Compartmentalized metabolism supports midgestation mammalian development.

Mammalian embryogenesis requires rapid growth and proper metabolic regulation1. Midgestation features increasing oxygen and nutrient availability concomitant with fetal organ development2,3. Understanding how metabolism supports development requires approaches to observe metabolism directly in model organisms in utero. Here we used isotope tracing and metabolomics to identify evolving metabolic programmes in the placenta and embryo during midgestation in mice. These tissues differ metabolically throughout midgestation, but we pinpointed gestational days (GD) 10.5-11.5 as a transition period for both placenta and embryo. Isotope tracing revealed differences in carbohydrate metabolism between the tissues and rapid glucose-dependent purine synthesis, especially in the embryo. Glucose's contribution to the tricarboxylic acid (TCA) cycle rises throughout midgestation in the embryo but not in the placenta. By GD12.5, compartmentalized metabolic programmes are apparent within the embryo, including different nutrient contributions to the TCA cycle in different organs. To contextualize developmental anomalies associated with Mendelian metabolic defects, we analysed mice deficient in LIPT1, the enzyme that activates 2-ketoacid dehydrogenases related to the TCA cycle4,5. LIPT1 deficiency suppresses TCA cycle metabolism during the GD10.5-GD11.5 transition, perturbs brain, heart and erythrocyte development and leads to embryonic demise by GD11.5. These data document individualized metabolic programmes in developing organs in utero.

Metabolic heterogeneity confers differences in melanoma metastatic potential.

Metastasis requires cancer cells to undergo metabolic changes that are poorly understood1-3. Here we show that metabolic differences among melanoma cells confer differences in metastatic potential as a result of differences in the function of the MCT1 transporter. In vivo isotope tracing analysis in patient-derived xenografts revealed differences in nutrient handling between efficiently and inefficiently metastasizing melanomas, with circulating lactate being a more prominent source of tumour lactate in efficient metastasizers. Efficient metastasizers had higher levels of MCT1, and inhibition of MCT1 reduced lactate uptake. MCT1 inhibition had little effect on the growth of primary subcutaneous tumours, but resulted in depletion of circulating melanoma cells and reduced the metastatic disease burden in patient-derived xenografts and in mouse melanomas. In addition, inhibition of MCT1 suppressed the oxidative pentose phosphate pathway and increased levels of reactive oxygen species. Antioxidants blocked the effects of MCT1 inhibition on metastasis. MCT1high and MCT1-/low cells from the same melanomas had similar capacities to form subcutaneous tumours, but MCT1high cells formed more metastases after intravenous injection. Metabolic differences among cancer cells thus confer differences in metastatic potential as metastasizing cells depend on MCT1 to manage oxidative stress.

Gene delivery available in molluscan cells by strong promoter discovered from bivalve-infectious virus.

Understanding gene functions in marine invertebrates has been limited, largely due to the lack of suitable assay systems. Such a system requires investigative methods that are reproducible and can be quantitatively evaluated, such as a cell line, and a strong promoter that can drive high expression of a transgene. In this study, we established primary cell culture from a marine bivalve mollusc, Mizuhopecten yessoensis. Using scallop primary cells, we optimized electroporation conditions for transfection and carried out a luciferase-based promoter activity assay to identify strong promoter sequences that can drive expression of a gene of interest. We evaluated potential promoter sequences from genes of endogenous and exogenous origin and discovered a strong viral promoter derived from a bivalve-infectious virus, ostreid herpesvirus-1 (OsHV-1). This promoter, we termed OsHV-1 promoter, showed 24.7-fold and 16.1-fold higher activity than the cytomegalovirus immediate early (CMV IE) promoter and the endogenous EF1α promoter, the two most commonly used promoters in bivalves so far. Our GFP assays showed that the OsHV-1 promoter is active not only in scallop cells but also in HEK293 cells and zebrafish embryos. The OsHV-1 promoter practically enables functional analysis of marine molluscan genes, which can contribute to unveiling gene-regulatory networks underlying astonishing regeneration, adaptation, reproduction, and aging in marine invertebrates.

Loss of glucose 6-phosphate dehydrogenase function increases oxidative stress and glutaminolysis in metastasizing melanoma cells.

The pentose phosphate pathway is a major source of NADPH for oxidative stress resistance in cancer cells but there is limited insight into its role in metastasis, when some cancer cells experience high levels of oxidative stress. To address this, we mutated the substrate binding site of glucose 6-phosphate dehydrogenase (G6PD), which catalyzes the first step of the pentose phosphate pathway, in patient-derived melanomas. G6PD mutant melanomas had significantly decreased G6PD enzymatic activity and depletion of intermediates in the oxidative pentose phosphate pathway. Reduced G6PD function had little effect on the formation of primary subcutaneous tumors, but when these tumors spontaneously metastasized, the frequency of circulating melanoma cells in the blood and metastatic disease burden were significantly reduced. G6PD mutant melanomas exhibited increased levels of reactive oxygen species, decreased NADPH levels, and depleted glutathione as compared to control melanomas. G6PD mutant melanomas compensated for this increase in oxidative stress by increasing malic enzyme activity and glutamine consumption. This generated a new metabolic vulnerability as G6PD mutant melanomas were more dependent upon glutaminase than control melanomas, both for oxidative stress management and anaplerosis. The oxidative pentose phosphate pathway, malic enzyme, and glutaminolysis thus confer layered protection against oxidative stress during metastasis.

Human umbilical cord mesenchymal stem cells-derived exosomal circDLGAP4 promotes angiogenesis after cerebral ischemia-reperfusion injury by regulating miR-320/KLF5 axis.

Accumulating evidence suggests that human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSCs-Exos) are a promising therapeutic strategy for cerebral ischemia-reperfusion injury (CIRI). However, the underlying mechanism remains unclear. hUC-MSCs-Exos were identified by electron microscopy, NTA, and Western blotting. In the hypoxia/reoxygenation (H/R) cell model, human brain microvascular endothelial cells (HBMECs) were cocultured with hUC-MSCs-Exos. Then, cell viability, migration, apoptosis, and tube formation were measured by MTT, flow cytometry, transwell, and tube formation assays. RT-qPCR and Western blotting were used to detect the changes in RNA and protein. RNA pull-down and dual luciferase reporter assays confirmed the relationship between circDLGAP4, miR-320, and KLF5. Ischemia-reperfusion (I/R) rat model was established for in vivo experiments. hUC-MSCs-Exos increased the expression levels of circDLGAP4 and KLF5 but decreased miR-320 in H/R-treated HBMECs by transferring exosomal circDLGAP4. Knockdown of circDLGAP4 in hUC-MSCs-Exos reversed the promoting effects of hUC-MSCs-Exos on cell viability, migration, and tube formation in H/R-treated HBMECs in vitro and also abolished the protective effects of hUC-MSCs-Exos on cerebrovascular injury in I/R rats. Mechanistically, exosomal circDLGAP4 negatively regulated miR-320 in HBMECs, which directly bound to KLF5. In addition, the downregulation of miR-320 could reverse the regulatory effect of exosomal shcircDLGAL5 in H/R-treated HBMECs by upregulating KLF5. hUC-MSCs-Exos-derived circDLGAP4 reduced cerebrovascular injury by regulating miR-320/KLF5 signaling. These results provide a stem cell-based approach to treat CIRI.

Fe-Based Metal Organic Framework-Derived FeNiP/N-Doped Carbon Heterogeneous Core-Shell Structures for Oxygen Evolution.

It is of great significance to explore high activity, low overpotential, and outstanding durability electrocatalysts without precious metals for oxygen evolution reaction to reduce the energy consumption in the electrolysis of water to product hydrogen. Metal organic frameworks (MOFs) with periodic structure and uniform pore distribution have been widely used as precursors for the synthesis of transition metal electrocatalysts. Herein, we first synthesized nanoscale Fe-soc-MOFs with relatively high specific surface area and in situ converted it into nickel-iron double layer hydroxide/MOF (FeNi LDH/MOF) by Ni2+ etching. Finally, a nickel-iron phosphide/nitrogen-doped carbon cubic nanocage (FeNiP/NC) was obtained by calcination and phosphating. FeNiP/NC with its unique core-shell structure has an overpotential of only 240 mV at a current density of 10 mA/cm2 and can be continuously electrolyzed for 45 h. High catalytic activity of FeNiP/NC is mainly attributed to the action of Fe and Ni bimetals and the synergistic effect between FeNiP and N-doped porous carbon, which was confirmed by the calculation of density functional theory (i.e., Gibbs free energy). After a long period of electrolysis, FeNiP was converted to MOOH (M = Fe and Ni) and became the new active site. This study provides a feasible optimization strategy for the development of high-efficiency three-dimensional electrode materials without precious metals.

Assessment of sedation by automated pupillometry in critically ill patients: a prospective observational study.

BACKGROUND: Quantitative measurement of pupil change has not been assessed against the Richmond Agitation and Sedation Scale (RASS) and spectral edge frequency (SEF) during sedation. The aim of this study was to evaluate pupillometry against these measures in sedated critically ill adult patients. METHODS: In ventilated and sedated patients, pupillary variables were measured by automated pupillometry at each RASS level from -5 to 0 after discontinuation of hypnotics, while processed electroencephalogram variables were displayed continuously and SEF was recorded at each RASS level. Correlations were made between percentage pupillary light reflex (%PLR) and RASS, and between %PLR and SEF. The ability of %PLR to differentiate light sedation (RASS ≥-2), moderate (RASS =-3), and deep sedation (RASS ≤-4) was assessed by areas under receiver operating characteristic (ROC) curves. RESULTS: A total of 163 paired measurements were recorded in 38 patients. With decreasing sedation depth, median %PLR increased progressively from 20% (interquartile range 17-25%) to 36% (interquartile range 33-40%) (P<0.001). Strong correlations were found between %PLR and RASS (Rho=0.635) and between %PLR and SEF (R=0.641). Area under the curve (AUC) of 0.87 with a %PLR threshold of 28% differentiated moderate/light sedation from deep sedation with sensitivity of 83% and specificity of 83%. An AUC of 0.82 with a threshold of 31% distinguished light sedation from moderate/deep sedation with a sensitivity of 81% and a specificity of 75%. CONCLUSIONS: Quantitative assessment of %PLR correlates with other indicators of sedation depth in critically ill patients.

Nomogram to Estimate the Risk of Chronic Kidney Disease-associated Pruritus in Patients with End-Stage Renal Disease Undergoing Peritoneal Dialysis: Model Development and Validation Study.

INTRODUCTION: Chronic kidney disease associated pruritus (CKD-aP) frequently occurs in patients with end-stage renal disease (ESRD) undergoing peritoneal dialysis (PD) and presents a therapeutic challenge to physicians owing to the diversity of its pathogenesis. Herein, we developed and validated a nomogram model for individualized risk estimation of CKD-aP and investigate the possible causes of CKD-aP in PD patients. METHODS: We retrospectively screened patients with CKD-aP who underwent PD between 2021 and 2023 at the First Affiliated Hospital of Xi'an Jiaotong University Peritoneal Dialysis Center. Nomograms for each outcome were computed from multivariate logistic regression models with the least absolute shrinkage and selection operator regression and univariate logistic regression for variable selection. The discriminative ability was estimated by Harrell's C-index, and the accuracy was assessed graphically with a calibration curve plot. Models were validated internally using bootstrapping and externally by calculating their performance on a validation cohort. Decision curve analysis was used to assess the model's clinical usefulness. RESULTS: In all, a total of 487 patients were entered in the analysis, including 325 in the development cohort and 162 in the validation cohort. The final nomogram incorporated four variables: age, interleukin-6, hemoglobin, residual urine volume, and renal Kt/V. The C-index of the model was 0.733 (95% CI 0.679-0.787), and the calibration curve was a straight line with a slope close to 1. Both internal and external validations confirmed the model's good performance, with C-index of 0.725 (95% CI 0.662-0.774) and 0.706 (95% CI 0.623-0.789), respectively. Decision curve analysis showed that the nomogram had good clinical benefits. CONCLUSION: Our study proposes a nomogram model for CKD-aP risk assessment in ESRD patients with PD. This nomogram might help in clinical decision-making and evidence-based selection of therapy.

Dietary Inflammatory Index and diabetic retinopathy risk in US adults: findings from NHANES (2005-2008).

BACKGROUND: Inflammation is associated with the pathophysiology of diabetic retinopathy (DR). Within the framework of complete dietary patterns, the Dietary Inflammatory Index (DII) was formulated to evaluate the inflammatory properties inherent in a diet. The main purpose of the current study was to assess the relationship between DII and DR using National Health and Nutrition Examination Survey (NHANES). METHODS: The original sample size included 1,148 diabetes patients out of 2005-2008 NHANES surveys. Twenty-four-hour dietary consumptions were used to calculate the DII scores. Demographic characteristics and retina examinations were collected for the comparison between DR and non-DR groups in diabetes patients. The relationship between DII and DR was analyzed by a logistic regression model. RESULTS: 227 subjects (110 non-DR and 117 DR) were selected in the analyses by using undersampling method to balance the sample size. Compared with non-DR group, DR group had higher DII values (1.14 ± 0.29 vs. 1.49 ± 0.21, p = 0.32), higher levels of HbA1c (6.8 ± 1.1% vs. 7.7 ± 2.6%, p < 0.001), longer duration of diabetes (6.52 ± 12 years vs. 14 ± 11 years, p < 0.001). The odds rate (OR) of DII for DR from the logistic regression was 1.38 (95%CI 1.06-1.81, p < 0.001). HbA1c, diabetes duration and obesity were important influencing factors, and their ORs were 1.81 (95% CI:1.31-2.50), 1.12 (95%CI:1.04-1.20), 4.01 (95%CI:1.12-14.32), respectively. In addition, the most important dietary indices for DR were different across males and females. CONCLUSIONS: The current study demonstrates that a higher DII is associated with an increased risk of DR in US adults. Considering diet as a modifiable factor, limiting pro-inflammatory diets or encouraging an anti-inflammatory diet may be a promising and cost-effective method in the management of DR.

Immune response regulation by transduced mesenchymal stem cells with decorin gene on bleomycin-induced lung injury, fibrosis, and inflammation.

BACKGROUND: Pulmonary fibrosis is a pathological hallmark of lung injury. It is an aggressive disease that replaces normal lung parenchyma by fibrotic tissue. The transforming growth factor-beta-mothers against decapentaplegic homolog 3 (TGF-ß1-Smad3) signaling pathway plays a key role in regulating lung fibrosis. Decorin (DCN), a small leucine-rich proteoglycan, has a modulatory effect on the immune system by reversibly binding with TGF-ß and reducing its bioavailability. Mesenchymal stem cell (MSC) therapy is a new strategy that has an immune-modulatory capacity. OBJECTIVE: The aim of this study was to introduce a new therapeutic approach to harness remodeling in injured lung. MATERIAL AND METHODS: Bone marrow MSCs were isolated and transduced by decorin gene. Lung injury was induced by bleomycin and mice were treated with MSCs, MSCs-decorin, and decorin. Then, oxidative stress biomarkers, remodeling biomarkers, bronchoalveolar lavage cells, and histopathology study were conducted. RESULTS: Reduced catalase and superoxide dismutase increased due to treatments. Elevated malondialdehyde, hydroxyproline, TGF-ß levels, and polymorphonuclear cells count decreased in the treated groups. Additionally, the histopathology of lung tissues showed controlled inflammation and fibrosis. CONCLUSION: Transfected decorin gene to MSCs and used cell therapy could control remodeling and bleomycin-induced lung injury.

Synthesis and Antifungal Activity of Norbornene Carboxamide/sulfonamide Derivatives as Potential Fungicides Targeting Laccase.

To explore more potential fungicides with new scaffolds, thirty-seven norbornene carboxamide/sulfonamide derivatives were designed, synthesized, and assayed for inhibitory activity against six plant pathogenic fungi and oomycetes. The preliminary antifungal assay suggested that the title derivatives showed moderate to good antifungal activity against six plant pathogens. Especially, compound 6 e presented excellent in vitro antifungal activity against Sclerotinia sclerotiorum (EC50=0.71 mg/L), which was substantially stronger than pydiflumetofen. In vivo antifungal assay indicated 6 e displayed prominent protective and curative effects on rape leaves infected by S. sclerotiorum. The preliminary mechanism research displayed that 6 e could damage the surface morphology and inhibit the sclerotia formation of S. sclerotiorum. In addition, the in vitro enzyme inhibition bioassay indicated that 6 e displayed pronounced laccase inhibition activity (IC50=0.63 µM), much stronger than positive control cysteine. Molecular docking elucidated the binding modes between 6 e and laccase. The bioassay results and mechanism investigation demonstrated that this class of norbornene carboxamide/sulfonamide derivatives could be promising laccase inhibitors for novel fungicide development.

Recognition on pharmacodynamic ingredients of natural products.

Natural products (NPs) play an irreplaceable role in the intervention of various diseases and have been considered a critical source of drug development. Many new pharmacodynamic compounds with potential clinical applications have recently been derived from NPs. These compounds range from small molecules to polysaccharides, polypeptides, proteins, self-assembled nanoparticles, and extracellular vesicles. This review summarizes various active substances found in NPs. The investigation of active substances in NPs can potentiate new drug development and promote the in-depth comprehension of the mechanism of action of NPs that can be beneficial in the prevention and treatment of human diseases.

Crizotinib-based proteolysis targeting chimera suppresses gastric cancer by promoting MET degradation.

As one of the common malignant cancer types, gastric cancer (GC) is known for late-stage diagnosis and poor prognosis. Overexpression of the receptor tyrosine kinase MET is associated with poor prognosis among patients with advanced stage GC. However, no MET inhibitor has been used for GC treatment. Like other tyrosine kinase inhibitors that fit the "occupancy-driven" model, current MET inhibitors are prone to acquired resistance. The emerging proteolysis targeting chimera (PROTAC) strategy could overcome such limitations through direct degradation of the target proteins. In this study, we successfully transformed the MET-targeted inhibitor crizotinib into a series of PROTACs, recruiting cereblon/cullin 4A E3 ubiquitin ligase to degrade the MET proteins. The optimized lead PROTAC (PRO-6 E) effectively eliminated MET proteins in vitro and in vivo, inhibiting proliferation and motility of MET-positive GC cells. In the MKN-45 xenograft model, PRO-6 E showed pronounced antitumor efficacy with a well-tolerated dosage regimen. These results validated PRO-6 E as the first oral PROTAC for MET-dependent GC.

980†nm electrically pumped continuous lasing of QW lasers grown on silicon.

Investigation of high-performance lasers monolithically grown on silicon (Si) could promote the development of silicon photonics in regimes other than the 1.3 -1.5 µm band. 980 nm laser, a widely used pumping source for erbium-doped fiber amplifier (EDFA) in the optical fiber communication system, can be used as a demonstration for shorter wavelength lasers. Here, we report continuous wave (CW) lasing of 980 nm electrically pumped quantum well (QW) lasers directly grown on Si by metalorganic chemical vapor deposition (MOCVD). Utilizing the strain compensated InGaAs/GaAs/GaAsP QW structure as the active medium, the lowest threshold current obtained from the lasers on Si was 40 mA, and the highest total output power was near 100 mW. A statistical comparison of lasers grown on native GaAs and Si substrates was conducted and it reveals a somewhat higher threshold for devices on Si. Internal parameters, including modal gain and optical loss are extracted from experimental results and the variation on different substrates could provide a direction to further laser optimization through further improvement of the GaAs/Si templates and QW design. These results demonstrate a promising step towards optoelectronic integration of QW lasers on Si.

A novel dehydroabietic acid-based multifunctional fluorescent probe for the detection and bioimaging of Cu2+/Zn2+/ClO.

A multifunctional dehydroabietic acid-based fluorescent probe (CPS) was designed and synthesized by introducing the 2,6-bis(1H-benzo[d]imidazol-2-yl)phenol fluorophore. The probe CPS could selectively recognize Cu2+, Zn2+ and ClO- ions from other analytes, and it showed fluorescence quenching behavior toward Cu2+ and a ratiometric response to Zn2+ and ClO- by changing from green fluorescence to blue and cyan, respectively. The detection limits toward Cu2+, Zn2+ and ClO- ions were 3.8 nM, 0.253 µM and 0.452 µM, respectively. In addition, CPS presented many fascinating merits, such as high selectivity, a short response time (15-20 s), a wide pH range (3-10) and high photostability. The sensing mechanisms of CPS were verified by 1H-NMR, ESI-MS, FT-IR and Job's plot methods. Meanwhile, CPS exhibited satisfactory detection performance in water samples. More importantly, the probe could be applied as a promising tool for visual bioimaging of three ions in living cells and zebrafishes.

PPARγ As a Potential Target for Adipogenesis Induced by Fine Particulate Matter in 3T3-L1 Preadipocytes.

Mounting evidence has shown that ambient PM2.5 exposure is closely associated with the development of obesity, and adipose tissue represents an important endocrine target for PM2.5. In this study, the 3T3-L1 preadipocyte differentiation model was employed to comprehensively explore the adipogenic potential of PM2.5. After 8 days of PM2.5 exposure, adipocyte fatty acid uptake and lipid accumulation were significantly increased, and adipogenic differentiation of 3T3-L1 cells was promoted in a concentration-dependent manner. Transcriptome and lipidome analyses revealed the systematic disruption of transcriptional and lipid profiling at 10 µg/mL PM2.5. Functional enrichment and visualized network analyses showed that the peroxisome proliferator-activated receptor (PPAR) pathway and the metabolism of glycerophospholipids, glycerolipids, and sphingolipids were most significantly affected during adipocyte differentiation. Reporter gene assays indicated that PPARγ was activated by PM2.5, demonstrating that PM2.5 promoted adipogenesis by activating PPARγ. The increased transcriptional and protein expressions of PPARγ and downstream adipogenesis-associated markers (e.g., Fabp4 and CD36) were further cross-validated using qRT-PCR and western blot. PM2.5-induced adipogenesis, PPARγ pathway activation, and lipid remodeling were significantly attenuated by the supplementation of a PPARγ antagonist (T0070907). Overall, this study yielded mechanistic insights into PM2.5-induced adipogenesis in vitro by identifying the potential biomolecular targets for the prevention of PM2.5-induced obesity and related metabolic diseases.

Synthesis, Structure and Near Infrared Fluorescence Property of a New Nd-MOF Based on a Triangular Benzylamine Ligand.

A new 3D metal-organic framework (Nd-MOF) {[Nd2L2]·2NH2(CH3)2·3H2O} was successfully established via a solvothermal method with Nd3+ ion and 5-(bis(4-carboxybenzyl) amino)-isophthalicacid (H4L), and has also been characterized by X-ray diffraction, powder X-ray diffraction (PXRD), IR and photoluminescence(PL)spectrum. The neodymium ions are free of coordinated solvents, and the Nd-MOF exhibits strong near-infrared (NIR) fluorescence. Besides, Its NIR fluorescence property shows low temperature resistance, which is favorable for being used in the low temperature environment. Besides, the fluorescence lifetime of Nd-MOF is 6.03 µs, and the quantum yield is 1.2%. The small quantum yield may owe to large energy gap between the T1 of the ligand H4L and the resonance energy level 4F3/2 of the Nd3+ ion, or due to large crystal size of the Nd-MOF.

A head-to-head comparison of the measurement properties of EQ-5D-3L and EQ-5D-5L in Chinese family caregivers of cancer patients.

BACKGROUND: Although both EQ-5D-3L(3L) and EQ-5D-5L(5L) have demonstrated good measurement properties in several patient populations, there is currently limited evidence comparing the measurement properties of 3L and 5L in family caregivers (FCs) of cancer patients. PURPOSE: This study aimed to compare the measurement properties of 3L and 5L in a sample of family caregivers of cancer patients. METHODS: A consecutive sample of FCs of cancer patients recruited from three tertiary hospitals were invited to complete the two versions of the EQ-5D in two rounds of interviews. We compared i) the ceiling effect using the McNemar's test, ii) test-retest reliability using intraclass correlation coefficient (ICC) and Cohen's Kappa, iii) convergent validity using Spearman's rank correlation coefficient, iv) known-group validity using F-statistic, v) and discriminant capacity using ordinal logistic regression. RESULTS: A total of 416 FCs completed the baseline questionnaire and 120 caregivers completed the follow-up questionnaire. Ceiling effects were smaller in 5L (12.5%) than in 3L (20.7%). The convergent validity (r = 0.344-0.771), known-groups validity (Fratio5L/3L = 2.06-4.09), discriminant capacity (ES = 0.341-0.396), and test-retest reliability (ICC = 0.725) of the 5L were slightly better than those of the 3L in China. CONCLUSION: The current study found both 3L and 5L to be suitable for use by FCs of cancer patients. However, 5L showed superior measurement properties compared to 3L and therefore could be the preferred instrument when EQ-5D data of cancer patients FCs is required.

Bifunctional catalytic degradation of diclofenac over Cu-Pd co-modified sponge iron-based trimetal: Parameter optimization.

Currently, the pharmaceutical and personal care products (PPCPs) have posed great challenge to advanced oxidation techniques (AOTs). In this study, we decorated sponge iron (s-Fe0) with Cu and Pd (s-Fe0-Cu-Pd) and further optimized the synthesis parameters with a response surface method (RSM) to rapidly degrade diclofenac sodium (DCF). Under the RSM-optimized conditions of Fe: Cu: Pd = 100: 4.23: 0.10, initial solution pH of 5.13, and input dosage of 38.8 g/L, 99% removal of DCF could be obtained after 60 min of reaction. Moreover, the morphological structure of trimetal was characterized with high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), X-ray diffraction (XRD), X-ray photoelectron spectra (XPS). Electron spin resonance (ESR) signals have also been applied to capture reactive hydrogen atoms (H*), superoxygen anions, hydroxyl radicals, and single state oxygen (1O2). Furthermore, the variations of DCF and its selective degradation products over a series of s-Fe0-based bi(tri)metals have been compared. Additionally, the degradation mechanism of DCF has also been explored. To our best knowledge, this is the first report revealing the selective dechlorination of DCF with low toxicity over Pd-Cu co-doped s-Fe0 trimetal.

Abnormal grey matter structural changes in patients with end-stage kidney disease and mild cognitive impairment: correlations with clinical features.

End-stage kidney disease and mild cognitive impairment (ESKD-MCI) affect the quality of life and long-term treatment outcomes of patients affected by these diseases. Clarifying the morphological changes from brain injuries in ESKD-MCI and their relationship with clinical features is helpful for the early identification and intervention of MCI before it progresses to irreversible dementia. This study gathered data from 23 patients with ESKD-MCI, 24 patients with ESKD and non-cognitive impairment (NCI), and 27 health controls (HCs). Structural magnetic resonance studies, cognitive assessments, and general clinical data were collected from all participants. Voxel-based morphometry analysis was performed to compare grey matter (GM) volume differences between the groups. The patients' GM maps and clinical features were subjected to univariate regression to check for possible correlations. Patients with ESKD-MCI displayed significantly more impairments in multiple cognitive domains, including global cognition, visuospatial and executive function, and memory, compared to patients with ESKD-NCI. Using a more liberal threshold (P < 0.001, uncorrected), we found that compared to patients with ESKD-NCI, patients with ESKD-MCI exhibited clusters of regions with lower GM volumes, including the right hippocampus (HIP), parahippocampal gyrus (PHG), Rolandic operculum, and supramarginal gyrus. The volumes of the right HIP and PHG were negatively correlated with serum calcium levels. ESKD-MCI was associated with a subtle volume reduction of GM in several brain areas known to be involved in memory, language, and auditory information processing. We speculate that these slight morphometric impairments may be associated with disturbed calcium metabolism.