Search

The visualization of drugs in living systems has become key techniques in modern therapeutics. Recent advancements in optical imaging technologies and molecular design strategies have revolutionized drug visualization. At the subcellular level, super-resolution microscopy has allowed exploration of the molecular landscape within individual cells and the cellular response to drugs. Moving beyond subcellular imaging, researchers have integrated multiple modes, like optical near-infrared II imaging, to study the complex spatiotemporal interactions between drugs and their surroundings. By combining these visualization approaches, researchers gain supplementary information on physiological parameters, metabolic activity, and tissue composition, leading to a comprehensive understanding of drug behavior. This review focuses on cutting-edge technologies in drug visualization, particularly fluorescence imaging, and the main types of fluorescent molecules used. Additionally, we discuss current challenges and prospects in targeted drug research, emphasizing the importance of multidisciplinary cooperation in advancing drug visualization. With the integration of advanced imaging technology and molecular design, drug visualization has the potential to redefine our understanding of pharmacology, enabling the analysis of drug micro-dynamics in subcellular environments from new perspectives and deepening pharmacological research to the levels of the cell and organelles.

Small molecule drugs play a pivotal role in the arsenal of anticancer pharmacological agents. Nonetheless, their small size poses a challenge when directly visualizing their localization, distribution, mechanism of action (MOA), and target engagement at the subcellular level in real time. We propose a strategy for developing triple-functioning drug beacons that seamlessly integrate therapeutically relevant bioactivity, precise subcellular localization, and direct visualization capabilities within a single molecular entity. As a proof of concept, we have meticulously designed and constructed a boronic acid fluorescence drug beacon using coumarin–hemicyanine (CHB). Our CHB design includes three pivotal features: a boronic acid moiety that binds both adenosine triphosphate (ATP) and adenosine diphosphate (ADP), thus depleting their levels and disrupting the energy supply within mitochondria; a positively charged component that targets the drug beacon to mitochondria; and a sizeable conjugated luminophore that emits fluorescence, facilitating the application of structured illumination microscopy (SIM). Our study indicates the exceptional responsiveness of our proof-of-concept drug beacon to ADP and ATP, its efficacy in inhibiting tumor growth, and its ability to facilitate the tracking of ADP and ATP distribution around the mitochondrial cristae. Furthermore, our investigation reveals that the micro-dynamics of CHB induce mitochondrial dysfunction by causing damage to the mitochondrial cristae and mitochondrial DNA. Altogether, our findings highlight the potential of SIM in conjunction with visual drug design as a potent tool for monitoring the in situ MOA of small molecule anticancer compounds. This approach represents a crucial advancement in addressing a current challenge within the field of small molecule drug discovery and validation.

Unlike chemosynthetic drugs designed for specific molecular and disease targets, active small-molecule natural products typically have a wide range of bioactivities and multiple targets, necessitating extensive screening and development. To address this issue, we propose a strategy for the direct in situ microdynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action. As a proof-of-concept, we investigated the behavior of mussel oligosaccharide (MOS-1) by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells. We recorded the entire dynamic process of the localization of fluorescein isothiocyanate (FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the cell. Remarkably, lysosomes containing FITC-MOS-1 actively recruited lipid droplets, leading to fusion events and increased cellular lipid consumption. These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases. Furthermore, in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E (ApoE)−/− mice, MOS-1 significantly promoted triglyceride degradation, reduced lipid droplet accumulation, lowered serum triglyceride levels, and mitigated liver damage and steatosis. Overall, our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase, as this methodology contributes to the rapid identification of drug indications. Collectively, this methodology is significant for the screening and development of selective small-molecule drugs, and is expected to expedite the identification of candidate molecules with medicinal effects.

The scale of distributed energy resources is increasing, but imperfect business models and value transmission mechanisms lead to low utilization ratio and poor responsiveness. To address this issue, the concept of cleanness value of distributed energy storage (DES) is proposed, and the spatiotemporal distribution mechanism is discussed from the perspectives of electrical energy and cleanness. Based on this, an evaluation system for the environmental benefits of DES is constructed to balance the interests between the aggregator and the power system operator. Then, an optimal low-carbon dispatching for a virtual power plant (VPP) with aggregated DES is constructed, where-in energy value and cleanness value are both considered. To achieve the goal, a green attribute labeling method is used to establish a correlation constraint between the nodal carbon potential of the distribution network (DN) and DES behavior, but as a cost, it brings multiple nonlinear relationships. Subsequently, a solution method based on the convex envelope (CE) linear re-construction method is proposed for the multivariate nonlinear programming problem, thereby improving solution efficiency and feasibility. Finally, the simulation verification based on the IEEE 33-bus DN is conducted. The simulation results show that the multidimensional value recognition of DES motivates the willingness of resource users to respond. Meanwhile, resolving the impact of DES on the nodal carbon potential can effectively alleviate overcompensation of the cleanness value.

Nanostructural contact sites formed by interorganelle membrane contacts, including mitochondria and lysosome contacts (MLC), facilitate the exchange of substances during various life processes. However, existing bioanalytical technologies have yet to provide accurate information on the exchange of substances, as these techniques exhibit limited spatial and temporal resolution. To address this limitation, a strategy is proposed that combines fluorescence resonance energy transfer (FRET) probes with high spatial resolution detection and super‐resolution microscopes (SRM) that feature time‐resolved imaging. Specifically, a proof‐of‐concept approach is presented for monitoring H+ fluctuations during MLC with a spatial H+ biosensor targeting lysosomes, BDP‐RhB. The biosensor comprises H+‐sensitive rhodamine B as a FRET acceptor connected by a flexible chain to a BODIPY derivative as a donor. The acidity of MLC sites may vary, influencing the spatial distance of the flexible chain and causing a fluorescence transition in BDP‐RhB. Consequently, the spatial distribution of H+ can be identified using SRM. Furthermore, an algorithm has been developed to screen and identify potential compounds that control substance exchange in the MLC. Collectively, this work presents the dynamic of H+ in lysosomes within living cells, which provides a drug screening tool for studying substance exchange through interorganelle membrane contacts.

The online interactive workloads and offline batch computing services of Internet data centers (IDCs) have scheduling flexibility. Batch computing tasks with low latency sensitivity and priority can adjust the processing time and provide flexibility temporally. In contrast, interactive workloads with high latency sensitivity and priority can change the physical server for processing and provide flexibility spatially. Considering the change of power supply cost with time and space, the load flexibility of IDCs brought by Internet workload scheduling can be utilized to respond to the power system for more economical operation. To take full advantage of the flexibility of IDCs’ load demand, IDCs coordinated by an Internet service company (ISC) as a special controllable load with both temporal and spatial flexibility potential are considered. Instead of operating separately in normal optimal power flow (OPF) models, a two-stage interactive framework of the distribution system operator (DSO) and ISC is established. The operating state of the ISC is considered in OPF and is introduced as regularization terms into the objective function, thus fully exploiting its load flexibility. Some operation constraints are also added to guarantee the quality of service (QoS) of the ISC. The effectiveness of the model and the interactive framework are evaluated in a typical 33-bus medium-voltage distribution network. The results validate the further reduction of the power grid operation cost compared with the traditional OPF operation.

Circular RNAs (circRNAs) play a critical regulatory role in degenerative diseases; however, their functions and therapeutic applications in intervertebral disc degeneration (IVDD) have not been explored. Here, we identified that a novel circATXN1 highly accumulates in aging nucleus pulposus cells (NPCs) accountable for IVDD. CircATXN1 accelerates cellular senescence, disrupts extracellular matrix organization, and inhibits mitochondrial respiration. Mechanistically, circATXN1, regulated by heterogeneous nuclear ribonucleoprotein A2B1-mediated splicing circularization, promotes progerin translocation from the cell nucleus to the cytoplasm and inhibits the expression of insulin-like growth factor 1 receptor (IGF-1R). To demonstrate the therapeutic potential of circATXN1, siRNA targeting the backsplice junction of circATNX1 was screened and delivered by tetrahedral framework nucleic acids (tFNAs) due to their unique compositional and tetrahedral structural features. Our siRNA delivery system demonstrates superior abilities to transfect aging cells, clear intracellular ROS, and enhanced biological safety. Using siRNA–tFNAs to silence circATXN1, aging NPCs exhibit reduced mislocalization of progerin in the cytoplasm and up-regulation of IGF-1R, thereby demonstrating a rejuvenated cellular phenotype and improved mitochondrial function. In vivo, administering an aging cell-adapted siRNA nucleic acid framework delivery system to progerin pathologically expressed premature aging mice (zmpste24−/−) can ameliorate the cellular matrix in the nucleus pulposus tissue, effectively delaying IVDD. This study not only identified circATXN1 functioning as a cell senescence promoter in IVDD for the first time, but also successfully demonstrated its therapeutic potential via a tFNA-based siRNA delivery strategy.

AbstractObjective The study aimed to compare the incidence of intraoperative endplate injury in patients who underwent Transforaminal interbody fusion (TLIF) and mini-open lumbar interbody fusion (LLIF) surgery. The independent risk factors related to endplate injury in LLIF procedure were analyzed.Methods A total of 199 patients who underwent LLIF (n = 106) or TLIF (n = 93) surgery from June 2019 to September 2021 were reviewed. The endplate injury was assessed by postoperative sagittal CT scan. A binary logistic analysis model were used to identify independent risk factors related to LLIF endplate injury based on univariate analysis.Results There was an obvious difference in the occurrence of intraoperative endplate injury between LLIF (42/106, 39.6%) and TLIF group (26/93, 28%), although it did not reach the significant level. L1 CT value (OR = 0.985, 95% CI = 0.972–0.998), cage position (OR = 3.881, 95% CI = 1.398–10.771) and height variance (OR = 1.263, 95% CI = 1.013–1.575) were independent risk factors for endplate injury in LLIF procedure. According to the cage settlement patterns, there 5 types of A to E. The severity of the facet joint degeneration was positively related to the occurrence of endplate injury.Conclusions The incidence of intraoperative endplate injury is higher in LLIF than in TLIF procedures. Low bone quantity, cage posterior position and larger height variance are risk factors to induce endplate injury in LLIF surgery. The facet joint degeneration may be related to severe endplate injuries and even fractures.

Summary: Mitochondria are dynamic organelles that undergo fusion and fission events, in which the mitochondrial membrane and DNA (mtDNA) play critical roles. The spatiotemporal organization of mtDNA reflects and impacts mitochondrial dynamics. Herein, to study the detailed dynamics of mitochondrial membrane and mtDNA, we rationally develop a dual-color fluorescent probe, mtGLP, that could be used for simultaneously monitoring mitochondrial membrane and mtDNA dynamics via separate color outputs. By combining mtGLP with structured illumination microscopy to monitor mitochondrial dynamics, we discover the formation of nucleoid condensates in damaged mitochondria. We further reveal that nucleoid condensates promoted the peripheral fission of damaged mitochondria via asymmetric segregation. Through simulations, we find that the peripheral fission events occurred when the nucleoid condensates interacted with the highly curved membrane regions at the two ends of the mitochondria. Overall, we show that mitochondrial nucleoid condensates utilize peripheral fission to maintain mitochondrial homeostasis.

Abstract Spinal cord injury (SCI) causes blood‐spinal cord barrier (BSCB) disruption, leading to secondary damage, such as hemorrhagic infiltration, inflammatory response, and neuronal cell death. It is of great significance to rebuild the BSCB at the early stage of SCI to alleviate the secondary injury for better prognosis. Yet, current research involved in the reconstruction of BSCB is insufficient. Accordingly, we provide a thermosensitive hydrogel‐based G protein‐coupled receptor 124 (GPR124) delivery strategy for rebuilding BSCB. Herein, we firstly found that the expression of GPR124 decreased post‐SCI and demonstrated that treatment with recombinant GPR124 could partially alleviate the disruption of BSCB post‐SCI by restoring tight junctions (TJs) and promoting migration and tube formation of endothelial cells. Interestingly, GPR124 could also boost the energy metabolism of endothelial cells. However, the absence of physicochemical stability restricted the wide usage of GPR124. Hence, we fabricated a thermosensitive heparin‐poloxamer (HP) hydrogel that demonstrated sustained GPR124 production and maintained the bioactivity of GPR124 (HP@124) for rebuilding the BSCB and eventually enhancing functional motor recovery post‐SCI. HP@124 hydrogel can encapsulate GPR124 at the lesion site by injection, providing prolonged release, preserving wounded tissues, and filling injured tissue cavities. Consequently, it induces synergistically efficient integrated regulation by blocking BSCB rupture, decreasing fibrotic scar formation, minimizing inflammatory response, boosting remyelination, and regenerating axons. Mechanistically, giving GPR124 activates energy metabolism via elevating the expression of phosphoenolpyruvate carboxykinase 2 (PCK2), and eventually restores the poor state of endothelial cells. This research demonstrated that early intervention by combining GPR124 with bioactive multifunctional hydrogel may have tremendous promise for restoring locomotor recovery in patients with central nervous system disorders, in addition to a translational approach for the medical therapy of SCI.

Disordered reactive oxygen/nitrogen species are a common occurrence in various diseases, which usually cause cellular oxidative damage and inflammation. Despite the wide range of applications for biomimetic nanoparticles with antioxidant or anti-inflammatory properties, designs that seamlessly integrate these two abilities with a synergistic effect in a simple manner are seldom reported. In this study, we developed a novel PEI-Mn composite nanoparticle (PM NP) using a chelation method, and the curcumin was loaded onto PM NPs via metal–phenol coordination to form PEI-Mn@curcumin nanoparticles (PMC NPs). PMC NPs possessed excellent dispersibility and cytocompatibility, was engineered to serve as an effective nanozyme, and exhibited specific SOD-like and CAT-like activities. In addition, the incorporation of curcumin granted PMC NPs the ability to effectively suppress the expression of inflammatory cytokines in microglia induced by LPS. As curcumin also has antioxidant properties, it further amplified the synergistic efficiency of ROS scavenging. Significantly, PMC NPs effectively scavenged ROS triggered by H2O2 in SIM-A9 microglia cells and Neuro-2a cells. PMC NPs also considerably mitigated DNA and lipid oxidation in Neuro-2a cells and demonstrated an increase in cell viability under various H2O2 concentrations. These properties suggest that PMC NPs have significant potential in addressing excessive ROS and inflammation related to neural diseases.

Objective To verify the effect of single‐door laminoplasty combined with atlantoaxial fusion in the treatment of symptomatic atlas canal stenosis. Methods This is a single‐center retrospective analysis. From February 2014 to January 2019, 16 patients (five were females) with an average age of 63.4 years (56–71 years) were enrolled in this study. Patients with compressive cervical myelopathy with CT scan showed an inner sagittal diameter (ISD) of C1 less than 29 mm or C1 canal space available for cord (SAC) of

The current effective method for treatment of spinal cord injury (SCI) is to reconstruct the biological microenvironment by filling the injured cavity area and increasing neuronal differentiation of neural stem cells (NSCs) to repair SCI. However, the method is characterized by several challenges including irregular wounds, and mechanical and electrical mismatch of the material-tissue interface. In the current study, a unique and facile agarose/gelatin/polypyrrole (Aga/Gel/PPy, AGP3) hydrogel with similar conductivity and modulus as the spinal cord was developed by altering the concentration of Aga and PPy. The gelation occurred through non-covalent interactions, and the physically crosslinked features made the AGP3 hydrogels injectable. In vitro cultures showed that AGP3 hydrogel exhibited excellent biocompatibility, and promoted differentiation of NSCs toward neurons whereas it inhibited over-proliferation of astrocytes. The in vivo implanted AGP3 hydrogel completely covered the tissue defects and reduced injured cavity areas. In vivo studies further showed that the AGP3 hydrogel provided a biocompatible microenvironment for promoting endogenous neurogenesis rather than glial fibrosis formation, resulting in significant functional recovery. RNA sequencing analysis further indicated that AGP3 hydrogel significantly modulated expression of neurogenesis-related genes through intracellular Ca2+ signaling cascades. Overall, this supramolecular strategy produces AGP3 hydrogel that can be used as favorable biomaterials for SCI repair by filling the cavity and imitating the physiological properties of the spinal cord.

Equilibrium analysis has been widely studied as an effective tool to model gaming interactions and predict market results. However, as competition modes are fundamentally changed by the decarbonization and decentralization of power systems, analysis techniques must evolve. This article comprehensively reviews recent developments in modelling methods, practical settings and solution techniques in equilibrium analysis. Firstly, we review equilibrium in the evolving wholesale power markets which feature new entrants, novel trading products and multi-stage clearing. Secondly, the competition modes in the emerging distribution market and distributed resource aggregation are reviewed, and we compare peer-to-peer clearing, cooperative games and Stackelberg games. Furthermore, we summarize the methods to treat various information acquisition degrees, risk preferences and rationalities of market participants. To deal with increasingly complex market settings, this review also covers refined analytical techniques and agent-based models used to compute the equilibrium. Finally, based on this review, this paper summarizes key issues in the gaming and equilibrium analysis in power markets under decarbonization and decentralization.

Cell-based regenerative therapy utilizes the differentiation potential of stem cells to rejuvenate tissues. But the dynamic fate of stem cells is calling for precise control to optimize their therapeutic efficiency. Stem cell fate is regulated by specific conditions called “microenvironments.” Among the various factors in the microenvironment, the cell-surface glycan acts as a mediator of cell-matrix and cell-cell interactions and manipulates the behavior of cells. Herein, metabolic glycoengineering (MGE) is an easy but powerful technology for remodeling the structure of glycan. By presenting unnatural glycans on the surface, MGE provides us an opportunity to reshape the microenvironment and evoke desired cellular responses. In this review, we firstly focused on the determining role of glycans on cellular activity; then, we introduced how MGE influences glycosylation and subsequently affects cell fate; at last, we outlined the application of MGE in regenerative therapy, especially in the musculoskeletal system, and the future direction of MGE is discussed.

Objective To describe the anatomical feature positioned beneath the psoas muscle at the lateral aspect of the lower lumbar, and to create a new location system to identify the risk factors of lateral lumbar interbody fusion. Methods Six cadavers were dissected and analyzed. The anatomy and neurovascular distribution beneath the psoas major from L3 to S1 was observed and recorded, with particular focus on the L4/5 disc and below. The psoas major surface was divided homogeneously into four parts, from the anterior border of psoas major to the transverse process. The cranial‐to‐caudal division was from the lower edge of the psoas muscle attachment on the L4 vertebrae to the upper part of the S1 vertebrae, and was divided into five segments. Then a grid system was used to create 20 grids on the psoas major surface, from the anterior border of the muscle to the transverse process and from L4 to superior S1, which was used to determine the anatomical structures' distribution and relationship beneath the psoas major. Results A cleft was identified beneath the psoas major, from the level of L4/5 downwards. It was filled with loose connective tissue and neurovascular structures. We termed it the cleft of psoas major (CPM). The sympathetic trunk, ascending lumbar vein, iliolumbar vessels, obturator nerve, femoral nerve and occasionally the great vessels are contained within the CPM, although there is significant interpersonal variation. The grid system on the psoas major surface helped to identify the anatomical structures in CPM. There was a considerably lower frequency of occurrence of neurovascular structures in the grids of I/II at the L4/5 level where can be considered the “safe zones” for the lateral lumbar interbody fusion. In contrast, the distribution of neurovascular structures at the L5S1 level is dense, where the operation risk is high. Conclusion The CPM exists lateral to the vertebral surface from L4 and below. Although the occurrence and distribution of neurovascular structures within the CPM is complex and varies greatly, it can provide a potential cavity for visualization during lateral lumbar interbody fusion. Using psoas major as a reference, this novel grid system can be used to identify the risk factors in CPM and thus identify a safe entry point for surgery.

Cell transplantation has been proved the promising therapeutic effects on intervertebral disc degeneration (IVDD). However, the increased levels of reactive oxygen species (ROS) in the degenerated region will impede the efficiency of human adipose-derived stem cells (human ADSCs) transplantation therapy. It inhibits human ADSCs proliferation, and increases human ADSCs apoptosis. Herein, we firstly devised a novel amphiphilic copolymer PEG-PAPO, which could self-assemble into a nanosized micelle and load lipophilic kartogenin (KGN), as a single complex (PAKM). It was an injectable esterase-responsive micelle, and showed controlled release ability of KGN and apocynin (APO). Oxidative stimulation promoted the esterase activity in human ADSCs, which accelerate degradation of esterase-responsive micelle. Compared its monomer, the PAKM micelle possessed better bioactivities, which were attributed to their synergistic effect. It enhanced the viability, autophagic activation (P62, LC3 II), ECM-related transcription factor (SOX9), and ECM (Collagen II, Aggrecan) maintenance in human ADSCs. Furthermore, it is demonstrated that the injection of PAKM with human ADSCs yielded higher disc height and water content in rats. Therefore, PAKM micelles perform promoting cell survival and differentiation effects, and may be a potential therapeutic agent for IVDD.

Abstract Lysosome–autophagosome fusion is critical to autophagosome maturation. Although several proteins that regulate this fusion process have been identified, the prefusion architecture and its regulation remain unclear. Herein, we show that upon stimulation, multiple lysosomes form clusters around individual autophagosomes, setting the stage for membrane fusion. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein on lysosomes—vesicle-associated membrane protein 8 (VAMP8)—plays an important role in forming this prefusion state of lysosomal clusters. To study the potential role of phosphorylation on spontaneous fusion, we investigated the effect of phosphorylation of C-terminal residues of VAMP8. Using a phosphorylation mimic, we observed a decrease of fusion in an ensemble lipid mixing assay and an increase of unfused lysosomes associated with autophagosomes. These results suggest that phosphorylation not only reduces spontaneous fusion for minimizing autophagic flux under normal conditions, but also preassembles multiple lysosomes to increase the fusion probability for resuming autophagy upon stimulation. VAMP8 phosphorylation may thus play an important role in chemotherapy drug resistance by influencing autophagosome maturation.

The power system is in change, and the most fundamental changes are happening in the distribution grid. Formerly passive consumers get active and smart, storage and distributed generation appears, and the “grid edge” is upgraded with Intenet of Things (IoT). Gone are the days where distribution infrastructure consisted of passive assets, dimensioned for the worst case of load. We are now entering a new phase where active distribution grids are operated with the help of local markets, machine learning techniques, and distribution automation. Integrating renewable energy or electric vehicles and electrifying the last remaining fossil applications require a flexible and powerful active distribution grid.

The repair and motor functional recovery after spinal cord injury (SCI) remains a worldwide challenge. The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI. Using mesenchymal stem cells (MSCs) derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation. However, the effective preservation and controlled release of extracellular vesicles in the injured spinal cord tissue are still not satisfied. Herein, we fabricated an injectable adhesive anti-inflammatory F127-polycitrate-polyethyleneimine hydrogel (FE) with sustainable and long term extracellular vesicle release (FE@EVs) for improving motor functional recovery after SCI. The orthotopic injection of FE@EVs hydrogel could encapsulate extracellular vesicles on the injured spinal cord, thereby synergistically induce efficient integrated regulation through suppressing fibrotic scar formation, reducing inflammatory reaction, promoting remyelination and axonal regeneration. This study showed that combining extracellular vesicles into bioactive multifunctional hydrogel should have great potential in achieving satisfactory locomotor recovery of central nervous system diseases.

Abstract The continuous growth of renewable generation in power systems brings serious challenges to electricity markets due to their characteristics different from conventional generation technologies. These challenges come from two dimensions, including short‐term (energy and ancillary service markets) and long‐term (long‐term bilateral and capacity markets) aspects. Under this background, the design of energy and ancillary service markets is studied for power systems with a high penetration level of variable renewable generation. In the proposed spot market mechanism, energy and frequency regulation service (FRS) bids are jointly cleared, where renewable generators are motivated to proactively manage the intermittency and uncertainty of their power outputs. The proposed market mechanism can also ensure the adequacy of FRS capacity for compensating variability of renewables. Besides, in order to ensure the execution of spot market clearing outcomes, this paper established a penalty scheme for mitigating the real‐time fluctuations of renewable generation outputs in the spot market. Differences between real‐time generation outputs and market clearing outcomes are managed within a certain limit by imposing the designed penalty prices on deviations. Finally, the feasibility and efficiency of the developed market mechanism and algorithms are manifested in the case studies.

Summary: The rapid development of distributed photovoltaic (PV) systems poses great challenges to the integration capability of distribution networks. Traditionally, the transfer capacity of power distribution equipment is calculated as the maximum loading that prevents overheating under the assumption of extreme weather conditions. Dynamic thermal rating (DTR), which evaluates equipment capacity based on real-time weather conditions, could enhance the transfer capacity to improve distributed PV integration. Through case studies in Texas, Switzerland, and China, we show that the application of DTR on power distribution equipment could increase installed PV capacities by 15%–27% and improve net revenues by 4%–27%. We also find that the application of DTR would be positively affected by climate change and is more profitable under the PV policies with higher tariffs for the surplus generation fed into the grid. Compared to energy storage systems, DTR provides a more cost-competitive option to enhance the integration capability of distribution networks.

Abstract SLC25A46 mutations have been found to lead to mitochondrial hyper-fusion and reduced mitochondrial respiratory function, which results in optic atrophy, cerebellar atrophy, and other clinical symptoms of mitochondrial disease. However, it is generally believed that mitochondrial fusion is attributable to increased mitochondrial oxidative phosphorylation (OXPHOS), which is inconsistent with the decreased OXPHOS of highly-fused mitochondria observed in previous studies. In this paper, we have used the live-cell nanoscope to observe and quantify the structure of mitochondrial cristae, and the behavior of mitochondria and lysosomes in patient-derived SLC25A46 mutant fibroblasts. The results show that the cristae have been markedly damaged in the mutant fibroblasts, but there is no corresponding increase in mitophagy. This study suggests that severely damaged mitochondrial cristae might be the predominant cause of reduced OXPHOS in SLC25A46 mutant fibroblasts. This study demonstrates the utility of nanoscope-based imaging for realizing the sub-mitochondrial morphology, mitophagy and mitochondrial dynamics in living cells, which may be particularly valuable for the quick evaluation of pathogenesis of mitochondrial morphological abnormalities.

Abstract Background This study was to evaluate and compare the biomechanical features of multilevel lateral lumbar interbody fusion (LLIF) with or without supplemental instrumentations. Methods Six human lumbar specimens were tested under multidirectional nondestructive moments (7.5 N·m), with a 6 degree-of-freedom spine simulator. The overall and intervertebral range of motion (ROM) were measured optoelectronically. Each specimen was tested under the following conditions at L2–5 levels: intact; stand-alone; cage supplemented with lateral plate (LP); cage supplemented with unilateral or bilateral pedicle screw/rod (UPS or BPS). Results Compared with intact condition, the overall and intersegmental ROM were significantly reduced after multilevel stand-alone LLIF. The ROM was further reduced after using LP instrumentation. In flexion-extension (FE) and axial rotation (AR), pedicle screw/rod demonstrated greater overall ROM reduction compared to LP (P

Background and ObjectivesEarly diagnosis of patients with acute myocardial infarction (AMI) who are at a high risk of heart failure (HF) progression remains controversial. This study aimed at identifying new predictive biomarkers of post-AMI HF and at revealing the pathogenesis of HF involving these marker genes.Methods and ResultsA transcriptomic dataset of whole blood cells from AMI patients with HF progression (post-AMI HF, n = 16) and without progression (post-AMI non-HF, n = 16) was analyzed using the weighted gene co-expression network analysis (WGCNA). The results indicated that one module consisting of 720 hub genes was significantly correlated with post-AMI HF. The hub genes were validated in another transcriptomic dataset of peripheral blood mononuclear cells (post-AMI HF, n = 9; post-AMI non-HF, n = 8). PRKAR1A, SDCBP, SPRED2, and VAMP3 were upregulated in the two datasets. Based on a single-cell RNA sequencing dataset of leukocytes from heart tissues of normal and infarcted mice, PRKAR1A was further verified to be upregulated in monocytes/macrophages on day 2, while SDCBP was highly expressed in neutrophils on day 2 and in monocytes/macrophages on day 3 after AMI. Cell–cell communication analysis via the “CellChat” package showed that, based on the interaction of ligand–receptor (L–R) pairs, there were increased autocrine/paracrine cross-talk networks of monocytes/macrophages and neutrophils in the acute stage of MI. Functional enrichment analysis of the abovementioned L–R genes together with PRKAR1A and SDCBP performed through the Metascape platform suggested that PRKAR1A and SDCBP were mainly involved in inflammation, apoptosis, and angiogenesis. The receiver operating characteristic (ROC) curve analysis demonstrated that PRKAR1A and SDCBP, as well as their combination, had a promising prognostic value in the identification of AMI patients who were at a high risk of HF progression.ConclusionThis study identified that PRKAR1A and SDCBP may serve as novel biomarkers for the early diagnosis of post-AMI HF and also revealed their potentially regulatory mechanism during HF progression.

Abstract Background Acute myocardial infarction (AMI) is a major contributor of heart failure (HF). Peripheral blood mononuclear cells (PBMCs), mainly monocytes, are the essential initiators of AMI-induced HF. The powerful biomarkers for early identification of AMI patients at risk of HF remain elusive. We aimed to identify monocyte-related critical genes as predictive biomarkers for post-AMI HF. Methods We performed weighted gene co-expression network analysis (WGCNA) on transcriptomics of PBMCs from AMI patients who developed HF or did not. Functional enrichment analysis of genes in significant modules was performed via Metascape. Then we obtained the single-cell RNA-sequencing data of recruited monocytes/macrophages from AMI and control mice using the Scanpy and screened 381 differentially expressed genes (DEGs) between the two groups. We validated the expression changes of the 25 genes in cardiac macrophages from AMI mice based on bulk RNA-sequencing data and PBMCs data mentioned above. Results In our study, the results of WGCNA showed that two modules containing 827 hub genes were most significantly associated with post-AMI HF, which mainly participated in cell migration, inflammation, immunity, and apoptosis. There were 25 common genes between DEGs and hub genes, showing close relationship with inflammation and collagen metabolism. CUX1, CTSD and ADD3 exhibited consistent changes in three independent studies. Receiver operating characteristic curve analysis showed that each of the three genes had excellent performance in recognizing post-AMI HF patients. Conclusion Our findings provided a set of three monocyte-related biomarkers for the early prediction of HF development after AMI as well as potential therapeutic targets of post-AMI HF.

Subcellular Zn2+ compartmentalisation is essential for cell biology. Here the authors make a turn-on fluorescent Zn2+ probe that localises to multiple organelles, and correlate its location using organelle morphology derived from structured illumination microscopy.

Dynamic labeling and tracking of organelle–organelle contacts is essential to understand the formation and function of these interactions. Here the authors present a small molecule probe, Coupa, that labels mitochondria and lysosomes with blue and red fluorescence, respectively.

Electricity price forecasting is very important for market participants in a deregulated market. However, only a few papers investigated the impact of forecasting errors on the market participants' behaviours and revenues. In this study, a general formulation of bidding in the electricity market is considered and the participant is assumed to be a price‐taker which is general for most of the participants in power markets. A numerical method for quantifying the impact of forecasting errors on the bidding curves and revenues based on multiparametric linear programming is proposed. The forecasted prices are regarded as exogenous parameters for both deterministic and stochastic bidding models. Compared with the existing method, the proposed method can calculate how much improvement will be achieved in the cost or revenue of the bidder if he reduces the price forecasting error level, and such calculation does not require any predefined forecasting results. Numerical results and discussions based on real‐market price data are conducted to show the application of the proposed method.

Abstract With the increasing incidence of cartilage-related diseases such as osteoarthritis (OA) and intervertebral disc degeneration (IDD), heavier financial and social burdens need to be faced. Unfortunately, there is no satisfactory clinical method to target the pathophysiology of cartilage-related diseases. Many gene expressions, signaling pathways, and biomechanical dysregulations were involved in cartilage development, degeneration, and regeneration. However, the underlying mechanism was not clearly understood. Recently, lots of long non-coding RNAs (lncRNAs) were identified in the biological processes, including cartilage development, degeneration, and regeneration. It is clear that lncRNAs were important in regulating gene expression and maintaining chondrocyte phenotypes and homeostasis. In this review, we summarize the recent researches studying lncRNAs’ expression and function in cartilage development, degeneration, and regeneration and illustrate the potential mechanism of how they act in the pathologic process. With continued efforts, regulating lncRNA expression in the cartilage regeneration may be a promising biological treatment approach.

Abstract Oncosis, depending on DNA damage and mitochondrial swelling, is an important approach for treating cancer and other diseases. However, little is known about the behavior of mitochondria during oncosis, due to the lack of probes for in situ visual illumination of the mitochondrial membrane and mtDNA. Herein, a mitochondrial lipid and mtDNA dual‐labeled probe, MitoMN, and a continuous add‐on assay, are designed to image the dynamic process of mitochondria in conditions that are unobservable with current mitochondrial probes. Meanwhile, the MitoMN can induce oncosis in a light‐activated manner, which results in the enlargement of mitochondria and the death of cancer cells. Using structured illumination microscopy (SIM), MitoMN‐stained mitochondria with a dual‐color response reveals, for the first time, how swelled mitochondria interacts and fuses with each other for a nonlinear enlargement to accelerate oncosis into an irreversible stage. With this sign of irreversible oncosis revealed by MitoMN, oncosis can be segregated into three stages, including before oncosis, initial oncosis, and accelerated oncosis.

ObjectivesPost-implantation survival and timely vascularization of stem-cell based constructs are critical factors in achieving successful outcomes in tissue regeneration approaches. Hypoxia inducible factor-1α (HIF-1α) is known to mediate adaptive functions to ischemic stress in many different cell types. The current study aimed to explore the role of HIF-1α in post-implantation survival and angio-/vasculogenesis of stem cells from human exfoliated deciduous teeth (SHED).MethodsHIF-1α in SHED was suppressed using siRNA or chemical inhibitor (YC-1) and used in Matrigel plug assay conducted on severe combined immunodeficient mice. The plugs were retrieved on day 3 or 7 post-injection and analyzed for hypoxia status, ki67 expression, DNA fragmentation (TUNEL), cellularity, and vascularization by histology and immunohistochemistry for CD31, HIF-1α, pyruvate dehydrogenase kinase-1 (PDK1), hexokinase 2 (HK2), and glucose transporter 1 (Glut1). Cell viability of HIF-1α silenced SHED under different stress conditions (hypoxia, H2O2, and low glucose) in vitro was measured by CCK-8 assay. CM-H2DCFDA and MitoSOX Red were used to detect cellular and mitochondrial reactive oxygen species (ROS) levels, respectively. PDK1, HK2, and Glut1 expression were measured by western blotting and immunofluorescence. Secretory protein levels of vascular endothelial growth factor (VEGF) and the respective paracrine effects on endothelial cell proliferation and migration were detected by ELISA, CCK-8 assay, and trans-well assay, respectively.ResultsHistological analysis of Matrigel plugs showed significantly reduced cell survival in HIF-1α silenced or chemically inhibited SHED groups, which could be attributed to diminished metabolic adaptations as shown by decreased PDK1, HK2, and Glut1 expression. HIF-1α inhibition in SHED also resulted in significantly low blood vessel formation as observed by a low number of perfused and non-perfused vessels of human or mouse CD31 origin. The viability of HIF-1α silenced SHED was significantly affected under hypoxia, H2O2, and low-glucose conditions in vitro, which was reflected in increased cytoplasmic and mitochondrial ROS levels. Significantly reduced levels of VEGF in HIF-1α silenced SHED resulted in decreased paracrine angiogenic effects as shown by low proliferation and migration of endothelial cells.ConclusionHIF-1α plays an indispensable role in post-implantation survival and angio-/vasculogenic properties of SHED by maintaining ROS homeostasis, inducing metabolic adaptations, and VEGF secretion.

Salient object detection in complex environments brings the challenge from the collections of large number of training images for deep learning algorithm. It is difficult to collect the enough number of training data for varied salient objects in different scenes, and furthermore the salient objects are usually compared with the background. This paper proposes a novel method to integrate the salient features into the deep learning framework, and design a parallel multi-scale structure of the neural network to enhance the ability to detect salient objects. In addition, a multiple stage method is proposed to optimize the training process and make the datasets more prominent in the commonality of the salient features, which effectively reduces the difficulty of correctly distinguishing salient objects in complex environments. Experiments show that the proposed approach enhances the ability of neural networks to learn specified features and improves the detection effect of salient objects in complex scenes.

Smart grids (SGs) are reforming towards utilizing massive data for operations and services. During this reform, the information and communication technologies (ICTs) play a critical role, especially for the computing model, which determines how data analytics in SG can be executed. Edge computing (EC), a novel computing paradigm innovation, has high potential to help with the digitization of SG. This paper seeks to provide a comprehensive review of interdisciplinary research on EC applications in SG. First, an in-depth analysis of EC, including the definition, architectures, characteristics, and key enabling technologies is conducted from the perspective of SG application requirements. Afterward, this paper systematically explores application scenarios of EC in SG based on its characteristics. Beyond that, the synergistic effect of the integration of EC and SG is also assessed: SG not only benefits from EC but also supports EC to become sustainable. Challenges and open questions are then investigated.

The O(3P) + C2H2 reaction plays an important role in hydrocarbon combustion. It has two primary competing channels: H + HCCO (ketenyl) and CO + CH2 (triplet methylene). To further understand the microscopic dynamic mechanism of this reaction, we report here a detailed quasi-classical trajectory study of the O(3P) + C2H2 reaction on the recently developed full-dimensional potential energy surface (PES). The entrance barrier TS1 is the rate-limiting barrier in the reaction. The translation of reactants can greatly promote reactivity, due to strong coupling with the reaction coordinate at TS1. The O(3P) + C2H2 reaction progress through a complex-forming mechanism, in which the intermediate HCCHO lives at least through the duration of a rotational period. The energy redistribution takes place during the creation of the long-lived high vibrationally (and rotationally) excited HCCHO in the reaction. The product energy partitioning of the two channels and CO vibrational distributions agree with experimental data, and the vibrational state distributions of all modes of products present a Boltzmann-like distribution.

Intervertebral disc (IVD) degeneration and consequent lower back pain is a common disease. Micro fragmented adipose tissue (MFAT) is promising for a wide range of applications in regenerative medicine. In this study, MFAT was isolated by a nonenzymatic method and co-cultured with nucleus pulposus cells (NPCs) using an indirect co-culture system in vitro . A pig disc degeneration model was used to investigate the regenerative effect of MFAT on degenerated IVDs in vivo . The mRNA expression of Sox9 , Acan , and Col2 in NPCs was significantly increased, while no significant increase was observed in the mRNA expression of proinflammatory cytokine genes after the NPCs were co-cultured with MFAT. Nucleus pulposus (NP)-specific markers were increased in MFAT cells after co-culture with NPCs. After injection of MFAT, the disc height, water content, extracellular matrix, and structure of the degenerated NP were significantly improved. MFAT promoted the matrix synthesis function of NPCs, and NPCs stimulated the NP-like differentiation of MFAT cells. In addition, MFAT also partly regenerated degenerated IVDs in the pig model.

Abstract The high penetration of distributed renewable energy raises a higher concern for the safe and economic operation of the smart grid. Distributed batteries equipped in demand-side can not only contribute to the reliability and security of the grid, but also make profits by participating in the electricity market, especially when distributed batteries are combined and operated by an aggregator. Considering the well-operated mechanism of performance based regulation (PBR) in the U.S. electricity market, it becomes increasingly lucrative for batteries to participate not only in energy markets for energy arbitrage, but also in ancillary service markets to provide regulation and peak-load shaving services. In this study, distributed batteries are operated and coordinated by the aggregator, which simultaneously submits offers to the energy and the ancillary service markets as an individual entity. An optimal decision model is formulated for the aggregator to determine the operation and bidding strategy for the distributed batteries by considering the characteristics of batteries, including the terms of capacity, efficiency and degradation cost. Finally, a numerical case is conducted to evaluate the benefits of the decision model.

Abstract Distributed generation (DG) are critical components for active distribution system (ADS). However, this may be a serious impact on power system due to their volatility. To this problem, interactive load and battery storage may be a best solution. This paper firstly investigates operation characteristics of interactive load and battery storage, including operation flexibility, inter-temporal operation relations and active-reactive power relations. Then, a multi-period coordinated active-reactive scheduling model considering interactive load and battery storage is proposed in order to minimize overall operation costs over a specific duration of time. The model takes into accounts operation characteristics of interactive load and battery storage and focuses on coordination between DGs and them. Finally, validity and effectiveness of the proposed model are demonstrated based on case study of a medium-voltage 135-bus distribution system.

Production quality indices of complex industrial processes are usually hard to be measured in real time, which leads to unavailability of closed-loop operational optimization and control. Therefore, data-driven modeling techniques have been extensively employed to estimate production quality indices online. However, the conventional data-driven modeling methods often fail to achieve good performance because of interference from outliers. To solve the above-mentioned problem, this paper proposes an improved random vector functional link network (RVFLN) using a novel training method, which adopts a ridge regularized model with weighted factor for each training sample to evaluate the output weights. The robustness of the model has been achieved by employing a nonparametric kernel density estimation method to assign the weighted factors according to the training sample. To ensure the quality and computational load of the network in online applications, various online learning versions are presented according to the scope of data sampling. The improved RVFLN called robust regularized RVFLN has been validated using UCI, Statlib standard data sets, and an industrial grinding operation data. Results show that our proposed modeling technique perform favorably, and demonstrate its good potential for real world applications.

Traumatic incarceration of the small bowel accompanied by vertebral fractures and dislocation is rare and usually misdiagnosed until laparotomy. This report presents a rare case of jejunum entrapment between lumbar spine fractures. A 43-year-old man was clamped between two railway tracks on the upper abdomen and lower back. Following ineffective conservative treatment, he underwent a laparotomy due to the development of guarding and rebound tenderness. Loss of vitality of the jejunal loop, which was incarcerated between the L3 and L4 vertebrae, was observed. The necrotic bowel was removed and end-to-end anastomosis was performed. When his condition was stable, anterior and posterior lumbar fixation surgery was performed. The patient had no abdominal complications and lower limb nerve function deficiency during the follow-up period. A review of the literature since 1979 on incarceration of the bowel associated with lumbar fracture and dislocation identified 12 cases: five patients showed persistent neurological symptoms, but none of the patients died as a result of their injuries. It should be borne in mind that patients with hyperextension or flexion-distraction injury of the lumbar spine could show symptoms of intestinal obstruction and bowel incarceration. Enhanced computed tomography or magnetic resonance imaging will be helpful for diagnosis.

Background. Cell replacement therapy is an attractive alternative for treating degenerated intervertebral discs (IVDs), which are related to the reduction of nucleus pulposus-like cells (NP-lCs) and the loss of the extracellular matrix. Induced pluripotent stem cells (iPSCs) which resemble embryonic stem cells are considered to be a potential resource for restoring NP-lCs and disc homeostasis. Here, we proposed an efficient two-step differentiation protocol of human iPSCs into NP-lCs and continuously tested their in vivo ability to regenerate IVDs. Methods. A polymeric gelatin microsphere (GM) was generated for sustained release of growth and differentiation factor-5 (GDF-5) and as a cell delivery vehicle of NP-lCs. By injecting NP-lC-seeded GDF-5-loaded GMs into the rat coccygeal intervertebral discs, the disc height and water content were examined with the molybdenum target radiographic imaging test and magnetic resonance imaging examination. Histology and immunohistochemistry results were shown with H&E, S-O-Fast Green, and immunohistochemistry staining. Results. We demonstrated that the injection of NP-lC-seeded GDF-5-loaded GMs could reverse IDD in a rat model. The imaging examination indicated that disc height recovered and water content increased. Histology and immunohistochemistry results indicated that the NP cells as well as their extracellular matrix were partially restored. Conclusions. The results suggest that NP-lC-seeded GDF-5-loaded GMs could partially regenerate degenerated intervertebral discs after transplantation into rat coccygeal intervertebral discs. Our study will help develop a promising method of stem cell-based therapy for IDD.

Spinal cord injuries impose a notably economic burden on society, mainly because of the severe after-effects they cause. Despite the ongoing development of various therapies for spinal cord injuries, their effectiveness remains unsatisfactory. However, a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming. In this review, we explore the metabolic changes that occur during spinal cord injuries, their consequences, and the therapeutic tools available for metabolic reprogramming. Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling. However, spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism, lipid metabolism, and mitochondrial dysfunction. These metabolic disturbances lead to corresponding pathological changes, including the failure of axonal regeneration, the accumulation of scarring, and the activation of microglia. To rescue spinal cord injury at the metabolic level, potential metabolic reprogramming approaches have emerged, including replenishing metabolic substrates, reconstituting metabolic couplings, and targeting mitochondrial therapies to alter cell fate. The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury. To further advance the metabolic treatment of the spinal cord injury, future efforts should focus on a deeper understanding of neurometabolism, the development of more advanced metabolomics technologies, and the design of highly effective metabolic interventions.

Human mesenchymal stem cells (MSCs) have the potential to differentiate into nucleus pulposus (NP)-like cells under specific stimulatory conditions. Thus far, the effects of bone morphogenetic protein 3 (BMP3) and the cocktail effects of BMP3 and transforming growth factor (TGF)-β on MSC proliferation and differentiation remain obscure. Therefore, this study was designed to clarify these unknowns. MSCs were cultured with various gradients of BMP3 and BMP3/TGF-β, and compared with cultures in basal and TGF-β media. Cell proliferation, glycosaminoglycan (GAG) content, gene expression, and signaling proteins were measured to assess the effects of BMP3 and BMP3/TGF-β on MSCs. Cell number and GAG content increased upon the addition of BMP3 in a dose-dependent manner. The expression of COL2A1, ACAN, SOX9, and KRT19 increased following induction with BMP3 and TGF-β, in contrast to that of COL1A1, ALP, OPN, and COMP. Smad3 phosphorylation was upregulated by BMP3 and TGF-β, but BMP3 did not affect the phosphorylation of extracellular-signal regulated kinase (ERK) 1/2 or c-Jun N-terminal kinase (JNK). Our results reveal that BMP3 enhances MSC proliferation and differentiation into NP-like cells, as indicated by increased cell numbers and specific gene expressions, and may also cooperate with TGF-β induced positive effects. These actions are likely related to the activation of TGF-β signaling pathway.

The hard-shelled mussel (Mytilus coruscus) has been used as Chinese traditional medicine for thousands of years; however, to date the ingredients responsible for the various beneficial health outcomes attributed to Mytilus coruscus are still unclear. An α-d-Glucan, called MP-A, was isolated from Mytilus coruscus, and observed to exert anti-inflammatory activity in THP-1 human macrophage cells. Specifically, we showed that MP-A treatment inhibited the production of inflammatory markers, including TNF-α, NO, and PGE2, inducible NOS (iNOS), and cyclooxygenase-2 (COX-2), in LPS-activated THP-1 cells. It was also shown to enhance phagocytosis in the analyzed cells, but to severely inhibit the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear translocation of NF-κB P65. Finally, MP-A was found to exhibit a high binding affinity for the cell surface receptor TLR4, but a low affinity for TLR2 and dectin-1, via surface plasmon resonance (SPR) analysis. The study indicates that MP-A suppresses LPS-induced TNF-α, NO and PEG2 production via TLR4/NF-κB/MAPK pathway inhibition, and suggests that MP-A may be a promising therapeutic candidate for diseases associated with TNF-α, NO, and/or PEG2 overproduction.

BackgroundDespite being considered the standard surgical procedure for symptomatic cervical disc disease, anterior cervical decompression and fusion invariably accelerates adjacent segment degeneration. Cervical total disc replacement is a motion-preserving procedure developed as a substitute to fusion. Whether cervical total disc replacement is superior to fusion remains unclear.MethodsWe comprehensively searched PubMed, EMBASE, Medline, and the Cochrane Library in accordance with the inclusion criteria to identify possible studies. The retrieved results were last updated on December 12, 2014. We classified the studies as short-term and midterm follow-up.ResultsNineteen randomized controlled trials involving 4516 cases were identified. Compared with anterior cervical decompression and fusion, cervical total disc replacement had better functional outcomes (neck disability index [NDI], NDI success, neurological success, neck pain scores reported on a numerical rating scale [NRS], visual analog scales scores and overall success), greater segmental motion at the index level, fewer adverse events and fewer secondary surgical procedures at the index and adjacent levels in short-term follow-up (P < 0.05). With midterm follow-up, the cervical total disc replacement group indicated superiority in the NDI, neurological success, pain assessment (NRS), and secondary surgical procedures at the index level (P < 0.05). The Short Form 36 (SF-36) and segmental motion at the adjacent level in the short-term follow-up showed no significant difference between the two procedures, as did the secondary surgical procedure rates at the adjacent level with midterm follow-up (P > 0.05).ConclusionsCervical total disc replacement presented favorable functional outcomes, fewer adverse events, and fewer secondary surgical procedures. The efficacy and safety of cervical total disc replacement are superior to those of fusion. Longer-term, multicenter studies are required for a better evaluation of the long-term efficacy and safety of the two procedures.