HuR-mediated nucleocytoplasmic translocation of HOTAIR relieves its inhibition of osteogenic differentiation and promotes bone formation

Bone marrow mesenchymal stem cell(BMSC)osteogenic differentiation and osteoblast function play critical roles in bone formation,which is a highly regulated process.Long noncoding RNAs(lncRNAs)perform diverse functions in a variety of biological processes,including BMSC osteogenic differentiation.Although several studies have reported that HOX transcript antisense RNA(HOTAIR)is involved in BMSC osteogenic differentiation,its effect on bone formation in vivo remains unclear.Here,by constructing transgenic mice with BMSC(Prx1-HOTAIR)-and osteoblast(Bglap-HOTAIR)-specific overexpression of HOTAIR,we found that Prx1-HOTAIR and Bglap-HOTAIR transgenic mice show different bone phenotypes in vivo.Specifically,Prx1-HOTAIR mice showed delayed bone formation,while Bglap-HOTAIR mice showed increased bone formation.HOTAIR inhibits BMSC osteogenic differentiation but promotes osteoblast function in vitro.Furthermore,we identified that HOTAIR is mainly located in the nucleus of BMSCs and in the cytoplasm of osteoblasts.HOTAIR displays a nucleocytoplasmic translocation pattern during BMSC osteogenic differentiation.We first identified that the RNA-binding protein human antigen R(HuR)is responsible for HOTAIR nucleocytoplasmic translocation.HOTAIR is essential for osteoblast function,and cytoplasmic HOTAIR binds to miR-214 and acts as a ceRNA to increase Atf4 protein levels and osteoblast function.BglapHOTAIR mice,but not Prx1-HOTAIR mice,showed alleviation of bone loss induced by unloading.This study reveals the importance of temporal and spatial regulation of HOTAIR in BMSC osteogenic differentiation and bone formation,which provides new insights into precise regulation as a target for bone loss.

Monolayer Graphitic Carbon Nitride as Metal-Free Catalyst with Enhanced Performance in Photo- and Electro-Catalysis

The exfoliation of bulk graphitic carbon nitride(g-C_(3)N_(4))into monolayer has been intensively studied to induce maximum sur-face area for fundamental studies,but ended in failure to realize chemi-cally and physically well-defined monolayer of g-C_(3)N_(4)mostly due to the difficulty in reducing the layer thickness down to an atomic level.It has,therefore,remained as a challenging issue in two-dimensional(2D)chemistry and physics communities.In this study,an“atomic monolayer of g-C_(3)N_(4)with perfect two-dimensional limit”was successfully prepared by the chemically well-defined two-step routes.The atomically resolved monolayer of g-C_(3)N_(4)was also confirmed by spectroscopic and micro-scopic analyses.In addition,the experimental Cs-HRTEM image was collected,for the first time,which was in excellent agreement with the theoretically simulated;the evidence of monolayer of g-C_(3)N_(4)in the perfect 2D limit becomes now clear from the HRTEM image of orderly hexagonal symmetry with a cavity formed by encirclement of three adjacent heptazine units.Compared to bulk g-C_(3)N_(4),the present g-C_(3)N_(4)monolayer showed significantly higher photocatalytic gen-eration of H2O2 and H2,and electrocatalytic oxygen reduction reaction.In addition,its photocatalytic efficiency for H2O2 production was found to be the best for any known g-C_(3)N_(4)nanomaterials,underscoring the remarkable advantage of monolayer formation in optimizing the catalyst performance of g-C_(3)N_(4).

The mechanosensitive lncRNA Neat1 promotes osteoblast function through paraspeckle-dependent Smurf1 mRNA retention

Mechanical stimulation plays an important role in bone remodeling. Exercise-induced mechanical loading enhances bone strength,whereas mechanical unloading leads to bone loss. Increasing evidence has demonstrated that long noncoding RNAs(lnc RNAs) play key roles in diverse biological, physiological and pathological contexts. However, the roles of lnc RNAs in mechanotransduction and their relationships with bone formation remain unknown. In this study, we screened mechanosensing lnc RNAs in osteoblasts and identified Neat1, the most clearly decreased lnc RNA under simulated microgravity. Of note, not only Neat1 expression but also the specific paraspeckle structure formed by Neat1 was sensitive to different mechanical stimulations, which were closely associated with osteoblast function. Paraspeckles exhibited small punctate aggregates under simulated microgravity and elongated prolate or larger irregular structures under mechanical loading. Neat1 knockout mice displayed disrupted bone formation, impaired bone structure and strength, and reduced bone mass. Neat1 deficiency in osteoblasts reduced the response of osteoblasts to mechanical stimulation. In vivo, Neat1 knockout in mice weakened the bone phenotypes in response to mechanical loading and hindlimb unloading stimulation. Mechanistically, paraspeckles promoted nuclear retention of E3 ubiquitin ligase Smurf1 m RNA and downregulation of their translation, thus inhibiting ubiquitination-mediated degradation of the osteoblast master transcription factor Runx2, a Smurf1 target. Our study revealed that Neat1 plays an essential role in osteoblast function under mechanical stimulation, which provides a paradigm for the function of the lnc RNA-assembled structure in response to mechanical stimulation and offers a therapeutic strategy for long-term spaceflight-or bedrest-induced bone loss and age-related osteoporosis.

分析化学实验多元化教学模式改革与实践

创新实验教学模式是解决当前高校理工科类实验教学困境的重要途径。总结分析化学实验教学面临的难题,依托基础性、设计型和科研型实验为教学内容,建立以微视频在线课前预习、翻转课堂的课中学习和软件联用处理实验结果的新型实验教学方法。这种多元化教学模式能有效提高学生的学习主动性和创新能力。以基础性实验和研究型实验为案例,阐述多元化教学模式的具体应用,为理工科类实验教学改革提供研究依据。

Hydrogen Inhalation Ameliorates Oxidative Stress and Glucose Metabolism Disorder in the Brain of Hindlimb Unloading Rats

Many studies have shown that spaceflight causes oxidative stress and induces brain disorder in astronauts,but the counter measurements are lacking.Increasing evidence demonstrated that hydrogen can act as a therapeutic antioxidant.In this study,rats were treated with or without about 5%hydrogen under hindlimb unloading or normal conditions for 28 d.We assessed rat’s brain function by open-field test,step-down passive avoidance test,the neurotransmitter’s level detected by liquid chromatography with tandem mass spectrometry,and Nissl and hematoxylin-eosin staining analysis.We also assessed the oxidative damage by changes of malondialdehyde level,the ratio of reduced glutathione to oxidized glutathione,and superoxide dismutase and catalase activity.Glucose metabolism disorder was disclosed through glucose metabolomic analysis.The underlying mechanism of the effects of hydrogen was analyzed by mRNA sequencing and detecting mRNA and protein levels.Our data showed that hindlimb unloading caused oxidative damage and glucose metabolism disorder in brain tissues and decreased brain function in rats.Hydrogen inhalation reduced oxidative damage,ameliorated glucose metabolism disorder,and alleviated the dysfunction of rat brain function.Peroxisome-proliferator-activated receptor gamma coactivator 1αand brain-derived neurotrophic factor,the key regulators of glucose metabolism and brain function,were obviously affected.This research confirms the protective effect of hydrogen inhalation on declining brain function under hindlimb unloading conditions and discloses the underlying mechanism,which provides a potential strategy for astronauts’health.

Bidirectional Light-Driven Ion Transport through Porphyrin Metal–Organic Framework-Based van der Waals Heterostructures via pH-Induced Band Alignment Inversion

Heterogeneous two-dimensional layered membranes reconstructed fromnatural or synthetic van derWaals materials enable novel ion transport mechanisms by coupling with the chemical and optoelectronic properties of the layered constituents.Here,we report a light-driven and pH-dependent bidirectional ion transport phenomenon through porphyrin metal–organic framework(PMOF)and transition metal dichalcogenides-based multilayer van der Waals heterostructures with sub-nanometer ionic channels.