Association of serum uric acid with all-cause and cardiovascular mortality in chronic kidney disease stages 3-5.

BACKGROUND AND AIMS: The role of serum uric acid (SUA) in the prognosis of chronic kidney disease (CKD) is inconclusive. To explore the association of SUA level with all-cause and cardiovascular disease (CVD) mortality in patients with CKD. METHODS AND RESULTS: Leveraging data from the National Health and Nutritional Examination Survey (NHANES) and linked national death records up to December 31 2019, we explored the association of SUA with all-cause and CVD mortality using weighted cox proportional hazards regression models and restricted cubic spline (RCS) models in patients with CKD stages 3-5. The study finally included 2644 patients with CKD stages 3-5, with a median SUA level of 6.5 mg/dL. After a median follow-up of 55 months, a total of 763 deaths were recorded, with 279 of them attributed to CVD. In the fully adjusted model, per 1 mg/dL increment in SUA concentration was found to be associated with increased HRs (95% CIs) of 1.07 (1.00, 1.14) for all-cause mortality and 1.11 (1.00, 1.24) for CVD mortality. Compared to Q2 (reference), those in Q4 had adjusted HRs of 1.72 (1.36, 2.17) for all-cause mortality and 2.17 (1.38, 3.41) for CVD mortality, while those in Q1 had adjusted HRs of 1.49 (1.19, 1.85) for all-cause mortality and 1.93 (1.26, 2.98) for CVD mortality. CONCLUSIONS: Both higher and lower SUA levels were associated with increased risks of all-cause and CVD mortality in patients with CKD stages 3-5.

Transient Dynamic Operation of G-Quadruplex-Gated Glucose Oxidase-Loaded ZIF-90 Metal-Organic Framework Nanoparticle Bioreactors.

Glucose oxidase-loaded ZIF-90 metal-organic framework nanoparticles conjugated to hemin-G-quadruplexes act as functional bioreactor hybrids operating transient dissipative biocatalytic cascaded transformations consisting of the glucose-driven H2O2-mediated oxidation of Amplex-Red to resorufin or the glucose-driven generation of chemiluminescence by the H2O2-mediated oxidation of luminol. One system involves the fueled activation of a reaction module leading to the temporal formation and depletion of the bioreactor conjugate operating the nickase-guided transient biocatalytic cascades. The second system demonstrates the fueled activation of a reaction module yielding a bioreactor conjugate operating the exonuclease III-dictated transient operation of the two biocatalytic cascades. The temporal operations of the bioreactor circuits are accompanied by kinetic models and computational simulations enabling us to predict the dynamic behavior of the systems subjected to different auxiliary conditions.

Diagnostic accuracy of the 3-minute diagnostic interview for confusion assessment method-defined delirium in delirium detection: a systematic review and meta-analysis.

BACKGROUND: Delirium is a common complication clinically and is associated with the poor outcomes, yet it is frequently unrecognised and readily disregarded. Although the 3-minute diagnostic interview for confusion assessment method-defined delirium (3D-CAM) has been used in a variety of care settings, a comprehensive evaluation of its accuracy in all available care settings has not been performed. OBJECTIVE: This study aimed to evaluate the diagnostic test accuracy of the 3D-CAM in delirium detection through a systematic review and meta-analysis. METHODS: We systematically searched PubMed, EMBASE, the Cochrane Library, Web of Science, CINAHL (EBSCO) and ClinicalTrials.gov published from inception to 10 July 2022. The quality assessment of the diagnostic accuracy studies-2 tool was applied to evaluate methodological quality. A bivariate random effects model was used to pool sensitivity and specificity. RESULTS: Seven studies with 1,350 participants and 2,499 assessments were included, which were carried out in general medical wards, intensive care units, internal medical wards, surgical wards, recovery rooms and post-anaesthesia care units. The prevalence of delirium ranged from 9.1% to 25%. The pooled sensitivity and specificity were 0.92 (95% confidence interval [CI] 0.87-0.95) and 0.95 (95% CI 0.92-0.97), respectively. The pooled positive likelihood ratio was 18.6 (95% CI 12.2-28.2), the negative likelihood ratio was 0.09 (95% CI 0.06-0.14) and the diagnostic odds ratio was 211 (95% CI 128-349). Moreover, the area under the curve was 0.97 (95% CI 0.95-0.98). CONCLUSIONS: The 3D-CAM has good diagnostic accuracy for delirium detection in different care settings. Further analyses illustrated that it had comparable diagnostic accuracy in older adults and patients with dementia or known baseline cognitive impairment. In conclusion, the 3D-CAM is recommended for clinical delirium detection.

Expansion of Escherichia-Shigella in Gut Is Associated with the Onset and Response to Immunosuppressive Therapy of IgA Nephropathy.

BACKGROUND: Gut dysbiosis is postulated to participate in the pathogenesis of IgA nephropathy (IgAN). However, the key bacterial taxa closely associated with IgAN onset and treatment response have not been identified. METHODS: We recruited 127 patients with IgAN who were treatment naive and 127 matched healthy controls (HCs) who were randomly divided into discovery and validation cohorts to investigate the characteristics of their gut microbiota and establish a bacterial diagnosis model for IgAN. A separate cohort of 56 patients and HCs was investigated to assess crossregional validation. A further 40 patients with primary membranous nephropathy (MN) were enrolled to probe disease-specific validation. A subgroup of 77 patients was prospectively followed to further dissect the association between alterations in gut microbiota and treatment response after 6 months of immunosuppressive therapy. Fecal microbiota samples were collected from all participants and analyzed using 16S ribosomal RNA sequencing. RESULTS: Decreased α-diversity (Shannon, P=0.03), altered microbial composition (Adonis, P=0.0001), and a striking expansion of the taxonomic chain Proteobacteria-Gammaproteobacteria-Enterobacteriales-Enterobacteriaceae-Escherichia-Shigella (all P<0.001) were observed in patients with IgAN who were treatment naive, which reversed only in patients who achieved clinical remission after 6 months of immunosuppressive therapy. Importantly, seven operational taxa units, of which Escherichia-Shigella contributed the most, were determined to be the optimal bacterial classifier of IgAN (AUC=0.8635, 0.8551, 0.8026 in discovery, validation, and cross-regional validation sets, respectively), but did not effectively distinguish patients with IgAN versus those with MN (AUC=0.6183). Bacterial function prediction further verified enrichment of the shigellosis infection pathway in IgAN. CONCLUSION: Gut dysbiosis, characterized by a striking expansion of genus Escherichia-Shigella, is a hallmark of patients with IgAN and may serve as a promising diagnostic biomarker and therapeutic target for IgAN. Further studies are warranted to investigate the potential contribution of Escherichia-Shigella in IgAN pathogenesis.

Alterations of the gut microbiota in the lupus nephritis: a systematic review.

BACKGROUND: Emerging evidence suggests that gut microbiota dysbiosis may play a critical role in the development of lupus nephritis (LN). However, the specific characteristics of the gut microbiota in individuals with LN have not been fully clarified. METHODS: The PubMed, Web of Science, and Embase databases were systematically searched for clinical and animal studies related to the relationship between LN and gut microbiota from inception until October 1, 2023. A semiquantitative analysis was used to assess the changes in gut microbial profiles. RESULTS: A total of 15 clinical studies were selected for analysis, which included 138 LN patients, 441 systemic lupus erythematosus patients, and 1526 healthy controls (HCs). Five different types of LN mouse models were included in 5 animal studies. The alpha diversity was decreased in LN patients compared to HCs. A significant decrease in the Firmicutes/Bacteroidetes (F/B) ratio is considered a hallmark of pathological conditions. Specifically, alterations in the abundance of the phylum Proteobacteria, genera Streptococcus and Lactobacillus, and species Ruminococcus gnavus and Lactobacillus reuteri may play a critical role in the pathogenesis of LN. Remarkably, the gut taxonomic chain Bacteroidetes-Bacteroides-Bacteroides thetaiotaomicron was enriched in LN patients, which could be a crucial characteristic of LN patients. The increased level of interleukin-6, imbalance of regulatory T cells and T helper 17 cells, and decreased level of the intestinal tight junction proteins zonula occludens-1 and claudin-1 also might be related to the pathogenesis of LN. CONCLUSIONS: Specific changes in the abundance of gut microbiota such as decreased F/B ratio, and the level of inflammatory indicators, and markers of intestinal barrier dysfunction may play a crucial role in the pathogenesis of LN. These factors could be effective diagnostic and potential therapeutic targets for LN.

[Retrospective Analysis of the Effect of Uric Acid on the Prognosis of Immunoglobulin A Nephropathy With Stage 3-4 Chronic Kidney Disease]. / å°¿é ¸æ°´å¹³å¯¹æ ¢æ€§è‚¾è„ç— 3-4期IgAè‚¾ç— é¢„åŽå½±å“çš„å›žé¡¾æ€§åˆ†æž.

Objective: To investigate the effect of uric acid on the clinicopathological characteristics and prognosis of immunoglobulin A nephropathy (IgAN) in patients with stage 3-4 chronic kidney disease (CKD). Methods: The clinical and pathological data of 263 IgAN patients who had stage 3-4 CKD and who had confrimed diagosis through renal biopsy at the First Affiliated Hospital of Air Force Medical University between December 2008 and January 2020 were retrospectively collected. According to the levels of uric acid, the patients were divided into a hyperuricemia group (n=102) and a normal uric acid group (n=161), and the clinicopathological characteristics of the two groups were compared accordingly. With progression to end-stage renal disease or death as the endpoint event, the renal survival rate of the two groups was compared by the Kaplan-Meier method and the relationship between uric acid and the prognosis was analyzed by Cox regression and LASSO regression. Results: Compared with the normal uric acid group, the hyperuricemia group had a significantly higher proportion of male patients and patients with a history of hypertension, a significantly higher level of blood urea nitrogen, and lower levels of estimated glomerular filtration rate and high-density lipoprotein. In terms of pathology, patients in the hyperuricemia group had significantly higher proportion of glomerulosclerosis, higher mesangial hypercellularity, and higher tubular atrophy/interstitial fibrosis (P<0.05). Kaplan-Meier curve showed that there was a significant difference in renal survival rate between the two groups (P<0.0001). LASSO regression showed that high uric acid was a risk factor for the prognosis of IgAN patients with stage 3-4 CKD. Further multivariate Cox analysis showed that, compared with the normal uric acid group, the hyperuricemia group had a higher risk of incurring composite outcomes (hazard ratio [HR]=1.61, 95% confidence interval [CI]: 1.10-2.34). When uric acid was used as a continuous variable, the increase of 1 mg/dL in uric acid concentration was associated with an increased HR of 1.18 (95% CI: 1.08-1.29) for the composite outcome. Conclusion: High uric acid is a risk factor for poor renal prognosis in IgAN patients with stage 3-4 CKD and reducing uric acid levels may effectively improve the prognosis of high-risk IgAN patients.

Specific Alterations of Gut Microbiota in Chinese Patients with Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: China has the largest absolute burden of hypertension (HTN) in the world. Gut dysbiosis may be a potentially modifiable risk factor for HTN. However, the characteristics of gut microbiota in Chinese populations with HTN remain to be determined. METHODS: We systematically searched for studies comparing the gut microbial in HTN with healthy controls in databases. The cut-off date was December 30, 2021. Semiquantitative analysis and meta-analysis with standardized mean differences of the alteration in gut microbiota were carried out. RESULTS: A total of 16 studies involving 2,372 patients with HTN and 849 controls were included, covering 16 Chinese provinces or regions. The present study supports that compared to healthy population, the diversity of patients with HTN is significantly compromised, while richness is overall preserved. To be specific, a significant increase of the Firmicutes (F)/Bacteroidetes (B) ratio is considered as a special parameter of gut microbiota in HTN patients. The increased abundance of phylum Firmicutes, genus Megasphaera, Escherichia_Shigella, and Klebsiella while the lower abundance of phylum Bacteroidetes, genus Bifidobacterium, Faecalibacterium, Roseburia, and Ruminococcus may be associated with HTN. The gut microbial metabolism in HTN was more abundant in lipopolysaccharide biosynthesis, membrane transport, and steroid degradation. CONCLUSIONS: Variation in gut microbial parameters is likely associated with Chinese patients with HTN. Further investigations should distinguish geographical and ethnic characteristics to develop in-depth knowledge of the underlying mechanisms by which gut dysbiosis contributes to HTN.

Serologic Testing of US Blood Donations to Identify Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Reactive Antibodies: December 2019-January 2020.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), was first identified in Wuhan, China, in December 2019, with subsequent worldwide spread. The first US cases were identified in January 2020. METHODS: To determine if SARS-CoV-2-reactive antibodies were present in sera prior to the first identified case in the United States on 19 January 2020, residual archived samples from 7389 routine blood donations collected by the American Red Cross from 13 December 2019 to 17 January 2020 from donors resident in 9 states (California, Connecticut, Iowa, Massachusetts, Michigan, Oregon, Rhode Island, Washington, and Wisconsin) were tested at the Centers for Disease Control and Prevention for anti-SARS-CoV-2 antibodies. Specimens reactive by pan-immunoglobulin (pan-Ig) enzyme-linked immunosorbent assay (ELISA) against the full spike protein were tested by IgG and IgM ELISAs, microneutralization test, Ortho total Ig S1 ELISA, and receptor-binding domain/ACE2 blocking activity assay. RESULTS: Of the 7389 samples, 106 were reactive by pan-Ig. Of these 106 specimens, 90 were available for further testing. Eighty-four of 90 had neutralizing activity, 1 had S1 binding activity, and 1 had receptor-binding domain/ACE2 blocking activity >50%, suggesting the presence of anti-SARS-CoV-2-reactive antibodies. Donations with reactivity occurred in all 9 states. CONCLUSIONS: These findings suggest that SARS-CoV-2 may have been introduced into the United States prior to 19 January 2020.

Carbon Nitride Quantum Dots Enhancing the Anodic Electrochemiluminescence of Ruthenium(II) Tris(2,2'-bipyridyl) via Inhibiting the Oxygen Evolution Reaction.

Although electrochemiluminescence (ECL) has been developed significantly in the past few decades, ECL efficiency in aqueous solutions remains quite low. Determination of the energy losses and development of new ECL-enhancing strategies are still of great value. In this work, we discovered a detrimental nonradiation relaxation pathway by a concurrent oxygen evolution reaction (OER) process in a well-known ruthenium(II) tris(2,2'-bipyridyl) (Ru(bpy)32+) aqueous ECL system due to similar surface-sensitive characteristics, and for the first time, a chemical strategy was developed by which carbon nitride quantum dots (CNQDs) could inhibit the surface OER process, alleviate the energy losses by nonradiation relaxation, and enhance the anodic ECL of Ru(bpy)32+. In the Ru(bpy)32+/CNQD system, CNQDs could enhance the anodic ECL of Ru(bpy)32+ in a nitrogen stream (10-fold) and ambient air (161-fold). The luminous and nitrogen-rich CNQDs were also confirmed not to serve as ECL luminophores, anodic coreactants, or donor/acceptors in ECL. The coreactant-free Ru(bpy)32+/CNQD system possesses several advantages over the common coreactant ECL system, such as low dosage (100 µg/mL CNQDs), favorable regeneration capacity, etc. As an example, ECL on-off detection of dopamine utilizing the Ru(bpy)32+/CNQD system was also developed to show prospects in ECL sensing. Besides, CNQDs were introduced into the classical Ru(bpy)32+/C2O42- coreactant ECL system, leading to suppressed OER and improved ECL signal. Overall, the proposed new ECL-enhancing strategy is promising for applicable ECL sensing, could be extended to other ECL luminophores with high oxidation potential, and enables an in-depth understanding of the ECL process and mechanism.

Solvent-controlled halohydroxylation or C3-C2 coupling of pyridinium salts through an interrupted dearomative reduction.

Herein, we report an efficient and easily operable method to halohydroxylate pyridiniums through an interrupted dearomative reduction strategy. In this process, we make the most of the halide anion from the pyridinium salts by performing the reaction in DMSO without the need of external HX added. Notably, by changing the solvents from DMSO into Et2O, the bimolecular C3-C2 coupling occurs successfully.

The protective mechanism of SIRT3 and potential therapy in acute kidney injury.

Acute kidney injury (AKI) is a complex clinical syndrome with a poor short-term prognosis, which increases the risk of the development of chronic kidney diseases and end-stage kidney disease. However, the underlying mechanism of AKI remains to be fully elucidated, and effective prevention and therapeutic strategies are still lacking. Given the enormous energy requirements for filtration and absorption, the kidneys are rich in mitochondria, which are unsurprisingly involved in the onset or progression of AKI. Accumulating evidence has recently documented that Sirtuin 3 (SIRT3), one of the most prominent deacetylases highly expressed in the mitochondria, exerts a protective effect on AKI. SIRT3 protects against AKI by regulating energy metabolism, inhibiting oxidative stress, suppressing inflammation, ameliorating apoptosis, inhibiting early-stage fibrosis and maintaining mitochondrial homeostasis. Besides, a number of SIRT3 activators have exhibited renoprotective properties both in animal models and in vitro experiments, but have not yet been applied to clinical practice, indicating a promising therapeutic approach. In this review, we unravel and summarize the recent advances in SIRT3 research and the potential therapy of SIRT3 activators in AKI.

Prognostic factors affecting long-term outcomes in patients with concurrent IgA nephropathy and membranous nephropathy.

Background: The incidence of concurrent immunoglobulin A nephropathy and membranous nephropathy (cIgAN/MN) is low and rarely reported, and the prognosis of patients with cIgAN/MN remains unclear. This study was designed to compare the clinical and prognostic characteristics of cIgAN/MN with IgAN and MN and to identify crucial factors influencing the outcomes of patients with cIgAN/MN. Methods: We included biopsy-proven cIgAN/MN patients between December 2012 and December 2020 at Xijing Hospital. In the same period, propensity score matching was employed to select an equal number of IgAN and MN patients according to the following criteria: age, sex, and follow-up time. The primary endpoint was defined as a composite of eGFR decline ≥30 %, end-stage renal disease, or death. The patient survival rate was examined using Kaplan-Meier survival curves. Univariate and multivariate Cox regression analysis models were utilized to identify the risk factors affecting renal prognosis. Results: A total of 135 patients were finally included in this study and 35 (25.9 %) reached the primary endpoint. The median follow-up time of cIgAN/MN was 45.9 (24.0, 72.0) months. Compared to the IgAN group, the cIgAN/MN group exhibited a lower cumulative incidence rate of composite renal endpoints (P = 0.044), while no significant difference was found between MN and cIgAN/MN patients (P = 0.211). Univariate Cox analysis revealed that mean arterial pressure, serum potassium, blood urea nitrogen, serum IgA, segmental glomerulosclerosis (S1), and MN staging were associated with an increased risk of renal composite endpoints. The multivariate Cox regression analysis of clinical variables plus histological lesion scoring demonstrated that potassium (HR = 14.350, 95 % CI 2.637-78.090, P = 0.002), serum IgA (HR = 1.870, 95 % CI 1.109-3.153, P = 0.019), and S1 (HR = 11.965, 95 % CI 2.166-66.105, P = 0.004) were independent risk factors influencing renal outcomes in cIgAN/MN patients. Conclusion: The prognosis of cIgAN/MN patients may exhibit an intermediate pattern between IgAN and MN, leaning towards being more similar to MN in certain aspects. Within the cIgAN/MN cohort, potassium, and serum IgA may be more predictive of rapid progression of renal endpoints, and S1 may indicate a more aggressive disease course.

Immune checkpoint activity exacerbate renal interstitial fibrosis progression by enhancing PD-L1 expression in renal tubular epithelial cells.

Renal interstitial fibrosis (RIF) is often associated with inflammatory cell infiltration and no effective therapy. Programmed death cell-1 (PD-1) and its ligand PD-L1 were playing critical roles in T cell coinhibition and exhaustion, but the role in RIF is unclear. Here the data analyses of serum from 122 IgA nephrology (IgAN) patients showed that high level of soluble PD-1(sPD-1) was an independent risk factor for RIF and renal function progression. PD-L1 was also overexpressed in renal interstitial tissues from both IgAN patients with high level of sPD-1 and the unilateral ureteral obstruction (UUO) mouse. PD-L1 was significantly overexpressed in HK-2 cells with upregulated collagen and α-SMA when stimulated by inflammation or hypoxia in vitro. Additionally, matrix metalloproteinases (MMP-2) could increase the level of sPD-1 in culture supernatant when added in co-culture system of HK-2 and jurkat cells, which implied serum sPD-1 of IgAN might be cleaved by MMP-2 from T cells infiltrated into the tubulointerstitial inflammatory microenvironment. Crucially, injection of PD-L1 fusion protein, the blocker of sPD-1, could ameliorate kidney fibrosis in UUO mice by increasing T cell coinhibition and exhaustion, suggesting the therapeutic potential of PD-L1 fusion targeting for renal fibrosis. Take together, it reveals a novel causal role of sPD-1 in serum and PD-L1 of renal interstitial tissues in the development of renal fibrosis of IgAN, and targeting sPD-1 in serum by PD-L1 fusion protein is a potential therapeutic approach to prevent renal fibrosis of IgAN.

Comparison of different peritoneal dialysis catheters on complication and catheter survival: A network meta-analysis of randomised controlled trials.

BACKGROUND: This network meta-analysis (NMA) aimed to compare the clinical advantage of four commonly used peritoneal dialysis catheters (PDCs) including the Swan neck segment with straight tip (Swan neck + S), Tenckhoff segment with straight tip (Tenckhoff + S), Swan neck segment with coiled tip (Swan neck + C) and Tenckhoff segment with coiled tip (Tenckhoff + C). METHODS: Randomised clinical trials were searched from PubMed, Embase, the Cochrane Register of clinical trials, China National Knowledge Infrastructure (CNKI) and ChinaInfo from their inception until July 31, 2022. Meta-analysis was performed using Stata 14.0 and RevMan 5.3.5 software to evaluate the four commonly used PDCs. RESULTS: Seventeen studies involved 1578 participants were included. NMA showed that compared with Swan neck + C, Swan neck + S significantly reduced catheter tip migration (OR 0.47 95% CI 0.22-0.99). Tenckhoff + S was more effective in reducing catheter dysfunction (OR 0.42, 95% CI 0.23-0.79), catheter tip migration with dysfunction (OR 0.19, 95% CI 0.05-0.78) and catheter removal (OR 0.56, 95% CI 0.34-0.93) which were consistent with the pairwise meta-analysis. According to the surface under the cumulative ranking curve, Swan neck + S emerged as the best PDC in the reduction of catheter tip migration (83.3%), followed by Tenckhoff + S (79.4%). Moreover, Tenckhoff + S (86.5%, 76.3%) and Swan neck + S (72.3, 86.9%) ranked as the first and second PDC for 1 and 2-year technique survival which was significantly higher than those of the other two PDCs. CONCLUSION: Our NMA showed Swan neck + S and Tenckhoff + S tended to be more efficacious than Swan neck + C and Tenckhoff + C in lowering the mechanical dysfunction and prolonging the technique survival, which may contribute to better clinical decisions. More randomised controlled trials with larger scales and higher quality are needed in order to obtain more credible evidence.

Machine learning for the prediction of delirium in elderly intensive care unit patients.

PURPOSE: This study aims to develop and validate a prediction model for delirium in elderly ICU patients and help clinicians identify high-risk patients at the early stage. METHODS: Patients admitted to ICU for at least 24 h and using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database (76,943 ICU stays from 2008 to 2019) were considered. Patients with a positive delirium test in the first 24 h and under 65 years of age were excluded. Two prediction models, machine learning extreme gradient boosting (XGBoost) and logistic regression (LR) model, were developed and validated to predict the onset of delirium. RESULTS: Of the 18,760 patients included in the analysis, 3463(18.5%) were delirium positive. A total of 22 significant predictors were selected by LASSO regression. The XGBoost model demonstrated superior performance over the LR model, with the Area Under the Receiver Operating Characteristic (AUC) values of 0.853 (95% confidence interval [CI] 0.846-0.861) and 0.831 (95% CI 0.815-0.847) in the training and testing datasets, respectively. Moreover, the XGBoost model outperformed the LR model in both calibration and clinical utility. The top five predictors associated with the onset of delirium were sequential organ failure assessment (SOFA), infection, minimum platelets, maximum systolic blood pressure (SBP), and maximum temperature. CONCLUSION: The XGBoost model demonstrated good predictive performance for delirium among elderly ICU patients, thus assisting clinicians in identifying high-risk patients at the early stage and implementing targeted interventions to improve outcome.

Examination of SARS-CoV-2 serological test results from multiple commercial and laboratory platforms with an in-house serum panel.

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19 diagnosis. Serological tests are valuable tools for serosurveillance programs and establishing correlates of protection from disease. This study evaluated the performance of one in-house enzyme linked immunosorbent assay (ELISA) utilizing the pre-fusion stabilized ectodomain of SARS-CoV-2 spike (S), two commercially available chemiluminescence assays Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Abbott SARS-CoV-2 IgG assay and one commercially available Surrogate Virus Neutralization Test (sVNT), GenScript USA Inc., cPass SARS-CoV-2 Neutralization Antibody Detection Kit for the detection of SARS-CoV-2 specific antibodies. Using a panel of rRT-PCR confirmed COVID-19 patients' sera and a negative control group as a reference standard, all three immunoassays demonstrated high comparable positivity rates and low discordant rates. All three immunoassays were highly sensitive with estimated sensitivities ranging from 95.4-96.6 %. ROC curve analysis indicated that all three immunoassays had high diagnostic accuracies with area under the curve (AUC) values ranging from 0.9698 to 0.9807. High positive correlation was demonstrated among the conventional microneutralization test (MNT) titers and the sVNT inhibition percent values. Our study indicates that independent evaluations are necessary to optimize the overall utility and the interpretation of the results of serological tests. Overall, we demonstrate that all serological tests evaluated in this study are suitable for the detection of SARS-CoV-2 antibodies.

Nucleic acid-functionalized nanozymes and their applications.

Nanozymes are inorganic, organic and metal-organic framework nanoparticles that reveal catalytic functions by emulating native enzyme activities. Recently, these nanozymes have attracted growing scientific interest, finding diverse analytical and medical applications. However, the catalytic activities and functions of nanozymes are limited, due to the lack of substrate binding sites that concentrate on the substrate at the catalytic site (molarity effect), introduce substrate specificity and allow functional complexity of the catalysts (cascaded, switchable and cooperative catalysis). The modification of nanozymes with functional nucleic acids provides means to overcome these limitations and engineer nucleic acid/nanozyme hybrids for diverse applications. This is exemplified with the synthesis of aptananozymes, which are supramolecular aptamer-modified nanozymes. Aptananozymes exhibit combined specific binding and catalytic properties that drive diverse chemical transformations, revealing enhanced catalytic activities, as compared to the separated nanozyme/aptamer constituents. Relationships of structure-catalytic functions in the aptananozyme constructs are demonstrated. In addition, modification of nanozymes exhibiting multimodal catalytic functions with aptamers allows the engineering of nanozyme-based bioreactors for cascaded catalysis. Also, the functionalization of reactive oxygen species (ROS)-generating nanozymes with cancer cell-recognizing aptamers yields aptananozymes for targeted chemodynamic treatment of cancer cells and cancer tumors elicited in mice. Finally, nucleic acid-modified enzyme (glucose oxidase)-loaded metal-organic framework nanoparticles yield switchable biocatalytic nanozymes that drive the ON/OFF biocatalyzed oxidation of Amplex Red, dopamine or the generation of chemiluminescence. Herein, future challenges of the topic are addressed.

Distribution of pathological types and epidemiological characteristics based on kidney biopsy in Northwest China.

BACKGROUND: The spectrum of biopsy-confirmed kidney disease varies with regions and periods. We describe the distribution of pathological types and epidemiological characteristics of kidney diseases in Northwest China due to regional differences in geographical environment, social economy, and dietary habits. METHODS: Kidney biopsy cases from 2005 to 2020 in Xijing Hospital were retrospectively analyzed. Pathological characteristics of patients in different periods were analyzed using the t test or chi-square test. Joinpoint regression was used to analyze trends in pathological types and disease spectrum. RESULTS: A total of 10,528 eligible patients were included. Primary glomerular disease (PGD) accounted for the majority of the cases and exhibited an obvious downward trend, whereas secondary glomerular disease (SGD) showed an obvious upward trend. Among PGD, immunoglobulin A nephropathy (IgAN) remained the most common pathological type, and the detection rate of membranous nephropathy (MN) was significantly increased. Among SGD, Henoch-Schönlein purpura nephritis (HSPN) was the most common pathological type and may present a significant characteristic of Northwest China. Diabetic nephropathy (DN) exhibited the most obvious upward trend in the whole process, whereas the fastest growth since 2012 was in hypertensive nephropathy. CONCLUSION: The proportion of SGD increased whereas PGD declined. IgAN remained the most common PGD, and HSPN was the most common SGD. MN and DN showed the most obvious upward trend among PGD and SGD, respectively. Changes in the spectrum of kidney disease, especially the constituent ratio of SGD, pose a great challenge to public health.

The Role of Tryptophan Metabolism in the Occurrence and Progression of Acute and Chronic Kidney Diseases.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common kidney diseases in clinics with high morbidity and mortality, but their pathogenesis is intricate. Tryptophan (Trp) is a fundamental amino acid for humans, and its metabolism produces various bioactive substances involved in the pathophysiology of AKI and CKD. Metabolomic studies manifest that Trp metabolites like kynurenine (KYN), 5-hydroxyindoleacetic acid (5-HIAA), and indoxyl sulfate (IS) increase in AKI or CKD and act as biomarkers that facilitate the early identification of diseases. Meanwhile, KYN and IS act as ligands to exacerbate kidney damage by activating aryl hydrocarbon receptor (AhR) signal transduction. The reduction of renal function can cause the accumulation of Trp metabolites which in turn accelerate the progression of AKI or CKD. Besides, gut dysbiosis induces the expansion of Enterobacteriaceae family to produce excessive IS, which cannot be excreted due to the deterioration of renal function. The application of Trp metabolism as a target in AKI and CKD will also be elaborated. Thus, this study aims to elucidate Trp metabolism in the development of AKI and CKD, and explores the relative treatment strategies by targeting Trp from the perspective of metabolomics to provide a reference for their diagnosis and prevention.

[Research progress of Wnt signaling pathway in the epidermal repair].

Wnt signaling pathway is a complex protein interaction network, and its function can most commonly or often be seen in embryonic development and cancer treatments, and meanwhile it is also involved in normal physiological processes in adult animals. Recently, with the rapid development of skin tissue engineering, there have been more and more researches on signal pathway in skin wound healing. At present, it is known that Wnt signaling pathway plays a vital role in the epidermal stem cells, epidermal growth factors, hair follicle development and other important factors related to the epidermal repair. The systemic research on Wnt signaling pathway has important clinical significance in the demonstration and functional process of the skin tissue. In this paper, we review the research development of the Wnt signaling pathway in the epidermal repair process.