Bone morphogenetic protein 1 (BMP1) is an astacin metalloprotease with important cellular functions and diverse substrates, including extracellular-matrix proteins and antagonists of some TGFβ superfamily members. Combining whole-exome sequencing and filtering for homozygous stretches of identified variants, we found a homozygous causative BMP1 mutation, c.34G>C, in a consanguineous family affected by increased bone mineral density and multiple recurrent fractures. The mutation is located within the BMP1 signal peptide and leads to impaired secretion and an alteration in posttranslational modification. We also characterize a zebrafish bone mutant harboring lesions in bmp1a, demonstrating conservation of BMP1 function in osteogenesis across species. Genetic, biochemical, and histological analyses of this mutant and a comparison to a second, similar locus reveal that Bmp1a is critically required for mature-collagen generation, downstream of osteoblast maturation, in bone. We thus define the molecular and cellular bases of BMP1-dependent osteogenesis and show the importance of this protein for bone formation and stability.

the setup as shown in Figure 6. Low frequency modulation with a sine AC voltage of 1 kHz and the DC bias voltages are added to measure the V . Light with TM polarization is coupled into the waveguide through a single mode fiber. The output light is coupled by another single mode fiber and received by a Ge detector. The detected optical response is simultaneously observed by an oscilloscope as illustrated in Figure 7. The measured V of the modulator is about 8.5 V with a 1.5-cm-long CPW electrode in a 3.5-cm-long device. The optical insert loss of for the TM mode is less than 20 dB. CONCLUSIONSIn conclusion, we have designed and successfully demonstrated a CPW MZ modulator using a strip-loaded waveguide structure based on the hybrid EO material with low cost and good poling stability. We obtain the propagating loss and insert loss of the waveguide at about 2.58 dB/cm and less than 20 dB at 1550 nm, respectively. The CPW modulator is successfully fabricated and the V 's of 8.5 V is obtained. Considering the thermal stabilities of the hybrid film are excellent and the simple processes for the device fabrication, this type of device has great potential for electro-optic devices applications. ACKNOWLEDGMENTS

Nanozymes that mimic peroxidase (POD) activity can convert H2O2 into bactericidal free radicals, which is referred to as chemodynamic therapy (CDT). High glutathione (GSH) levels in the infectious tissue severely limit the performance of CDT. Herein, we report a near-infrared-controlled antibacterial nanoplatform that is based on encapsulating tungsten sulfide quantum dots (WS2QDs) and the antibiotic vancomycin in a thermal-sensitive liposome. The system exploits the photothermal sensitivity of the WS2QDs to achieve selective liposome rupture for the targeted drug delivery. We determined that WS2QDs show a strong POD-like activity under physiological conditions and the oxidase-like activity, which can oxidate GSH to further improve the CDT efficacy. Moreover, we found that increased temperature promotes multiple enzyme-mimicking activities of WS2QDs. This platform exerts antibacterial effects against Gram-positive Mu50 (a vancomycin-intermediate Staphylococcus aureus reference strain) and Gram-negative Escherichia coli and disrupts biofilms for improved penetration of therapeutic agents inside biofilms. In vivo studies with mice bearing Mu50-caused skin abscess revealed that this platform confers potent antibacterial activity without obvious toxicity. Accordingly, our work illustrates that the photothermal and nanozyme properties of WS2QDs can be deployed alongside a conventional therapeutic to achieve synergistic chemodynamic/photothermal/pharmaco therapy for powerful antibacterial effects.

Background Cancer is one of the devastating diseases in the world. The development of nanocarrier provides a promising perspective for improving cancer therapeutic efficacy. However, the issues with potential toxicity, quantity production, and excessive costs limit their further applications in clinical practice. Results Herein, we proposed a nanocarrier obtained from aloe with stability and leak-proofness. We isolated nanovesicles from the gel and rind of aloe (gADNVs and rADNVs) with higher quality and yield by controlling the final centrifugation time within 20 min, and modulating the viscosity at 2.98 mPa S and 1.57 mPa S respectively. The gADNVs showed great structure and storage stability, antioxidant and antidetergent capacity. They could be efficiently taken up by melanoma cells, and with no toxicity in vitro or in vivo. Indocyanine green (ICG) loaded in gADNVs (ICG/gADNVs) showed great stability in both heating system and in serum, and its retention rate exceeded 90% after 30 days stored in gADNVs. ICG/gADNVs stored 30 days could still effectively damage melanoma cells and inhibit melanoma growth, outperforming free ICG and ICG liposomes. Interestingly, gADNVs showed prominent penetrability to mice skin which might be beneficial to noninvasive transdermal administration. Conclusions Our research was designed to simplify the preparation of drug carrier, and reduce production cost, which provided an alternative for the development of economic and safe drug delivery system. Graphical Abstract