Neutrophil-to-lymphocyte ratio and incident end-stage renal disease in Chinese patients with chronic kidney disease: results from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE)

Abstract Background Chronic kidney disease (CKD) leads to end-stage renal failure and cardiovascular events. An attribute to these progressions is abnormalities in inflammation, which can be evaluated using the neutrophil-to-lymphocyte ratio (NLR). We aimed to investigate the association of NLR with the progression of end stage of renal disease (ESRD), cardiovascular disease (CVD) and all-cause mortality in Chinese patients with stages 1–4 CKD. Methods Patients with stages 1–4 CKD (18–74 years of age) were recruited at 39 centers in 28 cities across 22 provinces in China since 2011. A total of 938 patients with complete NLR and other relevant clinical variables were included in the current analysis. Cox regression analysis was used to estimate the association between NLR and the outcomes including ESRD, CVD events or all-cause mortality. Results Baseline NLR was related to age, hypertension, serum triglycerides, total serum cholesterol, CVD history, urine albumin to creatinine ratio (ACR), chronic kidney disease-mineral and bone disorder (CKD-MBD), hyperlipidemia rate, diabetes, and estimated glomerular filtration rate (eGFR). The study duration was 4.55 years (IQR 3.52–5.28). Cox regression analysis revealed an association of NLR and the risk of ESRD only in patients with stage 4 CKD. We did not observe any significant associations between abnormal NLR and the risk of either CVD or all-cause mortality in CKD patients in general and CKD patients grouped according to the disease stages in particular. Conclusion Our results suggest that NLR is associated with the risk of ESRD in Chinese patients with stage 4 CKD. NLR can be used in risk assessment for ESRD among patients with advanced CKD; this application is appealing considering NLR being a routine test. Trial registration ClinicalTrials.gov Identifier NCT03041987. Registered January 1, 2012. (retrospectively registered) ( https://www.clinicaltrials.gov/ct2/show/NCT03041987?term=Chinese+Cohort+Study+of+Chronic+Kidney+Disease+%28C-STRIDE%29&rank=1 )https://deepblue.lib.umich.edu/bitstream/2027.42/148285/1/12967_2019_Article_1808.pd

Identification of common molecular signatures of SARS-CoV-2 infection and its influence on acute kidney injury and chronic kidney disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the main cause of COVID-19, causing hundreds of millions of confirmed cases and more than 18.2 million deaths worldwide. Acute kidney injury (AKI) is a common complication of COVID-19 that leads to an increase in mortality, especially in intensive care unit (ICU) settings, and chronic kidney disease (CKD) is a high risk factor for COVID-19 and its related mortality. However, the underlying molecular mechanisms among AKI, CKD, and COVID-19 are unclear. Therefore, transcriptome analysis was performed to examine common pathways and molecular biomarkers for AKI, CKD, and COVID-19 in an attempt to understand the association of SARS-CoV-2 infection with AKI and CKD. Three RNA-seq datasets (GSE147507, GSE1563, and GSE66494) from the GEO database were used to detect differentially expressed genes (DEGs) for COVID-19 with AKI and CKD to search for shared pathways and candidate targets. A total of 17 common DEGs were confirmed, and their biological functions and signaling pathways were characterized by enrichment analysis. MAPK signaling, the structural pathway of interleukin 1 (IL-1), and the Toll-like receptor pathway appear to be involved in the occurrence of these diseases. Hub genes identified from the protein–protein interaction (PPI) network, including DUSP6, BHLHE40, RASGRP1, and TAB2, are potential therapeutic targets in COVID-19 with AKI and CKD. Common genes and pathways may play pathogenic roles in these three diseases mainly through the activation of immune inflammation. Networks of transcription factor (TF)–gene, miRNA–gene, and gene–disease interactions from the datasets were also constructed, and key gene regulators influencing the progression of these three diseases were further identified among the DEGs. Moreover, new drug targets were predicted based on these common DEGs, and molecular docking and molecular dynamics (MD) simulations were performed. Finally, a diagnostic model of COVID-19 was established based on these common DEGs. Taken together, the molecular and signaling pathways identified in this study may be related to the mechanisms by which SARS-CoV-2 infection affects renal function. These findings are significant for the effective treatment of COVID-19 in patients with kidney diseases

Temporal and spatial variations in nutrient stoichiometry and regulation of phytoplankton biomass in Hong Kong waters : influence of the Pearl River outflow and sewage inputs

Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Marine Pollution Bulletin 57 (2008): 335-348, doi:10.1016/j.marpolbul.2008.01.020.In 2001, the Hong Kong government implemented the Harbor Area Treatment Scheme (HATS) under which 70% of the sewage that had been formerly discharged into Victoria Harbor is now collected and sent to Stonecutters Island Sewage Works where it receives chemically enhanced primary treatment (CEPT), and is then discharged into waters west of the Harbor. The relocation of the sewage discharge will possibly change the nutrient dynamics and phytoplankton biomass in this area. Therefore, there is a need to examine the factors that regulate phytoplankton growth in Hong Kong waters in order to understand future impacts. Based on a historic nutrient data set (1986-2001), a comparison of ambient nutrient ratios with the Redfield ratio (N:P:Si=16:1:16) showed clear spatial variations in the factors that regulate phytoplankton biomass along a west (estuary) to east (coastal/oceanic) transect through Hong Kong waters. Algal biomass was constrained by a combination of low light conditions, a rapid change in salinity, and strong turbulent mixing in western waters throughout the year. Potential stoichiometric Si limitation (up to 94% of the cases in winter) occurred in Victoria Harbor due to the contribution of sewage effluent with high N and P enrichment all year, except for summer when the frequency of stoichiometric Si limitation (48%) was the same as P, owing to the influence of the high Si in the Pearl River discharge. In the eastern waters, potential N limitation and N and P co-limitation occurred in autumn and winter respectively, because of the dominance of coastal/oceanic water with low nutrients and low N:P ratios. In contrast, potential Si limitation occurred in spring and a switch to potential N, P and Si limitation occurred in eastern waters in summer. In southern waters, there was a shift from P limitation (80%) in summer due to the influence of the N-rich Pearl River discharge, to N limitation (68%) in autumn, and to N and P co-limitation in winter due to the dominance of N-poor oceanic water from the oligotrophic South China Sea. Our results show clear temporal and spatial variations in the nutrient stoichiometry which indicates potential regulation of phytoplankton biomass in HK waters due to the combination of the seasonal exchange of the Pearl River discharge and oceanic water, sewage effluent inputs, and strong hydrodynamic mixing from SW monsoon winds in summer and the NE monsoon winds in winter.Financial support for this research was provided by the University Grants Council of Hong Kong AoE project (AoE/P-04/0401), and RGC project HKUST6478/05M. Support was also provided (to DMA) by U.S. National Science Foundation grants OCE-0402707 and OCE-0430724 and by NIEHS grant 1 P50-ES01274201

Machine learning for the prediction of all-cause mortality in patients with sepsis-associated acute kidney injury during hospitalization

BackgroundSepsis-associated acute kidney injury (S-AKI) is considered to be associated with high morbidity and mortality, a commonly accepted model to predict mortality is urged consequently. This study used a machine learning model to identify vital variables associated with mortality in S-AKI patients in the hospital and predict the risk of death in the hospital. We hope that this model can help identify high-risk patients early and reasonably allocate medical resources in the intensive care unit (ICU).MethodsA total of 16,154 S-AKI patients from the Medical Information Mart for Intensive Care IV database were examined as the training set (80%) and the validation set (20%). Variables (129 in total) were collected, including basic patient information, diagnosis, clinical data, and medication records. We developed and validated machine learning models using 11 different algorithms and selected the one that performed the best. Afterward, recursive feature elimination was used to select key variables. Different indicators were used to compare the prediction performance of each model. The SHapley Additive exPlanations package was applied to interpret the best machine learning model in a web tool for clinicians to use. Finally, we collected clinical data of S-AKI patients from two hospitals for external validation.ResultsIn this study, 15 critical variables were finally selected, namely, urine output, maximum blood urea nitrogen, rate of injection of norepinephrine, maximum anion gap, maximum creatinine, maximum red blood cell volume distribution width, minimum international normalized ratio, maximum heart rate, maximum temperature, maximum respiratory rate, minimum fraction of inspired O2, minimum creatinine, minimum Glasgow Coma Scale, and diagnosis of diabetes and stroke. The categorical boosting algorithm model presented significantly better predictive performance [receiver operating characteristic (ROC): 0.83] than other models [accuracy (ACC): 75%, Youden index: 50%, sensitivity: 75%, specificity: 75%, F1 score: 0.56, positive predictive value (PPV): 44%, and negative predictive value (NPV): 92%]. External validation data from two hospitals in China were also well validated (ROC: 0.75).ConclusionsAfter selecting 15 crucial variables, a machine learning-based model for predicting the mortality of S-AKI patients was successfully established and the CatBoost model demonstrated best predictive performance

Bacterial dynamics in the coastal waters of Hong Kong and the northern South China sea

The study of bacterial production and respiration is a relatively new field of investigation in Hong Kong waters and the South China Sea. The objectives of this thesis were to determine: 1) the temporal and spatial variations of bacteria and their role in oxygen consumption and carbon release; and 2) whether P is the most limiting nutrient for bacterial respiration in the coastal waters of Hong Kong. Surface bacterial production was 10 to 50 μg C L-1 d-1 in the eastern waters, and was significantly higher (20 to 150 μg C L-1 d-1) near the Stonecutters Island sewage outfall discharge site (p <0.05). Integrated bacterial respiration was ~1.2 to 4.5 g C m-2 d-1 in June and November 2005, which accounted for >90% of the dark community respiration (DCR) near the sewage discharge site, and 40 to 75% in the shelf waters. Bottom DO was usually >3 mg L-1 (i.e. ~75 % saturated) in Victoria Harbor. DO was often undersaturated and pCO2 supersaturated, indicating that Hong Kong waters were heterotrophic and a net source of CO2 to the atmosphere. Surface pCO2 averaged ~570 μatm at all 12 stations during the study period, except during the episodic periods of phytoplankton blooms when CO2 was <200 μatm. Surface pCO2 was significantly correlated with NH4 (p <0.05), an indicator of sewage effluent, and therefore, sewage effluent appeared to exert a strong influence on carbon dynamics and CO2 efflux. Only ~10% of the ambient DOC (~200 μM) near the sewage discharge site was consumed by bacteria, and the remainder was most likely transported to the coastal waters. The DIN:PO4 ratio could often be up to ~50:1 in the wet season, and hence PO4 might be the first nutrient to be depleted and became limiting for bacterial growth, especially during phytoplankton blooms in the wet season. In addition, bacteria require a higher proportion of P relative to N (N:P = ~5:1), and hence they are more susceptible to P limitation. The significant correlation between apparent oxygen utilization (AOU) and phosphorus also indicated that the lack of large areas of hypoxia in the area may be linked to phosphorus limitation. Therefore, a PO4 addition experiment was conducted to determine the responses in bacterial respiration, production and growth efficiency to PO4 limitation. Natural seawater was obtained from southern Hong Kong waters in July 2006. PO4 addition treatment increased both bacterial respiration (BR) and phytoplankton respiration (PR) by ~20% when phytoplankton assimilated most of the PO4. However, the >0.2 μM PO4 addition treatment did not further increase BR. Bacterial growth efficiency decreased with higher phytoplankton abundance, but increased due to PO4 addition. Therefore, despite the high nutrient loading from the Pearl River estuary and sewage effluent, there is still potential limitation of inorganic phosphorus for both bacterial and phytoplankton respiration, which may partially decrease eutrophication impacts in Hong Kong waters. In addition to the coastal waters of Hong Kong, the spatial variation in bacterial abundance and production were also investigated in the northern South China Sea during the summer of 2004 and 2005. The South China Sea (SCS) is an oligotrophic ocean with low nutrients, and low phytoplankton biomass and productivity in surface waters. Surface bacterial abundance was relatively high (~8 to 12 x 105 cells ml-1) in the Pearl River estuarine waters near Hong Kong due to high nutrient and organic matter concentrations. In the northwest SCS, high surface bacterial abundance (~12 x 105 cells ml-1) was observed near Hainan Island probably due to upwelling. In contrast, the invasion of the Pacific Ocean through Luzon Strait led to low surface bacterial abundance (~5 x 105 cells ml-1). Bacterial biomass and production were clearly related to Chl a in the shelf and open ocean, which indicated a bottom-up control by DOC produced by primary producers. Further evidence for bottom-up control was provided by bioassay nutrient addition experiments, which showed that a P addition enhanced bacterial production in coastal waters, and a DOC addition in combination with a NO3 or PO4 addition, gave the largest enhancement of bacterial growth in all bioassay experiments, indicating that inorganic nutrients exerted some control of labile DOC consumption in this oligotrophic ocean. UVR inhibited bacterial production (BP), phytoplankton production (PP), and enhanced viral decay rates (VDR) by 20, 14 and 36% respectively. UVR inhibition on BP was significantly higher than PP in most samples, which suggests that UVR inhibition on heterotrophic activities was higher than autotrophic activities in the northern South China Sea on sunny days

Double Maximum Ratios of Viruses to Bacteria in the Water Column: Implications for Different Regulating Mechanisms

The viruses play an important role in limiting bacterial abundance in oceans and, hence, in regulating bacterial biogeochemical functions. A cruise was conducted in September 2005 along a transect in the deep South China Sea (SCS). The results showed the double maxima in the ratio of viral to bacterial abundance (VBR) in the water column: a deep maximum at 800-1000 m coinciding with the oxygen minimum zone (OMZ) and a subsurface maximum at 50-100 m near the subsurface chlorophyll maximum (SCM) layer. At the deep maximum of VBR, both viral and bacterial abundances were lower than those in the upper layer, but the former was reduced less than the latter. In contrast, at the subsurface maximum of VBR, both viral and bacterial abundances increased to the maximum, with viral abundance increasing more than bacterial abundance. The results suggest that two VBR maxima were formed due to different mechanisms. In the SCM, the VBR maximum is due to an abundant supply of organic matter, which increases bacterial growth, and stimulates viral abundance faster. In contrast, in the OMZ, organic matter is consumed and limits bacterial growth, but viruses are less limited by organic matter and continue to infect bacteria, leading to the maximum VBR. The OMZ in the deep-water column of oceans is over hundreds of years old and receives a constant supply of organic matter from the water above. However, the oxygen level cannot be depleted to anoxia. Bacterial respiration is largely responsible for oxygen consumption in the OMZ; and hence, any process that limits bacterial abundance and respiration contributes to the variation in the OMZ. Viral control of bacterial abundance can be a potential mechanism responsible for slowing down oxygen consumption to anoxia in the OMZ. Our finding provides preliminary evidence that viruses are an important player in controlling bacterial abundance when bacterial growth is limited by organic matter, and thus, regulates the decomposition of organic matter, oxygen consumption and nutrient re-mineralization in deep oceans

Polyol Pathway Exacerbated Ischemia/Reperfusion-Induced Injury in Steatotic Liver

Background. The polyol pathway, a bypass pathway of glucose metabolism initiated by aldose reductase (AR), has been shown to play an important role in mediating tissue ischemia/reperfusion (I/R) impairment recently. Here, we investigated how and why this pathway might affect the fatty liver following I/R. Methods. Two opposite models were created: mice with high-fat-diet-induced liver steatosis were treated with aldose reductase inhibition (ARI) and subsequent I/R; and AR-overexpressing L02 hepatocytes were sequentially subjected to steatosis and hypoxia/reoxygenation. We next investigated (a) the hepatic injuries, including liver function, histology, and hepatocytes apoptosis/necrosis; (b) the NAD(P)(H) contents, redox status, and mitochondrial function; and (c) the flux through the caspase-dependent apoptosis pathway. Results. AR-inhibition in vivo markedly attenuated the I/R-induced liver injuries, maintained the homeostasis of NAD(P)(H) contents and redox status, and suppressed the caspase-dependent apoptosis pathway. Correspondingly, AR overexpression in vitro presented the opposite effects. Conclusion. The flux through the polyol pathway may render steatotic liver greater vulnerability to I/R. Interventions targeting this pathway might provide a novel adjunctive approach to protect fatty liver from ischemia

Elevated CO2 delays the early development of scleractinian coral Acropora gemmifera

Abstract The effects of elevated CO2 on the early life stages of coral were investigated by culturing the pelagic larvae and new recruits of Acropora gemmifera at three concentrations of CO2 (corresponding to pH = 8.1, 7.8 and 7.5, respectively). Acidified seawater resulted in fewer A. gemmifera larvae settling, and led to the production of smaller new recruits by slowing the development of the skeleton. The delayed development of new recruits due to elevated CO2 was consistent with the downregulation of calcification related genes. Several genes related to HCO3 − and Ca2+ transporters were downregulated by elevated CO2, with solute carriers (SLC) (membrane transport proteins) possibly playing an important role. The downregulation of these membrane transport proteins might suppress the transport of calcium, bicarbonate and organic matter, resulting in the delayed development of A. gemmifera

An Eight-Zonal Piezoelectric Tube-Type Threaded Ultrasonic Motor Based on Second-Order Bending Mode

In order to reduce the driving voltage and gain better output characteristics of piezoelectric actuators, an eight-zonal piezoelectric tube-type threaded ultrasonic motor based on two second-order bending modes was analyzed using the method of finite element analysis (FEA), and a prototype was fabricated and experimentally studied in this research. This piezoelectric motor was designed to be excited by four electrical sources applied simultaneously to four groups of electrodes on the customized lead zirconate titanate (PZT) tubular stator (inside diameter 5.35 mm, outside diameter 6.35 mm, length 30 mm), with &#177;90&#176; phase shifts between adjacent electrodes. Experimental results show that the threaded motor could output a stall force (stall force means the output pull or thrust force when the linear speed is set to be zero) of about 5.0 N and a linear velocity of 4.9 mm/s with no load at the driving voltage of 40 Vpp (Vpp means the peak-to-peak value of the voltage volts). This piezoelectric motor with a compact structure and screw drive mechanism shows relatively fine velocity controllability and has huge superiority in micro-positioning systems