCB-CD34(+) cell treatment inhibited lung vascular injury evident by decreased lung vascular permeability. In contrast, CD34(-) cells had no effects on lung vascular injury. Lung inflammation determined by myeloperoxidase activity, neutrophil sequestration and expression of pro-inflammatory mediators was attenuated in fCB-CD34(+) cell-treated mice at 26 h post-LPS challenge compared to PBS or CD34(-) cell-treated controls. Importantly, lung inflammation in fCB-CD34(+) cell-treated mice was returned to normal levels as seen in basal mice at 52 h post-LPS challenge whereas PBS or CD34(-) cell-treated control mice exhibited persistent lung inflammation. Accordingly, fCB-CD34(+) cell-treated mice exhibited a marked increase of survival rate. Employing in vivo 5-bromo-2'-deoxyuridine incorporation assay, we found a drastic induction of lung endothelial proliferation in fCB-CD34(+) cell-treated mice at 52 h post-LPS compared to PBS or CD34(-) cell-treated controls, which contributed to restoration of vascular integrity and thereby inhibition of lung inflammation. Taken together, these data have demonstrated the protective effects of fCB-CD34(+) cell on acute lung injury induced by LPS challenge, suggesting fCB-CD34(+) cells are an important source of stem cells for the treatment of acute lung injury.

Acute lung injury (ALI) is characterized by overwhelming lung inflammation and anti-inflammation treatment is proposed to be a therapeutic strategy for ALI. Poly (ADP-ribose) polymerase-1 has been demonstrated to be involved in tissue inflammation and one of its inhibitors, 3, 4-Dihydro-5[4-(1-piperindinyl)butoxy]-1(2H)-isoquinoline (DPQ), exerts anti-inflammatory effect. However, it is still unclear whether the DPQ possesses the protective effect on ALI and what mechanisms are involved. In this study, we tested the effect of DPQ on the lung inflammation induced by lipopolysaccharide (LPS) challenge in mice. We found that 6 h-LPS challenge induced significant lung inflammation and vascular leakage in mice. Treatment with DPQ at the dose of 10 μg/kg markedly reduced the neutrophil infiltration, myeloperoxidase activity and up-regulation of pro-inflammatory mediators and cytokines. LPS-elevated vascular permeability was decreased by DPQ treatment, accompanied by the inhibition of apoptotic cell death in mice lungs. In addition, we isolated mice peritoneal macrophages and showed pretreatment with DPQ at 10 μM inhibited the production of cytokines in the macrophages following LPS stimulation. DPQ treatment also inhibited the phosphorylation and degradation of IκB-α, subsequently blocked the activation of nuclear factor (NF)-κB induced by LPS in vivo and in vitro. Taken together, our results show that DPQ treatment inhibits NF-κB signaling in macrophages and protects mice against ALI induced by LPS, suggesting inhibition of Poly (ADP-ribose) polymerase-1 may be a potential and effective approach to resolve inflammation for the treatment of ALI.

Enhancing endothelial barrier integrity for the treatment of acute lung injury (ALI) is an emerging novel therapeutic strategy. Our previous studies have demonstrated the essential role of FoxM1 in mediating endothelial regeneration and barrier repair following lipopolysaccharide-induced lung injury. However, it remains unclear whether FoxM1 expression is sufficient to promote endothelial repair in experimental models of sepsis. Here, employing the FoxM1 transgenic (FoxM1 Tg) mice, we showed that transgenic expression of FoxM1 promoted rapid recovery of endothelial barrier function and survival in a clinically relevant model of sepsis induced by cecal ligation and puncture (CLP). We observed lung vascular permeability was rapidly recovered and returned to levels similar to baseline at 48 h post-CLP challenge in FoxM1 Tg mice whereas it remained markedly elevated in WT mice. Lung edema and inflammation were resolved only in FoxM1 Tg mice at 24 h post-CLP. 5-bromo-2-deoxyuridine incorporation assay revealed a drastic induction of endothelial proliferation in FoxM1 Tg lungs at 24h post-CLP, correlating with early induction of expression of FoxM1 target genes essential for cell cycle progression. Additionally, deletion of FoxM1 in endothelial cells, employing the mouse model with endothelial cell-restricted disruption of FoxM1 (FoxM1 CKO) resulted in impaired endothelial repair following CLP challenge. Together, these data suggest FoxM1 expression in endothelial cells is necessary and sufficient to mediate endothelial repair and thereby promote survival following sepsis challenge.

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide. The incidence rate and mortality rate of breast cancer continue to rise, which leads to a great burden on public health. Circular RNAs (circRNAs), a new class of noncoding RNAs (ncRNAs), have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression. In breast cancer, circRNAs have significant roles in tumorigenesis, recurrence and multidrug resistance that are mediated by various mechanisms. Therefore, circRNAs may serve as promising targets of therapeutic strategies for breast cancer management. This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis, treatment and prognosis evaluation, as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer. Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment. [ABSTRACT FROM AUTHOR]

The theory of cancer stem-like cell (or cancer stem cell, CSC) has been established to explain how tumor heterogeneity arises and contributes to tumor progression in diverse cancer types. CSCs are believed to drive tumor growth and elicit resistance to conventional therapeutics. Therefore, CSCs are becoming novel target in both medical researches and clinical studies. Emerging evidences showed that nanoparticles effectively inhibit many types of CSCs by targeting various specific markers (aldehyde dehydrogenases, CD44, CD90, and CD133) and signaling pathways (Notch, Hedgehog, and TGF-β), which are critically involved in CSC function and maintenance. In this review, we briefly summarize the current status of CSC research and review a number of state- of-the-art nanomedicine approaches targeting CSC. In addition, we discuss emerging therapeutic strategies using epigenetic drugs to eliminate CSCs and inhibit cancer cell reprogramming. [ABSTRACT FROM AUTHOR]

Background: The integrity of endothelial monolayer is a sine qua non for vascular homeostasis and maintenance of tissue-fluid balance. However, little is known about the signaling pathways regulating regeneration of the endothelial barrier after inflammatory vascular injury.Methods and Results: Using genetic and pharmacological approaches, we demonstrated that endothelial regeneration selectively requires activation of p110γPI3K signaling, which thereby mediates the expression of the endothelial reparative transcription factor Forkhead box M1 (FoxM1). We observed that FoxM1 induction in the pulmonary vasculature was inhibited in mice treated with a p110γ-selective inhibitor and in Pik3cg(-/-) mice after lipopolysaccharide challenge. Pik3cg(-/-) mice exhibited persistent lung inflammation induced by sepsis and sustained increase in vascular permeability. Restoration of expression of either p110γ or FoxM1 in pulmonary endothelial cells of Pik3cg(-/-) mice restored endothelial regeneration and normalized the defective vascular repair program. We also observed diminished expression of p110γ in pulmonary vascular endothelial cells of patients with acute respiratory distress syndrome, suggesting that impaired p110γ-FoxM1 vascular repair signaling pathway is a critical factor in persistent leaky lung microvessels and edema formation in the disease.Conclusions: We identify p110γ as the critical mediator of endothelial regeneration and vascular repair after sepsis-induced inflammatory injury. Thus, activation of p110γ-FoxM1 endothelial regeneration may represent a novel strategy for the treatment of inflammatory vascular diseases. [ABSTRACT FROM AUTHOR]

Monolith-based in-tube solid phase microextraction (MB/IT-SPME) has received wide attention because of miniaturization, automation, expected loading capacity, and environmental friendliness. However, the unsatisfactory extraction efficiency becomes the main disadvantage of MB/IT-SPME. To overcome this circumstance, magnetism-enhanced MB/IT-SPME (ME-MB/IT-SPME) was developed in the present work, taking advantage of magnetic microfluidic principles. First, modified Fe3O4 nanoparticles were mixed with polymerization solution and in situ polymerized in the capillary to obtain a magnetic monolith extraction phase. After that, the monolithic capillary column was placed inside a magnetic coil that allowed the exertion of a variable magnetic field. The effects of intensity of magnetic field, adsorption and desorption flow rate, volume of sample, and desorption solvent on the performance of ME-MB/IT-SPME were investigated in detail. The analysis of six steroid hormones in water samples by the combination of ME-MB/IT-SPME with high-performance liquid chromatography with diode array detection was selected as a paradigm for the practical evaluation of ME-MB/IT-SPME. The application of a controlled magnetic field resulted in an obvious increase of extraction efficiencies of the target analytes between 70% and 100%. The present work demonstrated that application of different magnetic forces in adsorption and desorption steps can effectively enhance extraction efficiency of MB/IT-SPME systems. [ABSTRACT FROM AUTHOR]

Excessive reactive oxygen/nitrogen species have been associated with the onset, progression, and outcome of sepsis, both in preclinical and clinical studies. However, the signaling pathways regulating oxidative/nitrative stress in the pathogenesis of sepsis-induced acute lung injury and acute respiratory distress syndrome are not fully understood. Employing the novel mouse model with genetic deletions of both caveolin-1 (Cav1) and adiponectin (ADPN) [double knockout (DKO) mice], we have demonstrated the critical role of Cav1 and ADPN signaling cross talk in regulating oxidative/nitrative stress and resulting inflammatory lung injury following LPS challenge. In contrast to the inhibited inflammatory lung injury in Cav1-/- mice, we observed severe lung inflammation and markedly increased lung vascular permeability in DKO mice in response to LPS challenge. Accordingly, the DKO mice exhibited an 80% mortality rate following a sublethal dose of LPS challenge. At basal state, loss of Cav1 and ADPN resulted in a drastic increase of oxidative stress and resultant nitrative stress in DKO lungs. Scavenging of superoxide by pretreating the DKO mice with MnTMPYP (a superoxide dismutase mimetic) restored the nflammatory responses to LPS challenge including reduced lung myeloperoxidase activity and vascular permeability. Thus oxidative/nitrative stress collectively modulated by Cav1 and ADPN signalings is a critical eterminant of inflammatory lung injury in response to LPS challenge. [ABSTRACT FROM AUTHOR]

In this study, a new cation-exchange coating for stir bar sorptive extraction (SBSE) based on poly (acrylic acid-ethylene dimethacrylate) monolithic material was synthesized. The effect of polymerization conditions such as the ratio of functional monomer to cross-linker and the content of porogenic solvent on the extraction efficiencies were investigated in detail. The monolithic material was characterized by elemental analysis, scanning electron microscopy and infrared spectroscopy. In order to evaluate the usability of the new coating for the extraction of inorganic cations, the analysis of soluble K+, Mg2+and Ca2+in milk by ion chromatography with conductivity detection was selected as a paradigm. Several extractive parameters, including pH value in sample matrix, desorption solvent, extraction and desorption time were optimized. Under the optimum conditions, low detection limits (S/N = 3) and quantification limits (S/N = 10) of the proposed method for the target cations were achieved within the range of 0.12–0.28 and 0.4–0.92 μg L−1, respectively. The method also showed good linearity, simplicity, practicality and low cost for the extraction of inorganic cations. Finally, the proposed method was successfully used to analyse three different trademarks of commercial milk samples with satisfactory recoveries in the range of 71.1% to 102.8%. [ABSTRACT FROM AUTHOR]

Despite the enormous successes of anti-PD-1/PD-L1 immunotherapy in multiple other cancer types, the overall response rates of breast cancer remain suboptimal. Therefore, exploring additional immune checkpoint molecules for potential cancer treatment is crucial. B7H3, a T-cell coinhibitory molecule, is specifically overexpressed in breast cancer compared with normal breast tissue and benign lesions, making it an attractive therapeutic target. However, the mechanism by which B7H3 contributes to the cancer phenotype is unclear. Here we show that the expression of B7H3 is negatively related to the number of CD8+ T cells in breast tumor sites. In addition, analysis of the differentially expressed B7H3 reveals that it is inversely correlated to autophagic flux both in breast cancer cell lines and clinical tumor tissues. Furthermore, block of autophagy by bafilomycin A1 (Baf A1) increases B7H3 levels and attenuates CD8+ T cell activation, while promotion of autophagy by V9302, a small-molecule inhibitor of glutamine metabolism, decreases B7H3 expression and enhances granzyme B (GzB) production of CD8+ T cells via regulation of reactive oxygen species (ROS) accumulation. We demonstrate that combined treatment with V9302 and anti-PD-1 monoclonal antibody (mAb) enhances antitumor immunity in syngeneic mouse models. Collectively, our findings unveil the beneficial effect of V9302 in boosting antitumor immune response in breast cancer and illustrate that anti-PD-1 together with V9302 treatment may provide synergistic effects in the treatment of patients insensitive to anti-PD-1 therapy. [ABSTRACT FROM AUTHOR]

In this work, a new stir cake sorptive extraction (SCSE) using polymeric ionic liquid monolith as sorbent was prepared. The sorbent was obtained by in situ copolymerization of an ionic liquid, 1-allyl-3-methylimidazolium bis[(trifluoro methyl)sulfonyl]imide (AMII) and divinylbenzene (DB) in the presence of N,N-dimethylformamide. The influence of the content of ionic liquid and the porogen in the polymerization mixture on extraction performance was studied thoroughly. The physicochemical properties of the polymeric ionic liquid were characterized by infrared spectroscopy, elemental analysis, scanning electron microscopy and mercury intrusion porosimetry. The usefulness of SCSE-AMIIDB was demonstrated by the enrichment of trace benzimidazole anthelmintics. Several parameters affecting the extraction efficiency were investigated, and under the optimized conditions, a simple and effective method for the determination of trace benzimidazoles residues in water, milk and honey samples was established by coupling SCSE-AMIIDB with high performance liquid chromatography/diode array detection (SCSE-AMIIDB-HPLC/DAD). Results indicated that the limits of detection (S/N = 3) for target compounds were 0.020-0.072 μg L-1, 0.035-0.10 μg L-1 and 0.026-0.076 μg L-1 in water, milk and honey samples, respectively. In addition, an acceptable reproducibility was achieved by evaluating the repeatability and intermediate precision with relative standard deviations (RSD) of less than 9% and 11%, respectively. Finally, the established AMII-SCSE-HPLC/DAD method was successfully applied for the determination of benzimidazoles residues in milk, honey and environmental water samples. Recoveries obtained for the determination of benzimidazole anthelmintics in spiking samples ranged from 70.2% to 117.6%, with RSD below 12% in all cases. [ABSTRACT FROM AUTHOR]