The important role of EPS in mediated biosynthesis of CdS QDs: Comparative study of EPS-intact and EPS-free.

In this study, we investigated the adsorption of Cd(II) and the biosynthesis of CdS quantum dots (QDs) mediated by cells of sulfate-reducing bacteria before and after the removal of EPS to determine whether EPS or the cell wall plays a major role. Potentiometric titration revealed that the concentration of proton-active binding sites on cells with EPS (EPS-intact) was notably higher than that on cells without EPS (EPS-free) and that the sites were predominantly carboxyl, phosphoryl, hydroxyl, and amine groups. The protein content in EPS-intact cells was higher, and thus the Cd(II) adsorption capacity was stronger. The CdS QDs biosynthesized using EPS-intact possessed better properties, including uniform size distribution, good crystallinity, small particle size, high fluorescence, and strong antimicrobial activity, and the yields were significantly higher than those of EPS-free by a factor of about 1.5-3.7. Further studies revealed that alkaline amino acids in EPS play a major role and serve as templates in the biosynthesis of QDs, whereas they were rarely detected in the cell wall. This study emphasizes the important role of EPS in the bacterial binding of metals and efficient recycling of hazardous waste in water.

Impacts of gene variants on drug effects-the foundation of genotype-guided pharmacologic therapy for long QT syndrome and short QT syndrome.

The clinical significance of optimal pharmacotherapy for inherited arrhythmias such as short QT syndrome (SQTS) and long QT syndrome (LQTS) has been increasingly recognised. The advancement of gene technology has opened up new possibilities for identifying genetic variations and investigating the pathophysiological roles and mechanisms of genetic arrhythmias. Numerous variants in various genes have been proven to be causative in genetic arrhythmias. Studies have demonstrated that the effectiveness of certain drugs is specific to the patient or genotype, indicating the important role of gene-variants in drug response. This review aims to summarize the reported data on the impact of different gene-variants on drug response in SQTS and LQTS, as well as discuss the potential mechanisms by which gene-variants alter drug response. These findings may provide valuable information for future studies on the influence of gene variants on drug efficacy and the development of genotype-guided or precision treatment for these diseases.

Bilobalide Prevents Apoptosis and Improves Cardiac Function in Myocardial Infarction.

Myocardial infarction (MI) is an extremely severe cardiovascular disease, which ranks as the leading cause of sudden death worldwide. Studies have proved that cardiac injury following MI can cause cardiomyocyte apoptosis and myocardial fibrosis. Bilobalide (Bilo) from Ginkgo biloba leaves have been widely reported to possess excellent cardioprotective effects. However, concrete roles of Bilo in MI have not been investigated yet. We here designed both in vitro and in vivo experiments to explore the effects of Bilo on MI-induced cardiac injury and the underlying mechanisms of its action. We conducted in vitro experiments using oxygen-glucose deprivation (OGD)-treated H9c2 cells. Cell apoptosis in H9c2 cells was assessed by conducting flow cytometry assay and evaluating apoptosis-related proteins with western blotting. MI mouse model was established by performing left anterior descending artery (LAD) ligation. Cardiac function of MI mice was determined by assessing ejection fraction (EF), fractional shortening (FS), left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD). Histological changes were analyzed, infarct size and myocardial fibrosis were measured by hematoxylin and eosin (H&E) and Masson staining in cardiac tissues from the mice. The apoptosis of cardiomyocytes in MI mice was assessed by TUNEL staining. Western blotting was applied to detect the effect of Bilo on c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinases (p38 MAPK) signaling both in vitro and in vivo. Bilo inhibited OGD-induced cell apoptosis and lactate dehydrogenase (LDH) release in H9c2 cells. The protein levels of p-JNK and p-p38 were significantly downregulated by Bilo treatment. SB20358 (inhibitor of p38) and SP600125 (inhibitor of JNK) suppressed OGD-induced cell apoptosis as Bilo did. In MI mouse model, Bilo improved the cardiac function and significantly reduced the infarct size and myocardial fibrosis. Bilo inhibited MI-induced cardiomyocytes apoptosis in mice. Bilo suppressed the protein levels of p-JNK and p-p38 in cardiac tissues from MI mice. Bilo alleviated OGD-induced cell apoptosis in H9c2 cells and suppressed MI-induced cardiomyocyte apoptosis and myocardial fibrosis in mice via the inactivation of JNK/p38 MAPK signaling pathways. Thus, Bilo may be an effective anti-MI agent.

A Phase 1b Study of Ivonescimab, a Programmed Cell Death Protein-1 and Vascular Endothelial Growth Factor Bispecific Antibody, as First- or Second-Line Therapy for Advanced or Metastatic Immunotherapy-Naive NSCLC.

INTRODUCTION: This study (HARMONi-5) aimed to evaluate the safety and efficacy of ivonescimab (a bispecific antibody against programmed cell death protein 1 and vascular endothelial growth factor) as first- or second-line monotherapy in patients with advanced immunotherapy-naive NSCLC. METHODS: Eligible patients received intravenous ivonescimab 10 mg/kg every 3 weeks (Q3W), 20 mg/kg every 2 weeks (Q2W), 20 mg/kg Q3W, or 30 mg/kg Q3W. The primary end points were safety and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: At data cutoff (October 5, 2022), 108 patients were enrolled and received ivonescimab. Programmed death ligand-1 tumor proportion score (TPS) was greater than or equal to 1% in 74 patients (68.5%), including 35 (32.4%) with TPS greater than or equal to 50%. The median follow-up was 10.4 months (range: 8.4-10.9 mo). For all patients, ORR and disease control rate were 39.8% and 86.1%, respectively. ORR by TPS was 14.7%, 51.4%, and 57.1% in patients with TPS less than 1%, greater than or equal to 1%, and greater than or equal to 50%, respectively. In the 67 programmed death ligand-1-positive patients receiving first-line ivonescimab, the ORR was 33.3%, 52.6%, 60.0%, and 75.0% at the doses of 10 mg/kg Q3W, 20 mg/kg Q2W, 20 mg/kg Q3W, and 30 mg/kg Q3W, respectively. Grade greater than or equal to 3 treatment-related adverse events (TRAEs) were observed in 24 patients (22.2%). TRAEs leading to treatment discontinuation occurred in one patient (0.9%). TRAEs leading to death occurred in three patients (2.8%) with squamous NSCLC. The occurrence of grade greater than or equal to 3 TRAEs and grade greater than or equal to 3 bleeding events in squamous versus nonsquamous NSCLC patients was 25.5% versus 18.9% and 0.0% versus 1.9%, respectively. CONCLUSIONS: Ivonescimab monotherapy was well tolerated and found to have a promising efficacy in patients with advanced or metastatic NSCLC. CLINICALTRIALS: gov identifier: NCT04900363.

Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial.

BACKGROUND: Immune checkpoint inhibitors targeting PD-1 or CTLA-4 individually have shown substantial clinical benefits in the treatment of malignancies. We aimed to assess the safety and antitumour activity of cadonilimab monotherapy, a bispecific PD-1/CTLA-4 antibody, in patients with advanced solid tumours. METHODS: This multicentre, open-label, phase 1b/2 trial was conducted across 30 hospitals in China. Patients aged 18 years or older with histologically or cytologically confirmed, unresectable advanced solid tumours, unsuccessful completion of at least one previous systemic therapy, and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible for inclusion. Patients who had previously received anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment were not eligible for inclusion. In the dose escalation phase of phase 1b, patients received intravenous cadonilimab at 6 mg/kg and 10 mg/kg every 2 weeks. In the dose expansion phase of phase 1b, cadonilimab at 6 mg/kg and a fixed dose of 450 mg were given intravenously every 2 weeks. In phase 2, cadonilimab at 6 mg/kg was administered intravenously every 2 weeks in three cohorts: patients with cervical cancer, oesophageal squamous cell carcinoma, and hepatocellular carcinoma. The primary endpoints were the safety of cadonilimab in phase 1b and objective response rate in phase 2, based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The safety analysis was done in all patients who received at least one dose of cadonilimab. Antitumour activity was assessed in the full analysis set for the cervical cancer cohort, and in all patients with measurable disease at baseline and who received at least one dose of cadonilimab in the oesophageal squamous cell carcinoma and hepatocellular carcinoma cohorts. The study is registered on ClinicalTrial.gov, NCT03852251, and closed to new participants; follow-up has been completed. FINDINGS: Between Jan 18, 2019, and Jan 8, 2021, 240 patients (83 [43 male and 40 female] in phase 1b and 157 in phase 2) were enrolled. Phase 2 enrolled 111 female patients with cervical cancer, 22 patients with oesophageal squamous cell carcinoma (15 male and seven female), and 24 patients with hepatocellular carcinoma (17 male and seven female). During dose escalation, no dose-limiting toxicities occurred. Grade 3-4 treatment-related adverse events occurred in 67 (28%) of 240 patients; the most frequent grade 3 or worse treatment-related adverse events were anaemia (seven [3%]), increased lipase (four [2%]), decreased bodyweight (three [1%]), decreased appetite (four [2%]), decreased neutrophil count (three [1%]), and infusion-related reaction (two [1%]). 17 (7%) patients discontinued treatment due to treatment-related adverse events. 54 (23%) of 240 patients reported serious treatment-related adverse events, including five patients who died (one due to myocardial infarction; cause unknown for four). In phase 2, in the cervical cancer cohort, with a median follow-up of 14·6 months (IQR 13·1-17·5), the objective response rate was 32·3% (32 of 99; 95% CI 23·3-42·5). In the oesophageal squamous cell carcinoma cohort, with a median follow-up of 17·9 months (IQR 4·0-15·1), the objective response rate was 18·2% (four of 22; 95% CI 5·2-40·3). In the hepatocellular carcinoma cohort, with a median follow-up of 19·6 months (IQR 8·7-19·8), the objective response rate was 16·7% (four of 24; 95% CI 4·7-37·4). INTERPRETATION: Cadonilimab showed an encouraging tumour response rate, with a manageable safety profile, suggesting the potential of cadonilimab for the treatment of advanced solid tumours. FUNDING: Akeso Biopharma. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Evaluation of the Efficacy of Sacubitril/Valsartan on Radiofrequency Ablation in Patients with Hypertension and Persistent Atrial Fibrillation.

OBJECTIVE: To evaluate whether the effect of radiofrequency ablation can be improved by using sacubitril/valsartan (S/V) to control blood pressure in hypertensive patients with persistent atrial fibrillation. METHODS: A total of 63 and 67 hypertension patients with persistent atrial fibrillation were enrolled in an S/V group and ACEI/ARB group, respectively. All patients underwent radiofrequency catheter ablation (RFCA). The blood pressure of the two groups was controlled within the range of 100-140 mmHg (high pressure) and 60-90 mmHg (low pressure). The clinical outcomes of the two groups were observed after 12 months of follow-up. RESULTS: No significant differences in blood pressure were observed between the S/V and ACEI/ARB groups. In addition, the recurrence rate of atrial fibrillation between the two groups was not different. The left atrial diameter was an independent predictor of recurrence (HR = 1.063, P = 0.008). However, in the heart failure subgroup, the recurrence rate of S/V was significantly lower than that of the ACEI/ARB group (P = 0.005), and Cox regression analysis showed that the recurrence risk of atrial fibrillation of the S/V group was 0.302 lower than that of the ACEI/ARB group. NT-proBNP, LVEF, and LAD were significantly improved in hypertension patients with heart failure when comparing cases before and at the end of follow-up. CONCLUSIONS: S/V is better than ACEI/ARB in reducing the recurrence of persistent atrial fibrillation in patients with hypertension and heart failure after RFCA.

A multicenter, open-label phase Ib/II study of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) monotherapy in previously treated advanced non-small-cell lung cancer (AK104-202 study).

PURPOSE: This study aimed to evaluate the efficacy and safety of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) in patients with previously treated metastatic non-small-cell lung cancer (NSCLC). METHODS: In this multicenter, open-label, phase Ib/II study, patients with previously treated NSCLC were enrolled in three different cohorts: Cohort A, patients who had failed previous platinum-based doublet chemotherapy and were immunotherapy naïve; Cohort B, patients who had failed previous platinum-based doublet chemotherapy and had primary resistance to immunotherapy (IO); Cohort C, patients who had failed previous platinum-based doublet chemotherapy and had acquired resistance to IO. Eligible patients were given cadonilimab 6 mg/kg intravenously every 2 weeks. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: A total of 53 patients were enrolled: including 30 patients in cohort A, 7 in cohort B, and 16 in cohort C. ORR was 10% in cohort A, and there were no responder in cohort B and cohort C. Median overall survival was 19.61 (95% CI 11.30-NE) months, 4.93 (95% CI 1.97-NE) months and 13.16 (95% CI 6.18-NE) months in cohort A, B and C, respectively. Grade 3-4 treatment-related adverse events were reported in 6 (11.3 %) patients, including alanine aminotransferase increased (1.9%), rash (1.9%), chest discomfort (1.9%), hypercalcaemia (1.9%), anaemia (1.9%) and infusion related reaction (1.9%). CONCLUSION: The study did not meet its primary endpoint. Cadonilimab demonstrated limited efficacy in patients with IO failure, especially in cases of primary resistance. However, cadonilimab might play a role as a second-line immune monotherapy after platinum-based doublet chemotherapy failure and IO naïve, as its efficacy is similar to other immune checkpoint inhibitors after first-line chemotherapy. Cadonilimab was well-tolerated with mild toxicity, making it a potential candidate for the combination strategy. Clinical trial number NCT04172454.

AK112, a novel PD-1/VEGF bispecific antibody, in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC): an open-label, multicenter, phase II trial.

Background: Inhibiting vascular endothelial growth factor (VEGF) function can improve the efficacy of immunotherapy by modulating the tumor immune microenvironment. AK112 is the first-in-class humanized IgG1 bispecific antibody targeting programmed death-1 (PD-1) and VEGF. This study aimed to evaluate the efficacy and safety of AK112 combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods: This open-label, multicenter, phase II clinical trial was conducted in 11 hospitals in China. Eligible participants were adults aged 18-75 years with locally advanced or metastatic NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, at least one measurable lesion, and an estimated life expectancy of at least 3 months. The participants were categorized into three cohorts based on prior therapy and functional genomic alterations. Patients in cohort 1 were previously untreated advanced NSCLC, had no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) gene modifications, and received AK112 combined with pemetrexed (500 mg/m2) for non-squamous (non-sq)-NSCLC or paclitaxel (175 mg/m2) for sq-NSCLC plus carboplatin (area under the curve of 5 mg/mL per min) for four cycles, followed by AK112 with pemetrexed for non-sq-NSCLC and AK112 alone for sq-NSCLC as maintenance therapy. The participants in cohort 2 had advanced NSCLC with EGFR-sensitive mutations, failed previous EGFR-tyrosine kinase inhibitor (TKI) therapy, and received pemetrexed plus AK112 and carboplatin for four cycles, followed by pemetrexed plus AK112 as maintenance therapy. The participants in cohort 3 had advanced NSCLC who failed systemic platinum-based chemotherapy and anti-PD-1/programmed death-ligand 1 (PD-L1) treatments and received AK112 plus docetaxel (75 mg/m2). Two dosages of AK112 (10 or 20 mg/kg) were examined in each cohort, and the drug was administered intravenously on day 1 of each 3-week treatment cycle. The primary endpoints were the investigator-assessed objective response rate (ORR) and safety. This study was registered with ClinicalTrials.gov (NCT04736823). Findings: Eighty-three patients were enrolled from February 2021 to August 2022 and received the study treatment. Cohorts 1, 2, and 3 had 44, 19, and 20 patients, respectively. The confirmed ORR was 53.5% (23/43) [95% CI, 36.9-67.1], 68.4% (13/19) [95% CI, 43.4-87.4], and 40.0% (8/20) [95% CI, 19.1-63.9] in cohorts 1, 2, and 3, respectively. In cohort 1, the median PFS was not reached, and the 12-month PFS rate was 59.1%. In cohorts 2 and 3, the median PFS were 8.5 [95% CI, 5.5-NE] and 7.5 [95% CI, 2.3-NE] months, and the 12-month PFS rates were 35.5% and 44.5%, respectively. The most common grade ≥3 treatment-related adverse events were decreased white blood cell count [7 (8.4%)], neutropenia [5 (6.0%)], thrombocytopenia [2 (2.4%)], anemia [4 (4.8%)], and myelosuppression [2 (2.4%)]. Interpretation: AK112 plus platinum-doublet showed promising antitumor activity and safety not only in first-line treatment of advanced NSCLC patients without driver mutation but also in patients with EGFR-functional mutation who failed previous EGFR-TKI therapy and advanced NSCLC patients who failed prior systemic platinum-based chemotherapy and PD-1/PD-L1 inhibitor treatments, suggesting a valuable potential new treatment option for this patient population. Funding: Akeso Biopharma, Inc., Zhongshan, China, and National Natural Science Foundation of China.

Extraction of Germanium from Low-Grade Germanium-Bearing Lignite by Reductive Volatilization.

Germanium (Ge) as an important strategic metal is widely used in many modern-technology fields such as optical fiber and thermal solar cells. In this study, the volatilization behavior of Ge from low-grade germanium-bearing lignite was investigated in detail through reductive volatilization. The results indicated that temperature and air flow rate in the semi-closed roasting system played a significant role in the process. The optimal volitation efficiency of Ge reached 98% at 1100 °C for 2 h with air flow rate of 0.7 L/min in a maffle furnace, respectively. Under optimal conditions, the contents of Ge lowered to 30 ppm in the roasting residue. Analysis of the enriched ash yielded 71,600 ppm for Ge. Chemical phase analysis of the Ge in the enrichment ash showed that soluble Ge accounted for 82.18% of the total Ge, which could be viewed as an excellent material for Ge extraction by chlorinated distillation.

Mediated biosynthesis of CdS QDs by EPS from Desulfovibrio desulfuricans sub sp. under carbon source-induced reinforcement.

This paper describes a unique molecular mechanism for the EPS-mediated synthesis of CdS QDs by sulfate-reducing bacteria (SRB) under carbon source-induced reinforcement. Under the induced by carbon sources (HCOONa, CH3COONa and C6H12O6), there was a significant increase in EPS production of SRB, particularly in protein, and the capacity of Cd(II) adsorption was further enhanced. CdS QDs were extracellularly synthesized by adding S2- after Cd(II) adsorption. The results showed that CdS QDs were wrapped or adhered by EPS, and the most significant increase in Arg and Lys among basic amino acids in EPS after HCOONa-induced was 133.34% and 63.89%, respectively. This may serve as a biological template for QD synthesis, producing protein gels with a large number of microcavities and controlling the nucleation of CdS QDs. The highest yield of HCOONa-CdS was achieved after induction, with 23.59 g/g biomass per unit strain, which was 447.34% higher than that before induction and was at a high level in previous studies. The synthesized CdS QDs were uniform in size distribution and had higher luminescence activity and a larger specific surface area than those synthesized by the chemical synthesis route, provides a new idea for EPS treatment of heavy metal wastewater and metal biorecovery.

SHP-1 alleviates atrial fibrosis in atrial fibrillation by modulating STAT3 activation.

Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1) has a well-established role in myocardial infarction, yet its involvement in atrial fibrosis and atrial fibrillation (AF) has not been elucidated. As cardiac arrhythmias caused by AF are a major global health concern, we investigated whether SHP-1 modulates AF development. The degree of atrial fibrosis was examined using Masson's trichrome staining, and SHP-1 expression in the human atrium was assessed using quantitative polymerase chain reaction (qPCR), immunohistochemistry (IHC), and western blotting (WB). We also examined SHP-1 expression in cardiac tissue from an AF mouse model, as well as in angiotensin II (Ang II)-treated mouse atrial myocytes and fibroblasts. We found that SHP-1 expression was reduced with the aggravation of atrial fibrosis in clinical samples of patients with AF. SHP-1 was also downregulated in the heart tissue of AF mice and Ang II-treated myocytes and fibroblasts, compared with that in the control groups. Next, we demonstrated that SHP-1 overexpression alleviated AF severity in mice by injecting a lentiviral vector into the pericardial space. In Ang II-treated myocytes and fibroblasts, we observed excessive extracellular matrix (ECM) deposition, reactive oxygen species (ROS) generation, and transforming growth factor beta 1 (TGF-ß1)/mothers against decapentaplegic homolog 2 (SMAD2) pathway activation, all of which were counteracted by the overexpression of SHP-1. Our WB data showed that STAT3 activation was inversely correlated with SHP-1 expression in samples from patients with AF, AF mice, and Ang II-treated cells. Furthermore, administration of colivelin, a STAT3 agonist, in SHP-1-overexpressing, Ang II-treated myocytes and fibroblasts resulted in higher levels of ECM deposition, ROS generation, and TGF-ß1/SMAD2 activation. These findings indicate that SHP-1 regulates AF fibrosis progression by modulating STAT3 activation and is thus a potential treatment target for atrial fibrosis and AF.

Ultrasound-Assisted Adsorption of Perchlorate Using Calcined Hydrotalcites and the Thermal Stabilization Effect of Recycled Adsorbents on Poly(vinyl chloride).

Due to their high anion exchange and memory effect, the layered double hydroxides (LHDs) have wide applications for some areas. In this work, an efficient and green recycling route for layered double hydroxide based adsorbents is proposed specifically for application as a poly(vinyl chloride) (PVC) heat stabilizer without requiring secondary calcination. Conventional magnesium-aluminum hydrotalcite was synthesized using the hydrothermal method followed by removal of carbonate anion (CO32-) between LDH layers by calcination. The adsorption of perchlorate anion (ClO4-) by the memory effect of calcined LDHs with and without ultrasound assistance was compared. Using ultrasound assistance, the maximum adsorption capacity of the adsorbents (291.89 mg/g) was increased, and the adsorption process was fitted using the kinetic Elovich rate equation (R2 = 0.992) and Langmuir adsorption model (R2 = 0.996). This material was characterized using XRD, FT-IR, EDS, and TGA which demonstrated that ClO4- was intercalated into the hydrotalcite layer successfully. The recycled adsorbents were used to augment a commercial calcium-zinc-based PVC stabilizer package applied in a epoxidized soybean oil plasticized cast sheet which is based on an emulsion type PVC homopolymer resin. Use of perchlorate intercalated LDH augmentation yielded significant improvement to static heat resistance as indicated by the degree of discoloration with a life extension of approximately 60 min. The improved stability was corroborated by evaluation of HCl gas evolved during thermal degradation using conductivity change curves and the Congo red test.

Radical-/non-radical-mediated catalyst activation of peroxymonosulfate for efficient atrazine degradation.

Efficient degradation technologies are urgent to be developed to avoid the ecological and healthy hazards brought from atrazine (ATZ). LaCoO3-δ/peroxymonosulfate (PMS) system was proved to have strong degradation capabilities to contaminants. In this work, we intended to investigate the effect of the synthesis method on LaCoO3-δ. However, the hydrothermal method yielded a new material (H-Co) with better catalytic performance than LaCoO3-δ, which showed stable catalytic ability at pH 3.0-9.0 and 5 consecutive cycles. The coexistence of inorganic Cl-, SO42-, NO3-, H2PO4-, HCO3- and organic humic acids exerted little influences on the H-Co/PMS system. In addition, the actual livestock and poultry breeding wastewater could be well degraded and mineralized by the H-Co/PMS system. Free radical burst experiments and EPR characterization were performed to verify the synergistic effects of free radicals and non-free radicals during ATZ degradation. Based on SEM, XRD, O2-TPD, FTIR, XPS, and electrochemistry characterizations, the efficient catalytic ability of H-Co could be attributed to the abundant oxygen vacancies, surface hydroxyl groups, zero-valent cobalt sites and high electronic conductivity. The degradation pathways were proposed based on the detection of degradation intermediates of ATZ by UPLC-MS. Moreover, the toxic of ATZ during the oxidation was evaluated by TEXT and E. coli inhibition assay. This work comprehensively analyzed the catalytic reaction mechanism of the H-Co/PMS system and provided a feasible pathway for the treatment of the actual livestock and poultry breeding wastewater.

Low molecular weight hyaluronan inhibits lung epithelial ion channels by activating the calcium-sensing receptor.

Herein, we tested the hypothesis that low molecular weight hyaluronan (LMW-HA) inhibits lung epithelial ions transport in-vivo, ex-vivo, and in-vitro by activating the calcium-sensing receptor (CaSR). Twenty-four hours post intranasal instillation of 50-150 µg/ml LMW-HA to C57BL/6 mice, there was a 75% inhibition of alveolar fluid clearance (AFC), a threefold increase in the epithelial lining fluid (ELF) depth, and a 20% increase in lung wet/dry (W/D) ratio. Incubation of human and mouse precision cut lung slices with 150 µg/ml LMW-HA reduced the activity and the open probability (Po) of epithelial sodium channel (ENaC) in alveolar epithelial type 2 (ATII) cells, and in mouse tracheal epithelial cells (MTEC) monolayers as early as 4 h. The Cl- current through cystic fibrosis transmembrane conductance regulator (CFTR) and the activity of Na,K-ATPase were both inhibited by more than 66% at 24 h. The inhibitory effects of LMW-HA on ion channels were reversed by 1 µM NPS-2143, or 150 µg/ml high molecular weight hyaluronan (HMW-HA). In HEK-293 cells expressing the calcium-sensitive Cl- channel TMEM16-A, CaSR was required for the activation of the Cl- current by LMW-HA. This is the first demonstration of lung ions and water transport inhibition by LMW-HA, and its mediation through the activation of CaSR.

MicroRNA-155 inhibition attenuates myocardial infarction-induced connexin 43 degradation in cardiomyocytes by reducing pro-inflammatory macrophage activation.

Background: Degradation of pro-inflammatory macrophage-mediated connexin 43 (Cx43) plays an important role in post-myocardial infarction (MI) arrhythmogenesis, microRNA (miR)-155 produced by macrophages has been shown to mediate post-MI effects. We hypothesized that miR-155 inhibition attenuated MI-induced Cx43 degradation by reducing pro-inflammatory macrophage activation. Methods: MI was induced by permanent ligation of the left anterior descending coronary artery in male C57BL/6 mice. Lipopolysaccharide (LPS)-stimulated mice bone marrow-derived macrophages (BMDMs) and hypoxia-induced neonatal rat cardiomyocytes (NRCMs) were used in vitro models. qRT-PCR, Western-blot and immunofluorescence were used to analyze relevant indicators. Results: The expression levels of miR-155, interleukin-1 beta (IL-1ß), and matrix metalloproteinase (MMP)7 were higher in MI mice and LPS-treated BMDMs than in the sham/control groups, treatment with a miR-155 antagomir reversed these effects. Moreover, miR-155 inhibition reduced ventricular arrhythmias incidence and improved cardiac function in MI mice. Cx43 expression was decreased in MI mice and hypoxia-exposed NRCMs, and hypoxia-induced Cx43 degradation in NRCMs was reduced by application of conditioned medium from LPS-induced BMDMs treated with the miR-155 antagomir, but increased by conditioned medium from BMDMs treated with a miR-155 agomir. Importantly, NRCMs cultured in conditioned medium from LPS-induced BMDMs transfected with small interfering RNA against IL-1ß and MMP7 showed decreased hypoxia-mediated Cx43 degradation, and this effect also was diminished by BMDM treatment with the miR-155 agomir. Additionally, siRNA-mediated suppressor of cytokine signaling 1 (SOCS1) knockdown in LPS-induced BMDMs promoted Cx43 degradation in hypoxia-exposed NRCMs, and the effect was reduced by the miR-155 inhibition. Conclusions: MiR-155 inhibition attenuated post-MI Cx43 degradation by reducing macrophage-mediated IL-1ß and MMP7 expression through the SOCS1/nuclear factor-κB pathway.

Characteristics of EPS from Pseudomonas aeruginosa and Alcaligenes faecalis under Cd(II) stress: changes in chemical components and adsorption performance.

EPS (extracellular polymeric substance) production is a self-protection mechanism by which microorganisms slow or eliminate adverse effects in unfavorable environments. In this study, Pseudomonas aeruginosa and Alcaligenes faecalis were selected to explore changes in EPS components, especially protein components, under stress caused by different concentrations of Cd(II). The results showed that the protein content in EPS was the highest. The two strains achieved maximum EPS production levels of 109.17 and 214.96 mg/g VSS at Cd(II) stress concentrations of 20 and 50 mg/L, which were increased by 52.07% and 409.69% compared with the levels exhibited before stress, respectively. The protein content correlated very well with data from adsorption experiments. Furthermore, FTIR, 3D-EEM, and XPS results illustrated that after Cd(II) stress, C-N, C=O/-COOH, and R-NO2- moieties were formed in substantial quantities, and the stress effects of Pseudomonas aeruginosa were significantly higher than those of Alcaligenes faecalis. The results of this study showed that addition of Cd(NO3)2 effectively regulated the components of EPS, especially the protein content, and improved the adsorption capacity, which has application prospects for prevention and control of heavy metals.

High-efficiency treatment of electroless nickel plating effluent using core-shell MnFe2O4-C@Al2O3 combined with ozonation: Performance and mechanism.

Heterogeneous catalytic ozonation (HCO) has been widely applied for the treatment of wastewater. In order to maintain the structural stability and surface catalytic activity of heterogeneous catalysts during the HCO treatment of electroless nickel plating effluent (ENPE), a MnFe2O4-C@Al2O3 catalyst with a core-shell structure was synthesized. MnFe2O4-C@Al2O3 was characterized and applied in the removal of total nickel (TNi) and organic contaminants from actual ENPE, using a coupled system of HCO combined with a magnetic dithiocarbamate chelating resin (MnFe2O4-C@Al2O3/O3-MDCR). Results show that embedding Al2O3 with C and MnFe2O4 significantly increased the TNi removal efficiency (99.3%), enhanced the O3-utilization efficiency and improved the generation of reactive oxygen species (ROS). The reaction rate (k = 0.7641 min-1) and O3-utilization efficiency established for TNi removal (ΔTNi/ΔO3 =0.221) by the MnFe2O4-C@Al2O3/O3-MDCR system, were 220% and 140% higher than the Al2O3/O3-MDCR system, respectively. Catalytic mechanism analysis demonstrated that surface hydroxyl groups, oxygen vacancy, metals, the carbon surface and its functional groups, can all potentially serve as catalytic active sites, with 1O2 and •OH considered to the predominant ROS. Overall, these findings verify that the synthesized MnFe2O4-C@Al2O3 catalyst possesses excellent catalytic capabilities and outstanding structural stability, making it suitable for practical application in the treatment of wastewater effluent.

Removal of Zn(II) by magnetic composite adsorbent: synthesis, performance, and mechanism.

In this study, L-methionine and nano-Fe3O4 were encapsulated and cured on sodium alginate by the ionic cross-linking method to form magnetic composite gel spheres (SML) as an adsorbent for the removal of Zn(II) from water. The influence of adsorbent dosages, pH, reaction time, and initial ion concentration on the ability of the gel spheres to adsorb Zn(II) was investigated, and the adsorption mechanism was identified. The experimental results showed that under the optimum conditions (pH = 5, t = 60 min, dosage of SML is 0.7 g·L-1), the maximum amount of Zn(II) adsorbed by the adsorbent gel spheres reached 86.84 mgˑg-1. The reaction process of this adsorbent fits well with the Langmuir and pseudo-second-order kinetic models and is a heat absorption reaction. The adsorbent would preferentially adsorb Pb(II), and the adsorption efficiency of Zn(II) decreased when the concentration of interfering ions increased in the coexistence system. Further mechanistic research showed that this magnetic composite adsorbent is a mesoporous material with superior adsorption performance, and the amino and carboxyl groups on it react with Zn(II) via ligand chelation; the ion exchange effect of Ca(II) also plays a role. The adsorption amount of Zn(II) was maintained at a higher level after 5 cycles, and the loss of Fe was approximately 0.2%. In summary, SML, which is environmentally friendly, efficient, and recyclable, is an ideal adsorbent for Zn(II) removal.

Evaluating Common NOS1AP Variants in Patients with Implantable Cardioverter Defibrillators for Secondary Prevention : Evaluating SNPs in NOS1AP.

BACKGROUND: Recent research has found that single nucleotide polymorphisms (SNPs) in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene are associated with altered QT intervals and sudden cardiac death (SCD). However, the clinical utility and implications of NOS1AP SNPs remain unclear. Thus, this study aimed to explore the influence of NOS1AP SNPs in patients with implantable cardioverter defibrillator (ICD) for secondary prevention. METHODS: We conducted a case-control study to evaluate the most studied SNPs in NOS1AP (rs12143842, rs10494366, rs12567209, and rs16847548) in patients with ICD for secondary prevention. Patients were followed for up to 36 months from the time of ICD implantation. ICD interrogation data at 3 and 12 months, including rapid ventricular arrhythmia episodes and appropriate therapies, were then analyzed.  RESULTS: A significant association was observed between rs10494366 and ICD recipients who experienced appropriate therapies. After a mean follow-up time of 31.70 ± 9.15 months, we detected significant differences among the three rs10494366 genotype groups in the distribution of ICD shocks and appropriate therapies, as well as in the correlation of rs10494366 and ICD shocks. According to Kaplan-Meier and Cox regression analyses, patients with the TT genotype had a higher risk of SCD than those with the GG genotype. CONCLUSIONS: The present study revealed that NOS1AP SNP rs10494366 was associated with appropriate therapies. Specifically, the TT genotype increased ICD shocks and SCD risk in patients with ICD for secondary prevention for the first time.

Effects of different exogenous cadmium compounds on the chemical composition and adsorption properties of two gram-negative bacterial EPS.

Three different Cd(II) compounds were used to regulate Pseudomonas aeruginosa and Alcaligenes faecalis EPS (extracellular polymeric substances). The purpose of this study was to improve the content of EPS protein and the adsorption capacity of Cd(II) by different Cd(II) compounds. The results showed that Cd(NO3)2 had the best stress/induction effect on the two strains. Under the best stress/induction, the protein in EPS of the two strains increased most obviously, and the adsorption capacity of Cd(II) was increased by more than 40%. Under these conditions, the kinetics of the adsorption process of Cd(II) by Cd(NO3)2-EPSA. F (EPS produced by Alcaligenes faecalis under Cd(NO3)2 stress) could be well fitted by the Langmuir isotherm model, and the theoretical maximum adsorption amount of 1111.11 mg/g EPS could be obtained. The results of 3D-EEM, FTIR and XPS indicated that proteins, especially CO, CN and NH in proteins, played a major role in the removal of Cd(II) by Cd(NO3)2-EPSA. F. The results of this study show that the addition of Cd(NO3)2 can effectively regulate the content of chemical components, especially the content of protein, and thus greatly improve the removal efficiency of heavy metals, which shows great application prospects in the prevention and control of heavy metal pollution.