Clinical features, epidemiology, and treatment of Shwachman-Diamond syndrome: a systematic review.

BACKGROUND: Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease which results in inherited bone marrow failure (IBMF) and is characterized by exocrine pancreatic dysfunction and diverse clinical phenotypes. In the present study, we reviewed the internationally published reports on SDS patients, in order to summarize the clinical features, epidemiology, and treatment of SDS. METHODS: We searched the WangFang and China National Knowledge Infrastructure databases with the keywords "Shwachman-Diamond syndrome," "SDS," "SBDS gene" and "inherited bone marrow failure" for relevant articles published from January 2002 to October 2022. In addition, studies published from January 2002 to October 2022 were searched from the Web of Science, PubMed, and MEDLINE databases, using "Shwachman-diamond syndrome" as the keyword. Finally, one child with SDS treated in Tongji Hospital was also included. RESULTS: The clinical features of 156 patients with SDS were summarized. The three major clinical features of SDS were found to be peripheral blood cytopenia (96.8%), exocrine pancreatic dysfunction (83.3%), and failure to thrive (83.3%). The detection rate of SDS mutations was 94.6% (125/132). Mutations in SBDS, DNAJC21, SRP54, ELF6, and ELF1 have been reported. The male-to-female ratio was approximately 1.3/1. The median age of onset was 0.16 years, but the diagnostic age lagged by a median age of 1.3 years. CONCLUSIONS: Pancreatic exocrine insufficiency and growth failure were common initial symptoms. SDS onset occurred early in childhood, and individual differences were obvious. Comprehensive collection and analysis of case-related data can help clinicians understand the clinical characteristics of SDS, which may improve early diagnosis and promote effective clinical intervention.

Single-cell profiles of human bone marrow-derived mesenchymal stromal cells after IFN-γ and TNF-α licensing.

BACKGROUND: Pre-licensing mesenchymal stromal cells (MSCs) with IFN-γ and TNF-α can empower their immune fate and induce a more effective immune regulation. However, the cellular heterogeneity of MSCs limits our understanding of this inflammatory licensing. METHODS: The publicly available Gene Expression Omnibus single-cell RNA sequencing (scRNA-seq) data of human bone marrow-derived MSCs with or without IFN-γ and TNF-α licensing were analyzed. Based on the scRNA-seq data and related marker genes, the cell-cycle, stemness, differentiative potencies, and immunomodulate capability of unlicensed and licensed MSCs were compared. RESULTS: After removing low-quality cells and regressing out the ribosomal gene effects, high-quality data reflecting IFN-γ and TNF-α effect on MSCs were chosen for further analysis. Despite the heterogeneity, pre-licensing didn't influence the cell-cycle and stemness of human bone marrow-derived MSCs. The osteogenesis potencies were decreased, the chondrogenesis potencies were increased while the adipogenesis potencies were stable in licensed MSCs. Licensed MSCs also showed more effective immunomodulate capability including expression of related chemokines, cytokines, surface molecules, and receptors. CONCLUSION: Collectively, our study showed the expression profiles of human bone marrow-derived unlicensed and licensed MSCs about the cell cycle, stemness, differentiative potencies, and immunomodulate capability at single-cell resolution, which may help the comprehensive understanding about the inflammatory licensing of human bone marrow-derived MSCs and their further clinical application.

Boosting oxygen evolution through phase and electronic modulation of highly dispersed tungsten carbide with nickel doping.

Exploring efficient, stable, and earth-abundant electrocatalysts for oxygen evolution reaction (OER) is of great significance for clean and renewable energy conversion technologies. In this work, in situ uniform Ni-doped tungsten carbide (Ni/WCX) nanoparticles (~3 nm) on carbon nanofibers (Ni/WCX-CNFs) that were to function as efficient OER catalysts were developed. Both the composition and electronic state of tungsten carbide (WCX: W-WC-W2C) could be regulated through varied Ni coupling. Owing to the synergistic effect between Ni and WCX, the reaction kinetics were facilitated, resulting in improved OER activity with low overpotentials of η10 = 350 mV (modified glassy carbon electrode) and η10 = 335 mV (self-supporting electrode). This work opens a facile territory for the development of cost-effective and highly promising OER electrocatalysts for use in real life applications.

Identification of Differentially Expressed lncRNAs and mRNAs in Children with Acquired Aplastic Anemia by RNA Sequencing.

BACKGROUND: The effects of long noncoding RNAs (lncRNAs) and their related messenger RNAs (mRNAs) remain unknown in children with acquired aplastic anemia (AA). The aim of this study is to screen key lncRNAs and mRNAs and investigate their potential roles in the pathology of acquired AA in children. METHODS: RNA sequencing was performed to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) between blood samples of acquired AA children and healthy controls. cis-regulation, trans-regulation, competing endogenous (Ce) regulation networks of DElncRNAs and DEmRNAs were constructed. A literature search was performed to identify immune- or hematopoietic-related DElncRNA-DEmRNA pairs, and qPCR was conducted to validate the expression of the immune- or hematopoietic-related DElncRNA and DEmRNA. RESULTS: 60 DElncRNAs and 364 DEmRNAs were identified. 13 DElncRNAs were predicted to have 15 cis-regulated target DEmRNAs, 16 DElncRNAs might have 28 trans-regulated DEmRNAs, and 2 DElncRNAs might have 9 Ce-regulated DEmRNAs. After literature screen and qPCR validation, 6 immune- or hematopoietic-related DElncRNA-DEmRNA pairs in the networks above were identified as key RNAs in the pathology of acquired AA. CONCLUSION: This study revealed key lncRNAs in children with acquired AA and proposed their potential functions by predicting their target mRNAs, which lay the foundation for future study of potential effects of lncRNAs in children with acquired AA.

Identification of potential miRNA-mRNA interaction network in bone marrow T cells of acquired aplastic anemia.

Background: MicroRNAs(miRNAs) can regulate T cell differentiation and plasticity by targeting their corresponding message RNAs (mRNAs), which play important roles in many autoimmune diseases. But the effect of miRNAs and their targeted mRNAs in acquired AA is not fully understood.Methods: The Gene Expression Omnibus data-sets of bone marrow T cells in acquired AA patients were performed to integrated analysis. Differently expressed miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) were identified. Target mRNAs of DE-miRNAs predicted by miRNet were compared with DE-mRNAs, the intersection mRNAs of two groups were negatively matched with the DE-miRNAs and defined as dysregulated mRNAs. GO and KEGG analyses for dysregulated mRNAs were performed. Protein-protein interaction (PPI) networks for dysregulated mRNAs were established. Modules in the PPI networks were identified, and the miRNA-mRNA networks were constructed.Results: 40 DE-miRNAs and 1511 DE-mRNAs were accessed. 303 negative correlation pairs of miRNA-mRNA were identified. Hsa-mir-34a-5p, hsa-mir-195-5p and hsa-mir-424-5p may be the central hubs. GO and KEGG analyses revealed that dysregulated mRNAs were involved in T cell differentiation and plasticity. Finally, the miRNA-mRNA networks were constructed. Has-mir-34a-5p, hsa-mir-195-5p and hsa-mir-424-5p were all involved in the central network and the target mRNA for them were histone genes and histone methylation gene KMT2D.Conclusion: The miRNA-mRNA network in our study show that hsa-mir-34a-5p, hsa-mir-195-5p, and hsa-mir-424-5p may regulate the T cell differentiation and plasticity by targeting histone gene expression and histone modification.

Interannual variation, ecological risk and human health risk of heavy metals in oyster-cultured sediments in the Maowei Estuary, China, from 2011 to 2018.

Heavy metals (HMs) in aquaculture-influenced sediments pose a threat to both aquatic ecosystems and human health via aquatic product intake. Based on a long-term (from 2011 to 2018) study, the concentrations of five HMs in oyster-cultured sediments in the Maowei Estuary, China, were ranked as follows: Pb (17.58 ± 10.82 mg/kg) > Cu (17.15 ± 8.61 mg/kg) > As (10.27 ± 5.24 mg/kg) > Cd (0.16 ± 0.14 mg/kg) > Hg (0.067 ± 0.033 mg/kg). These concentrations were all close to the guide values in China and those reported in other studies. However, through the Mann-Kendall test, Cu showed obvious increasing interannual trends, and according to ecological risk assessment, the sediments were highly contaminated with Cu and Hg. The health risks to local residents via oyster intake showed that both noncarcinogenic and carcinogenic risk did not exceed the safety criteria (THQ = 1, TCR = 10-6). The current study suggests that ecological and human health risks be integrated to control HMs in the Maowei Estuary.

In situ interfacial engineering of nickel tungsten carbide Janus structures for highly efficient overall water splitting.

Regulating chemical bonds to balance the adsorption and disassociation of water molecules on catalyst surfaces is crucial for overall water splitting in alkaline solution. Here we report a facile strategy for designing Ni2W4C-W3C Janus structures with abundant Ni-W metallic bonds on surfaces through interfacial engineering. Inserting Ni atoms into the W3C crystals in reaction progress generates a new Ni2W4C phase, making the inert W atoms in W3C be active sites in Ni2W4C for overall water splitting. The Ni2W4C-W3C/carbon nanofibers (Ni2W4C-W3C/CNFs) require overpotentials of 63 mV to reach 10 mA cm-2 for hydrogen evolution reaction (HER) and 270 mV to reach 30 mA cm-2 for oxygen evolution reaction (OER) in alkaline electrolyte, respectively. When utilized as both cathode and anode in alkaline solution for overall water splitting, cell voltages of 1.55 and 1.87 V are needed to reach 10 and 100 mA cm-2, respectively. Density functional theory (DFT) results indicate that the strong interactions between Ni and W increase the local electronic states of W atoms. The Ni2W4C provides active sites for cleaving H-OH bonds, and the W3C facilitates the combination of Hads intermediates into H2 molecules. The in situ electrochemical-Raman results demonstrate that the strong absorption ability for hydroxyl and water molecules and further demonstrate that W atoms are the real active sites.

MOF-derived cobalt-nickel phosphide nanoboxes as electrocatalysts for the hydrogen evolution reaction.

The development of high-efficiency nonprecious electrocatalysts based on inexpensive and Earth abundant elements is of great significance for renewable energy technologies. Group VIII transition metal phosphides (TMPs) gradually stand out due to their intriguing properties including low resistance and superior catalytic activity and stability. Herein, we adopt a unique MOF-derived strategy to synthesize transition metal phosphide nanoboxes which can be employed as electrocatalysts for the hydrogen evolution reaction. During this process, we converted a Co-MOF to a CoNi-MOF by ion exchange and low-temperature phosphating to achieve CoNiP nanoboxes. The CoNiP nanoboxes can reach a current density of 10 mA cm-2 at a low overpotential of 138 mV with a small Tafel slope of 65 mV dec-1.

Evaluating the Efficacy and Anti-infective Effect of High-dose Intravenous Immunoglobulin Adjuvant Therapy for Acquired Aplastic Anemia Children.

BACKGROUND: The efficacy and anti-infective effect of high-dose intravenous immunoglobulin (HDIVIG) in severe or very severe aplastic anemia children were evaluated. PATIENTS AND METHODS: In total, 61 patients who underwent immunosuppressive therapy were retrospectively reviewed. The non-IVIG group (30 cases) received rabbit-antithymocyte protein (R-ATG, 3 to 5 mg/kg/d, for 5 consecutive days)+cyclosporin A (CSA), and the HDIVIG group (31 cases) underwent R-ATG+CSA+immunoglobulin (1 g/kg/d, for 2 consecutive days, once a month, 6 times). RESULTS: The early effective rate was higher in the HDIVIG group (P=0.020). However, the long-term effective rate and the 5-year overall survival rates difference were not statistically significant (P=0.717, 0.419). The infection rate and severe infection rate in the HDIVIG group were lower (P=0.003, 0.008). The infection-related mortality differences were not statistically significant after ATG application (P>0.05). In the HDIVIG group, 9 patients were nonresponders. Among the nonresponders, 8 patients' first-dose IVIG was given within 7 days before ATG. CONCLUSIONS: HDIVIG may increase the early effective rate and reduce early infection and serious infection for aplastic anemia children, but failed to reduce the infection-related mortality.

Fabrication of Multifoliate PtRu Bimetallic Nanocomplexes for Computed Tomography Imaging and Enhanced Synergistic Thermoradiotherapy.

To improve the efficiency of cancer therapy, we developed multifoliate PEGylated PtRu bimetallic nanocomplexes (PtRu-PEG BNCs) as multifunctional theranostic nanoagents for computed tomography (CT) imaging and synergistic thermoradiotherapy. The synthesized PtRu-PEG BNCs with uniform size and morphology exhibit excellent stability, notable photothermal effect, and good biocompatibility. As compared with other platinum nanomaterials, the PtRu-PEG BNCs are able to absorb near-infrared laser energy and present excellent photothermal conversion efficiency (44.5%). Multifoliate PtRu-PEG BNCs can be applied to CT imaging and radiotherapy (RT) because of the presence of platinum. Unlike a single therapy method, the integration of photothermal therapy with RT can effectively induce cell apoptosis and generate an obvious synergistic effect. Hence, the as-prepared nanocomplexes can be used as multifunctional theranostic nanoagents.

Elevated Serum Interleukin-6 Predicts Favorable Response to Immunosuppressive Therapy in Children With Aplastic Anemia.

BACKGROUND: Immunosuppressive therapy (IST) is the standard treatment for aplastic anemia (AA) children who lack a sibling donor, but the clinical response rate to IST varies. Predictors of response to IST are valuable for stratifying AA patients and making clinical decisions. METHODS: The serum interleukin (IL)-6 levels of 41 AA patients were measured at the time of diagnosis and the response rate of the patients to IST was evaluated at 3, 6, and 12 months after IST. Receiver-operator characteristic (ROC) analysis was used to calculate the predictive value of initial IL-6 levels in determining response at 6 months after IST. RESULTS: The initial IL-6 levels were significant higher in responders than nonresponders at 6 months after IST (211.89 vs. 18.09 pg/mL; P=0.005), using 36.8 pg/mL as a threshold, there were 80% sensitivity and 81% specificity for discriminating responders and nonresponders to IST. Patients with initial high IL-6 level (>36.8 pg/mL) have favorable response rates than those with initial low IL-6 level (<36.8 pg/mL) at 3, 6, and 12 months after IST (P<0.01). CONCLUSION: High levels of IL-6 at the time of diagnosis predict a favorable response to IST in children with AA and this may be helpful for patient's stratification and clinical decisions.

Facile preparation of hybrid core-shell nanorods for photothermal and radiation combined therapy.

The hybrid platinum@iron oxide core-shell nanorods with high biocompatibility were synthesized and applied for combined therapy. These hybrid nanorods exhibit a good photothermal effect on cancer cells upon irradiation with a NIR laser. Furthermore, due to the presence of a high atomic number element (platinum core), the hybrid nanorods show a synergistic effect between photothermal and radiation therapy. Therefore, the as-prepared core-shell nanorods could play an important role in facilitating synergistic therapy between photothermal and radiation therapy to achieve better therapeutic efficacy.