Vascular Endothelial Growth Factor Mimetic Peptide and Parathyroid Hormone (1-34) Delivered via a Blue-Light-Curable Hydrogel Synergistically Accelerate Bone Regeneration.

Safe and effective biomaterials are in urgent clinical need for tissue regeneration and bone repair. While numerous advances have been made on hydrogels promoting osteogenesis in bone formation, co-stimulation of the angiogenic pathways in this process remains to be exploited. Here, we have developed a gelatin-based blue-light-curable hydrogel system, functionalized with an angiogenic vascular endothelial growth factor (VEGF) mimetic peptide, KLTWQELYQLKYKGI (KLT), and an osteoanabolic peptide, parathyroid hormone (PTH) 1-34. We have discovered that the covalent modification of gelatin scaffold with peptides can modulate the physical properties and biological activities of the produced hydrogels. Furthermore, we have demonstrated that those two peptides orchestrate synergistically and promote bone regeneration in a rat cranial bone defect model with remarkable efficacy. This dual-peptide-functionalized hydrogel system may serve as a promising lead to functional biomaterials in bone repair and tissue engineering.

[Arbuscular mycorrhizal fungi enhanced cadmium uptake in Photinia frase through altering root transcriptomes and root-associated microbial communities].

As a non-essential metal, cadmium (Cd) pollution poses severe threats to plant growth, environment, and human health. Phytoextraction using nursery stocks prior to their transplantation is a potential useful approach for bioremediation of Cd contaminated soil. A greenhouse pot experiment was performed to investigate the growth, Cd accumulation, profiles of transcriptome as well as root-associated microbiomes of Photinia frase in Cd-added soil, upon inoculation of two types of arbuscular mycorrhizal fungi (AMF) Sieverdingia tortuosa and Funneliformis mosseae. Compared with the control, inoculation of F. mosseae increased Cd concentrations in root, stem and leaf by 57.2%, 44.1% and 71.1%, respectively, contributing to a total Cd content of 182 µg/plant. KEGG pathway analysis revealed that hundreds of genes involved in 'Mitogen-activated protein kinase (MAPK) signaling pathway', 'plant hormone signal transduction', 'biosynthesis of secondary metabolites' and 'glycolysis/gluconeogenesis' were enriched upon inoculation of F. mosseae. The relative abundance of Acidobacteria was increased upon inoculation of S. tortuosa, while Chloroflexi and Patescibacteria were increased upon inoculation of F. mosseae, and the abundance of Glomerales increased from 23.0% to above 70%. Correlation analysis indicated that ethylene-responsive transcription factor, alpha-aminoadipic semialdehyde synthase, isoamylase and agmatine deiminase related genes were negatively associated with the relative abundance of Glomerales operational taxonomic units (OTUs) upon inoculation of F. mosseae. In addition, plant cysteine oxidase, heat shock protein, cinnamoyl-CoA reductase and abscisic acid receptor related genes were positively associated with the relative abundance of Patescibacteria OTUs upon inoculation of F. mosseae. These finding suggested that AMF can enhance P. frase Cd uptake by modulating plant gene expression and altering the structure of the soil microbial community. This study provides a theoretical basis for better understanding the relationship between root-associated microbiomes and root transcriptomes of P. frase, from which a cost-effective and environment-friendly strategy for phytoextraction of Cd in Cd-polluted soil might be developed.

Tumor-targeted biomimetic nanoplatform precisely integrates photodynamic therapy and autophagy inhibition for collaborative treatment of oral cancer.

Oral cancer is a common malignant tumor in the maxillofacial region. Surgical resection is the preferred treatment, but the severe functional impairment after surgery forces us to look for noninvasive treatments. As a promising noninvasive treatment method, photodynamic therapy (PDT) has received widespread attention in the field of cancer therapy, but the inefficient uptake capacity of tumor cells and the damage repair mechanisms limit the actual therapeutic effect. The establishment of a targeted therapy function and autophagy inhibition strategy is considered to be an important way to further enhance the effect of PDT. Based on this, we developed the biomimetic nanomaterial PCN-CQ@CCM. The metal-organic framework material PCN-224 was used as a carrier to load the autophagy inhibitor chloroquine (CQ) and it was coated onto the surface with isolated oral squamous cell carcinoma (OSCC) cell membranes. Owing to the immune evasion and homologous targeting ability of the biomimetic functionalized surface, PCN-CQ@CCM can escape macrophage phagocytosis and homologously adhere to tumor cells, enhancing the retention and uptake of nanomaterials in the tumor microenvironment. After being activated with a 660 nm laser, the generated reactive oxygen species (ROS) triggered the apoptosis pathway, as assessed by mitochondrial damage, and the released CQ further aggravated the ROS lethal pathway by effectively inhibiting the protective autophagic flux. Therefore, PCN-CQ@CCM achieves the precise synergy of PDT and autophagy inhibition through the biomimetic homologous targeting method, and the highly effective tumor suppression effect expands the field of vision for the noninvasive diagnosis and treatment of oral cancer.

Fruit extracts from Phyllanthus emblica accentuate cadmium tolerance and accumulation in Platycladus orientalis: A new natural chelate for phytoextraction.

A key challenge for phytoextraction is the identification of high efficiency, growth-supporting, and low cost chelating agents. To date, no substance has satisfied all above criteria. This study investigated nine traditional Chinese herbs and found that Phyllanthus emblica fruit (FPE) extract could be utilised as an optimal chelate for the phytoextraction of cadmium (Cd)-contaminated soils. FPE application into soil at a ratio of 0.1% (w/w) significantly increased extractable Cd (by 43%) compared to the control. The success of FPE as a chelating agent was attributed to high quantities of polyphenol compounds (0.76%) and organic acids (9.6%), in particular, gallic acid (7.6%). Furthermore, antioxidative properties (1.4%) and free amino acids in FPE alleviated Cd-induced oxidant toxicity and enhanced plant biomass. FPE promoted 78% higher phytoextraction efficiency in Platycladus orientalis compared to traditional chelating agents (EDTA). Furthermore, 76% of FPE was degraded 90 days after the initial application, and there was no difference in extractable Cd between the treatment and control. FPE has been commercially produced at a lower market price than other biodegradable chelates. As a commercially available and cost-effective chelator, FPE could be utilised to treat Cd-contaminated soils without adverse environmental impacts.

Azolla incorporation under flooding reduces grain cadmium accumulation by decreasing soil redox potential.

Cadmium (Cd) presents severe risks to human health and environments. The present study proposed a green option to reduce bioavailable Cd. Rice pot experiments were conducted under continuous flooding with three treatments (T1: intercropping azolla with rice; T2: incorporating azolla into soil before rice transplantation; CK: no azolla). The results showed that azolla incorporation reduced soluble Cd by 37% compared with the CK treatment, which may be explained by the decreased soil redox potential (Eh) (r = 0.867, P < 0.01). The higher relative abundance of Methylobacter observed in azolla incorporation treatment may account for dissolved organic carbon increase (r = 0.694; P < 0.05), and hence decreased the Cd availability for rice. Azolla incorporation increased the abundance of Nitrospira, indicating the potentially prominent role of nitrogen mineralization in increasing rice yields. Further, lower soluble Cd decreased the expression of OsNramp5, but increased OsHMA3 levels in rice roots, which decreased Cd accumulation in grains. Through these effects, azolla incorporation decreased Cd concentrations in rice grains by 80.3% and increased the production by 13.4%. The negligible amount of Cd absorbed by azolla would not increase the risk of long-term application. Thus, intercropping azolla with early rice and incorporating azolla into soil before late rice transplantation can contribute to safe production at large scales of double rice cultivation.

Senescent Mesenchymal Stem Cells in Myelodysplastic Syndrome: Functional Alterations, Molecular Mechanisms, and Therapeutic Strategies.

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic disorders related to hematopoietic stem and progenitor cell dysfunction. However, therapies that are currently used to target hematopoietic stem cells are not effective. These therapies are able to slow the evolution toward acute myeloid leukemia but cannot eradicate the disease. Mesenchymal stem cells (MSCs) have been identified as one of the main cellular components of the bone marrow microenvironment, which plays an indispensable role in normal hematopoiesis. When functional and regenerative capacities of aging MSCs are diminished, some enter replicative senescence, which promotes inflammation and disease progression. Recent studies that investigated the contribution of bone marrow microenvironment and MSCs to the initiation and progression of the disease have offered new insights into the MDS. This review presents the latest updates on the role of MSCs in the MDS and discusses potential targets for the treatment of MDS.

Salicylic Acid Signals Plant Defence against Cadmium Toxicity.

Salicylic acid (SA), as an enigmatic signalling molecule in plants, has been intensively studied to elucidate its role in defence against biotic and abiotic stresses. This review focuses on recent research on the role of the SA signalling pathway in regulating cadmium (Cd) tolerance in plants under various SA exposure methods, including pre-soaking, hydroponic exposure, and spraying. Pretreatment with appropriate levels of SA showed a mitigating effect on Cd damage, whereas an excessive dose of exogenous SA aggravated the toxic effects of Cd. SA signalling mechanisms are mainly associated with modification of reactive oxygen species (ROS) levels in plant tissues. Then, ROS, as second messengers, regulate a series of physiological and genetic adaptive responses, including remodelling cell wall construction, balancing the uptake of Cd and other ions, refining the antioxidant defence system, and regulating photosynthesis, glutathione synthesis and senescence. These findings together elucidate the expanding role of SA in phytotoxicology.

Endogenous salicylic acid is required for promoting cadmium tolerance of Arabidopsis by modulating glutathione metabolisms.

A few studies with NahG transgenic lines of Arabidopsis show that depletion of SA enhances cadmium (Cd) tolerance. However, it remains some uncertainties that the defence signaling may be a result of catechol accumulation in NahG transgenic lines but not SA deficiency. Here, we conducted a set of hydroponic assays with another SA-deficient mutant sid2 to examine the endogenous roles of SA in Cd tolerance, especially focusing on the glutathione (GSH) cycling. Our results showed that reduced SA resulted in negative effects on Cd tolerance, including decreased Fe uptake and chlorophyll concentration, aggravation of oxidative damage and growth inhibition. Cd exposure significantly increased SA concentration in wild-type leaves, but did not affect it in sid2 mutants. Depletion of SA did not disturb the Cd uptake in either roots or shoots. The reduced Cd tolerance in sid2 mutants is due to the lowered GSH status, which is associated with the decreased expression of serine acetyltransferase along with a decline in contents of non-protein thiols, phytochelatins, and the lowered transcription and activities of glutathione reductase1 (GR1) which reduced GSH regeneration. Finally, the possible mode of SA signaling through the GR/GSH pathway during Cd exposure is discussed.

Cadmium stabilization with nursery stocks through transplantation: a new approach to phytoremediation.

Disposal of heavy metal contaminated biomass after phytoremediation is still unfeasible. This paper presents a viable phyto-extraction approach in which metals in contaminated soils are stabilized by nursery stocks before transplantation for greening. In this respect, two pot-experiments are reported comparing seven nursery stocks species exposed to different Cd levels. The first experiment revealed that Cd was mainly stabilized in the roots of all species studied. Greater amounts of Cd were accumulated in the epidermis than cortex plus stele. Cupressus Blue Ice showed greatest tolerance to the 100 and 200 mg kg(-1) Cd stresses. The second experiment additionally evaluated the possible risk of Cd release after transplanting the Cd treated plants into uncontaminated soil. After 120 days of transplantation, the relatively trace amounts of Cd in the roots of Euonymus japonicus, Pittosporum tobira and C. Blue Ice had either been partially transferred into the shoots or released into the soil. The highest Cd concentration increase in bulk soil (0.428 mg kg(-1)), however, was much lower than the environmental quality standard for soils of China (1 mg kg(-1)). The potential effectiveness of this technique in the use of Cd-contaminated soil and further investigation needed in the field trials were also evaluated.