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Hepatitis-associated aplastic anemia (HAAA), a rare subtype of aplastic anemia (AA), is defined as bone marrow failure occurring after acute hepatitis. Severe HAAA requires immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT) as lifesaving treatment. The outcomes of HAAA patients who underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) have not been systematically evaluated. We retrospectively compared the characteristics of 15 patients with HAAA and 60 non-hepatitis-associated aplastic anemia (non-HAAA) patients, all 75 of whom underwent haplo-HSCT in our hospital between January 2006 and October 2021. The median ages of the patients were 18 years old (range, 3-36) for HAAA patients and 13 years (range, 2-45) for non-HAAA patients (p = 0.693). The median time for neutrophil engraftment was 14 days (range, 11-22) in the HAAA group and 12 days (range, 10-21) in the non-HAAA group (p = 0.363). At the time of analysis, 15 HAAA patients and 58 non-HAAA patients were alive, and their median follow-up times were 37 (range, 3-87) months and 31 (range, 2-110) months (p = 0.347), respectively. There were no significant differences in the three-year overall survival (OS) rates (100% vs. 96.7 ± 0.33%, P = 0.638) or liver event-free survival (LEFS) (80.0 ± 0.17% vs. 76.7 ± 0.19%, P = 0.747) between the two groups. Despite the small number of HAAA patients due to the rarity of the disease, these results, such as the similar incidence rates of 3-year OS and fewer liver events than expected, suggest that haplo-HSCT is a feasible treatment for HAAA a when there are no human leukocyte antigen (HLA)-matched donors available and has a low risk of transplant-related mortality and complications.

It is essential to solve the problem of phosphorus pollution in urban landscape water and reduce the degree of eutrophication. In this paper, lanthanum-modified bentonite (La-B) was prepared by high-temperature calcination and liquid-phase precipitation. Then La-B was modified with chitosan to prepare a low-cost environment-friendly functional material: lanthanum/chitosan co-modified bentonite (La-BC). It can reach the adsorption equilibrium within 30 min, and the maximum adsorption capacity is 15.5 mg/g (initial phosphate concentration 50 mg/L); when the target concentration is 2 mg/L, the removal rate can reach 98.5%. La-BC has a stronger anti-interference ability to common coexisting anions SO42−, HCO3−, NO3− and Cl− in the urban landscape water body. La-BC has excellent performance in weakly acidic to neutral water, and its pH applicable range has been improved, making it possible to apply in practical water. The fitting results show that the adsorption behavior conforms to the pseudo-second-order kinetic model and the Freundlich model. After 5 regenerations, the removal efficiency remained around 80%. In the actual water test results, the phosphate concentration can be controlled below 0.1 mg/L and the removal rate is above 75%. Due to its low cost and reusability, it has great potential in the practical application of phosphate removal from landscape water.

Haploidentical hematopoietic stem cell transplant (haplo-HSCT) provides an important alternative for children and adolescents with acquired severe aplastic anemia (SAA) lacking matched donors. To test whether pretransplant serum ferritin (SF) represents a candidate predictor for survival and a potential biomarker for graft-versus-host disease (GvHD) in pediatric haplo-HSCT, we retrospectively evaluated 147 eligible patients with SAA who underwent haplo-HSCT. The patients were divided into the low-SF group ( 1000 ng/mL) and the high-SF group (≥ 1000 ng/mL). We found that SF ≥1000 ng/mL independently increased the risk of grade II-IV aGvHD (HR = 2.596; 95% CI, 1.304-5.167, P = 0.007) and grade III-IV aGvHD (HR = 3.350; 95% CI, 1.162-9.658, P = 0.025). Similar probabilities of transplant-related mortality at 100 days were observed in the two groups (6.19 ± 2.45% vs 8.00 ± 3.84%, P = 0.168). The two-year overall survival (85.29 ± 3.89% vs 92.00% ± 3.84%, P = 0.746) and failure-free survival (83.23% ± 4.08% vs 83.37% ± 6.27%, P = 0.915) were comparable. GvHD-/failure-free survival were 60.06 ± 5.10% and 75.56 ± 6.87%, respectively (P = 0.056). In conclusion, elevated pretransplant SF level is associated with higher incidences of grade II-IV aGvHD and grade III-IV aGvHD. However, it is not associated with worse survival after haplo-HSCT for children and adolescent patients with SAA.

Diabetic kidney disease (DKD) is one of the most common and devastating complications of diabetic mellitus, and its prevalence is rising worldwide. Klotho, an anti-aging protein, is kidney protective in DKD. However, its large size, prohibitive cost and structural complexity hamper its potential utility in clinics. Here we report that Klotho-derived peptide 6 (KP6) mimics Klotho function and ameliorates DKD. In either an accelerated model of DKD induced by streptozotocin and advanced oxidation protein products in unilateral nephrectomized mice or db/db mice genetically prone to diabetes, chronic infusion of KP6 reversed established proteinuria, attenuated glomerular hypertrophy, mitigated podocyte damage, and ameliorated glomerulosclerosis and interstitial fibrotic lesions, but did not affect serum phosphorus and calcium levels. KP6 inhibited β-catenin activation in vivo and blocked the expression of its downstream target genes in glomerular podocytes and tubular epithelial cells. In vitro, KP6 prevented podocyte injury and inhibited β-catenin activation induced by high glucose without affecting Wnt expression. Co-immunoprecipitation revealed that KP6 bound to Wnt ligands and disrupted the engagement of Wnts with low density lipoprotein receptor-related protein 6, thereby interrupting Wnt/β-catenin signaling. Mutated KP6 with a scrambled amino acid sequence failed to bind Wnts and did not alleviate DKD in db/db mice. Thus, our studies identified KP6 as a novel Klotho-derived peptide that ameliorated DKD by blocking Wnt/β-catenin. Hence, our findings also suggest a new therapeutic strategy for the treatment of patients with DKD.

The aim of this study is to evaluate the safety of low-volume tidal peritoneal dialysis (TPD) and intermittent peritoneal dialysis (IPD) in ESRD patients initiating automated peritoneal dialysis (APD) after an acute catheter insertion. Clinical outcomes of patients who received either TPD or IPD using an APD system were compared in a randomized, open-label, prospective control study in a single-center setting. From May 2011 to May 2013, 49 patients were enrolled and 27 patients received low-volume TPD treatment, whereas 22 patients underwent low-volume IPD right after Tenckhoff catheter insertion. The incidence of complications during the 14-day APD treatment were observed. After APD treatment, all the patients were transferred to continuous ambulatory peritoneal dialysis and followed up for 2 years. The IPD group demonstrated a significantly higher incidence of catheter-related complications (omental wrapping 27.3% vs. 0% and suction pain 18.2% vs. 0%) than the TPD group after adjusting for age, gender, baseline diabetes, systolic blood pressure, BMI, and the experience of the operators. However, the short duration of APD treatment with either IPD or TPD mode did not affect the long-time technical survival. In patients immediately after catheter insertion, low-volume TPD mode demonstrated a lower incidence of catheter-related complications compared to IPD. Although our results provided evidence that TPD is a preferable APD mode for this specific population, definitive conclusions about TPD benefit cannot be made, owing to early termination of the trial.

Matrix metalloproteinase-10 (MMP-10) is a zinc-dependent endopeptidase involved in regulating a wide range of biologic processes, such as apoptosis, cell proliferation, and tissue remodeling. However, the role of MMP-10 in the pathogenesis of acute kidney injury (AKI) is unknown. In this study, we show that MMP-10 was upregulated in the kidneys and predominantly localized in the tubular epithelium in various models of AKI induced by ischemia/reperfusion (IR) or cisplatin. Overexpression of exogenous MMP-10 ameliorated AKI, manifested by decreased serum creatinine, blood urea nitrogen, tubular injury and apoptosis, and increased tubular regeneration. Conversely, knockdown of endogenous MMP-10 expression aggravated kidney injury. Interestingly, alleviation of AKI by MMP-10 in vivo was associated with the activation of epidermal growth factor receptor (EGFR) and its downstream AKT and extracellular signal-regulated kinase-1 and 2 (ERK1/2) signaling. Blockade of EGFR signaling by erlotinib abolished the MMP-10-mediated renal protection after AKI. In vitro, MMP-10 potentiated EGFR activation and protected kidney tubular cells against apoptosis induced by hypoxia/reoxygenation or cisplatin. MMP-10 was colocalized with heparin-binding EGF-like growth factor (HB-EGF) in vivo and activated it by a process of proteolytical cleavage in vitro. These studies identify HB-EGF as a previously unrecognized substrate of MMP-10. Our findings also underscore that MMP-10 can protect against AKI by augmenting EGFR signaling, leading to promotion of tubular cell survival and proliferation after injury.

Podocyte injury or dysfunction plays an essential role in causing proteinuria and glomerulosclerosis in chronic kidney diseases. To search for new players involved in podocyte injury, we performed gene expression profiling in the glomeruli by RNA sequencing. This unbiased approach led us to discover matrix metalloproteinase-10 (MMP-10), a secreted zinc-dependent endopeptidase, as one of the most upregulated genes after glomerular injury. In animal models and patients with proteinuric chronic kidney diseases, MMP-10 was upregulated specifically in the podocytes of injured glomeruli. Patients with chronic kidney diseases also had elevated circulating levels of MMP-10, which correlated with the severity of kidney insufficiency. In transgenic mice with podocyte-specific expression of MMP-10, proteinuria was aggravated after injury induced by Adriamycin. This was accompanied by more severe podocytopathy and glomerulosclerotic lesions. In contrast, knockdown of MMP-10 in vivo protected mice from proteinuria, restored podocyte integrity and reduced kidney fibrosis. Interestingly, MMP-10 reduced podocyte tight junctional protein zonula occludens-1 (ZO-1) but did not affect its mRNA level. Incubation of purified ZO-1 with MMP-10 directly resulted in its proteolytic degradation in vitro, suggesting ZO-1 as a novel substrate of MMP-10. Thus, our findings illustrate that induction of MMP-10 could lead to podocyte injury by degrading ZO-1, thereby promoting proteinuria and glomerulosclerosis in chronic kidney diseases.

Wnt/β-catenin is an evolutionarily conserved, developmental signalling pathway that regulates embryogenesis, injury repair and pathogenesis of human diseases. Dysregulated activation of Wnt/β-catenin is associated with the development and progression of renal fibrotic lesions after injury. Wnt are induced and β-catenin is activated in various models of experimental chronic kidney disease (CKD) and in human nephropathies. Recent findings indicate that pro(renin) receptor is an amplifier of Wnt/β-catenin by acting as a downstream target and an obligatory component for its signal transduction. Genetic blockade of Wnt secretion in a cell type-specific manner uncovers renal tubular epithelium as the major source of Wnt ligands in CKD. Wnt/β-catenin controls the expression of a wide variety of downstream mediators implicated in kidney fibrosis, such as fibronectin, Snail1, matrix metalloproteinase-7, hepatocyte growth factor and various components of the renin-angiotensin system. Targeted inhibition of Wnt/β-catenin is able to ameliorate kidney fibrotic lesions in pre-clinical settings. In this review, we summarize recent advances in our understanding of the regulation, signal transduction, role and mechanisms of Wnt/β-catenin signalling in the pathogenesis of kidney fibrosis. We also discuss the therapeutic potential of targeting this pathway for the treatment of fibrotic CKD.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has proven to be downregulated in podocytes challenged with high glucose (HG), and knockout of PTEN in podocytes aggravated the progression of diabetic kidney disease (DKD). However, whether podocyte-specific knockin of PTEN protects the kidney against hyperglycemia in vivo remains unknown. The inducible podocyte-specific PTEN knockin (PPKI) mice were generated by crossing newly created transgenic loxP-stop- loxP-PTEN mice with podocin-iCreERT2 mice. Diabetes mellitus was induced in mice by intraperitoneal injection of streptozotocin at a dose of 150 mg/kg. In vitro, small interfering RNA and adenovirus interference were used to observe the role of PTEN in HG-treated podocytes. Our data demonstrated that PTEN was markedly reduced in the podocytes of patients with DKD and focal segmental glomerulosclerosis, as well as in those of db/db mice. Interestingly, podocyte-specific knockin of PTEN significantly alleviated albuminuria, mesangial matrix expansion, effacement of podocyte foot processes, and incrassation of glomerular basement membrane in diabetic PPKI mice compared with wild-type diabetic mice, whereas no alteration was observed in the level of blood glucose. The potential renal protection of overexpressed PTEN in podocytes was partly attributed with an improvement in autophagy and motility and the inhibition of apoptosis. Our results showed that podocyte-specific knockin of PTEN protected the kidney against hyperglycemia in vivo , suggesting that targeting PTEN might be a novel and promising therapeutic strategy against DKD.

Background: Lipid deposition in glomeruli is one of the pathological characteristics of focal segmental glomerulosclerosis (FSGS). We have showed that phosphatase and tensin homolog (PTEN) is down-regulated in podocytes from patients with FSGS. However, the role of PTEN in FSGS is still largely unknown. Methods: PTEN partial knockout mice and podocyte-specific PTEN knockin mice were used to establish a glomerulosclerosis mouse model induced by uninephrectomy and high fat diet. Oxidized low-density lipoprotein (ox-LDL) stimulated mouse podocyte (cell line) was used to explore the pathway involved in PTEN mediated lipid accumulation. Findings: We revealed that partial deletion of PTEN increased lipid accumulation and fibrotic proteins deposition in glomeruli segmentally, and boosted albuminuria in glomerulosclerosis mouse model. Conversely, podocyte-specific overexpression of PTEN induced a marked alleviation in lipid retention in podocytes, albuminuria, and glomerulosclerosis. In cultured podocytes, PTEN was down-regulated by ox-LDL. Overexpression of PTEN reduced endocytic ox-LDL via down-regulating scavenger receptor A (SR-A), decreased intracellular cholesterol content, and thus prevented podocytes from lipid overload. In contrast, inhibition of PTEN aggravated podocytes damage due to more lipid accumulation. Mechanistically, we identified PTEN as a regulator of SR-A by dephosphorylating its nuclear transcription factor, yes-associated protein (YAP), at Ser127 in cytoplasm of ox-LDL treated podocytes. Interpretation: These findings implicate a central role of PTEN in a signaling cascade mediating lipid-loading in podocytes which contributes to glomerulosclerosis, and provide evidence for PTEN/YAP as a target for FSGS therapy. Funding: This study was supported by the National Natural Science Foundation Committee of China and GDUPS. Declaration of Interest: None. Ethical Approval: All animal studies were carried out with the approval of the animal care and use committee of Guangdong General Hospital. All human studies were performed with the approval of the Ethics Committee of Guangdong General Hospital, and written informed consent was obtained from the patients.

Xanthate-modified cross-linked chitosan (chitosan-SH) was synthesized by hydrothermal method. The adsorption mechanism and capacity of removing ruthenium [Ru(Ⅲ)] from aqueous solutions with chitosan-SH as an adsorbent was investigated. The characterization results indicated that carbon disulfide (CS2) was successfully loaded into cross-linked chitosan. Structural characterization of the samples was performed by Fourier transform infrared (FTIR), X-ray photoelectron spectrometer (XPS), scanning electron microscope (SEM), specific surface area and porosity analysis (BET) analysis methods. The results of kinetics data suggested that the ruthenium ion adsorption process by chitosan-SH could be fast to reach equilibrium within 30 min. Additionally, the removal percentage of uranium was obtained 94.7% at pH 7.0. Several parameters affecting adsorption capacity, including pH, contact time, initial Ru(Ⅲ) concentration and solution volume, and adsorbent concentration, were also investigated. Overall, chitosan-SH could be applied as a superior adsorbent for Ru(Ⅲ) in wastewater.

In this work, uniform polydopamine (PDA) layers by self-polymerization of dopamine were successfully coated around titanate nanotubes (TNTs) to enhance its adsorption ability. The polydopamine-functionalized titanate nanotubes (PDA-TNTs) exhibited outstanding U(VI) adsorption capacity (247.53 mg/g) and rapid adsorption efficiency. The nitrogenous groups and phenolic hydroxyl groups of PDA coordinating with UO22+ was dominant, while ion exchange between Na+/H+ and U(VI) was of secondary importance. Besides, the introduction of PDA significantly alleviated the competitive adsorption between U(VI) and coexisting metal ions, making it possible for PDA-TNTs to be an effective sorbent to remove U(VI) in radioactive wastewater.

Titanate nanotubes was rapidly synthetized by nano anatase with mild hydrothermal method, and its protonation was carried by Nitric acid to prepare TNTs and TNTs-H with different H+/Na+ for further application of uranium removal in the wastewater. It was characterized by XRD, TEM and FT-IR. The results showed that at 298 K and pH 7, the adsorption rates of TNTs and TNTs-H to 10 mg/L U(VI) were 77.90% and 97.78% respectively, and the maximum adsorption capacity of U(VI) were 41.494 mg/g and 49.505 mg/g respectively. The adsorption processes all followed a pseudo second-order kinetic model and were in accordance with isotherm adsorption models like Langmuir model.

The time-averaged serum potassium was more comprehensive to reflect the all-time changes of serum potassium levels during peritoneal dialysis (PD). However, the association of fluctuation of time-averaged serum potassium level with long-time survival of PD patients remains unknown. In this retrospective study, we included 357 incident PD patients in 2 centers from January 1, 2007 to October 31, 2012 with follow-up through October 31, 2014. Our data demonstrated that it was the lower time-averaged serum potassium level rather than baseline of serum potassium level that was associated with high risk of death. Patients with higher standard deviation (SD) had significantly poorer all-cause (p = 0.016) and cardiovascular mortality (p = 0.041). Among the patients with time-averaged serum potassium levels below 4.0 mEq/L, a lower mean value was more important than its SD to predict death risk. In contrast, the patients with time-averaged serum potassium levels above 4.0 mEq/L, those with serum potassium SD