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Green technology innovation is increasingly becoming an important driver of modern development. Facing the pressure of the carbon neutrality target, China has been strengthening environmental regulations in recent years, and the green technology innovation ability of market players has been affected. Moreover, the impact of environmental regulations on green technology innovation and the strategies to develop green technology innovation still need to be further explored. Here, we used 285 cities from 2010–2020 as research subjects, constructed indicators such as environmental regulation and green technology innovation capability, and used panel regression, threshold effect and mediating effect methods. The results reveal that: (1) environmental regulation has a disincentive effect on green technology innovation, as increased environmental regulation increases production costs, external costs and opportunity costs for firms, causing a mismatch of resources and creating a “crowding-out effect” that inhibits innovation development; (2) further study finds that when the human capital level reaches a certain threshold value, the impact of environmental regulation on green technology innovation shifts significantly, i.e., there is a threshold effect; (3) industrial structure can further be upgraded and optimized by environmental regulation, which will have an impact on green technology innovation, thus industrial structure optimization plays a mediating role. We conclude with recommendations for improving green innovation techniques for market players, and provide some lessons for accelerating the goal of carbon neutrality and promoting quality economic development.

To address the problems of low accuracy of existing deep learning-based micro-expression recognition models, numerous network parameters, and the difficulty of mobile deployment of micro-expression recognition models, this paper proposes DCBAM-EfficientNet, a micro-expression recognition model that uses the lightweight network EfficientNet as the backbone network and incorporates the attention module. The network can guarantee the accuracy of micro-expression recognition with relatively few network parameters. The attention mechanism allows the more expressive micro-expression features to be highlighted, and the CBAM attention is improved into a DCBAM model, where the large convolution kernel in the spatial attention module of CBAM is replaced by a dilated convolution with the same receptive field, reducing the network parameters while better preserving the spatial features of the image. The integration of the DCBAM model into the main structure of EfficientNet enables better integration of contextual information. Data enhancement is used to process the micro-expression dataset to decrease the occurrence of overfitting and improve the generalization ability of the model. The results demonstrate that the optimized model DCBAM-EfficientNet can effectively promote the recognition accuracy of micro-expressions, significantly reduce the quantity and volume of model parameters, and provide a reference for the deployment of mobile micro-expression recognition models.

Targeting immune checkpoints such as programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for treating melanoma, gastric cancer (GC) and bladder cancer with clinical benefit. Nevertheless, many patients failed to respond to anti-PD-1/PD-L1 treatment, so it is necessary to seek an alternative strategy for traditional PD-1/PD-L1 targeting immunotherapy. Here with the data from The Cancer Genome Atlas (TCGA) and our in-house tissue library, PD-L1 expression was found to be positively correlated with the expression of ubiquitin-specific processing protease 7 (USP7) in GC. Furthermore, USP7 directly interacted with PD-L1 in order to stabilize it, while abrogation of USP7 attenuated PD-L1/PD-1 interaction and sensitized cancer cells to T cell killing in vitro and in vivo. Besides, USP7 inhibitor suppressed GC cells proliferation by stabilizing P53 in vitro and in vivo. Collectively, our findings indicate that in addition to inhibiting cancer cells proliferation, USP7 inhibitor can also downregulate PD-L1 expression to enhance anti-tumor immune response simultaneously. Hence, these data posit USP7 inhibitor as an anti-proliferation agent as well as a novel therapeutic agent in PD-L1/PD-1 blockade strategy that can promote the immune response of the tumor., Graphical abstract This study supports that small molecule USP7 inhibitors may be used as novel promoter of the tumor immune response.Image 1

Rationale: Local hypoxia is a challenge for fabrication of cellular grafts and treatment of peripheral nerve injury. In our previous studies, we demonstrated that perfluorotributylamine (PFTBA) could provide short term oxygen supply to Schwann cells (SCs) and counteract the detrimental effects of hypoxia on SCs during the early stages of nerve injury. However, the quick release of oxygen in PFTBA compromised its ability to counteract hypoxia over an extended time, limiting its performance in peripheral nerve injury. Methods: In this study, PFTBA-based oxygen carrier systems were prepared through coaxial electrospinning to prolong the time course of oxygen release. Core-shell structures were fabricated, optimized, and the oxygen kinetics of PFTBA-enriched core-shell fibers evaluated. The effect of core-shells on the survival and function of SCs was examined in both 2D and 3D systems as well as in vivo. The system was used to bridge large sciatic nerve defects in rats. Results: PFTBA core-shell fibers provided high levels of oxygen to SCs in vitro, enhancing their survival, and increasing NGF, BDNF, and VEGF expression in 2D and 3D culture systems under hypoxic condition. In vivo analysis showed that the majority of GFP-expressing SCs in the PFTBA conduit remained viable 14 days post-implantation. We found that axons in PFTBA oxygen carrier scaffold improved axonal regeneration, remyelination, and recovery. Conclusion: A synthetic oxygen carrier in core-shell fibers was fabricated by the coaxial electrospinning technique and was capable of enhancing SC survival and nerve regeneration by prolonged oxygen supply. These findings provide a new strategy for fabricating cellular scaffolds to achieve regeneration in peripheral nerve injury treatment and other aerobic tissue injuries.

In this paper, an integrated optimal scheduling and predictive control scheme with a hierarchical structure is proposed for energy management of an urban complex (UC). The proposed scheme consists of a scheduling layer optimizing the energy usage of the UC and a control layer controlling the heating, ventilation, and air conditioning (HVAC) in each individual building. In the control layer, a detailed physical model of the individual building with HVAC system is developed to predict its energy consumption while considering the thermal dynamics of the building envelope with multiple layers of construction material. In the scheduling layer, a multi-objective optimal scheduling is formulated based on the predictive energy consumption of the buildings to reduce the peak-valley load difference and minimize the operating cost of the UC. Finally, the optimal control schedules are obtained and issued to the individual HVACs. Numerical results show that the proposed method can reduce the operating cost and reduce the peak-valley load difference for the UC. Meanwhile, the HVACs can be controlled in an optimal way within the limits of indoor temperature.

A simple dynamic model to simulate heating/cooling energy consumption in a building was proposed in this paper. The model consists of several transient energy balance equations for external walls and internal air, in which the convective heat transfer, conductive heat transfer and heat storage in the heat transfer process are considered. The proposed model has been implemented utilizing the SIMULINK/MATLAB platform. Then, a model predictive control (MPC) approach for the building Microgrid considering the dynamic thermal characteristics of the building was proposed. The MPC approach aims to minimize the total energy consumption of the building Microgrid by combining the model predictive and the short-term control, and guarantees the customer temperature comfort level at the same time. Two comparative cases are presented to verify the effectiveness of the proposed MPC approach.

Delivery of multiple neurotrophic factors (NTFs), especially with time-restricted release kinetics, holds great potential for nerve repair. In this study, we utilized the tetracycline-regulatable Tet-On 3G system to control the expression of c-Jun, which is a common regulator of multiple NTFs in Schwann cells (SCs). In vitro, Tet-On/c-Jun-modified SCs showed a tightly controllable secretion of multiple NTFs, including glial cell line-derived NTF, nerve growth factor, brain-derived NTF, and artemin, by the addition or removal of doxycycline (Dox). When Tet-On/c-Jun-transduced SCs were grafted in vivo, the expression of NTFs could also be regulated by oral administration or removal of Dox. Fluoro-Gold retrograde tracing results indicated that a biphasic NTF expression scheme (Dox+3/-9, NTFs were up-regulated for 3 wk and declined to physiologic levels for another 9 wk) achieved more axonal regeneration than continuous up-regulation of NTFs (Dox+12) or no NTF induction (Dox-12). More importantly, the Dox+3/-9-group animals showed much better functional recovery than the animals in the Dox+12 and Dox-12 groups. Our findings, for the first time, demonstrated drug-controllable expression of multiple NTFs in nerve repair cells both in vitro and in vivo. These findings provide new hope for developing an optimal therapeutic alternative for nerve repair through the time-restricted release of multiple NTFs using Tet-On/c-Jun-modified SCs.-Huang, L., Xia, B., Shi, X., Gao, J., Yang, Y., Xu, F., Qi, F., Liang, C., Huang, J., Luo, Z. Time-restricted release of multiple neurotrophic factors promotes axonal regeneration and functional recovery after peripheral nerve injury.

This paper aims to develop a hierarchical management strategy for the building microgrid. The proposed hierarchical framework is presented as day-ahead scheduling stage and a two-layer intra-hour adjustment stage. Firstly, a virtual storage system (VSS) model is developed by utilizing the heat storage characteristics of a building. Then, the VSS model is integrated into the developed hierarchical management strategy of the building microgrid, which is presented as a day-ahead optimal economic scheduling stage for the minimum operation cost and an intra-hour adjustment stage to follow the tie-line power set-points. In the intra-hour real-time adjustment, a master–client structure is designed. The VSS and plug-in electric vehicles (EVs) are coordinated by a method with two different time scales in order to execute the schedule and handle uncertainties from the load demand, outdoor environment and the renewable generation in the intra-hour adjustment stage. Numerical studies demonstrate that the proposed strategy can contribute to the operation cost reduction in day-ahead scheduling stage and tie-line power smoothing in intra-hour adjustment stage, while guarantee the customer temperature comfort level and EVs travelling demands at the same time.

In this paper, a model predictive control (MPC) based scheduling method for a building microgrid was proposed. Firstly, a dynamic model to simulate heating/cooling energy consumption for a building was proposed. The model consists of several transient energy balance equations for external walls and internal air, in which the convective heat transfer, conductive heat transfer and heat storage in the heat transfer process are considered. The proposed model has been implemented utilizing the Simulink/MATLAB platform. Then, a MPC based scheduling method for the building microgrid considering the dynamic thermal characteristics of the building was proposed. The MPC method aims to minimize the total energy consumption of the building microgrid by combining the model predictive and the short-term control, and guarantees the customer temperature comfort level at the same time. Two comparative cases are presented to verify the effectiveness of the proposed MPC method. Numerical studies demonstrate that the proposed MPC based scheduling method can not only contribute to cost reduction, but also contribute to better renewables hosting capability for the building microgrid.

As one of the most successfully commercialized distributed energy resources, the long-term effects of microturbines (MTs) on the distribution network has not been fully investigated due to the complex thermo-fluid-mechanical energy conversion processes. This is further complicated by the fact that the parameter and internal data of MTs are not always available to the electric utility, due to different ownerships and confidentiality concerns. To address this issue, a general modeling approach for MTs is proposed in this paper, which allows for the long-term simulation of the distribution network with multiple MTs. First, the feasibility of deriving a simplified MT model for long-term dynamic analysis of the distribution network is discussed, based on the physical understanding of dynamic processes that occurred within MTs. Then a three-stage identification method is developed in order to obtain a piecewise MT model and predict electro-mechanical system behaviors with saturation. Next, assisted with the electric power flow calculation tool, a fast simulation methodology is proposed to evaluate the long-term impact of multiple MTs on the distribution network. Finally, the model is verified by using Capstone C30 microturbine experiments, and further applied to the dynamic simulation of a modified IEEE 37-node test feeder with promising results.

The treatment of lengthy peripheral nerve defects is challenging in the field of the regenerative medicine. Thus far, many nerve scaffolds with seeded cells have been developed, which hold great potential to replace nerve autograft in bridging lengthy nerve defects by providing guiding and bioactive cues. However, low oxygen status has been found within nerve scaffolds after their implantation in vivo, which has been shown to result in death or loss of function of supportive cells, and significantly limit nerve regeneration and functional recovery after nerve injury. In the present study, perfluorotributylamine (PFTBA) was introduced into a collagen-chitosan conduit within which olfactory ensheathing cells (OECs) were seeded to increase oxygen supply to OECs, as well as regenerating axons. The “PFTBA-OECs” enriched scaffolds were then used to bridge a 15-mm-long sciatic nerve defect in rats. Both nerve regeneration and functional recovery were examined at pre-defined time points after surgery. We found that the number of GFP-labeled OECs was significantly higher in the “PFTBA-OECs” scaffold than that in the single OECs scaffold. In addition, PFTBA was found to enhance the beneficial effect of OECs-enriched scaffold on axonal regeneration and functional recovery. All these findings indicate that the “PFTBA-OECs” enriched scaffolds are capable of promoting nerve regeneration and functional recovery, which might be attributable, at least in part, to their beneficial effect on the survival of OECs after their implantation in vivo.

This paper proposes a simplified microturbine (MT) model which allows for dynamic heat and power output prediction. Considering the time-scale difference of various dynamic processes occuring within MTs, the electromechanical subsystem is treated as a fast quasi-linear system while the thermo-mechanical subsystem is treated as a slow process with high nonlinearity. A subspace model identification method is utilized to capture dominant dynamics and predict outputs of the electromechanical subsystem. For the thermo-mechanical process, a fast recursive algorithm assisted radial basis function model is employed to handle the strong nonlinear characteristics. Experimental tests on a Capstone C30 MT show that the proposed modeling method can well capture the system dynamics and produce a good model to predict the interrelated heat and electricity outputs.

In this paper, a building based virtual storage system (VSS) model is developed by utilizing the heat storage characteristics of the building. Then, the VSS is integrated to the optimal scheduling model of the building microgrid (BM) for operation cost reduction. The indoor temperature of the building is adjusted within the customer temperature comfort level range to manage the charging/discharging power of the VSS. Finally, two different types of BM cases under the summer refrigeration scenario are carried out to demonstrate the effectiveness of the proposed optimal scheduling approach. Numerical studies demonstrate that the proposed optimal scheduling approach can make full use of the potential of the VSS and furthermore contribute to the operation cost reduction of the BM, while guarantee the customer temperature comfort level at the same time.

Background Artifical nerve scaffold can be used as a promising alternative to autologous nerve grafts to enhance the repair of peripheral nerve defects. However, current nerve scaffolds lack efficient microstructure and neurotrophic support. Methods Microsphere–Scaffold composite was developed by incorporating chitosan microspheres loaded with nerve growth factor (NGF–CMSs) into collagen-chitosan scaffolds (CCH) with longitudinally oriented microchannels (NGF–CMSs/CCH). The morphological characterizations, in vitro release kinetics study, neurite outgrowth assay, and bioactivity assay were evaluated. After that, a 15-mm-long sciatic nerve gap in rats was bridged by the NGF–CMSs/CCH, CCH physically absorbed NGF (NGF/CCH), CCH or nerve autograft. 16 weeks after implantation, electrophysiology, fluoro-gold retrograde tracing, and nerve morphometry were performed. Results The NGF–CMSs were evenly distributed throughout the longitudinally oriented microchannels of the scaffold. The NGF–CMSs/CCH was capable of sustained release of bioactive NGF within 28 days as compared with others in vitro. In vivo animal study demonstrated that the outcomes of NGF–CMSs/CCH were better than those of NGF/CCH or CCH. Conclusion Our findings suggest that incorporation of NGF–CMSs into the CCH may be a promising tool in the repair of peripheral nerve defects.

Schwann cell (SC), which plays a key role in peripheral nerve regeneration, is one of the most classic supportive cells in neural tissue engineering. However, the biological activity of SCs seeded in nerve scaffolds decays subsequently due to local hypoxia induced by ischemia. Thus, we aimed to investigate whether a synthetic oxygen carrier-enriched fibrin gel would provide a sustained oxygen release to cultured SCs in vitro for overcoming a temporary (48 h) oxygen deprivation. In this study, perfluorotributylamine (PFTBA)-based oxygen carrying fibrin gel was prepared to provide oxygen for SCs under normoxic or hypoxic conditions. The dissolved oxygen within the culture media was measured by a blood-gas analyzer to quantify the time course of oxygen release from the PFTBA-enriched fibrin gel. SCs were cultured in the presence or absence of PFTBA-enriched fibrin gel under normoxic or hypoxic conditions. The tolerance of SCs to hypoxia was examined by a cell apoptosis assay. The growth of cells was characterized using S-100 staining and a CCK-8 assay. The migration of cells was examined using a Transwell chamber. The mRNA of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial cell derived neurotrophic factor (GDNF), neural cell adhesion molecule (N-CAM) and vascular endothelial growth factor (VEGF) in SCs were assayed by RT-PCR. In addition, SCs cultured in 3D PFTBA-enriched hydrogel were characterized by Live/Dead staining and the mRNA levels of BDNF, NGF, GDNF, N-CAM and VEGF were assayed by RT-PCR. The results showed that the PFTBA-enriched fibrin hydrogel was able to promote cell adhesion, migration, and proliferation under hypoxic conditions. Interestingly, PFTBA applied through the fibrin hydrogel dramatically enhanced the mRNA of BDNF, NGF, GDNF, N-CAM and VEGF under hypoxic condition. These findings highlight the possibility of enhancing nerve regeneration in cellular nerve grafts through PFTBA increased neurotropic secretion in SCs.

Electrical stimulation (ES) applied to a conductive nerve graft holds the great potential to improve nerve regeneration and functional recovery in the treatment of lengthy nerve defects. A conductive nerve graft can be obtained by a combination of conductive nerve scaffold and olfactory ensheathing cells (OECs), which are known to enhance axonal regeneration and to produce myelin after transplantation. However, when ES is applied through the conductive graft, the impact of ES on OECs has never been investigated. In this study, a biodegradable conductive composite made of conductive polypyrrole (PPy, 2.5%) and biodegradable chitosan (97.5%) was prepared in order to electrically stimulate OECs. The tolerance of OECs to ES was examined by a cell apoptosis assay. The growth of the cells was characterized using DAPI staining and a CCK-8 assay. The mRNA and protein levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neural cell adhesion molecule (N-CAM), vascular endothelial growth factor (VEGF) and neurite outgrowth inhibitor-A (NOGO-A) in OECs were assayed by RT-PCR and Western blotting, and the amount of BDNF, NGF, N-CAM, VEGF and NOGO-A secreted was determined by an ELISA assay. The results showed that the PPy/chitosan membranes supported cell adhesion, spreading, and proliferation with or without ES. Interestingly, ES applied through the PPy/chitosan composite dramatically enhanced the expression and secretion of BDNF, NGF, N-CAM and VEGF, but decreased the expression and secretion of NOGO-A when compared with control cells without ES. These findings highlight the possibility of enhancing nerve regeneration in conductive scaffolds through ES increased neurotrophin secretion in OECs.

Tissue-engineering nerve conduits have been studied for a long time in bridging large nerve defects. However, the low oxygen availability within the nerve conduits, which results in death of migratory Schwann cells (SC) or loss of the newly formed tissue's function, is still an obstacle for axonal regeneration. Thus, it was hypothesized that an oxygen-enriched conduit would enhance axonal regeneration and functional recovery in vivo. To address this issue, perfluorotributylamine (PFTBA) enriched fibrin hydrogel was prepared and injected into collagen-chitosan conduits. The conduit containing PFTBA-enriched fibrin hydrogel was then used to bridge a 12-mm sciatic nerve defect in rats. The control rats were bridged with collagen-chitosan conduits filled with fibrin matrices without PFTBA. It was found that axonal regeneration and functional recovery in the combined PFTBA group were significantly higher than those in the control group without PFTBA. Further investigations showed that the mRNA and protein levels of S-100, brain-derived neurotrophic factor and nerve growth factor were enhanced by PFTBA at 1 and 3weeks after surgery. However, the mRNA and protein levels of vascular endothelial growth factor were in a similar range between the combined PFTBA group and the control group without PFTBA. In addition, immunohistochemical results showed that the morphological appearances of regenerated nerve and survival of SC were enhanced by PFTBA at 4 and 12weeks after surgery. In conclusion, PFTBA-enriched nerve conduit is capable of enhancing axonal regeneration, which provides a new avenue for achieving better functional recovery in the treatment of nerve defect.