Unimolecular Cascaded Multienzyme Conjugates Modulate the Microenvironment of Diabetic Wound to Promote Healing.

An abnormal microenvironment underlies poor healing in chronic diabetic chronic wounds. However, effectively modulating the microenvironment of the diabetic wound remains a great challenge due to sustained oxidative stress and chronic inflammation. Here, we present a unimolecular enzyme-polymer conjugate that demonstrates excellent multienzymatic cascade activities. The cascaded enzyme conjugates (CECs) were synthesized by grafting poly(N-acryloyl-lysine) (pLAAm) from the glycan moieties of glucose oxidase (GOx) via glycan-initiated polymerization. The resulting CECs exhibited multiple enzymatic properties of GOx, superoxide dismutase mimic, and catalase mimic activities simultaneously. The CECs facilitated the depletion of high blood glucose, ROS scavenging, bacteria-killing, anti-inflammatory effects, and sustained oxygen generation, which restored the microenvironment in diabetic wounds. In vivo results from a diabetic mouse model confirmed the capacity and efficiency of the cascade reaction for diabetic wound healing. Our findings demonstrate that the three-in-one enzyme-polymer conjugates alone can modulate the diabetic microenvironment for wound healing.

Green credit and low-carbon development in China: Fresh evidence on spatial spillover insights.

The promulgation and execution of green credit (GC) policies have had a significant influence on the development of the economy and society, and their impact on low-carbon development (LCD) needs to be taken seriously. On the basis of elaborating the mechanism of the role of GC on LCD, this study constructs a panel fixed effects (FE) model to test the direct impact of GC on LCD by using Chinese provincial-level data from 2007 to 2020. An intermediary effect model is constructed to investigate its indirect effects. A dynamic SDM is further constructed to examine the spatial effects of GC on LCD in neighbouring regions. The results show that GC is helping China to achieve LCD. GC can promote LCD through promoting green innovation, optimizing energy structure and upgrading industrial structure. It is crucial to acknowledge that all three pathways are essential channels of influence and should not be disregarded. GC not only fosters LCD in the local areas, but also has a positive spatial spillover effect in adjacent regions. Based on the above conclusions, this study proposes policy recommendations such as increasing support for GC, smoothing the transmission channel from GC to LCD, and establishing a synergistic linkage mechanism between interregional credit and environmental governance. This study provides valuable insights for China to realize LCD, as well as for other countries to actively engage in energy conservation and emission reduction efforts.

Does digital finance enhance industrial green total factor productivity? Theoretical mechanism and empirical test.

The development and application of digital finance has brought profound changes to the real economy, and its impact on industrial green total factor productivity is worthy of attention and evaluation. The industrial green total factor productivity of each province in China is measured by using EBM-ML index with the provincial panel data collected from 2011 to 2020. The panel fixed effects model is used to estimate the impact of digital finance on industrial green total factor productivity. The intermediary effect model is constructed to analyze its conduction mechanisms. The heterogeneity of the impact of digital finance on industrial green total factor productivity is further explored. The results indicate that digital finance makes a significant contribution to the promotion of industrial green total factor productivity. Digital finance indirectly promotes the enhancement of industrial green total factor productivity by promoting technological innovation, driving industrial upgrading and stimulating entrepreneurial dynamism. The impact of digital finance on industrial green total factor productivity has obvious sub-dimension heterogeneity and regional heterogeneity. Based on the above conclusions, we also suggest policy recommendations such as unblocking the conduction channels of digital finance and implementing the differentiated digital finance development strategy. The highlight of this paper is that it takes digital finance as the entry point and shifts the research content to the real economy, broadening the research perspective of "digital finance".

How does digital economy affect green total factor productivity? Evidence from China.

To date, digital economy has become an emerging driving force of economic growth in various countries. To further explore the green value of digital economy, full array polygon graphic index method and Global Malmquist productivity index are used to evaluate China's digital economy development and green total factor productivity respectively. Based on a comprehensive explanation of the influence mechanism, spatial econometric model and intermediary effect model are constructed to test the spatial spillover effect and transmission mechanism between digital economy and green total factor productivity. The results show that digital economy has a positive direct impact and spatial spillover effect on green total factor productivity with the significant U-shaped characteristics, and these effects mainly come from the promotion of green technology progress by digital economy. Industrial structure upgrading and factor market distortion respectively account for 22 % and 5.875 % of the impact of digital economy on green total factor efficiency, which means that they are the two primary channels for digital economy to influence green total factor productivity. Results of heterogeneity analysis show that digital economy is the key factor for resource-based cities to break the "resource curse", but the unbalanced development of digital economy leads to the "digital gap" between the central and peripheral cities.

The impact of national values on the prevention and control of COVID-19: An empirical study.

The outbreak of COVID-19 at the end of 2019 has become the most devastating public health event of the 21st century. The different performances of governments and people in different countries and regions show that national values may play an important role in the prevention and control of COVID-19. Based on data from the seventh wave of World Values Survey (WVS-7) and the Human Freedom Index (HFI) report in 2020, three national value factors are extracted in this manuscript, including religious belief, government satisfaction and individual freedom. Then ordinary least squares regression (OLS) regression model is constructed to explore the influence of these three value factors on the prevention and control of COVID-19 and some heterogeneity analysis is implemented. The results show that religious belief and individual freedom significantly increased the COVID-19 infection rate, while government satisfaction significantly reduced the COVID-19 infection rate. The study findings have the ability to hold up after a range of robustness. For countries and regions with different COVID-19 testing policies, the influence of national values is different. Only in countries and regions with high testing rate policies and complete systems of the prevention and control of COVID-19, the influence of national values is significant. Based on these findings, a series of targeted policy recommendations for building national values in the post-epidemic era are proposed.

The "Local Neighborhood" Effect of Environmental Regulation on Green Innovation Efficiency: Evidence from China.

Current research has generally concentrated on the motivations of environmental policies on local green innovation while ignoring the effect they may have on green innovation in neighboring places. To obtain a thorough understanding and explanation of the influencing mechanism of environmental regulation (ER) on green innovation efficiency (GIE), the super-slack based measure-data envelopment analysis (Super-SBM-DEA) method was applied to evaluate Chinese provinces' GIE, a spatial Durbin model was developed to evaluate the effect of ER on GIE from the perspective of the "local neighborhood" effect, and a mediating effect model was built to analyze the transmission mechanism of the neighborhood effect of ER on GIE. The study indicated that China's regional GIE is high in the east and low in the west, with large spatial variability and significant positive spatial clustering characteristics. The effect of ER on local GIE is "U" shaped, while the influence on green innovation efficiency in neighboring areas is an inverted "U" shape. The influence of environmental regulation on GIE in neighboring areas is mainly achieved through the transfer of local polluting industries to neighboring areas. Based on the results, policy recommendations from the perspectives of choosing environmental regulation tools and transferring polluting industries are made to promote and realize the coordinated development of ER and green innovation.

The impact of land price distortion on green development efficiency: mechanism discussion and empirical test.

Based on the panel data of 30 Chinese provinces, the Cobb-Douglas production function and GML index were constructed to measure the degree of land price distortion and green development efficiency, respectively, in China, and the System Generalised Method of Moments model was employed to explore the relationship between land price distortion and green development efficiency, and a mediating effect model was further constructed to analyse the transmission mechanism. The results show that, first, land price in China is characterised by a negative distortion, but the degree of negative distortion tends to decrease after 2010. Second, land price distortion significantly inhibits the improvement of green development efficiency; this conclusion still holds after a series of robustness tests, and land price distortion significantly promotes the progress of green technology, while significantly inhibiting the improvement of green technology efficiency. Third, the results of the mediating effect show that the inhibiting effect of land price distortion on green development efficiency is mainly achieved through three channels: house price, industrial structure and infrastructure. Finally, policy recommendations for green sustainable development are put forward from the aspects of land supply structure adjustment and so on.

Evodiamine Induces Apoptosis in SMMC-7721 and HepG2 Cells by Suppressing NOD1 Signal Pathway.

Hepatocellular cancer (HCC) is a lethal malignancy with poor prognosis and easy recurrence. There are few agents with minor toxic side effects that can be used for treatment of HCC. Evodiamine (Evo), one of the major bioactive components derived from fructus Evodiae, has long been shown to exert anti-hepatocellular carcinoma activity by suppressing activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK). In addition, in the Nucleotide-Binding Oligomerization Domain 1 (NOD1) pathway, NOD1 could initiate NF-κB-dependent and MAPK-dependent gene transcription. Recent experimental studies reported that the NOD1 pathway was related to controlling development of various tumors. Here we hypothesize that Evo exerts anti-hepatocellular carcinoma activity by inhibiting NOD1 to suppress NF-κB and MAPK activation. Therefore, we proved the anti-hepatocellular carcinoma activity of Evo on HCC cells and detected the effect of Evo on the NOD1 pathway. We found that Evo significantly induced cell cycle arrest at the G2/M phase, upregulated P53 and Bcl-2 associated X proteins (Bax) proteins, and downregulated B-cell lymphoma-2 (Bcl-2), cyclinB1, and cdc2 proteins in HCC cells. In addition, Evo reduced levels of NOD1, p-P65, p-ERK, p-p38, and p-JNK, where the level of IκBα of HCC cells increased. Furthermore, NOD1 agonist γ-D-Glu-mDAP (IE-DAP) treatment weakened the effect of Evo on suppression of NF-κB and MAPK activation and cellular proliferation of HCC. In an in vivo subcutaneous xenograft model, Evo also exhibited excellent tumor inhibitory effects via the NOD1 signal pathway. Our results demonstrate that Evo could induce apoptosis remarkably and the inhibitory effect of Evo on HCC cells may be through suppressing the NOD1 signal pathway in vitro and in vivo.

Contralateral C7 Nerve Root Transfer for Function Recovery in Adults: A Meta-analysis.

BACKGROUND: Root avulsion to all 5 roots of the brachial plexus is a common presentation and keeps a major reconstructive challenge. The contralateral C7 (CC7) nerve transfer has been used in treating brachial plexus avulsion injury (BPAI) since 1986. However, the effectiveness of the procedure remains a subject of controversy. The aim of this meta-analysis was to study surgical outcomes regarding motor and sensory recovery after CC7 nerve transfer. METHODS: Chinese or English (i.e., "contralateral c-7", "contralateral c7", "c7 nerve root", and "seventh cervical nerve root") keywords were used for a literature search for articles related to CC7 nerve transfer in several databases (i.e., PubMed, Cochrane, Embase, CNKI, CQVIP, and Wanfang Data). Clinical research articles were screened, and animal studies as well as duplicate publications were excluded. Muscle strength and sensory recovery were considered to be effective only when the scores on the United Kingdom Medical Research Council scale were equal to or higher than M3 and S3, respectively. RESULTS: The overall ipsilateral recipient nerve recovery rates were as follows: the efficiency rate for muscle strength recovery after CC7 nerve transfer was 0.57 (95% confidence interval [CI]: 0.48-0.66) and for sensory recovery was 0.52 (95% CI: 0.46-0.58). When the recipient nerve was the median nerve, the efficiency rate for muscle strength recovery was 0.50 (95% CI: 0.39-0.61) and for sensory was 0.56 (95% CI: 0.50-0.63). When the recipient nerve was the musculocutaneous nerve and the radial nerve, the efficiency rate for muscle strength recovery was 0.74 (95% CI: 0.65-0.82) and 0.50 (95% CI: 0.31-0.70), respectively. CONCLUSIONS: Transfer of CC7 nerves to musculocutaneous nerves leads to the best results. CC7 is a reliable donor nerve, which can be safely used for upper limb function reconstruction, especially for entirely BPAI. When modifying procedures, musculocutaneous nerves and median nerve can be combined as recipient nerves.

An Analysis of Paravertebral Ossification in Cervical Artificial Disc Replacement: A Novel Classification Based on Computed Tomography.

OBJECTIVE: Cervical artificial disc replacement (CADR) is a new technology in cervical spine surgery. However, CADR may result in paravertebral ossification (PO) after surgery and affect the mobility of the related spinal segments. The present widely used assessment method based on X-ray tomography cannot provide the position information of PO, and also PO detection rates by X-ray are low. The incidence of PO varies dramatically between studies. This study built a novel classification system based on cervical computer tomography (CT) scan to re-evaluate the incidence of PO and its influence on CADR, and also analyzed the predisposing factors of PO. METHODS: In this retrospective study, 71 patients (from January 2004 to December 2009) who received cervical artificial disc replacement in our hospital were enrolled, and 82 cervical segments were replaced by Bryan discs. The range of motion (ROM) of the related cervical segments and scores of neurological symptoms (neck disability index [NDI] and Japanese Orthopaedic Association [JOA] scores) for both pre-surgery and last follow-up were acquired, respectively. After the establishment of a novel grading system for PO based on CT scan, we analyzed the CT images acquired before surgery and at the last time follow-up. Occurrence and distribution of PO at both time points were calculated. ROM between pre-surgery and post-surgery was compared by paired t-test stratified by PO stages. One-way ANOVA was used to compare NDI and JOA scores between high-grade and low-grade PO groups after surgery. The χ2 -test was used to evaluate the risk (odds ratio) of predisposing factors in developing high-grade PO after surgery. RESULTS: The CT-based classification system has good inter-observer and intra-observer reliability. The detection rate of PO by CT scan is higher than for traditional X-ray examination. The incidence of low-grade PO in all 82 segments at last follow-up is 32.9%. The occurrences of high-grade PO at preoperational and last follow-up time are 15.9% and 67.1%, respectively. The high-grade PO is mainly distributed around the uncovertebral joint. The pre-surgery and post-surgery ROM are similar in patients with low-grade PO at last follow-up time (9.80° ± 3.65° vs 10.03° ± 3.73°, P = 0.801); however, in patients with high-grade PO the post-surgery ROM decreases significantly compared to the pre-surgery ROM (9.73° ± 4.03° vs 6.63° ± 4.21°, P < 0.001). There is no statistical difference for JOA and NDI scores after surgery between high-grade and low-grade PO patients at final follow-up (P = 0.264, P = 0.703). The χ2 -test indicates that patients with preoperational existence of PO have a high risk of high-grade PO after surgery (OR = 4, P = 0.012). CONCLUSIONS: The novel CT image-based PO classification system has good intra-observer reliability. The incidence of PO after Bryan cervical disk replacement is relative high, and the high-grade PO is mainly distributed at the uncovertebral joint. The high-grade PO will affect the ROM after surgery; however, it does not affect the neurologic symptoms.

Lumbar spine superior-level facet joint violations: percutaneous versus open pedicle screw insertion using intraoperative 3-dimensional computer-assisted navigation.

BACKGROUND: Percutaneous pedicle screw use has a high rate of cranial facet joint violations (FVs) because of the facet joint being indirectly visualized. Computer-assisted navigation shows the anatomic structures clearly, and may help to lower the rate of FVs during pedicle screw insertion. This study used computed tomography (CT) to evaluate and compare the incidence of FVs between percutaneous and open surgeries employing computer-assisted navigation for the implantation of pedicle screw instrumentation during lumbar fusions. METHODS: A prospective study, including 142 patients having lumbar and lumbosacral fusion, was conducted between January 2013 and April 2014. All patients had bilateral posterior pedicle screw-rod instrumentation (top-loading screws) implanted by the same group of surgeons; intraoperative 3-dimensional computer navigation was used during the procedures. All patients underwent CT examinations within 6 months postoperation. The CT scans were independently reviewed by three reviewers blinded to the technique used. RESULTS: The cohort comprised 68 percutaneous and 74 open cases (136 and 148 superior-level pedicle screw placements, respectively). Overall, superior-level FVs occurred in 20 patients (20/142, 14.1%), involving 27 top screws (27/284, 9.5%). The percutaneous technique (7.4% of patients, 3.7% of top screws) had a significantly lower violation rate than the open procedure (20.3% of patients, 14.9% of top screws). The open group also had significantly more serious violations than did the percutaneous group. Both groups had a higher violation rate when the cranial fixation involved the L5. A 1-level open procedure had a higher violation rate than did the 2- and 3-level surgeries. CONCLUSIONS: With computer-assisted navigation, the placement of top-loading percutaneous screws carries a lower risk of adjacent-FVs than does the open technique; when FVs occur, they tend to be less serious. Performing a single-level open lumbar fusion, or the fusion of the L5-S1 segment, requires caution to avoid cranial adjacent FVs.