Chaperone-mediated autophagy protects the bone formation from excessive inflammation through PI3K/AKT/GSK3ß/ß-catenin pathway.

Multiple regulatory mechanisms are in place to ensure the normal processes of bone metabolism, encompassing both bone formation and absorption. This study has identified chaperone-mediated autophagy (CMA) as a critical regulator that safeguards bone formation from the detrimental effects of excessive inflammation. By silencing LAMP2A or HSCA8, we observed a hindrance in the osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. To further elucidate the role of LAMP2A, we generated LAMP2A gene knockdown and overexpression of mouse BMSCs (mBMSCs) using adenovirus. Our results showed that LAMP2A knockdown led to a decrease in osteogenic-specific proteins, while LAMP2A overexpression favored the osteogenesis of mBMSCs. Notably, active-ß-catenin levels were upregulated by LAMP2A overexpression. Furthermore, we found that LAMP2A overexpression effectively protected the osteogenesis of mBMSCs from TNF-α, through the PI3K/AKT/GSK3ß/ß-catenin pathway. Additionally, LAMP2A overexpression significantly inhibited osteoclast hyperactivity induced by TNF-α. Finally, in a murine bone defect model, we demonstrated that controlled release of LAMP2A overexpression adenovirus by alginate sodium capsule efficiently protected bone healing from inflammation, as confirmed by imaging and histological analyses. Collectively, our findings suggest that enhancing CMA has the potential to safeguard bone formation while mitigating hyperactivity in bone absorption.

Engineering Magnetic Nanoclusters for Highly Efficient Heating in Radio-Frequency Nanowarming.

Effective thawing of cryopreserved samples requires rapid and uniform heating. This is achievable through nanowarming, an approach that heats magnetic nanoparticles by using alternating magnetic fields. Here we demonstrate the synthesis and surface modification of magnetic nanoclusters for efficient nanowarming. Magnetite (Fe3O4) nanoclusters with an optimal diameter of 58 nm exhibit a high specific absorption rate of 1499 W/g Fe under an alternating magnetic field at 43 kA/m and 413 kHz, more than twice that of commercial iron oxide cores used in prior nanowarming studies. Surface modification with a permeable resorcinol-formaldehyde resin (RFR) polymer layer significantly enhances their colloidal stability in complex cryoprotective solutions, while maintaining their excellent heating capacity. The Fe3O4@RFR nanoparticles achieved a high average heating rate of 175 °C/min in cryopreserved samples at a concentration of 10 mg Fe/mL and were successfully applied in nanowarming porcine iliac arteries, highlighting their potential for enhancing the efficacy of cryopreservation.

KDELR2 promotes bone marrow mesenchymal stem cell osteogenic differentiation via GSK3ß/ß-catenin signaling pathway.

Nonunion is a challenging complication of fractures for the surgeon. Recently the Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum protein retention receptor 2 (KDELR2) has been found that involved in osteogenesis imperfecta. However, the exact mechanism is still unclear. In this study, we used lentivirus infection and mouse fracture model to investigate the role of KDELR2 in osteogenesis. Our results showed that KDELR2 knockdown inhibited the osteogenic differentiation of mBMSCs, whereas KDELR2 overexpression had the opposite effect. Furthermore, the levels of active-ß-catenin and phospho-GSK3ß (Ser9) were upregulated by KDELR2 overexpression and downregulated by KDELR2 knockdown. In the fracture model, mBMSCs overexpressing KDELR2 promoted healing. In conclusion, KDELR2 promotes the osteogenesis of mBMSCs by regulating the GSK3ß/ß-catenin signaling pathway.

Natural Polysaccharide Film-Based Triboelectric Sensor for Fruit Transportation Collision Monitoring.

Transportation-induced damage to fresh produce is a big challenge in logistics. Current acceleration and pressure sensors for collision monitoring face issues of power dependency, high cost, and environmental concerns. Here, a self-powered and environmentally friendly triboelectric sensor has been developed to monitor fruit collisions in transportation packaging. Microcrystalline cellulose/chitosan and sodium alginate films were prepared as positive and negative tribo-layers to assemble a natural polysaccharide film-based triboelectric nanogenerator (NP-TENG). The NP-TENG's electrical output was proportional to the structure parameters (contact surface roughness and separation gap of the tribo-layers) and the vibration factors (force and frequency) and exhibited excellent stability and durability (over 100,000 cycles under 13 N at 10 Hz). The high mechanical-to-electrical conversion efficiency (instantaneous areal power density of 9.6 mW/m2) and force sensitivity (2.2 V/N) enabled the NP-TENG to be a potential sensor for monitoring fresh produce collisions in packaging during logistics. Transportation simulation measurements of kiwifruits verified that the sensor's electrical outputs increased with the vibration frequency and stacking layer while varying at different packaging locations. This study suggests that the NP-TENG can effectively monitor collision damage during fruit transportation, providing new insights into developing intelligent food packaging systems to reduce postharvest supply chain losses.

Magnetic Assembly of Eu-Doped NaYF4 Nanorods for Field-Responsive Linearly and Circularly Polarized Luminescence.

Colloidal assembly has emerged as an effective avenue for achieving polarized light emission. Here, we showcase the efficacy and versatility of the magnetic colloidal assembly in enabling both linearly and circularly polarized luminescence. Colloidal europium-doped NaYF4 nanorods with surface-bound Fe3O4 nanoparticles are magnetically assembled into linear or chiral superstructures using corresponding fields created in permanent magnets. In a uniform magnetic field generated by opposing poles, the assemblies exhibit photoluminescence with intensity tunable in response to the magnetic field direction, which is higher when the nanorods are perpendicular to light propagation than when they are parallel. The obtained superstructures display strong linearly polarized luminescence when the nanorods are aligned vertically, exhibiting a high degree of polarization up to 0.61. In a quadrupole chiral field generated by permanent magnets, the assemblies emit left-handed or right-handed polarized light depending on the position of the sample placement, attaining a g-factor of 0.04. Furthermore, the superstructures immobilized in a hydrogel film are found to retain their chirality, exhibiting opposite chiroptical responses depending on the sample orientation. The magnetic colloidal assembly approach facilitates the convenient and efficient generation of polarized light emissions from nonmagnetic luminescent materials, thus creating opportunities for tailoring light behavior in developing innovative optoelectronic devices.

Eicosapentaenoic acid supplementation modulates the osteoblast/osteoclast balance in inflammatory environments and protects against estrogen deficiency-induced bone loss in mice.

BACKGROUND: An imbalance of osteoblasts (OBs) and osteoclasts (OCs) in a chronic inflammatory microenvironment is an important pathological factor leading to osteoporosis. Eicosapentaenoic acid (EPA) has been shown to suppress inflammation in macrophages and adipocytes. However, the effect of EPA on OBs and OCs has yet to be fully elucidated. AIMS: We explored the roles of EPA in the differentiation of OBs and OCs, as well as the coupling between OBs and OCs in an inflammatory microenvironment. The effects of EPA on estrogen deficiency-induced osteoporosis were also evaluated. METHODS: Mouse bone marrow mesenchymal stem cells (mBMSCs) and mouse bone marrow-derived macrophages (mBMMs) were used for in vitro OBs and OCs differentiation. TNF-α was used to create an inflammatory microenvironment. We examined the effects of EPA on osteoblastogenesis in the absence or presence of TNF-α and collect OBs' culture medium as the conditioned medium (CM). Then we examined the effects of EPA and CM on RANKL-induced osteoclastogenesis. The in vivo effects of EPA were determined using an ovariectomized (OVX) mouse model treated with EPA or vehicle. RESULTS: High-dose EPA was shown to promote osteoblastogenesis in an inflammatory environment in vitro, as well as upregulate expression of OBs-specific proteins and genes. ARS and ALP staining also showed that high-dose EPA-treated groups restored mBMSCs' impaired osteogenic capacity caused by TNFa. Mechanistically, EPA suppressed the NF-κB pathway activated by TNF-α in mBMSCs and rescued TNF-α-mediated inhibition of osteoblastogenesis. EPA was also shown to inhibit expression of RANKL and decrease the RANKL/OPG ratio in OBs in an inflammatory environment. CM from TNF-α-stimulated OBs promoted osteoclastogenesis of mBMMs; EPA-treated CM prevented this. In the OVX mouse model, EPA supplementation prevented bone loss in an estrogen deficiency-induced inflammatory environment. CONCLUSIONS: EPA was demonstrated for the first time to restore mBMSCs' impaired osteogenic capacity caused by TNFa-induced inflammation and rescue the OBs/OCs balance via regulation of RANKL and OPG expression in OBs. EPA showed a remarkable ability to prevent bone loss in OVX mice, suggesting a potential application of EPA in postmenopausal osteoporosis.

A magnetic assembly approach to chiral superstructures.

Colloidal assembly into chiral superstructures is usually accomplished with templating or lithographic patterning methods that are only applicable to materials with specific compositions and morphologies over narrow size ranges. Here, chiral superstructures can be rapidly formed by magnetically assembling materials of any chemical compositions at all scales, from molecules to nano- and microstructures. We show that a quadrupole field chirality is generated by permanent magnets caused by consistent field rotation in space. Applying the chiral field to magnetic nanoparticles produces long-range chiral superstructures controlled by field strength at the samples and orientation of the magnets. Transferring the chirality to any achiral molecules is enabled by incorporating guest molecules such as metals, polymers, oxides, semiconductors, dyes, and fluorophores into the magnetic nanostructures.

LAMP2A regulates the balance of mesenchymal stem cell adipo-osteogenesis via the Wnt/ß-catenin/GSK3ß signaling pathway.

Chaperone-mediated autophagy (CMA) plays multiple roles in cell metabolism. We found that lysosome-associated membrane protein type 2A (LAMP2A), a crucial protein of CMA, plays a key role in the control of mesenchymal stem cell (MSC) adipo-osteogenesis. We identified a differentially expressed CMA gene (LAMP2) in GEO datasets (GSE4911 and GSE494). Further, we performed co-expression analyses to define the relationships between CMA components genes and other relevant genes including Col1a1, Runx2, Wnt3 and Gsk3ß. Mouse BMSCs (mMSCs) exhibiting Lamp2a gene knockdown (LA-KD) and overexpression (LA-OE) were created using an adenovirus system; then we investigated LAMP2A function in vitro by Western blot, Oil Red staining, ALP staining, ARS staining and Immunofluorescence analysis. Next, we used a modified mouse model of tibial fracture to investigate LAMP2A function in vivo. LAMP2A knockdown in mMSCs decreased the levels of osteogenic-specific proteins (COL1A1 and RUNX2) and increased those of the adipogenesis markers PPARγ and C/EBPα; LAMP2A overexpression had the opposite effects. The active-ß-catenin and phospho-GSK3ß (Ser9) levels were upregulated by LAMP2A overexpression and downregulated by LAMP2A knockdown. In the mouse model of tibial fracture, mMSC-overexpressing LAMP2A improved bone healing, as demonstrated by microcomputed tomography and histological analyses. In summary, LAMP2A positively regulates mMSC osteogenesis and suppresses adipo-osteogenesis, probably via Wnt/ß-catenin/GSK3ß signaling. LAMP2A promoted fracture-healing in the mouse model of tibial fracture. KEY MESSAGES: • LAMP2 positively regulates the mBMSCs osteogenic differentiation. • LAMP2 negatively regulates the mBMSCs adipogenic differentiation. • LAMP2 regulates mBMSCs osteogenesis via Wnt/ß-catenin/GSK3ß signaling pathway. • LAMP2 overexpression mBMSCs promote the fracture healing.

EGFL7 Secreted By Human Bone Mesenchymal Stem Cells Promotes Osteoblast Differentiation Partly Via Downregulation Of Notch1-Hes1 Signaling Pathway.

BACKGROUND: Epidermal growth factor-like domain protein 7 (EGFL7) is a secreted protein that is differentially expressed in the bone microenvironment; however, the effect of EGFL7 on the osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) is largely unknown. METHODS: EGFL7 expression in the fracture microenvironment was analyzed based on the Gene Expression Omnibus (GEO) database. Knockdown of EGFL7 by small interfering RNA (siRNA) and in vitro stimulation with recombinant human EGFL7 (rhEGFL7) protein were used to assess alterations in downstream signaling and changes in the osteogenic differentiation and proliferation of hBMSCs. A γ-secretase inhibitor was used to further explore whether inhibition of Notch signaling rescued the osteogenic-inhibitory effect of EGFL7 knockdown in hBMSCs. A femoral defect model was established to verify the effect of recombinant mouse EGFL7 on bone healing in vivo. RESULTS: EGFL7 expression increased during hBMSC osteogenesis. Knockdown of EGFL7 impaired hBMSC osteogenesis and activated Notch1/NICD/Hes1 signaling. rhEGFL7 promoted hBMSC osteogenesis and downregulated Notch1 signaling. The osteoblast-inhibitory effect of EGFL7 knockdown was rescued by Notch1 signaling inhibition. Recombinant EGFL7 led to enhanced bone healing in mice with femoral defects. CONCLUSIONS: EGFL7 promotes osteogenesis of hBMSCs partly via downregulation of Notch1 signaling.

Knockdown of FOXA1 enhances the osteogenic differentiation of human bone marrow mesenchymal stem cells partly via activation of the ERK1/2 signalling pathway.

BACKGROUND: The available therapeutic options for large bone defects remain extremely limited, requiring new strategies to accelerate bone healing. Genetically modified bone mesenchymal stem cells (BMSCs) with enhanced osteogenic capacity are recognised as one of the most promising treatments for bone defects. METHODS: We performed differential expression analysis of miRNAs between human BMSCs (hBMSCs) and human dental pulp stem cells (hDPSCs) to identify osteogenic differentiation-related microRNAs (miRNAs). Furthermore, we identified shared osteogenic differentiation-related miRNAs and constructed an miRNA-transcription network. The Forkhead box protein A1 (FOXA1) knockdown strategy with a lentiviral vector was used to explore the role of FOXA1 in the osteogenic differentiation of MSCs. Cell Counting Kit-8 was used to determine the effect of the knockdown of FOXA1 on hBMSC proliferation; real-time quantitative reverse transcription PCR (qRT-PCR) and western blotting were used to investigate target genes and proteins; and alkaline phosphatase (ALP) staining and Alizarin Red staining (ARS) were used to assess ALP activity and mineral deposition, respectively. Finally, a mouse model of femoral defects was established in vivo, and histological evaluation and radiographic analysis were performed to verify the therapeutic effects of FOXA1 knockdown on bone healing. RESULTS: We identified 22 shared and differentially expressed miRNAs between hDPSC and hBMSC, 19 of which were downregulated in osteogenically induced samples. The miRNA-transcription factor interaction network showed that FOXA1 is the most significant and novel osteogenic differentiation biomarker among more than 300 transcription factors that is directly targeted by 12 miRNAs. FOXA1 knockdown significantly promoted hBMSC osteo-specific genes and increased mineral deposits in vitro. In addition, p-ERK1/2 levels were upregulated by FOXA1 silencing. Moreover, the increased osteogenic differentiation of FOXA1 knockdown hBMSCs was partially rescued by the addition of ERK1/2 signalling inhibitors. In a mouse model of femoral defects, a sheet of FOXA1-silencing BMSCs improved bone healing, as detected by microcomputed tomography and histological evaluation. CONCLUSION: These findings collectively demonstrate that FOXA1 silencing promotes the osteogenic differentiation of BMSCs via the ERK1/2 signalling pathway, and silencing FOXA1 in vivo effectively promotes bone healing, suggesting that FOXA1 may be a novel target for bone healing.

Aucubin promotes bone-fracture healing via the dual effects of anti-oxidative damage and enhancing osteoblastogenesis of hBM-MSCs.

BACKGROUND: Aucubin (AU), an iridoid glucoside isolated from many traditional herbal medicines, has anti-osteoporosis and anti-apoptosis bioactivities. However, the effect of AU on the treatment of bone-fracture remains unknown. In the present study, the aims were to investigate the roles and mechanisms of AU not only on osteoblastogenesis of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) and anti-oxidative stress injury in vitro, but also on bone-fracture regeneration by a rat tibial fracture model in vivo. METHODS: CCK-8 assay was used to assess the effect of AU on the viability and proliferation of hBM-MSCs. The expression of specific genes and proteins on osteogenesis, apoptosis and signaling pathways was measured by qRT-PCR, western blotting and immunofluorescence analysis. ALP staining and quantitative analysis were performed to evaluate ALP activity. ARS and quantitative analysis were performed to evaluate calcium deposition. DCFH-DA staining was used to assess the level of reactive oxygen species (ROS). A rat tibial fracture model was established to validate the therapeutic effect of AU in vivo. Micro-CT with quantitative analysis and histological evaluation were used to assess the therapeutic effect of AU locally injection at the fracture site. RESULTS: Our results revealed that AU did not affect the viability and proliferation of hBM-MSCs. Compared with control group, western blotting, PCR, ALP activity and calcium deposition proved that AU-treated groups promoted osteogenesis of hBM-MSCs. The ratio of phospho-Smad1/5/9 to total Smad also significantly increased after treatment of AU. AU-induced expression of BMP2 signaling target genes BMP2 and p-Smad1/5/9 as well as of osteogenic markers COL1A1 and RUNX2 was downregulated after treating with noggin and LDN193189. Furthermore, AU promoted the translocation of Nrf2 from cytoplasm to nucleus and the expression level of HO1 and NQO1 after oxidative damage. In a rat tibial fracture model, local injection of AU promoted bone regeneration. CONCLUSIONS: Our study demonstrates the dual effects of AU in not only promoting bone-fracture healing by regulating osteogenesis of hBM-MSCs partly via canonical BMP2/Smads signaling pathway but also suppressing oxidative stress damage partly via Nrf2/HO1 signaling pathway.

Role of Lysosomal Acidification Dysfunction in Mesenchymal Stem Cell Senescence.

Mesenchymal stem cell (MSC) transplantation has been widely used as a potential treatment for a variety of diseases. However, the contradiction between the low survival rate of transplanted cells and the beneficial therapeutic effects has affected its clinical use. Lysosomes as organelles at the center of cellular recycling and metabolic signaling, play essential roles in MSC homeostasis. In the first part of this review, we summarize the role of lysosomal acidification dysfunction in MSC senescence. In the second part, we summarize some of the potential strategies targeting lysosomal proteins to enhance the therapeutic effect of MSCs.

Efficacy and safety of recombinant Bifidobacterium breve carrying HPV16 E7 shRNA and IL-12 gene against mouse cervical cancer xenografts / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：评价口服携带HPV16 E7 shRNA和IL-12基因的重组短双歧杆菌在小鼠体内抗宫颈癌移植瘤的效果。方法：将pMG36e-E7 shRNA、pMG36e-mIL-12D质粒分别转化短双歧杆菌，经筛选鉴定并扩增获得携带HPV16 E7 shRNA和IL-12 基因的重组短双歧杆菌。通过小鼠皮下宫颈癌细胞移植建立荷瘤小鼠模型。口服重组短双歧杆菌1、7 d后，检测小鼠主要器官（心、肝、脾、肺、肾）和肿瘤组织匀浆液或血清在PYG培养基中形成的菌落数量，评价短双歧杆菌的肿瘤靶向性，以小鼠体内肿瘤生长曲线评估重组短双歧杆菌的抗肿瘤效果，通过主要器官切片H-E染色和检测荷瘤小鼠血清相关细胞因子水平评价口服重组短双歧杆菌的安全性。结果：成功制备重组短双歧杆菌和宫颈癌TC-1细胞移植瘤小鼠。7 d后，移植瘤组织匀浆液和血清的菌落数量证实短双歧杆菌具有靶向体内瘤组织的定殖能力，口服重组短双歧杆菌明显抑制荷瘤小鼠的肿瘤生长（P<0.05或P<0.01），但联合使用携带HPV16 E7 shRNA和IL-12基因的重组双歧杆菌的肿瘤抑制率与单独使用的并无显著差异，治疗后未见对荷瘤小鼠主要器官的损伤和血清中IL-12及IFN-γ的水平明显变化。结论：短双歧杆菌可用作靶向肿瘤的治疗性基因分子递送载体，其对宫颈癌移植瘤的疗效明显且安全可控。

An emerging role of Prevotella histicola on estrogen deficiency-induced bone loss through the gut microbiota-bone axis in postmenopausal women and in ovariectomized mice.

BACKGROUND: The gut microbiota (GM)-bone axis has emerged as a crucial mediator of bone homeostasis. Estrogen deficiency-induced bone loss is closely associated with an altered GM. However, the underlying mechanisms remain unclear. OBJECTIVES: We sought to explore the putative effects of GM on estrogen deficiency-induced bone loss and determine a potential mechanism. METHODS: Fecal samples collected from postmenopausal women with osteoporosis (PMO) and with normal bone mass (PMN) were examined by 16S ribosomal RNA (rRNA) gene sequencing and analysis. Prevotella histicola, a typical species of Prevotella, was orally given to female C57BL6/J mice after ovariectomy [ovariectomized (OVX)]. The primary outcomes were changes in bone microstructures as measured by micro-computed tomography scanning and bone histomorphometry analysis. Secondary outcomes included changes in osteoclast activity, the expression of osteoclastogenic cytokines, and gut permeability, which were measured by ELISA, qRT-PCR, western blot, and immunofluorescence. RESULTS: As demonstrated through 16S rRNA gene sequencing and analysis, the GM in the PMO group featured a significantly decreased proportion of the genus Prevotella in comparison with that in the PMN group (∼60%, P < 0.05). In animal experiments, P. histicola-treated OVX mice maintained a relatively higher bone volume than OVX controls. Mechanistically, the protective effects of P. histicola on bone mass were found to be associated with its modulation of gut permeability as well as its inhibitory effects on osteoclast activity which function by attenuating osteoclastogenic cytokine expression. CONCLUSIONS: The GM diversity and composition between the PMN and PMO groups were significantly different. In particular, the proportion of the genus Prevotella was notably higher in the PMN group, demonstrating its potential bone-protective effects on osteoporosis. Further animal study using osteoporotic mice showed P. histicola could prevent estrogen deficiency-induced bone loss through the GM-bone axis. Thus, P. histicola may serve as a therapeutic agent or target for osteoporosis treatment.

Prevotella histicola Mitigated Estrogen Deficiency-Induced Depression via Gut Microbiota-Dependent Modulation of Inflammation in Ovariectomized Mice.

BACKGROUND: Estrogen deficiency-induced depression is closely associated with an imbalance in intestinal microbiota and inflammation. Prevotella histicola (P. histicola), an emerging probiotic, apparently improves inflammatory responses. This study aims to verify the antidepressant-like effects of P. histicola and clarify its potential mechanisms. METHODS: Mice were treated with P. histicola and cohousing after ovariectomy (OVX). The changes in depression-like behaviors among mice were examined by behavioral tasks, and alterations in the microbiota were detected through 16S rRNA sequencing. Changes in neuronal injury, protein synthesis, inflammatory factors, intestinal permeability, and nerve proliferation were observed by H&E, Nissl staining, qRT-PCR, western blotting, and immunofluorescence. RESULTS: P. histicola significantly reduces depression-like behaviors and neuronal damage induced by estrogen deficiency. Additionally, P. histicola significantly increases the abundance of intestinal flora, especially Lactobacillus and Akkermansia. Meanwhile, the cohoused mice also had a better emotional state and neutral structure compared with OVX mice. P. histicola was also found to upregulate tight junction proteins ZO-1, occludin, claudin-1, and MUC2 in the ileum and colon and reduce the levels of inflammatory factors VCAM, MCP-1, IL-6, IL-8, and TNF-α, mainly in the ileum, colon, and decrease the expression of COX-2, TLR4, Myd88, JNK, MCP-1, IL-6, IL-8, and TNF-α in the hippocampus. Moreover, significant downregulation of apoptosis (caspase-3 and caspase-8) and upregulation of neurotrophic factors (BDNF and Ki-67) were observed after P. histicola treatment. CONCLUSION: Our data show that P. histicola significantly mitigates depression of OVX mice through improvement in intestinal microbiota to repair intestinal leakage and inhibit central inflammation to promote the expression of BDNF for hippocampal neurogenesis. P. histicola may be therapeutically beneficial for PMD.

Influence of Metal-Ligand Coordination on the Elemental Growth and Alloying Composition of Pt-Ni Octahedral Nanoparticles for Oxygen Reduction Electrocatalysis.

Understanding the role of surfactants or ligands on the growth mechanism of metal/alloy nanoparticles (NPs) is important for controlled synthesis of functional metallic NPs with tailored structures and properties. There have been a number of works showing the significant impact of surfactants/ligands on the shape-controlled synthesis of nanocrystals with well-defined surfaces. Beyond the morphological shape control, impact of the surfactants/ligands on the alloying structure of bimetallic nanocrystals, however, still remains largely unaddressed. We reveal here a significant effect of benzoic acid ligand on the elemental growth and alloying phase structure of octahedral Pt-Ni NPs, a class of highly active electrocatalyst for oxygen reduction reaction in fuel cells. Contrary to previous reports showing the critical role of benzoic acid in directing the growth of octahedral Pt-Ni NPs, we found that benzoic acid played a minor role in forming the octahedral shape; instead, it can strongly coordinate with Ni cation and significantly slows down its reduction rate, leading to a phase separation in the Pt-Ni NP products (a mixture of Pt-rich octahedral NPs and nearly pure Ni NPs). Such phase separation further resulted in a lower catalytic activity and stability. These results help us comprehensively understand the effect of metal-ligand coordination chemistry on the elemental growth mechanism and alloying phase structure of bimetallic NPs, complementing previous emphasis on the role of surfactants in purely morphological shape control.

A 34.5 day quasi-periodic oscillation in γ-ray emission from the blazar PKS 2247-131.

Since 2016 October, the active galaxy PKS 2247-131 has undergone a γ-ray outburst, which we studied using data obtained with the Fermi Gamma-ray Space Telescope. The emission arises from a relativistic jet in PKS 2247-131, as an optical spectrum only shows a few weak absorption lines, typical of the BL Lacertae sub-class of the blazar class of active galactic nuclei. Here we report a ≃34.5 day quasi-periodic oscillation (QPO) in the emission after the initial flux peak of the outburst. Compared to one-year time-scale QPOs, previously identified in blazars in Fermi energies, PKS 2247-131 exhibits the first clear case of a relatively short, month-like oscillation. We show that this QPO can be explained in terms of a helical structure in the jet, where the viewing angle to the dominant emission region in the jet undergoes periodic changes. The time scale of the QPO suggests the presence of binary supermassive black holes in PKS 2247-131.

Endothelial nitric oxide synthase gene polymorphisms associated with susceptibility to high altitude pulmonary edema in Chinese railway construction workers at Qinghai-Tibet over 4 500 meters above sea level / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To examine whether the polymorphisms of endothelial nitric oxide synthase (eNOS) gene are associated with the susceptibility to high altitude pulmonary edema (HAPE) in Chinese railway construction workers at Qinghai-Tibet where the altitude is over 4 500 m above sea level.</p><p><b>METHODS</b>A case-control study was conducted including 149 HAPE patients in the construction workers and 160 healthy controls randomly recruited from their co-workers, matching the patients in ethnicity, age, sex, lifestyle, and working conditions. Three polymorphisms of eNOS gene, T-786C in promoter, 894G/T in exon 7, and 27bp variable number tandem repeat (VNTR) in intron 4, were genotyped using polymerase chain reaction (PCR) and confirmed with DNA sequencing.</p><p><b>RESULTS</b>The frequencies of 894T allele and heterozygous G/T of the 894G/T variant were significantly higher in HAPE patients group than in the control group (P=0.0028 and P=0.0047, respectively). However, the frequencies of the T-786C in promoter and the 27bp VNTR in intron 4 were not significantly different between the two groups. Haplotypic analysis revealed that the frequencies of two haplotypes (H3,T-T-b, b indicates 5 repeats of 27 bp VNTR; H6, C-G-a, a indicates 4 repeats of 27 bp VNTR) were significantly higher in HAPE patients (both Pü0.0001). On the contrary, the frequencies of H1 (T-G-b) and H2 (T-G-a) were lower in HAPE patients than in healthy controls (both Pü0.001).</p><p><b>CONCLUSIONS</b>Two haplotypes (T-T-b and C-G-a) may be strongly associated with susceptibility to HAPE. Compared with the individual alleles of eNOS gene, the interaction of multiple genetic markers within a haplotype may be a major determinant for the susceptibility to HAPE.</p>

A debris disk around an isolated young neutron star.

Pulsars are rotating, magnetized neutron stars that are born in supernova explosions following the collapse of the cores of massive stars. If some of the explosion ejecta fails to escape, it may fall back onto the neutron star or it may possess sufficient angular momentum to form a disk. Such 'fallback' is both a general prediction of current supernova models and, if the material pushes the neutron star over its stability limit, a possible mode of black hole formation. Fallback disks could dramatically affect the early evolution of pulsars, yet there are few observational constraints on whether significant fallback occurs or even the actual existence of such disks. Here we report the discovery of mid-infrared emission from a cool disk around an isolated young X-ray pulsar. The disk does not power the pulsar's X-ray emission but is passively illuminated by these X-rays. The estimated mass of the disk is of the order of 10 Earth masses, and its lifetime (> or = 10(6) years) significantly exceeds the spin-down age of the pulsar, supporting a supernova fallback origin. The disk resembles protoplanetary disks seen around ordinary young stars, suggesting the possibility of planet formation around young neutron stars.