Silencing circ_0000644 inhibits papillary thyroid cancer cell malignancy by combining with miR-671-5p to release the inhibition on ANXA2.

BACKGROUND: Papillary thyroid cancer (PTC) is life-threatening due to its malignant progression. Considerable evidence demonstrates that circular RNA (circRNA) regulates PTC development. This study aims to explore the mechanism of circ_0000644 modulating PTC malignant progression. METHODS: The RNA levels of circ_0000644, microRNA-671-5p (miR-671-5p) and annexin A2 (ANXA2) were detected by quantitative real-time polymerase chain reaction. Western blot was performed to check protein expression. Cell proliferation and cell apoptosis were investigated by 5-ethynyl-29-deoxyuridine and flow cytometry. Angiogenic capacity, migration and invasion were analyzed by tube formation assay and transwell assay. The interaction between miR-671-5p and circ_0000644 or ANXA2 was identified by dual-luciferase reporter assay. Xenograft mouse model assay was performed to analyze the effect of circ_0000644 on tumor formation in vivo. RESULTS: Circ_0000644 and ANXA2 expression was significantly upregulated, while miR-671-5p was downregulated in PTC tissues and cells when compared with control groups. Circ_0000644 knockdown inhibited PTC cell proliferation, tube formation, migration, and invasion, but induced apoptosis in vitro. Moreover, circ_0000644 knockdown led to delayed tumorigenesis in vivo. In addition, circ_0000644 acted as a miR-671-5p sponge and mediated PTC cell tumor properties through miR-671-5p. ANXA2 was identified as a target gene of miR-671-5p, and its overexpression relieved miR-671-5p-induced effects in PTC cells. Furthermore, circ_0000644 depletion inhibited ANXA2 production by combining with miR-671-5p. CONCLUSION: Circ_0000644 depletion repressed PTC cell tumor properties through the miR-671-5p/ANXA2 axis.

ROS-responsive liposomes as an inhaled drug delivery nanoplatform for idiopathic pulmonary fibrosis treatment via Nrf2 signaling.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with pathophysiological characteristics of transforming growth factor-ß (TGF-ß), and reactive oxygen species (ROS)-induced excessive fibroblast-to-myofibroblast transition and extracellular matrix deposition. Macrophages are closely involved in the development of fibrosis. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a key molecule regulating ROS and TGF-ß expression. Therefore, Nrf2 signaling modulation might be a promising therapy for fibrosis. The inhalation-based drug delivery can reduce systemic side effects and improve therapeutic effects, and is currently receiving increasing attention, but direct inhaled drugs are easily cleared and difficult to exert their efficacy. Therefore, we aimed to design a ROS-responsive liposome for the Nrf2 agonist dimethyl fumarate (DMF) delivery in the fibrotic lung. Moreover, we explored its therapeutic effect on pulmonary fibrosis and macrophage activation. RESULTS: We synthesized DMF-loaded ROS-responsive DSPE-TK-PEG@DMF liposomes (DTP@DMF NPs). DTP@DMF NPs had suitable size and negative zeta potential and excellent capability to rapidly release DMF in a high-ROS environment. We found that macrophage accumulation and polarization were closely related to fibrosis development, while DTP@DMF NPs could attenuate macrophage activity and fibrosis in mice. RAW264.7 and NIH-3T3 cells coculture revealed that DTP@DMF NPs could promote Nrf2 and downstream heme oxygenase-1 (HO-1) expression and suppress TGF-ß and ROS production in macrophages, thereby reducing fibroblast-to-myofibroblast transition and collagen production by NIH-3T3 cells. In vivo experiments confirmed the above findings. Compared with direct DMF instillation, DTP@DMF NPs treatment presented enhanced antifibrotic effect. DTP@DMF NPs also had a prolonged residence time in the lung as well as excellent biocompatibility. CONCLUSIONS: DTP@DMF NPs can reduce macrophage-mediated fibroblast-to-myofibroblast transition and extracellular matrix deposition to attenuate lung fibrosis by upregulating Nrf2 signaling. This ROS-responsive liposome is clinically promising as an ideal delivery system for inhaled drug delivery.

The ratio of red blood cell distribution width to serum calcium predicts severity of patients with acute pancreatitis.

BACKGROUND: Illness severity of patients with acute pancreatitis (AP) at early stage is crucial because the identified moderate and severe cases need early intensive care to reduce the risk of serious complications such as multi-organ failure. Although red blood cell distribution width(RDW)and serum calcium(Ca)alone can be used as predictors of the severity of AP, they have low sensitivity and specificity. Thus, this study is aimed at evaluating the value of the ratio of RDW to serum calcium, which can all be acquired on admission, in predicting the severity of AP. METHODS: This study was based on a retrospective cohort study on patients with AP at the emergency department (ED) of West China Hospital Hospital from January 2016 to June 2016. We divided the patients with AP into two groups, mild acute pancreatitis (MAP) and moderate severe acute pancreatitis (MSAP) + severe acute pancreatitis (SAP). A receiver-operating characteristic (ROC) curve analysis was used to valuate the predictive value of the ratio of RDW to serum calcium for the severity of AP patients and the cut-off value for the ratio of RDW to serum calcium was calculated with sensitivity and specificity. P < 0.05 was considered statistically significant. RESULTS: A total of 666 AP patients were enrolled in this study. These patients were divided into MAP (n = 518) and MSAP+SAP (n = 148) groups. The AUC of RDW/ Ca was 0.912 (95% CI 0.887 to 0.937, P < 0.001), larger than the AUCs of RDW (AUC = 0.768, 95% CI 0.723 to 0.812, P < 0.001) and Ca (AUC = 0.875, 95% CI 0.844 to 0.906, P < 0.001). The optimal cut-off value for RDW/ Ca to predict MSAP and SAP was 7.04 (sensitivity = 0.885, specificity = 0.834). CONCLUSION: The RDW/Ca might be a valuable predictor of the severity of patients with AP.

Use of polysorbate 20 and sodium thiosulfate to enhance sewage sludge dewaterability by bioleaching.

Dewatering of sludge is a key problem that must be solved in the sewage sludge disposal industry. In this study, a series of process optimization tests were conducted to learn how to improve sludge treatment. The optimum process of sludge leaching treatment was studied in a specially designed 100-L reactor system. Four factors were investigated and nine batches of bioleaching tests were run at three levels of these factors. Orthogonal experiments showed that the effect of sludge return ratio and aeration rate on the sludge moisture content was significant and hydraulic retention time (HRT) had a clear effect, but nutrient types had a reduced effect on the moisture content of sludge. The primary and secondary order of each factor is reflux ratio > aeration rate > HRT > nutrient type. Under the optimal process, three batches of sludge were processed and the moisture content of the filter press cake was reduced to less than 60%, the organic matter content reduced to below 5%, and the concentration of heavy metals (Cu, Zn, Pb, and Cr) was much lower than the agricultural standard limit, which is suitable for landscaping, composting, and incineration power generation and other resource applications.

The Impact of Cysteine-Rich Intestinal Protein 1 (CRIP1) on Thyroid Carcinoma.

BACKGROUND/AIMS: CRIP1 (cysteine-rich intestinal protein 1) has been found in several tumor types; however, its prognostic impact and role in cellular processes, particularly in thyroid carcinoma, are still unclear. METHODS: To elucidate the prognostic impact of CRIP1, we analyzed tissues from 58 primary invasive thyroid carcinomas using immunohistochemistry. Western blotting was performed to investigate CRIP1 protein expression in the thyrocyte cell line Nthy-ori 3-1 and four different thyroid carcinoma cell lines, K1, TPC-1, TT, and SW579. Endogenous expression of CRIP1 was suppressed using a siRNA (si-CRIP1). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to investigate cell viability. Flow cytometric analysis was used to detect cell cycle progression and cell apoptosis. The effects of silencing CRIP1 on cell migration and invasion were detected using the transwell assay. RESULTS: The immunohistochemistry results showed that CRIP1 was overexpressed in thyroid carcinoma. CRIP1 expression was associated with tumor size, TNM stage, and lymphatic metastasis, but not with age, gender, and tumor location. In addition, the expression of CRIP1 in K1, TPC-1, TT, and SW529 cells was higher than that in the Nthy-ori 3-1 cells. The highest expression was observed in the SW579 and TT cells. Furthermore, silencing CRIP1 inhibited the proliferation, migration, and invasion of thyroid carcinoma cell lines SW579 and TT. We also found that silencing CRIP1 induced G1 arrest and apoptosis of thyroid carcinoma cell lines SW579 and TT. CONCLUSION: In conclusion, CRIP1 acts as an oncogene in the cell proliferation, migration, and invasion processes of thyroid carcinoma. CRIP1 may serve well as an independent prognostic marker with significant predictive power for use in thyroid carcinoma therapy.

Occurrence, distribution and potential environmental risks of pollutants in aquaculture ponds during pond cleaning in Taihu Lake Basin, China.

During the process of cleaning aquaculture ponds, the drainage contributes significantly to antibiotic pollution in the surrounding water environment. Therefore, we conducted a study on the distribution of 26 antibiotics in 57 ponds within the Taihu Lake basin. The results revealed that the detection frequency of antibiotics ranged from 1.75 % to 80.7 %, with the overall detection concentrations ranging from 3.27 to 708.72 ng/L. Among them, the detection rate of 8 antibiotics exceeded 50 %. Regarding the spatial distribution, the concentration of antibiotics was relatively high in aquaculture ponds located in the Changzhou area, with the highest concentration reaching 708.72 ng/L. This observation is likely due to the large size and intensive breeding practices in Changzhou. Fish ponds exhibited a significantly higher total antibiotic concentration of 3.27 to 445.57 ng/L compared to crab ponds (13.01 to 206.30 ng/L) and shrimp ponds (23.17 to 107.40 ng/L). Quinolones and sulfonamides were the predominant antibiotic classes found in fish ponds, accounting for 51.49 % of the total antibiotic concentration. Notably, sulfamethoxazole (SMX) and enrofloxacin (ENR) exhibited the highest antibiotic concentrations. Risk assessments demonstrated that SMX, ENR, and ofloxacin (OFX) contributed significantly to ecological risks. Furthermore, the study found that the tertiary constructed wetland treatment process achieved a remarkable removal rate of 92.44 % for antibiotics in aquaculture wastewater, while other treatment processes displayed limited effectiveness in removing antibiotics. This study addresses the knowledge gap concerning antibiotic pollution during the cleaning process of aquaculture ponds within the Taihu Lake basin.

A novel combined therapeutic strategy of Nano-EN-IR@Lip mediated photothermal therapy and stem cell inhibition for gastric cancer.

Recurrence and metastasis of gastric cancer is a major therapeutic challenge for treatment. The presence of cancer stem cells (CSCs) is a major obstacle to the success of current cancer therapy, often leading to treatment resistance and tumor recurrence and metastasis. Therefore, it is important to develop effective strategies to eradicate CSCs. In this study, we developed a combined therapeutic strategy of photothermal therapy (PTT) and gastric cancer stem cells (GCSCs) inhibition by successfully synthesizing nanoliposomes loaded with IR780 (photosensitizer) and EN4 (c-Myc inhibitor). The nanocomposites are biocompatible and exhibit superior photoacoustic (PA) imaging properties. Under laser irradiation, IR780-mediated PTT effectively and rapidly killed tumor cells, while EN4 synergistically inhibited the self-renewal and stemness of GCSCs by suppressing the expression and activity of the pluripotent transcription factor c-Myc, preventing the tumor progression of gastric cancer. This Nano-EN-IR@Lip is expected to be a novel clinical nanomedicine for the integration of gastric cancer diagnosis, treatment and prevention.

The association between lipoprotein(a) and atrial fibrillation: A systemic review and meta-analysis.

Lipoprotein(a) (Lp[a]) is a particle consisting of a low-density lipoprotein (LDL)-like core connected to an apolipoprotein(a) chain, which is an established risk factor for cardiovascular disease. However, studies addressing the relationship between atrial fibrillation (AF) and Lp(a) demonstrated conflicted results. Thus, we sought to evaluate this relationship by conducting this systemic review and meta-analysis. We performed a comprehensive systematic search of health science databases, including PubMed, Embase, Cochrane Library, Web of Science, MEDLINE, and ScienceDirect, to identify all relevant literature from their inception to March 1, 2023. We identified nine related articles, which were eventually included in this study. Our study showed no association between Lp(a) with new-onset AF (HR = 1.45, 95% confidence interval [CI]: 0.57-3.67, p = .432). In addition, genetically elevated Lp(a) was not associated with the risk of atrial fibrillation (OR = 1.00, 95% CI: 1.00-1.00, p = .461). Different stratification of Lp(a) levels may have different outcomes. Also, higher Lp(a) levels may be inversely associated with the risk of developing AF compared to those with lower levels. Lp(a) levels were not associated with incident AF. Further research is needed to identify the mechanism underlying these results and better understand Lp(a) stratification for AF and the possible inverse association between Lp(a) and AF.

Engineered Biomimetic Copper Sulfide Nanozyme Mediates "Don't Eat Me" Signaling for Photothermal and Chemodynamic Precision Therapies of Breast Cancer.

The rapid development of nanomedicine has brought hope and confidence to the precise treatment of tumors. However, the efficacy of nanoparticle-mediated therapy is severely limited due to phagocytosis and clearance by macrophages. CD47 is a well-documented ″don't eat me″ signaling molecule that binds to the SIRPα receptor on the macrophage surface, inhibiting the phagocytic behavior of the macrophages. In this study, CD47-overexpressing cancer cell membranes were used to coat hollow copper sulfide nanoparticles. The nanoparticles were shown to have an extended circulatory half-life and to actively target breast cancer, leading to increased accumulation in the tumor tissue. An excellent photothermal therapeutic effect was produced by near-infrared laser irradiation. At the same time, ß-lapachone within the nanoparticles generated large amounts of hydrogen peroxide in the tumor environment, which was then catalyzed by the copper sulfide nanozyme to cytotoxic hydroxyl radicals, exerting a chemodynamic therapeutic effect. This engineered biomimetic nanozyme, through the mediation of the ″don't eat me″ signal, achieved both photothermal and chemodynamic precision treatments of breast cancer, creating a new mode of safe and effective tumor treatment.

Development and Validation of a Novel Prognostic Score Based on Thrombotic and Inflammatory Biomarkers for Predicting 28-Day Adverse Outcomes in Patients with Acute Pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a multifactorial disease that is associated with substantial morbidity and mortality. Thrombosis and inflammation are involved in the development and progression of AP. AIM: To develop and validate a novel and simple scoring system for predicting 28-day adverse outcomes in AP patients based on a thrombotic and an inflammatory biomarker. METHODS: A single-center, retrospective cohort study was used to establish the new scoring system (thrombo-inflammatory prognostic score; TIPS), and another study was used to verify it. The study end points were 28-day mortality, requirement for mechanical ventilation (MV), persistent organ failure (POF), and admission to the intensive care unit (AICU). Receiver operating characteristic (ROC) curves was drawn to validate the predictive value of the TIPS. The performance of the TIPS was compared with that of conventional predictive scoring systems. Logistic regression models were used to investigate the relationship between the TIPS and the different end points. RESULTS: Among 440 patients with AP in the derivation group, 27 patients died within the 28-day follow-up period. Prothrombin time (PT) and interleukin-6 (IL-6) were used to calculate the TIPS. The TIPS (AUC=0.843) showed a performance comparable to that of the more established APACHE II (AUC=0.841), SOFA (AUC=0.797), BISAP (AUC=0.762), and Balthazar CT (AUC=0.655) in predicting 28-day mortality in AP. The 28-day mortality and the incidence of MV, POF, and AICU were significantly higher among patients with a higher TIPS (P<0.001). The results of logistic regression analyses indicated that the TIPS was independently associated with the risks of 28-day mortality, AICU, MV and POF. CONCLUSION: The TIPS can enable prediction of 28-day adverse clinical outcomes with AP patients in the ED.

Water quality assessment and source identification of the Shuangji River (China) using multivariate statistical methods.

Multivariate statistical techniques, including cluster analysis (CA), discriminant analysis (DA), principal component analysis (PCA) and factor analysis (FA), were used to evaluate temporal and spatial variations in and to interpret large and complex water quality datasets collected from the Shuangji River Basin. The datasets, which contained 19 parameters, were generated during the 2 year (2018-2020) monitoring programme at 14 different sites (3192 observations) along the river. Hierarchical CA was used to divide the twelve months into three periods and the fourteen sampling sites into three groups. Discriminant analysis identified four parameters (CODMn, Cu, As, Se) loading more than 68% correct assignations in temporal analysis, while seven parameters (COD, TP, CODMn, F, LAS, Cu and Cd) to load 93% correct assignations in spatial analysis. The FA/PCA identified six factors that were responsible for explaining the data structure of 68% of the total variance of the dataset, allowing grouping of selected parameters based on common characteristics and assessing the incidence of overall change in each group. This study proposes the necessity and practicality of multivariate statistical techniques for evaluating and interpreting large and complex data sets, with a view to obtaining better information about water quality and the design of monitoring networks to effectively manage water resources.

Efficiency of red cell distribution width in predicting severity and mortality of patients with acute pancreatitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Previous studies have showed that red cell distribution width (RDW) may be an inflammatory status, and it may be used to predict prognosis of acute pancreatitis (AP). However, there are no systematic reviews for the evidence, and the association between RDW and AP is still not completely understood. Therefore, we will undertake a systematic review of the literature to summarize previous evidence regarding this topic, in order to clarify the value of RDW predicting prognosis of patients with AP. METHODS: We will search EMBASE, Web of Knowledge, PubMed, ClinicalTrials.gov and Cochrane Library from their inception to Mar 2021 to retrieve relevant studies. Two authors independently judged study eligibility and extracted data. Heterogeneity will be examined by computing the Q statistic and I2 statistic. RESULTS: This study proved the Efficiency of RDW in predicting mortality and severity of patients with AP. And provided easy method for clinical evaluation for AP patients. CONCLUSIONS: The findings of this systematic review will show the value of RDW predicting prognosis of patients with AP. ETHICS AND DISSEMINATION: Ethical approval is unnecessary as this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference.

Preparation of a New Iron-Carbon-Loaded Constructed Wetland Substrate and Enhanced Phosphorus Removal Performance.

Iron-carbon substrates have attracted extensive attention in water treatment due to their excellent processing ability. The traditional iron-carbon substrate suffers from poor removal effects, separation of the cathode and anode, hardening, secondary pollution, etc. In this study, a new type of iron-carbon-loaded substrate (NICLS) was developed to solve the problems of traditional micro-electrolytic substrates. Through experimental research, a preparation method for the NICLS with Fe and C as the core, zeolite as the skeleton, and water-based polyurethane as the binder was proposed. The performance of the NICLS in phosphorus-containing wastewater was analyzed. The results are as follows: The optimal synthesis conditions of the NICLS are 1 g hydroxycellulose, wood activated carbon as the cathode, an activated carbon particle size of 200-60 mesh, and an Fe/C ratio of 1:1. Acidic conditions can promote the degradation of phosphorus by the NICLS. Through the characterization of the NICLS (scanning electron microscope (SEM), X-ray diffractometer (XRD), and energy-dispersive spectrometer (EDS), etc.), it is concluded that the mechanism of the NICLS phosphorus removal is a chemical reaction produced by micro-electrolysis. Using the NICLS to treat phosphorus-containing wastewater has the advantages of high efficiency and durability. Therefore, it can be considered that the NICLS is a promising material to remove phosphorus.

Serum ammonia levels on admission for predicting sepsis patient mortality at D28 in the emergency department: A 2-center retrospective study.

We assessed the predictive value of serum ammonia level on admission for the 28-day mortality of patients with sepsis.We retrospectively included septic patients admitted to the emergency department of West China Hospital, Sichuan University and The Fourth People's Hospital of Zigong city from June 2017 to May 2018. Patients were divided into 2 groups according to 28-day survival. Comparisons of serum ammonia level and sequential organ failure assessment (SOFA) score were made between 2 groups. Multivariate logistic regression models were employed to determine independent risk factors affecting 28-day mortality rate, and receiver operating characteristic (ROC) curve was also used to evaluate the efficacy of risk factors.Total of 316 patients were included into the study, 221 survived to 28 days and 95 were died before 28 days. The 28-day mortality rate was 30.06%. Multivariate logistic regression analyses revealed that the ammonia level, C reactive protein, SOFA score, and the leukocyte were independent risk factors for the 28-day mortality rate. In predicting the 28-day mortality rate, the SOFA score presented an area under the ROC curve (AUC) of 0.815, and the ammonia levels presented the AUC of 0.813.The ammonia level, C reactive protein, SOFA score, and the leukocyte are independent risk factors for 28-day mortality rate in septic patients. Moreover, the serum ammonia and SOFA score have similar predictive values. The serum ammonia level is also a suitable early indicator for prognostic evaluation of patients with sepsis as well.

The effects of thoracic cage dimension and chest subcutaneous adipose tissue on outcomes of adults with in-hospital cardiac arrest: A retrospective study.

BACKGROUND: The associations between thoracic cage dimension, chest subcutaneous adipose tissue (SAT) depth and outcomes of adults with in-hospital cardiac arrest (IHCA) remain unknown. METHODS: We retrospectively evaluated IHCA patients between January 2016 and October 2017. The thoracic cage transverse diameter, internal AP diameter, cross-sectional area, anterior and posterior SAT depths were measured in computed-tomography (CT) images. Using logistic regression models, we determined the adjusted associations between thoracic cage dimension, SAT depths and the prognosis for IHCA. The primary outcome was sustained return of spontaneous circulation (ROSC) and the secondary outcome was survival to hospital discharge. RESULTS: Among 423 IHCA patients, 258 patients achieved ROSC and 70 survived to discharge. Smaller cross-sectional area and posterior SAT depth were significantly related to ROSC. Smaller posterior SAT depth was associated with ROSC. After multivariate adjustment, the smaller cross-sectional area was independently associated with ROSC (Odds ratio [OR] 0.99, 95% confidence interval [95%CI] 0.99-1.00; p = 0.008) and survival to discharge (OR 0.99, 95%CI 0.98-1.00; p = 0.024), and the smaller posterior SAT depth was independently related to ROSC (OR 0.65, 95%CI 0.44-0.96; p = 0.030), whereas no relation to survival to discharge was found. CONCLUSIONS: In adults with IHCA, the smaller thoracic cage dimension and posterior SAT depth are associated with better survival. An adjustable compression depth based on the thoracic cage dimension might be better than the "one-size-fits-all" compression depth for resuscitating CA patients. In addition, physicians should pay extra attention to compression efficacy when resuscitating obese patients.