O-alg-THAM/gel hydrogels functionalized with engineered microspheres based on mesenchymal stem cell secretion recruit endogenous stem cells for cartilage repair

Lacking self-repair abilities,injuries to articular cartilage can lead to cartilage degeneration and ultimately result in osteoarthritis.Tissue engineering based on functional bioactive scaffolds are emerging as promising approaches for articular cartilage regeneration and repair.Although the use of cell-laden scaffolds prior to implantation can regenerate and repair cartilage lesions to some extent,these approaches are still restricted by limited cell sources,excessive costs,risks of disease transmission and complex manufacturing practices.Acellular approaches through the recruitment of endogenous cells offer great promise for in situ articular cartilage regeneration.In this study,we propose an endogenous stem cell recruitment strategy for cartilage repair.Based on an injectable,adhesive and self-healable o-alg-THAM/gel hydrogel system as scaffolds and a biophysio-enhanced bioactive microspheres engineered based on hBMSCs secretion during chondrogenic differentiation as bioactive supplement,the as proposed functional material effectively and specifically recruit endogenous stem cells for cartilage repair,providing new insights into in situ articular cartilage regeneration.

Phosphorus speciation and colloidal phosphorus responses to short-term cessation of fertilization in a lime concretion black soil

Long-term excessive application of mineral fertilizer has led to soil acidification and phosphorus(P) accumulation, increasing the risk of P loss and environmental pollution, and cessation of fertilization is widely considered as a cost-effective management strategy to relieve this situation;however, how such cessation influences P speciation and concentrations in a bulk soil and colloidal fractions and whether decreasing P concentration might maintain soil fertility remain unclear. In this study, the effects of long-term fertilization(ca. 40 years) and short-term cessation of fertilization(ca. 16 months) on inorganic, organic,and colloidal P in lime concretion black soil were investigated using P sequential fractionation and31P nuclear magnetic resonance spectroscopy. After long-term fertilization, available P, dicalcium phosphate, iron-bound P, orthophosphate monoesters, and orthophosphate diesters increased significantly, but soil p H decreased by ca. 2.8 units, indicating that long-term fertilization caused soil acidification and P accumulation and changed P speciation markedly. In contrast, short-term fertilization cessation increased soil p H by ca. 0.8 units and slightly reduced available and inorganic P. Available P after fertilization cessation was 22.9–29.8 mg kg-1, which was still sufficient to satisfy crop growth requirements. Additionally, fertilization cessation increased the proportions of fine colloids(100–450 nm, including nontronite and some amorphous iron oxides) and drove a significant release of iron/aluminum oxide nanoparticles(1–100 nm) and associated P with orthophosphate and pyrophosphate species. In summary, short-term fertilization cessation effectively alleviated soil acidification and inorganic P accumulation, while concomitantly maintaining soil P fertility and improving the potential mobilization of P associated with microparticles.

Mechanistic insights to sorptive removal of four sulfonamide antibiotics from water using magnetite-functionalized biochar

Magnetite-functionalized biochar(MBC)is a promising engineered material for remediation of antibiotic-contaminated fields.However,sorption mechanisms of ionizable organic compounds such as sulfonamide antibiotics(SAs)on MBC are still unclear.This study employed four representative SAs including sulfamethazine(SMT),sulfamerazine(SMR),sulfadiazine(SDZ),and sulfamethoxazole(SMX),to compare the difference in sorption on MBC.Results showed that the sorption capacities and affinities of the four SAs varied with their substituents,hydrophobic properties,and dissociation constants(pKa).Synergistic effect during co-pyrolysis with Fe^(3+)enhanced the sorption performance of MBC towards SAs compared to original BC.Spectral methods confirmed structural changes of MBC such as the variance in oxygen-containing groups and defective/graphitized phases.Results of modeling pH-dependent sorption revealed that H-bonding orπ-bond assisted H-bonding determined the sorption affinities and capacities of SAs.In particular,the SAs with lower pKa were thermodynamically favorable to form H-bonding with MBC via proton exchange with water molecules.Quantum calculation results quantified the contributions of H-bonding strengths and found that the energies of H-bonding were correlated with affinities of SAs.Moreover,contributions of oxygencontaining groups instead of minerals dominated the H-bonding energies.Mechanistic insights from this study can be valuable in exploring engineered BC composites for practical application in field remediation.

The PI3K/AKT Pathway and Renal Cell Carcinoma

The phosphatidylinositol 3 kinase （PI3K）/AKT pathway is genetically targeted in more pathway components and in more tumor types than any other growth factor signaling pathway, and thus is frequently activated as a cancer driver. More importantly, the PI3K/AKT pathway is composed of multiple bifurcating and converging kinase cascades, providing many potential targets for cancer therapy. Renal cell carcinoma （RCC） is a high-risk and high-mortality cancer that is notoriously resistant to traditional chemotherapies or radiotherapies. The PI3K/AKT pathway is modestly mutated but highly activated in RCC, representing a promising drug target. Indeed, PI3K pathway inhibitors of the rapalog family are approved for use in RCC. Recent large-scale integrated analyses of a large number of patients have provided a molecular basis for RCC, reiterating the critical role of the PI3K/AKT pathway in this cancer. In this review, we summarize the genetic alterations of the PI3K/AKT pathway in RCC as indicated in the latest large-scale genome sequencing data, as well as treatments for RCC that target the aberrant activated PI3K/AKT pathway.

Impact of taxanes on androgen receptor signaling

The development and progression of metastatic castration-resistant prostate cancer is the major challenge in the treatment of advanced prostate cancer. The androgen receptor signaling pathway remains active in metastatic castration-resistant prostate cancer. Docetaxel and cabazitaxel are the first- and second-line chemotherapy, respectively, for patients with metastatic castration-resistant prostate cancer. These two taxanes, in general, function by (i) inhibiting mitosis and inducing apoptosis and (ii) preventing microtubule-dependent cargo trafficking. In prostate cancer, taxanes have been reported to inhibit the nuclear translocation and activity of the androgen receptor. However, whether this is attainable or not clinically remains controversial. In this review, we will provide a comprehensive view of the effects of taxanes on androgen receptor signaling in prostate cancer.