phase-separated copolymer membranes, often suffer from dramatically declined proton conductivity at low relative humidity (RH), [6-10] because the severe water loss under low RH destructs watermediated hydrogen-bonding networks. [8,11] For decades, great effort has been devoted to reduce the humidity-dependence of conductivity through preserving membrane hydration under low RH, such as incorporating hydrophilic groups [12,13] or hygroscopic porous nanofillers into membranes [7,14] to improve water retention properties, and installing nanovalves to retard water desorption of membranes. [2] However, the water retention remains a daunting challenge due to the "flexible polymer networks" nature of these PEMs. The amorphous, flexible ion nanochannels are prone to shrinking and even breaking upon dehydration, leading to poorly connected water channels and consequently exponential decline in conductivity and fuel cell performance. [6,15] Therefore, the design of electrolyte materials with weakly humidity-dependent proton-conducting feature remains a challenge. Materials with crystalline and rigid nanochannels are able to firmly retain water by capillary forces [16-20] and may promote membrane hydration, thereby facilitating proton transport efficiently over a wide range of humidity. Covalent organic frameworks (COFs), a class of crystalline porous polymers with pre-designable pore structures, hold grand promise. [21-23] Unlike amorphous, flexible crosslinked networks, the crystalline, rigid organic frameworks of COFs are expected to afford well-defined and stable proton-conducting nanochannels, [24-30] as well as good water retention capability. [18] However, leveraging COF materials in the field of COF-based PEMs for practical application remains a great challenge arising from the poor processing ability of COF materials and the poor structural integrity of COF membranes. Moreover, the proton transport mechanism in crystalline and rigid nanochannels of COF membranes remains elusive. Herein, we report a diffusion and solvent co-mediated modulation strategy for the direct synthesis of highly crystalline IPC-COF nanosheets (NUS-9) that can be readily processed into defect-free, robust IPC-COF membranes by subsequent vacuum-assisted self-assembly. These IPC-COF membranes exhibit weakly humidity-dependent conductivity and fuel cell performance over a wide range of humidity (30-98%). We further demonstrate that the crystalline and rigid ion nanochannels render the IPC-COF membranes exceptional State-of-the-art proton exchange membranes (PEMs) often suffer from significantly reduced conductivity under low relative humidity, hampering their efficient application in fuel cells. Covalent organic frameworks (COFs) with pre-designable and well-defined structures hold promise to cope with the above challenge. However, fabricating defect-free, robust COF membranes proves an extremely difficult task due to the poor processability of COF materials. Herein, a bottom-up approach is developed to synthesize intrinsic proton-conducting COF...

Covalent organic frameworks (COFs) with intrinsic, tunable, and uniform pores are potent building blocks for separation membranes, yet poor processing ability and long processing time remain grand challenges. Herein, we report an engineered solid−vapor interface to fabricate a highly crystalline two-dimensional COF membrane with a thickness of 120 nm in 9 h, which is 8 times faster than that in the reported literature. Due to the ultrathin nature and ordered pores, the membrane exhibited an ultrahigh permeance (water, ∼411 L m −2 h −1 bar −1 and acetonitrile, ∼583 L m −2 h −1 bar −1 ) and excellent rejection of dye molecules larger than 1.4 nm (>98%). The membrane exhibited long-term operation which confirmed its outstanding stability. Our solid−vapor interfacial polymerization method may evolve into a generic platform to fabricate COFs and other organic framework membranes

We investigated whether polycystin-1 is a bone mechanosensor. We conditionally deleted Pkd1 in mature osteoblasts/osteocytes by crossing Dmp1-Cre with Pkd1(flox/m1Bei) mice, in which the m1Bei allele is nonfunctional. We assessed in wild-type and Pkd1-deficient mice the response to mechanical loading in vivo by ulna loading and ex vivo by measuring the response of isolated osteoblasts to fluid shear stress. We found that conditional Pkd1 heterozygotes (Dmp1-Cre;Pkd1(flox/+)) and null mice (Pkd1(Dmp1-cKO)) exhibited a ∼ 40 and ∼ 90% decrease, respectively, in functional Pkd1 transcripts in bone. Femoral bone mineral density (12 vs. 27%), trabecular bone volume (32 vs. 48%), and cortical thickness (6 vs. 17%) were reduced proportionate to the reduction of Pkd1 gene dose, as were mineral apposition rate (MAR) and expression of Runx2-II, Osteocalcin, Dmp1, and Phex. Anabolic load-induced periosteal lamellar MAR (0.58 ± 0.14; Pkd1(Dmp1-cKO) vs. 1.68 ± 0.34 μm/d; control) and increases in Cox-2, c-Jun, Wnt10b, Axin2, and Runx2-II gene expression were significantly attenuated in Pkd1(Dmp1-cKO) mice compared with controls. Application of fluid shear stress to immortalized osteoblasts from Pkd1(null/null) and Pkd1(m1Bei/m1Bei)-derived osteoblasts failed to elicit the increments in cytosolic calcium observed in wild-type controls. These data indicate that polycystin-1 is essential for the anabolic response to skeletal loading in osteoblasts/osteocytes.

Quantum of solace: Fluorescent carbon dots (surface‐passivated carbon nanoparticles) are developed as an alternative to classical semiconductor quantum dots. Gel column chromatography afforded carbon dots with emission yields close to 60 %. Their optical properties resemble band‐gap transitions found in nanoscale semiconductors, thus suggesting that nanoscale carbon particles acquire essentially semiconductorlike characteristics.

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PC1 (polycystin-1) is a highly conserved, receptor-like multidomain membrane protein widely expressed in various cell types and tissues (1, 2). Mutations of human PKD1 (polycystic kidney disease gene 1) cause autosomal dominant polycystic kidney disease (ADPKD) 2 (3, 4). The genetics of ADPKD is complex, because it is widely held that inactivation of the normal copy of the PKD1 gene by a second somatic mutation in conjunction with the inherited mutation of the other allele is required for renal cyst formation, which occurs in only a subset of the dually affected tubules (5). Although primarily affecting the kidney, ADPKD is also a multisystem disorder (6, 7). Extrarenal manifestations include intracranial and aortic aneurysms and cystic disease of liver and pancreas (8 -11). The biological functions of PC1 are poorly defined in some tissues that express PKD1 transcripts, such as bone. Indeed, the absence of clinically demonstrable skeletal abnormalities in patients with ADPKD initially delayed the investigation of PKD1 function in bone. The apparent lack of abnormalities in other tissues expressing PC1 may arise because of differences in the frequency of a second hit somatic mutation, the presence of other modifying factors that may compensate for lack of PC1 function in other organs (12), or failure to detect more subtle phenotypes. For example, lung was not thought to be affected by PKD1 mutations until computed tomography scans of lungs of ADPKD patients showed a 3-fold increase in the prevalence of bronchiectasis compared with controls (13).Pkd1 is highly expressed in bone, and several mouse models with inactivating mutations of Pkd1 have skeletal abnormalities in the setting of polycystic kidney disease and embryonic lethality (6, 7, 14 -16). Most recently, however, the heterozygous Pkd1 m1Bei mouse, which has an inactivating mutation of Pkd1 and survives to adulthood without polycystic kidney disease, has been shown to develop osteopenia and impaired osteoblastic differentiation (17,18), suggesting that Pkd1 may function in bone. Because homozygous PKD1/Pkd1 mutations in humans and mice are lethal, and most of the existing models are globally Pkd1-deficient, the significance of inactivation of Pkd1 in osteoblasts remains uncertain, and the bone changes might reflect an indirect effect due to loss of PKD1, in the kidney or other tissues.In the current study, to determine if PKD1 in osteoblasts has a direct function in regulating postnatal skeletal functions, we used mouse genetic approaches to conditionally delete Pkd1 in osteoblasts. We demonstrate that conditional deletion of Pkd1 from osteoblasts using Oc-Cre results defective osteoblast function in vivo and in vitro, and osteopenia, indicating that PKD1 has a direct role to regulate osteoblast function and skeletal homeostasis. EXPERIMENTAL PROCEDURES

Increases in fibroblastic growth factor 23 (FGF23 or Fgf23) production by osteocytes result in hypophosphatemia and rickets in the Hyp mouse homologue of X-linked hypophosphatemia (XLH). Fibroblastic growth factor (FGF) signaling has been implicated in the pathogenesis of Hyp. Here, we conditionally deleted FGF receptor 1 (FGFR1 or Fgfr1) in osteocytes of Hyp mice to investigate the role of autocrine/paracrine FGFR signaling in regulating FGF23 production by osteocytes. Crossing dentin matrix protein 1 (Dmp1)-Cre;Fgfr1 null/+ mice with female Hyp;Fgfr1 flox/flox mice created Hyp and Fgfr1 (Fgfr1Dmp1-cKO)-null mice (Hyp;Fgfr1 Dmp1-cKO) with a 70% decrease in bone Fgfr1 transcripts. Fgfr1Dmp1-cKO-null mice exhibited a 50% reduction in FGF23 expression in bone and 3-fold reduction in serum FGF23 concentrations, as well as reductions in sclerostin (Sost), phosphate regulating endopeptidase on X chromosome (PHEX or Phex), matrix extracellular phosphoglycoprotein (Mepe), and Dmp1 transcripts, but had no demonstrable alterations in phosphate or vitamin D homeostasis or skeletal morphology. Hyp mice had hypophosphatemia, reductions in 1,25(OH)2D levels, rickets/osteomalacia and elevated FGF2 expression in bone. Compared to Hyp mice, compound Hyp;Fgfr1 Dmp1-cKO-null mice had significant improvement in rickets and osteomalacia in association with a decrease in serum FGF23 (3607 to 1099 pg/ml), an increase in serum phosphate (6.0 mg/dl to 9.3 mg/dl) and 1,25(OH)2D (121±23 to 192±34 pg/ml) levels, but only a 30% reduction in bone FGF23 mRNA expression. FGF23 promoter activity in osteoblasts was stimulated by FGFR1 activation and inhibited by overexpression of a dominant negative FGFR1(TK−), PLCγ and MAPK inhibitors. FGF2 also stimulated the translation of an FGF23 cDNA transfected into osteoblasts via a FGFR1 and PI3K/Akt-dependent mechanism. Thus, activation of autocrine/paracrine FGF pathways is involved in the pathogenesis of Hyp through FGFR1-dependent regulation of FGF23 by both transcriptional and post-transcriptional mechanisms. This may serve to link local bone metabolism with systemic phosphate and vitamin D homeostasis.

2D heterostructured materials combining ultrathin nanosheet morphology, defined pore configuration, and stable hybrid compositions, have attracted increasing attention for fast mass transport and charge transfer, which are highly desirable features for efficient energy storage. Here, the chemical space of 2D-2D heterostructures is extended by covalently assembling covalent organic frameworks (COFs) on MXene nanosheets. Unlike most COFs, which are generally produced as solid powders, ultrathin 2D COF-LZU1 grows in situ on aminated Ti 3 C 2 T x nanosheets with covalent bonding, producing a robust MXene@COF heterostructure with high crystallinity, hierarchical porosity, and conductive frameworks. When used as lithium hosts in Li metal batteries, lithium storage and charge transport are significantly improved. Both spectroelectrochemical and theoretical analyses demonstrate that lithiated COF channels are important as fast Li + transport layers, by which Li ions can be precisely nucleated. This affords dendrite-free and fast-charging anodes, which would be difficult to achieve using individual components.