Data_Sheet_1_Efficacy and safety of roxadustat for the treatment of anemia in non-dialysis chronic kidney disease patients: A systematic review and meta-analysis of randomized double-blind controlled clinical trials.pdf

ObjectiveTo evaluate the efficacy and safety of roxadustat in the treatment of anemia in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients.Materials and methodsFor this systematic review and meta-analysis, we searched for randomized controlled trials (RCTs) of anemia in NDD-CKD patients to assess the efficacy and safety of roxadustat. The primary efficacy endpoint was the proportion of patients who achieved a hemoglobin (Hb) response. Secondary efficacy endpoints were hepcidin, serum iron, serum ferritin (SF), total iron-binding capacity (TIBC), transferrin saturation (TAST), and low-density lipoprotein (LDL). In addition, adverse events (AEs) were compared. Meta-analyses were performed using Revman 5.4 software. The quality of the evidence was assessed using the Cochrane risk of bias tool. This study was conducted under a pre-established protocol registered with PROSPERO (registration number: CRD42021252331).ResultsSeven studies enrolled 4,764 patients, of whom 2,730 received roxadustat and 2,034 received placebo. The results of this meta-analysis showed that roxadustat increased Hb levels [weighted mean difference (WMD) = 1.43, 95% CI: 1.17 to 1.68, P 2 = 95%], and Hb response [relative ratio (RR) = 8.12, 95% CI: 5.80 to 11.37, P 2 = 61%]. In addition, roxadustat significantly increased transferrin TAST. During the treatment period in patients with anemia, the AEs of roxadustat compared with placebo was not statistically significant.ConclusionRoxadustat can improve anemia in NDD-CKD patients by increasing Hb levels and regulating iron metabolism, but does not increase the incidence of AEs.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021252331].</p

Characteristics of randomized controlled trails.

<p>Characteristics of randomized controlled trails.</p

Characteristic of cohort studies.

<p>Characteristic of cohort studies.</p

Forest plot of all cohort studies in clinical remission.

<p>Pooled estimate of 40.5% (95% CI 24.7%-60.4%).</p

Forest plot of all cohort studies in clinical response.

<p>Pooled estimate of 66.1% (95% CI 43.7%-83.0%).</p

Backcrossing of B6N (hGFAP-ECFP)GCFD mice to FVB for a single generation re-activated transgenic ECFP expression.

<p>(A and B) Cerebellar slices of 8-week-old mice were immunostained with anti-GFP and anti-S100β antibodies and analyzed. Only single ECFP expressing Bergmann glia (S100β positive cells) were detected in B6N(hGFAP-ECFP)_GCFD mice (A, upper panel), while ∼91.5% of Bergmann glia were ECFP positive in FVB(hGFAP-ECFP)_GCFD mice (A, lower panel). Backcrossing of B6N(hGFAP-ECFP)_GCFD for one generation with FVB WT mouse led to increased ECFP expression in B6NxFVB1 littermates (A, middle panel). (C) GFAP and ECFP mRNA levels in B6N, FVB and B6NxFVB1 mice (8 w). Relative expression is normalized to GFAP mRNA level in B6N mice. *: p<0.05 and ***: p<0.001. Data are obtained from three independent experiments with samples from three mice (n = 3) in every experiment. Scale bars indicate 100 µm.</p

hGFAP promoter controlled transgene expression in five different mouse lines.

<p>(A) Transgenic constructs used for oocyte injection. (B) Widespread expression of ECFP in FVB(hGFAP-ECFP)_GCFD mice with high levels in the cerebellum. Scale bar indicates 1 mm. (C) Abundant fluorescent signals from Bergmann glia of FVB(hGFAP-ECFP)_GCFD, FVB(hGFAP-EGFP)_GFEA/C, B6N(hGFAP-AmCyan)_GCYM and FVB(hGFAP-CT2_GCFT × R26tdTom). Transgene copy numbers are indicated below the respective mouse lines. Scale bars indicate 100 µm.</p

Quantitative RT-PCR analysis of transgene and endogenous GFAP mRNA levels in FVB and B6N mice.

<p>(A) Cerebellar GFAP mRNA levels in wild type B6N and FVB mice (1 w and 8 w). (B-D) Transgenic mRNA levels compared to endogenous GFAP mRNA levels in the cerebellum of B6N and FVB mice (1 w and 8 w). (B) hGFAP-ECFP_GCFD. (C) hGFAP-EGFP_GFEC. (D) hGFAP-CT2_GCTF. Relative expression is normalized to GFAP mRNA level in 1 w B6N mice. *: p<0.05, **: p<0.01, ***: p<0.001. Data are obtained from three independent experiments with samples from three mice (n = 3) in every experiment.</p

Immunohistochemical analysis of reporter protein expression in different transgenic mouse lines showed lower expression in the B6N background when compared to FVB.

<p>Cerebellar vibratome slices (cb) of 8-week-old mice were immunolabeled with anti-GFP (A and C) and anti-S100β antibodies (A, C and E), endogenous fluorescence of tdTomato in E. Upper panels depict transgene expression in B6N, lower panels in FVB. The S100β staining indicates all Bergmann glia. Results of comparative analysis in B6N and FVB mice are presented as percentage of transgene expressing Bergmann glia (S100β positive cells) (B, D and F). ***: p<0.001, **: p<0.01. Scale bars indicate 50 µm.</p

Photothermal Coupling Factor Achieving CO₂ Reduction Based on Palladium-Nanoparticle-Loaded TiO₂

Solar fuels have attracted great interest as an alternative use for solar energy. However, the challenges are high temperatures and low solar utilization for thermochemical and photochemical conversion methods, respectively. To lower the temperature in thermochemistry and increase solar energy utilization, a photothermochemical cycle (PTC) has been reported for carbon dioxide (CO₂) reduction and improved by palladium-nanoparticle-loaded TiO₂ (PNT). A maximum and stable carbon monoxide (CO) production of 11.05 μmol/(h g) is demonstrated using 1.0PNT, which is 8.27× the CO produced by P25 in the PTC. The PNT can enhance light utilization by a red-shifted photoresponse range and visible light absorbance of localized surface plasmon resonances (LSPRs). Photoinduced electron and hole pairs (EHPs) could be more readily separated. More available charge carriers would induce more photoinduced vacancies in the photoreaction, which serve a key role in the PTC. Additionally, Pd can promote CO₂ absorbance to form Pd-CO₂^– and Pd-CO₂^–-V_O on the defective surface in the thermal reaction. Finally, CO production can be enhanced by a photothermal coupling factor, and a reaction mechanism is proposed for the complete cycle on the basis of both theoretical calculations and experiments