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Graphic Abstract The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide for almost 2 years. It starts from viral adherence to host cells through an interaction between spike glycoprotein 1 (S1) containing a receptor-binding domain (RBD) and human angiotensin-converting enzyme-2 (ACE2). One of the useful strategies to prevent SARS-CoV-2 infection is to inhibit the attachment of RBD to ACE2. Therefore, the current work proposed potent peptides against SARS-CoV-2 infection by carrying out MM-PBSA calculation based on the binding of 52 antiviral peptides (AVPs) to RBD. Considering the binding free energies of AVPs to RBD, cyanovirin-N (CV-N) showed the strongest RBD binding affinity among 52 AVPs. Upon structural analysis of RBD complex with CV-N, it was observed that 12 of the 13 key residues of RBD binding to ACE2 were hijacked by CV-N. CV-N bound to RBD at a smaller affinity of 14.9 nM than that of ACE2 and inhibited the recruitment of S1 to human alveolar epithelial cells. Further analysis revealed that CV-N suppressed SARS-CoV-2 S pseudovirion infection with a half-maximal inhibitory concentration (IC50) of 18.52 μg/mL. This study demonstrated a drug screening for AVPs against SARS-CoV-2 and discovered a peptide with inspiring antiviral properties, which provided a promising strategy for the COVID-19 therapeutic approach. Supplementary Information The online version contains supplementary material available at 10.1007/s12539-021-00477-w.

Hepatitis B virus (HBV) infections are associated with an increased risk of kidney diseases. However, the effects of HBV infection on the prognosis of immunoglobulin A nephropathy (IgAN) are unclear. A total of 838 patients with biopsy-confirmed IgAN were enrolled in this retrospective cohort study. The patients were categorized into either affected by IgAN and HBV infection (HBsAg-IgAN) or by primary IgAN with no sign of HBV infection (P-IgAN). A 1:1 propensity-score matching was performed between the two groups, followed by a Kaplan–Meier survival analysis, to compare the prognoses, and a Cox regression analysis, to identify factors influencing the HBsAg-IgAN outcomes. A total of 176 pairs of patients were successfully matched. A significant difference in the systolic blood pressure and urea, serum creatinine, uric acid, and 24-h urine protein levels was observed between the groups. A renal pathological analysis also revealed a significant difference in the mesangial hypercellularity between the groups. During a median follow-up period of 2.4 years, Kaplan–Meier analysis also revealed a significant difference in the renal survival between the groups. Furthermore, multivariate Cox analysis confirmed that HBV infection is an independent risk factor for IgAN progression (hazard ratio [HR] 2.096; 95% confidence interval [CI] 1.091–4.026). Finally, the HBsAg-IgAN patients who received treatment with renin–angiotensin–aldosterone system inhibitors had a better overall prognosis than those who received immunosuppressive therapy and antiviral treatment. Our results indicate that the clinicopathological features and outcomes of patients with IgAN differ significantly between those with and without HBV infection, and that HBV is an independent risk factor for IgAN progression.

Immunotherapy base on immune checkpoint inhibitor had obtained significant progress in extending the survival of clear cell renal carcinoma (ccRCC) patients. In order to further improve the efficiency of immunotherapy, novel immune checkpoint inhibitors needed to be developed. Differentially expressed genes (DEGs) between healthy kidney tissues and ccRCC tissues had been found from GSE68417 by GEO2R online analysis tool. Correlation analysis and Kaplan-Meier survival analyses were based on UALCAN database. Analyses of the outcome of anti-PD1 treatment had been found from GSE67501 dataset. At first, 9 genes with higher expression were associated with shorter overall survival time. More importantly, higher expression of LGALS1 was correlated with a profitable outcome of anti-PD1 treatment and the combined the expression level of PD-L1 and LGALS1 together could more efficiently predict the outcome of anti-PD1 treatment than using PD-L1 alone. At last, the genes which correlated with LGALS1 expression in ccRCC patients were enriched in TNF alpha Signaling Pathway which is mainly correlated with T cell apoptosis and survival. Together, these suggest LGALS1 could be a potential immune checkpoint, which could promote tumor progression through affecting T cell survival.

It is indisputable that immunosuppressive therapy and pathological diagnosis of renal biopsy have greatly improved the prognosis of childhood nephrotic syndrome. Unfortunately, there is no "one-size-fits-all" approach for precise patient stratification and treatment when facing the huge challenges posed by steroid-resistant nephrotic syndrome (SRNS). But genomic medicine has brought a glimmer of light, and the cognition of SRNS has entered a new stage. Based on this, identification of single genetic variants of SRNS has recognized the key role of podocyte injury in its pathogenesis. Targeted treatment of podocyte injury is paramount, and immunosuppressant with podocyte-targeted therapy seems to be more suitable as the first choice for SRNS, that is, we need to pay attention to their additional non-immunosuppressive effects. In the same way, other effect factors of nephrotic syndrome and the related causes of immunosuppressive therapy resistance require us to select reasonable and targeted non-immunosuppressive therapies, instead of only blindly using steroids and immunosuppressants, which may be ineffective and bring significant side effects. This article provides a summary of the clinical value of identification of genetic variants in podocytes and non-immunosuppressive therapy for nephrotic syndrome in children.

Our aim was to evaluate the pathogenic role of anti-neutrophil cytoplasmic antibodies (ANCAs) in patients with IgA nephropathy (IgAN). A total of 2390 patients with biopsy-confirmed IgAN were analyzed retrospectively. Thirty-five IgAN patients with ANCA and 40 IgAN patients without ANCA were enrolled. According to the Birmingham Vasculitis Activity Score (BVAS) items, the ANCA-positive patients were further divided into two subgroups which with or without systemic symptoms. The cumulative renal survival rate was calculated using Kaplan–Meier analysis. Comparisons between groups were made using the log rank test. Among the 35 ANCA-positive patients, 14 (40%) had systemic symptoms. Compared with ANCA-positive patients without systemic symptoms, ANCA-positive patients with systemic symptoms had a shorter duration of disease (1.0 [IQR, 0.3–6.8] vs. 6.0 [IQR, 2.0–21.0], P = 0.011); showed worse renal function with lower levels of eGFR (24.2 [IQR, 11.7–74.9] vs. 100.1 [IQR, 59.6–130.2] mL/min/1.73 m2, P = 0.002), serum albumin (30.4 [IQR, 27.4–34.8] vs. 41.5 [IQR, 35.1–44.4] g/L, P = 0.001), and hemoglobin (96.1 ± 21.5 vs. 118.2 ± 22.4 g/L, P = 0.006); and presented relatively higher incidences of rapidly deteriorating kidney function (28.6 vs. 0.0%, P = 0.039) and moderate-to-severe tubular atrophy (78.6 vs. 23.8%, P = 0.001). Kaplan–Meier analysis had shown that ANCA-positive patients with systemic symptoms had lower cumulative renal survival rate compared with both ANCA-positive patients without systemic symptoms and ANCA-negative patients (log rank = 14.40, P

Renal fibrosis is the most common outcome of chronic kidney disease (CKD), while the pathogenesis of renal fibrosis is not fully understood. In this study, we first showed that the progress of renal fibrosis was positively related to serum levels of indoxyl sulfate, a typical protein-bound toxin, and that there was a close correlation between serum indoxyl sulfate levels and β-catenin expression in the kidneys (r = 0.908, p 0.001) of CKD patients. We then demonstrated that intraperitoneal injections of indoxyl sulfate (100 mg/kg/day) for 4 weeks in uninephrectomized mice explicitly induced renal fibrosis, which was accompanied by a significant activation of Wnt/β-catenin signaling. In vitro investigations in human renal tubular HK-2 cells revealed that indoxyl sulfate exhibited a potent ability to induce Wnt/β-catenin activation through the downregulation of sFRP5, a gene that codes for an extracellular antagonist of Wnt signaling, by increasing the DNA methylation level of its promoter CpG islands. The increased expression of DNA methyltransferases following the activation of ROS/ERK1/2 signaling was responsible for the DNA hypermethylation of sFRP5 induced by indoxyl sulfate. Conversely, treatment with 5-aza-2'-deoxycytidine, an inhibitor of DNA methyltransferases, significantly reduced indoxyl sulfate-induced sFRP5 downregulation and Wnt/β-catenin activation. In vivo, intraperitoneal injections of recombinant sFRP5 protein or 5-aza-2'-deoxycytidine substantially alleviated renal fibrosis in indoxyl sulfate-treated uninephrectomized mice. Our results suggest that indoxyl sulfate promotes renal fibrosis through the induction of DNA hypermethylation of sFRP5, and thereafter the activation of Wnt/β-catenin signaling. These findings provide new insights into the pathogenesis of renal fibrosis in CKD patients.IS induces renal fibrosis by increasing ß-catenin expression in CKD mice. IS-induced Wnt signaling activation is due to sFRP5 hypermethylation in HK-2 cells. ROS/ERK1/2 signaling activation is involved in IS-induced sFRP5 hypermethylation. sFRP5 upregulation attenuates IS-induced renal fibrosis by inhibiting Wnt signaling.

A significant enhancement in the thermoelectric performance was observed for three-dimensional conducting aerogels, which were obtained from poly(3,4-ethylenedioxythiophene) : poly(4-styrenesulfonic) (PEDOT:PSS) and multiwalled carbon nanotubes (MWCNTs) suspensions by adding different concentrations of metallic silver (Ag). It was found that the electrical conductivity and Seebeck coefficient could be simultaneously increased with the unique structure. Moreover, the conducting aerogels have an ultralow thermal conductivity (0.06 W m−1 K−1) and a large Brunauer-Emmett-Teller surface area (228 m2 g−1). The highest figure of merit ( zT) value in this study was 7.56×10−3 at room temperature upon the addition of 33.32 wt.% Ag. Although the zT value was too low, our work may provide new insights into the design and development of the thermoelectric material for applications. Further investigation with PEDOT:PSS aerogels will be continued to get an economical, lightweight, and efficient polymer thermoelectric material.

Estrogen is reported to be involved in thrombopoiesis and the disruption of its signaling may cause myeloproliferative disease, yet the underlying mechanisms remain largely unknown. GATA-binding factor 1 (GATA1) is a key regulator of megakaryocyte (MK) differentiation and its deficiency will lead to megakaryoblastic leukemia. Here we show that estrogen can dose-dependently promote MK polyploidization and maturation via activation of estrogen receptor beta (ERβ), accompanied by a significant upregulation of GATA1. Chromatin immunoprecipitation and a dual luciferase assay demonstrate that ERβ can directly bind the promoter region of GATA1 and activate its transcription. Steroid receptor coactivator 3 (SRC3) is involved in ERβ-mediated GATA1 transcription. The deficiency of ERβ or SRC3, similar to the inhibition of GATA1, leads to the impediment of estrogen-induced MK polyploidization and platelet production. Further investigations reveal that signal transducer and activator of transcription 1 signaling pathway downstream of GATA1 has a crucial role in estrogen-induced MK polyploidization, and ERβ-mediated GATA1 upregulation subsequently enhances nuclear factor erythroid-derived 2 expression, thereby promoting proplatelet formation and platelet release. Our study provides a deep insight into the molecular mechanisms of estrogen signaling in regulating thrombopoiesis and the pathogenesis of ER deficiency-related leukemia.

The association between body mass index (BMI) combined with albumin: creatinine ratio (ACR) and all-cause mortality in the general population has not been established. To address this, we examined a representative sample from the general population of China. The study included 46,854 participants with a follow-up of 4.6 years. Compared to the normal weight with ACR 10 mg/g, normal weight with ACR >10 mg/g, overweight with ACR >10 mg/g, and obese with ACR >10 mg/g groups, were 2.22 (95% CI, 1.41 to 3.49), 1.70 (95% CI, 1.42 to 2.04), 1.52 (95% CI, 1.22 to 1.89), and 2.05 (95% CI, 1.45 to 2.89), respectively. After multivariable adjustments for age, race, comorbidities, and baseline eGFR, the HRs for the underweight with ACR >10 mg/g and normal weight with ACR >10 mg/g groups were 1.85 (95% CI, 1.17 to 2.91) and 1.36 (95% CI, 1.13 to 1.63), respectively. The results indicate that BMI combined with ACR can better predict all-cause mortality than BMI alone in the general Chinese population. Underweight and normal weight people with elevated ACR are at a higher risk of all-cause mortality than those in the same BMI category with ACR

Introduction Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterised by the autoinflammation and necrosis of blood vessel walls. The renal involvement is commonly characterised by a pauci-immune crescentic glomerulonephritis (PiCGN) with a very rapid decline in renal function. Cathelicidin LL37, an endogenous antimicrobial peptide, has recently been implicated in the pathogenesis of autoimmune diseases. To assess whether serum LL37 reflects renal crescentic formation, we measured the serum levels of LL37 in AAV patients with and without crescentic glomerulonephritis (crescentic GN) as compared to healthy controls (HCs). We also analysed the correlation of the serum levels of LL37 and interferon-α (IFN-α) with the clinical characteristics of the patients. Methods The study population consisted of 85 AAV patients and 51 HCs. In 40 ANCA-positive patients, a parallel analysis was performed, including the assessment of LL37 and IFN-α levels in the serum and renal biopsies. Of those studied, 15 AAV patients had biopsy-proven crescentic GN, and 25 AAV patients lacked crescent formation. The serum levels of cathelicidin LL37 and IFN-α were both measured by ELISA, and the clinical and serological parameters were assessed according to routine procedures. Immunofluorescence staining was performed on frozen sections of kidney needle biopsies from AAV patients with crescentic GN. Results The serum levels of LL37 and IFN-α were significantly increased in AAV patients with crescentic GN compared to AAV patients without crescentic formation and HCs, and patients with high LL37 and IFN-α levels were more likely to be in the crescentic GN group. The LL37 levels were positively correlated with the IFN-α levels, and both LL37 and IFN-α levels showed a positive correlation with serum creatinine and no correlation with complement C3. The renal tissue of crescentic GN patients showed expression of LL37 and IFN-α at the Bowman’s capsule and extracellular sites, suggesting the active release of LL37 and IFN-α. Conclusions Significantly higher levels of LL-37 and IFN-α were observed in AAV patients, particularly those with crescentic formation, and LL37 and IFN-α were expressed in the renal tissue of patients with crescentic GN. These data suggest that serum levels of LL37 and IFN-α may reflect both local renal inflammation and systemic inflammation.