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Growth plate cartilage has limited self-repair ability, leading to poor bone bridge formation post-injury and ultimately limb growth defects in children. The current corrective surgeries are highly invasive, and outcomes can be unpredictable. Following growth plate injury, the direct loss of extracellular matrix (ECM) coupled with further ECM depletion due to the inhibitory effects of inflammation on the cartilage matrix protein greatly hinder chondrocyte regeneration. We designed an exosome (Exo) derived from bone marrow mesenchymal stem cells (BMSCs) loaded ECM-mimic hydrogel to promote cartilage repair by directly supplementing ECM and anti-inflammatory properties. Aldehyde-functionalized chondroitin sulfate (OCS) was introduced into gelatin methacryloyl (GM) to form GMOCS hydrogel. Our results uncovered that GMOCS hydrogel could significantly promote the synthesis of ECM due to the doping of OCS. In addition, the GMOCS-Exos hydrogel could further promote the anabolism of chondrocytes by inhibiting inflammation and ultimately promote growth plate injury repair through ECM remodeling., Graphical abstract Image 1, Highlights • Chondrocytes are difficult to regenerate after growth plate injury due to extensive degradation of ECM (extracellular matrix). • GMOCS-Exos can promote the synthesis of ECM by directly supplementing ECM and anti-inflammatory properties. • GMOCS-Exos can boost cartilage regeneration after growth plate injury and reduce bone bridge formation.

Electrochemical production of hydrogen peroxide (H2 O2 ) through two-electron (2 e- ) oxygen reduction reaction (ORR) is an on-site and clean route. Oxygen-doped carbon materials with high ORR activity and H2 O2 selectivity have been considered as the promising catalysts, however, there is still a lack of direct experimental evidence to identify true active sites at the complex carbon surface. Herein, we propose a chemical titration strategy to decipher the oxygen-doped carbon nanosheet (OCNS900 ) catalyst for 2 e- ORR. The OCNS900 exhibits outstanding 2 e- ORR performances with onset potential of 0.825 V (vs. RHE), mass activity of 14.5 A g-1 at 0.75 V (vs. RHE) and H2 O2 production rate of 770 mmol g-1 h-1 in flow cell, surpassing most reported carbon catalysts. Through selective chemical titration of C=O, C-OH, and COOH groups, we found that C=O species contributed to the most electrocatalytic activity and were the most active sites for 2 e- ORR, which were corroborated by theoretical calculations.

Platinum is generally known as the most effective electrocatalyst for hydrogen evolution reaction because it can greatly lower the overpotential and accelerate the reaction kinetics, while its commercial potential always suffers from scarcity, high cost, low utilization, and poor durability particularly in acidic electrolytes. We herein demonstrate a facile method to improve the hydrogen evolution performance of Pt-based electrocatalysts by simply decorating the-state-of-the-art and commercially available Pt/C with hydrophobic protic ([DBU][NTf2]) or aprotic ([BMIm][NTf2]) ionic liquid. The current densities of [BMIm]@Pt/C and [DBU-H]@Pt/C with 10% ionic liquid at an overpotential of 40 mV are 2.81 and 4.15 times, respectively, higher than that of the pristine Pt/C. More importantly, ionic liquid-decoration significantly improves the long-term stability of Pt nanoparticles. After 8 h of chronoamperometric measurements, [DBU-H]@Pt/C and [BMIm]@Pt/C can still retain 83.7% and 78.3% of their original activity, respectively, which is much higher than that of the pristine Pt/C (24.4%). The improved performance of Pt/C decorated with ionic liquid is considered to arise from the improved proton conductivity (particularly for protic ionic liquid) and hydrophobic microenvironment created by the supported ionic liquid phase. The presence of ionic liquid layer not only de-coordinates H+ from hydronium ions nearby the Pt nanoparticles, but it also protects Pt nanoparticles from dissolution in the acidic media.

Chronic stress-induced brain injury (CSBI) is the organic damage of brain tissue caused by long-term psychological and environmental stress. However, there is no effective drug for the treatment of CSBI. The present study aimed to investigate possible mechanisms of CSBI and to explore related therapeutic targets. A rat model of CSBI was established by combining chronic restraint and cold water immersion. Our CSBI model was validated via Nissl staining, Western blotting, and behavioral tests. RNA sequencing (RNA-seq) was used to identify differentially expressed genes (DEGs) within brain tissue during CSBI. Both Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to determine signaling pathways associated with CSBI-induced DEGs. Agonists/antagonists were used to validate the pharmacodynamics of potential therapeutic targets. A combination of chronic restraint and cold water immersion successfully induced a rat model of CSBI, as indicated by various markers of brain injury and cell apoptosis that were verified via Nissl staining, Western blotting, and behavioral tests. RNA-seq analysis identified 1,131 DEGs in CSBI rats. Of these DEGs, 553 genes were up-regulated and 778 genes were down-regulated. GO and KEGG pathway analyses revealed that significant DEGs were predominantly related to membrane-bound ion channels, among which the potassium channel function was found to be significantly affected. Pharmacological experiments revealed that retigabine, a voltage-gated potassium channel opener, demonstrated a protective effect in CSBI rats. Taken together, our findings suggest that potassium channel function is disrupted in CSBI, and that potassium channel regulators may function as anti-CSBI drugs.

Background aims Stem cell transplantation is a potential treatment for intractable spinal cord injury (SCI), and allogeneic human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate because of the advantages of immune privilege, paracrine effect, immunomodulatory function, convenient collection procedure and little ethical concern, and there is an urgent need to develop a safe and effective protocol regarding their clinical application. Methods A prospective, single-center, single-arm study in which subjects received four subarachnoid transplantations of hUC-MSCs (1 × 106 cells/kg) monthly and were seen in follow-up four times (1, 3, 6 and 12 months after final administration) was conducted. At each scheduled time point, safety and efficacy indicators were collected and analyzed accordingly. Adverse events (AEs) were used as a safety indicator. American Spinal Injury Association (ASIA) and SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) total scores at the fourth follow-up were determined as primary efficacy outcomes, whereas these two indicators at the remaining time points as well as scores of pinprick, light touch, motor and sphincter, muscle spasticity and spasm, autonomic system, bladder and bowel functions, residual urine volume (RUV) and magnetic resonance imaging (MRI) were secondary efficacy outcomes. Subgroup analysis of primary efficacy indicators was also performed. Results Safety and efficacy assessments were performed on 102 and 41 subjects, respectively. Mild AEs involving fever (14.1%), headache (4.2%), transient increase in muscle tension (1.6%) and dizziness (1.3%) were observed following hUC-MSC transplantation and resolved thoroughly after conservative treatments. There was no serious AE. ASIA and IANR-SCIFRS total scores revealed statistical increases when compared with the baselines at different time points during the study, mainly reflected in the improvement of pinprick, light touch, motor and sphincter scores. Moreover, subjects showed a continuous and remarkable decrease in muscle spasticity. Regarding muscle spasm, autonomic system, bladder and bowel functions, RUV and MRI, data/imaging at final follow-up showed significant improvements compared with those at first collection. Subgroup analysis found that hUC-MSC transplantation improved neurological functions regardless of injury characteristics, including level, severity and chronicity. Conclusions The authors’ present protocol demonstrates that intrathecal administration of' allogeneic hUC-MSCs at a dose of 106 cells/kg once a month for 4 months is safe and effective and leads to significant improvement in neurological dysfunction and recovery of quality of life.

Electrochemical CO

Highly efficient electrocatalysts towards hydrogen evolution reaction (HER) with large current density at all-pH values are critical for the sustainable hydrogen production. Herein, we report a free-standing HER electrode, phosphorous-doped molybdenum nitride nanoparticles embedded in 3-dimentional carbon nanosheet matrix (P-Mo2N-CNS) fabricated via one-step carbonization and in-situ formation. The as-prepared catalyst shows free-standing architecture with interconnected porous microstructure. P-doped Mo2N nanoparticles with an average diameter of 4.4 nm are well embedded in the 3-dimentional vertical carbon nanosheets matrix. Remarkable electrocatalytic HER performance is observed in alkaline, neutral and acidic media at large current densities. The overpotential of P-Mo2N-CNS to drive a current density of 100 mA cm−2 in 0.5 M H2SO4 and 1.0 M PBS is only 181 and 221 mV, respectively. In particular, the current density reaches up to 1000 mA cm−2 at a low overpotential of 256 mV in 1.0 M KOH, much better than that of the commercial Pt/C catalyst. Density functional theory calculations suggest the optimized H sorption kinetics on Mo2N after P doping, elucidating the superior activity.

Ruthenium (Ru)-based catalysts, with considerable performance and desirable cost, are becoming highly interesting candidates to replace platinum (Pt) in the alkaline hydrogen evolution reaction (HER). The hydrogen binding at Ru sites (Ru-H) is an important factor limiting the HER activity. Herein, density functional theory (DFT) simulations show that the essence of Ru-H binding energy is the strong interaction between the 4 d z 2 orbital of Ru and the 1s orbital of H. The charge transfer between Ru sites and substrates (Co and Ni) causes the appropriate downward shift of the 4 d z 2 -band center of Ru, which results in a Gibbs free energy of 0.022 eV for H* in the RuCo system, much lower than the 0.133 eV in the pure Ru system. This theoretical prediction has been experimentally confirmed using RuCo alloy-nanosheets (RuCo ANSs). They were prepared via a fast co-precipitation method followed with a mild electrochemical reduction. Structure characterizations reveal that the Ru atoms are embedded into the Co substrate as isolated active sites with a planar symmetric and Z-direction asymmetric coordination structure, obtaining an optimal 4 d z 2 modulated electronic structure. Hydrogen sensor and temperature program desorption (TPD) tests demonstrate the enhanced Ru-H interactions in RuCo ANSs compared to those in pure Ru nanoparticles. As a result, the RuCo ANSs reach an ultra-low overpotential of 10 mV at 10 mA cm-2 and a Tafel slope of 20.6 mV dec-1 in 1 M KOH, outperforming that of the commercial Pt/C. This holistic work provides a new insight to promote alkaline HER by optimizing the metal-H binding energy of active sites.

Electrocatalytic hydrogen evolution reaction (HER) in alkaline media is a promising electrochemical energy conversion strategy. Ruthenium (Ru) is an efficient catalyst with a desirable cost for HER, however, the sluggish H2O dissociation process, due to the low H2O adsorption on its surface, currently hampers the performances of this catalyst in alkaline HER. Herein, we demonstrate that the H2O adsorption improves significantly by the construction of Ru–O–Mo sites. We prepared Ru/MoO2 catalysts with Ru–O–Mo sites through a facile thermal treatment process and assessed the creation of Ru–O–Mo interfaces by transmission electron microscope (TEM) and extended X-ray absorption fine structure (EXAFS). By using Fourier-transform infrared spectroscopy (FTIR) and H2O adsorption tests, we proved Ru–O–Mo sites have tenfold stronger H2O adsorption ability than that of Ru catalyst. The catalysts with Ru–O–Mo sites exhibited a state-of-the-art overpotential of 16 mV at 10 mA cm–2 in 1 M KOH electrolyte, demonstrating a threefold reduction than the previous bests of Ru (59 mV) and commercial Pt (31 mV) catalysts. We proved the stability of these performances over 40 h without decline. These results could open a new path for designing efficient and stable catalysts.

Atomically dispersed transition metal sites have been extensively studied for CO

Long noncoding RNA (lncRNAs) UCA1 has been known to be critical for the chondrogenic differentiation of marrow mesenchymal stem cells (MSCs). In this study, we explore the effects and mechanisms of UCA1 on the promotion of chondrogenesis of MSCs. During the processes of chondrogenic differentiation of MSCs, UCA1, miRNA-145-5p or miRNA-124-3p was overexpressed into MSCs. UCA1 substantially improved chondrogenesis of MSCs. Furthermore, UCA1 obviously down-regulated the expression of miRNA-145-5p and miRNA-124-3p, which attenuated the chondrogenic differentiation of MSCs. In addition, UCA1 significantly stimulated TGF-β pathway member SMAD5 and SMAD4, which is targeted by miRNA-145-5p and miRNA-124-3p. Collectively, these outcomes suggest that UCA1 enhances chondrogenic differentiation of MSCs via the miRNA-145-5p/SMAD5 and miRNA-124-3p/SMAD4 axis.

Background: Surgical treatment of cervical vertigo has been rarely reported. This is the first retrospective study to evaluate the clinical outcomes of percutaneous disc decompression with coblation nucleoplasty (PDCN) for treatment of cervical vertigo. Objectives: To assess the clinical outcomes of patients with cervical vertigo who failed to improve with conservative care and who were subsequently treated with PDCN. Study Design: This study used a retrospective design. Setting: The research was conducted within an interventional vertigo management and spine practice. Methods: Seventy-four consecutive patients with cervical vertigo underwent PDCN and were followed for at least one year. Outcome measures included the dizziness intensity Visual Analog Scale (VAS), dizziness frequency, the Dizziness Handicap Inventory (DHI), and neck pain intensity. Clinical efficacy was assessed by rating scale and the modified MacNab evaluation criteria. Surgical complications during the operation and follow-up were also recorded. Results: The vertigo VAS score, frequency of dizziness, DHI, and neck pain intensity were all decreased significantly from evaluation before surgery to one week after surgery and to the last follow-up, giving a mean effective rate of 94.6% one week after surgery and 90.6% at the last follow-up. Good to excellent results were attained in 85.1% of these patients one week after PDCN and in 75.7% of the sufferers at the last follow-up (P < 0.001). There were 5 patients with transient adverse effects (6.25%) reported within the first month after surgery; they all recovered after conservative treatment. No neurological complications were found and no patient went on to spinal fusion surgery thereafter. Limitations: The rate of follow-up was 70% and a placebo effect cannot be excluded. There is no gold standard for the diagnosis and treatment of cervical vertigo so far. Conclusion: The clinical outcomes of PDCN for cervical vertigo were satisfactory in both the early and late postoperative period. PDCN is an effective, low-complication, minimally invasive procedure used to treat cervical vertigo. Further prospective randomized controlled trials are essential to verify this conclusion. Key words: Cervical vertigo, percutaneous disc decompression, coblation nucleoplasty, longterm outcome, dizziness intensity, dizziness frequency, dizziness handicap inventory, clinical efficacy, surgical complication, retrospective study

Osteoporosis is a disease where increased bone weakness increases the risk of a broken bone. Until a broken bone occurs, there are typically no symptoms. Osteoporosis affects more than 75 million people in the United States, Europe and Japan. The diagnosis of osteoporosis is primarily determined by measuring bone mineral density using dual-energy X-ray absorptiometry, but for men under 50 years of age, premenopausal women should not be made on the basis of densitometric criteria alone. Bone biomarkers are a useful tool in detecting osteoporotic. A two-step dual-label time-resolved fluorescence immunoassay (TRFIA) was developed for the simultaneous detection of serum C-terminal telopeptide (β-CTX) and amino-terminal propeptide (P1NP) of Type I procollagen in a single run. The performance of this assay was first evaluated using clinical serum samples, and then compared with commercialized kits. The sensitivity of this assay for β-CTX was 1 ng/L (dynamic range, 0-1000 ng/L), and the sensitivity for P1NP detection was 1 μg/L (dynamic range, 1-1000 μg/L). High correlation coefficients (R) were obtained between the present dual-label TRFIA and commercially available kits (R = 0.99 for β-CTX and P1NP). The present dual-label TRFIA has high sensitivity, specificity and accuracy in clinical sample analysis. It is a good alternative to the single-label diagnostic methods.

Objectives: In order to research the erucamide effect on Stress-induced rats liver injury and potential mechanism of the protect effect.Methods: Stress-induced liver injury in SD rats was used as an in vivo model. Adult female SD rats were differentiated into three groups: Normal group, SLI(Stress-induced liver injury)-group and [SLI+Erucamide (95.4uM/Kg)]-treated group. In addition, the transcriptomes from 9 liver tissues were sequenced using an Illumina sequencing platform, screened the differentially expressed genes and related cell signal transduction pathways. Gene expression was measured by RT-qPCR. Furthermore, observe the pathological changes of rats liver tissues by HE staining , and levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by microplate method. Human LO2 cells was used for in vitro model, the cells in the logarithmic growth phase were differentiated into normal group, corticosterone groups, erucamide, and glycine intervention groups. Corticosterone (300uM) was used to induce LO2 cell damage in vitro. And using tetrazolium (MTT) colorimetric method to determine and calculate cells viability. Hoechst 33342 staining was used to observe the morphology of hepatocyte apoptosis.Result: This study showed that erucamide has a significant effect on Stress-induced liver injury in rats, which is proved by HE staining test and ALT / AST detection experiment (pConclusions: In this research, erucamide inhibits the cleavage of glycine to anti-stress liver injury in rats.

Conductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, conductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell-derived exosomes (BMSC-exos) have shown immunomodulatory and tissue regeneration effects, therefore, we developed neural tissue-like conductive hydrogels loaded with BMSC-exos for the synergistic treatment of SCI. These exos-loaded conductive hydrogels modulated microglial M2 polarization via the NF-κB pathway, and synergistically enhanced neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increased axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exos combined conductive hydrogels significantly decreased the number of CD68-positive microglia, enhanced local neurogenesis, and promoted axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of conductive hydrogels and BMSC-exos is a promising therapeutic strategy for SCI repair.

The hemodialysis therapy is the primary treatment for the end-stage renal disease (ESRD) patients to extend their lives. To reduce the pathogenic infection during hemodialysis treatment, mussel-inspired polydopamine (PDA) was self-polymerized onto poly(ether sulfone) (PES) membranes to immobilize copper ions, because PDA coating could firmly adhere to the PES membranes and immobilize antimicrobial metal ions with its functional groups. The immobilized copper ions through PDA can penetrate deeply into the inner surface of the pores of PES membrane. Water permeability test further indicates PDA coating can obviously enhance the hydrophilicity of PES membranes. And copper ion immobilized PES membranes showed effective antibacterial activity with a relative safe release amount of copper ions (below 1 ppm). Furthermore, hemolysis test results revealed that PDA-assisted antibacterial PES membranes can relieve red blood cells damage compared to the pure PES membranes. To sum up, PES hemodialysis membranes obtained the antibacterial ability by the PDA-assisted copper ion immobilization, which can reduce the abuse of antibiotics and is beneficial to the patient suffering from kidney disease.

To improve the osteointegration property of biomedical titanium, nano-architectured electroactive coating was synthesized through the electrochemical polymerization of dopamine and pyrrole. The highly binding affinity of Ca2+ to the catechol moiety of doped dopamine enabled efficient interaction between polypyrrole/polydopamine nanowires and mineral ions. The results indicate that the PPy/PDA nanowires preserved its efficient electro-activity and accelerated the hydroxyapatite deposition in a simulated body fluid. The PPy/PDA nanowires coating could be applied to promote the osteointegration of titanium implant., Graphical abstract Image 1, Highlights • Nanowires were constructed through electrochemical polymerization of pyrrole and dapamine • The PPy/PDA nanowires possessed wonderful electroactivity. • The PPy/PDA nanowires could promote Hydroxyapatite formation.

Induced pluripotent stem cells (iPSCs) possess the potential to differentiate into neural lineage cells. Matrix metalloproteinase 2 (MMP2), an endopeptidase in the extracellular matrix, has been shown to protect neural cells from injury. However, the mechanisms and effects of MMP2 on neural differentiation of iPSCs remain poorly understood. Here, we demonstrated a role for MMP2 in the differentiation of iPSCs to neurons via the AKT pathway. Treatment of iPSCs with MMP2 promoted their proliferation and differentiation into neural stem cells (NSCs), and then into neurons. The transcript and protein expression of Nestin and microtubule-associated protein 2 (MAP2) increased. Moreover, MMP2 markedly induced the expression of phospho-AKT (pAKT) during these differentiation stages. Consistently, silencing MMP2 using siRNA attenuated the expression of Nestin, MAP2 and pAKT, compared with the control group. In addition, the increasing levels of Nestin, MAP2 and pAKT in the MMP2 group were declined by pretreatment with the phosphoinositide 3-kinase (PI3K)/AKT inhibitor, LY294002. Furthermore, the study detected that TrkA and TrkB were perhaps the potential receptors for these effects of MMP2 on neural differentiation through PI3K/AKT signaling pathway. Taken together, these results suggest that MMP2 induces the differentiation of iPSCs into neurons by regulating the AKT signaling pathway.

The disease diagnosis by detecting single microRNAs (miRNAs) can produce high false positive rate. Herein, a novel fluorescence biosensor method for one-step simultaneous detection of multiple miRNAs was proposed by using single-stranded DNA (ssDNA) functionalized double quantum dots (QDs) and black hole quencher (BHQ)-decorated magnetic nanobeads (MNs). MNs were linked with two black hole quenchers (BHQ1 and BHQ3) via a complementary DNA (cDNA). The ssDNA/cDNA hybridization contributed to the fluorescence quenching of double QDs due to the fluorescence resonance energy transfer (FRET) between double QDs and BHQ. In the presence of target miRNA-33 (miR-33) and miRNA-125b (miR-125b), the ssDNA1 and ssDNA2 were respectively hybridized with miR-33 and miR-125b to form more stable duplexes. Thus, the double QDs were released into supernatant after the magnetic separation, leading to the fluorescence signals recovery at 537 nm and 647 nm. A wide linear range (0.5 nM–320 nM for miR-33 and 0.1 nM–250 nM for miR-125b) and low limits of detection (0.09 nM for miR-33 and 0.02 nM for miR-125b) were achieved. Moreover, our approach has been demonstrated to simultaneously detect miR-33 and miR-125b in cell extracts. With advantages of high sensitivity, strong specificity, low background and low cost, the strategies show great potentials for the detection of various targets in bioanalysis and disease diagnosis.

The critical effects that impair diabetic wound healing are characterized by poor vascularization and severe peripheral neuropathy. Current management strategies for diabetic wound healing are unsatisfactory, due to the paucity of neurovascular regeneration at the wound site. Importantly, conductivity in skin tissue is reported to be essential for modulating myriad biological processes especially vascular and nerve regeneration. Herein, an extracellular matrix (ECM)-based conductive dressing is synthesized from an interpenetrating polymer network hydrogel composed of gelatin methacryloyl, oxidized chondroitin sulfate (OCS), and OCS-polypyrrole conductive nanoparticles that can promote diabetic wound repairing by enhancing local neurovascular regeneration. The conductive hydrogels combine the advantageous features of water-swollen hydrogels with conductive polymers (CPs) to provide tissue-matching electrical conductivity and mechanical properties for neurovascular regeneration. In vitro and in vivo studies show that the conductive hydrogel can promote neurovascular regeneration by increasing intracellular Ca2+ concentration, which subsequently promotes phosphorylation of proteins in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways. Furthermore, the conductive hydrogel stimulates full-thickness diabetic wound repair on day 14 by promoting local neurovascular regeneration and collagen deposition. These findings corroborate that the ECM-based conductive interpenetrating network hydrogel dressing significantly promotes wound repairing due to its neurovascular regeneration properties, suggesting that they are suitable candidates for diabetic wound repair.

Electrochemical carbon dioxide (CO2) reduction reaction (CO2RR) to obtain C2/multi-carbon fuels is an appealing technology to reduce carbon emission and store intermittent renewable electricity. The C–C coupling process, as the most critical step for generating C2/multi-carbon fuels, strongly depends on the concentration of *CO intermediates around the active sites. In this work, we prepared porous copper nanospheres (P-Cu) that greatly improved the C–C coupling process by enriching *CO intermediates in the pore structure. The specific pore features of P-Cu were characterized in detail by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nitrogen adsorption/desorption tests. Obviously, the P-Cu exhibits higher specific surface area and richer pore structure than the control sample compact copper nanosphere (C-Cu). The CO gas sensor and temperature programmed desorption (TPD) tests prove that the P-Cu has better CO adsorption and enrichment capacity than C-Cu due to the rich pore structure. As a result, P-Cu exhibited a high C2 selectivity with a Faradaic efficiency (FEC2) of 57.22% at −1.3 V (vs. RHE), which is about 2.5-fold than the C-Cu (FEC2 of 22.71%). This work provides an effective strategy to improve the activity and selectivity of C2 products in CO2RR by optimizing the adsorption/enrichment property of intermediates.

Construction of functional porous titanium scaffold is drawing ever growing attention, due to its effectiveness in solving the mechanical mismatch between titanium implant and bone tissue. However, the poor water permeability as well as the problem in achieving uniform surface modification inside scaffold hinders the further biomedical application of porous titanium scaffold. In this study, large-scale functional TiO2 nanostructures (nanonetwork, nanoplate and nanowire) were constructed on three-dimensional porous titanium scaffolds surface via an effective hydrothermal treatment method. These nanostructures increase the hydrophilicity of the titanium scaffold surface, facilitating the cell culture medium to penetrate into the inner pore of the scaffold. Zeta potential analyses indicate that the surface electrical properties depend on the nanostructure, with nanowire exhibiting the lowest potential at pH 7.4. The influence of the nano-functionalized scaffold on protein adsorption and cell adhesion was examined. The results indicate that the nano-functionalized surface could modulate protein adsorption and bone marrow derived mesenchymal stem cells (BMSCs) adhesion, with the nanowire functionalized porous scaffold homogeneously promoting protein adsorption and BMSCs adhesion. Our research will facilitate future research on the development of novel functional porous scaffold.

Mineralization plays a crucial role in the formation and remodeling of bone and charge has a positive influence on the mineralization by manipulating apatite deposition. In this paper, micropatterned piezoelectric K0.5Na0.5NbO3 (MPK) was constructed via laser-irradiation induced micro-zonal phase transition to manipulate set-selective apatite deposition. Two types of piezoelectric micro-zones on polarized MPK showed different charge densities, namely, higher charge density zone (H-zone) and lower charge density zone (L-zone). The micro-zonal piezoelectric difference on negatively polarized MPK (N-MPK) was ascertained by scanning Kelvin probe force microscopy (SKPM). With the manipulation of spatial charge, apatite selectively deposited on H-zone rather than L-zone, forming stripped zonal distribution. The furry platelet morphology of apatite was observed by scanning electron microscopy (SEM). Energy-dispersive spectroscopy (EDS) mapping observation indicated selective distribution of Ca and P elements in apatite. Phase composition of deposited apatite also can be regulated effectively via X-ray diffraction (XRD), which confirmed the existence of hydroxyapatite phase. Meanwhile, the apatite was further identified as carbonated hydroxyapatite by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). The feasible and convenient way of manipulating apatite deposition selectively with spatial charge realized by micro-zonal piezoelectric materials will inspire future development in biomimetic materials designation for biomedical applications.

Study design A prospective randomized controlled study. Objective To clarify whether percutaneous transforaminal endoscopic discectomy (PTED) has better clinical outcomes and less surgical trauma compared with microendoscopic discectomy (MED). Summary of background data Two kinds of minimally invasive spine surgeries, PTED and MED, are now widely used for the treatment of lumbar disc herniation (LDH). It is still a controversial issue to choose the proper surgical approach. Methods In this single-center, open-label, randomized controlled trial, patients were included if they had persistent signs and symptoms of radiculopathy with corresponding imaging-confirmed LDH, and were randomly allocated to PTED or MED group. The primary outcome was the score of Oswestry Disability Index (ODI) and the secondary outcomes included the score of Medical Outcomes Study 36-Item Short-Form Health Survey bodily pain and physical function scales, European Quality of Life-5 Dimensions, and Visual Analogue Scales for back pain and leg pain. Results A total of 250 participants were randomly assigned to two treatment groups, 241 of that received the specific surgical procedure. Two hundred twenty-two patients (92.1%) have completed the 2-year follow-up. Both the primary and secondary outcomes did not differ significantly between the two treatment groups at each prespecified follow-up time (P > 0.05). For PTED, the postoperative improvement of ODI score in the median herniation subgroup was less compared with paramedian subgroup. For MED, less improvement of ODI score was found in far-lateral herniation subgroup compared with paramedian subgroup. Total complication rate over the course of 2 year was 13.44% in PTED group and 15.57% in MED group (P = 0.639). Ten cases (8.40%) in PTED group and five cases (4.10%) in MED group suffered from residue/recurrence of herniation, for which reoperation was required. Conclusion Over the 2-year follow-up period, PTED did not show superior clinical outcomes and did not appear to be safer procedure for patients with LDH compared with MED. PTED had inferior results for median disc herniation, whereas MED did not appear to be the best option for far-lateral disc herniation. Level of evidence 2.

Background: It is unclear whether surgery or conservative treatment is more suitable for elderly patients with type II and type III odontoid fractures. We performed this meta-analysis to compare the efficacy of surgical and conservative treatments for type II and type III odontoid fractures. Methods: A literature search was performed in PubMed, Embase, Web of Science, and Cochrane Library in January 2017. Only articles comparing surgery with conservative treatment in elderly patients with type II and type III odontoid fractures were selected. After 2 authors independently assessed the retrieved studies, 18 articles were included in this meta-analysis, and the primary endpoints were the nonunion rate and mortality rate. The secondary outcomes were patient satisfaction, complications, and the length of the hospital stay. The quality of the included studies was evaluated using the modified Newcastle–Ottawa scale. Sensitivity analyses were performed for high-quality studies, and the publication bias was evaluated using a funnel plot. Results: Lower nonunion (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.18–0.40, P

OBJECTIVE: To analyze the medium and long-term effectiveness of microendoscope-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for lumbar degenerative diseases in comparison with conventional tubular retractor-assisted MIS-TLIF. METHODS: Between November 2008 and March 2013, 53 patients with single segment lumbar degenerative diseases were enrolled. According to the different working channel performed, 28 patients were treated by microendoscope-assisted MIS-TLIF (observation group), while the remaining cases received conventional tubular retractor-assisted MIS-TLIF via Wiltse approach (control group). Preoperative baseline data, including age, gender, body mass index, disease etiology, operated level, the ration for requiring bilateral canal decompression, and preoperative visual analogue scale (VAS) socre of low back pain and leg pain, Japanese Orthopedic Association (JOA) score, Oswestry disability index (ODI) score, showed no significant difference between the two groups (P>0.05). The operation time, intraoperative blood loss, intraoperative fluoroscopy time, postoperative analgesic drug dose, postoperation in-bed time, and perioperative complication incidence were recorded respectively and compared between the two groups. Radiographic evaluation of interbody fusion was performed based on Bridwell grading system at 2 years after operation. VAS scores of low back pain and leg pain, JOA score, and ODI score were assessed before operation, at 2 years after operation, and at last follow-up respectively. Surgical outcome satisfaction was assessed by modified MacNab criteria at last follow-up. RESULTS: When compared with those in control group, both intraoperative blood loss and postoperative analgesic drug dose were significantly decreased in observation group (P0.05). At last follow-up, the results of patients’ satisfaction with surgery evaluated by modified MacNab criteria, and the excellent and good rates of the observation group and the control group were 96.4% and 92.0%, respectively, showing no significant difference (χ(2)=0.485, P=0.486). CONCLUSION: The medium and long-term effectiveness of microendoscope-assisted MIS-TLIF are similar to those of conventional tubular retractor-assisted MIS-TLIF for lumbar degenerative diseases. The former operation has the additional advantages in terms of more clear surgical site visually, less intraoperative blood loss, and reduced postoperative analgesic dose, all of which seem more feasible to clinical teaching.

OBJECTIVE: To investigate the changes in the expression of voltage-gated potassium channel subunit KCNA2 in the dorsal root ganglion (DRG) neurons of rats with osteoarthritis (OA) pain induced by sodium monoiodoacetate and explore the mechanism. METHODS: A total of 156 adult male Sprague-Dawley rats were randomly divided into blank control group, saline group and intra-articular monoiodoacetate injection-induced OA group. The paw withdrawal mechanical threshold (PWMT) was measured before and at 1, 2, 4, and 6 weeks after monoiodoacetate injection. At 4 weeks after the injection, the pathological changes in the knee joints were analyzed using HE staining and Safranin O-Fast Green staining, and the expression of activating transcription factor 3 (ATF-3) and inducible nitric oxide synthase (iNOS) in the DRG neurons were detected by immunofluorescence staining. The expression of Kcna2 mRNA in the DRG neurons was detected by RT-qPCR at 1, 2, 4 and 6 weeks after the injection. The expression of KCNA2 in the DRG was measured by Western blotting, and the methylation level of Kcna2 promoter region was measured by MSPCR at 4 weeks after the injection. RESULTS: The PWMT of the rats in OA group was significantly decreased at 2, 4, and 6 weeks after the injection as compared with the baseline (P < 0.05 or P < 0.001) as well as the control group (P < 0.05 or P < 0.001). Four weeks after the intra-articular injection, fractures and defects on the surface of the articular cartilage, bone hyperplasia, and blurred tidal line were observed in the rats in OA group, but no obvious pathological changes were detected in the control or saline groups. Compared with those in the control group, the expressions of ATF-3 and iNOS were significantly increased (P < 0.01) at 4 weeks after injection; the expression of Kcna2 mRNA at 2, 4 and 6 weeks and the expression of KCNA2 protein at 4 weeks were all significantly decreased (P < 0.05 or P < 0.01), and the methylation level of Kcna2 gene was significantly increased at 4 weeks after the injection in OA group (P < 0.01). CONCLUSION: The expression of KCNA2 is decreased in the DRG neurons of rats with OA pain likely as a result of enhanced methylation of Kcna2 promoter region.

Neural stem cell (NSC) transplantation exerts a therapeutic effect on spinal cord injury (SCI) but is limited to an unregulated differentiation pattern by which NSCs preferentially differentiate into astrocytes, with relatively few neurons. It is well established that the increased NSC-derived astrocytes exhibit aberrant axonal sprouting associated with allodynia-like symptoms of the forepaws. Some strategies have been used to overcome this issue, such as regulation of major pathways, ex vivo gene transfer, and genetic overexpression. However, lack of efficiency, viral vector safety issues and the risk of tumorigenesis have hindered the clinical application of these treatments. Here, we show that astrocytic differentiation of NSCs in vitro and in vivo can be inhibited by encapsulation of cells in a three-dimensional chondroitin sulfate methacrylate (CSMA) hydrogel. When CSMA hydrogels were used to transplant NSCs, the combinatory implant promoted functional recovery and attenuated the hypersensitivity responses of the forepaws. Further analysis showed that transplantation of NSCs within CSMA hydrogels reduced injured cavity areas and promoted neurogenesis rather than fibroglial formation after graft implantation. Furthermore, the treatment prevented allodynia-related CGRP/GAP43-positive nociception due to fibers sprouting into inappropriate lamina regions. Taken together, these findings show that CSMA/NSCs combined transplantation helps prevent adverse side effects of NSCs treatment and promotes recovery of SCI.

Curzerene is a sesquiterpene and component used in oriental medicine. It was originally isolated from the traditional Chinese herbal medicine Curcuma rhizomes. In this study, anticancer activity of curzerene was examined in both in vitro and in vivo models. The result of the MTT assay showed that curzerene exhibited antiproliferative effects in SPC-A1 human lung adenocarcinoma cells in a time-dependent and dose-dependent manner. The anticancer IC50s were 403.8, 154.8, and 47.0 µM for 24, 48, and 72 hours, respectively. The flow cytometry analysis indicated curzerene arrested the cells in the G2/M cell cycle and promoted or induced apoptosis of SPC-A1 cells. The percentage of cells arrested in the G2/M phase increased from 9.26 % in the control group cells to 17.57 % in the cells treated with the highest dose (100 µM) of curzerene. Western blot and RT-PCR analysis demonstrated that curzerene induced the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Tumor growth was significantly inhibited in SPC-A1 cell-bearing nude mice by using curzerene (135 mg/kg daily), meanwhile, curzerene did not significantly affect body mass and the organs of the mice, which may indicate that curzerene has limited toxicity and side effects in vivo. In conclusion, curzerene could inhibit the proliferation of SPC-A1 human lung adenocarcinoma cells line in both in vitro and in vivo models. Focusing on its relationship with GSTA1, curzerene could induce the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Curzerene might be used as an anti-lung adenocarcinoma drug candidate compound for further development.

In this work, we designed and synthesized N-(2-[18F]-flouroptopionyl)-l-arginine ([18F]FPARG), which was an analogue of l-arginine for tumor positron emission tomography (PET) imaging. Semi-automated radiosynthesis of [18F]FPARG was performed from the reaction of l-arginine with 4-nitropheyl-2-[18F]flouropropionate ([18F]NFP) by multi-step procedure on the modified PET-MF-2V-IT-1 synthesizer. The uncorrected radiochemical yield of [18F]FPARG was 15 ± 3 % (n = 10) with more than 98 % radiochemical purity. The small-animal PET/CT fused imaging showed that liver and urinary bladder were the primary excretion route of this tracer.

The development of both H2–O2 proton exchange membrane fuel cells (PEMFCs) and Zn-air batteries are challenged by high-efficiency air cathodes with a high oxygen reduction reaction (ORR) electrocatalytic-activity. The increase of density and accessibility of active sites are widely accepted effective approach to boost the oxygen reduction reaction. In this work, we develop a template-free g-C3N4-assisted pyrolysis strategy to transform ZIF-8 polyhedrons to hierarchically open-porous carbon networks incorporated exclusive Fe–Nx active sites. Due to the integration of high specific surface area, highly open porous architecture with meso/micro-pores, and high-density Fe-Nx active species, the electro-catalysis performance of optimal catalysts exceed commercial Pt/C in alkaline solution, and is comparable to that of commercial Pt/C in acidic solution, which is one of the best recently reported carbon-based electrocatalysts. Impressively, when it is used as an air cathode catalyst, it achieves a high power density of 481 mW·cm−2 in acidic H2–O2 proton exchange membrane fuel cell (PEMFC) and an excellent performance in the alkaline Zn–air battery (a high power density of 121 mW·cm−2).

Mimicking soft tissue mechanical properties and the high conductivity required for electrical transmission in the native spinal cord is critical in nerve tissue regeneration scaffold designs. However, fabricating scaffolds of high conductivity, tissue-like mechanical properties, and excellent biocompatibility simultaneously remains a great challenge. Here, a soft, highly conductive, biocompatible conducting polymer hydrogel (CPH) based on a plant-derived polyphenol, tannic acid (TA), cross-linking and doping conducting polypyrrole (PPy) chains is developed to explore its therapeutic efficacy after a spinal cord injury (SCI). The developed hydrogels exhibit an excellent electronic conductivity (0.05-0.18 S/cm) and appropriate mechanical properties (0.3-2.2 kPa), which can be achieved by controlling TA concentration. In vitro, a CPH with a higher conductivity accelerated the differentiation of neural stem cells (NSCs) into neurons while suppressing the development of astrocytes. In vivo, with relatively high conductivity, the CPH can activate endogenous NSC neurogenesis in the lesion area, resulting in significant recovery of locomotor function. Overall, our findings evidence that the CPHs without being combined with any other therapeutic agents have stimulated tissue repair following an SCI and thus have important implications for future biomaterial designs for SCI therapy.