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Three-dimensional nitrogen-doped graphene/polyaniline hydrogels (RGNP) was synthesized by facile hydrothermal method with graphene oxide (GO) and polyaniline nanorods (PANI-NRs), and urea as the reducing agent and nitrogen source. The structures and morphologies of the composites were characterized by various techniques, and electrochemical properties were also investigated. X-ray photoelectron spectroscopy (XPS) demonstrated nitrogen atom was doped into graphene and scanning electron microscopy (SEM) indicated PANI-NRs fully inset into the three-dimensional graphene layers. The RGNP composite electrode exhibited the significantly improved electrochemical performances compared to the undoped equivalents or the separate components. The specific capacitance is up to 589.3 Fg −1 at current density of 3 mA cm −2 in 1 M H 2 SO 4 electrolyte, which also displays superior pseudocapacitive cycling stability (retention of 80.5% after 500 cycles). In addition, good capacitance retention rate (80.2% at 30 mA cm −2 ) has been achieved. These results indicate that the RGNP composite electrode can be applied for high performance supercapacitor.

Spinal cord injury (SCI) is a severe trauma to the central nervous system that often leads to motor and sensory dysfunction in patients, severely affecting their quality of life. Autophagy plays a role in the pathological process of SCI, but the specific mechanism of autophagy in this case is unknown. COL1A1 and CD44, as potentially important genes in the autophagic process, may regulate the signaling pathway and thus affect the autophagic process through protein interactions. The aim of this study was to investigate the interaction between COL1A1 and CD44 and its mechanism of regulating autophagy through the JAK1/STAT3 pathway, providing new targets for SCI treatment. An SCI rat model was established, along with a PC12 cell model induced by oxygen–glucose deprivation (OGD). COL1A1 and CD44 in rat spinal cord tissues and cells were assessed using RT‐qPCR and Western blot. Motor function in rats was assessed by BBB score, and the pathological conditions of the rat spinal cord tissues and neuronal numbers were observed by HE staining and Nissl staining. COL1A1 and CD44 localization in PC12 cells was confirmed via immunofluorescence analysis, and their targeting binding was verified by Co‐IP. In the cell model, apoptosis, proliferation, and autophagy were evaluated through flow cytometry, CCK‐8, and mRFP‐GFP‐LC3 transfection, respectively. The activation of the JAK1/STAT3 cascade in spinal cord tissues and PC12 cells was assessed, along with its function in the cell model. COL1A1 and CD44 were significantly overexpressed in spinal cord tissues of SCI rats and OGD‐treated PC12 cells. COL1A1 silencing promoted functional recovery and autophagy after SCI in rats, ameliorated OGD‐induced PC12 cell injury, upregulated autophagy proteins, and increased the number of autophagosomes and autolysosomes. COL1A1 was able to bind to CD44 in a targeting fashion and regulated the JAK1/STAT3 cascade. CD44 overexpression counteracted the positive effects of COL1A1 silencing on both the functional recovery of SCI rats and OGD‐induced PC12 cell injury. COL1A1 targets and binds to CD44 to activate autophagy mediated by the JAK1/STAT3 signaling pathway, inhibiting functional recovery after SCI.

Despite recent advances in the therapy of non-small cell lung cancer (NSCLC), the chemotherapy efficacy against NSCLC is still unsatisfactory. Previous studies show the herbal antimalarial drug dihydroartemisinin (DHA) displays cytotoxic to multiple human tumors. Here, we showed that DHA decreased cell viability and colony formation, induced apoptosis in A549 and PC-9 cells. Additionally, we first revealed DHA inhibited glucose uptake in NSCLC cells. Moreover, glycolytic metabolism was attenuated by DHA, including inhibition of ATP and lactate production. Consequently, we demonstrated that the phosphorylated forms of both S6 ribosomal protein and mechanistic target of rapamycin (mTOR), and GLUT1 levels were abrogated by DHA treatment in NSCLC cells. Furthermore, the upregulation of mTOR activation by high expressed Rheb increased the level of glycolytic metabolism and cell viability inhibited by DHA. These results suggested that DHA-suppressed glycolytic metabolism might be associated with mTOR activation and GLUT1 expression. Besides, we showed GLUT1 overexpression significantly attenuated DHA-triggered NSCLC cells apoptosis. Notably, DHA synergized with 2-Deoxy-D-glucose (2DG, a glycolysis inhibitor) to reduce cell viability and increase cell apoptosis in A549 and PC-9 cells. However, the combination of the two compounds displayed minimal toxicity to WI-38 cells, a normal lung fibroblast cell line. More importantly, 2DG synergistically potentiated DHA-induced activation of caspase-9, -8 and -3, as well as the levels of both cytochrome c and AIF of cytoplasm. However, 2DG failed to increase the reactive oxygen species (ROS) levels elicited by DHA. Overall, the data shown above indicated DHA plus 2DG induced apoptosis was involved in both extrinsic and intrinsic apoptosis pathways in NSCLC cells.

Continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants urges the development of new vaccines. We assessed the safety and immunogenicity of SYS6006.32, a bivalent vaccine (XBB.1.5/BQ.1), in healthy adults who had received SARS-CoV-2 primary vaccination. In a randomised, double-blinded, active-controlled trial, 200 participants were randomised to receive one dose of SYS6006.32 (N = 100) or a prototype-based, monovalent control vaccine SYS6006 (N = 100). Adverse events (AEs) were collected through the study. Immunogenicity was assessed by live-virus neutralising antibody (Nab) and pseudovirus Nab. 61 (61.0 %) and 60 (60.0 %) participants reported AE in the SYS6006.32 and SYS6006 groups, respectively. Most AEs were grade 1 or 2. Pain and fever were the most common injection-site and systemic AEs, respectively. No serious AEs were observed. SYS6006.32 heterologous boosting induced robust Nab responses against BA.5, XBB.1.5 and EG.5 with live-virus Nab geometric mean titres (GMTs) increased by 17.1-, 34.0-, and 48.0-fold, and pseudovirus Nab GMTs increased by 12.2-, 32.0-, and 35.1-fold, respectively, 14 days after vaccination. SYS6006.32 demonstrated a superior immunogenicity to SYS6006. SYS6006.32 also induced robust pseudovirus Nab responses against XBB.1.16, XBB.2.3, and BA.2.86, with GMTs 3- to 6-fold higher than those induced by SYS6006. In conclusion, SYS6006.32 showed good safety profile and superior immunogenicity to the monovalent vaccine SYS6006.

Many practical networks, such as city networks, road networks and neural networks, usually grow up on basis of topological structures and geographical measures. Big hubs, importance of which have been well known in complex networks, still play crucial roles in growing networks with geographical measures. Therefore, it is very necessary to investigate the underlying mechanisms of statistical features of different top hubs in such networks. Here, we propose a growing network model based on optimal policy in geographical ground. Through the statistics of a great number of geographical networks, we find that the degree and position distributions of top four hubs are diverse between them and closely interrelated with each other, and further gain the relationships between the upper limits of top hubs and the size of networks. Then, the underlying mechanisms are explored. Meanwhile, we are diligent to obtain the corresponding relationships of different spatial distribution areas for different top hubs, and compute their abnormal average degrees at different spatial positions, which show significant differences and imply the advantage of spatial positions and intense competition between top hubs. We hope our results could offer useful inspirations for related practical network studies.

Purpose To explore whether probiotic supplementation could attenuate serum trimethylamine-N-oxide (TMAO) level and impact the intestinal microbiome composition. Design Forty healthy males (20–25 years old) were randomized into the probiotic group (1.32 × 10 11  CFU live bacteria including strains of Lactobacillus acidophilus , Lactobacillus rhamnosus GG, Bifidobacterium animalis, and Bifidobacterium longum daily) or the control group for 4 weeks. All participants underwent a phosphatidylcholine challenge test (PCCT) before and after the intervention. Serum TMAO and its precursors (TMA, choline and betaine) were measured by UPLC-MS/MS. The faecal microbiome was analyzed by 16S rRNA sequencing. Results Serum TMAO and its precursors were markedly increased after the PCCT. No statistical differences were observed in the probiotic and the control group in area under the curve (AUC) (14.79 ± 0.97 μmol/L 8 h vs. 19.17 ± 2.55 μmol/L 8 h, P  = 0.106) and the pre- to post-intervention AUC alterations (∆AUC) (− 6.33 ± 2.00 μmol/L 8 h vs. − 0.73 ± 3.04 μmol/L 8 h, P  = 0.131) of TMAO; however, higher proportion of participants in probiotic group showed their TMAO decrease after the intervention (78.9% vs. 45.0%, P  = 0.029). The abundance of Faecalibacterium prausnitzii ( P  = 0.043) and Prevotella ( P  = 0.001) in the probiotic group was significantly increased after the intervention but without obvious differences in α - and β -diversity. Conclusions The current probiotic supplementation resulted in detectable change of intestinal microbiome composition but failed to attenuate the serum TMAO elevation after PCCT. Clinicaltrials.gov Identifier NCT03292978. Clinicaltrials.gov website https://clinicaltrials.gov/ct2/show/NCT03292978 .

s Glucocorticoid (GC) resistance is the major obscule in the treatment of pemphigus vulgaris (PV) for both patients and clinicans with unclear mechanism. A hypotheis for this resistance is the mutations or polymorphisms present in the nuclear receptor subfamily 3, group C, member 1 (NR3C1) gene that encodes receptors for steroid hormones. This study aimed to investigate the association between NR3C1 gene polymorphisms and GC effectiveness in PV patients. 94 PV patients (64 GC-sensitive and 30 GC-resistant) and 100 healthy volunteers were enrolled in this case-control study. The genotyping of single nucleotide polymorphisms (SNPs) in BCL1, Arg23Lys, Asn363Ser 1548 t-insert, and le747Met, together with tag-SNP sites of the NR3C1 gene were evaluated. No significant differences were observed in genotypic and allelic frequencies of the 16 SNPs between PV patients and healthy volunteers. However, SNPs rs 11745958 C/T (OR: 8.95) and rs17209237 A/G (OR: 4.07) may be associated with an increased risk of GC resistance, while rs 33388 A/T (OR: 0.45) and rs7701443 A/G (OR: 0.51) may indicate a decreased risk of GC resistance in PV patients. NR3C1 gene variation may be associated with GC resistance in PV patients. More extensive genetic analyses and mechanistic analysis are required for further exploration.

This study aimed to evaluate the efficacy and safety of topical treatment with natural herbal medicines on recurrent aphthous stomatitis (RAS). Nine electronic databases were searched to identify the randomized controlled trials and clinical controlled trials that reported the potential effect of natural herbal medicines on RAS published in Chinese or English. Ulcer size and duration, and remission of pain were assessed as main outcome measures. The methodological quality of the studies was evaluated using the Cochrane Handbook for Systemic Review of Interventions and Rev Man software. Thirteen trials with a total of 1,515 patients were included in the present analysis, which showed that topical treatment with natural herbal medicines seemed to benefit RAS patients by reducing ulcer size, shortening ulcer duration, and relieving pain without severe side effects. In conclusion, there is some evidence of the efficacy of topically applied natural herbal medicines with regards to improved RAS outcome measures and fewer side effects. However, given the limitations of this study, the evidence remains insufficient. Well-designed and high-quality randomized controlled trials are required for further exploration.

Purpose Down-regulation of let-7 microRNA (miRNA) plays an important role in the pathogenesis of lung cancer. k-Ras and c-Myc, two key oncogenes in lung cancer, have been found to be targeted by let-7 in vitro. However, the in vivo relevance of these findings is unknown. The aim of the present study is to determine the effect of let-7a, a member of let-7 family, on the growth of lung cancer in vivo and to investigate whether let-7-induced suppression of k-Ras and c-Myc is involved in lung cancer. Methods A549-let-7a cell line and A549-control cell line, two stable transfected cell lines over-expressing let-7a and the control miRNA, were established and preserved in our lab. A549, A549-control, and A549-let-7a cells were injected subcutaneously into nude mice, respectively. After 30 days, the mice were killed; the xenografts were excised and weighed. The expression of let-7a in tumor xenografts was assessed by real-time reverse transcription-PCR (RT-PCR). The expression of k-Ras and c-Myc in xenografts were determined by western blot and immunohistochemistry detection. Results Real-time RT-PCR showed the expression of let-7a was increased significantly in A549-let-7a cells-injected group, compared with A549-control cells-injected group and A549 cells-injected group (P < 0.01). In the xenografts of A549-let-7a cells-injected group, a significant depression in tumor weight (P < 0.05) and significant decrease of k-Ras and c-Myc protein were observed (P < 0.01), compared to A549 cells-injected group and A549-control cells-injected group. Conclusion Overexpression of let-7a can inhibit the growth of lung cancer transplanted subcutaneously in nude mice by suppression of k-Ras and c-Myc.

We explored the applicability of Facescan three-dimensional (3D) facial reconstruction technology for adjunctive diagnosis and therapeutic evaluation of cheilitis granulomatosa (CG) in 33 patients with CG and 29 healthy controls at the Dept. of Oral Medicine, Peking University, School and Hospital of Stomatology (PKUSS), from January 2015 to May 2016. The Facescan structured-light 3D facial reconstruction scanner was used to scan the scope of lips in both groups, in order to acquire 3D morphological data of the lips. The lengths of six characteristic line segments were measured from the 3D lip model of the two groups, and the acquired data were compared. The results showed that the distance between the labiale superius and labiale inferius, and the lengths of the upper and lower vermilion borders showed significant differences between the CG and control groups, by using the 3D lip model. Thus, Facescan 3D facial reconstruction technology showed good reproducibility in the evaluation of lip swelling in CG patients, and it can be used to analyse the degree of lip swelling and evaluate the therapeutic efficacy of different treatments for CG.