DDX5 inhibits hyaline cartilage fibrosis and degradation in osteoarthritis via alternative splicing and G-quadruplex unwinding.

Hyaline cartilage fibrosis is typically considered an end-stage pathology of osteoarthritis (OA), which results in changes to the extracellular matrix. However, the mechanism behind this is largely unclear. Here, we found that the RNA helicase DDX5 was dramatically downregulated during the progression of OA. DDX5 deficiency increased fibrosis phenotype by upregulating COL1 expression and downregulating COL2 expression. In addition, loss of DDX5 aggravated cartilage degradation by inducing the production of cartilage-degrading enzymes. Chondrocyte-specific deletion of Ddx5 led to more severe cartilage lesions in the mouse OA model. Mechanistically, weakened DDX5 resulted in abundance of the Fn1-AS-WT and Plod2-AS-WT transcripts, which promoted expression of fibrosis-related genes (Col1, Acta2) and extracellular matrix degradation genes (Mmp13, Nos2 and so on), respectively. Additionally, loss of DDX5 prevented the unfolding Col2 promoter G-quadruplex, thereby reducing COL2 production. Together, our data suggest that strategies aimed at the upregulation of DDX5 hold significant potential for the treatment of cartilage fibrosis and degradation in OA.

Diverse Structural Design Strategies of MXene-Based Macrostructure for High-Performance Electromagnetic Interference Shielding.

There is an urgent demand for flexible, lightweight, mechanically robust, excellent electromagnetic interference (EMI) shielding materials. Two-dimensional (2D) transition metal carbides/nitrides (MXenes) have been potential candidates for the construction of excellent EMI shielding materials due to their great electrical electroconductibility, favorable mechanical nature such as flexibility, large aspect ratios, and simple processability in aqueous media. The applicability of MXenes for EMI shielding has been intensively explored; thus, reviewing the relevant research is beneficial for advancing the design of high-performance MXene-based EMI shields. Herein, recent progress in MXene-based macrostructure development is reviewed, including the associated EMI shielding mechanisms. In particular, various structural design strategies for MXene-based EMI shielding materials are highlighted and explored. In the end, the difficulties and views for the future growth of MXene-based EMI shields are proposed. This review aims to drive the growth of high-performance MXene-based EMI shielding macrostructures on basis of rational structural design and the future high-efficiency utilization of MXene.

Single-cell transcriptomics reveals the natural product Shi-Bi-Man promotes hair regeneration by activating the FGF pathway in dermal papilla cells.

BACKGROUND: Finasteride and minoxidil are two commonly used drugs for the treatment of hair loss. However, these two drugs have certain side effects. Thus, the further elucidation of treatments for hair loss, including those using Chinese herbal medicine, remains important clinically. Shi-Bi-Man (SBM) is a hair health supplement that darkens hair and contains ginseng radix, tea polyphenols, polygonum multiflorum, radix angelicae sinensis, aloe, linseed, and green tea extract. PURPOSE: This study aimed to find potential effective monomer components to promote hair regeneration from SBM and to explore the mechanism of SBM to promote hair regeneration. METHODS: Supplementation with the intragastric administration or smear administration of SBM in artificially shaved C57BL/6 mice, observe its hair growth. UPLC/MS and UPLC/LTQ-Orbitrap-MS detect the main components in SBM and the main monomers contained in the skin after smearing, respectively. A network pharmacology study on the main components of SBM and single-cell RNA sequencing was performed to explore the role of SBM for hair regeneration. RESULTS: SBM significantly induced hair growth compared with a control treatment. TSG and EGCG were the main monomers in the skin after SBM smearing. The results of single-cell sequencing revealed that after SBM treatment, the number of hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs) increased significantly. Cell interactions and volcano dots show that the interaction of the FGF signaling pathway was significantly enhanced, in which Fgf7 expression was especially upregulated in DPCs. In addition, the Wnt signaling pathway also had a partially enhanced effect on the interactions between various cells in the skin. The network pharmacology study showed that the promotion of the FGF and Wnt pathways by SBM was also enriched in alopecia diseases. CONCLUSION: We report that SBM has a potential effect on the promotion of hair growth by mainly activating the FGF signaling pathway. The use of SBM may be a novel therapeutic option for hair loss.

Moderate Specific Surface Areas Help Three-Dimensional Frameworks Achieve Dendrite-Free Potassium-Metal Anodes.

The inevitable problem of dendrites growth has hampered the further development of K metal anodes. Constructing a three-dimensional anode framework and potassiophilic nanocoating is an effective way to enlarge the specific surface area, reduce the local current density, and inhibit the formation of K dendrites. However, the effects of the electrochemically active surface area (ECSA) of the framework on deposition behavior have not been clarified. Hence, SnS2 nanosheets with different sizes are loaded on the surface of carbon paper (SnS2@CP) to improve the potassiophilicity and realize dendrite-free K-metal anodes. Experiments reveal that the size of SnS2 nanosheets would determine the ECSA of the framework, while the ECSA reveals the relative sizes of specific surface areas of frameworks. Excessive or limited specific surface areas will cause morphological collapse or weak potassiophilicity during potassiation, respectively, thus leading to high nucleation overpotential. The moderate specific surface area and abundant and stable potassiophilic sites prompt the SnS2@CP framework to achieve uniform electrodeposition of K. A low nucleation overpotential of 11.2 mV and a cycle life of more than 800 h are exhibited at a current density of 0.25 mA cm-2, indicating the directional strategy for stable and safe K metal anodes.

SH2 Domain-Containing Phosphatase 2 Inhibition Attenuates Osteoarthritis by Maintaining Homeostasis of Cartilage Metabolism via the Docking Protein 1/Uridine Phosphorylase 1/Uridine Cascade.

OBJECTIVE: Protein tyrosine kinases regulate osteoarthritis (OA) progression by activating a series of signal transduction pathways. However, the roles of protein tyrosine phosphatases (PTPs) in OA remain obscure. This study was undertaken to identify specific PTPs involved in OA and investigate their underlying mechanisms. METHODS: The expression of 107 PTP genes in human OA cartilage was analyzed based on a single-cell sequencing data set. The enzyme activity of the PTP SH2 domain-containing phosphatase 2 (SHP-2) was detected in primary chondrocytes after interleukin-1ß (IL-1ß) treatment and in human OA cartilage. Mice subjected to destabilization of the medial meniscus (DMM) and IL-1ß-stimulated mouse primary chondrocytes were treated with an SHP-2 inhibitor or celecoxib (a drug used for the clinical treatment of OA). The function of SHP-2 in OA pathogenesis was further verified in Aggrecan-CreERT ;SHP2flox/flox mice. The downstream protein expression profile and dephosphorylated substrate of SHP-2 were examined by tandem mass tag labeling-based global proteomic analysis and stable isotope labeling with amino acids in cell culture-labeled tyrosine phosphoproteomic analysis, respectively. RESULTS: SHP-2 enzyme activity significantly increased in human OA samples with serious articular cartilage injury and in IL-1ß-stimulated mouse chondrocytes. Pharmacologic inhibition or genetic deletion of SHP-2 ameliorated OA progression. SHP-2 inhibitors dramatically reduced the expression of cartilage degradation-related genes and simultaneously promoted the expression of cartilage synthesis-related genes. Mechanistically, SHP-2 inhibition suppressed the dephosphorylation of docking protein 1 and subsequently reduced the expression of uridine phosphorylase 1 and increased the uridine level, thereby contributing to the homeostasis of cartilage metabolism. CONCLUSION: SHP-2 is a novel accelerator of the imbalance in cartilage homeostasis. Specific inhibition of SHP-2 may ameliorate OA by maintaining the anabolic-catabolic balance.

Realizing Spherical Lithium Deposition by In Situ Formation of a Li2S/Li-Sn Alloy Mixed Layer on Carbon Paper for Stable and Safe Li Metal Anodes.

Uncontrollable formation of Li dendrites and volume expansion have always been serious obstacles to the practical application of Li metal anodes. Three-dimensional (3D) frameworks are proven to accommodate Li to suppress volume expansion, but the lithiophobic surface tends to cause uncontrollable formation of Li dendrites. Here, uniform SnS2 nanosheets are coated on the carbon paper (SnS2@CP) skeleton and then transformed into a mixed layer of Li2S/Li-Sn after lithiation. Under the joint action of the lithiophilic Li-Sn alloy and low-diffusion energy barrier Li2S, the dual effects of strong adsorption and rapid diffusion of Li are realized. As a result, Li deposits homogeneously within the whole framework; as the plating amount increases, dendrite-free spherical Li is demonstrated, and the thickness of the electrode stays almost unchanged even at a high areal capacity of 10 mA h cm-2. The SnS2@CP electrodes present an ultralow nucleation overpotential (ca. 4 mV), high Coulombic efficiency (above 96.6% for more than 450 cycles), and stable cycle life (>1500 h), indicating that the 3D framework with the Li2S/Li-Sn alloy mixed coating has excellent lithiophilicity and fast Li transport kinetics, thus effectively inhibiting the formation of Li dendrites. All the findings give new insights into the design strategy for stable and safe Li metal anodes.

Sandwich-structured graphene hollow spheres limited Mn2SnO4/SnO2 heterostructures as anode materials for high-performance lithium-ion batteries.

Sn-based metal oxides and composites have been widely investigated as candidate anodes for lithium-ion batteries. However, continuous capacity fade caused by serious volumetric expansion and crystal pulverization is often noticed during lithiation and alloying processes. In this study, we design a novel heterogeneous structural composite by constructing sandwich-structured graphene hollow spheres limited Mn2SnO4/SnO2 heterostructures (Mn2SnO4/SnO2@SG), of which infiltration of Mn source promotes the dissolution-redeposition of SnO2 in hollow-spherical graphene (SnO2@SG) and their in-situ transformation into Mn2SnO4; and the uniform distributed Mn2SnO4 and SnO2 nanoparticles are adjacent each other to form heterostructure within the sandwiched graphene hollow spheres. By comparing with the single metal oxide SnO2@SG material, the influence of the microstructure, chemical composition, element valence state and electrochemical properties of the heterostructured Mn2SnO4/SnO2@SG is investigated. The results show that the construction of Mn2SnO4/SnO2 heterostructure dramatically improves electronic/ionic transport kinetics and increases lithium storage reversibility, therefore leading to distinctly superior rate capability (823.8 mAh g-1 at 5 C) and cycling capacity. An ultra-high discharge capacity of 1180.4 mA h g-1 is maintained up to 100 cycles at 100 mA g-1. The promising electrochemical performances can be attributed to the sandwiched-structure hollow graphene spherical skeleton and the formation of unique Mn2SnO4/SnO2 heterostructures.

Prognosis for patients with hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) after surgical treatment.

Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rarely seen in clinical practice, and its treatment strategies and prognosis are still a subject of debate. To ascertain the characteristics of and prognosis for HCC with BDTT, 49 patients with HCC with BDTT were studied out of 763 consecutive patients with HCC who underwent surgical treatment from July 2004 to May 2018. The clinical characteristics of and prognosis for those 49 patients were reviewed and analyzed retrospectively. Of the 49 patients, 25 underwent radical resection, 7 underwent thrombectomy through a choledochotomy, and 17 underwent palliative internal and external bile duct drainage. Results indicated that patients who underwent a radical resection had a better prognosis than patients in the other two groups, with a median survival of 19 months vs. 8 months and 3 months (p < 0.001). Moreover, the preoperative bilirubin level (p = 0.025), intraoperative blood loss (p = 0.006), tumor size (p = 0.005), and the presence of portal and hepatic vein tumor thrombi (p = 0.021) were significant prognostic factors associated with long-term survival for patients who underwent radical resection in this study. Radical resection should be performed with adequate preoperative preparation for patients with HCC with BDTT in whom surgery is not contraindicated.