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Black phosphorus (BP) is attracting more and more interest for the biomedical application. The absorption in a wide spectral range and high photothermal conversion efficiency make BP suitable for photothermal therapy. However, BP alone is hard to realize the targeted therapy, which limits the precision and efficiency of the therapy. Magnetic microbubbles (MBs) are favored drug carriers because they can resist the sheer force of blood flow in a magnetic field, which improves the efficiency of MBs adhesion to the vascular wall for targeted ultrasound diagnosis and therapy. This study first optimized the magnetic MBs configurations through controlling the connecting polyethylene glycol (PEG) chain length. The magnetic MBs with PEG2000 have been chosen for targeted BP nanosheets delivery due to the better stability and magnetic responsiveness. The magnetic black phosphorus microbubbles (MBBPM) can realize the targeted tumor theranostics in vitro and in vivo. They could be applied for the targeted ultrasound imaging with an enhanced echogenicity by three times when accumulated at the target site where the magnetic field is applied. As the NIR laser irradiation was applied on the accumulated MBBPM, they dynamited and the temperature increased rapidly. It improved the cell membrane permeability, thus accelerating and enhancing a precision photothermal killing effect to the breast cancer cells, compared to BP alone.

Objective: We sought to determine the long-term bioavailability of single doses of intramuscular (IM) vita-min D2 (D2) in healthy adults. Methods: Forty healthy volunteers with hypovitaminosis D received a single dose of 200,000, 400,000, or 600,000 IU intramuscular D2 or no treatment. Levels of 25-hydroxyvitamin D2 (25lOH]D2) and 25-hydroxyvitamin D3 (25lOH]D3) in serum were measured by liquid chromatography-tandem mass spectrometry. Vitamin D binding protein (DBP) and intact parathyroid hormone (iPTH), bone turnover markers (BTMs), and serum and urinary calcium were also measured. Results: After a single dose of D2 injection, the level of 25(OH)D2 increased slowly and reached a plateau at 8 weeks. The plateau remained stable for 12 weeks. The mean increase in 25(OH)D2 was 6.8, 9.6, or 15.6 ng/mL after injection of 200,000 IU, 400,000 IU, or 600,000 IU D2. Although endogenous 25(OH)D3 levels were reduced by IM D2, the total 25(OH)D levels increased by 5.0, 7.0, or 10.3 ng/mL in average after injection of 200,000 IU, 400,000 IU, or 600,000 IU D2. The iPTH levels were also decreased by IM D2. However, levels of serum calcium, BTMs, and DBP and urinary calcium were not altered by IM D2. Conclusion: A single dose of 200,000 IU, 400,000 IU, or 600,000 IU IM D2 raises total 25-hydroxyvitamin D levels by 5.0, 7.0, or 10.3 ng/mL on average for at least 12 weeks and reduces iPTH and endogenous 25(OH)D3 levels without affecting levels of serum calcium, BTMs, DBP, and urinary calcium.

Tellurium(Te) nanomaterials have aroused a wide interest in semiconductor, thermoelectric, piezoelectric, as well as biomedical applications. The last decades of reports indicated a major nanostructure of one-dimensional (1D) Te on account of its inherent structural anisotropy. Two-dimenional(2D) Te has been newly developed and drawn a lot of interests recently. This review presents the intrinsic biological potential of Te-based nanomaterials and summarizes their up-to-date advance in phototherapy and reactive oxygen species(ROS)-related applications in the biomedical field.

Wonderful black phosphorus (BP) and some BP analogs (BPAs) have been increasingly studied for their biomedical applications owing to their fascinating properties and biodegradability, but opportunities and challenges have always coexisted in their study. Poor stability upon exposure to the natural environment is the major obstacle hampering their in vivo applications. BP/polymer and BPAs/polymer nanocomposites can not only efficiently prevent their oxidation and aggregation but also exhibit "biological activity" due to synergistic effects. In this review, we briefly describe the synthesis methods and stability strategies of BP/polymer and BPAs/polymer. Then, advances pertaining to their exciting therapeutic applications in various fields are systematically introduced, such as cancer therapy (phototherapy, drug delivery, and synergistic immunotherapy), bone regeneration, and neurogenesis. Some challenges for future clinical trials and possible directions for further study are finally discussed.

The exfoliation of phosphorene from black phosphorus to afford mono-elemental two-dimensional (2D) materials (Xenes) has caused a boom in various fields since 2014. Among the Xenes, an emerging class of material, 2D pnictogens, which includes phosphorene, arsenene, antimonene, and bismuthene, has drawn a great deal of attention in the field of catalysis owing to their high specific surface area, mechanical properties, biocompatibility, and optical and electrical performance. With the development of interdisciplinary research, it has become a new trend of scientific research, especially the application of catalysis in medicine, to break the barriers between disciplines and achieve multidisciplinary joint investigation. Herein, firstly, the structures, general properties, and synthetic methods of 2D pnictogen (group VA) materials are reviewed. Then, we summarize the various state-of-the-art catalytic applications of the 2D pnictogen family, such as photocatalysis, electrocatalysis, and medical catalysis, especially in terms of strategies to improve their catalytic performance, such as doping, functionalization, and heterostructures. We also shed some light on the cross-subject of photocatalytic and electrocatalytic processes for biomedical applications. Finally, we summarize the research progress, outlooks, and challenges for these 2D catalysts in terms of their catalytic performance, characterization, reaction mechanisms, exploration of new systems, and commercial applications. This review aims to highlight the catalytic effects of 2D pnictogen materials in enhancing the performance of reactions.

The past decades have witnessed a rapid expansion in investigations of two-dimensional (2D) monoelemental materials (Xenes), which are promising materials in various fields, including applications in optoelectronic devices, biomedicine, catalysis, and energy storage. Apart from graphene and phosphorene, recently emerging 2D Xenes, specifically graphdiyne, borophene, arsenene, antimonene, bismuthene, and tellurene, have attracted considerable interest due to their unique optical, electrical, and catalytic properties, endowing them a broader range of intriguing applications. In this review, the structures and properties of these emerging Xenes are summarized based on theoretical and experimental results. The synthetic approaches for their fabrication, mainly bottom-up and top-down, are presented. Surface modification strategies are also shown. The wide applications of these emerging Xenes in nonlinear optical devices, optoelectronics, catalysis, biomedicine, and energy application are further discussed. Finally, this review concludes with an assessment of the current status, a description of existing scientific and application challenges, and a discussion of possible directions to advance this fertile field.

Optoelectronic science and 2D nanomaterial technologies are currently at the forefront of multidisciplinary research and have numerous applications in electronics and photonics. The unique energy and optically induced interfacial electron transfer in these nanomaterials, enabled by their relative band alignment characteristics, can provide important therapeutic modalities for healthcare. Given that nano-heterostructures can facilitate photoinduced electron-hole separation and enhance generation of reactive oxygen species (ROS), 2D nano-heterostructure-based photosensitizers can provide a major advancement in photodynamic therapy (PDT), to overcome the current limitations in hypoxic tumor microenvironments. Herein, a bismuthene/bismuth oxide (Bi/BiOx)-based lateral nano-heterostructure synthesized using a regioselective oxidation process is introduced, which, upon irradiation at 660 nm, effectively generates 1 O2 under normoxia but produces cytotoxic •OH and H2 under hypoxia, which synergistically enhances PDT. Furthermore, this Bi/BiOx nano-heterostructure is biocompatible and biodegradable, and, with the surface molecular engineering used here, it improves tumor tissue penetration and increases cellular uptake during in vitro and in vivo experiments, yielding excellent oxygen-independent tumor ablation with 660 nm irradiation, when compared with traditional PDT agents.

Photothermal therapy (PTT) based on two-dimensional (2D) nanomaterials has shown significant potential in cancer treatment. However, developing 2D nanomaterial-based theranostic agents with good biocompatibility and high therapeutic efficiency remains a key challenge. Bulk titanium (Ti) has been widely used as biomedical materials for their reputable biocompatibility, whereas nanosized Ti with a biological function remains unexplored. In this work, the 2D Ti nanosheets (NSs) are successfully exfoliated from nonlayer bulk Ti and utilized as an efficient theranostic nanoplatform for dual-modal computed tomography/photoacoustic (CT/PA) imaging-navigated PTT. Besides the excellent biocompatibility obtained by TiNSs as expected, they are found to show strong absorption ability with an extinction coefficient of 20.8 L g-1 cm-1 and high photothermal conversion ability with an efficiency of 61.5% owing to localized surface plasmon resonances, which exceeds most of other well-known photothermal agents, making it quite promising for PTT against cancer. Furthermore, the metallic property and light-heat-acoustic transformation endow 2D Ti with the strong CT/PA imaging signal and efficient cancer therapy, simultaneously. This work highlights the enormous potential of nanosized Ti in both the diagnosis and treatment of cancer. As a paradigm, this study also paves a new avenue for the elemental transition-metal-based cancer theranostics.

Basal-like breast cancer exhibits a triple-negative phenotype and has a poor prognosis, even with traditional chemical and anti-human epidermal growth factor receptor (HER) treatments. However, the high mutation rate of this obstinate cancer type renders it suitable for immunotherapy. Photothermal therapy (PTT) is a high-efficiency method for inducing tumor neoantigen release in situ, which has great potential for use in cancer immunotherapy. Here, we prepared a biomimetic black phosphorus quantum dot (BPQDs) formulation to induce breast cancer cell apoptosis in situ by near-infrared (NIR) laser irradiation to mobilize the immune system to eliminate the residual and metastatic cancer cells. Erythrocyte membranes (RMs) were used to coat the BPQDs, forming a BPQD-RM nanovesicle (BPQD-RMNV) biomimetic formulation that exhibited a long circulation time and tumor accumulation in vivo. The basal-like 4T1 breast tumor underwent apoptosis and necrosis with the irradiation and recruited dendritic cells (DCs) to capture the tumor antigens in vivo. Furthermore, programmed cell death protein 1 (PD-1) antibody (aPD-1) was employed to prevent the CD8+ T cells from exhaustion. Notably, BPQD-RMNV-mediated PTT combined with aPD-1 treatment significantly delayed residual and metastatic tumor growth in vivo. Hence, BPQD-RMNV-mediated PTT combined with immune checkpoint blockade antibody increased the infiltration and activity of CD8+ T cells in the tumor, which directly restrained basal-like breast tumor growth in vivo.

Black phosphorus quantum dots(BPQDs) have shown a good application prospect in the field of tumor therapy due to their photoelectric effect and good biodegradability. Due to the active endocytosis and fast metabolic efficiency of tumor cells, BPQDs are easy to be absorbed by tumor cells. However, this does not guarantee that BPQDs will be completely targeted to tumor cells, and normal cells will also absorb BPQDs. Because the cell membrane is negatively charged, BPQDs are also negatively charged and are not easily absorbed by cells under the action of electrostatic repulsion. Surface pegylation is the most common modification method of black phosphorus at present. However, surface pegylation can reduce the uptake of BPQDs by tumor cells. Positive PEG is also easy to be recognized and swallowed by the reticuloendothelial system. The inherent instability and poor tumor targeting of BPQDs under physiological conditions limit further research and clinical application. For this purpose, we selected cationic polymer polyethylenimine (PEI) to modify BPQDs and then added RGD peptides targeting tumor cells. An outer layer of negatively charged PEG+DMMA makes the nanosystem more stable . In the acidic environment of the tumor, the PEG layer has a charge reversal, and the positively charged PEI and the RGD polypeptide BPQDs targeted by the tumor cells are released into the tumor cells. It provides a new method for efficiently and accurately transporting BPQDs, a novel photosensitive nanomaterial, into tumor cells for photodynamic therapy.

p120-catenin (p120) serves as a stabilizer of the calcium-dependent cadherin-catenin complex and loss of p120 expression has been observed in several types of human cancers. The p120-dependent E-cadherin-β-catenin complex has been shown to mediate calcium-induced keratinocyte differentiation via inducing activation of plasma membrane phospholipase C-γ1 (PLC-γ1). On the other hand, PLC-γ1 has been shown to interact with phosphatidylinositol 3-kinase enhancerin the nucleus and plays a critical role in epidermal growth factor-induced proliferation of oral squamous cell carcinoma (OSCC) cells. To determine whether p120 suppresses OSCC proliferation and tumor growth via inhibiting PLC-γ1, we examined effects of p120 knockdown or p120 and PLC-γ1 double knockdown on proliferation of cultured OSCC cells and tumor growth in xenograft OSCC in mice. The results showed that knockdown of p120 reduced levels of PLC-γ1 in the plasma membrane and increased levels of PLC-γ1 and its signaling in the nucleus in OSCC cells and OSCC cell proliferation as well as xenograft OSCC tumor growth. However, double knockdown of p120 and PLC-γ1 or knockdown of PLC-γ1 alone did not have any effect. Immunohistochemical analysis of OSCC tissue from patients showed a lower expression level of p120 and a higher expression level of PLC-γ1 compared withthat of adjacent noncancerous tissue. These data indicate that p120 suppresses OSCC cell proliferation and tumor growth by inhibiting signaling mediated by nuclear PLC-γ1.

Nanozymes are more stable, economical, and easier to produce than natural enzymes; however, their low activity in non-acidic environments and lack of substrate selectivity severely limit the applications of nanozymes. In this study, we developed Co- and N-doped carbon dot nanozymes (CoNCDs) that specifically exhibited peroxidase-like activity toward o-phenylenediamine in a non-acidic environment. Based on the peroxidase-like activity and fluorescence property of CoNCDs in a neutral environment, a one-pot multi-mode sensing platform (colorimetric and ratiometric fluorescence imaging) was developed to detect cholesterol and xanthine in solution and human serum samples. This platform was simple to operate, and the CoNCDs demonstrated a reduced detection time and an improved analytical performance compared to most of the reported nanozymes. Moreover, the improved peroxidase activity at neutral pH, good biocompatibility, and photostability of CoNCDs facilitated their use for monitoring endogenous H2O2 levels in vivo. This study not only provides a novel approach for developing an acid pH-independent and substrate selectivity nanozyme but also demonstrates the application of ratiometric fluorescence imaging using the developed CoNCDs both in vitro and in vivo.

This review focuses on the biologic importance of the vitamin D binding protein (DBP) with emphasis on its regulation of total and free vitamin D metabolite levels in various clinical conditions. Nearly all DBP is produced in the liver, where its regulation is influenced by estrogen, glucocorticoids and inflammatory cytokines but not by vitamin D itself. DBP is the most polymorphic protein known, and different DBP alleles can have substantial impact on its biologic functions. The three most common alleles-Gc1f, Gc1s, Gc2-differ in their affinity with the vitamin D metabolites and have been variably associated with a number of clinical conditions. Although DBP has a number of biologic functions independent of vitamin D, its major biologic function is that of regulating circulating free and total levels of vitamin D metabolites. 25 hydroxyvitamin D (25(OH)D) is the best studied form of vitamin D as it provides the best measure of vitamin D status. In a normal non-pregnant individual, approximately 0.03% of 25(OH)D is free; 85% is bound to DBP, 15% is bound to albumin. The free hormone hypothesis postulates that only free 25(OH)D can enter cells. This hypothesis is supported by the observation that mice lacking DBP, and therefore with essentially undetectable 25(OH)D levels, do not show signs of vitamin D deficiency unless put on a vitamin D deficient diet. Similar observations have recently been described in a family with a DBP mutation. This hypothesis also applies to other protein bound lipophilic hormones including glucocorticoids, sex steroids, and thyroid hormone. However, tissues expressing the megalin/cubilin complex, such as the kidney, have the capability of taking up 25(OH)D still bound to DBP, but most tissues rely on the free level. Attempts to calculate the free level using affinity constants generated in a normal individual along with measurement of DBP and total 25(OH)D have not accurately reflected directly measured free levels in a number of clinical conditions. In this review, we examine the impact of different clinical conditions as well as different DBP alleles on the relationship between total and free 25(OH)D, using only data in which the free 25(OH)D level was directly measured. The major conclusion is that a number of clinical conditions alter this relationship, raising the question whether measuring just total 25(OH)D might be misleading regarding the assessment of vitamin D status, and such assessment might be improved by measuring free 25(OH)D instead of or in addition to total 25(OH)D.

Renal 25-hydroxyvitamin D-1α-hydroxylase (1αOHase, CYP27B1) and 24-hydroxylase (24OHase, CYP24A1) are tightly regulated. However, little is known about the regulation of 1α(OH)ase and 24(OH)ase in extrarenal tissue such as the epidermis. This study was to determine the roles of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF 23) in the regulation of 1α(OH)ase and 24(OH)ase in epidermal keratinocytes as well as epidermal keratinocyte proliferation and differentiation. The results showed that PTH increased the protein level of 1α(OH)ase in human epidermal keratinocyte cell line HaCaT, but had no effect on the level of 24(OH)ase. The effect of PTH on 1α(OH)ase was blocked by the PKC inhibitor. Treatment with FGF23 decreased mRNA and protein levels of 1α(OH)ase and increased mRNA and protein levels of 24(OH)ase in HaCaT cells. The effect of FGF23 on 1α(OH)ase and 24(OH)ase was blocked by the mitogen-activated protein kinase/extracellular regulated protein kinase (MAPK/ERK) inhibitor. In addition, treatment with PTH enhanced levels of differentiation markers including keratin 1, involucrin, loricrin, and filaggrin but reduced levels of BrdU incorporation in HaCaT cells. These effects were inhibited by the PKC inhibitor. FGF23 enhanced proliferation of HaCaT cells, but reduced levels of early differentiation markers including keratin 1 and involucrin and enhanced levels of the later differentiation markers including loricrin and filaggrin. These results suggest that PTH stimulates 1α(OH)ase expression and differentiation of HaCaT cells and inhibits proliferation via PKC. The data also suggest that FGF23 inhibits 1α(OH)ase expression and stimulates 24(OH)ase expression via MAPK/ERK. In addition, FGF23 enhances proliferation and late differentiation and inhibits early differentiation of HaCaT keratinocytes.

Various categories of biomaterials have been utilized for drug delivery, genetic modification, photodynamic and photothermal therapies due to their distinct physicochemical properties, including photothermal convertibility, stimuli-responsiveness, and inherent capability to generate photodynamical radicals. However, successful treatments of cancer are largely hindered by the limited accessibility of nanomaterials into hypoxic or metastatic tumor tissues. Among the various tumor-targeting strategies, bacterial fabrication exhibits particular advantages such as specific hypoxia tropism, high motility, and rapid self-replication. Biomineralization, i.e. bacterial modification, involves the fabrication of bacteria by nanomaterials for precise cancer imaging as well as targeted drug delivery, overcoming the physiological barriers and improving the therapeutic efficiency. Fabrication of bacteria strains can be conducted by various methods, including direct adsorption, electrostatic interaction, covalent ligation, and surface precipitation. In this review, a brief introduction to commonly-utilized biomaterials and bacteria species is provided. A systemic overview of recent advances of bacteria fabrication strategies and techniques are then discussed, followed by future prospective of bacteria-facilitated cancer therapy and diagnostics.

As one of the main elements in the living organisms, phosphorus makes an important impact on the life activity. Phosphorus contained compounds have been widely applied in the biomedical field. As nanotechnology develops, a variety of phosphorus-based nanomaterials have also been developed for the biomedical application. The recently discovered superior biological property of two-dimensional black phosphorus (2D BP), i.e. phosphorene, including low toxicity and biodegradability, makes it especially outstanding, such as biosensors for the disease diagnosis. Upon light or ultrasound irradiation on the phosphorene, reactive oxygen species (ROS) or heat can be generated for the disease therapy. Moreover, phosphorene can smartly and efficiently deliver drugs. Thus, it is suitable in many single or combined therapy modalities. This short article reviews the progress from phosphorus to phosphorene to be used as biomedical materials, especially the phosphorene as the biosensor and sensitizer for the disease diagnosis and therapy, including the tumor, the neurodegenerative disease, the bone disease and other diseases. The challenges and prospective of the phosphorene for the biomedical applications are also discussed.

Two-dimensional (2D) monoelemental bismuth (Bi) crystal, one of the pnictogens (group VA), has recently attracted increasing interest because of its intriguing characteristics. Here, uniformly sized 2D Bi quantum dots (BiQDs) with an average diameter (thickness) of 4.9 ± 1.0 nm (2.6 ± 0.7 nm) were fabricated through a facile liquid-phase exfoliation (LPE) method, and the corresponding photoresponse was evaluated using photoelectrochemical (PEC) measurements. The as-fabricated BiQDs-based photodetector not only exhibits an appropriate capacity for self-driven broadband photoresponse but also shows high-performance photoresponse under low bias potentials ranging from UV to visible light in association with long-term stability of the ON/OFF switching behavior. In terms of these findings, it is further anticipated that the resultant BiQDs possess promising potential in UV–visible photodetection as well as in liquid optoelectronics. Our work may open a new avenue for delivering high-quality monoelemental pnict...

Previous studies have shown that dietary calcium suppresses oral carcinogenesis, but the mechanism is unclear. p120-catenin (p120) is a cytoplasmic protein closely associated with E-cadherin to form the E-cadherin-β-catenin complex and may function as a tumor suppressor in the oral epithelium. To determine whether p120 is involved in the mechanism by which dietary calcium suppresses oral carcinogenesis, The normal, low, or high calcium diet was fed control mice (designated as floxed p120 mice) or mice in which p120 was specifically deleted in the oral squamous epithelium during the adult stage (designated as p120cKO mice). All mice were exposed to a low dose of oral cancer carcinogen 4-nitroquinoline 1-oxide and rates of oral squamous cell carcinoma (OSCC) and proliferation and differentiation in the cancerous and non-cancerous oral epithelium of these mice were examined. The results showed that the low calcium diet increased rates of OSCC and proliferation of the non-cancerous oral epithelium and decreased differentiation of the non-cancerous oral epithelium, but had no effect on cancerous oral epithelium. In contrast, the high calcium diet had opposite effects. However, the effect of the dietary calcium on the rates of OSCC, proliferation, and differentiation of the non-cancerous epithelium were not seen in p120cKO mice. Based on these results, we conclude that p120 is required for dietary calcium suppression of oral carcinogenesis and oral epithelial proliferation and dietary calcium induction of oral epithelial differentiation. J. Cell. Physiol. 232: 1360-1367, 2017. © 2016 Wiley Periodicals, Inc.

Nanomaterials are playing an advancing critical role in the prevention, diagnosis, and treatment of today’s human problems. By engineering with multi-active probes including biocompatible molecules, drugs, and target ligands, nanomaterials are able to inhibit or enhance the immune responses and prevent the detection ability of the immune system, thus treating autoimmune diseases. The present discussion systematically reviews the recent progress to treat autoimmune inflammation using nanomaterials of 0D, 1D, 2D, and composite systems. In addition, emphasis has laid on the using of nanomaterials-based immunotherapeutic strategies and the related autoimmune pathogenesis. Briefly discussions on current challenges and speculates on future directions have been provided to complement our drawbacks of present treatments on the basis of fascinating nanomaterials and novel nanotechnologies.

Borophene is composed purely of boron atoms and arranged in a hexagonal structure with conventional covalent bonds between each boron atom. Recently, researchers have shown a burgeoning research interest in borophene, not only regarding industrial applications but also in the field of biomedicine. Here, we provide an up-to-date summary of the recent advances in borophene-based nano-medicine. We firstly introduce the structural, mechanical, electrical, optical, thermal conductivity, biocompatibility, toxicity, photothermal and photodynamic effects of borophene. Subsequently, we fully discuss the differences between borophene, MXenes and graphene synthesized using traditional methods. Finally, we review the emerging use of borophenes as biosensors and therapeutics. We used strengths, weaknesses, opportunities, threats (SWOT) analysis to assess both the current and future marketing potential of 2D based nanomaterials in cancer therapeutics. Current challenges and future perspectives for the use of borophene are additionally discussed.

Conventional chemotherapy and photothermal therapy (PTT) face many major challenges, including systemic toxicity, low bioavailability, ineffective tissue penetration, chemotherapy/hyperthermia‐induced inflammation, and tumor angiogenesis. A versatile nanomedicine offers an exciting opportunity to circumvent the abovementioned limitations for their successful translation into clinical practice. Here, a promising biophotonic nanoplatform is developed based on the zirconium carbide (ZrC) nanosheet as a deep PTT‐photosensitizer and on‐demand designed anticancer prodrug SN38‐Nif, which is released and activated by photothermia and tumor‐overexpressed esterase. In vitro and in vivo experimental evidence shows the potent anticancer effects of the integrated ZrC@prodrug biophotonic nanoplatform by specifically targeting malignant cells, chemotherapy/hyperthermia‐induced tumor inflammation, and angiogenesis. In mouse models, the ZrC@prodrug system markedly inhibits tumor recurrence, metastasis, inflammation and angiogenesis. The findings unravel a promising biophotonic strategy for precision treatment of cancer., A biophotonic nanoplatform based on the zirconium carbide (ZrC) nanosheet as a deep photothermal therapy‐photosensitizer and on‐demand designed anticancer prodrug SN38‐Nif is developed. Both physically controlled and bioresponsive mode are employed to smartly release drugs. The ZrC@prodrug system markedly inhibits tumor recurrence, metastasis, inflammation, and angiogenesis. The findings unravel a promising biophotonic strategy for precision treatment of cancer.

Although immunoassays in measuring 25-hydroxyvitamin D [25(OH)D] have been improved recently, relatively large differences are still seen between results of 25(OH)D measured by immunoassays and by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In the present studies, we compared two immunoassays with LC-MS/MS for measuring 25(OH)D concentrations. Concentrations of 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] in serum samples from 59 healthy subjects were measured by two immunoassays including Siemens ADVIA Centaur Vitamin D Total (Centaur) and Roche Elecsys Vitamin D Total (Elecsys) and LC-MS/MS. To determine the cross reactivity of Elecsys and Centaur toward 25(OH)D2, a dosage of 200,000 IU vitamin D2 was given after first sampling. Serum samples were obtained 30 days later and concentrations of 25(OH)D2 and 25(OH)D3 were measured again. The results showed poor agreement between the immunoassays and LC-MS/MS in 25(OH)D2 and 25(OH)D3 measurements. The percentage of 25(OH)D2 cross-reactivity was 45.3% for Centaur and 41.2% for Elecsys and there was no significant difference between Centaur and Elecsys. In conclusion, Centaur and Elecsys perform unsatisfactorily in measuring 25(OH)D levels, especially for 25(OH)D2 cross-reactivity. Therefore, clinicians need to be aware of the underestimation of vitamin D status when using these immunoassays for measuring individuals supplemented with vitamin D2.

Extracellular calcium is a major regulator of keratinocyte differentiation in vitro and appears to play that role in vivo, but the mechanism is unclear. We have previously demonstrated that, following calcium stimulation, PIP5K1αis recruited by the E-cadherin-β-catenin complex to the plasma membrane where it provides the substrate PIP2 for both PI3K and PLC-γ1. This signaling pathway is critical for calcium-induced generation of second messengers including IP3 and intracellular calcium and keratinocyte differentiation. In this study, we explored the upstream regulatory mechanism by which calcium activates PIP5K1αand the role of this activation in calcium-induced keratinocyte differentiation. We found that treatment of human keratinocytes in culture with calcium resulted in an increase in serine dephosphorylation and PIP5K1αactivation. PP1 knockdown blocked extracellular calcium-induced increase in serine dephosphorylation and activity of PIP5K1αand induction of keratinocyte differentiation markers. Knockdown of PLC-γ1, the downstream effector of PIP5K1α, blocked upstream dephosphorylation and PIP5K1αactivation induced by calcium. Coimmunoprecipitation revealed calcium induced recruitment of PP1 to the E-cadherin-catenin-PIP5K1αcomplex in the plasma membrane. These results indicate that PP1 is recruited to the extracellular calcium-dependent E-cadherin-catenin-PIP5K1αcomplex in the plasma membrane to activate PIP5K1α, which is required for PLC-γ1 activation leading to keratinocyte differentiation.

Water shortage is one of the most concerning global challenges in the 21st century. Solar‐inspired vaporization employing photothermal nanomaterials is considered to be a feasible and green technology for addressing the water challenge by virtue of abundant and clean solar energy. 2D nanomaterials aroused considerable attention in photothermal evaporation‐induced water production owing to their large absorption surface, strong absorption in broadband solar spectrum, and efficient photothermal conversion. Herein, the recent progress of 2D nanomaterials‐based photothermal evaporation, mainly including emerging Xenes (phosphorene, antimonene, tellurene, and borophene) and binary‐enes (MXenes and transition metal dichalcogenides), is reviewed. Then, the optimization strategies for higher evaporation performance are summarized in terms of modulation of the intrinsic photothermal performance of 2D nanomaterials and design of the complete evaporation system. Finally, the challenges and prospective of various kinds of 2D photothermal nanomaterials are discussed in terms of the photothermal performance, stability, environmental influence, and cost. One important principle is that solutions for water challenges should not introduce new environmental and social problems. This Review aims to highlight the role of 2D photothermal nanomaterials in solving water challenges and provides a viable scheme toward the practical use in photothermal materials selection, design, and evaporation systems building., The recent progress of two‐dimensional (2D) nanomaterials‐based photothermal evaporation owing to the unique advantages of 2D photothermal nanomaterials, such as the large absorption surface, strong absorption in broadband solar spectrum, and efficient photothermal conversion is reviewed. This Review aims to highlight the role of 2D photothermal nanomaterials in solving the water challenges through employing the abundant and clean solar energy.

p120-catenin (p120) is an important regulator in the function and stability of E-cadherin. However, the role of p120 in the epidermis is unclear. Previous studies have shown that globally knockout of p120 caused increased epidermal proliferation but little changes in epidermal differentiation and permeability. In the present study, we generated a conditional knockout mouse model and examined epidermal proliferation, differentiation and permeability. The results showed that conditional knockout of p120 in the epidermis caused not only increased epidermal proliferation but also decreased epidermal differentiation and increased permeability. These data suggest that p120 is required for suppressing epidermal proliferation, promoting epidermal differentiation and maintaining permeability barrier function of the epidermis.

Black phosphorus (BP) has recently emerged as an intriguing photothermal agent in photothermal therapy (PTT) against cancer by virtue of its high photothermal efficiency, biocompatibility, and biodegradability. However, naked BP is intrinsically characterized by easy oxidation (or natural degradation) and sedimentation inside the tumor microenvironment, leading to a short-term therapeutic and inhomogeneous photothermal effect. Development of BP-based nanocomposites for PTT against cancer therefore remains challenging. The present work demonstrates that green and injectable composite hydrogels based on cellulose and BP nanosheets (BPNSs) are of great efficiency for PTT against cancer. The resultant cellulose/BPNS-based hydrogel possesses 3D networks with irregular micrometer-sized pores and thin, strong cellulose-formed walls and exhibits an excellent photothermal response, enhanced stability, and good flexibility. Importantly, this hydrogel nanoplatform is totally harmless and biocompatible both in vivo and in vitro. This work may facilitate the development of BP-polymer-based photothermal agents in the form of hydrogels for biomedical-related clinic applications.

Two-dimensional (2D) materials exhibit many interesting properties, but most 2D materials are exfoliated from layered bulk materials, limiting the development of the 2D material group. Recently, non-layered 2D materials have aroused great attention due to their excellent catalysis performance, favored compatibility with silicon substrates and high chemical activity. With high photoconductivity, high responsivity and fast response time, non-layered selenium (Se) exhibits important applications in the field of optoelectronics. In this work, we use a simple liquid phase exfoliation method to fabricate 2D Se nanoflakes from bulk Se which possesses a unique chain structure. The thickness of 2D Se nanoflakes was measured to be in the range of 5-10 nm. As-fabricated Se nanoflakes were used in a photodetector by the photoelectrochemical method, showing a high photocurrent density (1.28 μA cm-2) and photoresponsivity (10.45 μA W-1). In addition, the long-term photoelectric measurements indicate that the 2D Se-based photodetector has good time and cycle stability. Our results show that 2D Se has promising potential in liquid-based photo-detectors.

Over the past few decades, there has been a growing interest in understanding the multifunctional characteristics and clinical importance of vitamin D binding protein (DBP). Multiple studies have shed light on DBP, giving rise to hopes of identifying novel mechanisms as well as utilizing DBP as a potential therapeutic agent. The current issue is comprised of 6 manuscripts, two of which are review articles. The areas covered in this special issue mostly highlight the potential role of DBP in several conditions including periodontitis and frailty, implying that measurement of DBP may provide useful information in addition to total 25-hydroxy vitamin D concentration. In this issue, the review by P. Yousefzadeh et al. titled “Vitamin D binding protein impact on 25-hydroxyvitamin D levels under different physiologic and pathologic conditions” calls for the implementation of DBP testing during the interpretation of 25-hydroxyvitamin D [25(OH)D] results under different clinical situations. I. Bhan reviews the recent findings regarding the association between the differences in vitamin D binding protein levels and bone density in his paper titled “Vitamin D binding protein and bone health.” The author has compiled studies concerned with DBP, including DBP polymorphisms in relation to bone health and its association with vitamin D bioavailability. These findings may impact not only strategies for designing novel therapeutic agents that influence DBP or its binding, but also our understanding of the mechanism of vitamin D in the context of bone health. Evidence is emerging that the DBP polymorphisms are associated with race and ethnicity, resulting in differences in DBP levels and binding affinity that affect the transport and metabolism of vitamin D and its metabolites. Using serum samples from various populations with varying DBP levels, J. Freeman et al., in their paper titled “Influence of vitamin D binding protein on accuracy of 25-hydroxyvitamin D measurement using the ADVIA Centaur vitamin D total assay,” assessed the agreement between the ADVIA Centaur vitamin D total assay for 25(OH)D testing and the liquid chromatography mass spectrometry (LS-MS/MS) method and concluded that the ADVIA Centaur vitamin D total assay demonstrated good performance compared to the LS-MS/MS method across the normal range of DBP concentrations. This is one example of methods development in the field to ensure accurate and simpler protocols for measuring circulating 25(OH)D in future study. X. Zhang et al., in their paper titled “Vitamin D-binding protein levels in plasma and gingival crevicular fluid (GCF) of patients with generalized aggressive periodontitis,” examined the association of DBP with generalized aggressive periodontitis (GAgP). The authors found that GAgP patients had higher plasma DBP concentrations but lower GCF DBP concentrations than healthy controls, suggesting that decreased GCF-DBP level and increased plasma DBP level are associated with periodontitis. This study adds to the growing evidence of the potential role of DBP in the pathogenesis of periodontitis. Existing evidence shows an association of high circulating 25(OH)D levels with low TSH levels in younger individuals, but there is insufficient information on whether it is the same in the elderly and middle-aged. Q. Zhang et al., in their paper titled “Association of high vitamin D status with low circulating thyroid-stimulating hormone independent of thyroid hormone levels in middle-aged and elderly males,” report that such an association does exist in middle-aged and elderly males, independent of thyroid hormone levels. The authors also demonstrated the link between vitamin D insufficiency and serum thyroid antibody levels. Y. Wang et al., in their paper entitled “Vitamin D binding protein affects the correlation of 25(OH)D and frailty in the older men,” assessed the frailty status in elderly men of Changsha city, China, and concluded that serum DBP levels should be measured when evaluating the 25(OH)D- frailty relationship. We hope that these articles convey new insights to readers and researchers into the current renewed interest in vitamin D and DBP research. Zhongjian Xie Arthur C. Santora Sue A. Shapses Xiangbing Wang

cited By 0; International audience; The Flory's model for high polymers is based on the assumption that the final stretched state is achieved by two separate steps: stretching and strain-induced crystallization (SIC). This assumption is valid in fast stretching process, where SIC cannot occur instantaneously. We check if Flory's assumption can influence the equilibrium crystallinity of SIC (Ce) for different elongation rates in natural rubber (NR). It is found that the Ce is independent on the elongation rate. Thus, the calculation of Ce in Flory's model is valid for all the equilibrium states of different elongation rates, not to be limited by the Flory's assumption. Furthermore, the calculated Ce in Flory's model is used to calculate the elastocaloric temperature change (ΔT), which agrees with the directly measured one. It can meet the theoretical requirement for the new potential cooling application of NR. © 2016 Elsevier Ltd

Calcium induces epidermal keratinocyte differentiation, but the mechanism is not completely understood. We have previously demonstrated that calcium-induced human keratinocyte differentiation requires an intracellular calcium rise caused by phosphatidylinositol 3-kinase (PI3K)-dependent activation of phospholipase C-gamma1. In this study we sought to identify the upstream signaling pathway necessary for calcium activation of PI3K and its subsequent activation of phospholipase C-gamma1. We found that calcium induces the recruitment of PI3K to the E-cadherin-catenin complex at the plasma membrane of human keratinocytes. Knocking-down E-cadherin, beta-catenin, or p120-catenin expression blocked calcium activation of PI3K and phospholipase C-gamma1 and calcium-induced keratinocyte differentiation. However, knocking-down gamma-catenin expression had no effect. Calcium-induced PI3K recruitment to E-cadherin stabilized by p120-catenin at the plasma membrane requires beta-catenin but not gamma-catenin. These data indicate that the recruitment of PI3K to the E-cadherin/beta-catenin/p120-catenin complex via beta-catenin at the plasma membrane is required for calcium-induced phospholipase C-gamma1 activation and, ultimately, keratinocyte differentiation.

Oyster has gained much attention recently for its anticancer activity but it is unclear whether calcium, the major antitumor ingredient in oyster shell, is responsible for the anticarcinogenic role of the oyster. To address this issue, C57BL/6 mice were fed with the carcinogen 4-nitroquinoline-1-oxide (4NQO, 50 µg/mL) and normal diet or a diet containing oyster powder, oyster calcium, or calcium depleted oyster powder. The tongue tissue specimens isolated from these mice were histologically evaluated for hyperplasia, dysplasia, and papillary lesions, and then analyzed for proliferation and differentiation markers by immunohistochemistry. The results showed that mice on the diet containing oyster calcium significantly reduced rates of tumors in the tongue and proliferation and enhanced differentiation in the oral epithelium compared with the diet containing calcium depleted oyster powder. These results suggest that calcium in oyster plays a critical role in suppressing formation of oral squamous cell carcinoma and proliferation and promoting differentiation of the oral epithelium.

Both calcium and 1,25(OH)(2)D promote the differentiation of keratinocytes in vitro. The autocrine or paracrine production of 1,25(OH)(2)D by keratinocytes combined with the critical role of the epidermal calcium gradient in regulating keratinocyte differentiation in vivo suggest the physiologic importance of this interaction. The interactions occur at a number of levels. Calcium and 1,25(OH)(2)D synergistically induce involucrin, a protein critical for cornified envelope formation. The involucrin promoter contains an AP-1 site essential for calcium and 1,25(OH)(2)D induction and an adjacent VDRE essential for 1,25(OH)(2)D but not calcium induction. Calcium regulates coactivator complexes that bind to the Vitamin D receptor (VDR). Nuclear extracts from cells grown in low calcium contain an abundance of DRIP(205), whereas calcium induced differentiation leads to reduced DRIP(205) and increased SRC 3 which replaces DRIP in its binding to the VDR. In vivo models support the importance of 1,25(OH)(2)D-calcium interactions in epidermal differentiation. The epidermis of 1alphaOHase null mice fails to form a normal calcium gradient, has reduced expression of proteins critical for barrier function, and shows little recovery of the permeability barrier when disrupted. Thus in vivo and in vitro, calcium and 1,25(OH)(2)D interact at multiple levels to regulate epidermal differentiation.

1,25 Dihydroxyvitamin D (1,25(OH)(2)D) regulates the differentiation of keratinocytes. 1,25(OH)(2)D raises intracellular free calcium (Cai) as a necessary early step toward stimulating differentiation. 1,25(OH)(2)D induces the calcium sensing receptor (CaR) in keratinocytes and enhances the calcium response of these cells. Activation of the CaR by calcium increases intracellular free calcium by a mechanism involving phospholipase C (PLC) cleavage of phosphatidylinositolbisphosphate into inositoltrisphosphate (IP(3)) and diacylglycerol (DG). 1,25(OH)(2)D induces the family of PLCs. PLC-gamma1 has a DR6 VDRE in its promoter which binds and is activated by VDR/RAR rather than VDR/RXR. The involucrin gene, which encodes a critical component of the cornified envelope, contains a DR3 VDRE in its promoter that acts in conjunction with a nearby AP-1 site. The sequential regulation of these genes is critical for the differentiation process. In undifferentiated keratinocytes, the VDR binds preferentially to the DRIP complex of coactivators. However, with differentiation DRIP 205 is no longer produced, and the VDR switches partners to the SRC family (SRC2 and 3). These studies suggest that at least part of the sequential activation of genes required during keratinocyte differentiation is regulated by the change (availability) of these different coactivator complexes.

Involucrin is a major protein of the cornified envelope of keratinocytes that provides much of the structural integrity of skin. Its expression is stimulated by a number of agents including calcium and 1,25-dihydroxy-vitamin D3 that promote the differentiation process in keratinocytes. Within the distal regulatory region of the involucrin promoter lies an AP-1 site and an element homologous to other vitamin D response elements. In previous studies mutation of the AP-1 site was found to reduce basal activity and block calcium stimulation of the involucrin promoter, whereas the vitamin D response element was not critical for calcium regulation. In this study both elements proved to be important for 1,25-dihydroxyvitamin D3 stimulation of the involucrin promoter. Mutation of the AP-1 site reduced basal activity and blocked 1,25-dihydroxyvitamin D3 stimulation of the involucrin promoter. In contrast, mutation of the vitamin D response element did not reduce basal expression of the involucrin promoter or prevent calcium stimulation of involucrin gene expression, but blocked 1,25-dihydroxyvitamin D3 stimulation. The vitamin D response element from the involucrin gene bound the vitamin D receptor and the retinoid X receptor, but not the retinoic acid receptor, in a specific manner. We conclude that the AP-1 site and the vitamin D response element in the involucrin promoter play important roles in mediating the action of 1,25-dihydroxyvitamin D3 on involucrin expression, but the vitamin D response element provides specificity for the 1,25-dihydroxyvitamin D3 response lacking at the AP-1 site.

OBJECTIVES Recent studies suggest that serum lipid profiles are related to bone mineral density (BMD). But data about this relationship on Chinese population are scarce. We investigated the relationships between serum lipid and BMD in postmenopausal Chinese women. METHODS A cross-sectional study was conducted in 790 Chinese postmenopausal women. BMDs were measured by dual X-ray absorptiometry. Serum lipid profiles were obtained after a 12-h fasting. RESULTS Women with serum high-density lipoprotein cholesterol (HDL-C) levels of at least 1·55 mmol/l had a greater prevalence of osteoporosis compared with women with lower HDL-C (≤1·54 mmol/l). After controlling for age, menopausal duration, body mass index, serum creatinine levels, outdoor activity, smoking and alcohol intake, high HDL-C levels were associated with osteoporosis (OR = 1·64, 95%CI 1·16-2·33, P < 0·01). BMD at femoral neck and total hip was significantly lower in the higher HDL-C class than the lower class (0·722 ± 0·118 vs 0·744 ± 0·120 g/cm(2) , P < 0·01; 0·800 ± 0·126 vs 0·824 ± 0·125 g/cm(2) , P < 0·01, respectively). No association was found between total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) with BMD. CONCLUSIONS In Chinese postmenopausal women, elevated levels of serum HDL-C had a greater probability of being osteoporosis than the lower HDL-C levels. Our analysis showed higher HDL-C level that is favourable for cardiovascular diseases should be regarded as a risk factor for osteoporosis.

Calcium and 1,25 dihydroxyvitamin D (1,25(OH)(2)D) regulate the differentiation of keratinocytes. We have examined the mechanisms by which such regulation takes place, focusing primarily on the events leading to cornified envelope (CE) formation, in particular the mechanisms by which calcium and 1,25(OH)(2)D regulate the induction of involucrin, a component of the CE, and transglutaminase, the enzyme cross-linking involucrin and other substrates to form the CE. Both extracellular calcium (Ca(o)) and 1,25(OH)(2)D raise intracellular free calcium (Ca(i)) as a necessary step toward stimulating differentiation. Cells lacking the calcium sensing receptor (CaR) or phospholipase C-gamma 1 (PLC-gamma 1) fail to respond to Ca(o) or 1,25(OH)(2)D with respect to differentiation. Residing in the promoter of involucrin is a region responsive to calcium and 1,25(OH)(2)D, the calcium response element (CaRE). The CaRE contains an AP-1 site, mutations of which result in loss of responsiveness to Ca(o) and 1,25(OH)(2)D, indicating a role for protein kinases C (PKC). PKC alpha is the major PKC isozyme involved at least for calcium-induced differentiation. Thus, the regulation of keratinocyte differentiation by calcium and 1,25(OH)(2)D involves a number of signaling pathways including PLC and PKC activation, leading to the induction of proteins required for the differentiation process.

Phospholipase C-gamma1 (PLC-gamma1) is the most abundant member of the phospholipase C family expressed in human keratinocytes. PLC-gamma1 is induced by 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) in normal keratinocytes via a DR6-type vitamin D responsive element. This regulation is not observed in transformed keratinocytes. The role of PLC-gamma1 in mediating 1alpha,25(OH)(2)D(3) and calcium-regulated differentiation was then tested. Both specific PLC inhibitors and antisense constructs which selectively block PLC-gamma1 production prevented 1alpha,25(OH)(2)D(3) and calcium from inducing markers of differentiation such as involucrin and transglutaminase. These studies demonstrate that PLC-gamma1 induction by 1alpha,25(OH)(2)D(3) is critical to the ability of this hormone to regulate keratinocyte differentiation.

Phospholipase C-gamma1 is the most abundant member of the phospholipase C family in keratinocytes and is induced by calcium. Phospholipase C-gamma1, therefore, may be involved in the signal transduction system leading to calcium regulation of keratinocyte differentiation. To test this hypothesis, expression of phospholipase C-gamma1 in human keratinocytes was blocked by transfecting cells with the antisense human phospholipase C-gamma1 cDNA construct. These cells demonstrated a dramatic reduction in phospholipase C-gamma1 protein level compared with the empty vector-transfected cells and a marked reduction in the mRNA and protein levels of the differentiation markers involucrin and transglutaminase following administration of calcium. Similarly, cotransfection of antisense phospholipase C-gamma1 constructs with a luciferase reporter vector containing involucrin or transglutaminase promoters led to a substantial reduction in calcium-stimulated involucrin and transglutaminase promoter activities. Similar results were seen following treatment with a specific phospholipase C inhibitor U73122. To determine whether phospholipase C-gamma1 regulated differentiation by controlling intracellular calcium, we examined the ability of antisense phospholipase C-gamma1 to block the calcium-induced rise in intracellular calcium and found that it could. These findings indicate that phospholipase C-gamma1 is a critical component of the signaling pathway mediating calcium regulation of keratinocyte differentiation via its mobilization of intracellular calcium.

Calcium is the major regulator of keratinocyte differentiation in vivo and in vitro. A calcium gradient within the epidermis promotes the sequential differentiation of keratinocytes as they traverse the different layers of the epidermis to form the permeability barrier of the stratum corneum. Calcium promotes differentiation by both outside–in and inside–out signaling. A number of signaling pathways involved with differentiation are regulated by calcium, including the formation of desmosomes, adherens junctions and tight junctions, which maintain cell–cell adhesion and play an important intracellular signaling role through their activation of various kinases and phospholipases that produce second messengers that regulate intracellular free calcium and PKC activity, critical for the differentiation process. The calcium receptor plays a central role by initiating the intracellular signaling events that drive differentiation in response to extracellular calcium. This review will discuss these mechanisms.

International audience; In the context of solid-state-cooling, the elastocaloric effect offers a very large controlled entropy change based in low-cost polymers, especially natural rubber which is environmentally friendly. However, large elastocaloric activity requires large elongation (>5), which makes this material impractical for cooling systems due to the large change in sample's area. By performing a pre-elongation, area change is limited, and β = - γ / λ (where γ is the specific entropy and λ is the elongation) is larger. The highest β value is obtained when pre-elongation is right before (at the "eve") the onset of the strain-induced crystallization, which is also interpreted in the view of molecular conformation. Experimental results obtained on a natural rubber sample showed an adiabatic temperature change of 4.3°C for pre-elongation of 4 with further elongation of 4 (true strain change of 69%). Furthermore, the entropy exhibits a quasi-linear dependence on elongation, and the β value is found to be 6400 J K-1 m-3.