Theoretical insights into selective extraction of uranium from seawater with tetradentate N,O-mixed donor ligands.

The competition of uranium and vanadium ions is a major challenge in extracting uranium from seawater. In-depth exploration of the complexation of uranium and vanadium ions with promising ligands is essential to design highly efficient ligands for selective recovery of uranium. In this work, we systematically explored the uranyl and vanadium extraction complexes with three tetradentate N,O-mixed donor analogues including the rigid backbone ligands 1,10-phenanthroline-2,9-dicarboxylic acid (PDA, L1) and 5H-cyclopenta[2,1-b:3,4-b']dipyridine-2,8-dicarboxylate acid (L3), as well as the flexible ligand [2,2'-bipyridine]-6,6'-dicarboxylate acid (L2) using density functional theory (DFT). These ligands coordinate to the uranyl cation in a tetradentate fashion, while L1 and L3 act as tridentate ligands toward VO2+ due to the smaller ionic radius of VO2+ and larger cleft sizes of L1 and L3. Bonding analyses show that the metal-ligand bonding orbitals of the uranyl complexes [UO2L(CO3)]2-, [UO2L(OH)]-, and [UO2L(H2O)] mainly arise from the interactions of the U 5f, 6d orbitals and N, O 2p orbitals. Because of the rigid structure and more suitable chelate ring size, the L1 ligand possesses a stronger complexing ability for uranyl ions than other ligands, while the L3 ligand has weaker binding affinity than L1 and L2. All these ligands prefer to coordinate with the uranyl cation rather than vanadium ion, indicating the selectivity of these ligands to [UO2(CO3)3]4- over H2VO4- and HVO42- in seawater. This is mainly attributed to the metal ion size-based selectivity and structural preorganization of the ligands. These results demonstrate that the backbone of these ligands affect their extraction behaviors. It is expected that this work might prove useful in designing efficient ligands for uranium extraction from seawater.

Bisimidazolium Salt Glycosyltransferase Inhibitors Suppress Hepatocellular Carcinoma Progression In Vitro and In Vivo.

Hepatocellular carcinoma is a leading cause of cancer death, and the disease progression has been related to glycophenotype modifications. Previously synthesized bisimidazolium salts (C20 and C22) have been shown to selectively inhibit the activity of glycosyltransferases in cultured cancer cell homogenates. The current study investigated the anticancer effects of C20/C22 and the possible pathways through which these effects are achieved. The therapeutic value of C20/C22 in terms of inhibiting cancer cell proliferation, metastasis, and angiogenesis, as well as inducing apoptosis, were examined with hepatic cancer cell line HepG2 and a xenograft mouse model. C20/C22 treatment downregulated the synthesis of SLex and Ley sugar epitopes and suppressed selectin-mediated cancer cell metastasis. C20/C22 inhibited HepG2 proliferation, induced cell-cycle arrest, increased intracellular ROS level, led to ER stress, and eventually induced apoptosis through the intrinsic pathway. Furthermore, C20/C22 upregulated the expressions of death receptors DR4 and DR5, substantially increasing the sensitivity of HepG2 to TRAIL-triggered apoptosis. In vivo, C20/C22 effectively inhibited tumor growth and angiogenesis in the xenograft mouse model without adverse effects on major organs. In summary, C20 and C22 are new promising anti-hepatic cancer agents with multiple mechanisms in controlling cancer cell growth, metastasis, and apoptosis, and they merit further development into anticancer drugs.

Diagnostic Value of Neutrophil/lymphocyte Ratio and Platelet/lymphocyte Ratio in Premature Rupture of Membranes Complicated by Sepsis.

OBJECTIVE: To investigate the predictive value of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in premature rupture of membranes complicated by sepsis. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Department of Paediatrics, Affiliated Hospital of Yanbian University, China, from January 2020 to June 2021. METHODOLOGY: Ninety-nine children with premature rupture of membranes and sepsis were included as group A and 99 children without sepsis were included as group B. Logistic regression analysis was used to analyse the risk factors for premature rupture of membranes complicated by sepsis. The diagnostic value of PLR and NLR in sepsis complicated by premature rupture of membranes was assessed by subject operating characteristic curve (ROC) curves. RESULTS: Univariate analysis showed significant differences between groups A and B in terms of mode of delivery, lymphocyte count, platelets, PLR and NLR (p <0.05). Logistic regression analysis showed that mode of delivery, platelets, PLR and NLR were independent risk factors for premature rupture of membranes complicated by sepsis (p <0.05). The ROC area for PLR was 0.781 (95% CI: 0.718-0.844, p <0.001), which was greater than that for NLR when premature rupture of membranes complicated by sepsis was predicted. When the PLR was >93.072, the sensitivity of predicting premature rupture of membranes complicated by sepsis was 67.7% and the specificity was 79.8%. CONCLUSION: PLR and NLR have a high predictive value for premature rupture of membranes complicated by sepsis. Among them, the predictive value of PLR was greater than NLR. KEY WORDS: Premature rupture of membranes, Sepsis, PLR, NLR, Subject operating characteristic curve (ROC).

N-Butyrylated Hyaluronic Acid Achieves Anti-Inflammatory Effects In Vitro and in Adjuvant-Induced Immune Activation in Rats.

Previously synthesized N-butyrylated hyaluronic acid (BHA) provides anti-inflammatory effects in rat models of acute gouty arthritis and hyperuricemia. However, the mechanism of action remains to be elucidated. Herein, the anti-inflammatory and antioxidative activities of BHA and the targeted signaling pathways were explored with LPS-induced RAW264.7 and an adjuvant-induced inflammation in a rat model. Results indicated that BHA inhibited the generation of pro-inflammatory cytokines TNFα, IL-1ß and IL-6, reduced ROS production and down-regulated JAK1-STAT1/3 signaling pathways in LPS-induced RAW264.7. In vivo, BHA alleviated paw and joint swelling, decreased inflammatory cell infiltration in paw tissues, suppressed gene expressions of p38 and p65, down-regulated the NF-κB and MAPK signaling pathways and reduced protein levels of TNFα, IL-1ß and IL-6 in joint tissues of arthritis rats. This study demonstrated the pivotal role of BHA in anti-inflammation and anti-oxidation, suggesting the potential clinical value of BHA in the prevention of inflammatory arthritis and is worthy for development as a new pharmacological treatment.

PtrHAT22, as a higher hierarchy regulator, coordinately regulates secondary cell wall component biosynthesis in Populus trichocarpa.

Homeodomain-leucine zipper (HD-Zip) II transcription factors (TFs) have been reported to play vital roles in diverse biological processes of plants. However, it remains unclear whether HD-Zip II TFs regulate secondary cell wall (SCW) in woody plants. In this study, we performed the functional characterization of a Populus trichocarpa HD-Zip II TF, PtrHAT22, which encodes a nuclear localized transcription repressor predominantly expressing in secondary developing tissues. Overexpression of PtrHAT22 showed arrested growths, including reduced heights and diameters above the ground, small leaves, and decreased biomass. Meanwhile, the contents of lignin, cellulose, and thickness of SCW significantly decreased, whilst the content of hemicellulose obviously increased in PtrHAT22 transgenic poplar. The expressions of some wood-associated TFs and structural genes significantly changed accordingly with the alternations of SCW characteristics in PtrHAT22 transgenic poplar. Furthermore, PtrHAT22 directly repressed the promoter activities of PtrMYB20, PtrMYB28, and PtrCOMT2, and bind two cis-acting elements that were specifically enriched in their promoter regions. Taken together, our results suggested that PtrHAT22, as a higher hierarchy TF like PtrWNDs, exerted coordination regulation of poplar SCW component biosynthesis through directly and indirectly regulating structural genes and different hierarchy TFs of SCW formation network.

Insulin-like growth factor-1: A potential target for bronchopulmonary dysplasia treatment (Review).

Bronchopulmonary dysplasia (BPD) is a common respiratory disorder among preterm infants, particularly low-birth-weight infants (LBWIs) and very-low-birth-weight infants (VLBWIs). Although BPD was first reported 50 years ago, no specific drugs or efficient measures are yet available for prevention or treatment. Insulin-like growth factor-1 (IGF-1) belongs to the insulin family. It promotes mitosis and stimulates cell proliferation and DNA synthesis, the primary factors involved in pulmonary development during the fetal and postnatal periods. Several studies have reported that IGF-1 exerts certain effects on BPD genesis and progression by regulating BPD-related biological processes. In addition, exogenous addition of IGF-1 can alleviate lung inflammation, cell apoptosis and eliminate alveolar development disorders in children with BPD. These findings suggest that IGF-1 could be a new target for treating BPD. Here, we summarize and analyze the definition, pathogenesis, and research status of BPD, as well as the pathogenesis of IGF-1 in BPD and the latest findings in related biological processes.

Theoretical Insights on Improving Amidoxime Selectivity for Potential Uranium Extraction from Seawater.

Extraction of uranium from seawater is one of the important ways to solve the shortage of terrestrial uranium resources. Thereinto, the competition between uranyl and vanadium cations is a significant challenge in the commonly used amidoxime-based adsorbents for extracting uranium from seawater. An in-depth understanding of the extraction behaviors of modified amidoxime groups with uranyl and vanadium ions is one of the effective means to design and develop efficient adsorbents for selective uranium sequestration. In this work, we have designed and systematically investigated the alkyl and amino functionalized amidoxime, (Z)-2-amino-N'-hydroxy-N,N-dimethylbenzimidamide (L1), and its phenyl and methoxy derivatives ((Z)-3-amino-N'-hydroxy-N,N-dimethyl-2-naphthimidamide (L2) and (Z)-2-amino-N'-hydroxy-4-methoxy-N,N-dimethylbenzimidamide (L3)) by quantum chemistry calculations. In the uranyl complexes, the amidoxime groups prefer to act as η2-coordinated ligands as the amidoximes increase, and there exist substantial hydrogen bond interactions, which are different from the vanadium complexes. Various bonding analyses show that the L1 ligand possesses a stronger binding affinity to UO22+, and the -C6H5 and -CH3O substituent groups seem to have no effect on the improvement of extraction ability. Thermodynamic analysis confirms that the L1 ligand has a stronger extraction capability to uranyl ion compared to L2 and L3. According to the calculations of the vanadium (V) (VO2+ and VO3+) complexes with the L1 ligand, L1 is more likely to react with [H2VO4]- and [HVO4]2- to form VO2+ complexes. Expectantly, thermodynamic analysis displays a higher extraction capacity for uranyl ions than vanadium ions. Therefore, these alkyl and amino functionalized amidoxime ligands demonstrate high selectivity for uranyl over vanadium ions, which is mainly due to the coordination mode changes of these ligands toward vanadium in conjunction with the considerable hydrogen bonds in the uranyl complexes. These results are expected to afford useful clues for the design of efficient adsorbents for uranium extraction from seawater.

Pompe Disease Complicated with Appendicular Torsion: A Rare Concurrence.

Pompe disease, also known as Glycogen Storage Disease Type II, is a rare disorder of glucose metabolism caused by congenital acid alpha-glucosidase (GAA) deficiency. A large amount of glycogen accumulates in the lysosomes, causing these to swell and rupture. Its incidence is about 1 in 40,000 to 1 in 50,000 newborns. The main features are hypotonia and cardiomyopathy. Only a few clinical cases of Pompe disease have been reported, and appendicular torsion has rarely been observed. Herein, we report a case of Pompe disease combined with appendicular torsion, both of which were diagnosed on autopsy pathology. The clinical diagnosis of this disease is difficult in developing countries, and it is mostly misdiagnosed as other types of heart disease. Once the clinical symptoms worsen, most of them die within a short period. Therefore, screening for neonatal genetic metabolic diseases for early diagnosis and treatment should be carried out. Key Words: Glycogen storage disease type II, Metabolic disease, Enzyme replacement therapy, Neonatal screening.

Salidroside Mitigates Airway Inflammation in Asthmatic Mice via the AMPK/Akt/GSK3ß Signaling Pathway.

INTRODUCTION: This study aimed to explore the effects and mechanisms of salidroside (SAL) in airway inflammation in asthmatic mice. METHODS: Mice were sensitized with ovalbumin (OVA) to establish an asthma model. They were divided into the control group, OVA group, SAL low-dose group (SAL-L), SAL high-dose group (SAL-H), and dexamethasone (DXM) group. The airway reactivity of the mice was measured, and the total cells, neutrophils, eosinophils, and lymphocytes were counted, respectively. The levels of IL-4, IL-5, IL-13, and IFN-γ in bronchoalveolar lavage fluid (BALF) were detected by ELISA. Immunohistochemistry was used to detect the expression levels of p-AMPK, p-Akt, and p-GSK3ß. Western blot was used to detect cytokine levels in lung tissue and p-AMPK, p-Akt, and p-GSK3ß levels in LPS-induced 16HBE cells. RESULTS: The airway hyperresponsiveness of asthmatic mice in the SAL-H group decreased (p < 0.05), and the total number of cells, neutrophils, eosinophils, and lymphocytes decreased significantly (p < 0.05). In addition, the airways of mice showed airway inflammatory infiltration and goblet cell proliferation, and the corresponding cellular inflammatory factors IL-4, IL-5, and IL-13 were significantly decreased. However, the expression of IFN-γ in BALF and lung tissues was increased (p < 0.05). Moreover, after the mice were treated with SAL, the phosphorylation level of AMPK was significantly increased, which further reduced the phosphorylation levels of Akt and GSK3ß (p < 0.05). Both SAL and AMPK inhibitors exerted effects on LPS-induced 16HBE cells, consistent with in vivo results. CONCLUSION: SAL can inhibit bronchial hyperresponsiveness and reduce tracheal inflammation by increasing AMPK phosphorylation and inhibiting Akt and GSK3ß signaling pathways.

Platelet-to-Lymphocyte and Neutrophil-to-Lymphocyte Ratio as Predictive Biomarkers for Early-onset Neonatal Sepsis.

OBJECTIVE: To determine the predictive significance of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in early-onset neonatal sepsis (EONS). STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: The Neonatal Intensive Care Unit (NICU), Affiliated Hospital of Yanbian University, Jilin, China, from January 2018 to January 2020. METHODOLOGY: Of the total 124 children, 74 children with EONS were enrolled in group A and 50 children without infection-related diseases were enrolled in group B (control). The EONS risk factors were evaluated by logistic regression. Besides, the PLR and NLR diagnostic performances in EONS were evaluated by plotting the receiving operating characteristic (ROC) curves. RESULTS: In the univariate analysis, the differences for platelet count, lymphocyte number, neutrophil number, NLR, and PLR, between group A and group B were of statistical significance (p = 0.02, 0.021, <0.001, <0.001, and <0.001 respectively). As suggested by logistic regression, PLR and NLR were identified as the factors to independently predict the risk of EONS (p = 0.012, and 0.003, respectively). In addition, the value of area under the ROC curve (AUC) of NLR in predicting EONS was 0.788 (95% CI: 0.708-0.868; p <0.001), which was greater than that of PLR. At the NLR value of ≥3.169, the sensitivity of predicting EONS was 77%, and the specificity was 78%. CONCLUSION: Peripheral blood NLR and PLR have high predictive value for EONS. The predictive value of NLR as a biomarker for EONS evaluation was greater than that of PLR. Key Words: Neonatal sepsis, Logistic models, ROC curve, Blood cell count.