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PurposeTo determine the effects of EV-A71 (Enterovirus A71) infection on ocular surface and its mechanism.MethodsAG6 mice aged two to three weeks were randomly divided into control and EV-A71 infected groups. Slit-lamp observation, fluorescein staining, and phenol red thread test were used to assess symptoms of ocular surface at 4 dpi (days post infection). The pathological changes of cornea and lacrimal gland were observed by H&E staining, PAS staining, TUNEL assay, IHC staining and qRT-PCR. Corneas and lacrimal glands from mice were obtained and processed for RNA sequencing analysis. Newly diagnosed HFMD patients caused by EV-A71 were recruited and ensured they met the inclusion criteria. Ocular surface parameters (TMH and NIKBUT) were measured using the OCULUS Keratograph 5M. Tear samples were taken to examine Cxcl1 and IL-6 levels through the ELISA method.ResultsMice studies revealed that EV-A71 infection caused tear film instability, decreased tear secretions, decreased in lacrimal gland size, and distinct goblet cell loss. It also resulted in increased large vacuoles within acinar cells and structural damage in lacrimal gland. Apart from minor damage to the epidermis, there was no obvious inflammatory changes or apoptosis in the cornea. However, there were significant inflammatory injury and apoptosis in the lacrimal gland. RNA-seq analysis showed IL-17 and NF-κB signaling pathways were activated in the lacrimal glands of mice infected with EV-A71. In HFMD patients, the THM was in a low range and NITBUT was significantly shorter than the control group by Oculus Keratograph 5M. ELISA assay showed a higher tear Cxcl1 and IL-6 level in them.ConclusionEV-A71 infection affected lacrimal gland structure and function and induced dry eye-like symptoms.

Osteoporosis is a common bone disease, characterized by a descent in bone mass due to the dysregulation of bone homeostasis. Although different studies have identified an association between osteoporosis and epigenetic alterations in osteogenic genes, the mechanisms of osteoporosis remain unclear. N6-methyladenosine (m6A) modification is a methylated adenosine nucleotide, which regulates the translocation, exporting, translation, and decay of RNA. FTO is the first identified m6A demethylase, which eliminates m6A modifications from RNAs. Variation in FTO disturbs m6A methylation in RNAs to regulate cell proliferation, differentiation, and apoptosis. Besides, FTO as an obesity-associated gene, also affects osteogenesis by regulating adipogenesis. Pharmacological inhibition of FTO markedly altered bone mass, bone mineral density and the distribution of adipose tissue. Small molecules which modulate FTO function are potentially novel remedies to the treatment of osteoporosis by adjusting the m6A levels. This article reviews the roles of m6A demethylase FTO in regulating bone metabolism and osteoporosis.

Ferric acetylacetonate/covalent organic framework (Fe(acac)3/COF) composite was synthesized by interfacial polymerization method at room temperature. The crystal structure, morphology and porosity property of the composite were characterized by X-ray diffraction, scanning electron microscope, transmission electron microscope and nitrogen adsorption. The interaction between Fe(acac)3 and COF was investigated by Fourier transform infrared spectra and X-ray photoelectron spectroscopy. The Fe(acac)3/COF composite was used as a photocatalyst for the oxidation of benzyl alcohol under mild conditions. It exhibits high activity and selectivity for the reaction, of which the mechanism was investigated by determining its photoelectric properties. The Fe(acac)3/COF catalyst developed in this work has application potential in other photocatalytic reactions.

Objective To assess the efficacy and safety of dual ultrasound-guided (DUG) totally implantable venous access port (TIVAP) implantation (namely, using ultrasound-guided percutaneous puncture with transesophageal echocardiography-guided catheterization) via the right internal jugular vein (IJV) in pediatric patients with cancer.Methods Fifty-five children with cancer requiring chemotherapy underwent DUG-TIVAP implantation via the right IJV. Clinical data were recorded, including the procedure success rate, first attempt success rate, and perioperative and postoperative complications.Results All 55 cases were successfully operated on. The first puncture success rate was 100%. The operation time was 22–41 min, with a mean time of 30.8±5.5 min. The mean TIVAP implantation time was 253±145 days (range 42–520 days). There were no perioperative complications. The postoperative complication rate was 5.4% (3/55), including skin infections around the port in one case, catheter-related infection in one case, and fibrin sheath formation in one case. The ports were all preserved after anti-infection or thrombolytic therapy. No unplanned port withdrawal was recorded in this study.Conclusions DUG-TIVAP implantation is a technique with a high success rate and a low complication rate; therefore, it provides an alternative for children with cancer. Further randomized controlled studies are needed to confirm the efficacy and safety of DUG-TIVAP via the right IJV in children.

IntroductionThis study was designed to investigate the effect of running exercise on improving bone health in aging mice and explore the role of the SIRT1 in regulating autophagy and osteogenic differentiation of Bone marrow Mesenchymal Stem Cells (BMSCs).MethodsTwelve-month-old male C57BL/6J mice were used in this study as the aging model and were assigned to treadmill running exercise for eight weeks. Non-exercise male C57BL/6J mice of the same old were used as aging control and five-month-old mice were used as young controls. BMSCs were isolated from mice and subjected to mechanical stretching stimulation in vitro.ResultsThe results showed that aging mice had lower bone mass, bone mineral density (BMD), and autophagy than young mice, while running exercise improved BMD and bone mass as well as upregulated autophagy in bone cells. Mechanical loading increased osteogenic differentiation and autophagy in BMSCs, and knockdown of SIRT1 in BMSCs demonstrated that SIRT1-regulated autophagy involved the mechanical loading activation of osteogenic differentiation.ConclusionTaken together, this study revealed that exercise improved bone health during aging by activating bone formation, which can be attributed to osteogenic differentiation of BMSCs through the activation of SIRT1-mediated autophagy. The mechanisms underlying this effect may involve mechanical loading.

Abstract The brain structure and language skills of children are understood to be in a phase of rapid development and are especially represented by key phonological‐semantic expressions that actively develop with age. In the present study, resting‐state functional magnetic resonance imaging data from 85 healthy children were retrospectively analyzed. Correlations of the phonological processing and speeded naming of specific brain regions of interest with age were assessed using the fractional amplitude of low‐frequency fluctuations (fALFF), degree centrality (DC), regional homogeneity (ReHo), and chain mediation effect analysis. Our results suggest that the developmental stages of children's posterior cingulate gyrus (PCC) and right inferior frontal gyrus (IFG) mediate language development in children. Additionally, the functional similarity of the bilateral IFG triangular part was noted during development as was the stronger activation and higher local and whole‐brain connectivity of the left IFG triangular part. Moreover, the PCC displayed stronger activation and higher local connectivity in the same period. Our data suggest that the development of the PCC and right IFG and the similarity of bilateral IFG function are important imaging markers of phonological processing and speeded naming in children and that the PCC and IFG show a more comprehensive development with age.

UiO-66-NH2, an important metal–organic framework, is usually synthesized by solvothermal method and the particle size is generally larger than 200 nm, which limits its catalytic applications in chemical reactions. It is very meaningful to produce UiO-66-NH2 nanoparticles with ultra-small size, but remains challenging. Herein, we synthesized UiO-66-NH2 nanoparticles in size of 8–15 nm that are immobilized on g-C3N4 nanosheets. Compared with the UiO-66-NH2 synthesized by the traditional solvothermal method (> 200 nm), the ultra-small UiO-66-NH2 nanoparticles immobilized on g-C3N4 have more unsaturated coordination positions and increased Lewis acidity. Owing to these combined advantages, the ultra-small UiO-66-NH2 nanoparticles exhibit greatly improved catalytic activity for Meerwein–Ponndorf–Verley reaction than larger UiO-66-NH2 particles.

PurposeExercise therapy and key regulators of bone quality exert anti-hyperglycemic effects on type 2 diabetes mellitus (T2DM) mice. A number of programs have been reported to have an effect on bone disease in T2DM. Major unanswered questions concern the potential correlation of exercise with the improvement of bone quality in T2DM mice and how the nonlinear optical properties of bone are correlated with changes to its crystal structure.MethodsSubjects were randomly divided into six groups: 1) control (C) group, which was fed a normal diet (n = 8); 2) T2DM quiet group, which was given a high-fat diet and quiet (n = 8); 3) T2DM plus swimming (T2DM+S) group, which received T2DM and swim training (n = 8); 4) T2DM plus resistance exercise (T2DM+RE) group, which was given T2DM and resistance exercise (n = 8); 5) T2DM plus aerobic exercise (T2DM+AE) group, with T2DM and medium-intensity treadmill exercise (n = 8); and 6) T2DM plus high-intensity interval training (T2DM+HIIT), with T2DM and high-intensity variable-speed intervention (n = 8). The levels of runt-related transcription factor 2 (RUNX2), osterix (OSX), and alkaline phosphatase (ALP), as well as the bone microstructure and morphometry, were measured at the end of the 8-week exercise intervention.ResultsCompared with the C group, the bone microstructure indexes [bone mineral density (BMD), bone volume/tissue volume (BV/TV), cortical thickness (Ct.Th), and connectivity density (Conn.D)], the bone biomechanical properties (maximum load, fracture load, yield stress, and elastic modulus), and the osteogenic differentiation factors (RUNX2, OSX, and BMP2) of the T2DM group were significantly decreased (all p

Sclerostin domain-containing protein-1 (Sostdc1) is a member of the sclerostin family and encodes a secreted 28–32 kDa protein with a cystine knot-like domain and two N-linked glycosylation sites. Sostdc1 functions as an antagonist to bone morphogenetic protein (BMP), mediating BMP signaling. It also interacts with LRP6, mediating LRP6 and Wnt signaling, thus regulating cellular proliferation, differentiation, and programmed cell death. Sostdc1 plays various roles in the skin, intestines, brain, lungs, kidneys, and vasculature. Deletion of Sostdc1 gene in mice resulted in supernumerary teeth and improved the loss of renal function in Alport syndrome. In the skeletal system, Sostdc1 is essential for bone metabolism, bone density maintenance, and fracture healing. Recently, Sostdc1 has been found to be closely related to the development and progression of multiple cancer types, including breast, renal, gastric, and thyroid cancers. This article summarises the role of Sostdc1 in skeletal biology and related cancers to provide a theoretical basis for the treatment of related diseases.

Fibrillin is the major constituent of extracellular microfibrils, which are distributed throughout connective tissues. Asprosin is derived from the C-terminal region of the FBN1 gene, which encodes profibrillin that undergoes cleavage by furin protein. In response to fasting with low dietary glucose, asprosin is released as a secreted factor from white adipose tissue, and is transported to the liver for the mediation of glucose release into the blood circulation. Through binding to OLFR734, an olfactory G-protein-coupled receptor in liver cells, asprosin induces a glucogenic effect to regulate glucose homeostasis. Bioinformatics analyses revealed that the FBN1 gene is abundantly expressed in human skeletal muscle-derived mesoangioblasts, osteoblast-like cells, and mesenchymal stem cells, indicating that the musculoskeletal system might play a role in the regulation of asprosin expression. Interestingly, recent studies suggest that asprosin is regulated by exercise. This timely review discusses the role of asprosin in metabolism, its receptor signalling, as well as the exercise regulation of asprosin. Collectively, asprosin may have a vital regulatory effect on the improvement of metabolic disorders such as diabetes mellitus and obesity via exercise.

Radioactive I2 (iodine) produced as a by-product of nuclear fission poses a risk to public health if released into the environment, and it is thus vital to develop materials that can capture I2 vapour. Materials designed for the capture and storage of I2 must have a high uptake capacity and be stable for long-term storage due the long half-life of 129I. UiO-66 is a highly stable and readily tuneable metal-organic framework (MOF) into which defect sites can be introduced. Here, a defective form of UiO-66 (UiO-66-FA) was synthesised and the presence of missing cluster moieties confirmed using confocal fluorescence microscopy and gas sorption measurements. The uptake of I2 vapour in UiO-66-FA was measured using thermal gravimetric analysis coupled mass spectrometry (TGA-MS) to be 2.25 g g−1, almost twice that (1.17 g g−1) of the pristine UiO-66. This study will inspire the design of new efficient I2 stores based upon MOFs incorporating structural defects.

Acrylate photoresists have gained considerable attention in recent years owing to their high resolution, high sensitivity, and versality. In this work, a series of thermally stable copolymers are synthesized by introducing an isobornyl group, and well characterized using Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectra (1H-NMR). The effects of polymerization conditions on the molecular weight and their further influence on lithography are explored. By analyzing the thermal properties, film-forming capabilities, and the patterning behavior of these copolymers, a direct correlation between lithography performance and polymerization conditions is established via the molecular weight. In addition, the baking temperature of lithography is also optimized by atomic force microscopy (AFM), after which a line resolution of 0.1 μm is observed under the exposure of a 248 nm UV light and electron beam. Notably, our synthesized photoresist displays dual-tone resist characteristics when different developers are applied, and the reaction mechanism of acid-catalyzed hydrolysis is finally proposed by comparing the structural changes before and after exposure.

Electrochemical reduction of carbon dioxide is a highly attractive strategy for the production of organic products of economic value. Here, the authors report the electrochemical reduction of carbon dioxide to formic acid over a copper-based metal–organic framework decorated electrode at low over-potential.

Osteoporosis is a prevalent bone disease of the aging population, which is characterized by a decrease in bone mass because of the imbalance of bone metabolism. Although the prevention and treatment of osteoporosis have been explored by different researchers, the mechanisms underlying osteoporosis are not clear exactly. N6 methyladenosine (m6A) is a methylated adenosine nucleotide, which functions through its interaction with the proteins called “writers,” “readers” and “erasers.” The epigenetic regulation of m6A has been demonstrated to affect mRNA processing, nuclear export, translation, and splicing. At the cellular level, m6A modification has been known to affect cell proliferation, differentiation, and apoptosis of bone-related cells, such as bone marrow mesenchymal stem cells (BMSC), osteoblasts, and osteoclasts by regulating the expression of ALP, Runx2, Osterix, VEGF, and other related genes. Furthermore, PTH/Pth1r, PI3K‐Akt, Wnt/β‐Catenin, and other signaling pathways, which play important roles in the regulation of bone homeostasis, are also regulated by m6A. Thus, m6A modification may provide a new approach for osteoporosis treatment. The key roles of m6A modification in the regulation of bone health and osteoporosis are reviewed here in this article.

Intramuscular fat (IMF) content is vital for pork quality, serving an important role in economic performance in pig industry. Non-coding RNAs, with mRNAs, are involved in IMF deposition; however, their functions and regulatory mechanisms in porcine IMF remain elusive. This study assessed the whole transcriptome expression profiles of the Longissimus dorsi muscle of pigs with high (H) and low (L) IMF content to identify genes implicated in porcine IMF adipogenesis and their regulatory functions. Hundreds of differentially expressed RNAs were found to be involved in fatty acid metabolic processes, lipid metabolism, and fat cell differentiation. Furthermore, combing co-differential expression analyses, we constructed competing endogenous RNAs (ceRNA) regulatory networks, showing crosstalk among 30 lncRNAs and 61 mRNAs through 20 miRNAs, five circRNAs and 11 mRNAs through four miRNAs, and potential IMF deposition-related ceRNA subnetworks. Functional lncRNAs and circRNAs (such as MSTRG.12440.1, ENSSSCT00000066779, novel_circ_011355, novel_circ_011355) were found to act as ceRNAs of important lipid metabolism-related mRNAs (LEP, IP6K1, FFAR4, CEBPA, etc.) by sponging functional miRNAs (such as ssc-miR-196a, ssc-miR-200b, ssc-miR10391, miR486-y). These findings provide potential regulators and molecular regulatory networks that can be utilized for research on IMF traits in pigs, which would aid in marker-assisted selection to improve pork quality.

Exercise training promotes physical and bone health, and is the first choice of non-drug strategies that help to improve the prognosis and complications of many chronic diseases. Irisin is a newly discovered peptide hormone that modulates energy metabolism and skeletal muscle mass. Here, we discuss the role of irisin in bone metabolism via exercise-induced mechanical forces regulation. In addition, the role of irisin in pathological bone loss and other chronic diseases is also reviewed. Notably, irisin appears to be a key determinant of bone mineral status and thus may serve as a novel biomarker for bone metabolism. Interestingly, the secretion of irisin appears to be mediated by different forms of exercise and pathological conditions such as diabetes, obesity, and inflammation. Understanding the mechanism by which irisin is regulated and how it regulates skeletal metabolism via osteoclast and osteoblast activities will be an important step toward applying new knowledge of irisin to the treatment and prevention of bone diseases such as osteolysis and other chronic disorders.

Incorporating mesopores and active sites into metal-organic framework materials has proven advantageous for their catalytic application, but remains challenging to achieve. Here the authors obtain mesoporous, defect-rich metal-organic frameworks through templated electrosynthesis using ionic liquids as both electrolyte and template.

While renewable CO2 conversion provides a means to remove and recycle waste emissions, there are few earth-abundant materials that are both efficient and active. Here, authors prepare N-doped carbon with atomic manganese as high-performance CO2 reduction electrocatalyst.

The effect of nitrogen fertilizer application on the quality of rice post-storage is not well understood. The eating and cooking quality (ECQ) of rice treated with 0 (CK, control), 160 (IN, insufficient nitrogen), 260 (AN, adequate nitrogen), and 420 (EN, excessive nitrogen) kg N/ha was analyzed over 12 months of storage. Results showed that the rate of nitrogen fertilizer application had no significant impact on the changes in taste value during storage. However, EN application significantly increased the hardness (p < 0.05), reduced the gumminess (p < 0.05), and delayed the decline in the viscosity of rice paste by two months after one-year storage, compared with other treatments. In conclusion, although EN application resulted in an inferior texture of rice, it delayed the quality change by two months during storage. It was demonstrated that a rational nitrogen application rate (0-260 kg N/ha) for rice cultivation is particularly important to obtain high ECQ; however, EN may be beneficial for the stability of the ECQ during storage.

In order to obtain the regularities of physicochemical properties of hydroxy protic ionic liquids (PILs) and broaden their potential application, a series of 2-hydroxyethylammonium sulfonate-based PILs were synthesized through proton transfer reaction and characterized by NMR and FT-IR and elemental analysis. Their phase transfer behavior (Tm) and initial decomposition point (Td) were characterized by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), respectively. Meanwhile, the regularities of density (ρ), viscosity (η) and electrical conductivity (σ) of synthesized PILs at different temperatures were measured. The results indicated that their physicochemical properties were tightly related with their structures and the interactions between cations and anions. In addition, the dissociation constants (pKa) of synthesized PILs were obtained by acid-base titration, which revealed that all synthesized PILs had pKa exceeding 7 and their cations were the crux of determining the pKa value. Moreover, several synthesized PILs with a low melting temperature also showed potential application in the deoxidation reaction of cyclohexanol, as they had conversion rates approximating 100% and the selectivity of cyclohexane or cyclohexene was about 80%.

Heart failure is a common, costly, and potentially fatal condition. The cardiac sarcoplasmic reticulum Ca-ATPase (SERCA2a) plays a critical role in the regulation of cardiac function. Previously, low SERCA2a expression was revealed in mice with heart failure. Epigallocatechin-3-gallate (EGCG) can function as an epigenetic regulator and has been reported to enhance cardiac function. However, the underlying epigenetic regulatory mechanism is still unclear. In this study, we investigated whether EGCG can up-regulate SERCA2a via histone acetylation and play role in preventing heart failure. For this, we generated a mouse model of heart failure by performing a minimally invasive transverse aortic constriction (TAC) operation and used this to test the effects of EGCG. The TAC+EGCG group showed nearly normal cardiac function compared to that in the SHAM group. The expression of SERCA2a was decreased at both the mRNA and protein levels in the TAC group but was enhanced in the TAC+EGCG group. Levels of AcH3 and AcH3K9 were determined to decrease near the promoter region of Atp2a2 (the gene encoding SERCA-2a) in the TAC group, but were elevated in the TAC+EGCG group. Meanwhile, HDAC1 activity and binding near the Atp2a2 promoter were increased in the TAC group but decreased with EGCG addition. Further, binding levels of GATA4 and Mef2c near the Atp2a2 promoter region were reduced in TAC hearts, which might have been caused by histone hypoacetylation; this was reversed by EGCG. Together, upregulation of SERCA2a via the modification of histone acetylation plays a role in EGCG-mediated prevention of pressure overload-induced heart failure, and this might represent a novel pharmacological target for the treatment of heart failure.

We have proposed a kind of memristive device based on the junctions employing Ti as the reactive electrodes. The role of electrically-derived redox of Ti in such memristive switching is shown. The structural and chemical evidence of the electrically-derived oxidation is presented by TEM and XPS experiment, respectively. Due to the redox of the top electrode Ti and the consequent drift of oxygen vacancies, the device shows two distinct resistance states under a sweeping voltage loading. ON state is controlled by tunneling process, while OFF state is controlled by Schottky emission conductive mechanism. The failure behaviors of such memristive junctions are also discussed. In the light of the redox principle, we demonstrate that the devices could be recovered by loading a long electrical reduction treatment.

Previously, we demonstrated that allopregnanolone (APα) promoted proliferation of rodent and human neural progenitor cells in vitro. Further, we demonstrated that APα promoted neurogenesis in the hippocampal subgranular zone (SGZ) and reversed learning and memory deficits in the male triple transgenic mouse model of Alzheimer's (3xTgAD). In the current study, we determined the efficacy of APα to promote the survival of newly generated neural cells while simultaneously reducing Alzheimer's disease (AD) pathology in the 3xTgAD male mouse model. Comparative analyses between three different APα treatment regimens indicated that APα administered 1/week for 6 months was maximally efficacious for simultaneous promotion of neurogenesis and survival of newly generated cells and reduction of AD pathology. We further investigated the efficacy of APα to impact Aβ burden. Treatment was initiated either prior to or post intraneuronal Aβ accumulation. Results indicated that APα administered 1/week for 6 months significantly increased survival of newly generated neurons and simultaneously reduced Aβ pathology with greatest efficacy in the pre-pathology treatment group. APα significantly reduced Aβ generation in hippocampus, cortex, and amygdala, which was paralleled by decreased expression of Aβ-binding-alcohol-dehydrogenase. In addition, APα significantly reduced microglia activation as indicated by reduced expression of OX42 while increasing CNPase, an oligodendrocyte myelin marker. Mechanistic analyses indicated that pre-pathology treatment with APα increased expression of liver-X-receptor, pregnane-X-receptor, and 3-hydroxy-3-methyl-glutaryl-CoA-reductase (HMG-CoA-R), three proteins that regulate cholesterol homeostasis and clearance from brain. Together these findings provide preclinical evidence for the optimal treatment regimen of APα to achieve efficacy as a disease modifying therapeutic to promote regeneration while simultaneously decreasing the pathology associated with Alzheimer's disease.