A Glial K/Cl Transporter Controls Neuronal Receptive Ending Shape by Chloride Inhibition of an rGC.

Neurons receive input from the outside world or from other neurons through neuronal receptive endings (NREs). Glia envelop NREs to create specialized microenvironments; however, glial functions at these sites are poorly understood. Here, we report a molecular mechanism by which glia control NRE shape and associated animal behavior. The C. elegans AMsh glial cell ensheathes the NREs of 12 neurons, including the thermosensory neuron AFD. KCC-3, a K/Cl transporter, localizes specifically to a glial microdomain surrounding AFD receptive ending microvilli, where it regulates K(+) and Cl(-) levels. We find that Cl(-) ions function as direct inhibitors of an NRE-localized receptor-guanylyl-cyclase, GCY-8, which synthesizes cyclic guanosine monophosphate (cGMP). High cGMP mediates the effects of glial KCC-3 on AFD shape by antagonizing the actin regulator WSP-1/NWASP. Components of this pathway are broadly expressed throughout the nervous system, suggesting that ionic regulation of the NRE microenvironment may be a conserved mechanism by which glia control neuron shape and function.

Dynamic Liver Chip Based on Well-Coupled Microfluidics: An Accurate NASH Model for Drug Evaluation.

The convenient liver model in vitro recapitulating the hepatic functions, metabolism, and even steatohepatitis to perform the accurate drug evaluation is still challenging because of the unattainable hominine physiological microenvironment in vitro. Here, the progressed stages of nonalcoholic steatohepatitis (NASH) disease were precisely modeled to accurately evaluate the performance of antilipemic based on the dynamic liver chip adopting the well-coupled microfluidics, which well recapitulated the normal and steatohepatitis of liver in vitro. In brief, the mild nutrient flow and sufficient oxygen supply for parenchymal liver cells could be well supplied through the endothelial cells layer that mimicked the real physiological barrier of endothelium, while the loading of drugs might be obtained by directly adding drug into the running nutrient flow to mimic the intravenously administrable. The progressed degree of steatohepatitis could be directly reflected by the amount of intramyocellular lipid content (IMLC) of the HepG2 cell hepatocyte layer in wells that were induced by different concentrations of free fatty acids (FFA). To prove the concept of the liver chip in drug evaluation, an accurate assessment of the performance of firsocostat, the acetyl-CoA carboxylase (ACC) inhibitor of hepatic mitochondria of hepatocytes, was carried out. The subtle time dependence of firsocostat treatment to different progressed stages of NASH was clearly figured out. Therefore, we prospect the liver chip that adopted well-coupled microfluidics could be an accurate and standard liver model in vitro to carry out the antilipemic evaluation and screening, which significantly enlightens the drug evaluation by liver on chip in vitro.

Antibiotic feeding changes the bacterial community of Chilo suppressalis and thereby affects its pesticide tolerance.

BACKGROUND: Owing to the widespread use of chemical pesticides to control agricultural pests, pesticide tolerance has become a serious problem. In recent years, it has been found that symbiotic bacteria are related to pesticides tolerance. To investigate the potential role of microorganisms in the pesticide tolerance of Chilo suppressalis, this study was conducted. RESULTS: The insect was fed with tetracycline and cefixime as the treatment group (TET and CFM, respectively), and did not add antibiotics in the control groups (CK). The 16S rDNA sequencing results showed that antibiotics reduced the diversity of C. suppressalis symbiotic microorganisms but did not affect their growth and development. In bioassays of the three C. suppressalis groups (TET, CFM, and CK), a 72 h LC50 fitting curve was calculated to determine whether long-term antibiotic feeding leads to a decrease in pesticide resistance. The CK group of C. suppressalis was used to determine the direct effect of antibiotics on pesticide tolerance using a mixture of antibiotics and pesticides. Indirect evidence suggests that antibiotics themselves did not affect the pesticide tolerance of C. suppressalis. The results confirmed that feeding C. suppressalis cefixime led to a decrease in the expression of potential tolerance genes to chlorantraniliprole. CONCLUSIONS: This study reveals the impact of antibiotic induced changes in symbiotic microorganisms on the pesticide tolerance of C. suppressalis, laying the foundation for studying the interaction between C. suppressalis and microorganisms, and also providing new ideas for the prevention and control of C. suppressalis and the creation of new pesticides.

The landscape of angiogenesis and inflammatory factors in eyes with myopic choroidal neovascularization before and after anti-VEGF injection.

INTRODUCTION: To investigate the levels of angiogenesis and inflammatory cytokines in individuals with myopic choroidal neovascularization (mCNV) and the changes in these factors following intravitreal anti-VEGF injection. METHODS: Aqueous humor samples were gathered from eyes with mCNV, those with single macular bleeding (SMB) without mCNV in highly myopic eyes, and those with age-related cataracts. Using a multiplex bead immunoassay, we analyzed 28 angiogenesis and inflammatory factors in the aqueous humor. Furthermore, clinical data were documented for correlation analysis. RESULTS: In this study, the levels of vascular endothelial growth factor A (VEGF-A), interleukin 8 (IL-8), and fibroblast growth factors 1 (FGF-1) were significantly elevated in mCNV compared to SMB eyes (p < 0.05). Their odds ratios for mCNV occurrence were 1.05, 3.45, and 2.64, respectively. Hepatocyte growth factor (HGF) and VEGF-C were notably higher in mCNV than in cataract patients (p < 0.05), and VEGF-C correlated to the degree of myopic atrophic maculopathy (p = 0.024). Axial length exhibited a negative correlation with VEGF-A and positive correlations with VEGF-C, HGF, and MCP-1 (p < 0.01). Following anti-VEGF treatment, a reduction in VEGF-A, endothelin-1, and FGF-2 was noted in mCNV patients (p < 0.05), but MCP-1 levels increased. CONCLUSION: Our findings highlight the predominant role of angiogenesis and inflammation factors in mCNV pathogenesis. VEGF-C's correlation with axial length and atrophy suggests its involvement in the process of myopic atrophic maculopathy.

A colorimetric/electrochemical sensor based on coral-like CuCo2O4@AuNPs composites for sensitive dopamine detection.

As a central neurotransmitter, DA (dopamine) plays a vital part in human metabolism, and its accurate detection is of great significance in disease diagnosis. In this work, we used Cu/Co bimetallic metal-organic frameworks (MOFs) as templates and gold nanoparticles (AuNPs) to construct novel nanocomposite coral-like CuCo2O4@AuNPs with strong peroxidase activity and electrochemical response. The coral-like CuCo2O4@AuNPs showed excellent peroxidase activity, and the Km value was as low as 0.358 mM. In the presence of H2O2, the colorless substrate 3,3',5,5', -tetramethylbenzidine (TMB) can be catalytically oxidized into a blue product. Simultaneously, coral-like CuCo2O4@AuNPs, as an electroactive substance, possess strong electrocatalytic activity, which enhances the electron-transfer rate and promotes excellent current response. In the presence of DA, coral-like CuCo2O4@AuNPs can catalyze the oxidation of DA to dopaquinone, which further enhances the electrochemical signal. In addition, DA captures hydroxyl radicals and inhibits the oxidation of TMB, resulting in an obvious color change (blue turns colorless) and realizing colorimetric detection with the naked eye. On this basis, we successfully established a dual-mode colorimetric/electrochemical sensor using coral-like CuCo2O4@AuNP nanocomposites as a dual-signal probe. Combining colorimetric and electrochemical detection, the sensor achieved a wide linear range (0-1 mM) and a low detection limit (0.07 µM) for DA concentration. It was also successfully used for the detection of DA in human serum and urine with good results. In summary, this work provides an intuitive, economical, sensitive, and promising platform for DA detection.

DIFFERENCES IN THE PROGRESSION BETWEEN MYOPIC MACULOSCHISIS EYES WITH AND WITHOUT MACULAR DETACHMENT IN THE NATURAL COURSE OF THE DISEASE: A Retrospective Longitudinal Study Based on the New Myopic Traction Maculopathy Staging System.

PURPOSE: To investigate the pace of visual acuity loss in myopic maculoschisis eyes with or without macular detachment and identify associated risk factors. METHODS: One thousand three hundred and thirty-four eyes of 991 patients with high myopia were reviewed. A new myopic traction maculopathy staging system classified four retinal stages and three foveal stages. To the myopic traction maculopathy eyes with normal fovea, maculoschisis with and without macular detachment was defined as Stage 3a and Stages 1a, 2a respectively. RESULTS: One hundred and ten (8.25%) eyes with maculoschisis were included, with a follow-up of 24.00 ± 17.47 months. Of them, 84 (76.36%) were Stages 1a, 2a, and 26 (23.64%) were Stage 3a. The visual acuity loss per year during the follow-up period was similar between eyes with Stages 1a, 2a and Stage 3a (3.13 ± 12.21 vs. 3.41 ± 18.42 letters, P = 0.930). Multivariate analyses revealed that vitreomacular interface factors were significantly associated with visual acuity loss during the follow-up, no matter in Stages 1a, 2a or Stage 3a ( P = 0.039 and P = 0.038, respectively). In the Stages 1a, 2a group, the percentage of eyes that lost at least 10 letters at the final visit compared with the baseline visual acuity was higher in eyes with vitreomacular interface factors than in those without vitreomacular interface factors (13 eyes, 50.00% vs. 14 eyes, 24.14%, P = 0.019). CONCLUSION: No differences were found in visual acuity loss pace between Stages 1a, 2a and Stage 3a. Surgical intervention or at least more intensive follow-up should be considered for Stages 1a, 2a eyes with vitreomacular interface factors, to promote a more favorable visual outcome.

VISION AND METAMORPHOPSIA OUTCOMES OF MACULAR BUCKLING FOR FOVEOSCHISIS-ASSOCIATED MACULAR DETACHMENT IN HIGHLY MYOPIC EYES.

PURPOSE: To assess the functional outcomes in visual acuity, metamorphopsia, and vision-related quality of life (VR-QOL) and to evaluate prognostic factors after macular buckling (MB) surgery in eyes with high myopia and foveoschisis (FS)-associated macular detachment (MD). METHODS: Thirty-nine eyes of 39 patients with FS-associated MD who underwent MB surgery were enrolled. Measured outcomes comprised best-corrected visual acuity (BCVA), metamorphopsia, VR-QOL, axial length (AL), macular reattachment, and resolution of foveoschisis. In addition, factors affecting final BCVA and metamorphopsia were analyzed. RESULTS: At 12 months postoperatively, 36 eyes (92.31%) achieved macular reattachment, 37 eyes (94.87%) achieved complete resolution of foveoschisis, and metamorphopsia diminished in 31 eyes (79.49%). LogMAR BCVAs at baseline and months 1, 3, 6, and 12 postoperatively were 0.62 ± 0.35 (20/83), 0.65 ± 0.3 (20/89), 0.59 ± 0.31 (20/77), 0.54 ± 0.31 (20/69), and 0.46 ± 0.27 (20/57) (P < 0.001), respectively. Metamorphopsia scores by M-CHARTS were 1.36° ± 0.51°, 1.04° ± 0.51°, 0.74° ± 0.47°, 0.59° ± 0.47°, and 0.13° ± 0.29° (P < 0.001). All Visual Function Questionnaire-25 subscales demonstrated significant improvement postoperatively, with the exception of "general health" (P = 0.08) and "driving" (P = 0.111). Preoperative BCVA was an independent risk factor for postoperative BCVA at month 12 (r = 0.638, P < 0.001), and the preoperative M-score was an independent risk factor for postoperative M-score at month 12 (r = 0.187, P = 0.045). CONCLUSION: MB surgery significantly improved BCVA, metamorphopsia, and VR-QOL in patients with FS-associated MD. Preoperative BCVA and metamorphopsia score were prognostic factors for postoperative BCVA and metamorphopsia score at month 12.

Nanoparticulate bioceramic putty suppresses osteoclastogenesis and inflammatory bone loss in mice via inhibition of TRAF6-mediated signalling pathways: A laboratory investigation.

AIM: This study aimed to determine the effects of iRoot BP Plus on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vitro and inflammation-mediated bone resorption in vivo and investigated the underlying molecular mechanisms. METHODOLOGY: CCK-8 was performed to test cell viability in RANKL-induced RAW 264.7 cells and BMDMs in response to iRoot BP Plus. The effect of iRoot BP Plus on osteoclastogenesis was determined using TRAP staining and phalloidin staining, respectively. Pit formation assay was conducted to measure osteoclast resorptive capacity. Western blot and qPCR were performed to examine osteoclast-related proteins and gene expression, respectively. Western blot was also used to investigate the signalling pathways involved. For in vivo experiments, an LPS-induced mouse calvarial bone resorption model was established to analyse the effect of iRoot BP Plus on bone resorption (n = 6 per group). At 7 days, mouse calvaria were collected and prepared for histological analysis. RESULTS: We identified that iRoot BP Plus extracts significantly attenuated RANKL-induced osteoclastogenesis, reduced sealing zone formation, restrained osteolytic capacity and decreased osteoclast-specific gene expression (p < .01). Mechanistically, iRoot BP Plus extracts reduced TRAF6 via proteasomal degradation, then suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), blocked the nuclear translocation of c-Fos and diminished nuclear factor-κB (NF-κB) p65 and NFATc1 accumulation. Consistent with the in vitro results, iRoot BP Plus extracts attenuated osteoclast activity thus protecting against inflammatory bone resorption in vivo (p < .05), which was accompanied by a suppression of TRAF6, c-Fos, NFATc1 and cathepsin K expression. CONCLUSION: These findings provide valuable insights into the signalling mechanisms underlying nanoparticulate bioceramic putty-mediated bone homeostasis.

Phosphate-functionalized Zirconium Metal-Organic Frameworks for Enhancing Lithium-Sulfur Battery Cycling.

Lithium-sulfur batteries are promising candidates for next-generation energy storage devices due to their outstanding theoretical energy density. However, they suffer from low sulfur utilization and poor cyclability, greatly limiting their practical implementation. Herein, we adopted a phosphate-functionalized zirconium metal-organic framework (Zr-MOF) as a sulfur host. With their porous structure, remarkable electrochemical stability, and synthetic versatility, Zr-MOFs present great potential in preventing soluble polysulfides from leaching. Phosphate groups were introduced to the framework post-synthetically since they have shown a strong affinity towards lithium polysulfides and an ability to facilitate Li ion transport. The successful incorporation of phosphate in MOF-808 was demonstrated by a series of techniques including infrared spectroscopy, solid-state nuclear magnetic resonance spectroscopy, and X-ray pair distribution function analysis. When employed in batteries, phosphate-functionalized Zr-MOF (MOF-808-PO4) exhibits significantly enhanced sulfur utilization and ion diffusion compared to the parent framework, leading to higher capacity and rate capability. The improved capacity retention and inhibited self-discharge rate also demonstrate effective polysulfide encapsulation utilizing MOF-808-PO4. Furthermore, we explored their potential towards high-density batteries by examining the cycling performance at various sulfur loadings. Our approach to correlate structure with function using hybrid inorganic-organic materials offers new chemical design strategies for advancing battery materials.

Colorimetric and handheld pH meter dual-signal readout platform for E. coli detection based on a cascade reaction.

A dual-signal readout has been designed detecting platform based on a cascade reaction for Escherichia coli (E. coli) detection by using colorimetric approach and a handheld pH meter. The immunoreaction was conducted using polydopamine@copper ferrite-Ag nanoparticles (PDA@CuFe2O4-Ag NP) and a glucose oxidase (GOD)-conjugated graphene oxide-gold nanosheet composite (GOD-GO/Au NS) to synthesize a sandwich complex mode between targets. Together with the formation of immune complexes, the GOD-GO/Au NS can catalyze glucose to produce gluconic acid and hydrogen peroxide (H2O2). The gluconic acid produced altered the pH of the detection solution. Since the PDA@CuFe2O4-Ag NP have good peroxidase-like activity, they can catalyze the oxidation of TMB to the blue product oxTMB once H2O2 is produced in the reaction system, and the absorbance change of oxTMB at 652 nm can be recorded using ultraviolet-visible (UV-Vis) spectroscopy. Interestingly, the PDA@CuFe2O4-Ag NP composites can consume the generated H2O2, and can create a reaction cycle that promotes glucose oxidation. Under optimal conditions, the proposed dual-channel signal platform is proportional to the logarithm of the E. coli concentration within a range of 102-107 cfu mL-1. Additionally, the devised approach was successfully used to detect E. coli at the required levels in real samples. This dual-mode detection method notably enhances the accuracy and diversity of detection, and curbs the false negative and positive rates.