CCN1 inhibition affects the function of endothelial progenitor cells under high-glucose condition.

BACKGROUND: The impact of cysteine-rich angiogenic inducer 61 (Cyr61, also called CCN1) on endothelial progenitor cells (EPCs) from diabetic-rat-derived whole peripheral and bone marrow remains poorly understood. Therefore, the expression levels of CCN1, CCN1-induced C-X-C chemokine receptor type 4 (CXCR4), and stromal-cell-derived factor-1 (SDF-1) were explored under high glucose (HG) conditions. OBJECTIVES: The aim of the study was to explore the effects of high CCN1 levels on EPC activity in diabetic rats through mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway modulation. MATERIAL AND METHODS: Primary EPCs were isolated from bone marrow and whole peripheral blood of streptozocin (STZ)-induced diabetic Sprague-Dawley rats and controls. Cell migration, tube formation ability and viability were determined using transwell, Cell Counting Kit-8 (CCK-8), and Matrigel®-based capillary-like tube formation assays. Protein and gene expression levels were measured by western blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The study findings showed that EPC migration, viability and tube formation ability were significantly lower under HG conditions. High CCN1 expression levels restored EPC function by inducing SDF-1 and CXCR4 in EPCs under HG conditions. Furthermore, HG suppressed MEK/ERK phosphorylation, while an ERK1/2 agonist rescued EPC CCN1-SDF-1/CXCR4 expression under HG conditions through the activation of the MEK/ERK pathway. CONCLUSIONS: This study demonstrates that high CCN1 expression levels restored EPC functions, partly by modulating MEK/ERK signaling. These findings provide a basis for developing novel therapeutic methods for diabetic vascular neogenesis and vascular injury repair.

Repeated pulmonary nodules as the primary symptom of familial hemophagocytic lymphohistiocytosis in adults: a case report and review.

Pulmonary nodules are usually considered to be associated with malignant tumors and benign lesions, such as granuloma, pulmonary lymph nodes, fibrosis, and inflammatory lesions. Clinical cases of pulmonary nodules associated with hemophagocytic lymphohistiocytosis have rarely been reported. Therefore, when patients develop pulmonary nodules, the possibility of developing hemophagocytic lymphohistiocytosis is often not considered. We report the first case of familial hemophagocytic lymphohistiocytosis with recurrent pulmonary nodules as the first symptom. Our findings will hopefully provide new ideas for the diagnosis and treatment of pulmonary nodules in the future.

Exploration and Validation of Potential Biomarkers and Therapeutic Targets in Ferroptosis of Asthma.

Purpose: Asthma is a chronic inflammatory airway disease involving multiple mechanisms, of which ferroptosis is a form of programmed cell death. Recent studies have shown that ferroptosis may play a crucial role in the pathogenesis of asthma, but no specific ferroptosis gene has been found in asthma, and the exact mechanism is still unclear. The present study aimed to screen ferroptosis genes associated with asthma and find therapeutic targets, in order to contribute a new clue for the diagnosis and therapy of asthma. Methods: Ferroptosis-related differentially expressed genes (FR-DEGs) in asthma were selected by the GSE41861, GSE43696 and ferroptosis datasets. Next, the FR-DEGs were subjected by GO and KEGG enrichment, and the mRNA-miRNA network was constructed. Then, GSEA and GSVA enrichment analysis and Immune infiltration analysis were performed, followed by targeted drug prediction. Finally, the expression of FR-DEGs was confirmed using GSE63142 dataset and RT-PCR assay. Results: We found 13 FR-DEGs by the GSE41861, GSE43696 and ferroptosis database. Functional enrichment analysis revealed that the 13 FR-DEGs were enriched in oxidative stress, immune response, ferroptosis, lysosome, necrosis, apoptosis etc. Moreover, our results revealed the mRNA-miRNA network of the FR-DEGs and identified candidate drugs. Also, immune infiltration revealed that ELAVL1, CREB5, CBR1 and NR1D2 are associated with the immune cells and may be potential targets in asthma. Finally, 10 FR-DEGs were validated by the GSE63142 database. It was verified that 7 FR-DEGs were differentially expressed by collecting asthma patients and healthy controls. Conclusion: This study ultimately identified 7 FR-DEGs for the diagnosis and therapy of asthma. These 7 FR-DEGs contribute to oxidative stress and immune responses. This study provides potential therapeutic targets and biomarkers for asthma patients, shedding further light on the pathogenesis of asthma as well as providing new insights into the treatment of asthma.

Predictors of COVID-19 Severity in Elderly Patients Infected by Omicron in China, 18 December 2022-5 February 2023.

Purpose: To analyze the clinical characteristics and prognosis of patients hospitalized with non-severe, severe pneumonia and death in Omicron COVID-19. Patients and Methods: We collected clinical data from 118 patients with COVID-19 in China from 18 December, 2022 and 5 February, 2023. According to the outcome, the patients were divided into non-severe group, severe group and death group. Subsequently, we statistically analyzed the general condition, clinical manifestations, laboratory parameters, NLR, MLR, PLR and HALP of these groups. We also retrospectively analyzed the possible factors affecting the prognostic regression of patients with COVID-19. Results: A total of 118 COVID-19 patients were enrolled in this study, including 64 non-severe patients, 38 severe patients and 16 death patients. Compared with the non-severe group, T lymphocytes, B lymphocytes, Th1, Th2, Th17, Treg cells, IgA, IgG, IgM in the severe and death groups decreased more significantly (P<0.05). The levels of myocardial markers, ALT, AST, BUN, Cr, D-dimer, fibrinogen, NLR, MLR and PLR in the severe and death groups were significantly higher than those in the non-severe group (P<0.05). The level of HALP was significantly lower than that of non-severe group (P<0.05). MLR is not only an independent risk factor for the transition from non-severe to severe disease, but also an independent risk factor for predicting the possibility of death in COVID-19 patients. Conclusion: The analysis of COVID-19 patients in China showed that severe patients were older, more likely to have related complications, lower lymphocyte count, liver and kidney function disorder, glucose and lipid metabolism disorders, myocardial injury, and abnormal coagulation function, suggesting the need for early anticoagulant therapy. In addition, NLR, MLR, PLR and HALP can be used as biomarkers to evaluate the severity and prognosis of COVID-19 patients.

Roles of catalytic ozonation by bimetallic Fe/Ce loading sludge-derived biochar in amelioration of sludge dewaterability: Performance and implementation mechanisms.

In this study, an environmentally friendly alternative was developed using catalytic ozonation by sludge-derived biochar loaded with bimetallic Fe/Ce (O3/SBC-FeCe) for enhanced sludge dewatering. The results indicated that the lowest capillary suction time (CST) of 20.9 s and water content of dewatered sludge cake (Wc) of 64.09% were achieved under the dosage of 40 mg O3/g dry solids (DS) and 0.4 g SBC-FeCe/g DS which were considered as the optimum condition. In view of excellent electron exchanging capacity of SBC-FeCe with rich Lewis acid sites and conversions of valence sates of Fe and Ce, more O3 were decomposed into reactive oxygen species under the catalytic action of SBC-FeCe, which strengthened oxidizing capacity. Enhanced oxidation rendered sludge cells inactivation and compact network structure rupture releasing intracellular water and organic substances. Subsequently, hydrophilic organic matters were attacked and eliminated lessening sludge viscosity and colloidal forces and intensifying hydrophobicity and flowability. In addition, changes of sludge morphology suggested that sludge roughness was alleviated, structural strength and compressibility were raised and porous and retiform structure was constructed providing channels for water outflow by adding skeleton builder of SBC-FeCe. Overall, the synergistic interaction of strengthened oxidation and skeleton construction improved sludge dewaterability.

A novel conditioning approach for amelioration of sludge dewaterability using activated carbon strengthening electrochemical oxidation and realized mechanism.

Sludge dewatering is an essential process for reduction of sludge volume to decrease cost of ultimate disposal. In this study, a novel method using activated carbon (AC) strengthening electrochemical (EC) treatment (EC/AC) was adopted to improve greatly sludge dewaterability. It was shown that capillary suction time (CST) and water content of dewatered sludge cake (Wc) were reduced to 55.9 ± 1.24 s and 64.3 ± 1.23%, respectively, under the optimal conditions of EC voltage 20 V, EC time 30 min and 0.2 g/g dry solid (DS) AC. AC with rich functional groups as "the third electrode" intensified electrooxidation by forming multiple microelectrodes and electron transfer capacity and conductivity of sludge were strengthened by AC in EC system, which were illustrated by electrochemical analysis. It could be found that zeta potential and particle size were increased and surface roughness was reduced after EC/AC treatment intensifying sludge hydrophobicity. Form the results of rheological behaviors of sludge, flowability was strengthened and viscosity was weakened under the conditioning of EC/AC. Besides, colloidal force and gel-like network strength were lessened, which was also verified by organic matters and percentage of inviable cells. At the same time, intracellular matters were released and degraded and bound water was released converting into free water. In addition, sludge compressibility and structural strength were increased and porous structure was formed facilitating water outflow via addition of mesoporous AC as skeleton builder, which eventually led to an improved separation efficiency of solid-water and sludge dewaterability. The results of heavy metals suggested that sludge cake after EC/AC treatment was favorable for land application.

Polyhexamethylene biguanidine used as a new type sewage sludge conditioning agent: Effect on sludge dewaterability and mechanism.

Dewatering is the basic procedure of sludge treatment and disposal, and environmentally friendly and efficient sludge conditioning methods are urgently needed. Polyhexamethylene biguanide (PHMB), a broad-spectrum germicide used in daily life and medicine, was proposed as a sludge conditioning reagent in this paper, and its effect on waste activated sludge (WAS) dewaterability was studied for the first time. Results showed that PHMB can improve sludge dewatering performance, and capillary suction time (CST) and water content (Wc) of dewatered sludge cake was reduced by 78.11% and 13.37% with 100 mg PHMB/g dry sludge (DS). Further investigation revealed that the sludge properties changed pronouncedly after PHMB conditioning, the bound water content decreased from 1.58 g/g DS to 1.29 g/g DS, the particle size (D50) increased from 34.3 µm to 39.2 µm, the zeta potential increased from -20.96 mV to -3.36 mV, and the flowability increased whilst the viscosity decreased. When the dose of PHMB was lower than 50 mg/g DS, it mainly reacted with extracellular polymeric substance (EPS), resulting in a decrease in its content, which was also manifested by the decrease of molecular weights. However, when the dose reached 100 mg/g DS, PHMB would disrupt the cytomembranes of microorganisms and release cellular contents, reflected by a corresponding growth of EPS contents and the intensity of Fourier transform infrared (FTIR) spectrum. And the scanning electron microscope (SEM) images showed that PHMB conditioning made cracks and holes on sludge microstructures. The key mechanism of PHMB improving sludge dewaterability was inferred as "organic molecules disrupting" and "sludge particles flocculating". These findings demonstrate that PHMB is promising to be a novel, effective, and environmentally friendly sludge conditioning reagent.

A comprehensive study on simultaneous enhancement of sludge dewaterability and elimination of polycyclic aromatic hydrocarbons by Fe2+ catalyzing O3 process.

Simultaneous removal of polycyclic aromatic hydrocarbons (PAHs) in the process of enhancement of sludge dewaterability via oxidation of hydroxyl radicals (•OH) and flocculation of Fe3+ by Fe2+-catalyzing O3 were investigated as a novel research focus. The results showed that capillary suction time (CST) and water content of dewatered sludge cake (Wc) were reduced from 57.9 s and 85.1% to 13.6 s and 69.65% under the optimum usage of 60 mg/g dry solids (DS) O3 and 80 mg/g DS FeSO4, respectively. The relevant dewatering mechanism of Fe2+-catalyzing O3 treatment was elucidated. It was found that extracellular polymeric substances-bound (EPS-bound) and intracellular water was dramatically released through destroying sludge cells and EPS gel-like structure by produced •OH. In addition, the results of X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) and 13C NMR spectroscopy revealed that •OH oxidized and mineralized hydrophilic organic matters intensifying hydrophobicity of sludge surface. Moreover, Fe3+ generated by oxidation of Fe2+ agglomerated fragmented fine particles into large aggregates and decreased exposure of hydrophilic sites by neutralizing negative charge, which promoted water-solids separation. Meanwhile, sludge surface roughness was decreased which was determined by material type upright confocal laser microscope (CLM). As a consequence, •OH and Fe3+ were mainly responsible for enhancement of sludge dewaterability. Moreover, more than 40% of removal rate of PAHs was accomplished by Fe2+-catalyzed O3 treatment mitigating the environmental risks of PAHs spread.

Enhanced waste activated sludge dewaterability by the ozone-peroxymonosulfate oxidation process: Performance, sludge characteristics, and implication.

Dewatering treatment is an essential step to diminish sludge volume, cut down transportation costs, and improve subsequent disposal efficiency. In this study, ozone-peroxymonosulfate (O3/PMS) oxidation process was employed to ameliorate sludge dewaterability. Sludge capillary suction time (CST) and water content (Wc) of dewatered sludge cake could reduce from 70.5 s and 81.93% to 26.7 s and 65.65%, respectively, under the optimal dosage of 30 mg/g TS O3 and 0.4 mmol/g TS PMS. The increased sludge zeta potential, particle size, and fluidity promoted sludge dewatering performance apparently. The decreased hydrophilic, fluorescent EPS components and proteins/peptides-like + Lipids percentage in EPS as well as the ratio of α-helix/(ß-sheet + random coil) of treated EPS protein secondary structure was greatly responsible for the enhanced sludge dewaterability. SO4- and OH were detected in ozone-peroxymonosulfate process to crack sludge flocs, eliminate hydrophilic substances and liberate bound water. Moreover, the concentrations of both heavy metals and polycyclic aromatic hydrocarbons (PAHs) of sludge after O3/PMS conditioning were decreased, and the stability and toxicity of heavy metals were also reduced, except Zn. In conclusion, this work offered a comprehensive insight based on ozone-peroxymonosulfate (O3/PMS) advanced oxidation for improving the sludge dewaterability and environmental implication.

C-reactive protein and thyroid-stimulating hormone levels as risk factors for hypothyroidism in patients with subacute thyroiditis.

OBJECTIVE: This study was designed to explore the relationships between the clinical characteristics and outcomes of patients with subacute thyroiditis (SAT). DESIGN: This is a single-center retrospective study. PATIENTS: Eighty-nine patients with SAT who were hospitalized in the Sir Run Run Shaw Hospital in Zhejiang, China, from October 2014 to September 2020 were included. METHODS: The Mann-Whitney U-test, chi-square test, and Cox regression analysis were conducted to identify the relationships between clinical characteristics and outcomes. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff levels of C-reactive protein (CRP) and thyroid-stimulating hormone (TSH). RESULTS: The hypothyroidism and recurrence rates were 15.7 and 16.9%, respectively. CRP (≥72.0 mg/L), TSH (<0.02 mIU/L), and free triiodothyronine (fT3) (≥4.10 pg/mL) were associated with hypothyroidism. The cutoff level was 97.80 mg/L for CRP (area under the curve (AUC), 0.717, P = 0.014; sensitivity, 57.1%; specificity, 84.0%) and 0.10 mIU/L for TSH (AUC, 0.752, P = 0.004; sensitivity, 100%; specificity, 46.0%) by ROC curve analysis for hypothyroidism. The factors under study were not associated with recurrence. CONCLUSION: CRP and TSH were risk factors for hypothyroidism in SAT. Thyroid functions should be monitored closely for the early detection of hypothyroidism, especially in patients with CRP levels of more than 97.80 mg/L and TSH levels of less than 0.10 mIU/L.

Insight into the roles of electrolysis-activated persulfate oxidation in the waste activated sludge dewaterability: Effects and mechanism.

Sludge dewatering, as one of the most important steps of sludge treatment, can facilitate transportation and improve disposal efficiency by reducing the volume of sludge. This study investigated the effects of electrolysis-activated persulfate oxidation on improving sludge dewaterability. The results indicated that the sludge capillary suction time (CST) and water content of dewatered sludge cake (Wc) reduced from 93.7 s and 87.8% to 9.7 s and 68.3% respectively at the optimized process parameters: electrolysis voltage of 40 V, electrolysis time of 20 min, and 1.2 mmol/g TS S2O82-. Correlation analysis revealed that the enhancement of sludge dewaterability was closely associated with the increased floc size and zeta potential, decreased protein content in three-layers extracellular polymeric substances (EPS) and viscosity (R = -0.868, p = 0.002; R = -0.703, p = 0.035; R ≥ 0.961, p < 0.001; R = 0.949, p < 0.001). Four protein fluorescence regions in EPS were analyzed by three-dimensional excitation-emission matrix parallel factor (3D-EEM-PARAFAC). The protein secondary structure was changed after the treatment, and the reduction of α-helix/(ß-sheet + random coil) indicated that more hydrophobic sites were exposed. Analysis by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) and rheological test demonstrated that the hydrophilic functional groups of the sludge were decreased and the sludge mobility was significantly enhanced after the treatment with electrolysis-activated persulfate oxidation. Moreover, bound water was converted to free water during SO4·- and ·OH generated by electrolysis-activated persulfate degraded EPS and attacked sludge cells. Meanwhile, scanning electron microscopy (SEM) images revealed that the treated sludge formed porous channel structures, which promoted the flowability of the water. These findings provide a new insight based on electrolysis-activated persulfate oxidation in sludge treatment for enhancing sludge dewaterability.

Insights into the enhancement of waste activated sludge dewaterability using sodium dichloroisocyanurate and dodecyl dimethyl ammonium chloride: Performance, mechanism, and implication.

Sludge dewatering is essential for reduction of sludge volume to cut the cost of transportation and disposal. Combined application of sodium dichloroisocyanurate (DCCNa) and dodecyl dimethyl ammonium chloride (DDAC) was attempted to promote sludge dewatering performance and physicochemical properties for the first time in this work. The results showed that capillary suction time (CST) and moisture content of dewatered sludge cake (Mc) decreased to 15.9 s and 61.54% compared to 144.5 s and 90.39% of raw sludge, respectively, with the addition of optimal dosage of 150 mg DCCNa/g DS and 125 mg DDAC/g DS. The conditioning mechanism of combined treatment was elucidated by investigating the variations of extracellular polymeric substances (EPS) composition, flocs morphological structure, rheological behavior, moisture distribution and Fourier transform infrared (FTIR) of sludge. It could be found that sludge floc cells were decomposed and bound water was released after DCCNa treatment. The bound water content was further decreased with the presence of DDAC. In addition, DDAC not only increased the zeta potential and flowability of sludge, but also reduced the surface tension and interact with oxygen-containing functional groups in sludge. As a result, the sludge dewaterability was significantly improved. Moreover, the calorific value analysis of dewatered sludge cake indicated that combined conditioning of DCCNa and DDAC presented the advantage of incineration disposal.

Perioperative safety and feasibility outcomes of stage IIIA-N2 non-small cell lung cancer following neoadjuvant immunotherapy or neoadjuvant chemotherapy: a retrospective study.

BACKGROUND: We sought to determine the perioperative safety and feasibility outcomes of stage IIIA (N2) non-small cell lung cancer (NSCLC) following neoadjuvant immunotherapy or neoadjuvant chemotherapy. METHODS: The clinical details of patients who attended the Affiliated Hospital of Qingdao University between January 2019 and December 2020 were retrospectively evaluated. Eligible patients had pathologically proven stage IIIA (N2) NSCLC and were randomly prescribed neoadjuvant therapy. Those in the neoadjuvant immunotherapy group received two cycles of nivolumab (3 mg/kg) and those in the control group received neoadjuvant chemotherapy (1,000 mg/m2 gemcitabine and 80 mg/m2 cisplatin). All patients were scheduled to undergo surgery. The primary endpoint was the risk of major complications within 30 days of surgery and the secondary endpoints were interval to surgery and 30-day mortality. RESULTS: A total of 107 eligible patients were evaluated of whom 25 were allocated to the neoadjuvant immunotherapy group and 82 to the neoadjuvant chemotherapy group. The median interval to surgery was similar in the two groups at 29.2 days [95% confidence interval (CI), 27.1 to 31.4 days] in the immunotherapy group and 28.7 days (95% CI, 27.6 to 29.8 days) in the chemotherapy group (P=0.656). While treatment-related adverse events were reported in most patients, all 25 patients completed two cycles of neoadjuvant immunotherapy and 80 of 82 patients completed two cycles of neoadjuvant chemotherapy, although one patient in the latter group died within 30 days of surgery. There was no statistically significant difference between the groups in the probability of grade 3 or higher postoperative complications within 30 days after surgery (P=0.757). CONCLUSIONS: Most patients achieved the primary and secondary endpoints of the study. However, the major pathological response (MPR) showed statistically significant differences between the neoadjuvant immunotherapy and neoadjuvant chemotherapy groups.

circFBXW7 attenuates malignant progression in lung adenocarcinoma by sponging miR-942-5p.

BACKGROUND: As a type of non-coding RNA, circular RNAs (circRNAs) are considered to be functional molecules associated with human cancers. An increasing number of circRNAs have been verified in malignant progression in a number of cancers. The circRNA, circFBXW7, has been proven to play an important role in tumor proliferation and metastasis. However, whether circFBXW7 influences progression in lung adenocarcinoma (LUAD) remains unclear. METHODS: Quantitative real-time reverse transcriptase PCR (qRT-PCR) was used to verify circFBXW7 in LUAD cell lines and LUAD tissues. Kaplan-Meier analysis was then used to compare the disease-free survival (DFS) and overall survival (OS) of these LUAD patients. The biological function of circFBXW7 was examined by overexpression and knockdown of circFBXW7 using MTT assay, EdU assay, wound-healing assay, and Transwell in vitro assays. To explore the mechanism of the circFBXW7, RNA pull-down assay, dual luciferase reporter assay, and RNA immunoprecipitation (RIP) assay were employed to examine the interaction between circFBXW7 and miR-942-5p. Western blot was used to study the fundamental proteins associated with the epithelial-mesenchymal transition (EMT) pathway. In vivo studies with BALB/c nude mice subcutaneously injected with cells stably overexpressing circFBXW7 were performed to further validate the in vitro results. RESULTS: circFBXW7 was downregulated in LUAD cell lines and tissues, and LUAD patients with lower levels had shorter DFS and OS. The in vitro study showed that circFBXW7 overexpression inhibited proliferation and migration of A549 and HCC2279 cell lines. These results were confirmed by circFBXW7 knockdown, which showed the reverse effect. The in vivo model showed that the circRNA levels influenced the tumor growth. Finally, we determined that circFBXW7 target miRNA-942-5p which regulates the EMT gene BARX2. The modulation of circFBXW7 levels produced significant changes in EMT genes in vitro and in vivo. CONCLUSIONS: Our findings showed that circFBXW7 inhibits proliferation and migration by controlling the miR-942-5p/BARX2 axis in LUAD cell lines and its levels correlates with patient survival suggesting that regulating circFBXW7 could have therapeutic value in treating LUAD patients.

Circ-AASDH functions as the progression of early stage lung adenocarcinoma by targeting miR-140-3p to activate E2F7 expression.

BACKGROUND: Lung adenocarcinoma (LUAD), which is the most common subtype of non-small cell lung cancer, is a leading course of cancer-related mortality worldwide. Recently, circular RNA (CircRNAs) has become a hot spot in cancer research because of its important role in tumorigenesis and development and its superior stability. This study aims to clarify the role of circ-AASDH in LUAD and explore its competitive endogenous RNA mechanism. METHODS: The circ-AASDH, miR-140-3p and E2F transcription factor 7 (E2F7) mRNA expression levels were detected via qRT-PCR. CCK-8 and colony formation assay were used to evaluate the ability of cell proliferation. Transwell assay and wound healing assay were performed to measure the invasion and migration ability. Flow cytometry was used to detect the apoptosis of cells. Moreover, Sanger sequencing, RNaseR treatment and divergent primers were used to verify the circular structure. Luciferase reporter and RNA pull-down experiment were performed to characterize the ceRNA mechanism of circ-AASDH. The xenograft model of mice was established to investigate the tumorigenicity of circ-AASDH to LUAD in vivo. RESULTS: By screening for differentially expressed circRNAs, we found that circ-AASDH was highly expressed in LUAD tissues and cells and correlated with tumor size, clinical stage and poor prognosis. Transfection of si-circ-AASDH can inhibit the proliferation and migration of LUAD cells and promote apoptosis in vitro. In mechanism, circ-AASDH could be used as a sponge of miR-140-3p to weaken its inhibition on the expression of E2F7. Additionally, the overexpression of circ-AASDH could deduce the suppression of miR-140-3p on the malignant progression of LUAD cells. Besides, silencing of circ-AASDH inhibited cell proliferation and migration by regulating the expression of E2F7. Furthermore, overexpression of circ-AASDH can promote the growth of LUAD in vivo. CONCLUSIONS: Circ-AASDH/miR-140-3p/E2F7 regulating axis promoted the progression in LUAD. Our results provided ideas for understanding the biological mechanism of circ-AASDH and clarify potential therapeutic targets in LUAD.

A sodium dichloroisocyanurate-based conditioning process for the improvement of sludge dewaterability and mechanism studies.

Sludge dewatering is necessary to reduce the volume of sludge for cost-effective transport and ultimate disposal. In this study, a novel combined chemical conditioning process was proposed to improve sludge dewatering performance in which sludge flocs were destructed by sodium dichloroisocyanurate (DCCNa) and re-flocculated by Al2(SO4)3 and the mechanism was elucidated. The results showed that sludge capillary suction time (CST) dropped to 15.4 s and moisture content of dewatered sludge cake (Mc) deceased to 71.01% respectively, after the application of combined conditioning with the optimal dosage of 200 mg DCCNa/g dry solids (DS) and 80 mg Al2(SO4)3/g DS. With chemical conditioning, sludge physicochemical properties were greatly changed. With the DCCNa application, the percentage of low-molecular-weight substances in soluble extracellular polymeric substances (S-EPS) increased. Also, the sludge zeta potential dropped from -16.85 mV to -25.45 mV and the median particle size (D50) decreased from 54.1 µm to 51.6 µm. However, the subsequent conditioning by Al2(SO4)3 dosing not only led to an increment of 18% in the portion of macromolecules in S-EPS, but also increased the zeta potential and D50 to -10.74 mV and 53.2 µm, respectively. The bound water content in sludge declined from 2.92 g/g DS to 1.98 g/g DS after combined conditioning. We concluded that DCCNa disintegrated the sludge flocs and microbial cells leading to the release of bound water, fine particles and organic substances with negative charge, and the fine colloidal particles can be flocculated into large dense aggregations with the dosing of Al2(SO4)3. In summary, the proposed combined conditioning provided a highly effective and environmental friendly approach to improve the sludge dewatering performance.

Enhancement of waste activated sludge dewaterability by ultrasound-activated persulfate oxidation: Operation condition, sludge properties, and mechanisms.

The study proposed the ultrasound-activated persulfate oxidation as a novel approach to enhance sludge dewaterability. The results demonstrated that the reduction of water content of dewatered sludge cake was 16.5% and the capillary suction time was reduced to 39.5 s at the optimal conditions of 1.0 mmol/g-TS S2O82- and ultrasound energy density of 2.0 kW L-1 within 15 min. The promotion of dewaterability was closely associated with the enlarged floc size, decreased viscosity, and near-neutral zeta potential. Meanwhile, the correlation analysis revealed that the protein in extracellular polymeric substances (EPS) governed sludge dewaterability, especially in loosely bound EPS. Three-dimensional excitation-emission matrix fluorescence spectroscopy, Fourier transform infrared spectroscopy and scanning electronic microscopy analysis revealed that ultrasound-activated persulfate oxidation treatment effectively degraded the gel-like EPS matrix and attacked cells, releasing the moisture which was trapped in EPS and cells. The aggregation of particles promoted the elimination of moisture. Furthermore, heavy metals in conditioned dewatered sludge cakes all satisfied the A level of agricultural land (GB4284-2018) requirements and the chemical speciation distribution of some heavy metals changed significantly.

Desmoglein 3 and Keratin 14 for Distinguishing Between Lung Adenocarcinoma and Lung Squamous Cell Carcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the leading major histological phenotypes of all non-small cell lung cancer (NSCLC). In this study, the candidate genes and the potential tumorigenesis distinguishing between LUAD and LUSC were analyzed. METHODS: The present study investigated two microarray datasets (GSE28571 and GSE10245) downloaded from the Gene Expression Omnibus (GEO) database. A protein-protein interaction (PPI) network was applied to screen out the candidate genes. In addition, differently expressed genes (DEGs) between lung adenocarcinoma and lung squamous cell carcinoma of the two datasets were functionally analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. R 4.0.2 was used to perform Kaplan-Meier analysis of DSG3 (desmoglein 3) and KRT14 (keratin 14) by analyzing the expression and clinical data from The Cancer Genome Atlas (TCGA) database. RESULTS: The results revealed that 47 DEGs of the two datasets were ascertained in our study. It was found that the DEGs were mainly involved in pathways related to p63 transcription factor network and validated transcriptional factor targeting TAp63, etc. Based on the analysis, we finally identified DSG3 and KRT14 as potential biomarkers for distinguishing between LUAD and LUSC. These results suggested that DSG3 and KRT14 could have the potential to play an important role in NSCLC patients, as diagnostic markers. At the same time, DSG3 or KRT14 indicated a worse prognosis in LUSC patients, which were associated with pathways relevant to the TRAIL signaling pathway and TNF receptor signaling pathway according to bioinformatic analysis. CONCLUSION: The DSG3 and KRT14 have the potential to be used as diagnostic markers, which presented here may facilitate improvements in distinguishing between LUAD and LUSC in advanced NSCLC patients.

First-Line Immune-Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Current Landscape and Future Progress.

Lung cancer is one of the most common cancers and the leading cause of cancer-related deaths worldwide. Most of these patients with non-small cell lung cancer (NSCLC) present with the advanced stage of the disease at the time of diagnosis, and thus decrease the 5-year survival rate to about 5%. Immune checkpoint inhibitors (ICIs) can act on the inhibitory pathway of cancer immune response, thereby restoring and maintaining anti-tumor immunity. There are already ICIs targeting different pathways, including the programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) pathway. Since March 2015, the US Food and Drug Administration (FDA) approved nivolumab (anti-PD-1 antibody) as the second-line option for treatment of patients with advanced squamous NSCLC. Additionally, a series of inhibitors related to PD-1/PD-L1 immune-checkpoints have helped in the immunotherapy of NSCLC patients, and modified the original treatment model. However, controversies remain regarding the use of ICIs in a subgroup with targeted oncogene mutations is a problem that we need to solve. On the other hand, there are continuous efforts to find biomarkers that effectively predict the response of ICIs to screen suitable populations. In this review, we have reviewed the history of the continuous developments in cancer immunotherapy, summarized the mechanism of action of the immune-checkpoint pathways. Finally, based on the results of the first-line recent trials, we propose a potential first-line immunotherapeutic strategy for the treatment of the patients with NSCLC.

1α, 25-dihydroxyvitamin D3 inhibits transforming growth factor ß1-induced epithelial-mesenchymal transition via ß-catenin pathway.

BACKGROUND: The transforming growth factor ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) has been proven associated with the pathogenesis of asthmatic airway remodeling, in which the Wnt/ß-catenin pathway plays an important role, notably with regard to TGF-ß1. Recent studies have shown that 1α, 25-dihydroxyvitamin D3(1α, 25(OH)2D3) inhibits TGF-ß1-induced EMT, although the underlying mechanism have not yet been fully elucidated. METHODS: Alveolar epithelial cells were exposed to 1α, 25(OH)2D3, ICG-001, or a combination of both, followed by stimulation with TGF-ß1. The protein expression of E-cadherin, α-smooth muscle actin, fibronectin, and ß-catenin was analyzed by western blotting and immunofluorescence analysis. The mRNA transcript of Snail was analyzed using RT-qPCR, and matrix metalloproteinase 9 (MMP-9) activity was analyzed by gelatin zymogram. The activity of the Wnt/ß-catenin signaling pathway was analyzed using the Top/Fop flash reporters. RESULTS: Both 1α, 25(OH)2D3 and ICG-001 blocked TGF-ß1-induced EMT in alveolar epithelial cells. In addition, the Top/Fop Flash reporters showed that 1α, 25(OH)2D3 suppressed the activity of the Wnt/ß-catenin pathway and reduced the expression of target genes, including MMP-9 and Snail, in synergy with ICG-001. CONCLUSION: 1α, 25(OH)2D3 synergizes with ICG-001 and inhibits TGF-ß1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/ß-catenin signaling pathway.