Advances in natural and synthetic macromolecules with stem cells and extracellular vesicles for orthopedic disease treatment.

Serious orthopedic disorders resulting from myriad diseases and impairments continue to pose a considerable challenge to contemporary clinical care. Owing to its limited regenerative capacity, achieving complete bone tissue regeneration and complete functional restoration has proven challenging with existing treatments. By virtue of cellular regenerative and paracrine pathways, stem cells are extensively utilized in the restoration and regeneration of bone tissue; however, low survival and retention after transplantation severely limit their therapeutic effect. Meanwhile, biomolecule materials provide a delivery platform that improves stem cell survival, increases retention, and enhances therapeutic efficacy. In this review, we present the basic concepts of stem cells and extracellular vesicles from different sources, emphasizing the importance of using appropriate expansion methods and modification strategies. We then review different types of biomolecule materials, focusing on their design strategies. Moreover, we summarize several forms of biomaterial preparation and application strategies as well as current research on biomacromolecule materials loaded with stem cells and extracellular vesicles. Finally, we present the challenges currently impeding their clinical application for the treatment of orthopedic diseases. The article aims to provide researchers with new insights for subsequent investigations.

Potamogeton crispus restoration increased the epiphytic microbial diversity and improved water quality in a micro-polluted urban river.

Special characterization and assembly of epiphytic microbial communities remain unclear in micro-polluted water column during submersed macrophytes restoration. In this study, an in-situ enclosure area sowing with turions of Potamogeton crispus (P. crispus) was conducted in a micro-polluted urban river to investigate the characterization of P. crispus and epiphytic microbial communities and their response to water environment under different water depths. Turions completely germinated in water column with <90 cm water depth and the germination speed decreased with increasing water depth within 18 days. There were obvious differences in morphological characteristics of P. crispus between deep and shallow water layers. P. crispus restoration decreased by 12-32%, 13-36%, 9-43% and 5-36% of COD, NH4+-N, TN and TP concentration, respectively, in enclosed overlying water compared to the river (P < 0.05) during 5 months of experiment. Illumina sequencing was employed to explore the epiphytic bacterial and microeukayotic communities at water depth 25-35 cm (shallow area) and 80-90 cm (deep area). A total of 9 bacterial and 12 microeukayotic dominant phyla were obtained in eight samples. It should be noted that the algae abundances were higher in shallow area than deep area but a reverse trend was observed for methanotrophs. Null model analysis revealed that dispersal limitation and undominated process was the most important assembly process, whereas stochastic processes gained more importance in shallow area than deep one. According to cooccurrence analysis (|r| > 0.6, P < 0.05), there were more strongly correlated edges in shallow area (456 edges) than deep area (340 edges). These results highlight that submerged macrophytes restoration can increase microbial diversity and improve water quality, and provide a "summer disease cured in winter" way by using could-resistant P. crispus for water purification in micro-polluted rivers in low-temperature season.

Discovery of a potent SCAP degrader that ameliorates HFD-induced obesity, hyperlipidemia and insulin resistance via an autophagy-independent lysosomal pathway.

SCAP (SREBF chaperone) regulates SREBFs (sterol regulatory element binding transcription factors) processing and stability, and, thus, becomes an emerging drug target to treat dyslipidemia and fatty liver disease. However, the current known SCAP inhibitors, such as oxysterols, induce endoplasmic reticulum (ER) stress and NR1H3/LXRα (nuclear receptor subfamily 1 group H member 3)-SREBF1/SREBP-1 c-mediated hepatic steatosis, which severely limited the clinical application of this inhibitor. In this study, we identified a small molecule, lycorine, which binds to SCAP, which suppressed the SREBF pathway without inducing ER stress or activating NR1H3. Mechanistically, lycorine promotes SCAP lysosomal degradation in a macroautophagy/autophagy-independent pathway, a mechanism completely distinct from current SCAP inhibitors. Furthermore, we determined that SQSTM1 captured SCAP after its exit from the ER. The interaction of SCAP and SQSTM1 requires the WD40 domain of SCAP and the TB domain of SQSTM1. Interestingly, lycorine triggers the lysosome translocation of SCAP independent of autophagy. We termed this novel protein degradation pathway as the SQSTM1-mediated autophagy-independent lysosomal degradation (SMAILD) pathway. In vivo, lycorine ameliorates high-fat diet-induced hyperlipidemia, hepatic steatosis, and insulin resistance in mice. Our study demonstrated that the inhibition of SCAP through the SMAILD pathway could be employed as a useful therapeutic strategy for treating metabolic diseases.Abbreviation: 25-OHD: 25-hydroxyvitamin D; 3-MA: 3-methyladenine; ABCG5: ATP binding cassette subfamily G member 5; ABCG8: ATP binding cassette subfamily G member 8; ACACA: acetyl-CoA carboxylase alpha; AEBSF: 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride; AHI: anhydroicaritin; AKT/protein kinase B: AKT serine/threonine kinase; APOE: apolipoprotein E; ATF6: activating transcription factor 6; ATG: autophagy-related; BAT: brown adipose tissue; CD274/PD-L1: CD274 molecule; CETSA: cellular thermal shift assay; CMA: chaperone-mediated autophagy; COPII: cytoplasmic coat protein complex-II; CQ: chloroquine; DDIT3/CHOP: DNA damage inducible transcript 3; DNL: de novo lipogenesis; EE: energy expenditure; EGFR: epithelial growth factor receptor; eMI: endosomal microautophagy; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FADS2: fatty acid desaturase 2; FASN: fatty acid synthase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GPT/ALT: glutamic-pyruvate transaminase; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase; HMGCS1: 3-hydroxy-3-methylglutaryl-CoA synthase 1; HSP90B1/GRP94: heat shock protein 90 beta family member 1; HSPA5/GRP78: heat hock protein family A (Hsp70) member 5; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; INSIG1: insulin induced gene 1; LAMP2A: lysosomal associated membrane protein 2A; LDLR: low density lipoprotein receptor; LyTACs: lysosome targeting chimeras; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MBTPS1: membrane bound transcription factor peptidase, site 1; MEF: mouse embryonic fibroblast; MST: microscale thermophoresis; MTOR: mechanistic target of rapamycin kinase; MVK: mevalonate kinase; PROTAC: proteolysis targeting chimera; RQ: respiratory quotient; SCAP: SREBF chaperone; SCD1: stearoyl-coenzemy A desaturase 1; SMAILD: sequestosome 1 mediated autophagy-independent lysosomal degradation; SQSTM1: sequestosome 1; SREBF: sterol regulatory element binding transcription factor; TNFRSF10B/DR5: TNF receptor superfamily member 10b; TRAF6: TNF receptor associated factor 6; UPR: unfolded protein response; WAT: white adipose tissue; XBP1: X-box binding protein 1.

Calcium carbonate modified urea-formaldehyde resin adhesive for strength enhanced medium density fiberboard production.

This study investigated the improved properties of calcium carbonate (CaCO3) modified urea-formaldehyde (UF) resin adhesive for medium density fiberboard (MDF) production. The CaCO3 modified UF resins were prepared by adding different proportions of CaCO3 to a low molar ratio UF resin at the initial stage of a typical synthetic process of the resin. The physicochemical properties of the resins were measured. The mechanical and environmental performances of the resin-bonded MDF panels were tested. The results show that the viscosity and free formaldehyde content of UF resins with or without CaCO3 modification were not significantly different. The solid content of the CaCO3 modified UF resin was significantly lower than that of the control group. In addition, the measured gel time of the CaCO3 modified UF resin was 111-149 s, which was longer than that of the control resin (82 s). The gel time was further extended with the increase of the CaCO3 content in the UF resin. The chemical group and crystal structure of UF resins with or without the modification of CaCO3 were not significantly different. The internal bonding (IB) strength of the MDF panels significantly increased from 0.75 MPa to 0.97 MPa when the UF resin was modified with 2% of CaCO3. This study provides scientific support for the preparation of inorganic mineral modified UF resins for strength enhanced wood-based panel manufacturing.

Nitrogen loading affects microbes, nitrifiers and denitrifiers attached to submerged macrophyte in constructed wetlands.

Submerged macrophytes and biofilms are important components of wetlands. However, little is known about the changes of microbes in biofilms attached to submerged macrophytes upon nitrogen loading. This study investigated the changes of microbes, algae, nitrifiers and denitrifiers in biofilms attached to the leaves of artificial plants (AP), Potamogeton malaianus (PM), Vallisneria natans (VN) and Hydrilla verticillata (HV) under varied initial concentrations of total nitrogen (TN). Nitrogen addition increased biofilm biomass and changed dissolved oxygen concentrations and pH values in overlaying water. Epiphytic algal densities showed the same trend at the same N level:AP>PM>VN>HV. As revealed by cluster analysis at phylum level, algae compositions in biofilm from four plants showed some host-specific at 2 and 12mgL-1 TN, but was clustered in the same group at 22mgL-1 TN regardless of plant species. Submerged macrophytes had better performance in total N removal than AP. In general, N application significantly increased the abundance of amoA, nirK, nirS, napA and cnorB in biofilm. The abundance of the denitrification genes (nirK, nirS, napA, narG and cnorB) was positively correlated with nitrogen application, while amoA was correlated with concentration of dissolved oxygen. These results indicate that N loadings stimulated the growth of biofilms attached to submerged macrophyte and the removal of total N can be partially ascribed to the synergistic interactions of submerged macrophyte and biofilms in wetlands. These results highlight the ecological role of submerged macrophyte-biofilm system in nitrogen removal in wetlands.