Magnetic Soft Microrobot Design for Cell Grasping and Transportation.

Manipulating cells at a small scale is widely acknowledged as a complex and challenging task, especially when it comes to cell grasping and transportation. Various precise methods have been developed to remotely control the movement of microrobots. However, the manipulation of micro-objects necessitates the use of end-effectors. This paper presents a study on the control of movement and grasping operations of a magnetic microrobot, utilizing only 3 pairs of electromagnetic coils. A specially designed microgripper is employed on the microrobot for efficient cell grasping and transportation. To ensure precise grasping, a bending deformation model of the microgripper is formulated and subsequently validated. To achieve precise and reliable transportation of cells to specific positions, an approach that combines an extended Kalman filter with a model predictive control method is adopted to accomplish the trajectory tracking task. Through experiments, we observe that by applying the proposed control strategy, the mean absolute error of path tracking is found to be less than 0.155 mm. Remarkably, this value accounts for only 1.55% of the microrobot's size, demonstrating the efficacy and accuracy of our control strategy. Furthermore, an experiment involving the grasping and transportation of a zebrafish embryonic cell (diameter: 800 µm) is successfully conducted. The results of this experiment not only validate the precision and effectiveness of the proposed microrobot and its associated models but also highlight its tremendous potential for cell manipulation in vitro and in vivo.

Glomerular IgG deposition predicts kidney disease progression in IgA nephropathy.

Objective: We aimed to explore the relationship between the presence and intensity of glomerular IgG deposition and the occurrence of kidney progression events in IgA nephropathy (IgAN). Methods: This retrospective study encompassed a total of 1207 patients with IgAN spanning the period from 2010 to 2022, and complete follow-up data were accessible for 736 patients. The IgG intensity was categorized as follows: low-level, defined as IgG (±) and IgG (+), and high-level, defined as IgG (++) and IgG (+++). Results: We found that the IgG-positive deposited group (N = 113, 9.36%) had significantly higher levels of ESR, TC, LDL, uric acid, proteinuria, and blood glucose, and lower serum albumin level compared to the IgG-negative deposited group (N = 1094, 90.64%). In terms of pathology, the IgG-positive deposited group had a significantly higher percentage of T2 score compared to the IgG-negative deposited group (p = 0.002). At the end of the follow-up period, the IgG-positive deposited group had a higher eGFR decline (-5.7 ± 4.37 ml/year) compared to the IgG-negative deposited group (-4 ± 2.52 ml/year), however, there was not a statistically significant difference between the two groups (p = 0.096). We observed that the high-IgG group had significantly higher level of TG compared to the low-IgG group (p = 0.042). Further analysis revealed that the group of patients with high level of IgG deposition in the kidney experienced a higher incidence of composite kidney outcomes compared to the group with low level of IgG deposition (p = 0.009). Logistic regression analyses showed that high level IgG deposition was an independent risk factor for kidney progression of IgAN (HR 13.419; 95% CI 2.690-66.943, P = 0.029). Further analyses for a solid conclusion using Cox regression that we found high level IgG deposition (HR 115.277; 95% CI 2.299-5.779E3, P = 0.017), eGFR (HR 0.932; 95% CI 0.870-0.999, P = 0.047), and urine protein excretion (HR 1.001; 95% CI 1.000-1.002, P = 0.015) were independent risk factor for kidney progression of IgAN. Conclusions: The intensity of IgG deposition has been found to be associated with the progression of IgAN. Future prospective studies should provide more robust evidence on the impact of IgG deposition on kidney outcomes in patients with IgAN.

Prognosis of IgA Nephropathy with Stage 3b-5 CKD.

Objective To investigate whether immunosuppressive therapy is beneficial in IgA nephropathy (IgAN) patients with eGFR < 45ml/min/1.73m2. Methods This retrospective study involved 110 IgAN patients for whom clinical data was available; of these, 90 had complete follow-up data. Patients were grouped based on whether they received immunotherapy during follow-up, their renal function, proteinuria levels, and the percentage of crescentic glomeruli observed at the time of renal biopsy. Results The mean eGFR for the participants was 32.0 ± 10.2 ml/min/1.73 m². The average follow-up duration was 46.1 ± 37.9 months. The mean rate of decline in eGFR was 3.6 ml/min/1.73 m² per year. There were 43 (47.8%) composite kidney endpoint occurred in these patients. In the group that received immunotherapy, the incidence of kidney endpoint events was lower than in the untreated group (45.1% vs. 57.9%), but the difference was not statistically significant (P = 0.320). Among patients with stage CKD 3b, the incidence of endpoint events was lower than in those with stages CKD 4 and 5 (36.8% vs. 66.7%, P = 0.006). Conversely, the high proteinuria group saw a higher incidence of endpoint events compared to the low proteinuria group (51.9% vs. 23.1%), although this difference was not statistically significant (P = 0.054). Meanwhile, there was no significant difference in the incidence of endpoint events between the two crescent glomerular ratio groups (48.7% vs. 41.7%, P = 0.649). Kaplan-Meier survival analysis indicated that renal function level (P＜0.001) and proteinuria (P = 0.023) were associated with renal survival in IgAN patients. In contrast, the administration of immunosuppressive therapy (P = 0.288) and the prevalence of C lesions (P = 0.982) did not show a significant association with renal survival. Further, Cox regression analysis identified systolic blood pressure, fibrinogen, and CKD stage as risk factors for eGFR decline in IgAN patients (all P < 0.05). Conclusions IgAN patients with stage 3b-5 CKD exhibited a poor prognosis. It appears that in this specific cohort of IgAN patients, immunosuppressive therapy may not provide significant advantages over supportive care therapeutic regimens in terms of disease management.

Second near-infrared fluorescent Metal-Organic framework sensors for in vivo extracellular adenosine triphosphate monitoring.

Plant nanobionic sensors enable real-time monitoring of signaling molecules in plants by interfacing them with specifically designed nanoprobes, which have been acknowledged as species-independent analytical tools. In this study, we developed a plant nanobionic sensor for in vivo detection of extracellular adenosine triphosphate (eATP) in living plants by designing a novel second near-infrared (NIR-II) fluorescent metal-organic framework (MOF) nanoprobe. The NIR-II fluorescent nanoprobe (IR-1061 micelle@ZIF-90) with a sandwich structure was synthesized by successive encapsulation of the hydrophobic NIR-II dye IR-1061 with the amphipathic polymer DSPE-mPEG 2000 and MOF ZIF-90. Interestingly, coating ZIF-90 around IR-1061 micelles increased the NIR-II fluorescence 16.6-fold. Utilizing the ultrahigh NIR-II fluorescent emission of the designed nanoprobes and specific recognition of ZIF-90 to ATP, the nanoprobes were applied to spatial and temporal monitoring eATP in model and non-model plants under environmental stress.

Clinical and pathological findings of IgA nephropathy following SARS-CoV-2 infection.

The features of IgA nephropathy (IgAN) after SARS-CoV-2 infection have not been well characterized. In this study, we compared the clinical and pathological characteristics of patients with IgAN who had experienced SARS-CoV-2 infection to those who had not. We conducted a retrospective study that enrolled 38 patients with biopsy-proven IgAN following SARS-CoV-2 infection with 4 months (post-SARS-CoV-2 infection group) and 1154 patients with IgAN prior to the pandemic (pre-SARS-CoV-2 infection group). Among the SARS-CoV-2 group cases, 61% were females. The average duration from SARS-CoV-2 infection to renal biopsy was 78.6 days. Prior to SARS-CoV-2 infection, the patients had different presentations of nephropathy. One patient had isolated hematuria, two had isolated proteinuria, twenty presented with both hematuria and proteinuria, and one patient had elevated serum creatinine. Additionally, there were eight cases with uncertain nephropathy history, and six cases did not have a history of nephropathy. Following SARS-CoV-2 infection, five patients experienced gross hematuria, one case exhibited creatinine elevation, and five cases showed an increase in proteinuria. The group of patients infected with SARS-CoV-2 after the COVID-19 pandemic exhibited older age, higher hypertension ratio and lower eGFR values compared to the pre-SARS-CoV-2 infection group. As for pathological parameters, a higher proportion of patients in the post-SARS-CoV-2 infection group exhibited a higher percentage of sclerotic glomeruli and glomerular ischemic sclerosis. There were no significant differences observed between the two groups in terms of therapy involving steroids, immunosuppressants, or RAS inhibitors. IgA nephropathy patients who were infected with SARS-CoV-2 were generally older and experienced more severe kidney damage compared to those without SARS-CoV-2 infection.

Effect of hematuria on the kidney disease progression in IgA nephropathy patients with mild proteinuria and well-preserved renal function.

OBJECTIVE: To investigate whether hematuria is a risk factor in IgA nephropathy (IgAN) patients with mild proteinuria and well-preserved renal function. METHODS: This retrospective study included a total of 63 IgAN patients, with complete clinical data available for 50 patients. Hematuria assessment was conducted using two methods: 1) an automated method using a urine particle analyzer, and 2) a manual method performed by a skilled examiner to examine microscopic urine sediment. RESULTS: The results of hematuria measurement using both automated and manual methods showed a strong linear correlation (r = 0.78, P < 0.001). In IgAN patients, those with high urinary red blood cell count (U-RBCs) exhibited higher serum IgA levels compared to patients with low U-RBCs. Additionally, patients with crescent formation had higher levels of proteinuria compared to those without crescents. Patients who received immunosuppressive treatment displayed higher levels of systolic blood pressure (SBP) and mean arterial pressure (MAP), as well as lower levels of serum hemoglobin and albumin. They also had a higher prevalence of T1 lesions compared to patients who did not undergo immunosuppression. Furthermore, among patients with crescent formation, those who received immunosuppressive agents exhibited higher levels of SBP, diastolic blood pressure (DBP), MAP, and U-RBCs, as well as lower levels of albumin and proteinuria at the time of renal biopsy. No composite kidney endpoint events were observed in these groups of patients. The U-RBCs level was not identified as a risk factor influencing the decline of estimated glomerular filtration rate (eGFR) in IgAN. CONCLUSIONS: The presence of hematuria at the time of biopsy was not found to be associated with kidney disease progression in IgAN patients who had mild proteinuria and well-preserved renal function. This suggests that it is possible that these patients may not derive significant benefits from immunosuppressive therapy.

Deciphering prognostic value of CD22 and its contribution to suppression of proinflammatory cytokines production in patients with IgA nephropathy.

BACKGROUND: CD22, mainly expressed in mature B cells, could negatively regulate the function of B cells by binding to sialic acid-positive IgG (SA-IgG). Soluble CD22 (sCD22) is generated by the cleavage of the extracellular domain of CD22 on the membrane surface. However, the role of CD22 in IgA nephropathy (IgAN) remains unknown. METHODS: A total of 170 IgAN patients with a mean follow-up of 18 months were included in this study. The sCD22, TGF-ß, IL-6 and TNF-α were detected using commercial ELISA kits. SA-IgG were purified to stimulate peripheral blood mononuclear cells (PBMCs) from IgAN patients. RESULTS: The plasma levels of sCD22 were lower in IgAN patients in comparison with healthy control. Furthermore, CD22 mRNA levels in PBMCs from patients with IgAN were significantly lower than those of healthy controls. The plasma levels of sCD22 were positively correlated to the mRNA levels of CD22. We found that patients with higher sCD22 levels had a lower level of serum creatinine and a higher level of eGFR on the time of renal biopsy and a higher remission rate of proteinuria and a lower risk of kidney events at the end of follow-up. The logistic regression analysis showed sCD22 was associated with an increased odd of proteinuria remission after being adjusted for eGFR, proteinuria, and SBP. After adjusting for confounding variables, sCD22 was a borderline significant predictor of less kidney composite endpoint. In addition, the sCD22 levels were positively associated with SA-IgG in plasma. The experimental results in vitro showed that addition of SA-IgG enhanced the release of sCD22 in cell supernatant and the phosphorylation of CD22 in PBMCs, further inhibiting the production of IL-6, TNF-α, and TGF-ß in cell supernatant in a dose-dependent manner. Pretreatment with CD22-antibody significantly increased the expression of cytokines in PBMCs. CONCLUSIONS: This is the first study to demonstrate that lower plasma soluble CD22 in IgAN patients and high soluble CD22 levels are associated with an increased odd of proteinuria remission and a decreased odd of kidney endpoint. The interaction between CD22 and SA-IgG can inhibit proliferation and inflammation release in PBMCs from IgAN patients.

Circulating platelets supply ST6Gal-1 in patients with IgA nephropathy.

BACKGROUND: Our previous study showed ST6 ß-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN). Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases. METHODS: A total of 180 patients with IgAN were included in this study. ST6Gal-1 levels were analyzed before and after activation of platelets by flow cytometry. RESULTS: We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group. There was a positive correlation between platelet counts and ST6Gal-1 levels in plasma. Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio compared with those patients with lower platelet counts. No differences were found in terms of the eGFR decline and composite kidney endpoints between two groups. Furthermore, we investigated whether platelets were activated and released ST6Gal-1 in patients with IgAN. The expression of CD62P in platelets in patients with IgAN was higher than those of healthy controls. There were no obvious changes in ST6Gal-1 levels between the rest and the activated platelets within 1 to 2-hour, however, the difference in ST6Gal-1 levels became more pronounced after 4-hour of incubation. CONCLUSIONS: In conclusion, human circulating platelets contain ST6Gal-1, which may be released by the activation of platelets in IgAN.

What is the context? Our previous study showed ST6 ß-galactoside α2,6-sialyltransferase 1 (ST6Gal-1) levels in plasma were associated with a slower progression of IgA nephropathy (IgAN).Platelets are the crucial regulator of cell surface glycosylation events in circulation by supplying glycosyltransferases.Whether elevated ST6Gal-1 in plasma is partly from platelets in IgAN has not been fully elucidated.What is new? A total of 180 patients with IgAN were included in this study.We found that IgAN patients in the higher platelet counts group exhibited higher levels of ST6Gal-1 compared with the lower platelet counts group.Patients with higher platelet counts had higher levels of IgA, serum C3, serum C4 and proteinuria, higher percentages of platelet crits, S1 and T1/2, lower levels of platelet distribution width and the mean platelet volume, as well as a lower percentage of platelet large cell ratio.There were no differences in terms of the eGFR decline and composite kidney endpoints between two groups.Furthermore, we explored whether platelets were activated and released ST6Gal-1 in patients with IgAN. The expression of CD62P in platelets in patients with IgAN was higher than that of healthy controls.There were no obvious changes in ST6Gal-1 levels between the rest and the activated platelets within 1 to 2-hour, however, the difference in ST6Gal-1 levels became more pronounced after 4-hour of incubation.What is the impact?Human circulating platelets contain ST6Gal-1, which can be released upon platelets activation. These findings suggest ST6Gal-1 is dynamically controlled by platelet activation to remodel cell surface glycans and alter cell behavior.

Elevated activating Fc gamma receptors levels correlated with susceptibility and severity of IgA nephropathy.

Background: It is still uncertain if a dysregulated expression of activating Fc gamma receptors (FcγRs) is associated with the development of immunoglobulin A nephropathy (IgAN). Methods: RNA sequencing was used to determine the mRNA levels of type I FcγRs, which were then verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Commercial ELISA kits were used to detect plasma soluble FcγRIIIb (sFcγRIIIb). Results: We first examined the expression of FcγRs genes in 17 patients with IgAN and six healthy controls. The expression of FcγRIa, FcγRIb, FcγRIIa, FcγRIIc, FcγRIIIa, and FcγRIIIb was shown to be higher in IgAN patients. Even without statistical significance, there was a downward trend in FcγRIIb mRNA levels in IgAN. We observed that the expression levels of activating FcγR mRNAs were consistently higher in an independent set of 20 IgAN patients and 20 healthy controls, confirming the RNA-seq results. FcγRIIIb was the IgG receptor with the greatest difference in expression between the two groups (log2 fold-change = 1.82). We observed a much higher percent of FcγRIIIb positive cells in IgAN by flow cytometry. Next, we measured plasma sFcRIIIb levels in 50 patients with IgAN and 50 healthy controls. The findings revealed that the mean sFcγRIIIb level in plasma in participants with IgAN was much higher than that of healthy controls. Increased sFcγRIIIb levels were associated with a substantial increase in body mass index (BMI), lipid levels, serum creatinine level, and a larger percentage of sclerosis compared with lower sFcRIIIb levels. Patients in the group with higher sFcγRIIIb levels were more likely to get glucocorticoid treatment. Conclusion: The results demonstrated that the mRNA levels of the activating Fc receptor of IgG were significantly increased in IgAN. Patients with higher plasma sFcγRIIIb levels may have had more severe illness than those with lower levels.

The difference between patients with nephrotic syndrome and nephrotic-range proteinuria in IgA nephropathy: a propensity score matched cohort study.

OBJECTIVE: To date, nephrotic syndrome (NS) has not been well characterized in patients with IgA nephropathy (IgAN). Whether decline in serum albumin is an ominous sign in IgAN patients with massive proteinuria remains unknown. In this study, we evaluated clinical and pathological features of IgAN with NS and compared the differences for these features and long-term outcomes between patients with nephrotic syndrome and nephrotic-range proteinuria. METHODS: A retrospective study was conducted, enrolling 1013 patients with biopsy-proven IgAN. The primary endpoint was the composite of a doubling of the base-line serum creatinine, 50% reduction in eGFR, ESKD (eGFR < 15 ml/min per 1.73 m2) or death. RESULTS: A total of 59 patients were presented with NS (5.8%). The patients with NS showed lower levels of hemoglobin, albumin and higher levels of serum creatinine, serum uric acid and urinary protein than patients without NS. As for pathological parameters, more patients with NS showed a higher prevalence of E1 lesions, T1/2 and C1/2 lesions. Furthermore, we used the propensity score matching method to select 57 patients with nephrotic-range proteinuria and normal serum albumin (NR group) who were comparable to 59 patients with NS. Patients with NS had lower levels of hemoglobin, albumin and IgG and higher levels of TC, LDL, FIB and D-dimer as well as more severe E1 and C1/2 lesions than those in NR group. The S1 lesion was more severe in the NR group than that in the NS group. There was no significant difference in long-term outcome between the two groups. In addition, we found that serum albumin level or the presence of hypoalbuminemia was not a risk factor affecting long-term outcome in patients with massive proteinuria. CONCLUSIONS: A prevalence of 5.8% of NS was presented in IgAN adult patients in our study. IgAN with NS patients had low levels of hemoglobin, albumin, high levels of serum creatinine, serum uric acid, urinary protein and more acute lesions. The prognosis of NS in patients with IgAN was not inferior to that of patients with nephrotic range proteinuria and normal serum albumin.

Sialylation of IgG inhibits the formation of galactose-deficient IgA1-containing immune complexes and protects mesangial cells from injury in IgA nephropathy.

BACKGROUND: The addition of sialic acid alters IgG from a pro-inflammatory state to an anti-inflammatory state. However, there is a lack of research on the changes of IgG sialylation in IgA nephropathy (IgAN). METHODS: This study included a total of 184 IgAN patients. The sialylated IgG (SA-IgG), IgG-galactose-deficient IgA1 complex (IgG-Gd-IgA1-IC), IL-6, TNF-α, and TGF-ß were detected using commercial ELISA kits. SA-IgG, non-sialylated IgG (NSA-IgG), sialylated IgG-IgA1 complex (SA-IgG-IgA1), and non-sialylated IgG-IgA1 complex (NSA-IgG-IgA1) were purified from IgAN patients and healthy controls (HCs). RESULTS: The mean SA-IgG levels in plasma and B lymphocytes in IgAN patients were significantly higher than those of healthy controls. A positive correlation was found between SA-IgG levels in plasma and B lymphocytes. In vitro, the results showed that the release of IgG-Gd-IgA1-IC was significantly decreased in peripheral blood mononuclear cells (PBMCs) cultured with SA-IgG from both IgAN patients and healthy controls. The proliferation ability and the release of IL-6, TNF-α, and TGF-ß in human mesangial cells (HMCs) were measured after stimulating with SA-IgG-IgA1-IC and NSA-IgG-IgA1-IC. The mesangial cell proliferation levels induced by NSA-IgG-IgA1-IC derived from IgAN patients were significantly higher than those caused by SA-IgG-IgA1-IC derived from IgAN patients and healthy controls. Compared with NSA-IgG-IgA1 from healthy controls, IgAN-NSA-IgG-IgA1 could significantly upregulate the expression of IL-6 and TNF-α in mesangial cells. The data showed that there weren't any significant differences in the levels of IL-6, TNF-α, and TGF-ß when treated with IgAN-SA-IgG-IgA1 and HC-NSA-IgG-IgA1. CONCLUSIONS: The present study demonstrated that the sialylation of IgG increased in patients with IgA nephropathy. It exerted an inhibitory effect on the formation of Gd-IgA1-containing immune complexes in PBMCs and the proliferation and inflammation activation in mesangial cells.

Plasma ST6GAL1 regulates IgG sialylation to control IgA nephropathy progression.

BACKGROUND: Our previous study revealed that plasma levels of a-2,6-sialyltransferase 1 (ST6GAL1) were increased in patients with IgA nephropathy (IgAN). ST6GAL1 catalyzes terminal sialylation of IgG to shift the antibody effector function to the anti-inflammatory pattern. However, the role of plasma ST6GAL1 in the progression of IgAN and underlying mechanisms are still unknown. METHODS: A total of 180 IgAN patients were included. The kidney outcomes were defined as the eGFR decline or proteinuria remission. Peripheral blood mononuclear cells (PBMCs) were either stimulated with purified sialylated IgG (SA-IgG) or with non-sialylated IgG (NSA-IgG) from IgAN patients to detect the levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) in supernatant. RESULTS: Compared with the lower ST6GAL1 (reference), the risk of eGFR decline decreased for the higher ST6GAL1 group after adjustment for baseline eGFR, systolic blood pressure (SBP), and proteinuria. The results showed that patients with higher ST6GAL1 levels had a higher rate of proteinuria remission. ST6GAL1, expressed as a continuous variable, was a protective factor for eGFR decline and proteinuria remission. An in vitro study showed that the administration of recombinant ST6GAL1 (rST6GAL1) decreased the levels of IL-6 and TNF-α in PBMCs. Furthermore, the administration of rST6GAL1 resulted in the enrichment of SA-IgG in a concentration-dependent manner. In addition, as compared to control, purified SA-IgG-treated PBMCs showed a significant decrease in the expression of IL-6 and TNF-α. CONCLUSION: Our study indicated that elevated ST6GAL1 was associated with a slower progression of IgAN, which may play a protective effect by increasing IgG sialylation to inhibit the production of proinflammatory cytokines in PBMCs.

Effects and Safety of a Novel Oral Potassium-Lowering Drug-Sodium Zirconium Cyclosilicate for the Treatment of Hyperkalemia: a Systematic Review and Meta-Analysis.

BACKGROUND: Oral sodium zirconium cyclosilicate (SZC) is a novel potassium binder capable of achieving a rapid reduction of serum potassium (sK+) and maintaining a long-term normokalemia. We undertook a meta-analysis to summarize and evaluate the effects surrounding SZC in patients with hyperkalemia. METHOD: We searched data sources from MEDLINE (from 1950 to Sep 2020), EMBASE (from 1970 to Sep 2020), and the Cochrane Library database (from 1950 to Sep 2020) for eligible studies. All randomized controlled trials (RCTs) regarding comparison of therapeutic effects of SZC in hyperkalemia participants were included. RESULTS: Seven studies, including 1697 patients with hyperkalemia, were analyzed. SZC significantly reduced mean sK+ (-0.42 mmol/L; 95% CI: -0.63 to -0.20 mmol/L, p = 0.0001) compared with placebo, with a significantly greater proportion of patients with normokalemia (RR 3.48, 95% CI 1.49 to 8.11, p = 0.004). Subgroup analyses showed that the longer durations of SZC treatment, the greater magnitudes of potassium reduction when compared with those of placebo (p between subgroups = 0.01) at correction phase. Besides, it also demonstrated sK+ tended to decrease more in patients who got longer treatment or larger dosage of SZC at maintenance phase; however, the difference did not reach statistical significance. Additionally, the drug was equally effective in studies with larger than 50% of patients with chronic kidney disease (CKD) or diabetes or patients using renin-angiotensin aldosterone system inhibitor (RAAS) inhibitors (all p < 0.05). The risk of edema (4.30, 1.17 to 15.84; p = 0.03) in SZC group was higher than those of placebo group. No statistically significant differences in the risks of other adverse events were observed between the two groups. CONCLUSIONS: SZC effectively decreased the sK+ level in patients with hyperkalemia within 48 h and had benefits in the long-term control of serum potassium in patients who continued to receive SZC with a favorable safety profile from available data.

ST6Gal1 is up-regulated and associated with aberrant IgA1 glycosylation in IgA nephropathy: An integrated analysis of the transcriptome.

Galactose-deficient IgA1 (Gd-IgA1) plays a crucial role in the development of Immunoglobulin A nephropathy (IgAN), however, the underlying pathogenic mechanisms driving Gd-IgA1 production in B cells are not well understood. In this study, RNA-seq analysis identified 337 down-regulated and 405 up-regulated genes in B cells from 17 patients with IgAN and 6 healthy controls. Among them, ST6Gal1, which was associated with IgAN in a previous genome-wide association study (GWAS), was up-regulated in IgAN and significantly positive correlated with elevated Gd-IgA1. In addition, we identified increased plasma ST6Gal1 levels in 100 patients with IgAN, which were associated with higher levels of proteinuria, plasma IgA, Gd-IgA1 levels, greater degrees of systemic complement activation including C3a, Bb, C4d, MAC and a lower proportion classified as C2 grade (crescent proportion ≥25%). Interesting, in vitro, recombinant ST6Gal1 (rST6Gal1) exposure reduced the production of Gd-IgA1 in cultured peripheral blood mononuclear cells from IgAN patients. rST6Gal1 stimuli also increased expression of C1GALT1, which were well-known proportional to the decrease in galactose deficiency of IgA1. In conclusions, we identified increased plasma ST6Gal1 levels and the association of ST6Gal1 with disease severity of IgAN. Additionally, rST6Gal1 administration in vitro increased expression of C1GALT1 and reduced the production of Gd-IgA1.

C1GALT1 expression is associated with galactosylation of IgA1 in peripheral B lymphocyte in immunoglobulin a nephropathy.

BACKGROUND: More and more studies demonstrated that genetic variation at C1GALT1 influences Gd-IgA1 level in IgAN. However, whether the expression of ß1, 3-galactosyltransferase (ß1, 3Gal-T) was influenced may provide insights into how Gd-IgA1 levels are controlled in IgAN. METHODS: Thirty IgAN patients diagnosed in Tianjin Medical University General Hospital from April to September 2018 and 30 healthy volunteers whose age and gender matched with patients were enrolled in this study. Total Gd-IgA1 levels in plasma were determined by ELISA and C1GALT1 levels were determined by RT-PCR. Four databases (PubMed, EMBASE, CNKI, WanFang Medical Network) were searched to identify eligible studies that evaluated a difference in the expression of C1GALT1 in IgAN patients compared with total controls (non-IgAN and health controls). The C1GALT1C1 expression levels, which was indispensable to ß1, 3Gal-T of IgA1, was also been compared. RESULTS: Gd-IgA1 levels were remarkable higher in IgAN patients compared with healthy control. The expression levels of C1GALT1 gene were remarkably down-regulated in IgAN patients compared with healthy control. And the mRNA level of C1GALT1 was inversely correlated to Gd-IgA1 levels. In meta-analysis, six articles including 316 participants that analyzed the expression of ß1, 3Gal-T were met inclusion criteria. There was no significant difference in the expression of C1GALT1 between IgAN patients compared with controls. And we found patients with IgAN had lower levels of C1GALT1 gene expression in the B cells compared to controls. The C1GALT1C1 levels in the IgAN patients were not different from the levels in the control group, which were unchanged no matter according to different ethnic population, different control group and different cell source. Two studies including 46 persons compared enzymatic activity of ß1, 3Gal-T in B cells, and the result showed the ß1, 3Gal-T activity was decreased in B cells. CONCLUSIONS: We found expression levels of C1GALT1 were remarkably downregulated in IgAN patients and negatively correlated with higher levels of Gd-IgA1. Subsequent meta-analysis validated the low expression and activity of ß1, 3Gal-T in B cells in patients with IgAN. However, there was no apparent disparity in the aspect of C1GALT1C1 expression between IgAN and control groups.

Effect and safety of LCZ696 in the treatment of hypertension: A meta-analysis of 9 RCT studies.

BACKGROUND: LCZ696 has been introduced in patients with hypertension in several trials. Here, we performed a meta-analysis to evaluate the effect and safety of LCZ696 in hypertensive patients. METHODS: PubMed, Embase, the Cochrane Library and ClinicalTrials.gov databases were searched to identify the available randomized controlled trials (RCTs) investigating the effect and safety of LCZ696 in hypertension patients. The last search date was October 31, 2018. RESULTS: Nine RCTs with 6765 subjects were finally included, in which 8 trials compared the effect and safety between LCZ696 and angiotensin receptor antagonists (ARBs). Evidences showed LCZ696, compared with ARBs, achieved a better blood pressure control rate (OR 1.24, 95% CI: 1.14-1.35), specifically, LCZ696 were better at reducing systolic blood pressure [WMD -4.11 mmHg, 95% CI: (-5.13, -3.08) mmHg], diastolic blood pressure [WMD -1.79 mmHg, 95% CI: (-2.22, -1.37) mmHg], mean 24-hour ambulatory systolic blood pressure [WMD -3.24 mmHg, 95% CI: (-4.48, -1.99) mmHg] and mean 24-hour ambulatory diastolic blood pressure [WMD -1.25 mmHg, 95% CI: (-1.81, -0.69) mmHg]. There was no difference in the events of adverse events (risk ratio [RR] 1.01, 95% CI: 0.39-1.09), serious adverse events (RR 0.80, 95% CI: 0.52-1.22) and discontinuation of treatment for any adverse events (RR 0.79, 95% CI: 0.56-1.11) between LCZ696 group and ARB/placebo group, except LCZ696 reduced the rate of headaches (RR 0.69, 95% CI: 0.48-0.99) while increased cough (RR 2.12, 95% CI: 1.11-4.04; P = .02; I = 25%). CONCLUSION: Our finding provides evidence that LCZ 696 was more effective than ARB on blood pressure control and was safe enough in patients with hypertension.

Environmental assessment of management options for nutrient flows in the food chain in China.

The nitrogen (N) and phosphorus (P) costs of food production have increased greatly in China during the last 30 years, leading to eutrophication of surface waters, nitrate leaching to groundwater, and greenhouse gas emissions. Here, we present the results of scenario analyses in which possible changes in food production-consumption in China for the year 2030 were explored. Changes in food chain structure, improvements in technology and management, and combinations of these on food supply and environmental quality were analyzed with the NUFER model. In the business as usual scenario, N and P fertilizer consumption in 2030 will be driven by population growth and diet changes and will both increase by 25%. N and P losses will increase by 44 and 73%, respectively, relative to the reference year 2005. Scenarios with increased imports of animal products and feed instead of domestic production, and with changes in the human diet, indicate reductions in fertilizer consumption and N and P losses relative to the business as usual scenario. Implementation of a package of integrated nutrient management measures may roughly nullify the increases in losses in the business as usual scenario and may greatly increase the efficiency of N and P throughout the whole food chain.

Phosphorus flows and use efficiencies in production and consumption of wheat, rice, and maize in China.

Increasing fertilizer phosphorus (P) application in agriculture has greatly contributed to the increase of crop yields during the last decades in China but it has also increased P flows in food production and consumption. The relationship between P use efficiency and P flow is not well quantified at national level. In present paper we report on P flows and P use efficiencies in rice, wheat, and maize production in China using the NUFER model. Conservation strategies for P utilization and the impact of these strategies on P use efficiency have been evaluated. Total amounts of P input to wheat, rice, and maize fields were 1095, 1240, and 1128 Gg, respectively, in China, approximately 80% of which was in chemical fertilizers. The accumulation of P annually in the fields of wheat, rice, and maize was 29.4, 13.6, and 21.3 kg ha(-1), respectively. Phosphorus recovered in the food products of wheat, rice, and maize accounted for only 12.5%, 13.5%, and 3.8% of the total P input, or 3.2%, 2.6%, and 0.9% of the applied fertilizer P, respectively. The present study shows that optimizing phosphorus flows and decreasing phosphorus losses in crop production and utilization through improved nutrient management must be considered as an important issue in the development of agriculture in China.

Nitrogen mass flow in China's animal production system and environmental implications.

China's economic boom in recent decades has stimulated consumer demand for animal products and consequently, a vast expansion in animal production. From 1978 to 2006, the number of animals increased by 322% for pigs, 209% for poultry, and 2770% for dairy cattle. The objective of the present study was to quantify nitrogen mass flow in China's animal production system at the national scale and to elucidate potential environmental implications. A comprehensive analysis was performed combining statistical records with data from the scientific literature and supplemental survey information. Results indicate that approximately 18 Mt of N flowed through the Chinese animal production system in 2006. Nitrogen input to the system was from various feed materials, including 6.8 Mt (38% of total) from roughage, 4.4 Mt (24%) from byproducts, 2.3 Mt (13%) from cereal grains, and 1.6 Mt (9%) each from crop residues and oilseed cakes, with the remaining N (16%) obtained from other feedstuffs. Nitrogen outputs from the system included edible animal products (2.4 t, 13% of total), nonedible animal parts (e.g., bones, skins) (3.8 Mt, 21%), and excreta (12 Mt, 66%). At the national level, the excreta would average 28 Mg (as excreted) and 90 kg N ha(-1) of cropland. However, at the provincial level, it varied from 1 Mg ha(-1) (5 kg N ha(-1)) in Qinghai to 97 Mg ha(-1) (243 kg N ha(-1)) in Sichuan. In regions with excreta in the intermediate rate (e.g., Hebei Province, 115 kg N ha(-1)) or high rare (e.g., Sichuan Province, 243 kg N ha(-1)), animal manure contributes significantly to nutrients polluting groundwater and/or surface waters. It is crucial for China to develop and implement proper management practices to maximum the beneficial use of the 12 Mt excreta N while minimizing its environmental footprint.