Unveiling diabetic nephropathy: a novel diagnostic model through single-cell sequencing and co-expression analysis.

BACKGROUND: Diabetic nephropathy (DN) is a severe complication of diabetes that affects the kidneys. Disulfidptosis, a newly defined type of programmed cell death, has emerged as a potential area of interest, yet its significance in DN remains unexplored. METHODS: This study utilized single-cell sequencing data GSE131882 from GEO database combined with bulk transcriptome sequencing data GSE30122, GSE30528 and GSE30529 to investigate disulfidptosis in DN. Single-cell sequencing analysis was performed on samples from DN patients and healthy controls, focusing on cell heterogeneity and communication. Weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA) were employed to identify disulfidptosis-related gene sets and pathways. A diagnostic model was constructed using machine learning techniques based on identified genes, and immunocorrelation analysis was conducted to explore the relationship between key genes and immune cells. PCR validation was performed on blood samples from DN patients and healthy controls. RESULTS: The study revealed significant disulfidptosis heterogeneity and cell communication differences in DN. Specific targets related to disulfidptosis were identified, providing insights into the pathogenesis of DN. The diagnostic model demonstrated high accuracy in distinguishing DN from healthy samples across multiple datasets. Immunocorrelation analysis highlighted the complex interactions between immune cells and key disulfidptosis-related genes. PCR validation supported the differential expression of model genes VEGFA, MAGI2, THSD7A and ANKRD28 in DN. CONCLUSION: This research advances our understanding of DN by highlighting the role of disulfidptosis and identifying potential biomarkers for early detection and personalized treatment.

Knockdown of lncRNA MALAT1 ameliorates acute kidney injury by mediating the miR-204/APOL1 pathway.

BACKGROUND: Acute kidney injury (AKI) was characterized by loss of renal function, associated with chronic kidney disease, end-stage renal disease, and length of hospital stay. Long non-coding RNAs (lncRNAs) participated in AKI development and progression. Here, we aimed to investigate the roles and mechanisms of lncRNA MALAT1 in AKI. METHODS: AKI serum samples were obtained from 129 AKI patients. ROC analysis was conducted to confirm the diagnostic value of MALAT1 in differentiating AKI from healthy volunteers. After hypoxic treatment on HK-2 cells, the expressions of inflammatory cytokines, MALAT1, miR-204, APOL1, p65, and p-p65, were measured by RT-qPCR and Western blot assays. The targeted relationship between miR-204 and MALAT1 or miR-204 and APOL1 was determined by luciferase reporter assay and RNA pull-down analysis. After transfection, CCK-8, flow cytometry, and TUNEL staining assays were performed to evaluate the effects of MALAT1 and miR-204 on AKI progression. RESULTS: From the results, lncRNA MALAT1 was strongly elevated in serum samples from AKI patients, with the high sensitivity and specificity concerning differentiating AKI patients from healthy controls. In vitro, we established the AKI cell model after hypoxic treatment. After experiencing hypoxia, we found significantly increased MALAT1, IL-1ß, IL-6, and TNF-α expressions along with decreased miR-204 level. Moreover, the targeted relationship between MALAT1 and miR-204 was confirmed. Silencing of MALAT1 could reverse hypoxia-triggered promotion of HK-2 cell apoptosis. Meanwhile, the increase of IL-1ß, IL-6, and TNF-α after hypoxia treatment could be repressed by MALAT1 knockdown as well. After co-transfection with MALAT1 silencing and miR-204 inhibition, we found that miR-204 could counteract the effects of MALAT1 on HK-2 cell progression and inflammation after under hypoxic conditions. Finally, NF-κB signaling was inactivated while APOL1 expression was increased in HK-2 cells after hypoxia treatment, and lncRNA MALAT1 inhibition reactivated NF-κB signaling while suppressed APOL1 expression by sponging miR-204. CONCLUSIONS: Collectively, these results illustrated that knockdown of lncRNA MALAT1 could ameliorate AKI progression and inflammation by targeting miR-204 through APOL1/NF-κB signaling.

[Influence of MGRN1 on the autophagy of Sertoli cells in mice].

OBJECTIVE: To study the effect of mahogunin ring finger-1 (MGRN1) on the autophagy of Sertoli cells in mice. METHODS: Using RNA interference, we down-regulated the expression of MGRN1 in the mouse TM4 Sertoli cells cultured in vitro, determined the expressions of the autophagy-related proteins LC3-II/I, ATG-5 and ATG-7 by Western blot, and detected the autophagosomes in the TM4 cells by immunofluorescence and electron microscopy. RESULTS: Western blot showed increased expressions of LC3-II/I, ATG-5 and ATG-7 in the mouse TM4 Sertoli cells after knockdown of MGRN1. Fluorescence microscopy revealed significantly more autophagosomes in the TM4 cells than in the control group (P < 0.05). CONCLUSIONS: MGRN1 affects the autophagy of mouse Sertoli cells, and its specific molecular mechanism needs to be further studied.

Optimal water and land resource allocation in pastoral areas based on a water-land forage-livestock balance: a case study of Otog Front Banner, Inner Mongolia, China.

Natural grasslands provide important land resources in pastoral areas, and greatly contribute to ecological functioning. Overgrazing and other unreasonable exploitations have led to the degradation and desertification of natural grasslands, exacerbating the forage-livestock imbalance. In areas suffering from water shortage, this imbalance gradually evolves into a water-land forage-livestock imbalance. In this study, a water-land forage-livestock balance-based model was developed to optimise the allocation of water, land, and forage resources in pastoral areas, while addressing economic and ecological benefits in a coupled manner. The model was applied in a case study of Otog Front Banner to simulate the comprehensive economic and ecological benefits to the development of water, land, and forage resources in different coupled allocations of artificial and natural grasslands. The results showed that as the duration of supplementary and barn feeding increased, local development was first constrained by the availability of natural grasslands and then by the availability of water resources. The optimal resource allocation in Otog Front Banner predicted for 2030 included a water consumption of 266,000,000 m3, an irrigation area of 43,000 ha, a natural grassland utilisation area of 684,700 ha, and a livestock farming scale of 1,188,500 sheep units.

[Angiogenic ability of 3 different tissues-derived mesenchymal stem cells on endothelial progenitor cells].

OBJECTIVE: To compare the ability between bone marrow-derived mesenchymal stem cells (MSCs) (BM-MSCs) and adipose-derived MSCs (AD-MSCs) or umbilical cord-derived MSCs (UC-MSCs) on promotion of vessels formation and vessels stabilization relevant to the functions of EPCs.
 Methods: In vitro, co-culture blood vessel test was performed to compare the angiogenic ability between BM-MSCs, AD-MSCs or UC-MSCs. In vivo, angiogenic assay dependent on basement membrane matrix Matrigel and immunohistochemistry were performed to compare the ability of vessels formation functions between BM-MSCs and AD-MSCs or UC-MSCs.
 Results: The lengths and dots of vascular structures formed by EPCs on AD-MSCs layer are greater than those by EPCs on BM-MSCs layer and UC-MSCs layer in angiogenic assay in vitro. The stability of the capillary-like structures formed by EPCs with AD-MSCs on Matrigel was more stable than that by the BM-MSCs, UC-MSCs or EPCs. AD-MSCs and EPCs could form abundant functional vessels with blood perfusion in Matrigelin vivo; UC-MSCs and EPCs could form a few functional vessels with blood perfusion in Matrigelin vivo; BM-MSCs and EPCs could form broken vessels with hemocytes leakage in Matrigel in vivo.
 Conclusion: AD-MSCs have the stronger ability to promote the angiogenesis and stabilize the vessels compared with BM-MSCs or UC-MSCs ex vivo and in vivo.

Human Adipose Mesenchymal Stem Cells Show More Efficient Angiogenesis Promotion on Endothelial Colony-Forming Cells than Umbilical Cord and Endometrium.

Angiogenesis is a complicated process in which perivascular cells play important roles. Multipotent mesenchymal stem/stromal cells (MSCs) from distinct tissues have been proved to be proangiogenic and share functional properties and gene expression profiles with perivascular cells. However, different tissues derived MSCs may exhibit different potential for clinical applications. Accordingly, comparative studies on different MSCs are essential. Here, we characterized MSCs from adipose (ADSCs), umbilical cord (UCMSCs), and endometrium (EMSCs) in terms of the surface antigen expression, differentiation ability, and the ability of angiogenesis promotion on endothelial colony-forming cells (ECFCs) both in vitro and in vivo. No significant differences in immunophenotype and differentiation were observed. In addition, three types of MSCs all located around tubular-like structures formed by ECFCs in coculture system on matrigel. But ECFCs seeded on ADSCs monolayer formed more organized capillary-like network than that on UCMSCs or EMSCs. When suspended with ECFCs in matrigel and implanted into nude mice, ADSCs promoted more functional vessel formation after 7 days. Moreover, in murine hindlimb ischemia model, cotransplantation of ECFCs with ADSCs was significantly superior to UCMSCs and EMSCs in promoting perfusion recovery and limb salvage. Furthermore, ADSC-conditioned medium (CM) contained more proangiogenic factors (such as vascular endothelial growth factor-A, platelet-derived growth factor BB, and basic fibroblast growth factor) and less inhibitory factor (such as thrombospondin-1), when compared with UCMSC-CM and EMSC-CM. And ADSC-CM more durably stabilized the vascular-like structures formed by ECFCs on matrigel and promoted ECFCs migration more efficiently. In summary, MSCs from adipose show significantly efficient promotion on angiogenesis both in vitro and in vivo than UCMSCs and EMSCs. Hence, ADSCs may be recommended as a more suitable source for treating hindlimb ischemia.

Impact of adipose tissue or umbilical cord derived mesenchymal stem cells on the immunogenicity of human cord blood derived endothelial progenitor cells.

The application of autologous endothelial progenitor cell (EPC) transplantation is a promising approach in therapeutic cardiovascular diseases and ischemic diseases. In this study, we compared the immunogenicity of EPCs, adipose tissue (AD)-derived mesenchymal stem cells (MSCs) and umbilical cord (UC)-derived MSCs by flow cytometry and the mixed lymphocyte reaction. The impact of AD-MSCs and UC-MSCs on the immunogenicity of EPCs was analyzed by the mixed lymphocyte reaction and cytokine secretion in vitro and was further tested by allogenic peripheral blood mononuclear cell (PBMC) induced immuno-rejection on a cell/matrigel graft in an SCID mouse model. EPCs and AD-MSCs express higher levels of MHC class I than UC-MSCs. All three kinds of cells are negative for MHC class II. UC-MSCs also express lower levels of IFN-γ receptor mRNA when compared with EPCs and AD-MSCs. EPCs can stimulate higher rates of proliferation of lymphocytes than AD-MSCs and UC-MSCs. Furthermore, AD-MSCs and UC-MSCs can modulate immune response and inhibit lymphocyte proliferation induced by EPCs, mainly through inhibition of the proliferation of CD8+ T cells. Compared with UC-MSCs, AD-MSCs can significantly improve vessel formation and maintain the integrity of neovascular structure in an EPC+MSC/matrigel graft in SCID mice, especially under allo-PBMC induced immuno-rejection. In conclusion, our study shows that AD-MSC is a powerful candidate to minimize immunological rejection and improve vessel formation in EPC transplantation treatment.

Decreased phosphorylation of PDGFR-ß impairs the angiogenic potential of expanded endothelial progenitor cells via the inhibition of PI3K/Akt signaling.

Human umbilical cord blood-derived endothelial progenitor cells (EPCs) have been proven to contribute to post-natal angiogenesis, and have been applied in various models of ischemia. However, to date, to the best of our knowledge, there is no available data on the angiogenic properties of EPCs during the process of in vitro expansion. In this study, we expanded EPCs to obtain cells at different passages, and analyzed their cellular properties and angiogenic ability. In the process of expansion, no changes were observed in cell cobblestone-like morphology, apoptotic rate and telomere length. However, the cell proliferative ability was significantly decreased. Additionally, the expression of CD144, CD90 and KDR was significantly downregulated in the later-passage cells. Vascular formation assay in vitro revealed that EPCs at passage 4 and 6 formed more integrated and organized capillary-like networks. In a murine model of hind limb ischemia, the transplantation of EPCs at passage 4 and 6 more effectively promoted perfusion recovery in the limbs on days 7 and 14, and promoted limb salvage and histological recovery. Furthermore, the phosphorylation levels of platelet­derived growth factor receptor-ß (PDGFR-ß) were found to be significantly decreased with the in vitro expansion process, accompanied by the decreased activation of the PI3K/Akt signaling pathway. When PDGFR inhibitor was used to treat the EPCs, the differences in the angiogenic potential and migratory ability among the EPCs at different passages were no longer observed; no significant differences were also observed in the levels of phosphorylated PI3K/Akt between the EPCs at different passages following treatment with the inhibitor. On the whole, our findings indicate that the levels of phosphorylated PDGFR-ß are decreased in EPCs with the in vitro expansion process, which impairs their angiogenic potential by inhibiting PI3K/Akt signaling. Our findings may aid in the more effective selection of EPCs of different passages for the clinical therapy of ischemic disease.

Ordered Porous Pd Octahedra Covered with Monolayer Ru Atoms.

Monolayer Ru atoms covered highly ordered porous Pd octahedra have been synthesized via the underpotential deposition and thermodynamic control. Shape evolution from concave nanocube to octahedron with six hollow cavities was observed. Using aberration-corrected high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy, we provide quantitative evidence to prove that only a monolayer of Ru atoms was deposited on the surface of porous Pd octahedra. The as-prepared monolayer Ru atoms covered Pd nanostructures exhibited excellent catalytic property in terms of semihydrogenation of alkynes.

Hollow Zn/Co ZIF Particles Derived from Core-Shell ZIF-67@ZIF-8 as Selective Catalyst for the Semi-Hydrogenation of Acetylene.

The rational design of metal-organic frameworks (MOFs) with hollow features and tunable porosity at the nanoscale can enhance their intrinsic properties and stimulates increasing attentions. In this Communication, we demonstrate that methanol can affect the coordination mode of ZIF-67 in the presence of Co(2+) and induces a mild phase transformation under solvothermal conditions. By applying this transformation process to the ZIF-67@ZIF-8 core-shell structures, a well-defined hollow Zn/Co ZIF rhombic dodecahedron can be obtained. The manufacturing of hollow MOFs enables us to prepare a noble metal@MOF yolk-shell composite with controlled spatial distribution and morphology. The enhanced gas storage and porous confinement that originate from the hollow interior and coating of ZIF-8 confers this unique catalyst with superior activity and selectivity toward the semi-hydrogenation of acetylene.

Utilization of Active Ni to Fabricate Pt-Ni Nanoframe/NiAl Layered Double Hydroxide Multifunctional Catalyst through In Situ Precipitation.

Integration of different active sites into metallic catalysts, which may impart new properties and functionalities, is desirable yet challenging. Herein, a novel dealloying strategy is demonstrated to decorate nickel-aluminum layered double hydroxide (NiAl-LDH) onto a Pt-Ni alloy surface. The incorporation of chemical etching of Pt-Ni alloy and in situ precipitation of LDH are studied by joint experimental and theoretical efforts. The initial Ni-rich Pt-Ni octahedra transform by interior erosion into Pt3 Ni nanoframes with enlarged surface areas. Furthermore, owing to the basic active sites of the decorated LDH together with the metallic sites of Pt3 Ni, the resulting Pt-Ni nanoframe/NiAl-LDH composites exhibit excellent catalytic activity and selectivity in the dehydrogenation of benzylamine and hydrogenation of furfural.

Heterogeneous selective hydrogenation of ethylene carbonate to methanol and ethylene glycol over a copper chromite nanocatalyst.

Heterogeneous selective hydrogenation of ethylene carbonate (EC), a key step in indirect conversion of CO2, was realized over a copper chromite nanocatalyst prepared via a hydrothermal method followed by calcination. The selectivities towards methanol (60%) and ethylene glycol (93%) were higher than those achieved over other usual hydrogenation catalysts.