hnRNPA1 SUMOylation promotes cold hypersensitivity in chronic inflammatory pain by stabilizing TRPA1 mRNA.

TRPA1 is pivotal in cold hypersensitivity, but its regulatory mechanisms in inflammatory cold hyperalgesia remain poorly understood. We show here that the upregulation of SUMO1-conjugated protein levels in a complete Freund's adjuvant (CFA)-induced inflammatory pain model enhances TRPA1 mRNA stability, ultimately leading to increased expression levels. We further demonstrate that hnRNPA1 binds to TRPA1 mRNA, and its SUMOylation, upregulated in CFA-induced inflammatory pain, contributes to stabilizing TRPA1 mRNA by accumulating hnRNPA1 in the cytoplasm. Moreover, we find that wild-type hnRNPA1 viral infection in dorsal root ganglia neurons, and not infection with the SUMOylation-deficient hnRNPA1 mutant, can rescue the reduced ability of hnRNPA1-knockdown mice to develop inflammatory cold pain hypersensitivity. These results suggest that hnRNPA1 is a regulator of TRPA1 mRNA stability, the capability of which is enhanced upon SUMO1 conjugation at lysine 3 in response to peripheral inflammation, and the increased expression of TRPA1 in turn underlies the development of chronic inflammatory cold pain hypersensitivity.

N-terminal α-amino SUMOylation of cofilin-1 is critical for its regulation of actin depolymerization.

Small ubiquitin-like modifier (SUMO) typically conjugates to target proteins through isopeptide linkage to the ε-amino group of lysine residues. This posttranslational modification (PTM) plays pivotal roles in modulating protein function. Cofilins are key regulators of actin cytoskeleton dynamics and are well-known to undergo several different PTMs. Here, we show that cofilin-1 is conjugated by SUMO1 both in vitro and in vivo. Using mass spectrometry and biochemical and genetic approaches, we identify the N-terminal α-amino group as the SUMO-conjugation site of cofilin-1. Common to conventional SUMOylation is that the N-α-SUMOylation of cofilin-1 is also mediated by SUMO activating (E1), conjugating (E2), and ligating (E3) enzymes and reversed by the SUMO deconjugating enzyme, SENP1. Specific to the N-α-SUMOylation is the physical association of the E1 enzyme to the substrate, cofilin-1. Using F-actin co-sedimentation and actin depolymerization assays in vitro and fluorescence staining of actin filaments in cells, we show that the N-α-SUMOylation promotes cofilin-1 binding to F-actin and cofilin-induced actin depolymerization. This covalent conjugation by SUMO at the N-α amino group of cofilin-1, rather than at an internal lysine(s), serves as an essential PTM to tune cofilin-1 function during regulation of actin dynamics.

Ultrasonography-assisted assessment of the influence of the volar prominence of the plate on the median nerve in distal radius fractures.

OBJECTIVE: The study aimed to explore the effect of differing volar locking plate (VLP) prominence on the median nerve (MN) in distal radius fracture (DRF) with ultrasound assistance to guide clinical treatment. METHODS: Forty-four patients who received VLP for DRF at our department were admitted and followed-up between January 2019 and May 2021. Different plate positions were graded using Soong classification; 13 were Grade 0, 18 were Grade 1, and 13 were Grade 2. The MN parameters at different wrist positions in patients with different Soong grades were measured with ultrasound assistance, including the median nerve cross-sectional area (MNCSA), diameter in the radial-ulnar direction (D1), and diameter in the dorsal-palmar direction (D2). The sensation in the affected finger and grip strength were collected at follow-up, scored using the Disabilities of the Arm, Shoulder, and Hand (DASH) scale to determine function, and statistically analysed. RESULTS: The MNCSA differed significantly across Soong grades. The MNCSA at the flexed, neutral, and extended wrist positions was smallest at Grade 0 and largest at Grade 2 (P < 0.05), and that at the neutral position was not significantly different between Grades 1 and 2 (P > 0.05). There was no significant interaction between the wrist positions and Soong grade (P > 0.05). The differences in D1 and D2 among different Soong grades were not statistically significant (P > 0.05). There were no statistical differences in grip strength, DASH, and sensation among different Soong grades (P > 0.05). CONCLUSIONS: Differing plate protrusions in DRF treatment did not cause clinical symptoms during follow-up; however, excessive plate protrusion (Soong Grade 2) increased the cross-sectional area of the MN. We recommend placing the plate as proximal as possible during VLP treatment of DRFs to avoid excessive bulges affecting the MN.

Scarcity Value Assessment of Ecosystem Services Based on Changes in Supply and Demand: A Case Study of the Yangtze River Delta City Cluster, China.

Rapid urbanization and economic development have resulted in a mismatch between the supply and demand of ecosystem services. The theoretical value of ecosystem services (ESTV) is not suitable for determining ecosystem service compensation, posing challenges for integrated regional ecological development. A scarcity value model was used to analyze the influence of changes in supply and demand on the scarcity value of ecosystem services (ESSV) in the context of land-use change. The spatio-temporal distribution characteristics and trends of the ESSV from 2010 to 2020 were assessed in the Yangtze River Delta (YRD) urban agglomeration in China, and the driving factors were analyzed to provide theoretical guidance for horizontal ecological compensation across regions. The results show the following: (1) In the scenario that did not consider the impact of supply and demand changes on the scarcity value, the total ESTV decreased by 8.67% from 2010 to 2020, and high-value areas shifted to the west and south, whereas low-value areas shifted to the central and northern region and the Jiangsu, Zhejiang, and Shanghai Ringbelt. The ESTV was low in Shanghai and Jiangsu and high in Zhejiang. (2) In the scenario that considered changes in the supply and demand of ecosystem services, the ESSV increased from RMB 213 million in 2010 to RMB 1.323 billion in 2020; an increase of 521.13%. The scarcity value showed high variability within the provinces, with a larger difference between Zhejiang and Jiangsu and a smaller difference between Anhui and Shanghai. The ESSV was higher in counties with increased urbanization and high population density and lower in counties with slower economic growth and fewer people. (3) Regional ecological integration planning and management should be strengthened, and the ESSV might be considered as the reference standard for ecological compensation. The ESSV showed that spatio-temporal heterogeneity might guide the conversion from ecological resources to ecological capital and promote the regulatory role of market mechanisms to achieve horizontal payments for ecosystem services across regions.

Influences of Land Policy on Urban Ecological Corridors Governance: A Case Study from Shanghai.

The analysis of land use change (LUC) characteristics and the impact of policies related to urban ecological space is required to improve spatial planning and to support decision making regarding green infrastructure (GI) investment. This study employed Geo-informatic Tupu analysis and Fluctuation Potential Tupu analysis methods to analyze the characteristics of LUC in an urban ecological corridor (EC). To help understand the influence of land use policy on GI governance and support the optimization of spatial planning, we proposed a situation-structure-implementation-outcome (SSIO) policy cascade analysis framework. SSIO takes "place" as its starting point, then couples the local policy with the governance structure to promote the sustainability of urban commons governance. The results show that the land use type within an EC in the city is mainly cultivated land. However, between 2009 and 2019, cultivated land, construction land, and facility agricultural land all showed a decreasing trend, while forest land and garden land types underwent increasing trends. The LUC Tupu unit highlights the transition from cultivated land to forest land. Forest land has the greatest increase in area and accounts for 52.34% of the area of increasing land use. Cultivated land shows the greatest decrease in area and accounts for 70.30% of the area of decreasing trends. Based on the local policy situation of the metropolis, a land policy governance mechanism can be constructed by the establishment of a governance structure with local government as the core, using land consolidation as the platform, taking ecological spatial planning and inefficient construction land reduction as typical policy tools, and experimentally integrating the concept of Nature-based Solutions (NbS). In general, these findings may be applicable to other rapidly urbanizing cities around the world that are developing complex land use policies for ecological space governance.

Inelastic phonon transport across atomically sharp metal/semiconductor interfaces.

Understanding thermal transport across metal/semiconductor interfaces is crucial for the heat dissipation of electronics. The dominant heat carriers in non-metals, phonons, are thought to transport elastically across most interfaces, except for a few extreme cases where the two materials that formed the interface are highly dissimilar with a large difference in Debye temperature. In this work, we show that even for two materials with similar Debye temperatures (Al/Si, Al/GaN), a substantial portion of phonons will transport inelastically across their interfaces at high temperatures, significantly enhancing interface thermal conductance. Moreover, we find that interface sharpness strongly affects phonon transport process. For atomically sharp interfaces, phonons are allowed to transport inelastically and interface thermal conductance linearly increases at high temperatures. With a diffuse interface, inelastic phonon transport diminishes. Our results provide new insights on phonon transport across interfaces and open up opportunities for engineering interface thermal conductance specifically for materials of relevance to microelectronics.

TRPV1 SUMOylation suppresses itch by inhibiting TRPV1 interaction with H1 receptors.

The molecular mechanism underlying the functional interaction between H1R and TRPV1 remains unclear. We show here that H1R directly binds to the carboxy-terminal region of TRPV1 at residues 715-725 and 736-749. Cell-penetrating peptides containing these sequences suppress histamine-induced scratching behavior in a cheek injection model. The H1R-TRPV1 binding is kept at a minimum at rest in mouse trigeminal neurons due to TRPV1 SUMOylation and it is enhanced upon histamine treatment through a transient TRPV1 deSUMOylation. The knockin of the SUMOylation-deficient TRPV1K823R mutant in mice leads to constitutive enhancement of H1R-TRPV1 binding, which exacerbates scratching behaviors induced by histamine. Conversely, SENP1 conditional knockout in sensory neurons enhances TRPV1 SUMOylation and suppresses the histamine-induced scratching response. In addition to interfering with binding, TRPV1 SUMOylation promotes H1R degradation through ubiquitination. Our work unveils the molecular mechanism of histaminergic itch by which H1R directly binds to deSUMOylated TRPV1 to facilitate the transduction of the pruritogen signal to the scratching response.

Combined Use of Chitosan-PGLA Nerve Grafts and Bone Marrow Mononuclear Cells to Repair a 50-mm-long Median Nerve Defect Combined with an 80-mm-long Ulnar Nerve Defect in the Human Upper Arm.

BACKGROUND: Severe peripheral nerve injury, especially the long-distance peripheral nerve defect, causes severe functional disability in patients. There is always a lack of effective repair methods for clinic, and those in practice are associated with side effects. A case study was performed to observe the regenerative outcomes of the surgical repair of long-distance peripheral nerve defects in the upper arm with chitosan-poly(glycolide-co-lactide) (PGLA) nerve grafts combined with bone marrow mononuclear cells (BMMCs). METHODS: The right upper arm of a 29-year-old woman was injured, leaving a 50-mm-long median nerve defect, an 80-mm-long ulnar nerve defect, and muscle and blood vessel disruptions. The nerve defects were repaired by implanting BMMC-containing chitosan-PGLA nerve grafts on the 40th day after injury. A series of functional assessments were carried out from 2 weeks to 66 months after surgical repair. Sensory function was assessed by the pinprick test, two-point discrimination test and Semmes-Weinstein monofilament test. Motor function was evaluated by the range of motion of the wrist joint and muscle power. Autonomic function was monitored by laser-Doppler perfusion imaging (LDPI). Tissue morphology was observed through ultrasonic investigations. RESULTS: No adverse events, such as infection, allergy, or rejection, caused by the treatment were detected during the follow-up period. Sensory and pinprick nociception in the affected thumb, index, and middle fingers gradually restored at 6th month after surgery. The monofilament tactile sensation was 0.4 g in the terminal finger pulp of the thumb and index finger, 2.0 g in the middle finger, and greater than 300 g in the ring finger and little finger at the 66th month. Motor function recovery was detected at the 5th month after surgery, when the muscle strength of the affected forearm flexors began to recover. At the 66th month after surgery, the patient's forearm flexor strength was grade 4, with 80° of palmar flexion, 85° of dorsal extension, 8° of radial deviation, 40° of ulnar deviation, 40° of anterior rotation, and 85° of posterior rotation of the affected wrist. The patient could perform holding, picking up, and some other daily activities with the affected hand. The patient's sweating function of the affected hand was close to the level of the healthy hand. LDPI showed that the skin blood flow perfusion was significantly increased, with perfusion similar to on the normal side in some areas. Neuromusculoskeletal ultrasonography showed the presence of nerve structures. CONCLUSION: These results suggest that chitosan-PGLA nerve grafts combined with BMMCs could effectively repair long-distance nerve defects and achieve good clinical results.

BMSC-derived extracellular matrix better optimizes the microenvironment to support nerve regeneration.

A favorable microenvironment plays an important role in nerve regeneration. Extracellular matrix (ECM) derived from cultured cells or natural tissues can facilitate nerve regeneration in the presence of various microenvironmental cues, including biochemical, spatial, and biomechanical factors. This study, through proteomics and three-dimensional image analysis, determines that the components and spatial organization of the ECM secreted by bone marrow mesenchymal cells (BMSCs) are more similar to acellular nerves than those of the ECMs derived from Schwann cells (SCs), skin-derived precursor Schwann cells (SKP-SCs), or fibroblasts (FBs). ECM-modified nerve grafts (ECM-NGs) are engineered by co-cultivating BMSCs, SCs, FBs, SKP-SCs with well-designed nerve grafts used to bridge nerve defects. BMSC-ECM-NGs exhibit the most promising nerve repair properties based on the histology, neurophysiology, and behavioral analyses. The regeneration microenvironment formed by the ECM-NGs is also characterized by proteomics, and the advantages of BMSC-ECM-NGs are evidenced by the enhanced expression of factors related to neural regeneration and reduced immune response. Together, these findings indicate that BMSC-derived ECMs create a more superior microenvironment for nerve regeneration than that by the other ECMs and may, therefore, represent a potential alternative for the clinical repair of peripheral nerve defects.

GPU_PBTE: an efficient solver for three and four phonon scattering rates on graphics processing units.

Lattice thermal conductivity (LTC) is a key parameter for many technological applications. Based on the Peierls-Boltzmann transport equation (PBTE), many unique phonon transport properties of various materials were revealed. Accurate calculation of LTC with PBTE, however, is a time-consuming task, especially for compounds with a complex crystal structure or taking high-order phonon scattering into consideration. Graphical processing units (GPUs) have been extensively used to accelerate scientific simulations, making it possible to use a single desktop workstation for calculations that used to require supercomputers. Due to its fundamental differences from traditional processors, GPUs are especially suited for executing a large group of similar tasks with minimal communication, but require completely different algorithm design. In this paper, we provide a new algorithm optimized for GPUs, where a two-kernel method is used to avoid divergent branching. A new open-source code, GPU_PBTE, is developed based on the proposed algorithm. As demonstrations, we investigate the thermal transport properties of silicon and silicon carbide, and find that accurate and reliable LTC can be obtained by our software. GPU_PBTE performed on NVIDIA Tesla V100 can extensively improve double precision performance, making it two to three orders of magnitude faster than our CPU version performed on Intel Xeon CPU Gold 6248 @2.5 GHz. Our work also provides an idea of accelerating calculations with other novel hardware that may come out in the future.

High-temperature phonon transport properties of SnSe from machine-learning interatomic potential.

As a promising thermoelectric material, tin selenide (SnSe) is of relatively low thermal conductivity. However, the phonon transport mechanisms in SnSe are not fully understood due to the complex phase transition, dynamical instability, and strong anharmonicity. In this work, we perform molecular dynamics simulations with a machine-learning interatomic potential to explore the thermal transport properties of SnSe at different temperatures. The developed interatomic potential is parameterized using the framework of moment tensor potential, exhibiting satisfactory predictions on temperature-dependent lattice constants and phonon dispersion, as well as phase transition temperature. From equilibrium molecular dynamics simulations, we obtained the thermal conductivity tensor from 200 K to 900 K. The origins of temperature-dependent thermal conductivity anisotropy and the roles of four-phonon scatterings are identified. The obtained interatomic potential can be utilized to study the mechanical and thermal properties of SnSe and related nanostructures in a wide range of temperatures.

Application of stem cells in peripheral nerve regeneration.

Traumatic peripheral nerve injury is a worldwide clinical issue with high morbidity. The severity of peripheral nerve injury can be classified as neurapraxia, axonotmesis or neurotmesis, according to Seddon's classification, or five different degrees according to Sunderland's classification. Patients with neurotmesis suffer from a complete transection of peripheral nerve stumps and are often in need of surgical repair of nerve defects. The applications of autologous nerve grafts as the golden standard for peripheral nerve transplantation meet some difficulties, including donor nerve sacrifice and nerve mismatch. Attempts have been made to construct tissue-engineered nerve grafts as supplements or even substitutes for autologous nerve grafts to bridge peripheral nerve defects. The incorporation of stem cells as seed cells into the biomaterial-based scaffolds increases the effectiveness of tissue-engineered nerve grafts and largely boosts the regenerative process. Numerous stem cells, including embryonic stem cells, neural stem cells, bone marrow mesenchymal stem cells, adipose stem cells, skin-derived precursor stem cells and induced pluripotent stem cells, have been used in neural tissue engineering. In the current review, recent trials of stem cell-based tissue-engineered nerve grafts have been summarized; potential concerns and perspectives of stem cell therapeutics have also been contemplated.

Lithium promotes proliferation and suppresses migration of Schwann cells.

Schwann cell proliferation, migration and remyelination of regenerating axons contribute to regeneration after peripheral nervous system injury. Lithium promotes remyelination by Schwann cells and improves peripheral nerve regeneration. However, whether lithium modulates other phenotypes of Schwann cells, especially their proliferation and migration remains elusive. In the current study, primary Schwann cells from rat sciatic nerve stumps were cultured and exposed to 0, 5, 10, 15, or 30 mM lithium chloride (LiCl) for 24 hours. The effects of LiCl on Schwann cell proliferation and migration were examined using the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, Transwell and wound healing assays. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays showed that 5, 10, 15, and 30 mM LiCl significantly increased the viability and proliferation rate of Schwann cells. Transwell-based migration assays and wound healing assays showed that 10, 15, and 30 mM LiCl suppressed the migratory ability of Schwann cells. Furthermore, the effects of LiCl on the proliferation and migration phenotypes of Schwann cells were mostly dose-dependent. These data indicate that lithium treatment significantly promotes the proliferation and inhibits the migratory ability of Schwann cells. This conclusion will inform strategies to promote the repair and regeneration of peripheral nerves. All of the animal experiments in this study were ethically approved by the Administration Committee of Experimental Animal Center of Nantong University, China (approval No. 20170320-017) on March 2, 2017.

Monitoring anharmonic phonon transport across interfaces in one-dimensional lattice chains.

Modeling thermal transport through interfaces has been one of the most challenging problems in nanoscale heat transfer. Although continuous theoretical efforts have been made, there has been no consensus on how to rigorously incorporate temperature effect and anharmonicity. In this paper, we adopt the self-consistent anharmonic phonon concept for nonlinear lattices to investigate phonon propagation within the materials as well as across interfaces based on equilibrium molecular dynamics simulations. Based on linear response theory, we propose an efficient method to calculate the frequency-dependent transmission coefficient in a nonlinear lattice. The transmission spectrum is extracted directly from velocity correlations, which naturally includes anharmonic effects. Phonon renormalization at finite temperature can also be easily handled using the proposed method. Our results are consistent with the atomistic Green's function method at the limit of weak anharmonicity. For nonlinear lattices under high temperatures, the anharmonicity is found to increase the cutoff frequency of the transmission coefficient due to phonon renormalization. Further analysis shows that the anharmonicity also promotes interfacial thermal conductance by causing the redistribution of the spectral flux of the excited vibrational waves during their propogation.

Biological characteristics of dynamic expression of nerve regeneration related growth factors in dorsal root ganglia after peripheral nerve injury.

The regenerative capacity of peripheral nerves is limited after nerve injury. A number of growth factors modulate many cellular behaviors, such as proliferation and migration, and may contribute to nerve repair and regeneration. Our previous study observed the dynamic changes of genes in L4-6 dorsal root ganglion after rat sciatic nerve crush using transcriptome sequencing. Our current study focused on upstream growth factors and found that a total of 19 upstream growth factors were dysregulated in dorsal root ganglions at 3, 9 hours, 1, 4, or 7 days after nerve crush, compared with the 0 hour control. Thirty-six rat models of sciatic nerve crush injury were prepared as described previously. Then, they were divided into six groups to measure the expression changes of representative genes at 0, 3, 9 hours, 1, 4 or 7 days post crush. Our current study measured the expression levels of representative upstream growth factors, including nerve growth factor, brain-derived neurotrophic factor, fibroblast growth factor 2 and amphiregulin genes, and explored critical signaling pathways and biological process through bioinformatic analysis. Our data revealed that many of these dysregulated upstream growth factors, including nerve growth factor, brain-derived neurotrophic factor, fibroblast growth factor 2 and amphiregulin, participated in tissue remodeling and axon growth-related biological processes Therefore, the experiment described the expression pattern of upstream growth factors in the dorsal root ganglia after peripheral nerve injury. Bioinformatic analysis revealed growth factors that may promote repair and regeneration of damaged peripheral nerves. All animal surgery procedures were performed in accordance with Institutional Animal Care Guidelines of Nantong University and ethically approved by the Administration Committee of Experimental Animals, China (approval No. 20170302-017) on March 2, 2017.

A minimal Tersoff potential for diamond silicon with improved descriptions of elastic and phonon transport properties.

Silicon is an important material and many empirical interatomic potentials have been developed for atomistic simulations of it. Among them, the Tersoff potential and its variants are the most popular ones. However, all the existing Tersoff-like potentials fail to reproduce the experimentally measured thermal conductivity of diamond silicon. Here we propose a modified Tersoff potential and develop an efficient open source code called GPUGA (graphics processing units genetic algorithm) based on the genetic algorithm and use it to fit the potential parameters against energy, virial and force data from quantum density functional theory calculations. This potential, which is implemented in the efficient open source GPUMD (graphics processing units molecular dynamics) code, gives significantly improved descriptions of the thermal conductivity and phonon dispersion of diamond silicon as compared to previous Tersoff potentials and at the same time well reproduces the elastic constants. Furthermore, we find that quantum effects on the thermal conductivity of diamond silicon at room temperature are non-negligible but small: using classical statistics underestimates the thermal conductivity by about 10% as compared to using quantum statistics.

Dysregulated Transcription Factor TFAP2A After Peripheral Nerve Injury Modulated Schwann Cell Phenotype.

Transcription factors regulate the transcriptions and expressions of numerous target genes and direct a variety of physiological and pathological activities. To obtain a better understanding of the involvement of transcription factors during peripheral nerve repair and regeneration, significantly differentially expressed genes coding for transcription factors in rat sciatic nerves after sciatic nerve crush injury were identified. A total of 9 transcription factor genes, including GBX2, HIF3A, IRF8, LRRC63, SNAI3, SPIB, TBX21, TFAP2A, and ZBTB16 were identified to be commonly differentially expressed at 1, 4, 7, and 14 days after nerve injury. TFAP2A, a gene encoding transcription factor activating enhancer binding protein 2 alpha, was found to be critical in the regulatory network. PCR validation and immunohistochemistry staining of injured rat sciatic nerves showed that TFAP2A expression was significantly up-regulated in the Schwann cells after nerve injury for at least 2 weeks. Schwann cells transfected with TFAP2A-siRNA exhibited elevated proliferation rate and migration ability, suggesting that TFAP2A suppressed Schwann cell proliferation and migration. Collectively, our study provided a global overview of the dynamic changes of transcription factors after sciatic nerve injury, discovered key transcription factors for the regeneration process, and deepened the understanding of the molecular mechanisms underlying peripheral nerve repair and regeneration.

Dual-wavelength erbium-doped fluoride fiber laser.

The laser source with 3 µm/2 µm output wavelength has many application prospects in clinical medicine, photoelectric countermeasure, and scientific research measurement. An Er3+ doped ZBLAN fiber laser with output wavelength of 2 .8 µm and 1 .6 µm is experimentally studied. By setting the pump power to 5 W, a continuous dual-wavelength output with a central wavelength of 2.803 µm and 1.61 µm is obtained and the corresponding maximum output power is 362.4 mW and 108.6 mW. The slope efficiency is 12.1% and 4.94% respectively. What's more, the slope efficiency is 12.1% and 4.94% respectively, and the fluctuation rates of peak power of the two wavelengths are 9.7% and 2.1% within 4 h which indicate that the laser has relatively good stability.

Spatial Accessibility to Healthcare Services in Metropolitan Suburbs: The Case of Qingpu, Shanghai.

Spatial accessibility is an important factor for planning healthcare services to maintain a quality life for the metropolitan area. The metropolitan suburb is a special area for its location and rapidly changing population during urbanization. Taking Qingpu district, a suburb of Shanghai as a case, this study evaluated the spatial accessibility to healthcare services of 203 villages and neighborhoods based on the Two-Step Floating Catchment Area (2SFCA) method by ArcGIS software. The result shows that the spatial accessibility in the whole district is quite uneven under lower thresholds, and the spatial differences are beyond the traditional zoning of East Qingpu, New City and West Qingpu. The worst accessibility was mainly distributed at the edges of Jinze, Liantang and Zhujiajiao, while the best accessibility was mainly distributed in the New City and the region close around it. The average value of the spatial accessibility in Qingpu is 2.84, with a reach equal under 90 min threshold by bus index of 2.85, or an under 60 min threshold by self-driving index of 2.70. Secondly, the difference shows a new pattern, that is the spatial accessibility could be affected by both the New City and the Central City. Thirdly, the transportation mode, urbanization, the density of road network and bus lines, as well as the number of doctors in each healthcare service would directly affect the spatial accessibility. Lastly, in order to improve the spatial accessibility in metropolitan suburbs, greater effort is needed in increasing the numbers of bus stations and doctors, especially the areas which are farthest from the New City or the Central City, such as Jinze, and Lian Tang town in Qingpu. We acknowledge that the public transportation is vital to the accessibility to healthcare services. We also emphasize that healthcare services should be planned based on the anticipated future trends of population agglomeration. Our results for Shanghai are applicable to other big cities that are experiencing similar rapid urbanization in China, or other developing countries in Southeast Asia, South Asia, South America and Africa.

Electrospun silk fibroin-based neural scaffold for bridging a long sciatic nerve gap in dogs.

Silk fibroin (SF)-derived silkworms represent a type of highly biocompatible biomaterial for tissue engineering. We have previously investigated biocompatibility of SF with neural cells isolated from the central nervous system or peripheral nerve system in vitro, and also developed a SF-based nerve graft conduit or tissue-engineered nerve grafts by introducing bone marrow mesenchymal stem cells, as support cells, into SF-based scaffold and evaluated the outcomes of peripheral nerve repair in a rat model. As an extension of the previous study, the electrospun technique was performed here to fabricate SF-based neural scaffold inserted with silk fibres for bridging a 30-mm-long sciatic nerve gap in dogs. Assessments including functional, histological and morphometrical analyses were applied 12 months after surgery. All the results indicated that the SF-based neural scaffold group achieved satisfactory regenerative outcomes, which were close to those achieved by autologous nerve grafts as the golden-standard for peripheral nerve repair. Overall, our results raise a potential possibility for the translation of SF-based electrospun neural scaffolds as an alternative to nerve autografts into the clinic.