Interferon g (IFN-g) is a cytokine produced locally in the bone microenvironment by cells of immune origin as well as mesenchymal stem cells. However, its role in normal bone remodeling is still poorly understood. In this study we first examined the consequences of IFN-g ablation in vivo in C57BL/6 mice expressing the IFN-g receptor knockout phenotype (IFNgR1 À/À ). Compared with their wild-type littermates (IFNgR1 þ/þ ), IFNgR1 À/À mice exhibit a reduction in bone volume associated with significant changes in cortical and trabecular structural parameters characteristic of an osteoporotic phenotype. Bone histomorphometry of IFNgR1 À/À mice showed a low-boneturnover pattern with a decrease in bone formation, a significant reduction in osteoblast and osteoclast numbers, and a reduction in circulating levels of bone-formation and bone-resorption markers. Furthermore, administration of IFN-g (2000 and 10,000 units) to wildtype C57BL/6 sham-operated (SHAM) and ovariectomized (OVX) female mice significantly improved bone mass and microarchitecture, mechanical properties of bone, and the ratio between bone formation and bone resorption in SHAM mice and rescued osteoporosis in OVX mice. These data therefore support an important physiologic role for IFN-g signaling as a potential new anabolic therapeutic target for osteoporosis. ß
Nanocarrier surface chemistry plays a vital role in mediating cell internalization and enhancing delivery efficiency during in vivo chemotherapy. Inspired by the ability of proteins to alter their conformation to mediate functions, a pH-/thermal-/glutathione-responsive polymer zipper consisting of cell-penetrating poly(disulfide)s and thermosensitive polymers bearing guanidinium/phosphate (Gu /pY ) motifs to spatiotemporally tune the surface composition of nanocarriers for precise tumor targeting and efficient drug delivery is developed. Surface engineering allows the nanocarriers to remain undetected during blood circulation and favors passive accumulation at tumor sites, where the acidic microenvironment and photothermal heating break the pY /Gu binding and rupture the zipper, thereby exposing the penetrating shell and causing enhanced cellular uptake via counterion-/thiol-/receptor-mediated endocytosis. The in vivo study demonstrates that by manipulating the surface states on command, the nanocarriers show longer blood circulation time, minimized uptake and drug leakage in normal organs, and enhanced accumulation and efficient drug release at tumor sites, greatly inhibiting tumor growth with only slight damage to normal tissues. If integrated with a photothermal dye approved by the U.S. Food and Drug Administration (FDA), polymer zipper would provide a versatile protocol for engineering nanomedicines with high selectivity and efficiency for clinical cancer treatment.
Lithium–sulfur
(Li–S) batteries have a high theoretical
specific energy; however, their performance is plagued by the shuttle
effect of lithium polysulfides and the instability of the lithium
anode interface. Great efforts have been made using electrolyte additives
to address the issues. Herein, we report a class of electrolyte additives,
i.e., benzenedithiols (BDTs). Among the three isomers of BDTs, 1,4-BDT
shows the best effect on the performance improvement of a Li–S
battery because it can bond more sulfur atoms than the other two.
The functionality of 1,4-BDT on the cathode and anode involves the
chemical reactions of thiol groups. The S–S bonds were generated
from 1,4-BDT and sulfur through oligomerization, which change the
original redox path of sulfur and inhibit the shuttle effect of lithium
polysulfides. In addition, 1,4-BDT can form a smooth and stable solid-electrolyte
interphase (SEI), which can enable the Li/Li symmetric cell with an
ultralow overpotential of 0.08 V at a high current density of 5 mA
cm–2 for over 300 h. The Li–S cell with 1,4-BDT
displays the highest cycling stability at a C/5 rate, with an initial
capacity of 1548.5 mAh g–1 and a reversible capacity
of 1306.9 mAh g–1 after 200 cycles. The Li–S
pouch cell with 1,4-BDT and 2.8 g of sulfur exhibits an initial capacity
of 2640 mAh and a capacity retention rate of 84.2% after 26 cycles
at a C/10 rate. This work demonstrates that organodithiol compounds
can be used as functional electrolyte additives and provides a new
direction to design materials for advanced Li–S batteries.
Understanding the responses of vegetation characteristics and soil properties to grazing disturbance is useful for grassland ecosystem restoration and management in semiarid areas. Here, we examined the effects of long-term grazing on vegetation characteristics, soil properties, and their relationships across four grassland types (meadow, Stipa steppe, scattered tree grassland, and sandy grassland) in the Horqin grassland, northern China. Our results showed that grazing greatly decreased vegetation cover, aboveground plant biomass, and root biomass in all four grassland types. Plant cover and aboveground biomass of perennials were decreased by grazing in all four grasslands, whereas grazing increased the cover and biomass of shrubs in Stipa steppe and of annuals in scattered tree grassland. Grazing decreased soil carbon and nitrogen content in Stipa steppe and scattered tree grassland, whereas soil bulk density showed the opposite trend. Long-term grazing significantly decreased soil pH and electrical conductivity (EC) in annual-dominated sandy grassland. Soil moisture in fenced and grazed grasslands decreased in the following order of meadow, Stipa steppe, scattered tree grassland, and sandy grassland. Correlation analyses showed that aboveground plant biomass was significantly positively associated with the soil carbon and nitrogen content in grazed and fenced grasslands. Species richness was significantly positively correlated with soil bulk density, moisture, EC, and pH in fenced grasslands, but no relationship was detected in grazed grasslands. These results suggest that the soil carbon and nitrogen content significantly maintains ecosystem function in both fenced and grazed grasslands. However, grazing may eliminate the association of species richness with soil properties in semiarid grasslands.
This paper describes a simple method for preparing protein microarrays that is compatible with high throughput manufacturing. The microarrays were formed by maskless photolithography and pin spotting to study protein adsorption on a fluorinated/methoxy-poly(ethylene glycol) (PEG) self-assembled monolayer (SAM). The mixed nonionic surfactants, Tween20 and PEG200, were utilized to control nonspecific protein adsorption on both of the SAMs. Measurements using double-antibody sandwich quantum dots-linked immunosorbent assay (DAS-QDLISA) showed that the fluorinated SAM could effectively minimize nonspecific adsorption in the presence of Tween 20 and PEG 200 (inhibitors of nonspecific protein adsorption (INSPAs)) while the PEGylated surface was biofouling. Additionally, pin spotting was used to fabricate high-throughput protein arrays on the fluorinated SAM. The results displayed that fluorinated SAM could not only effectively immobilize protein by hydrophobic interactions, but could also resist the other nonspecific adsorption with the INSPA. In this way, protein microarrays would be formed more conveniently and environmentally friendly. It is believed that simple, practical, and high-throughput protein immunosensing could be established with these mixed nonionic surfactants.
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