Calcium carbonate: controlled synthesis, surface functionalization, and nanostructured materials.

Calcium carbonate (CaCO3) is an important inorganic mineral in biological and geological systems. Traditionally, it is widely used in plastics, papermaking, ink, building materials, textiles, cosmetics, and food. Over the last decade, there has been rapid development in the controlled synthesis and surface modification of CaCO3, the stabilization of amorphous CaCO3 (ACC), and CaCO3-based nanostructured materials. In this review, the controlled synthesis of CaCO3 is first examined, including Ca2+-CO32- systems, solid-liquid-gas carbonation, water-in-oil reverse emulsions, and biomineralization. Advancing insights into the nucleation and crystallization of CaCO3 have led to the development of efficient routes towards the controlled synthesis of CaCO3 with specific sizes, morphologies, and polymorphs. Recently-developed surface modification methods of CaCO3 include organic and inorganic modifications, as well as intensified surface reactions. The resultant CaCO3 can then be further engineered via template-induced biomineralization and layer-by-layer assembly into porous, hollow, or core-shell organic-inorganic nanocomposites. The introduction of CaCO3 into nanostructured materials has led to a significant improvement in the mechanical, optical, magnetic, and catalytic properties of such materials, with the resultant CaCO3-based nanostructured materials showing great potential for use in biomaterials and biomedicine, environmental remediation, and energy production and storage. The influences that the preparation conditions and additives have on ACC preparation and stabilization are also discussed. Studies indicate that ACC can be used to construct environmentally-friendly hybrid films, supramolecular hydrogels, and drug vehicles. Finally, the existing challenges and future directions of the controlled synthesis and functionalization of CaCO3 and its expanding applications are highlighted.

Phase I trial of human umbilical cord-derived mesenchymal stem cells for treatment of severe bronchopulmonary dysplasia.

Severe bronchopulmonary dysplasia (BPD) is a chronic lung disorder that primarily affects premature babies with extremely low birth weight and involves in multiple organ system; no effective pharmacotherapy for this disease exists, and mortality remains high. Based on the evidence from previous preclinical studies and phase I clinical trials, this study aims to test the safety of intravenous application of a single dose of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in patients with severe BPD. The Mesenchymal Stem cells for Bronchopulmonary Dysplasia Treatment (MSBDT) trial is a single center, open-label, dose-escalation phase I clinical trial. Severe BPD patients were enrolled in Children Hospital of Chongqing Medical University, Chongqing, China. The first six patients were treated with low-dose hUC-MSCs (1 × 106 cells/kg) and the next seven patients were treated with high-dose hUC-MSCs (5 × 106 cells/kg). This study is registered with ClinicalTrials.gov, number NCT03558334. No prespecified infusion-associated adverse events, immediate complication, respiratory or cardiovascular compromise were observed during infusion and 24 h after infusion. No significant changes in safety laboratory values were observed. One death event occurred in the low-dose group on study day 10, and one death event occurred in the high-dose group on study day 24, while, after review in detail, the two cases are not believed to be infusion-associated events. In conclusion, intravenous application of a single dose of hUC-MSCs was tolerated in thirteen patients with severe BPD.

Epigenetic Modifications in Tumor-Associated Macrophages: A New Perspective for an Old Foe.

Tumorigenesis is frequently accompanied by chronic inflammation, and the tumor microenvironment (TME) can be considered an ecosystem that consists of tumor cells, endotheliocytes, fibroblasts, immune cells and acellular components such as extracellular matrix. For tumor cells, their survival advantages are dependent on both genetic and epigenetic alterations, while other cells mainly present epigenetic modifications. Macrophages are the most plastic type of immune cells and undergo diverse epigenetic alterations in the TME. Some of these epigenetic modifications mitigate against cancer progression, and others accelerate this process. Due to the complex roles of macrophages in the TME, it is urgent to understand their epigenetic modifications associated with the TME. Here, we mainly summarize recent findings on TME-associated epigenetic alterations of tumor-associated macrophages (TAMs), including DNA methylation, posttranslational modifications of histone proteins, chromatin remodeling, and noncoding RNA-mediated epigenetic regulation. At the end of this review, we also discuss the translational potential of these epigenetic modifications for developing novel cancer therapies targeting TAMs.

The aberrant upregulation of exon 10-inclusive SREK1 through SRSF10 acts as an oncogenic driver in human hepatocellular carcinoma.

Deregulation of alternative splicing is implicated as a relevant source of molecular heterogeneity in cancer. However, the targets and intrinsic mechanisms of splicing in hepatocarcinogenesis are largely unknown. Here, we report a functional impact of a Splicing Regulatory Glutamine/Lysine-Rich Protein 1 (SREK1) variant and its regulator, Serine/arginine-rich splicing factor 10 (SRSF10). HCC patients with poor prognosis express higher levels of exon 10-inclusive SREK1 (SREK1L). SREK1L can sustain BLOC1S5-TXNDC5 (B-T) expression, a targeted gene of nonsense-mediated mRNA decay through inhibiting exon-exon junction complex binding with B-T to exert its oncogenic role. B-T plays its competing endogenous RNA role by inhibiting miR-30c-5p and miR-30e-5p, and further promoting the expression of downstream oncogenic targets SRSF10 and TXNDC5. Interestingly, SRSF10 can act as a splicing regulator for SREK1L to promote hepatocarcinogenesis via the formation of a SRSF10-associated complex. In summary, we demonstrate a SRSF10/SREK1L/B-T signalling loop to accelerate the hepatocarcinogenesis.

Analysis of the Effect of Nine Consecutive Years' Intensive Management and Number of Times Achieving the Target Control on Endpoint Events in T2DM Patients in Sanlitun Community Health Service Center in Beijing.

OBJECTIVE: To investigate the effect of intensive management and achieving the target control more than 3 times on endpoint events during 9 consecutive years' annual assessment in type 2 diabetes (T2DM) patients in the Sanlitun Community Health Service Center in Beijing, including blood glucose, blood pressure, lipids profiles, and the joint target control. METHODS: In Beijing Community Diabetes Study (BCDS), 224 patients with T2DM from the Sanlitun Community Health Service Center were enrolled in 2008. All patients were randomly assigned to the intensive management group (n = 113) and the standard management group (n = 113) and the standard management group (. RESULTS: During the nine-year follow-up, the abscission number was 35 (14.29%), among which 14 (12.39%) was in the intensive management group and 21 (18.92%) was in the standard management group. The incidence of diabetic retinopathy (6 cases, 5.41%) and diabetic nephropathy (13 cases, 11.71%) in the standard management group was significantly higher than that in the intensive management group (1 case, 0.88%; 5 cases, 4.42%), respectively (P < 0.05). However, there were no significant differences on the other endpoint events between the two groups (P < 0.05). However, there were no significant differences on the other endpoint events between the two groups (P < 0.05). However, there were no significant differences on the other endpoint events between the two groups (P < 0.05). However, there were no significant differences on the other endpoint events between the two groups (P < 0.05). However, there were no significant differences on the other endpoint events between the two groups (. CONCLUSIONS: The intensive management can effectively reduce the occurrence of microvascular complications. The incidence of all-cause death and the other endpoint events decreased in T2DM patients who achieved the joint target control more than 3 times during the nine-year management, which improved survival time and life quality. This trial is registered with ChiCTR-TRC-13003978 and ChiCTR-OOC-15006090.

Neuritin 1 expression in human normal tissues and its association with various human cancers.

OBJECTIVE(S): Neuritin (Nrn1) is a glycophosphatidylinositol-linked protein that can be induced by neural activity in the central nervous system. However, its expression outside the nervous system and association with human cancers is unclear. This study investigated the expression of Nrn1 in human tissues as well as its association with human cancers. MATERIALS AND METHODS: Nrn1 gene expression in human adult tissues was evaluated with the Clontech Multiple Tissue cDNA panel. Nrn1 protein in various tissues was detected by immunohistochemistry. Signal v.4.0 and TMHMM v.2.0 software were used to identify the signal peptide and transmembrane helix of Nrn1. The subcellular localization of Nrn1 in cultured SH-SY5Y cells was assessed by immunocytochemistry and western blotting. The expression of Nrn1 in human cancers were assessed using the online tools GEPIA. RESULTS: Nrn1 mRNA was expressed in various tissues, compared to mRNA levels in the brain tissues, expression was high in the placenta, lungs, skeletal muscle, thymus, pancreas, liver and the heart tissues; lower levels were detected in the small intestine, ovary, spleen, and testes, but there was no detectable expression in the kidneys, colon, prostate or leukocytes. In SY5Y cells, Nrn1 was colocalized with caveolin 1 at the plasma membrane. Nrn1 was downregulated in Bladder Urothelial Carcinoma (BLCA); Breast invasive carcinoma (BRCA); Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC); Colon adenocarcinoma (COAD); Glioblastoma multiforme (GBM); Kidney Chromophobe (KIHC); Kidney renal papillary cell carcinoma (KIRP); Lower Grade GLioma (LGG); Rectum adenocarcinoma (READ); Uterine Corpus Endometrial Carcinoma (UCEC); Lung adenocarcinoma (LUA), Ovarian serous cystadenocarcinoma (OV) and upregulated in Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC). A combination of the overall survival analysis of the 12 kinds of human tumors with Nrn1 downregulation revealed that patients with high levels of Nrn1 present a long term survival. But there is no significant effect on DLBC patients' survival. CONCLUSION: Nrn1 is expressed in various human tissues including the nervous system, specifically in the lipid rafts of cell membranes. We also provided the strong evidence that Nrn1 is associated with 13 kinds of human cancers and could function as biomarkers and therapeutic targets for these cancers.