Enhancing Solar-Driven Water Purification by Multiscale Biomimetic Evaporators Featuring Lamellar MoS2/GO Heterojunctions.

Solar-powered steam generation holds a strong sustainability in facing the global water crisis, while the production efficiency and antifouling performance remain challenges. Inspired by river moss, a multiscale biomimetic evaporator is designed, where the key photothermal conversion film composed of lamellar MoS2/graphene oxides (GO) can significantly enhance the evaporation efficiency and solve the problem of fouling. First-level leaf-like MoS2/GO nanosheets, obtained by a modified hydrothermal synthesis with an assisted magnetic-field rotation stirring, are self-assembled into a second-level nanoporous film, which achieves an evaporation rate (ER) of 1.69 kg m-2 h-1 under 1 sun illumination and an excellent self-cleaning ability. The tertiary-bionic evaporator with a macroscopic crownlike shape further enhances the ER to 3.20 kg m-2 h-1, 189% above that of planar film, yielding 20.25 kg m2 of freshwater from seawater during a daytime exposure of 6 h. The exceptional outcomes originate from the macroscopic biomimetic design and the microscopic integration of heterojunction interfaces between the MoS2 and GO interlayers and the nanoporous surface. The biomimetic evaporator indicates a potential direction through surface/interface regulation of photothermal nanomaterials for water desalination.

Serum Metabolomics Reveals a Potential Benefit of Methionine in Type 1 Diabetes Patients with Poor Glycemic Control and High Glycemic Variability.

Glycemic variability (GV) in some patients with type 1 diabetes (T1D) remains heterogeneous despite comparable clinical indicators, and whether other factors are involved is yet unknown. Metabolites in the serum indicate a broad effect of GV on cellular metabolism and therefore are more likely to indicate metabolic dysregulation associated with T1D. To compare the metabolomic profiles between high GV (GV-H, coefficient of variation (CV) of glucose ≥ 36%) and low GV (GV-L, CV < 36%) groups and to identify potential GV biomarkers, metabolomics profiling was carried out on serum samples from 17 patients with high GV, 16 matched (for age, sex, body mass index (BMI), diabetes duration, insulin dose, glycated hemoglobin (HbA1c), fasting, and 2 h postprandial C-peptide) patients with low GV (exploratory set), and another 21 (GV-H/GV-L: 11/10) matched patients (validation set). Subsequently, 25 metabolites were significantly enriched in seven Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between the GV-H and GV-L groups in the exploratory set. Only the differences in spermidine, L-methionine, and trehalose remained significant after validation. The area under the curve of these three metabolites combined in distinguishing GV-H from GV-L was 0.952 and 0.918 in the exploratory and validation sets, respectively. L-methionine was significantly inversely related to HbA1c and glucose CV, while spermidine was significantly positively associated with glucose CV. Differences in trehalose were not as reliable as those in spermidine and L-methionine because of the relatively low amounts of trehalose and the inconsistent fold change sizes in the exploratory and validation sets. Our findings suggest that metabolomic disturbances may impact the GV of T1D. Additional in vitro and in vivo mechanistic studies are required to elucidate the relationship between spermidine and L-methionine levels and GV in T1D patients with different geographical and nutritional backgrounds.

S100A9 induces reactive oxygen species-dependent formation of neutrophil extracellular traps in abdominal sepsis.

Recent evidence suggests that targeting S100A9 reduces pathological inflammation in abdominal sepsis. Herein, we investigated the role of S100A9 in neutrophil extracellular trap (NET) formation in septic lung damage. NETs were detected by electron microscopy in the lung and by confocal microscopy in vitro. Stimulation of isolated mouse bone marrow-derived neutrophils with S100A9 triggered formation of NETs. Blocking TLR4 and RAGE reduced S100A9-induced generation of NETs and DNA-histone complexes. Moreover, S100A9 challenge increased generation of reactive oxygen species (ROS) in bone marrow neutrophils. Co-incubation with the NADPH oxidase inhibitor not only decreased ROS formation but also attenuated induction of DNA-histone complexes in S100A9-stimulated neutrophils. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in male C57BL/6 mice. Administration of the S100A9 inhibitor ABR-238901 decreased CLP-induced formation of NETs in lungs and DNA-histone complexes in plasma. In addition, transmission electron microscopy revealed that S100A9 was abundantly expressed on NETs in the lungs in CLP mice. By use of intravital microscopy, we found that local injection of NETs increased leukocyte adhesion and migration in the mouse cremaster muscle microvasculature. Notably, treatment with ABR-238901 attenuated NET-induced leukocyte adhesion and extravasation in the cremaster muscle, suggesting that NET-associated S100A9 promotes leukocyte recruitment in vivo. Taken together, these novel findings suggest that S100A9 triggers ROS-dependent formation of NETs via TLR4 and RAGE signaling in neutrophils. Moreover, S100A9 regulates both formation of NETs and NET-induced leukocyte recruitment in vivo. Thus, targeting S100A9 might be useful to ameliorate lung damage in abdominal sepsis.

Analysis of detrended fluctuation function derived from continuous glucose monitoring may assist in distinguishing latent autoimmune diabetes in adults from T2DM.

Background: We aimed to explore the performance of detrended fluctuation function (DFF) in distinguishing patients with latent autoimmune diabetes in adults (LADA) from type 2 diabetes mellitus (T2DM) with glucose data derived from continuous glucose monitoring. Methods: In total, 71 LADA and 152 T2DM patients were enrolled. Correlations between glucose parameters including time in range (TIR), mean glucose, standard deviation (SD), mean amplitude of glucose excursions (MAGE), coefficient of variation (CV), DFF and fasting and 2-hour postprandial C-peptide (FCP, 2hCP) were analyzed and compared. Receiver operating characteristics curve (ROC) analysis and 10-fold cross-validation were employed to explore and validate the performance of DFF in diabetes classification respectively. Results: Patients with LADA had a higher mean glucose, lower TIR, greater SD, MAGE and CV than those of T2DM (P<0.001). DFF achieved the strongest correlation with FCP (r = -0.705, P<0.001) as compared with TIR (r = 0.485, P<0.001), mean glucose (r = -0.337, P<0.001), SD (r = -0.645, P<0.001), MAGE (r = -0.663, P<0.001) and CV (r = -0.639, P<0.001). ROC analysis showed that DFF yielded the greatest area under the curve (AUC) of 0.862 (sensitivity: 71.2%, specificity: 84.9%) in differentiating LADA from T2DM as compared with TIR, mean glucose, SD, MAGE and CV (AUC: 0.722, 0.650, 0.800, 0.820 and 0.807, sensitivity: 71.8%, 47.9%, 63.6%, 72.7% and 78.8%, specificity: 67.8%, 83.6%, 80.9%, 80.3% and 72.4%, respectively). The kappa test indicated a good consistency between DFF and the actual diagnosis (kappa = 0.551, P<0.001). Ten-fold cross-validation showed a stable performance of DFF with a mean AUC of 0.863 (sensitivity: 78.8%, specificity: 77.8%) in 10 training sets and a mean AUC of 0.866 (sensitivity: 80.9%, specificity: 84.1%) in 10 test sets. Conclusions: A more violent glucose fluctuation pattern was marked in patients with LADA than T2DM. We first proposed the possible role of DFF in distinguishing patients with LADA from T2DM in our study population, which may assist in diabetes classification.

The continuous spectrum of glycaemic variability changes with pancreatic islet function: A multicentre cross-sectional study in China.

AIMS: To investigate glycaemic variability (GV) patterns in patients with type 1 diabetes (T1D), type 2 diabetes (T2D), and latent autoimmune diabetes in adults (LADA). MATERIALS AND METHODS: A total of 842 subjects (510 T1D, 105 LADA, 227 T2D) were enrolled and underwent 1 week of continuous glucose monitoring (CGM). Clinical characteristics and CGM parameters were compared among T1D, LADA, and T2D. LADA patients were divided into two subgroups based on glutamic acid decarboxylase autoantibody titres (≥180 U/mL [LADA-1], <180 U/mL [LADA-2]) and compared. The C-peptide cut-offs for predicting a coefficient of variation (CV) of glucose ≥36% and a time in range (TIR) > 70% were determined using receiver operating characteristic analysis. RESULTS: Twenty-seven patients (9 T1D, 18 T2D) were excluded due to insufficient CGM data. Sex, diabetes duration and HbA1c were comparable among the three groups. Fasting and 2-h postprandial C-peptide (FCP, 2hCP) increased sequentially across T1D, LADA, and T2D. T1D and LADA patients had comparable TIR and GV, whereas those with T2D had much higher TIR and lower GV (p < 0.001). The GV of LADA-1 was close to that of T1D, while the GV of LADA-2 was close to that of T2D. CP exhibited the strongest negative correlation with GV. The cut-offs of FCP/2hCP for predicting a CV ≥ 36% and TIR >70% were 121.6/243.1 and 128.9/252.8 pmol/L, respectively. CONCLUSIONS: GV presented a continuous spectrum across T1D, LADA-1, LADA-2, and T2D. More frequent glucose monitoring is suggested for patients with impaired insulin secretion. CLINICAL TRAIL REGISTRATION: Chinese Clinical Trial Registration (ChiCTR) website approved by WHO; http://www.chictr.org.cn/ - ChiCTR2200065036.

Corrigendum: Effect of the Chinese New Year public holiday on the glycemic control of T1DM with intensive insulin therapy.

[This corrects the article DOI: 10.3389/fendo.2022.915482.].

Effect of the Chinese New Year Public Holiday on the Glycemic Control of T1DM With Intensive Insulin Therapy.

Aims: There is limited evidence that evaluates the glycemic control of type 1 diabetes mellitus (T1DM) during the Chinese New Year public holiday in China. The Chinese New Year public holiday represents various challenges to glycemic control, especially in T1DM patients, in China. We aimed to assess the effect of the Chinese New Year public holiday on several glucose metrics using flash glucose monitoring (FGM) in patients with T1DM. Methods: Complete FGM data for 1 week before, 1 week during and 1 week after the Chinese New Year public holiday were available for 71 T1DM patients treated with multiple daily insulin injection (MDI) therapy (n = 51) or continuous subcutaneous insulin infusion (CSII) treatment (n = 20). The mean age of the study participants was 13 (9, 30) years. Of note, 59.2% of the patients (n = 42) were adults, and 40.8% of the patients (n = 29) were minors. The interval between each two adjacent periods was one week. The indicators of mean glucose, glucose variability and time in different glycemic ranges were analyzed. Results: The Chinese New Year public holiday was associated with an increase in mean blood glucose (8.4 ± 1.7 vs. 9.2 ± 2.5; P < 0.001) and time above range (TAR) (27.9% ± 16.6% vs. 35.0% ± 22.3%; P< 0.001) but a decrease in time in range (TIR) (65.1% ± 15.5% vs. 58.0% ± 19.0%; P < 0.001) and coefficient of variation (CV) (65.1% ± 15.5% vs. 58.0% ± 19.0%; P < 0.001). There was no significant difference in time below range (TBR). The glycemic control deteriorated during the Chinese New Year public holiday in our study population regardless of age. Interestingly, in the CSII group, none of the metrics of glucose control significantly changed during the Chinese New Year public holiday. Conclusions: These results suggested that less self-management may worsen glycemic control in the short term, indicating a need for more refined management algorithms during the Chinese New Year public holiday for T1DM patients.

Actin-related protein 2/3 complex regulates neutrophil extracellular trap expulsion and lung damage in abdominal sepsis.

Neutrophil extracellular trap (NET) formation is a key feature in sepsis. The aim of the present study was to examine the role of the actin cytoskeleton in regulating the expulsion of NETs. Actin-related protein 2/3 (Arp 2/3) complex is an important regulator of F-actin polymerization. Coincubation with CK666, a specific Arp 2/3 inhibitor, decreased 12-phorbol 13-myristate acetate-induced NET formation in vitro. CK666 not only abolished F-actin polymerization but also caused intracellular retention of NETs. Inhibition of Arp 2/3 reduced NET formation on circulating neutrophils and in the bronchoalveolar space in mice undergoing cecal ligation and puncture (CLP). Notably, treatment with CK666 attenuated CLP-induced neutrophil recruitment, edema formation, and tissue damage in the lungs. Moreover, Arp 2/3 inhibition decreased levels of C-X-C motif chemokine ligand 1 (CXCL-1) and interleukin-6 in the lung and plasma of septic animals. Taken together, this study shows that expulsion of NETs is regulated by the actin cytoskeleton and that inhibition of Arp 2/3-dependent F-actin polymerization not only decreases NET formation but also protects against pathological inflammation and tissue damage in septic lung injury. Thus, we suggest that targeting NET release is a novel and useful way to ameliorate lung damage in abdominal sepsis.

c-Abl kinase regulates neutrophil extracellular trap formation and lung injury in abdominal sepsis.

Sepsis is associated with exaggerated neutrophil responses although mechanisms remain elusive. The aim of this study was to investigate the role of c-Abelson (c-Abl) kinase in neutrophil extracellular trap (NET) formation and inflammation in septic lung injury. Abdominal sepsis was induced by cecal ligation and puncture (CLP). NETs were detected by electron microscopy in the lung and by confocal microscopy in vitro. Plasma levels of DNA-histone complexes, interleukin-6 (IL-6) and CXC chemokines were quantified. CLP-induced enhanced phosphorylation of c-Abl kinase in circulating neutrophils. Administration of the c-Abl kinase inhibitor GZD824 not only abolished activation of c-Abl kinase in neutrophils but also reduced NET formation in the lung and plasma levels of DNA-histone complexes in CLP mice. Moreover, inhibition of c-Abl kinase decreased CLP-induced lung edema and injury. Administration of GDZ824 reduced CLP-induced increases in the number of alveolar neutrophils. Inhibition of c-Abl kinase also markedly attenuated levels of CXC chemokines in the lung and plasma as well as IL-6 levels in the plasma of septic animals. Taken together, this study demonstrates that c-Abl kinase is a potent regulator of NET formation and we conclude that c-Abl kinase might be a useful target to ameliorate lung damage in abdominal sepsis.

E3 Ubiquitin Ligase Midline 1 Regulates Endothelial Cell ICAM-1 Expression and Neutrophil Adhesion in Abdominal Sepsis.

Septic lung damage is associated with endothelial cell and neutrophil activation. This study examines the role of the E3 ubiquitin ligase midline 1 (Mid1) in abdominal sepsis. Mid1 expression was increased in endothelial cells derived from post-capillary venules in septic mice and TNF-α challenge increased Mid1 levels in endothelial cells in vitro. The siRNA-mediated knockdown of Mid1 decreased TNF-α-induced upregulation of ICAM-1 and neutrophil adhesion to endothelial cells. Moreover, Mid1 silencing reduced leukocyte adhesion in post-capillary venules in septic lungs in vivo. The silencing of Mid1 not only decreased Mid1 expression but also attenuated expression of ICAM-1 in lungs from septic mice. Lastly, TNF-α stimulation decreased PP2Ac levels in endothelial cells in vitro, which was reversed in endothelial cells pretreated with siRNA directed against Mid1. Thus, our novel data show that Mid1 is an important regulator of ICAM-1 expression and neutrophil adhesion in vitro and septic lung injury in vivo. A possible target of Mid1 is PP2Ac in endothelial cells. Targeting the Mid1-PP2Ac axis may be a useful way to reduce pathological lung inflammation in abdominal sepsis.

Targeting S100A9 Reduces Neutrophil Recruitment, Inflammation and Lung Damage in Abdominal Sepsis.

S100A9, a pro-inflammatory alarmin, is up-regulated in inflamed tissues. However, the role of S100A9 in regulating neutrophil activation, inflammation and lung damage in sepsis is not known. Herein, we hypothesized that blocking S100A9 function may attenuate neutrophil recruitment in septic lung injury. Male C57BL/6 mice were pretreated with the S100A9 inhibitor ABR-238901 (10 mg/kg), prior to cercal ligation and puncture (CLP). Bronchoalveolar lavage fluid (BALF) and lung tissue were harvested for analysis of neutrophil infiltration as well as edema and CXC chemokine production. Blood was collected for analysis of membrane-activated complex-1 (Mac-1) expression on neutrophils as well as CXC chemokines and IL-6 in plasma. Induction of CLP markedly increased plasma levels of S100A9. ABR-238901 decreased CLP-induced neutrophil infiltration and edema formation in the lung. In addition, inhibition of S100A9 decreased the CLP-induced up-regulation of Mac-1 on neutrophils. Administration of ABR-238901 also inhibited the CLP-induced increase of CXCL-1, CXCL-2 and IL-6 in plasma and lungs. Our results suggest that S100A9 promotes neutrophil activation and pulmonary accumulation in sepsis. Targeting S100A9 function decreased formation of CXC chemokines in circulation and lungs and attenuated sepsis-induced lung damage. These novel findings suggest that S100A9 plays an important pro-inflammatory role in sepsis and could be a useful target to protect against the excessive inflammation and lung damage associated with the disease.

Transcriptomic Analysis Reveals Differential Expression of Genes between Lung Capillary and Post Capillary Venules in Abdominal Sepsis.

Lung endothelial cell dysfunction plays a central role in septic-induced lung injury. We hypothesized that endothelial cell subsets, capillary endothelial cells (capEC) and post capillary venules (PCV), might play different roles in regulating important pathophysiology in sepsis. In order to reveal global transcriptomic changes in endothelial cell subsets during sepsis, we induced sepsis in C57BL/6 mice by cecal ligation and puncture (CLP). We confirmed that CLP induced systemic and lung inflammation in our model. Endothelial cells (ECs) from lung capillary and PCV were isolated by cell sorting and transcriptomic changes were analyzed by bioinformatic tools. Our analysis revealed that lung capEC are transcriptionally different than PCV. Comparison of top differentially expressed genes (DEGs) of capEC and PCV revealed that capEC responses are different than PCV during sepsis. It was found that capEC are more enriched with genes related to regulation of coagulation, vascular permeability, wound healing and lipid metabolic processes after sepsis. In contrast, PCV are more enriched with genes related to chemotaxis, cell-cell adhesion by integrins, chemokine biosynthesis, regulation of actin filament process and neutrophil homeostasis after sepsis. In addition, we predicted some transcription factor targets that regulate a significant number of DEGs in sepsis. We proposed that targeting certain DEGs or transcriptional factors would be useful in protecting against sepsis-induced lung damage.

Microvascular Mechanisms of Polyphosphate-Induced Neutrophil-Endothelial Cell Interactions in vivo.

BACKGROUND: Polyphosphates (PolyPs) have been reported to exert pro-inflammatory effects. However, the molecular mechanisms regulating PolyP-provoked tissue accumulation of leukocytes are not known. The aim of the present investigation was to determine the role of specific adhesion molecules in PolyP-mediated leukocyte recruitment. METHODS: PolyPs and TNF-α were intrascrotally administered, and anti-P-selectin, anti-E-selectin, anti-P-selectin glycoprotein ligand-1 (PSGL-1), anti-membrane-activated complex-1 (Mac-1), anti-lymphocyte function antigen-1 (LFA-1), and neutrophil depletion antibodies were injected intravenously or intraperitoneally. Intravital microscopy of the mouse cremaster microcirculation was used to examine leukocyte-endothelium interactions and recruitment in vivo. RESULTS: Intrascrotal injection of PolyPs increased leukocyte accumulation. Depletion of neutrophils abolished PolyP-induced leukocyte-endothelium interactions, indicating that neutrophils were the main leukocyte subtype responding to PolyP challenge. Immunoneutralization of P-selectin and PSGL-1 abolished PolyP-provoked neutrophil rolling, adhesion, and emigration. Moreover, immunoneutralization of Mac-1 and LFA-1 had no impact on neutrophil rolling but markedly reduced neutrophil adhesion and emigration evoked by PolyPs. CONCLUSION: These results suggest that P-selectin and PSGL-1 exert important roles in PolyP-induced inflammatory cell recruitment by mediating neutrophil rolling. In addition, our data show that Mac-1 and LFA-1 are necessary for supporting PolyP-triggered firm adhesion of neutrophils to microvascular endothelium. These novel findings define specific molecules as potential targets for pharmacological intervention in PolyP-dependent inflammatory diseases.

Layer-by-layer self-assembly and disassembly of single charged inorganic small molecules: towards surface patterning.

The patterning of layer-by-layer (LbL) polyelectrolyte multilayers with metal ions is important for the facile fabrication of circuits or selective catalysis. The strategy includes two issues: the incorporation of metal ions and their controlled assembly-disassembly, which require a good understanding of the assembly mechanism. Therefore, we explored the LbL assembly between a polycation, poly-(diallyldimethylammonium chloride) (PDDA) and an inorganic single charged molecule, [AuCl4](-), which could assemble at pH = 3.7 and disassemble at lower pH values. Moreover, we have demonstrated that the driving force in the assembly is a ligand-to-metal charge transfer interaction. Combining the controlled assembly-disassembly of PDDA-[AuCl4](-) multilayers and photolithography, we obtained a surface pattern of PDDA-[AuCl4](-) multilayers.

The influence of fluid physicochemical properties on vibrating-mesh nebulization.

In this study, the effect of fluid physicochemical properties and the vibrating-mesh mechanism on the aerosols generated from vibrating-mesh nebulizers have been evaluated using fluids having a range of viscosity, surface tension and ion concentration. Two nebulizers were investigated: the Omron MicroAir NE-U22 (passively vibrating) and the Aeroneb Pro (actively vibrating) mesh nebulizers. For both devices, the total aerosol output was generally unaffected by fluid properties. Increased viscosity or ion concentration resulted in a decrease in droplet volume median diameter (VMD) and an increase in fine particle fraction (FPF). Moreover, increased viscosity resulted in prolonged nebulization and reduced output rate, particularly for the Omron nebulizer. Both nebulizers were unsuitable for delivery of viscous fluids since nebulization was intermittent or completely ceased at >1.92cP. The presence of ions reduced variability particularly for the Aeroneb Pro nebulizer. No clear effect of surface tension was observed on the performance of nebulizers employing a vibrating-mesh technology. However, when viscosity was low, reduced surface tension seemed advantageous in shortening the nebulization time and increasing the output rate, but for the Omron nebulizer this also increased the droplet VMD and decreased the FPF. This study has shown that vibrating-mesh nebulization was highly dependent on fluid characteristics and nebulizer mechanism of operation.