Renal thrombotic microangiopathy is associated with poor renal survival in children with immunoglobulin A nephropathy.

AIM: The aim of this study was to examine the clinical and pathological characteristics as well as the prognosis of immunoglobulin A nephropathy (IgAN) accompanied by renal thrombotic microangiopathy (rTMA) in paediatric patients. METHODS: After balancing epidemiological characteristics and pathological types between groups, 427 patients (rTMA group: 23, non-rTMA group: 46) were included. The clinical and pathological features, prognosis and clinical risk factors of the two groups were analysed. RESULTS: IgAN-rTMA children showed more severe clinical and pathological manifestations. The findings from the logistic regression analysis indicated that hypercellularity 1 (E1) (HR: 0.805, 95% CI: 0.763 ~ 1.452, P = .016), endocapillary proliferation (HR: 1.214, 95% CI: 0.093 ~ 4.815, P = .025) and C3 staining (HR: 7.554, 95% CI: 2.563 ~ 15.729, P = .037) were the risk factors for rTMA in children with IgAN. The renal survival in rTMA group was lower than non-rTMA group (χ2 = 18.467, P = .000). Cox regression analysis showed that E1 (HR: 7.441, 95% CI: 1.095 ~ 10.768, P = .037), C3 disposition (HR: 3.414, 95% CI: 0.834 ~ 11.578, P = .027) and rTMA (HR: 8.918, 95% CI: 1.032 ~ 16.754, P = .041) were identified as independent risk factors for the development of end-stage renal disease (ESRD). CONCLUSION: The presence of rTMA had a significant impact on the severity and prognosis of IgAN. And rTMA has been identified as an independent risk factor for the development of renal failure in children diagnosed with IgAN.

Ultrafine Ni-MoOx Nanoparticles Anchored on Nitrogen-Doped Carbon Nanosheets: A Highly Efficient Noble-Metal-Free Catalyst for Ammonia Borane Hydrolysis.

The development of low-cost and high-efficiency catalysts for the hydrolytic dehydrogenation of ammonia borane (AB, NH3BH3) is still a challenging technology. Herein, ultrafine MoOx-doped Ni nanoparticles (~3.0 nm) were anchored on g-C3N4@glucose-derived nitrogen-doped carbon nanosheets via a phosphate-mediated method. The strong adsorption of phosphate-mediated nitrogen-doped carbon nanosheets (PNCS) for metal ions is a key factor for the preparation of ultrasmall Ni nanoparticles (NPs). Notably, the alkaline environment formed by the reduction of metal ions removes the phosphate from the PNCS surface to generate P-free (P)NCS so that the phosphate does not participate in the subsequent catalytic reaction. The synthesized Ni-MoOx/(P)NCS catalysts exhibited outstanding catalytic properties for the hydrolysis of AB, with a high turnover frequency (TOF) value of up to 85.7 min-1, comparable to the most efficient noble-metal-free catalysts and commercial Pt/C catalyst ever reported for catalytic hydrogen production from AB hydrolysis. The superior performance of Ni-MoOx/(P)NCS can be ascribed to its well-dispersed ultrafine metal NPs, abundant surface basic sites, and electron-rich nickel species induced by strong electronic interactions between Ni-MoOx and (P)NCS. The strategy of combining multiple modification measures adopted in this study provides new insights into the development of economical and high-efficiency noble-metal-free catalysts for energy catalysis applications.

Carbon bowl-confined subnanometric palladium-gold clusters for formic acid dehydrogenation and hexavalent chromium reduction.

Formic acid (FA), a high-value product of CO2 hydrogenation and biomass conversion, is considered a promising liquid organic hydrogen carrier for its high hydrogen content, easy accessibility, and relative stability. The development of an efficient heterogeneous catalyst toward FA dehydrogenation and Cr(VI) reduction by FA is needed to boost its sluggish kinetics but still remains a challenge. Herein, uniformly dispersed subnanometric PdAu alloy clusters (i.e., 0.9 nm) were successfully prepared and confined by amine-functionalized carbon bowls (ACB). By virtue of the tiny size and abundant active sites of PdAu clusters, the promotional effect of surface amine groups, and electronic interaction between subnanometric PdAu clusters and support, this as-prepared PdAu/ACB catalyst exhibits superior catalytic property for additive-free FA dehydrogenation (turnover frequency, 10597 h-1 at 323 K) and Cr(VI) reduction (rate constant, 0.47 min-1 at 298 K) under mild conditions, higher than most of the catalysts reported so far. This study offers insight into the design of efficient and durable catalysts for various catalytic applications in energy and environment.

TLR8 agonist Motolimod-induced inflammatory death for treatment of acute myeloid leukemia.

The clinical treatment of AML is dominated by "7 + 3" therapy, but it often shows great toxicity and limited therapeutic efficacy in application. Therefore, it is urgent to develop novel therapeutic strategies to achieve safe and efficient treatment of AML. Small-molecule inhibitors have the characteristics of high specificity, low off-target toxicity and remarkable therapeutic effect, and are receiving more and more attention in tumor therapy. In this study, we screened a library of 1972 FDA-approved small molecular compounds for those that induced the inflammatory death of AML cells, among which the TLR8 agonist Motolimod (MTL) showed stronger anti-AML activity in the animal model but slight affection on normal lymphocytes in control mice. In terms of mechanism, cellular experiments in AML cell lines proved that TLR8 and LKB1/AMPK are the key distinct mechanisms for MTL triggered caspase-3-dependent cell death and the expression of a large number of inflammatory factors. In conclusion, our findings identified the immunoactivator MTL as a single agent exerting significant anti-AML activity in vitro and in vivo, with strong potential for clinical translation.

Amine-Functionalized Carbon Bowl-Supported Pd-La(OH)3 for Formic Acid Dehydrogenation.

Formic acid (HCOOH, FA) is emerging as an appealing carrier for hydrogen storage owing to its renewability, a high volumetric capacity of 53 g H2/L, and convenient storage/transportation as a liquid. It is highly desired but still a challenge to search highly efficient catalysts to realize hydrogen evolution from FA. Here, monodispersed and ultrasmall Pd-La(OH)3 nanoparticles (NPs) anchored on amine-functionalized N-doped porous carbon bowl (N-PCB-NH2) substrates have been fabricated through a facile wet chemistry approach. As a result of the ultrafine size of Pd-La(OH)3 NPs (1.6 nm), the deprotonation ability of La(OH)3 and amine groups, and the strong metal-support interaction between Pd-La(OH)3 and N-PCB-NH2, the as-prepared Pd-La(OH)3/N-PCB-NH2 catalyst exhibits 100% H2 selectivity and exceptional catalytic property with a high turnover frequency value up to 9585 h-1 for FA dehydrogenation at 323 K, which is superior to most of the heterogeneous catalysts ever reported. Kinetic isotope effect measurements demonstrate that the C-H bond cleavage is a rate-determining step in the FA dehydrogenation reaction as compared to the O-H bond dissociation. This work presents a feasible approach to synthesize supported ultrafine metal NP catalysts with porous bowl structures for H2 generation from FA.

Derivation of the toxicological threshold of silicon element in the extractables and leachables from the pharmaceutical packaging and process components.

Silicon is one of the most monitored elements in extractables and leachables studies of pharmaceutical packaging systems and related components. There is a need to review and evaluate toxicological thresholds of silicon because of its direct contact with drug products (DP) especially a liquid form of DP with the widely used pharmaceutical packaging systems made of silicon materials like glass and silicone. It is required by regulatory authorities to test silicon content in DP; however, there are no official guidelines on the toxicology of silicon that are currently available, yet the knowledge of toxicological thresholds of silicon is critical to justify the analytical limit of quantification (LOQ). Therefore, we reviewed the toxicity of silicon to derive a toxicological threshold by literature review of toxicity studies of both inorganic and organic silicon compounds. Oral toxicity is low for inorganic silicon like silicon dioxide or organic silicon polymers such as silicone tube/silicone oil (polydimethylsiloxane, or namely, PDMS as the major ingredient). In comparison, inhalational toxicity of silicon dioxide leads to pulmonary silicosis or even lung cancer. When orally administered, the toxicity of silicon dioxide, glass, polymers, or PDMS oligomers varies depending on their morphology, molecular weight (MW), and degrees of polymerization. PDMS with high MW has minimal toxic symptoms with non-detectable degradation/elimination by both intraperitoneal and subcutaneous administration routes, while exposure to either PDMS or small molecule dimethyl silicone compounds by the intravenous administration route may lead to death. We here determined a general parenteral permitted daily exposure (PDE) of 93 µg/day for inorganic silicon element and 100 µg/day for organic silicon element by reviewing toxicological data of both forms of silicon. In conclusion, this work provides evidence for pharmaceutical companies and regulatory agencies on the PDEs of silicon elements in pharmaceutical packaging and process components through a variety of administration routes.

Comparison of Mitoxantrone in Combination with Intermediate-dose Cytarabine versus High-dose Cytarabine as Consolidation Therapies for Young Non-APL Acute Myeloid Leukemia Patients with Favorable and Intermediate Cytogenetics.

In this study, we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine (HAM) with that of high-dose cytarabine alone (HiDAC) as consolidation regimens in non-acute promyelocytic leukemia (APL) acute myeloid leukemia patients with favorable and intermediate cytogenetics. A total of 62 patients from Shenzhen People's Hospital were enrolled in this study. All patients enrolled received standard induction chemotherapy and achieved the first complete remission (CR1). In these patients, 24 received HiDAC and 38 received HAM as consolidation. The median relapse free survival (RFS) and overall survival (OS) were similar between these two consolidation regimens. Even in subgroup analysis according to risk stratification, the combination regimen conferred no benefit in longterm outcome in patients with favorable or intermediate cytogenetics. However, in patients receiving HAM regimen, the lowest neutrophil count was lower, neutropenic period longer, neutropenic fever rate higher, and more platelet transfusion support was required. HAM group also tended to have higher rate of sepsis than HiDAC group. According to our results, we suggest that combination treatment with mitoxantrone and intermediate-dose cytarabine has limited value as compared to HiDAC, even in young non-APL AML patients with favorable and intermediate cytogenetics.

H2 adsorption and dissociation on PdO(101) films supported on rutile TiO2 (110) facet: elucidating the support effect by DFT calculations.

To explore metal oxide-support interactions and their effect, H2 adsorption and dissociation on PdO(101)/TiO2(110) films with different film thicknesses, in comparison with that on pure PdO(101) surface without TiO2(110) support, were studied by density functional theory calculation. A monolayer PdO(101) film supported on TiO2 facet shows different properties to a pure PdO(101) surface. On the monolayer PdO(101)/TiO2(110) film, TiO2 support leads to stronger molecular adsorption of H2 on coordinatively unsaturated Pd top sites than that on a pure PdO surface. H2 dissociation with the formation of OH was preferred thermodynamically but slightly unfavorable kinetically on the monolayer PdO film due to the TiO2 support effect. Graphical abstract On the monolayer PdO(101)/TiO2(110) film, the TiO2 support effect leads to stronger H2 molecular adsorption on coordinatively unsaturated Pd top sites than on pure PdO surface. H2 dissociation with the formation of OH is preferred thermodynamically but slightly unfavorable kinetically on the film due to the TiO2 support effect.

O2 adsorption on MO2 (M=Ru, Ir, Sn) films supported on rutile TiO2(110) by DFT calculations: Probing the nature of metal oxide-support interaction.

To explore metal oxide-support interaction and its effect on O2 adsorption, periodic DFT calculations were used to explore the most preferred O2 molecular and dissociative adsorption on stoichiometric (MO2) and defective (MO2-x) (M=Ru, Ir, Sn) films supported on rutile TiO2(110), and compared with that on pure surfaces without TiO2(110) support. For defective RuO2-x films, it is revealed that the TiO2(110) support and the film thickness have an evident impact on the O2 adsorbed species. On the contrary, the two factors show little influence for defective IrO2-x and SnO2-x films. The analyses for Bader charge and density of states indicate that the reducibility change of the unsaturated surface Ru atoms, which are adjacent to the bridge oxygen vacancies, is responsible for this O2 adsorption alteration. These results provide insights into the oxide-oxide interaction, and its effect on the properties of supported oxide catalysts.

[Flow cytometric detection of minimal residual disease in pre-cursor-B-acute lymphoblastic leukemia on the basis of phenotypic aberrancies on minor leukemic cell populations].

To test the European BIOMED-1 Concerted Action proposed technique to detect minimal residual disease (MRD) in the chinese patients with precursor-B-acute lymphoblastic leukemia (precursor-B-ALL) by triple-staining flow cytometry and to define both normal and aberrant phenotypic profiles of precursor B cells, a series of bone marrow samples, 35 from precursor-B-ALL (13 in newly diagnosed cases, 15 at the end of remission induction therapy and 7 at end of the consolidations), and 19 from normal controls, were immunophenotyped with the five triple-staining antibodies (TdT/CD10/CD19, CD10/CD20/CD19, CD34/CD38/CD19, CD34/CD22/CD19 and CD19/CD34/CD45) recom-mended by the BIOMED-1 using common flow cytometric protocols. Further, with different ratios of the leukemic cells with CD34/CD38/CD19 phenotype and normal mononuclear cells, a serial dilution test was analyzed. The results showed that three major CD19(+) cell subpopulations were identified in the normal controls, representing three consecutive maturation stages. The subpopulations in the precursor-B-ALL cases disappeared and were replaced with a great number of luekemic cells which had different characteristics of phenotypes, and then they reappeared with almost same characteristics as the normal CD19(+) cells after the patients achieved complete remission. When the five triple-staining antibody combinations were used, the phenotypic aberrancies could be identified in 12/13 (92.3%) cases with newly diagnosed precursor-B-ALL, at least one triple-labeling per case at the level of 0.01% or more. The frequencies of phenotypic aberrations detected with the triple-staining were 8/13 (61.5%) for CD10/CD20/CD19, 5/13 (38.5%) for CD34/CD38/CD19, 4/13 (30.8%) for CD10/TdT/CD19, 3/13 (23.1%) for CD34/CD22/CD19, and 2/13 (15.4%) for CD34/CD45/CD19. At the end of remission induction, the phenotypic aberrancies could be detected in 5/15 (33.3%), of which, 3/8 (37.5%) cases with the leukemic phenotypes detected both at the newly diagnosis and at the end of induction. The dilution test indicated that the cells with CD34/CD38/CD19 detected by flow cytometry correlated well with the leukemic cells added (r = 0.85, P < 0.05) over 1:1 to 1:400,000. It is concluded that the flow cytometric detection of precursor-B-ALL-MRD proposed by BIOMED-1 Concerted Action were well realized in this study. The one precursor-B-ALL cell can be effectively detected out of 10(4) normal bone marrow cells.