Self-powered soft robot in the Mariana Trench.

The deep sea remains the largest unknown territory on Earth because it is so difficult to explore1-4. Owing to the extremely high pressure in the deep sea, rigid vessels5-7 and pressure-compensation systems8-10 are typically required to protect mechatronic systems. However, deep-sea creatures that lack bulky or heavy pressure-tolerant systems can thrive at extreme depths11-17. Here, inspired by the structure of a deep-sea snailfish15, we develop an untethered soft robot for deep-sea exploration, with onboard power, control and actuation protected from pressure by integrating electronics in a silicone matrix. This self-powered robot eliminates the requirement for any rigid vessel. To reduce shear stress at the interfaces between electronic components, we decentralize the electronics by increasing the distance between components or separating them from the printed circuit board. Careful design of the dielectric elastomer material used for the robot's flapping fins allowed the robot to be actuated successfully in a field test in the Mariana Trench down to a depth of 10,900 metres and to swim freely in the South China Sea at a depth of 3,224 metres. We validate the pressure resilience of the electronic components and soft actuators through systematic experiments and theoretical analyses. Our work highlights the potential of designing soft, lightweight devices for use in extreme conditions.

Site-Specific Anchoring a Luminescent Tag in a Protein with Non-Emissive Iridium(III) Complex.

Site-specific modification of proteins with synthetic fluorescent tag effectively improves the resolution of imaging, and such a labeling method with negligible three-dimensional structural perturbations and minimal impact on the biological functions of proteins is of high interest to dissect the high-resolution activities of biomolecules in complex systems. To this end, several non-emissive iridium(III) complexes [Ir(C-N)2 (H2 O)2 ]+ OTF- (C-N denotes various cyclometalated ligands) were designed and synthesized. These complexes were tested for attaching a protein by coordinating to H/X (HisMet, HisHis, and HisCys) that are separated by i and i+4 in α-helix. Replacement of the two labile water ligands in the iridium(III) complex by a protein HisHis pair increases the luminescent intensity up to over 100 folds. This labeling approach has been demonstrated in a highly specific and efficient manner in a number of proteins, and it is also feasible for labeling target proteins in cell lysates.

Immobilized Tetraalkylammonium Cations Enable Metal-free CO2 Electroreduction in Acid and Pure Water.

Carbon dioxide reduction reaction (CO2 RR) provides an efficient pathway to convert CO2 into desirable products, yet its commercialization is greatly hindered by the huge energy cost due to CO2 loss and regeneration. Performing CO2 RR under acidic conditions containing alkali cations can potentially address the issue, but still causes (bi)carbonate deposition at high current densities, compromising product Faradaic efficiencies (FEs) in present-day acid-fed membrane electrode assemblies. Herein, we present a strategy using a positively charged polyelectrolyte-poly(diallyldimethylammonium) immobilized on graphene oxide via electrostatic interactions to displace alkali cations. This enables a FE of 85 %, a carbon efficiency of 93 %, and an energy efficiency (EE) of 35 % for CO at 100 mA cm-2 on modified Ag catalysts in acid. In a pure-water-fed reactor, we obtained a 78 % CO FE with a 30 % EE at 100 mA cm-2 at 40 °C. All the performance metrics are comparable to or even exceed those attained in the presence of alkali metal cations.

IKKα aggravates renal fibrogenesis by positively regulating the Wnt/ß-catenin pathway.

AKI (acute kidney injury) with maladaptive repair plays exacerbated role in renal fibrosis characterized by tubulointerstitial fibrosis. Previously, we reported that IKKα contributed to kidney regeneration and inhibited inflammation. Here, we first identified the role and mechanism of IKKα on TGF-ß1-induced fibrosis in human tubular epithelial cells and fibrotic kidneys. IKKα was up-regulated in kidney tubular epithelium in unilateral ureteral obstruction (UUO) and unilateral ischemic reperfusion injury (UIRI) mice. Immunohistochemical staining showed that IKKα was positively correlated with the extent of kidney fibrosis in tissue biopsies from chronic kidney disease (CKD) patients. Compared with wild-type controls, Ksp-IKKα-/- mice exhibited inactivated Wnt/ß-catenin pathway, decreased serum creatinine and interstitial fibrosis in the kidney after IRI. In TGF-ß1-stimulated human tubular epithelial cells, IKKα overexpression enhanced ß-catenin nuclear translocation. Blocking IKKα by siRNA specifically suppressed ß-catenin activation and downstream profibrotic genes such as fibronectin and α-smooth muscle actin (α-SMA). Taken together, our study demonstrated that IKKα aggravated renal fibrogenesis by activating Wnt/ß-catenin signalling pathway, providing a new target for the treatment of kidney fibrosis.

A novel explainable online calculator for contrast-induced AKI in diabetics: a multi-centre validation and prospective evaluation study.

BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI), contrast-induced acute kidney injury (CIAKI) is a frequent complication, especially in diabetics, and is connected with severe mortality and morbidity in the short and long term. Therefore, we aimed to develop a CIAKI predictive model for diabetic patients. METHODS: 3514 patients with diabetes from four hospitals were separated into three cohorts: training, internal validation, and external validation. We developed six machine learning (ML) algorithms models: random forest (RF), gradient-boosted decision trees (GBDT), logistic regression (LR), least absolute shrinkage and selection operator with LR, extreme gradient boosting trees (XGBT), and support vector machine (SVM). The area under the receiver operating characteristic curve (AUC) of ML models was compared to the prior score model, and developed a brief CIAKI prediction model for diabetes (BCPMD). We also validated BCPMD model on the prospective cohort of 172 patients from one of the hospitals. To explain the prediction model, the shapley additive explanations (SHAP) approach was used. RESULTS: In the six ML models, XGBT performed best in the cohort of internal (AUC: 0.816 (95% CI 0.777-0.853)) and external validation (AUC: 0.816 (95% CI 0.770-0.861)), and we determined the top 15 important predictors in XGBT model as BCPMD model variables. The features of BCPMD included acute coronary syndromes (ACS), urine protein level, diuretics, left ventricular ejection fraction (LVEF) (%), hemoglobin (g/L), congestive heart failure (CHF), stable Angina, uric acid (umol/L), preoperative diastolic blood pressure (DBP) (mmHg), contrast volumes (mL), albumin (g/L), baseline creatinine (umol/L), vessels of coronary artery disease, glucose (mmol/L) and diabetes history (yrs). Then, we validated BCPMD in the cohort of internal validation (AUC: 0.819 (95% CI 0.783-0.855)), the cohort of external validation (AUC: 0.805 (95% CI 0.755-0.850)) and the cohort of prospective validation (AUC: 0.801 (95% CI 0.688-0.887)). SHAP was constructed to provide personalized interpretation for each patient. Our model also has been developed into an online web risk calculator. MissForest was used to handle the missing values of the calculator. CONCLUSION: We developed a novel risk calculator for CIAKI in diabetes based on the ML model, which can help clinicians achieve real-time prediction and explainable clinical decisions.

Serum Cystatin C within 24 hours after admission: a potential predictor for acute kidney injury in Chinese patients with community acquired pneumonia.

BACKGROUND: Acute kidney injury (AKI) is common in patients with community-acquired pneumonia (CAP), and is associated with poor prognosis. Therefore, in this study, we evaluated whether AKI in Chinese patients with CAP could be well predicted by serum Cystatin C within 24 h after admission. METHODS: Univariate and multivariate logistic regression analyses were used to investigate independent factors of AKI in patients with CAP. RESULTS: Totally, 2716 patients with CAP were included in this study. 766 (28%) patients developed AKI. After multivariate logistic regression analysis, serum Cystatin C (odds ratio [OR] 4.27, 95% confidence interval [CI] 3.36-5.44; p < 0.001) was an independent factor for AKI in patients with CAP. Serum Cystatin C had an area under the receiver operating characteristic curve (AUC) of 0.81 for predicting AKI, with an optimal cutoff value of 1.37 mg/L, computing 68% sensitivity, 80% specificity. Furthermore, serum Cystatin C within 24 h after admission still had a good and stable prediction efficiency for AKI in various subgroups (age, gender, hypertension, diabetes, coronary artery disease, cardiac insufficiency, cerebrovascular disease, atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease, and tumor, albumin, anemia, platelet count, white blood cell count, and uric acid, confusion, uremia, respiratory rate, blood pressure, and age 65 years or older [CURB-65] score, acute respiratory failure, intensive care unit admission, and mechanical ventilation) of patients with CAP (AUCs: 0.69-0.84). CONCLUSION: Serum Cystatin C within 24 h after admission appears to be a good biomarker for predicting AKI in Chinese patients with CAP.

The arrival ward requiring help by wheelchair or medical cart, arterial oxygenation index, age, albumin and neutrophil count score: Predicting in-hospital mortality in Chinese patients with acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: In this study, we will derive and validate a prognostic tool to predict in-hospital death based on Chinese acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients. METHODS: Independent predictors of in-hospital death were identified by logistic regression analysis and incorporated into a clinical prediction tool. RESULTS: The clinical prediction model was developed with data from 1121 patients and validated with data from 245 patients. The five predictors of in-hospital death from the development cohort (Arrival ward requiring help by wheelchair or medical cart, Arterial oxygenation index, Age, Albumin and Neutrophil count) were combined to form the AAAAN Score. The AAAAN Score achieved good discrimination (AUC = 0.85, 95% CI 0.81-0.89) and calibration (Hosmer-Lemeshow chi-square value was 3.33, p = 0.65). The AAAAN Score, which underwent internal bootstrap validation, also showed excellent discrimination for mortality (AUC = 0.85, 95% CI 0.81 to 0.89) and performed more strongly than other clinical prediction tools. Patients were categorized into 3 risk groups based on the scores: low risk (0-2 points, 0.7% in-hospital mortality), intermediate risk (3-4 points, 4.1% in-hospital mortality), and high risk (5-7 points, 23.4% in-hospital mortality). Predictive performance was confirmed by external validation. CONCLUSIONS: The AAAAN Score is a prognostic tool to predict in-hospital death in Chinese AECOPD patients.

Gut Microbial Divergence Between Three Hadal Amphipod Species from the Isolated Hadal Trenches.

Amphipods are the dominant scavenging metazoan species in the hadal trenches at water depths below 6,000 m. The gut microbiota have been considered to be contribution to the adaptation of deep-sea organisms; however, few comparative analyses of animal gut microbiota between different isolated hadal environments have been done so far. Here, we employed high-throughput 16S rRNA sequencing to compare the gut microbial taxonomic composition and functional potential diversity of three hadal amphipod species, Hirondellea gigas, Bathycallisoma schellenbergi, and Alicella gigantea, collected from the Mariana Trench, Marceau Trench, and New Britain Trench in the Pacific Ocean, respectively. Results showed that different community compositions were detected across all the amphipod specimens based on the analyses of alpha-diversity, hierarchical cluster tree, and PCoA (principal coordinate analysis). Moreover, almost no correlation was observed between genera overrepresented in different amphipods by microbe-microbe correlations analysis, which suggested that the colonization of symbionts were host-specific. At genus level, Psychromonas was dominant in H. gigas, and Candidatus Hepatoplasma was overall dominant in A. gigantea and B. schellenbergi. Comparison of the functional potential showed that, though three hadal amphipod species shared the same predominant functional pathways, the abundances of those most shared pathways showed distinct differences across all the specimens. These findings pointed to the enrichment of particular functional pathways in the gut microbiota of the different isolated trench amphipods. Moreover, in terms of species relative abundance, alpha-diversity and beta-diversity, there was high similarity of gut microbiota between the two A. gigantea populations, which dwelled in two different localities of the same hadal trench. Altogether, this study provides an initial investigation into the gut-microbial interactions and evolution at the hadal depths within amphipod. Each of these three amphipod species would be a model taxa for future studies investigating the influence habitat difference and geography on gut-microbial communities.

Two-Dimensional Palladium-Copper Alloy Nanodendrites for Highly Stable and Selective Electrochemical Formate Production.

Pd is the only metal that can catalyze electrochemical CO2 reduction to formate at close-to-zero overpotential. It is unfortunately subjected to severe poisoning by trace CO as the side product and suffers from deteriorating stability and selectivity with increasing overpotential. Here, we demonstrate that alloying Pd with Cu in the form of two-dimensional nanodendrites could enable highly stable and selective formate production. Such unique bimetallic nanostructures are formed as a result of the rapid in-plane growth and suppressed out-of-plane growth by carefully controlling a set of experimental parameters. Thanks to the combined electronic effect and nanostructuring effect, our alloy product catalyzes CO2 reduction to formate with remarkable stability and selectivity under the working potential as cathodic as -0.4 V. Our results are rationalized by computational simulations, evidencing that Cu atoms weaken the *CO adsorption and stabilize the *OCHO adsorption on neighboring Pd atoms.

Efficient Protein-Protein Couplings Mediated by Small Molecules under Mild Conditions.

Protein-protein coupling reactions under physiological conditions that do not impact the three-dimensional structures of the proteins are in high demand. Owing to the combination of phenylsulfonyl and aldehyde groups in 5-fluoro-4-(phenylsulfonyl)picolinaldehyde (FPPA), the fluorine substituent shows high reactivity toward free thiols. In FPPA, the fluorine is more reactive than phenylsulfonyl for free thiols. Thus the first quantitative nucleophilic substitution can be followed by selective substitution of phenylsulfonyl by an additional thiol or cyclization of aldehyde with a 1,2-aminothiol molecule. The FPPA mediated protein-protein coupling proceeds efficiently under mild conditions, resulting in stable protein conjugates. This coupling method has negligible 3D structural perturbations on the target proteins, and it produces overall intact, nearly traceless, and native structural folds of proteins. It is highly suitable for reconstruction of proteins that are difficult to make and segmental isotopic labeling of multidomain proteins.

Tailoring a Nanochaperone to Regulate α-Synuclein Assembly.

Protein misassembly leads to the formation of dysfunctional and toxic molecular species relating to neurodegeneration in Parkinson's disease and Alzheimer's disease. Here, we tailored a nanochaperone (αS-nChap) for α-synuclein to regulate its assembly. The αS-nChap is capable of i) specifically recognizing α-synuclein; ii) dynamically capturing and stabilizing monomeric α-synuclein and retarding oligomerization; iii) tightly capturing oligomeric α-synuclein to prevent fibrillization; and iv) transporting α-synuclein oligomers to the lysosomal degradation system. The regulation of α-synuclein assembly by αS-nChap was studied in vitro. Moreover, the role of αS-nChap preventing α-synuclein pathology in cells and protecting neurons from apoptosis was investigated. The strategy of tailoring a nanochaperone to regulate aberrant assembly of pathogenic proteins provides important insights into protein misfolding diseases. We foresee that αS-nChap has therapeutic value for Parkinson's disease.

Indoleamine-2,3-Dioxygenase Activates Wnt/ß-Catenin Inducing Kidney Fibrosis after Acute Kidney Injury.

INTRODUCTION: As disorder of tryptophan metabolism is common in CKD, the rate-limiting enzyme of tryptophan, indoleamine-2,3-dioxygenase (IDO), has been reported to be involved in CKD, while the accurate mechanism remains unknown. This study was designed to explore correlations between IDO and kidney fibrosis after ischemia-reperfusion injury (IRI). METHODS: Wild-type (WT) mice and IDO knockout (IDO-/-) mice were divided into the sham group and acute kidney injury (AKI) group. Mice in the sham group underwent dorsal incision and exposure of renal pedicle without clamping renal artery, while mice in the AKI group received unique renal artery IRI, and the contralateral kidney was removed at day 13 after IRI. Blood and IRI kidneys were collected at day 14. Kidney function was analyzed by measuring serum Cr and BUN. Morphology was analyzed by tissue periodic acid-Schiff (PAS) staining and Masson staining. Further, fibrosis markers and Wnt/ß-catenin pathway proteins were determined by Western blot. Prostaglandin E2 (PGE2) was administrated for 2 weeks after the IRI mice model was established to observe whether it ameliorates kidney fibrosis after IRI. RESULTS: WT AKI mice revealed elevated expression of IDO compared with WT sham mice. Kidney function of IDO-/- AKI mice showed better than that of WT AKI mice. PAS staining exhibited less loss of tubular epithelial cells and atrophy tubules in IDO-/- AKI mice. Furthermore, kidney fibrosis areas and the expressions of fibrosis markers, including α-SMA, fibronectin, and vimentin, were increased in WT AKI mice. In addition, GSK-3ß and ß-catenin were significantly declined in IDO-/- AKI mice. On top of that, PGE2 administration revealed inhibited IDO expression and that reducing GSK-3ß and ß-catenin resulting in lower expressions of α-SMA, fibronectin, and vimentin in WT AKI mice. CONCLUSIONS: IRI could increase IDO expression to activate Wnt/ß-catenin pathway resulting kidney fibrosis. PGE2 could ameliorate kidney fibrosis via inhibiting IDO expression.

Phase-Dependent Electrocatalytic CO2 Reduction on Pd3 Bi Nanocrystals.

Alloying is a general strategy for modulating the electronic structures of catalyst materials. Compared to more common solid-solution alloys, intermetallic alloys feature well-defined atomic arrangements and provide the unique platform for studying the structure-performance correlations. It is, unfortunately, synthetically challenging to prepare the nanostructures of intermetallic alloys for catalysis research. In this contribution, we prepare intermetallic Pd3 Bi nanocrystals of a uniform size via a facile solvothermal method. These nanocrystals can phase-transform into solid solution alloy via thermal annealing while retaining a similar composition and size. In 0.1 M KHCO3 aqueous solution, the intermetallic Pd3 Bi can selectively reduce CO2 to formate with high selectivity (≈100 %) and stability even at <-0.35 V versus reversible hydrogen electrode, whereas the solid solution alloy has limited formate selectivity of <60 %. Such unique phase-dependence is understood via theoretical simulations showing that the crystallographic ordering of Pd and Bi atoms within intermetallic alloys can suppress CO poisoning and enhance the *OCHO adsorption during electrochemical CO2 reduction to formate.

Size-Dependent Selectivity of Electrochemical CO2 Reduction on Converted In2 O3 Nanocrystals.

The size modulation of catalyst particles represents a useful dimension to tune catalytic performances by impacting not only their surface areas but also local electronic structures. It, however, has remained inadequately explored and poorly elucidated. Here, we report the interesting size-dependent selectivity of electrochemical CO2 reduction on In2 O3 nanocrystals. 5-nm nanoparticles and 15-nm nanocubes with focused size distribution are prepared via a facile solvothermal reaction in oleylamine by carefully controlling a set of experimental parameters. They serve as the precatalysts, and are reduced to In nanocrystals while largely inherit the original size feature during electrochemical CO2 reduction. Catalyst derived from 15-nm nanocubes exhibits greater formate selectivity (>95 %) at lower overpotential and negligible side reactions compared to bulk-like samples (indium foil and 200-nm cubes) as well as the catalyst derived from smaller 5-nm nanoparticles. This unique size dependence is rationalized as a result of the competition among different reaction pathways by our theoretical computations. Smaller is not always better in the catalyst design.

Kidney injury induced by elevated histones in community-acquired pneumonia.

Previous studies showed that extracellular histones could damage organs, but the role of extracellular histones in pneumonia patients with acute kidney injury (AKI) is unknown. This study aims to investigate the impact of extracellular histones on patients with community-acquired pneumonia (CAP) developed AKI. Blood samples were obtained within 24 h after admission to hospital from patients who were diagnosed with CAP. According to the discharge diagnosis, the patients were divided into 2 groups (Non-AKI and AKI). In vitro, A549 cells were treated with lipopolysaccharides (LPS) and conditioned media were collected. HK2 cells were exposed to the conditioned media or not. Cells proliferation and apoptosis of HK2 were determined. Clinically, Log2 Histones (OR 3.068; 95% CI 1.544-6.097, P = 0.001) and estimated glomerular filtration rate (eGFR) (OR 0.945; 95% CI 0.914-0.978, P = 0.001) were predictors of AKI in CAP patients. Compared to the lower histones group, patients in the higher histones group were more likely to be admitted to ICU, receive mechanical ventilation, and have a longer length of in-hospital stay. In vitro, A549 cells injured by LPS released extracellular histones, in conditioned media which significantly promoted HK2 cells apoptosis. Extracellular histones was a high risk factor for developing AKI in CAP patients and a predictor of worse short-term outcomes. We also showed that extracellular histones in conditioned media damaged HK2 cells.Trial registration number: KY20181102-03; Date of registration: 20181102.

Complement C3 and Nonalcoholic Fatty Liver Disease in Chronic Kidney Disease Patients: A Pilot Study.

CONTEXT: Evidences have suggested complement C3 is a biomarker for nonalcoholic fatty liver disease (NAFLD) in the general population. OBJECTIVE: The present study was conducted to explore the predictive function of C3 for NAFLD in chronic kidney disease (CKD) patients. DESIGN, SETTING, AND PARTICIPANTS: CKD patients were recruited for evaluation of their liver function, kidney function, serum lipids, glycated hemoglobin, blood, and immune function. The glomerular filtration rate was calculated using the CKD-EPI equation. NAFLD was diagnosed according to predefined ultrasonographic criteria. RESULTS: A total of 648 consecutive CKD patients were included, with 216 (33.3%) patients diagnosed with NAFLD. The NAFLD group had significant higher levels of serum protein, serum albumin, triglycerides, glycated hemoglobin, complement C3, hemoglobin (p = 0.001), alanine aminotransferase (p = 0.002), estimated glomerular filtration rate (p = 0.007), and C4 (p = 0.043) and lower levels of cystatin C, ß2-microglobulin, proteinuria (p = 0.001), and high-density lipoprotein cholesterol (p = 0.008). In a logistic regression model, only complement C3 (OR = 1.003; 95% CI 1.002-1.004, p = 0.001) was associated with a higher likelihood of being diagnosed with NAFLD. Finally, we constructed ROC curves for complement C3 for prediction of having NAFLD. The best cut-off for complement C3 was 993.5 mg/L and it yielded a sensitivity of 63.9% and a specificity of 70.1%. CONCLUSION: Our study revealed that complement C3 can be used as a surrogate biomarker of NAFLD in CKD patients.

Genetic Diversity and Population Structure Analysis of Three Deep-Sea Amphipod Species from Geographically Isolated Hadal Trenches in the Pacific Ocean.

Amphipods of the superfamily Lysianassoidea that inhabit the hadal zone ( > 6000 m) have large bathymetric ranges and play a key role in deep ocean ecosystems. The endemism of these amphipod species makes them a good model for investigating potent natural selection and restricted dispersal in deep ocean trenches. Here, we describe genetic diversity and intraspecific population differentiation among three amphipod species from four Pacific trenches based on a mtDNA concatenated dataset (CO Ι and 16S rRNA genes) from 150 amphipod individuals. All amphipod populations had low genetic diversity, as indicated by haplotype and nucleotide diversity values. Population geographic relationship analysis of two Alicella gigantea populations revealed no genetic differentiation between these two localities (pairwise genetic differentiation coefficient = 0.00032, gene flow = 784.58), and the major variation (99.97%) was derived from variation within the populations. Historical demographic events were investigated using Tajima's D and Fu's F neutrality tests and analysis of mismatch distribution. Consistent results provided strong evidence to support the premise that demographic expansion occurred only for the Mariana population of Hirondellea gigas, possibly within the last 2.1-3.4 million years. These findings suggest that the formation of amphipod population structure might be the result of multiple factors including high hydrostatic pressure, food distribution, trench topographic forcing and potential ecological interactions.

Serum cystatin C: A potential predictor for hospital-acquired acute kidney injury in patients with acute exacerbation of COPD.

Hospital-acquired acute kidney injury (HA-AKI) is associated with poor prognosis. In this study, we evaluated whether serum cystatin C on admission could predict AKI in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The retrospective study was conducted using data on adult inpatients with AECOPD from January 2014 to January 2017. A total of 1035 patients were included, among which 79 (7.6%) with HA-AKI were identified. Univariate and multivariate logistic regression analyses were used to investigate predictors of HA-AKI in patients with AECOPD. HA-AKI was associated with poor prognosis, and patients with HA-AKI had higher inpatient mortality (34.2% vs. 2.6%, p < 0.001). Furthermore, after adjusting for confounders, HA-AKI was an independent risk factor for inpatient mortality for patients with AECOPD (odds ratio (OR) 11.02; 95% confidence interval (CI) 4.77-25.45; p < 0.001). Four independent risk factors for HA-AKI (age, levels of urea and cystatin C, and platelet count on admission) were identified in patients with AECOPD. Cystatin C (OR 5.22; 95% CI 2.49-10.95; p < 0.001) was a significant independent predictor of AKI in patients with AECOPD. HA-AKI in patients with AECOPD could be identified with a sensitivity of 73.5% and a specificity of 75.9% (area under the curve (AUC) = 0.803, 95% CI 0.747-0.859) by cystatin C level (cutoff value = 1.3 mg/L) and with a sensitivity of 75.9% and a specificity of 82.0% (AUC = 0.853, 95% CI 0.810-0.896) using a model comprising all significant predictors. Serum cystatin C has the potential for use to predict the risk of HA-AKI in patients with AECOPD.

Retinoic acid attenuates contrast-induced acute kidney injury in a miniature pig model.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) has been the third leading cause of hospital-acquired AKI. Retinoic acid (RA), the main derivative of vitamin A, has preventative and therapeutic effects in ischemia-reperfusion-AKI and UUO models, but little is known about its effects on CI-AKI. This study aimed to explore the effects of RA on CI-AKI as well as the underlying mechanisms. METHODS: We established a new miniature pig model of CI-AKI by catheterizing the external jugular vein and injecting a single dose of iohexol after dehydration. Bun, Scr, serum and urinary RBP and ß-MG levels were measured. Renal histological, TEM examination, LDH assays, TUNEL assays, GFP-LC3 plasmid transfection and western blotting were performed. RESULTS: The levels of Bun, Scr, serum and urinary RBP and ß-MG were increased after CI-AKI and decreased by RA pretreatment. The renal histology showed foamy degeneration and dilated tubules after CI-AKI, and the tissue damage was alleviated significantly by RA pretreatment. RA mitigated renal fibrosis after CI-AKI. In vitro, RA protected proximal TECs against iohexol-induced injury. RA inhibited TECs apoptosis and activated autophagy in vivo and in vitro. CONCLUSIONS: RA alleviates CI-AKI and mitigates renal fibrosis after CI-AKI. Autophagy activation and apoptosis inhibition are involved in the protective effect of RA on CI-AKI. RA may be a new agent for the prevention and therapeutic treatment of CI-AKI in the future.

Coordination of Platinum to α-Synuclein Inhibits Filamentous Aggregation in Solution.

Accumulation of filamentous aggregates of α-synuclein (AS) in Lewy bodies and neurites is characteristic of neurodegenerative diseases such as Parkinson's disease. Inhibition of AS fibrillation is helpful for understanding of AS aggregate structure and for developing chemical therapies. Herein, we report that the PtII -containing antitumor drug cisplatin suppresses filamentous aggregation of AS in solution. PtII thus contrasts strongly with reported transition-metal ions such as MnII , FeIII , and CuII , which accelerate AS aggregation. Interaction between PtII and the side chains of methionine and histidine residues was essential for inhibition of AS fibrillation. Binding of PtII to AS did not change the protein's overall random coil structure, as indicated by solution-state two-dimensional NMR and circular dichroism spectroscopy; and a solution of the AS⋅PtII complex remained free of filamentous aggregates. Our results constitute interesting new information about the biological chemistry of metal ions in Parkinson's disease and might open new lines of research into the suppression of filamentous aggregation.