Search

Purpose. To determine how the shape of vertebral in thoracolumbar zoon may be associated with spine saggital balance and upper lumbar disc degeneration(ULDD). Methods. Assessed the imaging of 58 patients who underwent operation at The Tenth People’s Hospital of Shanghai. MRI, CT and plain radiographs of the lumbar spine were evaluated. Vertebral deformities on plain radiographs were identified by wedge-shaped vertebral (WSV, wedge-shaped angle>5). These deformities were assessed for association with saggital balance alignment and ULDD. Results. Cervical lordosis (CL), thoracic kyphosis (TK), and thoracolumbar kyphosis (TLK) in thoracolumbar wedge-shaped vertebral (TLWSV) group were significantly greater than none wedged-shaped vertebral (NWSV) group (p0.05), which might is related with the compensation mechanism of spine. Conclusion. This is the first study to examine WSV on plain radiographs of the lumbar spine for saggital balance alignment and ULDD. Patients with WSV in thoracolumbar regeion reported worsening spine saggital alignment and ULDD. This highlights the relationship between WSV and spine saggital alignment and suggests WSV may accelerate ULDD. Level of Evidence: 3

Background: Our study aimed to explore the prognostic factors of bladder cancer with bone metastasis (BCBM) and develop prediction models to predict the overall survival (OS) and cancer-specific survival (CSS) of BCBM patients. Methods: A total of 1438 patients with BCBM were obtained from the SEER database. Patients from 2010 to 2016 were randomly divided into training and validation datasets (7:3), while patients from 2017 were divided for external testing. Nomograms were established using prognostic factors identified through Cox regression analyses and validated internally and externally. The concordance index (C-index), calibration plots, and time-dependent receiver operating characteristic (ROC) curves were used to evaluate the discrimination and calibration of nomogram models, while decision curve analyses (DCA) and Kaplan-Meier (KM) curves were used to estimate the clinical applicability. Results: Marital status, tumor metastasis (brain, liver, and lung), primary site surgery, and chemotherapy were indicated as independent prognostic factors for OS and CSS. Calibration plots and the overall C-index showed a novel agreement between the observed and predicted outcomes. Nomograms revealed significant advantages in OS and CSS predictions. AUCs for internal and external validation were listed as follows: for OS, 3-month AUCs were 0.853 and 0.849; 6-month AUCs were 0.873 and 0.832; 12-month AUCs were 0.825 and 0.805; for CSS, 3-month AUCs were 0.849 and 0.847; 6-month AUCs were 0.870 and 0.824; 12-month AUCs were 0.815 and 0.797, respectively. DCA curves demonstrated good clinical benefit, and KM curves showed distinct stratification performance. Conclusion: The nomograms as web-based tools were proved to be accurate, efficient, and clinically beneficial, which might help in patient management and clinical decision-making for BCBM patients.

Objective The study introduced uniportal‐bichannel spinal endoscopic system (UBiSES) and explored the feasibility of applying UBiSES to conduct lumbar foraminoplasty in percutaneous endoscopic transforaminal discectomy (PETD). Methods This is a cohort study. 36 patients confirmed as L5/S1 lumbar disc herniation (LDH) in our hospital from March, 2019 to November, 2019 were enrolled. 36 patients were divided into two groups named the UBiSES group (n = 18, male: female = 8:10) and the TESSYS group (n = 18, male: female = 10:8). The average age of the UBiSES group and the TESSYS group were 40.94 ± 12.39 years old and 39.78 ± 13.02 years old respectively. PETD via uniportal‐bichannel foraminoplasty assisted by UBiSES was adopted on the UBiSES group while PETD via conventional foraminoplasty was performed on the TESSYS group. One experienced surgeon with more than 4000 cases of lumbar surgery performed PETD on all patients. The demographic data, the duration of working cannula placement (minutes), decompression time (minutes), radiation exposure time (seconds), complications, Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) scores and modified MacNab criteria were recorded and analyzed. The magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to evaluate the radiographic improvement. Results PETD via lumbar foraminoplasty was successfully performed in all cases. The follow‐up points were 3 months, 6 months, and 12 months. The average follow‐up period of all patients was 15.78 ± 2.29 months. There was no statistic difference in age (P = 0.81), sex (P = 0.51) and follow‐up (P = 0.14) between two groups. The duration of working cannula placement was 19.08 ± 2.30 min in the UBiSES group and 24.90 ± 4.71 min in the TESSYS group and there was significant difference between two groups (P, Lumbar foraminoplasty is a crucial and challenging step in PETD. In conventional TESSYS, surgeons could not get a direct view of the anatomic structure around the foramen during foraminoplasty with bone reamers or trephines, which is difficult to control the direction and may cause some unexpected complications including neural injury and bleeding. Also, the articular surface of facet joints is not in a sagittal plane or coronal plane, and oblique articular surface makes reamers and trephines easier deviated to ventral direction, which leads to unsatisfactory foraminoplasty. As an original designed technique, UBiSES allows operation with two surgical instruments simultaneously under full‐time and real‐time visualization in just one incision, which could be less invasive and more efficient. Uniportal‐bichannel foraminoplasty assisted by UBiSES could control the direction easier and get a satisfactory bone resect at the dorsal side of foramen with extensive view and space.

Gold nanoclusters (AuNCs) are a unique class of materials that exhibit visible luminescence. Amorphous calcium phosphate (ACP) is a widely used biomaterial for a variety of purposes, such as drug delivery, bone cementing, and implant coatings. In this study, a nanocomposite of AuNCs and ACP is prepared by biomimetic mineralization in a Dulbecco's modified Eagle's medium (DMEM). The strong interaction between AuNCs and Ca

Background Intradural disc herniation (IDH) is a rare type of disc degeneration that infrequently affects the upper lumbar spine. Pre- and intraoperative diagnosis and surgical management of IDH are challenging. The present case study provides insight into these aspects of upper lumbar IDH and discusses possible mechanisms. Case description A 63-year-old female with a history of chronic lower back and leg pain presented with an acute lumbar sprain that had occurred 1 month prior. The pain progressed and spread to the front of the left thigh, which affected her ability to lift her leg when ascending/descending stairs. Sagittal gadolinium-enhanced magnetic resonance imaging (MRI) revealed a disc protruding into the ventral dural sac showing a hawk-beak sign, and the posterior edge of the disc annulus and local posterior longitudinal ligament was broken. Total L2 laminectomy was performed, and the dorsal side of the dural sac was exposed and incised to enable exploration of the ventral side of the dura. We found two free fragments protruding into the inner wall of the dura through the left ventral dura mater defect. After carefully and completely removing the mass, we repaired the defect and performed internal fixation. Postoperative pathologic analysis confirmed that the mass was nucleus pulposus tissue from the degenerated disc. The patient's pain significantly improved after surgery, and she was able to walk normally at the 1-month follow-up. Conclusion Upper lumbar IDH is an extremely rare type of disc degeneration. An enhanced MRI scan can provide diagnostic evidence, but the final diagnosis requires surgical exploration of the path of herniation and pathologic examination of the mass lesion.

Objective The purpose of the present study was to discuss a new surgical strategy that combines percutaneous endoscopic transforaminal discectomy (PETD) with percutaneous endoscopic interlaminar discectomy (PEID) for L4/5 and L5/S1 two‐level disc herniation. Methods This was a retrospective study. A total of 19 patients with L4/5 and L5/S1 two‐level lumbar disc herniation (LDH) who underwent percutaneous endoscopic lumbar discectomy (PELD) in our hospital from January 2015 to June 2016 were retrospectively examined. The average age of these 19 patients was 42.21 ± 14.88 years old, including 12 men and 7 women. One experienced surgeon who had carried out more than 3000 lumbar surgeries performed PELD for these patients. During the PELD surgery, the transforaminal approach was adopted for L4/5 level disc herniation and the interlaminar approach was adopted for L5/S1 level disc herniation. The demographic data, operation time (min), fluoroscopy times, hospital stay (days), and complications were recorded and analyzed. The visual analogue scale (VAS), Oswestry disability index (ODI) scores, and the modified MacNab criteria were used to evaluate the surgical outcomes. MRI was conducted to evaluate the radiographic improvement. Results All patients underwent PELD via the transforaminal approach combined with the interlaminar approach successfully and achieved satisfactory efficacy. The follow‐up points were 3, 12, and 18 months. The average hospital stay (days) and the average follow up (months) were 3.32 ± 0.98 and 18.63 ± 3.84, respectively. The operation time and fluoroscopy times were 85.79 ± 12.90 min and 39.05 ± 4.59 times, respectively. The fluoroscopy times (frequency) for L4/5 and L5/S1 were 26.95 ± 6.41 and 12.11 ± 3.49 (t = 7.00, P, Neither PETD nor PEID is a good option for two‐level LDH. These approaches are associated with longer surgical time, massive radiation exposure, or unexpected complications. This retrospective study showed that PELD via the transforaminal approach combined with the interlaminar approach under epidural anesthesia can treat L4/5 and L5/S1 two‐level disc herniation safely and effectively.

The formation and metabolic balance of bone tissue is a controllable process of biomineralization, which is regulated by various cells, biomolecules, and ions. Enzyme molecules play an important role in this process, and alkaline phosphatase (ALP) is one of the most critical factors. In this study, inspired by the process of bone biomineralization, a biomimetic strategy is achieved for the preparation of mineralized ALP nanoparticles (MALPNs), by taking advantages of the unique reaction between ALP and calcium ions in Dulbecco's modified Eagle's medium. Benefiting from the mild biomineralization reaction, the MALPN system highly maintains the activity of ALP. Furthermore, the in vitro studies show that the MALPN system significantly enhances the proliferation of bone marrow mesenchymal stem cells and upregulates their osteogenic differentiation. When evaluated as synthetic graft materials for bone regeneration, the MALPN-incorporated gelatin methacryloyl graft shows excellent mechanical properties, a sustained release profile of ALP, and high biocompatibility and efficacy in guiding bone regeneration and vascularization for critical-sized rat calvarial defect. Moreover, we also demonstrate that the biomimetic mineralization strategy can be adopted for other proteins such as acid phosphatase, bovine serum albumin, fibrinogen, and gelatin, suggesting its universality for constructing mineralized protein-/enzyme-based bioactive materials for the application of tissue regeneration.

Diffraction patterns observed in surface plasmon resonance imaging (SPRI) microscopy measurements of single gold nanorods (AuNRs) exhibit a complex behavior at wavelengths near the longitudinal plasmonic resonance band. SPRI microscopy measurements at 814 nm from AuNRs in three samples with resonance extinction maxima at 670, 816, and 980 nm reveal a variety of diffraction patterns with central peaks that are either positive, negative, or biphasic. A unitless ratio parameter MR (-1 ≤ MR ≤ 1) is created to describe the distribution of diffraction patterns. A purely negative (MR = -1) central peak is observed for 30%, 57%, and 98% of the diffraction patterns in the 670, 816, and 980 nm samples, respectively. These results along with a theoretical modeling of the diffraction patterns with an anisotropic complex scattering coefficient suggests that this behavior only occurs for AuNRs when the laser wavelength used in SPRI experiments is shorter than the AuNR plasmonic resonance maxima, that is, in the anomalous dispersion region.

Refractory bone fracture, which is difficult to be treated, is a common clinical disease. Taking inspiration from the natural process of bone regeneration, we provide a biomimetic strategy to develop a new injectable biomaterial for repairing bone defects, which is mainly composed of platelets, fibrins, and biominerals. Biomineral nanoparticles (EACPNs) with an amorphous phase are prepared by an enzyme-catalyzed route and display a platelet-activating property. The composite hydrogel (EPH) of EACPNs, fibrins, and platelets is injectable, and has similar chemical properties to natural materials in bone regeneration. The dried EPH samples display a highly porous structure, which would be favorable for cell attachment and growth. The results from in vitro studies indicate that EPH has high biocompatibility and superior bioactivity in promoting the osteogenic differentiation of rat bone marrow stem cells (rBMSCs). Furthermore, the results from in vivo studies clearly indicate that EPH can induce the formation of new collagen and vessels in the defect area, thus leading to faster regeneration of bone defects at 2 weeks. Our study provides a strategy for designing new biomimetic materials, which may be favorable in the treatment of refractory bone fracture.

Intervertebral disc degeneration is a very common medical condition causing pain and disability, and it cannot be reversed by available treatment options. Here we report that targeting β-catenin, a pivotal factor associated with disc degeneration, ameliorates disc degeneration in a mouse model of disc injury. Degenerative changes in the disc in response to disc injury include decompression of nucleus pulposus (NP), replacement of notochordal cells in the NP by chondrocyte-like cells, and disorganization of annulus fibrosus (AF). Importantly, downregulation of β-catenin through intradiscal injection of CRISPR-Cas9-expressing adeno-associated virus significantly mitigated all these pathological changes, by preserving notochordal cells and attenuating chondro-osteogenesis in the NP, as well as maintaining the AF structure. Moreover, β-catenin loss-of-function decelerated the rapid induction of catabolic reactions in disc matrix and attenuated pain-related neural events during disc degeneration. Thus, our data demonstrate that targeting β-catenin in disc cells through CRISPR-Cas9 has multifaceted therapeutic effects on disc degeneration, and we suggest that β-catenin plays a fundamental role in the remodeling and degenerative processes of the disc. In addition, this study proposes that CRISPR-Cas9 is a useful tool for identifying new drug targets and developing therapeutic strategies for disc degeneration.

In this work, we describe the preparation and use of a thin metal film modified Indium Tin Oxide (ITO) electrode as a highly conductive, transparent, and electrocatalytically active electrode material for studying nanobubbles generated at the electrode/solution interface. Hydrogen and oxygen nanobubbles were generated from water electrolysis on the surface of a Au/Pd alloy modified ITO electrode. The formation of single H2 and O2 nanobubbles was imaged in real time during a potential scan using single-molecule fluorescence microscopy. Our results show that while O2 nanobubbles can be detected at an early stage in the oxygen evolution reaction (OER), the formation of H2 nanobubbles requires a significant overpotential. Our study shows that thin-film-coated ITO electrodes are simple to make and can be useful electrode substrates for (single molecule) spectroelectrochemistry research.

The glycemic indices (GI) of pea and chickpea are normally lower than 60, which are commonly considered as middle or low GI foods. Different processing conditions would influence proportions of rapidly digestible starch (RDS), slowly digestible starch (SDS), and resistant starch (RS) in the processed pea and chickpea. In general, high-temperature cooking followed by high-temperature drying (HCHD) largely kept total starch (68.58% and 61.99% of dry matter in pea and chickpea, respectively), increased RDS (29.89% and 33.40% of total starch in pea and chickpea, respectively) and RS proportions (25.78% and 17.08% of total starch in pea and chickpea, respectively) while the opposite effect in pea and chickpea was observed. Glycemic response of panelists after consuming HCHD pea or chickpea would cause a faster increase of incremental plasma glucose concentration within 30 min, followed by a rapid decrease to baseline compared with the pea or chickpea processed by low-temperature cooking followed by low-temperature drying (LCLD). The GI of HCHD pea and chickpea were 59.02 and 49.15, respectively, which were significantly higher than those processed by LCLD (pea: 32.63, chickpea: 31.91). Both in vitro and in vivo digestibility indicated that LCLD was more suitable to process pea and chickpea powder.

We report the observation of transient bipolar electrochemical coupling on freely moving 40 nm silver nanoparticles. The use of an asymmetric nanoelectrochemical environment at the nanopore orifice, for example, an acid inside the pipette and halide ions in the bulk, enabled us to observe unusually large current blockages of single Ag nanoparticles. We attribute these current blockages to the formation of H2 nanobubbles on the surface of Ag nanoparticles due to the coupled faradaic reactions, in which the reduction of protons and water is coupled to the oxidation of Ag and water under potentials higher than 1 V. The appearance of large current blockages was strongly dependent on the applied voltage and the choice of anions in the bulk solution. The correlation between large current blockages with the oxidation of Ag nanoparticles and their nanopore translocation was further supported by simultaneous fluorescence and electric recordings. This study demonstrates that transient bipolar electrochemistry can t...

The seek of bioactive materials for promoting bone regeneration is a challenging and long-term task. Functionalization with inorganic metal ions or drug molecules is considered effective strategies to improve the bioactivity of various existing biomaterials. Herein, amorphous calcium magnesium phosphate (ACMP) nanoparticles and simvastatin (SIM)-loaded ACMP (ACMP/SIM) nanocomposites were developed via a simple co-precipitation strategy. The physiochemical property of ACMP/SIM was explored using transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) and high-performance liquid chromatograph (HPLC), and the role of Mg2+ in the formation of ACMP/SIM was revealed using X-ray absorption near-edge structure (XANES). After that, the transformation process of ACMP/SIM in simulated body fluid (SBF) was also tracked to simulate and explore the in vivo mineralization performance of materials. We find that ACMP/SIM releases ions of Ca2+, Mg2+ and PO43−, when it is immersed in SBF at 37°C, and a phase transformation occurred during which the initially amorphous ACMP turns into self-assembled hydroxyapatite (HAP). Furthermore, ACMP/SIM displays high cytocompatibility and promotes the proliferation and osteogenic differentiation of MC3T3-E1 cells. For the in vivo studies, lamellar ACMP/SIM/Collagen scaffolds with aligned pore structures were prepared and used to repair a rat defect model in calvaria. ACMP/SIM/Collagen scaffolds show a positive effect in promoting the regeneration of calvaria defect after 12 weeks. The bioactive ACMP/SIM nanocomposites are promising as bone repair materials. Considering the facile preparation process and superior in vitro/vivo bioactivity, the as-prepared ACMP/SIM would be a potential candidate for bone related biomedical applications.

AlkB homolog 5 (ALKBH5) has been reported as a key m6A demethylase that is involved in development and diseases; however, the function of ALKBH5 in osteogenesis remains unknown. In this study, we report that ALKBH5 mRNA and protein expression were upregulated during osteoblast differentiation and that ALKBH5 knockdown suppressed osteoblast differentiation, mineralization, and the expression of osteogenic biomarkers. Conversely, ALKBH5 overexpression promoted osteogenesis. Moreover, the expression of wild-type ALKBH5, but not the m6A-modified active site mutant ALKBH5, could rescue ALKBH5 knockdown-induced osteogenesis inhibition. Furthermore, knockdown of ALKBH5 significantly impaired the mRNA stability of the transcription factor Runx2, which plays a key role in osteoblast differentiation. Taken together, our results suggest that ALKBH5 promotes osteogenesis through modulating Runx2 mRNA stability.

Additional file 2. Multivariate analysis

Additional file 1. WBR

ObjectivesOsteoarthritis (OA) is a painful and debilitating disease and it is associated with aberrant upregulation of multiple factors, including matrix metalloproteinase 13 (MMP13), interleukin-1β (IL-1β) and nerve growth factor (NGF). In this study, we aimed to use the CRISPR/Cas9 technology, a highly efficient gene-editing tool, to study whether the ablation of OA-associated genes has OA-modifying effects.MethodsWe performed intra-articular injection of adeno-associated virus, which expressed CRISPR/Cas9 components to target each of the genes encoding MMP13, IL-1β and NGF, in a surgically induced OA mouse model. We also tested triple ablations of NGF, MMP13 and IL-1β.ResultsLoss-of-function of NGF palliates pain but worsens joint damage in the surgically induced OA model. Ablation of MMP13 or IL-1β reduces the expression of cartilage-degrading enzymes and attenuates structural deterioration. Targeting both MMP13 and IL-1β significantly mitigates the adverse effects of NGF blockade on the joints.ConclusionsCRISPR-mediated ablation of NGF alleviates OA pain, and deletion of MMP13-1β or IL-1β attenuates structural damage in a post-traumatic OA model. Multiplex ablations of NGF, MMP13 and IL-1β provide benefits on both pain management and joint structure maintenance. Our results suggest that CRISPR-based gene editing is useful for the identification of promising drug targets and the development of feasible therapeutic strategies for OA treatment.

Photodynamic therapy is widely used in clinics and for anti-bacterial applications. The major challenge is the limited depth of tissue penetration of light and poor targetability. In this study, magnetite nanoparticles were used as a highly sensitive T2-weighted MR imaging contrast agents to target the tumor and mimic horseradish peroxidase (HRP), which could catalyze the decomposition of hydrogen peroxide to generate reactive oxygen species (ROS) to inhibit the tumor in vivo. In these experiments, MNPs were demonstrated to possess the enzyme-mimicking activity in different pH values, and the activity was dependent on the size of the MNPs: the smaller the size, the higher the activity. We demonstrated that MNPs showed highly efficient anti-bacterial (E. coli) activity in presence of H2O2. The E. coli inhibition ratio reached nearly 100% at optimal concentration. The anti-tumor activity was evaluated through HeLa cell viability under treatment with MNPs and H2O2. Consequently, the cell viability was significantly decreased and more than 80% of HeLa cells were dead after treatment with MNPs and H2O2 under different pH values. MR imaging was used to demonstrate the tumor targetability of 13 nm MNPs in vitro and in vivo. Consequently, the relaxivity of the 13 nm MNPs was determined to be r2 = 104 s-1 mM-1. The MR signal was much more negative and the intensity was significantly diminished with the increase of the concentration of 13 nm MNPs in vitro. The tumor signal was clearly visualized and a 3-fold decrease of the MR signal intensity of the tumor site of the mice was observed after 24 h-post treatment with the 13 nm MNPs. Finally, the tumor inhibition in vivo was investigated using 6 nm MNPs in BALB/c nude female mice bearing subcutaneously implanted HeLa cells on the right flank. The results show statistically significant efficacy in delaying tumor growth from day 6, and an approximately 99% tumor inhibition ratio was shown by the combination of MNPs and H2O2 after treatment for 17 days. By leveraging the passive targeting and MR imaging properties, we expect that the enzyme-mimicking MNPs could be used for cancer theranostics and may open up a new avenue for the treatment of epidermal infections.

Runx2 plays an essential role in embryonic disc tissue development in mice. However, the role of runt-related transcription factor 2 (Runx2) in postnatal disc tissue growth and development has not been defined. In the present studies, we generated Runx2 conditional knockout (KO) mice (Runx2(Agc1ER)), in which Runx2 was deleted in Aggrecan-expressing cells in disc tissue at postnatal 2-weeks of age. We then analyzed changes in disc tissue growth and development using histology and immunohistochemical methods in 3-month-old mice. We found that large vacuolated notochordal cells were accumulated in the nucleus pulposus (NP) in Runx2 KO mice. The growth plate cartilage tissue in the disc was thicker in Runx2 KO mice. We also found a significant upregulation of Indian hedgehog (Ihh) expression in the cells in NP cells and in annulus fibrosus cells of Runx2 KO mice. These results demonstrated that Runx2 may play an important role in postnatal disc tissue development through interacting with Ihh signaling.

We report the observation of electrocatalytic water oxidation during transient collision and oxidation of single-Ag nanoparticles (NPs) on a gold ultra-microelectrode (UME). Collision and oxidation of single-Ag NPs are studied under higher positive potentials (≥1 V versus Ag/AgCl electrode) on a gold UME than previously used. The use of higher potentials allows us to observe several unique features not seen at lower potentials (0.6–0.8 V), including a greatly increased collision frequency and the appearance of subcollision peaks with a long current tail. Moreover, the average charge transferred in a collision event is 3–5 times more than that estimated from a complete NP oxidation. Our results suggest that the enhanced charge transfer is due to coupled water oxidation catalyzed by Ag oxide transiently formed upon NP collision. A pH-dependence study was further performed to reveal a characteristic feature of water oxidation, and the formation of silver oxide was directly confirmed by single-NP fluorescence...

Summary The field of single-molecule electrochemistry has seen many exciting advances since Bard and Fan demonstrated the use of redox cycling. Recent development of nanoelectrodes and microfabricated nanogap devices has enabled reproducible measurements of single redox molecules. Fluorescence and Raman spectroscopy are increasingly used to probe individual heterogeneous electron-transfer events. The use of bipolar coupling may allow optical recording of single redox events for conventional redox species.

A dynamic partnership between optical imaging and electrochemistry has generated a myriad of new opportunities in which both fields are mutually beneficial for understanding the nanoscale electrochemical interfaces. An in-depth understanding of the heterogeneity of the interfaces is crucial for determining the performance of electrochemical devices, including energy-related systems. Based on classical optical microscopies, innovative methodologies and tools such as super resolution fluorescence microscopy, electrochemiluminescence microscopy, surface plasmon resonance microscopy, dark-field microscopy, and Raman microscopy have been developed to monitor the dynamic processes of electrochemical reactions occurring on certain nanoscale interfaces, owing to their sufficient spatial and temporal resolution, diverse spectroscopic principles, excellent sensitivity, and non-invasive nature. These microscopic techniques are uniquely suited for probing the nanoscale interfaces in an operando, in situ, or in a real-time manner. Correspondingly, state-of-the-art optical microscopies and imaging are overwhelmingly utilized in nanoscale interfaces research, for example in direct visualization of nanoscale heterogeneous electrocatalytic reactions at the individual nanoparticle/molecule scale, monitoring the interfacial phenomena inside batteries, and studying electrochemical process at single entity scale. This review surveys the basic methodologies, key challenges in the field, and recent applications/ achievements of these microscopes in studying nanoscale electrochemical interfaces for energy applications. Extension to emerging optical microscopies is further discussed to promote new discoveries. Moreover, present compilation highlights the advantages and disadvantages, emerging research opportunities, and concludes in the potential future directions in advancing this field.

In this Technical Note, we describe a method to fabricate nanopore-supported Pt nanoparticle electrodes and their use in bipolar electrochemistry. A Pt nanoparticle is deposited on the orifice of a solid-state nanopore inside a focused-ion beam (FIB) system. Complete blockage of the nanopore with Pt metal forms a closed bipolar nanoparticle electrode whose size and shape can be tunable in one simple step. Nanoparticle electrodes and their arrays can be prepared on different substrates such as the tip of a glass pipet, a double-barrel pipet, and a freestanding silicon nitride membrane. Steady-state voltammetry can be performed on such nanoparticle electrodes via bipolar electrochemistry. Moreover, an array of Pt nanoparticles can be used for fluorescence-enabled electrochemical microscopy. Future use of highly advanced FIB systems may allow nanoparticles of10 nm to be fabricated which may enable coupled electrochemical reactions of single redox molecules. Pipette-supported single particle electrodes may also find useful applications in high resolution imaging with nanoscale scanning electrochemical microscopy (SECM) and neurochemical analysis inside single cells.

In this work, we describe the preparation and use of a thin metal film modified Indium Tin Oxide (ITO) electrode as a highly conductive, transparent, and electrocatalytically active electrode material for studying nanobubbles generated at the electrode/solution interface. Hydrogen and oxygen nanobubbles were generated from water electrolysis on the surface of a Au/Pd alloy modified ITO electrode. The formation of single H

Here we report the direct observation and quantitative analysis of single redox events on a modified indium–tin oxide (ITO) electrode. The key in the observation of single redox events are the use of a fluorogenic redox species and the nanoconfinement and hindered redox diffusion inside 3-nm-diameter silica nanochannels. A simple electrochemical process was used to grow an ultrathin silica film (~100 nm) consisting of highly ordered parallel nanochannels exposing the electrode surface from the bottom. The electrode-supported 3-nm-diameter nanochannels temporally trap fluorescent resorufin molecules resulting in hindered molecular diffusion in the vicinity of the electrode surface. Adsorption, desorption, and heterogeneous redox events of individual resorufin molecules can be studied using total-internal reflection fluorescence (TIRF). The rate constants of adsorption and desorption processes of resorufin were characterized from single-molecule analysis to be (1.73 ± 0.08) × 10−4 cm·s−1 and 15.71 ± 0.76 s−1, respectively. The redox events of resorufin to the non-fluorescent dihydroresorufin were investigated by analyzing the change in surface population of single resorufin molecules with applied potential. The scan-rate-dependent molecular counting results (single-molecule fluorescence voltammetry) indicated a surface-controlled electrochemical kinetics of the resorufin reduction on the modified ITO electrode. This study demonstrates the great potential of mesoporous silica as a useful modification scheme for studying single redox events on a variety of transparent substrates such as ITO electrodes and gold or carbon film coated glass electrodes. The ability to electrochemically grow and transfer mesoporous silica films onto other substrates makes them an attractive material for future studies in spatial heterogeneity of electrocatalytic surfaces.

Beginners usually need increased punctures and dozens of fluoroscopy in learning transforamimal percutaneous endoscopic lumbar discectomy (tPELD). Navigator-assisted spinal surgery (NASS) is a novel technique that could induce a definite trajectory. The retrospective study aimed to investigate the impact of a definite trajectory on the learning curve of tPELD.A total of 120 patients with symptomatic lumbar disc herniation who received tPELD between 2012 and 2014. Patients receiving tPELD with NASS technique by one surgeon were regarded as group A, and those receiving conventional methods by another surgeon were regarded as group B. Each group was divided into three subgroups (case 1-20, case 21-40, case 41-60).The fluoroscopy times were 22.62 ± 3.80 in group A and 34.32 ± 4.78 in group B (P 0.001). The pre-operative location time was 3.56 ± 0.60 minutes in group A and 5.49 ± 1.48 minutes in group B (P 0.001). The puncture-channel time was 21.85 ± 4.31 minutes in group A and 34.20 ± 8.88 minutes in group B (P 0.001). The operation time was 84.62 ± 9.20 minutes in group A and 101.97 ± 14.92 minutes in group B (P 0.001), and the learning curve of tPELD in group A was steeper than that in group B. No significant differences were detected in patient-reported outcomes, hospital stay, patient satisfaction, and complication rate between the two groups (p 0.05).Definite trajectory significantly reduced the operation time, preoperative location time, puncture-channel time, and fluoroscopy times of tPELD by beginners, and thus reshaped the learning curve of tPELD and minimized the radiation exposure.

Disc degeneration is a common clinical condition in which damaged discs cause chronic pain; however, a laboratory diagnosis method for its detection is not available. As circulating miRNAs have potential as biomarkers, their application in disc degeneration has not been explored. Here, we prepared serum miRNAs from a mouse disc degeneration model and performed miRNA‐Seq and quantitative PCR to characterize disc degeneration–associated miRNAs. We identified three miRNAs, including miR‐26a‐5p, miR‐122‐5p and miR‐215‐5p, undergoing perturbation during the pathogenesis of disc degeneration. Specifically, the levels of miR‐26a‐5p in the serum demonstrated steady increases in the model of disc degeneration, compared with those in the pre‐injury samples of younger age or compared with normal controls of the same age but without disc degeneration, whereas the miRNAs miR‐122‐5p and miR‐215‐5p exhibited lower expression in post‐injury samples than in their counterparts without the surgery. Moreover, we found that miR‐26a‐5p targets Smad1 expression, and Smad1 negatively regulates Vegfa expression in disc cells, and thus, miR‐26a‐5p promotes disc degeneration. In summary, we established a method that consistently profiles circulating miRNAs and identified multiple miRNAs as promising biomarkers for disc degeneration, among which miR‐26a‐5p enhances VEGF expression during disc degeneration through targeting Smad1 signalling.

Background: Percutaneous transforaminal endoscopic discectomy (PTED) under local anesthesia (LA) is growing popular in recent years because of its safety, effectiveness and increased patient demands for minimally invasive procedures. To avoid neural injuries, local anesthesia that can keep the patient conscious is recommended. However, many patients complain about the severe pain during surgery. Epidural anesthesia (EA) is an alternative choice. We put forward an anesthetic method that combined preemptive analgesia (PA) and local anesthesia. Objectives: The study aimed to assess the effectiveness of 3 methods of anesthesia for PTED, LA, EA and PA. Study Design: A prospective study. Methods: Three groups of patients were treated with standard PTED under LA, PA or EA, respectively. The data collected for analysis were operative time, x-ray exposure time, postoperative bed time, visual analog scale (VAS), Oswestry Back Pain Disability Index (ODI), the global outcome based on the Macnab outcome criteria, satisfaction rate of anesthesia, and complications. Results: A total of 240 consecutive patients were enrolled in this study from January 2014 to December 2016. Among 3 groups, 1-week postoperatively VAS (back and leg) and ODI were improved compared with preoperative data, and the excellent/good rates were all above 90%. However, satisfaction rate of anesthesia showed significant differences among the 3 groups. PA and EA showed significantly better performance in pain management intraoperatively and 1 hour postoperatively. The operation time of group PA was the shortest and group EA was the longest. No severe neural injuries occurred in any of the 3 groups. Transient paresis of lower limbs occurred in all 3 groups and showed no significant differences. Decreased muscle strength of lower limbs postoperatively occurred in 2 patients in group EA. The incidence of nausea and vomiting postoperatively was significantly higher in group PA (6 cases, 7.50%). There were 3 cases of dysuria postoperatively in group EA (3.75%). Limitation: First, this is a single center study. Second, this study investigated the effects of anesthesia on perioperative period and the follow-up time was relatively short. Third, we choose morphine in group PA and there are other types of anesthetics which may be used in preemptive analgesia in further study. Conclusion: All 3 of these anesthetic methods are safe to avoid neural injuries. EA and PA showed better performance in pain management but had more anesthesia-related complications. Key words: Percutaneous transforaminal endoscopic discectomy (PTED), local anesthesia, epidural anesthesia, preemptive analgesia, morphine, ropivacaine, pain management, visual analog scale (VAS), Oswestry Back Pain Disability Index (ODI)

Nucleation and growth of hydrogen nanobubbles are key initial steps in electrochemical water splitting. These processes remain largely unexplored due to a lack of proper tools to probe the nanobubble’s interfacial structure with sufficient spatial and temporal resolution. We report the use of superresolution microscopy to image transient formation and growth of single hydrogen nanobubbles at the electrode/solution interface during electrocatalytic water splitting. We found hydrogen nanobubbles can be generated even at very early stages in water electrolysis, i.e., ∼500 mV before reaching its thermodynamic reduction potential. The ability to image single nanobubbles on an electrode enabled us to observe in real time the process of hydrogen spillover from ultrathin gold nanocatalysts supported on indium–tin oxide.

Objective In percutaneous endoscopic transforaminal discectomy (PETD), surgeons are exposed to intraoperative radiographic radiation over a long-term career, which may be correlated with high risk of iatrogenic radiation hazards. The purpose of this prospective cohort study was to assess the impact of concentric stereotactic technique on radiation exposure to surgeons in PETD. Methods Patients who underwent conventional PETD were regarded as group A, whereas those undergoing PETD with concentric stereotactic technique were considered as group B. The primary outcomes were cumulative radiation dose to the surgeon's eye, thyroid gland, and breast. Results A total of 34 patients were treated in group A and 30 patients were treated in group B. The cumulative radiation dose of the eye per operation was 0.017 (0.58/34) mSv in group A and 0.010 (0.31/30) mSv in group B, which meant a reduction of 41.18%. The cumulative radiation dose of the thyroid gland per operation was 0.018 (0.60/34) mSv in group A and 0.011 (0.33/30) mSv in group B, which meant a reduction of 38.89%. The cumulative radiation dose of the chest per operation was 0.039 (1.33/34) mSv in group A and 0.023 (0.70/30) mSv in group B, which meant a reduction of 41.03%. There were no significant differences in hospital stay, visual analog scale score of waist and leg pain, Oswestry Disability Index score, MacNab satisfaction, and complications between the 2 groups (P > 0.05). Conclusions The concentric stereotactic technique can effectively reduce radiation exposure to surgeons by about 40%.

Nanoelectrodes have key advantages compared to electrodes of conventional size and are the tool of choice for numerous applications in both fundamental electrochemistry research and bioelectrochemical analysis. This Minireview summarizes recent advances in the development, characterization, and use of nanoelectrodes in nanoscale electroanalytical chemistry. Methods of nanoelectrode preparation include laser-pulled glass-sealed metal nanoelectrodes, mass-produced nanoelectrodes, carbon nanotube based and carbon-filled nanopipettes, and tunneling nanoelectrodes. Several new topics of their recent application are covered, which include the use of nanoelectrodes for electrochemical imaging at ultrahigh spatial resolution, imaging with nanoelectrodes and nanopipettes, electrochemical analysis of single cells, single enzymes, and single nanoparticles, and the use of nanoelectrodes to understand single nanobubbles.

Co-self-assembled vesicular nanoparticles of two structurally comparable amphiphilic boron-dipyrromethene (BODIPY) dyes with dequenchable dual colour fluorescence were prepared for ratiometric imaging of live cells.

The electrochemical interface is an ultrathin interfacial region between the electrode surface and the electrolyte solution and is often characterized by numerous dynamic processes, such as solvation and desolvation, heterogeneous electron transfer, molecular adsorption and desorption, diffusion, and surface rearrangement. Many of these processes are driven and modulated by the presence of a large interfacial potential gradient. The study and better understanding of the electrochemical interface is important for designing better electrochemical systems where their applications may include batteries, fuel cells, electrocatalytic water splitting, corrosion protection, and electroplating. This, however, has proved to be a challenging analytical task due to the ultracompact and dynamic evolving nature of the electrochemical interface. Here, we describe the use of an electrochemical nanocell to image the dynamic collision and oxidation process of single silver nanoparticles at the surface of a platinum nanoelectrode. A nanocell is prepared by depositing a platinum nanoparticle at the tip of a quartz nanopipette forming a bipolar nanoelectrode. The compact size of the nanocell confines the motion of the silver nanoparticle in a 1-D space. The highly dynamic process of nanoparticle collision and oxidation is imaged by single-particle fluorescence microscopy. Our results demonstrate that silver nanoparticle collision and oxidation is highly dynamic and likely controlled by a strong electrostatic effect at the electrode/solution interface. We believe that the use of a platinum nanocell and single molecule/nanoparticle fluorescence microscopy can be extended to other systems to yield highly dynamic information about the electrochemical interface.

The spontaneous release of drug payloads in the whole body always results in the compromised drug bioavailability and ultimate therapeutic efficacy. To achieve enhanced therapeutic efficacy and reduced side effects, pH-responsive targeted drug delivery systems have been studied due to their enhanced tumor accumulation and controllable maximum drug release feature. The present study described a co-assembly constructed by a pH responsive molecule (i.e., malachite green carbinol base (MG)) and liposome for highly efficient doxorubicin (DOX) release in tumor cells ( MG–DOX ⊂ L ). The structural transformation of MG effectively regulates the drug release profile in acidic environment. The pH-responsive sensitivity of co-assembly can be fine-tuned by altering the mixing ratios of building blocks with pH responders (i.e., MG molecules). MG–DOX ⊂ L was beneficial for the DOX release at pH 5.0 and showed a higher cytotoxicity in KB cells owing to the pH-responsive drug release in acidic organelles following endocytosis pathway. In vivo tumor targetability and growth inhibition were evaluated in KB cell-xenografted nude mice. We have demonstrated that effective tumor growth inhibition in vivo is attributed to the synergistic contributions from highly efficient cellular entry and responsive intracellular release of DOX from MG–DOX ⊂ L .

We report a convenient synthetic approach for one-pot preparation of poly(β-amino ester)s copolymerized with peptides. A family of copolymers with tertiary amine groups was synthesized by copolymerizing di(ethylene glycol) diacrylate (DEDA), poly(ethylene glycol) diacrylate (PEGDA), 3-(diethylamino)propylamine (DEPA) and GGRGD peptides using the Michael addition reaction. The hydrophobic/hydrophilic properties of the resulting copolymers are adjusted by altering the feed ratios of DEDA and PEGDA. The copolymers self-assembled into nanoparticles with sizes around 60–140 nm in aqueous media, which were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM) techniques. The copolymers exhibit pH sensitive properties upon introduction of DEPA moieties, which were proved by pyrene fluorescence and pH titration measurements. The acid-triggered dissociation behaviors of the nanoparticles were studied by DLS and Nile red (NR) release experiments, revealing that the sizes of dissociated copolymer nanoparticles were closely relevant to their compositions. The nanoparticles can load the hydrophobic anticancer drug, i.e., doxorubicin (DOX). The DOX-loaded nanoparticles were stable in a neutral phosphate buffer solution with a payload leakage less than 20% at 37 °C. However, a significant acid-triggered DOX release was accomplished at pH 5.0 with release efficiency up to 60–80%. Because of the decoration of Arg-Gly-Asp (RGD) peptides onto the poly(β-amino ester)s, the DOX-encapsulated nanoparticles formed by poly(RGD-co-β-amino ester)s can be internalized by cancer cells via an αvβ3 integrin-mediated endocytosis pathway and accumulated in the lysosomes that provide an acidic environment to promote the release of DOX. Finally, the DOX-encapsulated copolymer nanoparticles with the targeted RGD peptide exhibited higher efficiency to kill U87 human glioblastoma cancer cells than that without RGD, which was further proved by cellular uptake of DOX-loaded nanoparticles.

The matrix metalloproteinases (MMPs) are a family of proteases which are normally up-regulated in tumor tissues. Gelatin is a biocompatible and non-immunogenic substrate which can be degraded by MMPs. In this work, MMPs-degradable gelatin coated mesoporous silica nanoparticles (MSNs@Gel) were designed for endogenous tumor microenvironment-triggered release systems for cancer treatment in vivo. This drug delivery system is expected to attain preferential release of drugs in tumor microenvironment with diminished systemic toxicity. The gelatin corona can serve as both a protective layer for preventing drugs leakage and MMPs-digested substrates for responding the solid tumor microenvironment. Doxorubicin (DOX), as a model antitumor drug, was loaded into the mesopores of MSNs@Gel to give DOX⊂MSNs@Gel with controllable releasing feature upon the MMPs stimuli. Interestingly, the encapsulated DOX in the DOX⊂MSNs@Gel was barely delivered into the normal cells due to the less endocytosis activity compared to that of the cancerous cells, resulting in the decreased systemic toxicity and decreased side effect during the tumor treatment. Whilst in the tumor tissue, the gelatin layer of DOX⊂MSNs@Gel was degraded and the encapsulated DOX was released effectively. The released DOX was accumulated in the nucleus of tumor cells. In vivo studies demonstrated that the tumor growth of xenografted mice was significantly delayed without any appreciable body weight loss that indicated the lower systemic toxicity of DOX⊂MSNs@Gel compared to the free DOX.