How does digital inclusive finance affect the ecological environment? Evidence from Chinese prefecture-level cities.

Digital inclusive finance (DIF) is playing an increasingly prominent role in green development. This study analyses the ecological effects generated by DIF and its mechanism of action from the perspectives of emission reduction (pollution emissions index; ERI) and efficiency gains (green total factor productivity; GTFP). Using panel data from 285 cities in China from 2011 to 2020, we empirically test the effects of DIF on ERI and GTFP. The results reveal a significant dual ecological effect of DIF in terms of ERI and GTFP, but there are differences in the various dimensions of DIF. Influenced by national policies, DIF produced more substantial ecological effects after 2015, which are more pronounced in developed eastern regions. Human capital significantly enhances the ecological effects of DIF, and human capital and industrial structure are critical paths for DIF to reduce ERI and increase GTFP. This study provides policy insights for governments to leverage digital finance tools to advance sustainable development.

The effect of the digital economy on carbon emissions: an empirical study in China.

Under the new development model, the digital economy has become a new engine to promote the green development of the economy and achieve the goal of "double carbon." Based on panel data from 30 Chinese provinces and cities from 2011 to 2021, the impact of the digital economy on carbon emissions was empirically studied by constructing a panel model and a mediation model. The results show that firstly, the effect of the digital economy on carbon emissions is a non-linear inverted "U" shaped relationship, and this conclusion still holds after a series of robustness tests; secondly, the results of the benchmark regression show that economic agglomeration is an essential mechanism through which the digital economy affects carbon emissions and that the digital economy can indirectly suppress carbon emissions through economic agglomeration. Finally, the results of the heterogeneity analysis show that the impact of the digital economy on carbon emissions varies according to the level of regional development, and its effect on carbon emissions is mainly in the eastern region, while its impact on the central and western regions is weaker, indicating that the impact effect is primarily in developed regions. Therefore, the government should accelerate the construction of new digital infrastructure and implement the development strategy of the digital economy according to local conditions to promote a more significant carbon emission reduction effect of the digital economy.

SDC: An integrated database for sex differences in cancer.

Sex differences are evident in the incidence and mortality of diverse cancers. With the development of personalized approaches in cancer treatment, the impact of sex differences has not been systematically incorporated into preclinical and clinical cancer research. The molecular mechanisms underlying sex differences in cancer have not been elucidated. Here, we developed the first database of Sex Differences in Cancer (SDC), a web-based public database that integrates resources from multiple databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UCSC Xena, Broad Institute Cancer Cell Line Encyclopedia (CCLE), Genomics of Drug Sensitivity in Cancer (GDSC). SDC contains 27 types of cancers, 6 types of molecular data, more than 10,000 donors, 977 cancer cell lines were used to analyze sex differences among cancers. It provides five main modules: Survival and phenotype, Molecular differences, Signatures and pathways, Therapy response, Download. Users can download the all the visualized results and raw data after analysis. Collectively, SDC is the first integrated database to analyze sex differences in cancer on the web server, which will strengthen our understanding of the role of sex in cancers. It is implemented in Shiny-server and freely available for public use at http://sdc.anticancer.xyz.

Identification of the upstream regulators of KDM5B in gastric cancer.

AIMS: Lysine-specific demethylase 5B (KDM5B) is an epigenetic regulator of chromatin that catalyzes the demethylation of histone 3 lysine 4. It is overexpressed in multiple cancer types and acts as a therapeutic target in cancer therapy. Nevertheless, its upstream regulatory pathway is not completely understood, prompting the search for the underlying biological factors driving KDM5B overexpression. MATERIALS AND METHODS: A comprehensive analysis was performed to examine the association between KDM5B overexpression and copy number variation (CNV), somatic mutation, mRNA expression, miRNA expression, and clinical characters from The Cancer Genome Atlas database. Coexpression and function enrichment analyses were performed with KDM5B-coexpressed genes. The gastric cancer (GC) cell line MKN45 was utilized to verify the regulation of KDM5B using the transcription factor (TF) Yin Yang 1 (YY1) and miR-29a-3p. KEY FINDINGS: KDM5B was overexpressed and associated with poor prognosis in GC. KDM5B upregulation was driven by CNV amplification and DNA hypomethylation rather than by KDM5B mutations. Enrichment analysis revealed that KDM5B-coexpressed genes were primarily related to the transmembrane transport function and the ubiquitin-mediated proteolysis signaling pathway. As a TF, YY1 might bind to the KDM5B promoter region to regulate KDM5B expression. In addition, miR-29a-3p might bind to and negatively regulate KDM5B expression. SIGNIFICANCE: Our results demonstrate that KDM5B expression is regulated via CNV amplification, DNA hypomethylation, and YY1 and miR-29a-3p; KDM5B expression regulation is associated with patient survival and tumor cell proliferation.

Efficient enzymatic synthesis of L-ascorbyl palmitate using Candida antarctica lipase B-embedded metal-organic framework.

The Candida antarctica lipase B (CALB) was embedded in the metal-organic framework, zeolitic imidazolate framework-8 (ZIF-8), and applied in the enzymatic synthesis of L-ascorbic acid palmitate (ASP) for the first time. The obtained CALB@ZIF-8 achieved the enzyme loading of 80 mg g-1 with 11.3 U g-1 (dry weight) unit activity, 59.8% activity recovery, and 92.7% immobilization yield. Under the optimal condition, ASP was synthesized with over 75.9% conversion of L-ascorbic acid in a 10-batch reaction. Continuous synthesis of ASP was subsequently performed in a packed bed bioreactor with an outstanding average space-time yield of 58.1 g L-1  h-1 , which was higher than ever reported continuous ASP biosynthesis reactions.

Abrogation of USP7 is an alternative strategy to downregulate PD-L1 and sensitize gastric cancer cells to T cells killing.

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.

Oxygen carrier in core-shell fibers synthesized by coaxial electrospinning enhances Schwann cell survival and nerve regeneration.

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.

Time-restricted release of multiple neurotrophic factors promotes axonal regeneration and functional recovery after peripheral nerve injury.

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.

Incorporation of chitosan microspheres into collagen-chitosan scaffolds for the controlled release of nerve growth factor.

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.

A synthetic oxygen carrier-olfactory ensheathing cell composition system for the promotion of sciatic nerve regeneration.

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.

The effect of synthetic oxygen carrier-enriched fibrin hydrogel on Schwann cells under hypoxia condition in vitro.

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.

Schwann cell-seeded scaffold with longitudinally oriented micro-channels for reconstruction of sciatic nerve in rats.

To provide a more permissive environment for axonal regeneration, Schwann cells (SCs) were introduced into a collagen-chitosan scaffold with longitudinally oriented micro-channels (L-CCH). The SC-seeded scaffold was then used for reconstruction of a 15-mm-long sciatic nerve defect in rats. The axonal regeneration and functional recovery were examined by a combination of walking track analysis, electrophysiological assessment, Fluoro-Gold retrograde tracing, as well as morphometric analyses to both regenerated axons and target muscles. The findings showed that SCs adhered and migrated into the L-CCH scaffold and displayed a longitudinal arrangement in vitro. Axonal regeneration as well as functional recovery was in the similar range between SCs-seeded scaffold and autograft groups, which were superior to those in L-CCH scaffold alone group. These indicate that the SCs-seeded L-CCH scaffold, which resembles the microstructure as well as the permissive environment of native peripheral nerves, holds great promise in nerve regeneration therapies.

Electrical regulation of olfactory ensheathing cells using conductive polypyrrole/chitosan polymers.

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.