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Background: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are associated with significant cardiovascular benefit in type 2 diabetes (T2D). However, GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular co-morbidities., Aim: To explore whether combining GLP-1RA and SGLT-2I can achieve additional benefit in preventing cardiovascular diseases in T2D., Methods: The systematic review was conducted according to PRISMA recommendations. The protocol was registered on PROSPERO (ID: 42022385007). A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination treatment. Effect modification of prior myocardial infarction (MI) and heart failure (HF) was also explored to provide clinical insight as to when the combination treatment should be considered., Results: The estimated hazard ratios (HR) GLP-1RA/SGLT-2I vs Placebo (0.75-0.98) and HR Combination vs GLP-1RA/SGLT-2I (0.26-0.86) for primary and secondary cardiovascular outcomes suggested that the combination treatment may achieve additional cardiovascular benefit compared with GLP-1RA or SGLT-2I alone. In patients with prior MI or HF, the mono-therapies may not improve the overall cardiovascular outcomes, as the estimated HR MI+/HF+ (0.57-1.52) suggested that GLP-1RA or SGLT-2I alone may be associated with lower risks of hospitalization for HF but not cardiovascular death., Conclusion: Considering its greater cardiovascular benefit in T2D, the combination treatment of GLP-1RA and SGLT-2I might be prioritized in patients with prior MI or HF, where the monotherapies may not provide sufficient cardiovascular protection., Competing Interests: Conflict-of-interest statement: Zhu JJ and Gu XS have no conflict of interest or financial disclosures that are relevant to the content of this research report. Wilding JPH reports consultancy/advisory board work for the pharmaceutical industry contracted via the University of Liverpool (no personal payment) for Altimmune, AstraZeneca, Boehringer Ingelheim, Cytoki, Lilly, Napp, Novo Nordisk, Menarini, Pfizer, Rhythm Pharmaceuticals, Sanofi, Saniona, Tern, and Shionogi & Ysopia; research grants for clinical trials from AstraZeneca and Novo Nordisk and personal honoraria/lecture fees from AstraZeneca, Boehringer Ingelheim, Medscape, Napp, Novo Nordisk, and Rhythm. Wilding JPH is past president of the World Obesity Federation, a member of the Association for the Study of Obesity, Diabetes UK, EASD, ADA, Society for Endocrinology, and the Rank Prize Funds Nutrition Committee. Wilding JPH is national lead for the Metabolic and Endocrine Speciality Group of the UK NIHR Clinical Research Network., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The key regulators and regeneration-associated genes involved in axonal regeneration of neurons after injury have not been clarified. In high-throughput sequencing, various factors influence the final sequencing results, including the number and size of cells, the depth of sequencing, and the method of cell separation. There is still a lack of research on the detailed molecular expression profile during the regeneration of dorsal root ganglion neuron axon. In this study, we performed laser-capture microdissection coupled with RNA sequencing on dorsal root ganglion neurons at 0, 3, 6, and 12 hours and 1, 3, and 7 days after sciatic nerve crush in rats. We identified three stages after dorsal root ganglion injury: early (3-12 hours), pre-regeneration (1 day), and regeneration (3-7 days). Gene expression patterns and related function enrichment results showed that one module of genes was highly related to axonal regeneration. We verified the up-regulation of activating transcription factor 3 (Atf3), Kruppel like factor 6 (Klf6), AT-rich interaction domain 5A (Arid5a), CAMP responsive element modulator (Crem), and FOS like 1, AP-1 transcription factor Subunit (Fosl1) in dorsal root ganglion neurons after injury. Suppressing these transcription factors (Crem, Arid5a, Fosl1 and Klf6) reduced axonal regrowth in vitro. As the hub transcription factor, Atf3 showed higher expression and activity at the pre-regeneration and regeneration stages. G protein-coupled estrogen receptor 1 (Gper1), interleukin 12a (Il12a), estrogen receptor 1 (ESR1), and interleukin 6 (IL6) may be upstream factors that trigger the activation of Atf3 during the repair of axon injury in the early stage. Our study presents the detailed molecular expression profile during axonal regeneration of dorsal root ganglion neurons after peripheral nerve injury. These findings may provide reference for the clinical screening of molecular targets for the treatment of peripheral nerve injury., Competing Interests: None

Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson's disease using 6-hydroxydopamine. When SH-SY5Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson's disease and in a mouse model of Parkinson's disease. Next, we pretreated cell models of Parkinson's disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson's disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor down-regulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase (PI3K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulin-like growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson's disease treatment., Competing Interests: None

Percutaneous electrical nerve stimulation of an injured nerve can promote and accelerate peripheral nerve regeneration and improve function. When performing acupuncture and moxibustion, locating the injured nerve using ultrasound before percutaneous nerve stimulation can help prevent further injury to an already injured nerve. However, stimulation parameters have not been standardized. In this study, we constructed a multi-layer human forearm model using finite element modeling. Taking current density and activated function as optimization indicators, the optimal percutaneous nerve stimulation parameters were established. The optimal parameters were parallel placement located 3 cm apart with the injury site at the midpoint between the needles. To validate the efficacy of this regimen, we performed a randomized controlled trial in 23 patients with median nerve transection who underwent neurorrhaphy. Patients who received conventional rehabilitation combined with percutaneous electrical nerve stimulation experienced greater improvement in sensory function, motor function, and grip strength than those who received conventional rehabilitation combined with transcutaneous electrical nerve stimulation. These findings suggest that the percutaneous electrical nerve stimulation regimen established in this study can improve global median nerve function in patients with median nerve transection., Competing Interests: None

Egfr, a member of the ErbB gene family, plays a critical role in tissue development and homeostasis, wound healing, and disease. However, expression and regulators of Egfr during spinal cord development remain poorly understood. In this study, we investigated ErbB evolution and analyzed co-expression modules, miRNAs, and transcription factors that may regulate Egfr expression in rats. We found that ErbB family members formed via Egfr duplication in the ancient vertebrates but diverged after speciation of gnathostomes. We identified a module that was co-expressed with Egfr, which involved cell proliferation and blood vessel development. We predicted 25 miRNAs and nine transcription factors that may regulate Egfr expression. Dual-luciferase reporter assays showed six out of nine transcription factors significantly affected Egfr promoter reporter activity. Two of these transcription factors (KLF1 and STAT3) inhibited the Egfr promoter reporter, whereas four transcription factors (including FOXA2) activated the Egfr promoter reporter. Real-time PCR and immunofluorescence experiments showed high expression of FOXA2 during the embryonic period and FOXA2 was expressed in the floor plate of the spinal cord, suggesting the importance of FOXA2 during embryonic spinal cord development. Considering the importance of Egfr in embryonic spinal cord development, wound healing, and disease (specifically in cancer), regulatory elements identified in this study may provide candidate targets for nerve regeneration and disease treatment in the future., Competing Interests: None

Previous studies on the mechanisms of peripheral nerve injury (PNI) have mainly focused on the pathophysiological changes within a single injury site. However, recent studies have indicated that within the central nervous system, PNI can lead to changes in both injury sites and target organs at the cellular and molecular levels. Therefore, the basic mechanisms of PNI have not been comprehensively understood. Although electrical stimulation was found to promote axonal regeneration and functional rehabilitation after PNI, as well as to alleviate neuropathic pain, the specific mechanisms of successful PNI treatment are unclear. We summarize and discuss the basic mechanisms of PNI and of treatment via electrical stimulation. After PNI, activity in the central nervous system (spinal cord) is altered, which can limit regeneration of the damaged nerve. For example, cell apoptosis and synaptic stripping in the anterior horn of the spinal cord can reduce the speed of nerve regeneration. The pathological changes in the posterior horn of the spinal cord can modulate sensory abnormalities after PNI. This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission. The injured site of the peripheral nerve is also an important factor affecting post-PNI repair. After PNI, the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site. A slow speed of axon regeneration leads to low nerve regeneration. Therefore, it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site. From the perspective of target organs, long-term denervation can cause atrophy of the corresponding skeletal muscle, which leads to abnormal sensory perception and hyperalgesia, and finally, the loss of target organ function. The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping, addressing the excessive excitability of the dorsal root ganglion, alleviating neuropathic pain, improving neurological function, and accelerating nerve regeneration. Electrical stimulation of target organs can reduce the atrophy of denervated skeletal muscle and promote the recovery of sensory function. Findings from the included studies confirm that after PNI, a series of physiological and pathological changes occur in the spinal cord, injury site, and target organs, leading to dysfunction. Electrical stimulation may address the pathophysiological changes mentioned above, thus promoting nerve regeneration and ameliorating dysfunction.

Recovery from injury to the peripheral nervous system is different from that of the central nervous system in that it can lead to gene reprogramming that can induce the expression of a series of regeneration-associated genes. This eventually leads to axonal regeneration of injured neurons. Although some regeneration-related genes have been identified, the regulatory network underlying axon regeneration remains largely unknown. To explore the regulator of axon regeneration, we performed RNA sequencing of lumbar L4 and L5 dorsal root ganglion (DRG) neurons at different time points (0, 3, 6, 12 hours, 1, 3 and 7 days) after rat sciatic nerve crush. The isolation of neurons was carried out by laser capture microscopy combined with NeuN immunofluorescence staining. We found 1228 differentially expressed genes in the injured sciatic nerve tissue. The hub genes within these differentially expressed genes include Atf3, Jun, Myc, Ngf, Fgf2, Ezh2, Gfap and Il6. We verified that the expression of the enhancer of zeste homologue 2 gene (Ezh2) was up-regulated in DRG neurons after injury, and this up-regulation differed between large- and small-sized dorsal root ganglion neurons. To investigate whether the up-regulation of Ezh2 impacts axonal regeneration, we silenced Ezh2 with siRNA in cultured DRG neurons and found that the growth of the newborn axons was repressed. In our investigation into the regulatory network of Ezh2 by interpretive phenomenal analysis, we found some regulators of Ezh2 (including Erk, Il6 and Hif1a) and targets (including Atf3, Cdkn1a and Smad1). Our findings suggest that Ezh2, as a nerve regeneration-related gene, participates in the repair of the injured DRG neurons, and knocking down the Ezh2 in vitro inhibits the axonal growth of DRG neurons. All the experimental procedures approved by the Administration Committee of Experimental Animals of Jiangsu Province of China (approval No. S20191201-201) on March 21, 2019., Competing Interests: None

The purpose of this study was to investigate the effects of sacubitril/valsartan on right ventricular (RV) function in patients with pulmonary hypertension (PH) due to heart failure with reduced ejection fraction (HFrEF). We prospectively enrolled patients with HFrEF-induced PH admitted to the Department of Cardiology between August 2018 and December 2019. Patients were randomized to receive oral treatment with sacubitril/valsartan or enalapril. Epidemiological data were recorded before treatment. Echocardiography was performed at admission and 6 months of follow-up, and all parameters were compared. Major adverse cardiac events (MACEs) were compared between baseline and 6 months follow-up. There were no significant differences in the baseline characteristics between the two groups. After 6 months of treatment, both treatment groups improved the following parameters from baseline (mean ± SD): left atrium, left ventricle, the left ventricular ejection function (LVEF), RV systolic function (the tricuspid annular plane systolic excursion [TAPSE], the systolic pulmonary artery pressure [sPAP], and TAPSE/sPAP). After 6 months, sacubitril/valsartan improved significantly the following parameters compared with enalapril (all p  < 0.05): LVEF (47.07 ± 6.93% vs. 43.47 ± 7.95%); TAPSE (15.33 ± 1.31 vs. 14.78 ± 1.36 mm); sPAP (36.76 ± 14.32 vs. 42.26 ± 12.07 mmHg); and TAPSE/sPAP ratio (0.50 ± 0.23 vs. 0.39 ± 0.14), respectively. There was no difference in readmissions due to recurrent heart failure. Sacubitril/valsartan seems to provide more beneficial effects among patients with HFrEF-induced PH to improve RV function, along with a decrease in pulmonary pressure., Competing Interests: The authors declare that there are no conflicts of interests., (© 2022 The Authors. Pulmonary Circulation published by Wiley Periodicals LLC on behalf of the Pulmonary Vascular Research Institute.)

Autophagy has been shown to play an important role in Parkinson's disease. We hypothesized that skin-derived precursor cells exhibit neuroprotective effects in Parkinson's disease through affecting autophagy. In this study, 6-hydroxydopamine-damaged SH-SY5Y cells were pretreated with a culture medium containing skin-derived precursors differentiated into Schwann cells (SKP-SCs). The results showed that the SKP-SC culture medium remarkably enhanced the activity of SH-SY5Y cells damaged by 6-hydroxydopamine, reduced excessive autophagy, increased tyrosine hydroxylase expression, reduced α-synuclein expression, reduced the autophagosome number, and activated the PI3K/AKT/mTOR pathway. Autophagy activator rapamycin inhibited the effects of SKP-SCs, and autophagy inhibitor 3-methyladenine had the opposite effect. These findings confirm that SKP-SCs modulate the PI3K/AKT/mTOR pathway to inhibit autophagy, thereby exhibiting a neuroprotective effect in a cellular model of Parkinson's disease. This study was approved by the Animal Ethics Committee of Laboratory Animal Center of Nantong University (approval No. S20181009-205) on October 9, 2018., Competing Interests: None

Although implantation of biomaterials carrying mesenchymal stem cells (MSCs) is considered as a promising strategy for ameliorating neural function after spinal cord injury (SCI), there are still some challenges including poor cell survival rate, tumorigenicity and ethics concerns. The performance of the secretome derived from MSCs was more stable, and its clinical transformation was more operable. Cytokine antibody array demonstrated that the secretome of MSCs contained 79 proteins among the 174 proteins analyzed. Three-dimensional (3D) printed collagen/silk fibroin scaffolds carrying MSCs secretome improved hindlimb locomotor function according to the Basso-Beattie-Bresnahan scores, the inclined-grid climbing test and electrophysiological analysis. Parallel with locomotor function recovery, 3D printed collagen/silk fibroin scaffolds carrying MSCs secretome could further facilitate nerve fiber regeneration, enhance remyelination and accelerate the establishment of synaptic connections at the injury site compared to 3D printed collagen/silk fibroin scaffolds alone group according to magnetic resonance imaging, diffusion tensor imaging, hematoxylin and eosin staining, Bielschowsky's silver staining, immunofluorescence staining and transmission electron microscopy. These results indicated the implantation of 3D printed collagen/silk fibroin scaffolds carrying MSCs secretome might be a potential treatment for SCI., (© The Author(s) 2022. Published by Oxford University Press.)

Compared with non-degradable materials, biodegradable biomaterials play an increasingly important role in the repairing of severe bone defects, and have attracted extensive attention from researchers. In the treatment of bone defects, scaffolds made of biodegradable materials can provide a crawling bridge for new bone tissue in the gap and a platform for cells and growth factors to play a physiological role, which will eventually be degraded and absorbed in the body and be replaced by the new bone tissue. Traditional biodegradable materials include polymers, ceramics and metals, which have been used in bone defect repairing for many years. Although these materials have more or fewer shortcomings, they are still the cornerstone of our development of a new generation of degradable materials. With the rapid development of modern science and technology, in the twenty-first century, more and more kinds of new biodegradable materials emerge in endlessly, such as new intelligent micro-nano materials and cell-based products. At the same time, there are many new fabrication technologies of improving biodegradable materials, such as modular fabrication, 3D and 4D printing, interface reinforcement and nanotechnology. This review will introduce various kinds of biodegradable materials commonly used in bone defect repairing, especially the newly emerging materials and their fabrication technology in recent years, and look forward to the future research direction, hoping to provide researchers in the field with some inspiration and reference.

Host-plant volatiles play vital roles for insects to locate foraging, mating, and oviposition sites in the environment. As one of the devastating invasive forestry pests, Hyphantria cunea causes a great annual loss in China, and understanding its chemical ecology is an important task. The current research was done in terms of chemical analysis, electrophysiology, and behavioral assays on H. cunea to assess its olfactory reception toward host-plant volatiles. A screen of possible common host volatiles was done, targeting on five favored hosts of H. cunea , harvesting six potential bioactive compounds from a total of 78 odorant components. Six types of antennal sensilla were investigated on their distributions on the antennae, and sexual dimorphism was described. H. cunea showed responses to all selected host-related volatiles in electroantennogram tests, and linalyl butyrate elicited the strongest responses. Furthermore, mating rates in adult pairs that are exposed to dibutyl phthalate and phytol have been significantly increased, while oviposition rates and female fecundity were not influenced. The results of the current study provide initial evidence showing that universal host-derived volatile cues are essential for H. cunea moth in terms of mating, which can also provide insights into the development of botanical attractants., (Copyright © 2020 Bai, Wang, Liu, Li, Liu, Gu and Tang.)

Purpose: We performed a network meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of HER2-targeted agents in combination with taxanes and to identify the best strategy for HER2 + metastatic breast cancer (MBC)., Methods: Pubmed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials that evaluated any taxanes+HER2-targeted agents in the treatment of HER2 + MBC. The primary outcome was overall survival (OS). The secondary outcomes included overall response rate (ORR) and progression-free survival (PFS)., Results: A total of 13 RCTs were eligible, involving 4941 patients and 10 regimens. The result showed that single-HER2-targeted agent+a taxane did improve the effect on ORR and PFS than taxane alone, but only trastuzumab+a taxane had a significant improvement in OS outcomes. Single-HER2-targeted agent (trastuzumab) combined with taxane-based doublets (taxane+carboplatin/capecitabine/doxorubicin/bevacizumab) showed no further benefit than trastuzumab+a taxane. Doublet-HER2-targeted agents combined with a taxane(trastuzumab+pertuzumab+a taxane) showed further improvement in ORR, PFS, and all OS outcomes than single-HER2-targeted agent+a taxane. Ranking analysis based on their P-scores suggested that trastuzumab+pertuzumab+a taxane was the best combination treatment for all the efficacy outcomes., Conclusions: These findings demonstrate that combining two HER2-targeted agents (trastuzumab+pertuzumab) with a taxane is much more beneficial for the treatment of HER2 + MBC. Dual HER2-targeted agents combined with a taxane appears to be the preferred application of HER2 + MBC.

Background: Diabetes mellitus is a recognized risk factor for esophageal squamous cell carcinomas (ESCC), and metformin is a recognized protective factor for some gastrointestinal tumors. But knowledge is limited regarding the effect of metformin on survival outcome of ESCC patients with type 2 diabetes mellitus (T2DM). We assessed the impact of post-diagnosis metformin use on overall survival (OS) and disease-free survival (DFS) in ESCC with T2DM undergoing surgical resection., Methods: A retrospective analysis was performed on 3,523 patients with ESCC who met the study conditions after surgical resection. Log-rank and Cox regression models were used to evaluate the relationship between metformin and T2DM and ESCC survival rate, and adjusted according to age, gender, BMI, smoking, drinking and staging, et al., Results: Among included ESCC patients, 619 were associated with type 2 diabetes, while the remaining 2,904 were not associated with type 2 diabetes. The 5-year OS (28.43%) of patients with T2DM was significantly lower than that of patients without T2DM (32.75%), P=0.037. DFS in 5 years were 27.30% (with T2DM) and 31.75% (without T2DM) (P=0.030), respectively. Compared with patients without T2DM, patients with T2DM presented worse OS [adjusted risk ratio (HR adj ) =1.19] and DFS (HRadj =1.17; P<0.001). Among the 619 patients with type 2 diabetes, 485 were treated with metformin and 134 were not treated with metformin. Patients treated with metformin had significantly improved OS [adjusted risk ratio (HR adj ) =0.89; P=0.031) and DFS (HR adj =0.90; P=0.013)., Conclusions: T2DM was again associated with poorer survival in ESCC patients, and metformin may improve the prognosis of these patients., Competing Interests: Conflicts of Interest: JH serves as the unpaid Executive Editor-in-Chief of Journal of Thoracic Disease. The other authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

It is more economical and feasible to harvest above-ground plant tissues, especially leaves, than to uproot the entire plant during phytoremediation. The major goal of this study is to estimate the promoting effect of an external magnetic field on soil Cadmium (Cd) remediation efficiency by harvesting the leaves of Festuca arundinacea, irrigated by normal and magnetized water. Changes in the amount of emerging, mature, senescent, and dead leaves, as well as Cd concentrations in the corresponding tissues were compared. It was found that F. arundinacea irrigated by either kind of water accumulated significantly more Cd in senescent and dead leaves than in other tissues. After irrigation with magnetized water, the biomass of senescent and dead leaves increased from 15.7 and 6.4% to 17.2 and 11.6%, respectively, and a significantly higher amount of Cd (˜23.6%) was redistributed into dead leaves compared with the control. Thus, significantly more Cd was removed by harvesting the senescent and dead leaves of F. arundinacea. These results indicate that magnetic fields can increase the phytoremediation efficiency of F. arundinacea for Cd, and simultaneously reduce the cost of harvested residue disposal., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The background of this study was to explore the success rate and early complications concerning the implantation of totally implantable venous access devices (TIVADs) by percutaneous venipuncture and management strategies for early complications., Materials and Methods: This was a retrospective study of 1923 patients who received TIVAD implantation by percutaneous venipuncture (mostly via the supraclavicular route). The percutaneous access sites were internal jugular vein (810 patients; right/left: 158/652) or proximal right internal jugular vein, brachiocephalic vein, and proximal subclavian vein (1113 patients). Success rates and early complications related to TIVAD placement techniques were summarized, and strategies for managing complications were also analyzed., Results: In 627 patients, TIVAD implantation was first performed by interventional radiologists using a "blind" approach relying on anatomical landmarks, having a 91.9% success rate. In contrast, there was a 100% success rate among the remaining 1296 patients who received ultrasound-guided implantation, a difference which was statistically significant (P < 0.05). Ultrasound-guided implantation was also successful for the 51 patients for whom the first attempt failed using the blind technique. Further, we found that the incidence of early complications was 5.41% (104/1923) and that the occurrence of immediate complications was significantly higher in the blind technique group compared to the ultrasound-guided group (37 vs. 12; P < 0.05)., Conclusions: It is safe and feasible to implant TIVADs by supraclavicular venipuncture. Ultrasound guidance combined with X-ray monitoring during operation significantly improves the surgery success rate and reduces the risk of early complications. Unclear anatomical landmarks and vascular variation are the main factors affecting success using a blind (nonguided) technique., Competing Interests: None

Background: To investigate the effects of levosimendan on right ventricular (RV) function in patients with acute decompensated heart failure (ADHF)., Methods: Patients with ADHF admitted from January 2017 to October 2017 were enrolled in this study. The patients were randomized to receive 24-h intravenous levosimendan or placebo. Echocardiographic examinations were performed and the parameters were compared. Epidemiological data were recorded and compared before and after treatment. Major adverse cardiac events during hospitalization and during 1-month follow-up were compared., Results: The baseline characteristics were comparable. After 24-h infusion of levosimendan and placebo, the left ventricular ejection fraction and S' were significantly increased in the levosimendan group compared with the control group (both p < 0.05). The E value in the levosimendan group significantly decreased (75.38 ± 8.32 vs. 88.21 ± 10.36, p < 0.0001), and E/e' significantly increased in the control group (19.61 ± 6.52 vs. 27.58 ± 8.22, p < 0.0001). The levels of right ventricular fractional area change (24 ± 3 vs. 20 ± 2, p < 0.0001) and tricuspid annular plane systolic excursion (1.56 ± 0.36 vs. 1.38 ± 0.21, p < 0.0001) were significantly higher in the levosimendan group than in the control group. After treatment, the values of systolic pulmonary artery pressure (SPAP) decreased in both groups (both p < 0.05), and the value of SPAP in the levosimendan group was lower than that in the control group (47.22 ± 5.6 vs. 55.85 ± 7.41, p < 0.0001). After 1-month follow-up, there was no significance in readmissions due to recurrent heart failure., Conclusions: Levosimendan seems to provide more beneficial effects among patients with ADHF to improve RV function, along with a decrease in pulmonary pressure.

For path planning of two welding robots, intelligent robot path optimization with obstacle avoidance is introduced first, where the optimization objective is the shortest time. In the optimization process, grid method is used for modeling. Then, ant colony algorithm is applied as search strategy to realize obstacle avoidance between welding gun and workpiece. For obstacle avoidance of robot joints, the robot is modeled using the sphere and the capsule. Besides, two-level collision detection and geometrical collision avoidance are used to obtain collision free robots' path. At last, an improved particle swarm optimization algorithm is used to realize global path planning. Simulation results show that the proposed strategy could improve the effectiveness of the path planning. It can be used to shorten the teaching time and strengthen offline programming ability.

A protocol for highly enantioselective hydrogenation of racemic α-arylamino lactones with catalysis by site-specifically modified chiral spiro iridium complexes has been developed. With the optimized catalyst, racemic α-arylamino-γ-lactones and α-arylamino-δ-lactones could be hydrogenated to the corresponding chiral 2-amino diols with good to excellent enantioselectivities.

Objective: To evaluate efficacy, safety and feasibility of targeted intracoronary injection using pro-urokinase combined with anisodamine (TCA) versus thrombus aspiration (TA) in ST-elevation myocardial infarction (STEMI) patients with high thrombus loads., Background: The best method of avoiding thrombus detachment and stroke in PCI patients with high thrombus loads has not yet been established., Methods: STEMI patients receiving coronary artery angiography or percutaneous coronary intervention (CAG/PCI) with thrombus grade ≥ 3 from January 1, 2017 to June 30, 2018 were randomly assigned to targeted intracoronary thrombolysis (pro-urokinase and anisodamine via catheter (TCA) group), or the TA group which followed the standard thrombus aspiration procedure. Parameters compared included thrombus grade, index of microcirculatory resistance (IMR), postoperative myocardial SPECT, thrombosis in myocardial infarction (TIMI) scores including flow grade, corrected TIMI frame counts (CTFCs), and TIMI myocardial perfusion grade (TMPG). Adverse events were followed up within 3 months., Results: Thirty-nine patients were finally enrolled. In primary CAG/PCI, the TCA group had higher percentages of TIMI 3 flow and lower IMR values compared with the TA group. The ratio of TMPG 3 grade in the TCA group was higher in repeat CAG, and the perfusion descending area (PDA) presented by SPECT was lower than in the TA group. No significant difference was seen in major adverse coronary events (MACEs) or bleeding events at follow-up., Conclusions: TCA appears to be effective, safe, and feasible for repatency and reduction of high thrombus burden in primary PCI and may protect myocardial microcirculation with improved outcomes., (© 2019 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals, Inc.)

An artificial diet formulated for continuous rearing of the predator Arma chinensis was inferior to natural prey when evaluated using life history parameters. A transcriptome analysis identified differentially expressed genes in diet-fed and prey-fed A. chinensis that were suggestive of molecular mechanisms underlying the nutritive impact of the artificial diet. Changes in the diet formulation were made based on the transcriptome analysis and tested using life history parameters. The quantity of pig liver, chicken egg, tuna fish, biotin, nicotinamide, vitamin B6, thiamine, riboflavin, vitamin C, L-glutamine, and sucrose was reduced, and wheat germ oil, calcium pantothenate and folic acid were increased. Ecuadorian shrimp was added as a partial substitute for tuna fish. Several parameters improved over six generations, including increased egg viability, and decreased egg and adult cannibalism. Additionally, several parameters declined, including longer developmental times for 2nd-5th instars, and decreased nymphal weights. The improvements in life history parameters support the use of transcriptome analyses to help direct formulation improvements. However, the decline in some parameters suggests that additional information, e.g., proteomic data, may be useful as well to maximize diet formulations.

Background: Parkinson's disease (PD) is characterized by a chronic loss of dopaminergic neurons and the presence of proteinaceous inclusions (Lewy bodies) within some remaining neurons in the substantia nigra. Recently, astroglial inclusion body has also been found in some neurodegenerative diseases including PD. However, the underlying molecular mechanisms of how astroglial protein aggregation forms remain largely unknown. Here, we investigated the contribution of αB-crystallin (CRYAB), a small heat shock protein, in α-synuclein inclusion formation in astrocytes., Methods: Small interfering RNA (siRNA)-mediated CRYAB (siCRYAB) knockdown or CRYAB overexpression was performed to investigate the impact of CRYAB on the autophagy in human glioblastoma cell line U251 cells. Co-immunoprecipitation (co-IP) and immunoblotting were used to dissect the interaction among multiple proteins. The clearance of α-synuclein in vitro was evaluated by immunocytochemistry. CRYAB transgenic mice and transgenic mice overexpressing A30P mutant form of human α-synuclein were used to examine the influence of CRYAB to α-synuclein accumulation in vivo., Results: We found that knockdown of CRYAB in U251 cells or primary cultured astrocytes resulted in a marked augmentation of autophagy activity. In contrast, exogenous CRYAB disrupted the assembly of the BAG3-HSPB8-HSC70 complex via binding with BAG3, thereby suppressing the autophagy activity. Furthermore, CRYAB-regulated autophagy has relevance to PD pathogenesis. Knockdown of CRYAB remarkably promoted cytoplasmic clearance of α-synuclein preformed fibrils (PFFs). Conversely, selective overexpression of CRYAB in astrocytes markedly suppressed autophagy leading to the accumulation of α-synuclein aggregates in the brain of transgenic mice expressing human α-synuclein A30P mutant., Conclusions: This study reveals a novel function for CRYAB as a natural inhibitor of astrocytic autophagy and shows that knockdown of CYRAB may provide a therapeutic target against proteinopathies such as synucleinopathies., Competing Interests: All procedures performed were approved by the Institutional Animal Care and Use Committee and were in accordance with the US National Institutes of Health Guide for the Care and Use of Laboratory Animals.Not applicable.The authors declare that they have no competing interests.

Metal decontamination and leaching alleviation capacity of Eucalyptus globulus with and without electric field were investigated using ICP-MS. The biomass production of the chosen plant increased from 0.87 kg in planting control without electrokinetic treatment to 1.16 and 1.42 kg in experiments with electric field supplied by storage battery and solar cell, respectively. Under the influence of electric field with a voltage of 6.5 V, significantly more Cd, Pb and Cu were extracted by the species. Precipitation simulation was performed to evaluate the capacity of battery and solar panel to intercept leaching. The total volume of leachate gathered from the control decreased from 1012 mL to 299 and 336 mL in containers treated by storage battery and solar cell, respectively. In addition to reduction of leachate, the leaching mass of Cd, Pb and Cu was decreased significantly by electric fields (both battery and solar cell) treatments. The effect of remediation and environmental risk alleviation by solar cell was comparable with storage battery, at least during the 30-day experimental period. On the basis of the present study, solar cell should be a suitable substitute for conventional power supply to improve metal polluted soil when considering phytoremediation efficiency and energy consumption.

PM 2.5 samples (particles with aerodynamic diameter < 2.5 μm) were collected along the Guang-Shen expressway around the Qingming Festival, one of the most congested periods in China, which started from April 2-4, in 2016. Twenty-five trace elements and 16 priority polycyclic aromatic hydrocarbons (PAHs) of the samples were analyzed. Their major sources at different periods were identified. The concentrations of PAHs distinctly increased with growing traffic flow 2 days before the Qingming Festival (March 31th and April 1st), decreased gradually on the first 2 days of the 3-day festival (April 2nd and 3rd) and rose again on the last day (April 4th). The proportion changing of higher molecular weight containing 5- and 6-ring PAHs (HMW PAHs) closely related to the traffic flow variation were consistent with the concentration variation of PAHs during the experimental period. Indicators of gasoline/diesel engines emission, i.e., Mo, Co, Mn, and Pb showed similar concentration variation with PAHs. The concentrations of trace elements, mainly derived from wear instead of combustion process, such as Cu, Zn, Ti, and Sb, raised significantly during the rainy days. Incremental lifetime cancer risk (ILCR) values were calculated to evaluate the health risk caused by PAH around the Qingming Festival. The ILCR values increased by 3-10 times 2 days before and on the last day of the festival comparing with other days, as a result of traffic related sources, including engine emission and wearing of tires. It concluded by recommending the necessity of traffic diversion to alleviate the health risk to drivers and nearby residents during important festivals.

Eucalyptus globulus were used to remediate a real scale site endangered by e-waste with electric fields supplied by solar cell and conventional storage battery. The capacity of the species to produce biomass, absorb pollutants and decontaminate metals, as well as the soil moisture of various layers under different treatments was compared. During the 3-month experiment, the output potential of solar cell influenced by weather conditions was less stable (ranging from 0 to 8.3 V) comparing with traditional power supply. Solar cell and storage battery stimulated the growth of the species from 5.92 in control to 7.21 and 7.38 kg per plant, respectively, demonstrating their similar improvement effect. Electric fields of either power source increased the metal concentrations of plant roots and shoots in equal proportions and subsequently greatly promoted the efficiency to decontaminate pollutants. Relative to the control without electric field, solar cell and storage battery treatments reduced the soil moisture of each corresponding layer and consequently, alleviated the leaching risk. At the termination of the experiment, metals tended to distribute in the surface layer under electric field assisted phytoremediation either by solar cell or storage battery. Comparing with conventional battery, solar cell has similar effect on improving remediation and mitigating leaching risk, but is less energy consuming and easier to manage, especially under real scale field. Solar cell treatment was suggested to be a suitable supplementary means to improve phytoremediation efficiency., (Copyright © 2018 Elsevier Inc. All rights reserved.)

It has been well documented that Achyranthes bidentata polypeptides (ABPPs) are potent neuroprotective agents in several types of neurons. However, whether ABPPs protect dopaminergic neurons from apoptosis induced by neurotoxins is still unknown. This study was designed to observe the effect of ABPPk, a purified fraction of ABPPs, on apoptosis of dopaminergic neurons. SH-5YHY cells and primary dopaminergic neurons were pre-treated with ABPPk (25, 50, or 100 ng/mL) for 12 hours. Cells were then exposed to 6-hydroxydopamine (50 or 150 μM) or rotenone (50 or 200 μM) for 36 hours to induce cell apoptosis. Our results demonstrate that ABPPk markedly increased viability in SH-SY5Y cells and primary dopaminergic neurons, decreased lactate dehydrogenase activity and number of apoptotic dopaminergic neurons, elevated mitochondrial membrane potential, and increased Bcl-2/Bax ratio. These findings suggest that ABPPk protects dopaminergic neurons from apoptosis, and that ABPPk treatment might be an effective intervention for treating dopaminergic neuronal loss associated with disorders such as Parkinson's disease., Competing Interests: The authors declare that they have no competing financial interests

Objective: To investigate whether lncRNA H19 can regulate NF1 expression through competitive binding to microRNA-107, thereby participating in the occurrence and development of non-small cell lung cancer (NSCLC)., Patients and Methods: Expression levels of H19 and NF1 in NSCLC tissues, paracancerous tissues and NSCLC cell lines were detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The binding condition of microRNA-107, H19 and NF1 was detected by dual-luciferase reporter gene assay. Corresponding lentiviruses of H19 were constructed. The regulatory effects of H19 on proliferative and migratory abilities of A549 cells were detected by cell counting kit-8 (CCK-8) and transwell assay, respectively. Rescue experiments were conducted to explore the regulatory interaction between H19 and microRNA-107 in A549 cells., Results: H19 and NF1 were highly expressed in NSCLC tissues and NSCLC cell lines (A549 and HCC823) than those of controls. Overexpressed H19 increased proliferative and migratory abilities of A549 cells. Dual-luciferase reporter gene assay demonstrated that H19 regulates NF1 expression through competitive binding to microRNA-107, thereafter participating in NSCLC development., Conclusions: H19 is highly expressed in NSCLC, which promotes NSCLC development by regulating NF1 via competitive binding to microRNA-107.

The combined utilization of direct or alternating electric fields and phytoremediation was designed to decontaminate multi-metal polluted soil at a field scale e-waste recycling impacted site. Eucalyptus globulus was chosen for metal purification for its resilient and unpalatable nature. Biomass production, metal concentration and water use efficiency of the species under direct current (DC) and alternating current (AC) fields with various voltages were investigated. DC and AC fields stimulated the growth of the plant, except for DC field with high voltage (10 V). Metal concentrations increased in plant tissues under the influence of AC or DC fields irrespective of voltages. DC fields elevated the root and shoot metal contents of plants in equal proportions and AC fields tended to migrate metals from roots to the aboveground parts of the species. Compared to the control, soil moisture of various soil layers at the planted site was significantly lower and subsequently leading to the decrease of metal leaching. In soil profile metal distributes differently between DC and AC treatments. Compared to AC field, more metals tended to accumulate in soil surface under the influence of DC fields due to the stable converse gravitational pathway of metals. Considering decontamination efficiency, leaching interception and energy consumption, DC field with moderate voltage was a suitable candidate for real scale multi-metal polluted soil phytoremediation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To explore the relationship between coronary tortuosity and coronary microvascular disease (CMVD). Methods: Patients with typical angina symptoms and without serious coronary artery stenosis by coronary angiography were enrolled from June 2014 to December 2016, and CMVD was diagnosed by single photon emission tomography (SPECT). According to the SPECT results, patients were divided to the CMVD group and non-CMVD group. The baseline clinical characteristics, results of coronary angiography were compared between the two groups. The logistic analysis was used to analyze the relationship between coronary tortuosity and CMVD. Result: A total of 117 cases were enrolled, with 69 cases in the CMVD group and 48 cases in the non-CMVD group. No differences were found in gender distribution, age, hypertension, lipid abnormality, hyperuricemia and uses of statins between the two groups (all P >0.05). Incidence of diabetes (78.26%(54/69) vs. 35.42% (17/48) , P <0.05), hs-CRP ((4.29±2.15)mmol/L vs. (2.63±1.20)mmol/L, P <0.001), LDL-C ((2.98±0.96)mmol/L vs. (2.52±0.83)mmol/L, P= 0.008) and homocysteine ((13.7±5.61)mmol/L vs. (11.5±4.38)mmol/L, P= 0.025) levels were higher in the CMVD group than in the non-CMVD group. The data derived from echocardiographic examination were similar between the two groups. The Corrected TIMI frame counts were higher in the CMVD group than in non-CMVD group (LAD: 31.56±4.92 vs. 27.31±3.75, LCX: 29.47±4.18 vs. 26.62±3.19, RCA: 29.09±5.05 vs. 26.24±3.28, all P <0.001). The incidences of coronary atherosclerosis (76.81% (53/69) vs. 27.08% (13/48) , P <0.001) and coronary tortuosity ( (60.87% (42/69) vs. 33.33% (16/48) , P= 0.035) were also higher in the CMVD group than in non-CMVD group. Logistic analysis found that coronary tortuosity ( OR= 6.111, 95% CI 2.707-13.794, P <0.001), diabetes ( OR= 6.565, 95% CI 2.883-14.948, P <0.001) and coronary atherosclerosis ( OR= 8.918, 95% CI 3.822-20.808, P <0.001) were independent risk factors of CMVD. Conclusion: Coronary tortuosity, diabetes and coronary atherosclerosis are related to CMVD in this patient cohort.

The phytoremediation efficiency of multi-metal-polluted sites in an electronic waste recycling town by Eucalyptus globulus was evaluated through a series of 2-year field experiments. Different initial planting densities (2500, 5000, and 10,000 plants per ha), coppice rotations, and harvesting position (5 or 30 cm above the ground) protocols were designed to improve the remediation potential of the species. There were unnoticeable variations in metal concentrations and distribution characteristics in plant tissues in a low and medium planting-density field during the experimental period. At the end of the experiment, total biomass production per hectare in different protocols displayed a wide range with maximum yield produced in high density, moderate harvesting, and coppice rotation protocol being 2.9 times higher than the minimum yield. The moderate harvest protocol performed with medium planting density was the optimal Cd and Cu decontamination technique. Although the high planting-density field without coppice rotation had the strongest potential for Pb decontamination, it would take more time to remove other metals for the multi-metal-polluted soil decontamination. Considering the remediation efficiency and maintainability of the cultivation system, the moderate harvest protocol performed with the medium planting density was commended for phytoremediation of e-waste recycling impacted area.

The phytoremediation efficiency of various metals by Ficus microcarpa was evaluated through a real scale experiment in the present study. The root biomass production of the species varied significantly from 3.68 to 5.43 g because of the spatial heterogeneity of different metals. It would take 4-93 years to purify the excess Cd of the experimental site. Mercury was the most inflexible element which can barely be phytoremediated by F. microcarpa. After the species transplanted from the polluted soil to the clean site, Cd and Cu were transferred to the rhizosphere soil to different extent while the bulk soil was barely influenced. Relative to Cd and Cu, significantly fewer amounts of Pb and Hg were released. The highest concentrations of Cd, Cu, Hg and Pb in the clean soil were far below their corresponding safe thresholds for agricultural land after 3 months of the polluted plants were cultivated and metal concentrations of plant leaves were negligible, both indicated the low ecological risk of transplantation. Results from this study suggested a feasible disposal method for metal rich plants after phytoremediation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In this study, the complete mitochondrial genome (mitogenome) of Oberthueria lunwan Zolotuhin & Wang, 2013 (Lepidoptera: Oberthuerinae) is reported for the first time. The entire mitogenome is a circular DNA molecule of 15,673 bp in length (GenBank accession number: MF100143), consisting of 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs) genes, two ribosomal RNAs (rRNAs) genes, and a control region (A + T-rich region). The phylogenetic trees are based on 13 PCGs amino acid sequences of 31 related lepidopteran species in which mitogenome sequences were constructed. The Oberthuerinae consisting of O. lunwan + Andraca theae was strongly supported as a monophyletic clade by the posterior probability of 1.00 and the bootstrap value of 100%, but the relationships among Oberthuerinae, Bombycidae, Satruniidae, and Sphingidae are need to be further confirmed., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (© 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

As a serious forest pest on coniferous trees, Dendrolimus kikuchii has caused widespread concern in China. Here, its complete mitochondrial genome (mitogenome) has been sequenced with 15,382 bp in length. The mitogenome has a base composition of A (40.87%), T (37.83%), C (13.43%), and G (7.87%), and consists of 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and an A + T-rich region. The phylogenetic relationships among the lasiocampid species were ( Trabala vishnou + (( Apatelopteryx phenax +  Euthrix laeta ) + ( Dendrolimus kikuchii + ( D. spectabilis + ( D. tabulaeformis + D. punctatus ))))), which were supported by a posterior probability of 1.00 and a high bootstrap value of 100%., Competing Interests: The authors declare no conflict of interest. The authors alone are responsible for the content and writing of the paper., (© 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The complete mitochondrial genome (mitogenome) of Bombyx lemmepauli Lemée has been sequenced with 15,801 bp in length (Genbank no. KY620270), and has a base composition of A (43.17%), G (7.40%), C (11.90%), and T (37.86%). Similar to other bombyciod species, it contains a typically conserved structure including 13 protein-coding genes (PCGs), 22 transfer RNA genes, 2 ribosomal RNA genes, and an A + T-rich region. Excepting cox1 started with CGA, the start codons of the other 12 PCGs were ATN. Eleven of the 13 PCGs ended with TAA, expect for cox1 and cox2 , which ended with a single T. The complete mitogenome sequence provided here would be useful for further understanding the evolutional position of B. lemeepauli , which is a key species to relate the famous resource insect B. mori and the important insect pest Rondotia menciana (Lepidoptera: Bombycidae)., Competing Interests: The authors have declared that no competing interests exist. The authors alone are responsible for the content of the paper., (© 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: This study aimed to investigate the effects of intensive pitavastatin therapy on glucose control in patients with non-ST elevation acute coronary syndrome (ACS). Methods: Patients who had ACS with significant stenosis on initial coronary angiography and received successful percutaneous coronary intervention (PCI) in the Second Hospital of Hebei Medical University, Shijiazhuang, China from August 2015 to January 2016 were enrolled in this study. The patients were randomized to receive pitavastatin (4 mg daily) or atorvastatin (20 mg daily). PCI was performed within 72 hours after admission according to the current clinical practice at the physician's discretion. The examinations of blood lipid levels and blood markers of glucose metabolism were performed at baseline and after 6-month follow-up using standard techniques. The inflammatory markers, including white blood cell, high-sensitivity C-reactive protein (hs-CRP) and fibrinogen, were also assessed before PCI and 24 hours after PCI. An independent adverse event assessment committee evaluated major adverse cardiovascular events (MACE) and any other adverse events. Results: A total of 132 patients were enrolled and randomly divided into the pitavastatin group (n = 65) or the atorvastatin group (n = 67), which had similar baseline characteristics and PCI procedural characteristics. For the inflammatory biomarkers at 24 hours after PCI, the fibrinogen level was significantly increased in the atorvastatin group; the hs-CRP levels were significantly increased in both groups, however, the hs-CRP level in the pitavastatin group was lower than that in the atorvastatin group. In addition, the blood lipid parameters (e.g., TC, LDL-C, TG, non-HDL-C and Apo B) were significantly decreased in both groups after 6-month follow-up ( P < 0.01), but these parameters between the two groups had no significant difference. After 6-month follow-up, the FPG, IRI, HOMA-IR and HbA 1c levels were significantly decreased in the pitavastatin group ( P < 0.05) but slightly increased in the atorvastatin group, indicating that the glucose homeostasis was improved in patients in the pitavastatin group but not in the atorvastatin group. Furthermore, the incidence of MACE was not significantly different between the two groups ( P > 0.05). After 6-month antiplatelet treatment, the PAR value was significantly decreased in both groups ( P < 0.01), but the PAR value in the pitavastatin group was lower than that in the atorvastatin group. Conclusion: Pitavastatin therapy may improve the glucose homeostasis for patients with ACS undergoing PCI and has more favorable outcomes than atorvastatin therapy., Competing Interests: None.

The current study tested the anti-hepatocellular carcinoma (HCC) cell activity of TIC10, a first-in-class small-molecule tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL) inducer. TIC10 exerted potent anti-proliferative and pro-apoptotic actions in primary and established human HCC cells. TIC10 blocked Akt-Erk activation, leading to Foxo3a nuclear translocation, as well as TRAIL and death receptor-5 (DR5) transcription in HCC cells. We propose that DNA-PKcs is a major resistance factor of TIC10 possibly via inhibiting Foxo3a nuclear translocation. DNA-PKcs inhibition, knockdown or mutation facilitated TIC10-induced Foxo3a nuclear translocation, TRAIL/DR5 expression and cell apoptosis. Reversely, exogenous DNA-PKcs over-expression inhibited above actions by TIC10. In vivo, oral administration of TIC10 significantly inhibited HepG2 tumor growth in nude mice, which was further potentiated with Nu7026 co-administration. Thus, TIC10 shows promising anti-HCC activity, alone or together with DNA-PKcs inhibitors.

This study aimed to explore the relationship between computed tomography morphology and prognosis of patients with stage I non-small cell lung cancer (NSCLC). From May 2009 to May 2011, a total of 124 patients diagnosed with stage I NSCLC were included. All patients had complete chest computed tomography scans. Five-year follow-up was conducted. Univariate and multivariate Cox regression analyses were performed to estimate the prognostic factors for patients with stage I NSCLC. The 5-year survival rate was 67.74% (84/124). The 5-year survival rates of patients with stage T1a, T1b, and T2a were 89.19%, 75.00%, and 41.86%, respectively. The 5-year survival rates of patients with homogeneity, inhomogeneity, vacuole, and cavity were 68.42%, 72.09%, 59.46%, and 83.33%, respectively. The 5-year survival rates of patients with different margin features were 83.33% (slick margin), 79.73% (lobulation sign), and 39.47% (short burr). The 5-year survival rates of patients with normal, halo, vessel convergence, bronchial transection, and vascular bundle thickening were 84.38%, 72.73%, 71.79%, 52.00%, and 47.06%, respectively. The 5-year survival rates of patients with normal and pleura thickening/indentation were 81.93% and 39.02%. Univariate analysis demonstrated that tumor node metastasis staging, tumor margin, tumor periphery, and pleural invasion were related to the prognosis of stage I NSCLC patients. Cox regression analysis confirmed that T2a stage, pleura thickening/indentation were independent risk factors for poor prognosis of stage I NSCLC. In conclusion, our findings indicate that T2a stage, pleura thickening/indentation might be prognostic factors in stage I NSCLC., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

High-level black carbon (BC) pollution is associated with traffic emissions in metropolitan areas with high vehicle density. Mobile monitoring was conducted to assess the in-vehicle BC exposure on three backbone ring roads (inner, middle, and outer ring roads) on October 14 and October 18, 2015 in Shanghai. Ambient BC monitoring was also simultaneously conducted in three fixed roadside stations from October 14 to October 20, 2015. Results of the mobile monitoring showed median BC personal exposure concentrations ranging from 5.0 μg m -3 on the inner ring road to 13.5 μg m -3 on the outer ring road. The ambient BC concentrations during the entire observation period showed an arithmetic mean and a standard deviation of 3.5 ± 2.9 μg m -3 . The correlation analysis of urban roadside monitoring (Caoxi Road and South Zhongshan Road) and personal data showed a high and significant correlation. The results of this study highlight the critical level of BC pollution in Shanghai and facilitate the development of evidence-based public health interventions and control strategies to prevent the adverse health effects of BC pollution.

A highly efficient Ir-catalyzed asymmetric hydrogenation of racemic β-keto lactams via dynamic kinetic resolution (DKR) for the synthesis of optically active β-hydroxyl lactams has been described. With the Ir-SpiroSAP catalyst, a series of racemic β-keto lactams including β-keto γ-, δ-, and ε-lactams were hydrogenated to chiral β-hydroxy lactams in high yields (87-99%) with excellent enantio- and diastereoselectivity (83-99.9% ee, syn/anti: 97:3->99:1) at low catalyst loading under mild reaction conditions. This efficient method has been successfully applied in the synthesis of the chiral intermediate of fluoroquinolone antibiotic premafloxacine.

Myelination of Schwann cells in the peripheral nervous system is an intricate process involving myelin protein trafficking. Recently, the role and mechanism of the endosomal/lysosomal system in myelin formation were emphasized. Our previous results demonstrated that a small GTPase Rab27a regulates lysosomal exocytosis and myelin protein trafficking in Schwann cells. In this present study, we established a dorsal root ganglion (DRG) neuron and Schwann cell co-culture model to identify the signals associated with Rab27a during myelination. First, Slp2-a, as the Rab27a effector, was endogenously expressed in Schwann cells. Second, Rab27a expression significantly increased during Schwann cell myelination. Finally, Rab27a and Slp2-a silencing in Schwann cells not only reduced myelin protein expression, but also impaired formation of myelin-like membranes in DRG neuron and Schwann cell co-cultures. Our findings suggest that the Rab27a/Slp2-a complex affects Schwann cell myelination in vitro ., Competing Interests: Conflicts of Interest: None declared.

Paeoniflorin (PF) is the main active component extracted from the roots of Paeonialactiflora, a traditional Chinese medicine used for the treatment of neurodegenerative disorders, especially Parkinson's disease (PD). The degeneration of dopaminergic (DA-) neurons in PD may be caused by pathological activation of acid-sensing ion channels (ASICs). Thus, we designed a series of experiments to evaluate the therapeutic effects of PF and to test whether its effects are related to its inhibitory effect on ASIC1a. We found that systemic administration of PF or ASICs blockers (psalmotoxin-1 and amiloride) improved behavioral symptoms, delayed DA-neuronal loss and attenuated the reduction of dopamine (DA) and its metabolites in a rat model of 6-hydroxydopamine (6-OHDA)-induced PD. In addition, our data showed that PF, like ASICs blockers, regulated the expression of ASIC1a, decreased the level of α-synuclein (α-SYN), and improved autophagic dysfunction. Further experiments showed that ASIC1a knockdown down-regulated the α-SYN level and alleviated the autophagic injury in the 6-OHDA-treated ASIC1a-silenced PC12 cells. In summary, these findings indicate that PF enhanced the autophagic degradation of α-SYN and, thus, protected DA-neurons against the neurotoxicity caused by 6-OHDA. These findings also provide experimental evidence that PF may be a neuroprotectant for PD by acting on ASIC1a and that ASIC1a may be involved in the pathogenesis of PD.

Bradysia odoriphaga Yang & Zhang (Diptera: Sciaridae) is the most serious pest of Chinese chive, Allium tuberosum Chemical pesticide application has become a necessary step to control B. odoriphaga after each of the four to six harvests during the growing season. We compared the effects of application type (nematode-infected cadaver, aqueous nematode suspension, and mixture of cadaver and aqueous suspension) and nematode species (Heterorhabditis bacteriophora vs. Steinernema carpocapsae) on B. odoriphaga control. Nematode species combinations and the use of the cadaver method has only been tested in a relatively few studies, and has not been tested for this target pest, B. odoriphaga. Furthermore, this is the first report of combining application methods (aqueous and cadaver). Results indicated that the cadaver treatment produced higher mortality of B. odoriphaga than the aqueous treatment, and H. bacteriophora caused higher mortality of B. odoriphaga than S. carpocapsae. The mortality of B. odoriphaga was 96.7% in H. bacteriophora cadaver treatment and only 27.5% in control treatment without nematode addition. Cadaver treatments caused higher biomass of A. tuberosum than that of aqueous treatment. The plant biomass in H. bacteriophora cadaver treatment was 10 folds as much as that in the control treatment. The mixed aqueous suspension of H. bacteriophora and S. carpocapsae did not increase the mortality in pot trial. Our findings indicate that entomopathogenic nematodes applied as cadavers might be a potential alternative biological agent in the integrated management of B. odoriphaga for Chinese chive production., (© The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The bombycid moth, Andraca theae (Matsumura) (Lepidoptera: Bombycoidea) is an important pest of tea in southeastern China. In the present study, the mitochondrial genome (mitogenome) of A. theae was amplified by polymerase chain reaction and sequenced. The complete mitogenome of A. theae, encoding 37 genes, was 15,737 bp in length (Genbank no. KX365419), and consisted of 13 protein-coding genes (PCGs), 22 tRNA genes, 2 ribosomal RNA genes and an adenine (A) + thymine (T)-rich region (AT-rich region). The gene order of A. theae mitogenome was typical for Lepidoptera mitogenomes. Except for cox1, which started with CGA, all other 12 PCGs started with ATN. Eleven of the 13 PCGs ended with TAA, expect for cox1 and cox2, which ended with a single T. The maximum likelihood method and the Bayesian method were used to analyze the phylogenetic relationship among 22 representative bombycoid species with a matrix consisting of the 13 PCGs of the mitogenomes of the 22 species. The topological structures of the two phylogenetic trees we constructed were almost identical, with the results indicating that the bombycid species, including A. theae, clustered into a single clade with a bootstrap value of 58% and a posterior probability of 0.98. The phylogenetic relationship among the Bombycoidea species analyzed was Lasiocampidae + (Bombycidae + (Saturniidae + Sphingidae)) which was supported by a high bootstrap value of 100% and a posterior probability of 1.00., (© The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America.)

Tau, a primary component of microtubule-associated protein, promotes microtubule assembly and/or disassembly and maintains the stability of the microtubule structure. Although the importance of tau in neurodegenerative diseases has been well demonstrated, whether tau is involved in peripheral nerve regeneration remains unknown. In the current study, we obtained sciatic nerve tissue from adult rats 0, 1, 4, 7, and 14 days after sciatic nerve crush and examined tau mRNA and protein expression levels and the location of tau in the sciatic nerve following peripheral nerve injury. The results from our quantitative reverse transcription polymerase chain reaction analysis showed that compared with the uninjured control sciatic nerve, mRNA expression levels for both tau and tau tubulin kinase 1, a serine/threonine kinase that regulates tau phosphorylation, were decreased following peripheral nerve injury. Our western blot assay results suggested that the protein expression levels of tau and phosphorylated tau initially decreased 1 day post nerve injury but then gradually increased. The results of our immunohistochemical labeling showed that the location of tau protein was not altered by nerve injury. Thus, these results showed that the expression of tau was changed following sciatic nerve crush, suggesting that tau may be involved in peripheral nerve repair and regeneration., Competing Interests: Conflicts of Interest: None declared.

Myelination by oligodendrocytes in the central nervous system requires coordinated exocytosis and endocytosis of the major myelin protein, proteolipid protein (PLP). Here, we demonstrated that a small GTPase, Rab27b, is involved in PLP trafficking in oligodendrocytes. We showed that PLP co-localized with Rab27b in late endosomes/lysosomes in oligodendrocytes. Short hairpin-mediated knockdown of Rab27b not only reduced lysosomal exocytosis but also greatly diminished the surface expression of PLP in oligodendrocytes. In addition, knockdown of Rab27b reduced the myelin-like membranes induced by co-culture of oligodendrocytes and neurons. Our data suggest that Rab27b is involved in myelin biogenesis by regulating PLP transport from late endosomes/lysosomes to the cell membrane in oligodendrocytes.

MicroRNAs (miRNAs) are small, non-coding RNAs that negatively adjust gene expression in multifarious biological processes. However, the regulatory effects of miRNAs on Schwann cells remain poorly understood. Previous microarray analysis results have shown that miRNA expression is altered following sciatic nerve transaction, thereby affecting proliferation and migration of Schwann cells. This study investigated whether miR-148b-3p could regulate migration of Schwann cells by directly targeting cullin-associated and neddylation-dissociated 1 (Cand1). Up-regulated expression of miR-148b-3p promoted Schwann cell migration, whereas silencing of miR-148b-3p inhibited Schwann cell migration in vitro. Further experiments confirmed that Cand1 was a direct target of miR-148b-3p, and Cand1 knockdown reversed suppression of the miR-148b-3p inhibitor on Schwann cell migration. These results suggested that miR-148b-3p promoted migration of Schwann cells by directly targeting Cand1 in vitro.

Background: The risk of radial artery occlusion (RAO) needs particular attention in transradial intervention (TRI). Therefore, reducing vascular occlusion has an important clinical significance. The aim of this study was to determine the appropriate puncture site during TRI through comparing the occurrence of RAO between the different puncture sites to reduce the occurrence of RAO after TRI., Methods: We prospectively assessed the occurrence of RAO in 606 consecutive patients undergoing TRI. Artery occlusion was evaluated with Doppler ultrasound in 2 days and 1 year after the intervention. Risk factors for RAO were evaluated using a multivariate model analysis., Results: Of the 606 patients, the RAO occurred in 56 patients. Compared with TRI at 2-5 cm away from the radius styloid process, the odds ratio (OR) for occlusion risk at 0 cm and 1 cm were 9.65 (P = 0.033) and 8.90 (P = 0.040), respectively. The RAO occurred in the ratio of the arterial diameter to the sheath diameter ≤1 (OR = 2.45, P = 0.004)., Conclusion: Distal puncture sites (0-1 cm away from the radius styloid process) can lead to a higher rate of RAO., Trial Registration: ClinicalTrials.gov, NCT01979627; https://clinicaltrials.gov/ct2/show/NCT01979627?term = NCT01979627 and rank = 1.

Angiogenesis is a key process in regenerative medicine generally, as well as in the specific field of nerve regeneration. However, no convenient and objective method for evaluating the angiogenesis of tissue-engineered nerves has been reported. In this study, tissue-engineered nerves were constructed in vitro using Schwann cells differentiated from rat skin-derived precursors as supporting cells and chitosan nerve conduits combined with silk fibroin fibers as scaffolds to bridge 10-mm sciatic nerve defects in rats. Four weeks after surgery, three-dimensional blood vessel reconstructions were made through MICROFIL perfusion and micro-CT scanning, and parameter analysis of the tissue-engineered nerves was performed. New blood vessels grew into the tissue-engineered nerves from three main directions: the proximal end, the distal end, and the middle. The parameter analysis of the three-dimensional blood vessel images yielded several parameters, including the number, diameter, connection, and spatial distribution of blood vessels. The new blood vessels were mainly capillaries and microvessels, with diameters ranging from 9 to 301 μm. The blood vessels with diameters from 27 to 155 μm accounted for 82.84% of the new vessels. The microvessels in the tissue-engineered nerves implanted in vivo were relatively well-identified using the MICROFIL perfusion and micro-CT scanning method, which allows the evaluation and comparison of differences and changes of angiogenesis in tissue-engineered nerves implanted in vivo.