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A hybrid of halloysite nanotubes decorated with titanium dioxide nanoparticles (HNTs@TiO2) was synthesized by the sol–gel method and then mixed with ultra‐high molecular polyethylene (UHMWPE) by melt compounding to enhance its wear resistance properties. The incorporation of HNTs@TiO2 increased the crystallinity as well as the hardness of UHMWPE nanocomposites, which benefited less prone to plastic deformation during the friction process. In addition, the UHMWPE/HNTs@TiO2 maintained a high ductility character with a slight decrease in tensile strength compared to pure UHMWPE. With the addition of 3 wt% HNTs@TiO2, the UHMWPE nanocomposite achieved a remarkably low friction coefficient of 0.073 and a reduced wear rate of 6.67 × 10−6 mm3/N·m. These values represented a 32.4% decrease in friction coefficient and a 43.9% decrease in wear rate compared to pure UHMWPE. The improvement in wear resistance was due to the dislodged TiO2 and HNTs had good synergistic rolling effects at the counterface. Furthermore, the wear scan morphology observation revealed that the transferred HNTs@TiO2‐based materials could help to improve the quality of the tribofilms, which alleviated the abrasive wear from the metallic counterpart. This work offers a feasible way to enhance the wear resistance of UHMWPE nanocomposite without sacrificing the high ductility for expanding its engineering applications. Highlights: TiO2‐decorated halloysite nanotubes were synthesized by the sol–gel method.The addition of HNTs@TiO2 maintained the high ductility character of UHMWPE.The UHMWPE composite with 3 wt% HNTs@TiO2 had the best wear resistance. [ABSTRACT FROM AUTHOR]

Since 2007, ligation of the intersphincteric fistula tract (LIFT) for the management of anal fistula was all introduced with initial success and excitement. It remains controversial which surgical procedure is suitable for transsphincteric fistula, especially to complex anal fistula. This retrospective study was designed to evaluate the results in patients with recurrent anal fistula by LIFT. A retrospective study of 55 complex fistula patients who underwent LIFT procedure in a single medical center was analyzed. Patients and fistula characteristics, complications, and recurrences were reviewed. All 55 patients underwent the procedure with a median follow-up of 16 months. Median operative time was 44 (range 23–88) minutes. Of the 55 patients, 33 (60%) healed completely and did not require any further surgical treatment at end of follow-up. Twenty-two (40%) recurrences and six complications were observed. Compared with patients who had undergone more than two surgical procedures, LIFT was more suitable for patients who had undergone one to two surgical procedures, and significant difference was observed in number of operations before LIFT (p=0.002). Clinicians can consider the use of LIFT for the treatment of recurrent anal fistulas. A larger number of patients and prospective study are needed to be performed. [ABSTRACT FROM AUTHOR]

Objective The aim of this analysis was to compare the advantages of the anal fistula plug ( AFP) with the mucosa advancement flap ( MAF) for complex anal fistulas. Methods Comparative studies of the efficacy of AFP and MAF were included. Two independent reviewers selected articles for inclusion. After information collection, a meta-analysis was performed using data on overall healing rates, complications, incontinences and recurrences. The quality of postoperative life and cost were also included with the clinical results. Results Ten studies included 778 patients who were divided into AFP and MAF groups in this meta-analysis. During the follow-up period, no significant difference in healing rates, complications and recurrences were found ( P = 0.55, P = 0.78 and P = 0.23, respectively). The incontinence rate of AFP was lower than that of MAF ( P = 0.04). The postoperative quality of life of AFP patients was superior to that of MAF patients. The AFP patients had less persistent pain of a shorter duration and shortened healing time and hospital stay. The treatment cost of AFP patient was lower than that of MAF. Conclusion Compared to the MAF procedure, the AFP procedure has some advantages for complex anal fistulas, but more and large randomized clinical trials comparing the two procedures for fistula management need to be conducted. [ABSTRACT FROM AUTHOR]

To explore why some oligonucleotides in denaturing polyacrylamide gel could not be silver-stained, 134 different oligonucleotides were analyzed using denaturing polyacrylamide gel electrophoresis stained with silver and asymmetric cyanine. As a result, we found that the sensitivity of oligos (dA), (dC), (dG) and (dT) to silver staining could be ranged as (dA) > (dG) > (dC) > (dT) from high to low. It was unexpected that oligo (dT) was hard to be silver-stained. Moreover, the silver staining of an oligonucleotide containing base T could be partially or completely inhibited by base T. The inhibition of silver staining by base T was a competitive inhibition which could be affected by the amounts of the argyrophil nucleobase and base T, the cis-distance between the argyrophil nucleobase and base T, and the gel concentration. The changes of the intensity of an oligonucleotide band caused by the changes of DNA base composition were diverse and interesting. The intensity of some oligonucleotide bands would significantly change when the changes of DNA base composition accumulated to a certain extent (usually ≥ 4 nt). The sensitivity of cyanine staining of ≤ 11-nt long oligonucleotides could be enhanced about 250-fold by fixing the gels with methanol fixing solution. [ABSTRACT FROM AUTHOR]

Lignin is the only renewable aromatic material in nature and contains a large number of oxygen-containing functional groups. High-value and green utilization of "lignin-to-chemicals" can be realized via using lignin to produce fine chemicals such as phenols and carboxylic acids, which can not only reduce the waste of lignin in the process of lignocellulosic biomass treatment, but gradually make the substitution of traditional fossil fuels come true. The hydrogenolysis process under catalysis of metal catalyst has high product selectivity and less impurity, which is suitable for the production of same type or single fine chemicals. Hydrogenolysis of lignin via metal catalysts to produce lignin oil, and further modification of functional groups (e.g. methoxyl, alkyl and hydroxyl group) of depolymerized monomers in the bio-oil to yeild phenols and terephthalic acid are reviewed, and catalytic mechanisms are briefly summarized in this paper. Finally, the problems of lignin catalytic conversion existing currently are investigated, and the future development of this field is also prospected. [ABSTRACT FROM AUTHOR]

The sensitive detection of antioxidants in food is essential for the rational control of their usage and reducing potential health risks. A simple three-dimensional (3D) electrode integrated with an anti-fouling/anti-interference layer possesses great potential for the direct and sensitive electrochemical detection of antioxidants in food samples. In this work, a 3D electrochemical sensor was developed by integrating a 3D graphene electrode (3DG) with vertically ordered mesoporous silica film (VMSF), enabling highly sensitive detection of the common antioxidant, butylated hydroxyanisole (BHA), in food samples. A simple electrochemical polarization was employed to pre-activate the 3DG electrode (p3DG), enhancing its hydrophilicity. Using the p3DG as the supporting electrode, stable modification of VMSF was achieved using the electrochemical assisted self-assembly (EASA) method, without the need for any adhesive agents (VMSF/p3DG). Taking BHA in food as a model analyte, the VMSF/p3DG sensor demonstrated high sensitivity, due to the enrichment by nanochannels, towards BHA. Electrochemical detection of BHA was achieved with a linear range of 0.1 μM to 5 μM and from 5 μM to 150 μM with a low limit of detection (12 nM). Owing to the fouling resistance and anti-interference capabilities of VMSF, the constructed 3D electrochemical sensor can be directly applied for the electrochemical detection of BHA in complex food samples. [ABSTRACT FROM AUTHOR]

Background: Overweight is known to be an important risk factor for colorectal cancer (CRC), and the differences in intestinal flora among CRC patients with different BMI status have not been clearly defined. The purpose of this study was to elucidate the differences in the abundance, composition and biological function of intestinal flora in CRC patients with different BMI status. Method: A total of 170 CRC patients were included and grouped according to the BMI data of CRC patients. BMI ≥ 24 kg/m2 was defined as overweight group, and BMI within the range of 18.5–23.9 kg/m2 was defined as normal weight group. Preoperative stool collection of patients in both groups was used for 16S rRNA sequencing. Total RNA was extracted from 17 CRC tumor tissue samples for transcriptome sequencing, and then CIBERSORT algorithm was used to convert the transcriptome data into the relative content matrix of 22 kinds of immune cells, and the correlation between different intestinal flora and immune cells and immune-related genes under different BMI states was analyzed. Finally, we identified BMI-related differential functional pathways and analyzed the correlation between these pathways and differential intestinal flora. Result: There was no significant difference in α diversity and β diversity analysis between overweight group and normal weight group. Partial least square discriminant analysis (PLS-DA) could divide the flora into two different clusters according to BMI stratification. A total of 33 BMI-related differential flora were identified by linear discriminant effect size analysis (LEfSe), among which Actinomyces, Desulfovibrio and Bacteroides were significantly enriched in overweight group. ko00514: Other types of O-glycan biosynthesis are significantly enriched in overweight group. There was a significant positive correlation between Clostridium IV and Macrophages M2 and T cells regulatory (Tregs). There was a significant negative correlation with Dendritic cells activated and T cells CD4 memory activated. Conclusions: The richness and diversity of intestinal flora of CRC patients may be related to different BMI status, and the enrichment of Actinomyces, Desulphurvibrio and Bacteroides may be related to overweight status of CRC patients. The tumor microenvironment in which BMI-related differential flora resides has different immune landscapes, suggesting that some intestinal flora may affect the biological process of CRC by regulating immune cell infiltration and immune gene expression, but further experiments are needed to confirm this. [ABSTRACT FROM AUTHOR]

Heat shock proteins play crucial roles in various biochemical processes, encompassing protein folding and translocation. HSP90B1, a conserved member of the heat shock protein family, growing evidences have demonstrated that it might be closely associated with cancer development. In the present study, we employed multi-omics analyses and cohort validations to explore the dynamic expression of HSP90B1 in pan-cancer and comprehensively evaluate HSP90B1 as a novel biomarker that hold promise for precision cancer diagnostics and therapeutics. The results suggest HSP90B1 was highly expressed in various kinds of tumors, often correlating with a poor prognosis. Notably, methylation of HSP90B1 emerged as a protective factor in several cancer types. In immune infiltration analysis, the expression of HSP90B1 in most tumors showed a negative association with CD8 + T cells. HSP90B1 expression was positively correlated with microsatellite instability and tumor mutational burden. HSP90B1 expression was also discovered to be positively correlated with tumor metabolism, cell cycle-related pathways and the expression of immune checkpoint genes. The expression of HSP90B1 was mainly negatively correlated with immunostimulatory genes and positively correlated with immunosuppressive genes, as well as strongly correlated with chemokines and their receptor genes. In addition, the HSP90B1 inhibitor PU-WS13 demonstrated significant efficacy in suppressing cancer cell proliferation in both leukemic and solid tumor cells, and remarkably reduced the expression of the cancer cell surface immune checkpoint PD-L1. The single-cell RNA sequencing analysis further highlighted that HSP90B1 was significantly higher in tumor cells compared to surrounding cells, revealing a potential target therapeutic window. Taken together, HSP90B1 emerges as a promising avenue for breakthroughs in cancer diagnosis, prognosis and therapy. This study provides a rationale for HSP90B1 targeted cancer diagnosis and therapy in future. [ABSTRACT FROM AUTHOR]

The rapid development of artificial intelligence (AI) and big data technologies has profoundly changed the way of human life and work, and in the healthcare field, the related product design is moving towards the trend of digitalization, intelligence, and personalization. The growing demands for personalised healthcare have contributed to a boom in product design theories in related fields. However, it is difficult to measure product users' preferences in precise numerical terms to make strategic decisions in product design. To fill this gap, this study proposes a framework for virtual reality (VR) healthcare product design based on a data-driven concept and develops a VR virtual roaming system for system users guided by this theory. The data-driven concept incorporates AI and big data technologies into product design, helping to shift the design of medical products towards a data-centred approach. Ultimately, an ergonomic experiment was conducted and a case study was carried out to assess the user's experience using brain function data to enable data-driven VR value-added services. This study provides a new perspective on rehabilitation product design, opening the way for better personalised healthcare delivery. [ABSTRACT FROM AUTHOR]

Abnormal epigenetic regulation is identified to correlate with cancer progression and renders tumor refractory and resistant to reactive oxygen species (ROS)‐based anti‐tumor actions. To address it, a sequential ubiquitination and phosphorylation epigenetics modulation strategy is developed and exemplified by the well‐established Fe‐metal‐organic framework (Fe‐MOF)‐based chemodynamic therapy (CDT) nanoplatforms that load the 26S proteasome inhibitor (i.e., MG132). The encapsulated MG132 can blockade 26S proteasome, terminate ubiquitination, and further inhibit transcription factor phosphorylation (e.g., NF‐κB p65), which can boost pro‐apoptotic or misfolded protein accumulations, disrupt tumor homeostasis, and down‐regulate driving genes expression of metastatic colorectal cancer (mCRC). Contributed by them, Fe‐MOF‐unlocked CDT is magnified to considerably elevate ROS content for repulsing mCRC, especially after combining with macrophage membrane coating‐enabled tropism accumulation. Systematic experiments reveal the mechanism and signaling pathway of such a sequential ubiquitination and phosphorylation epigenetics modulation and explain how it could blockade ubiquitination and phosphorylation to liberate the therapy resistance to ROS and activate NF‐κB‐related acute immune responses. This unprecedented sequential epigenetics modulation lays a solid foundation to magnify oxidative stress and can serve as a general method to enhance other ROS‐based anti‐tumor methods. [ABSTRACT FROM AUTHOR]

Ferroptosis is an iron-dependent form of cell death induced by lipid oxidation with an essential role in diseases, including cancer. Since prognostic value of ferroptosis-dependent related genes (FDRGs) in colorectal cancer (CRC) remains unclear, we explored the significance of FDRGs in CRC through comprehensive single-cell analysis. We downloaded the GSE161277 dataset for single-cell analyses and calculated the ferroptosis-dependent gene score (FerrScore) for each cell type. According to each cell type-specific median FerrScore, we categorized the cells into low- and high-ferroptosis groups. By analyzing differentially-expressed genes across the two groups, we identified FDRGs. We further screened these prognosis-related genes used to develop a prognostic signature and calculated its correlation with immune infiltration. We also compared immune checkpoint gene efficacy among different risk groups, and qRT-PCR was performed in colorectal normal and cancer cell lines to explore whether the signature genes could be used as clinical prognostic indicators. In total, 523 FDRGs were identified. A prognostic signature including five signature genes was constructed, and patients were divided into two risk groups. The high-risk group had poor survival rates and displayed high levels of immune infiltration. Our newly developed ferroptosis-based prognostic signature possessed a high predictive ability for CRC. [ABSTRACT FROM AUTHOR]

Objective: The relationship between intestinal microbiome and colorectal cancer (CRC) progression is unclear. This study aims to identify the intestinal microbiome associated with CRC progression and construct predictive labels to support the accurate assessment and treatment of CRC. Method: The 192 patients included in the study were divided into stage I-II and stage III-IV CRC patients according to the pathological stages, and preoperative stools were collected from both groups for 16S rDNA sequencing of the intestinal microbiota. Pearson correlation and Spearman correlation coefficient analysis were used to analyze the differential intestinal microbiome and the correlation with tumor microenvironment and to predict the functional pathway. XGBoost model (XGB) and Random Forest model (RF) were used to construct the microbiome-based signature. The total RNA extraction from 17 CRC tumor simples was used for transcriptome sequencing. Result: The Simpson index of intestinal microbiome in stage III-IV CRC were significantly lower than those in stage I-II CRC. Proteus, Parabacteroides, Alistipes and Ruminococcus etc. are significantly enriched genus in feces of CRC patients with stage III-IV. ko00514: Other types of O − glycan biosynthesis pathway is relevant with CRC progression. Alistipes indistinctus was positively correlated with mast cells, immune activators IL-6 and IL6R, and GOBP_PROTEIN_FOLDING_IN_ENDOPLASMIC_RETICULUM dominantly. The Random Forest (RF) model and eXtreme Gradient Boosting (XGBoost) model constructed with 42 CRC progression-associated differential bacteria were effective in distinguishing CRC patients between stage I-II and stage III-IV. Conclusions: The abundance and diversity of intestinal microbiome may increase gradually with the occurrence and progression of CRC. Elevated fetal abundance of Proteus, Parabacteroides, Alistipes and Ruminococcus may contribute to CRC progression. Enhanced synthesis of O − glycans may result in CRC progression. Alistipes indistinctus may play a facilitated role in mast cell maturation by boosting IL-6 production. Alistipes indistinctus may work in the correct folding of endoplasmic reticulum proteins in CRC, reducing ER stress and prompting the survival and deterioration of CRC, which may owe to the enhanced PERK expression and activation of downstream UPR by Alistipes indistinctus. The CRC progression-associated differential intestinal microbiome identified in our study can be served as potential microbial markers for CRC staging prediction. [ABSTRACT FROM AUTHOR]

Bone morphogenetic protein-9 (BMP9) shows great osteoinductive potential in bone regeneration. Periodontal ligament stem cells (PDLSCs) with multi-differentiation capability and low immunogenicity are increasingly used as seed cells for periodontal regenerative therapies. In the present study, we investigated the potent osteogenic activity of BMP9 on human PDLSCs (hPDLSCs), in which the c-Jun N-terminal kinase (JNK) pathway is possibly involved. Our results showed that JNK inhibition by the specific inhibitor SP600125 or adenovirus expressing small interfering RNA (siRNA) targeting JNK (AdR-si-JNK) significantly decreased BMP9-induced gene and protein expression of early and late osteogenic markers, such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN), in hPDLSCs. We also confirmed the in-vivo positive effect of JNKs on ectopic bone formation induced by hPDLSCs injected into the musculature of athymic nude mice and BMP9 ex vivo gene delivery. For the cellular mechanism, we found that BMP9 activated the phosphorylation of JNKs and Smad2/3, and that JNKs may engage in cross-talk with the Smad2/3 pathway in BMP9-mediated osteogenesis. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the efficacy of fistulectomy compared to fistulotomy, and which procedure was the best procedure for patients with low anal fistula. Methods: The literature search included PubMed, EMBASE, Cochrane library, Google original studies and a manual search of reference on the topic of fistulectomy compared to fistulotomy for anal fistula that had a deadline for publication by June 2016. Randomized controlled trials studies were included in the review. The outcome variables were analyzed which including operative time, healing time, postoperative complications, recurrence and incontinence. Results: Six randomized controlled trials (fistulectomy = 280, fistulotomy = 285) were considered suitable for the meta-analysis, with a total of 565 patients. The result of meta-analysis indicated no statistically significant difference in operative time [OR 4.74, 95 % CI −2.74, 12.23, p = 0.21] and healing time [OR −3.32, 95 % CI −19.86, 13.23, p = 0.69] between the fistulectomy and fistulotomy procedures. Three main postoperative complications were included, and the combined result indicated no statistically significant difference in overall complications [OR 1.39, 95 % CI 0.51, 3.78, p = 0.52] and subgroup complication. At the end of follow up, two kinds of surgical methods have the same low recurrence rate and faecal incontinence. The result revealed that there was no significant difference in rate of fistula recurrence between the fistulectomy and the fistulotomy [OR 1.39, 95 % CI 0.70, 2.73, p = 0.34]. Conclusion: The meta-analysis indicates that there is no conclusive evidence if fistulectomy or fistulotomy procedure is better in the treatment of low anal fistula. [ABSTRACT FROM AUTHOR]

Background. Colorectal cancer is a digestive tract malignant tumor, ranking the second mortality and the third incidence cancer worldwide. The abnormal expression of NEAT1 is related to the occurrence and development of colorectal cancer. However, the specific mechanism of NEAT1 mediated-inflammatory pathway in the progression of colorectal cancer is still unclear. Methods. In this study, expression of NEAT1 in colorectal cancer patients was analyzed by bioinformatics. Clinical samples including peripheral blood and colorectal cancer tissues were collected for qRT-PCR, Western blot, and immunohistochemistry assay. The role of NEAT1 in the colorectal cancer progression was further confirmed by both in-vivo and in-vitro functional experiments. Results. By bioinformatics prediction, it is found that NEAT1 expression level is significantly higher in the peripheral blood of patients with colorectal cancer and is associated with poor prognosis. In-vitro functional studies indicated that NEAT1 knockdown suppressed the proliferation and migration of colorectal cancer cells by mediating inflammatory response. In-vivo tumorigenesis experiments showed that NEAT1 knockdown suppressed tumor growth. Conclusion. Abnormal high expression level of NEAT1 in colorectal cancer tissues and cells leads to poor prognosis. Mechanistically, NEAT1 triggers off the proliferation and migration of colorectal cancer cells through promoting the inflammatory reaction. Clinically, the expression level of NEAT1 in serum may be a marker for diagnosis and prognosis of colorectal cancer. [ABSTRACT FROM AUTHOR]

Objectives: Posthepatectomy liver failure (PHLF) is a challenging complication after resection to treat hepatocellular carcinoma (HCC), and it is associated with high mortality. Preoperative prediction of PHLF may improve patient subsequent and reduce such mortality. This study examined whether a functional liver imaging score (FLIS) based on preoperative gadoxetic acid–enhanced magnetic resonance imaging (MRI) could predict PHLF. Materials and methods: The study included 502 patients who underwent preoperative gadoxetic acid–enhanced MRI, followed by HCC resection. Significant preoperative predictors of PHLF were identified using logistic regression analysis. The ability of FLIS to predict PHLF was evaluated using receiver operating characteristic curves, and its predictive power was compared to that of the model for end-stage liver disease (MELD) score, albumin–bilirubin (ALBI) score, and indocyanine green 15-min retention rate (ICG-R15). Results: In multivariate analysis, PHLF was independently associated with FLIS (OR 0.452, 95% CI 0.361 to 0.568, p < 0.001) and major resection (OR 1.898, 95% CI 1.057 to 3.408, p = 0.032). FLIS was associated with a higher area under the receiver operating characteristic curve (0.752) than the MELD score (0.557), ALBI score (0.609), or ICG-R15 (0.605) (all p < 0.05). Patients with FLIS ≤ 4 who underwent major resection were at 9.4-fold higher risk of PHLF than patients with lower FLIS who underwent minor resection. Conclusion: FLIS is an independent predictor of PHLF, and it may perform better than the MELD score, ALBI score, and ICG-R15 clearance. We propose treating elevated FLIS and major resection as risk factors for PHLF. Key Points: • A functional liver imaging score can independently predict posthepatectomy liver failure in patients with HCC. • The score may predict such failure better than MELD and ALBI scores and ICG-R15. • Patients with scores ≤ 4 who undergo major hepatic resection may be at nearly tenfold higher risk of posthepatectomy liver failure. [ABSTRACT FROM AUTHOR]

Dual-coordinated atomically dispersed Pt nanozymes (Pt-NS/HCS) exhibit selectively enhanced peroxidase (POD)-like activity, inducing efficient GSDMD and GSDME-mediated pyroptosis, thereby synergistically enhancing programmed cell death 1 ligand 1 (PD-L1) immunotherapies. The revealed signal pathways present a promising enhancement strategy for PD-L1 immunotherapies and provide a guideline for designing single-atom-based nanozymes for pyroptosis regulation and immunotherapy. [Display omitted] • Dual-coordinated atomically dispersed Pt nanozymes (Pt-NS/HCS) are synthesized. • Pt-NS/HCS exhibits selectively enhanced peroxidase-like activity. • Pt-NS/HCS effectively induces gasdermin (GSDM) D and E-mediated pyroptosis. • Pt-NS/HCS and programmed cell death 1 ligand 1 synergistically enhance the efficiency of immunotherapies. Pyroptosis, a distinct form of inflammatory programmed cell death, has emerged as novel therapeutic targets for igniting the immune system. Transition metal single-atom nanozymes (TM-SAzymes) hold great promise in inducing pyroptosis for enhanced immunotherapy due to their excellent catalytic activity and maximum atom utilization. However, fundamental understanding towards TM-SAzymes-induced pyroptosis and its associated signaling pathways in immunotherapy remains elusive. Herein, we developed atomically dispersed platinum nanozymes (Pt-NS/HCS) with sulfur (S) and nitrogen (N) coordination to effectively induce pyroptosis for enhanced immunotherapy. The obtained Pt-NS/HCS exhibited impressive peroxidase (POD)-like activity with a specific activity of 102 Umg−1. In vitro results demonstrate that Pt-NS/HCS effectively triggers Gasdermin D (GSDMD) and Gasdermin E (GSDME)-mediated pyroptosis, further causing robust immunogenic cell death (ICD). In vivo results further verify synergistically enhanced therapeutic effect of Pt-NS/HCS with programmed death ligand 1 (PD-L1) immunotherapies. This work provides valuable insights for the development of efficient TM-SAzymes and advanced synergistic approaches in clinical colon cancer treatment. [ABSTRACT FROM AUTHOR]

Background: The greater omentum has played a unique biological role in regenerative surgery. The aim of our study was to alter the anterior sacral structure by filling the anterior sacral space with the greater omentum and evaluate its effect on the low anterior resection syndrome (LARS) after total mesorectal excision (TME) surgery for low rectal cancer. Methods: We retrospectively collected clinical data of patients with primary low rectal cancer who underwent TME and ileostomy closure in our hospital from March 2018 to March 2020. Spearman correlation analysis was conducted to analyze the correlation between postoperative mesorectal fascia (MRF) thickness and LARS score. Subsequently, we prospectively used a tipped greater omental flap graft to reconstruct the anterior rectal sacral structures (MRF reconstruction) in 17 patients and compared LARS scores and rectal compliance (RC) at week 12 after closure of the ileostomy in both groups. Results: There were 47 patients with No-MRF reconstruction (31 males, mean age 60.68 ± 9.21 years) and 17 with MRF reconstruction (10 males, mean age 49.82 ± 14.74 years). Correlation analysis indicated that MRF thickness and RC were negatively correlated with LARS severity (p < 0.05). The LARS score of patients with MRF reconstruction at 12 weeks was significantly better than that of those with No-MRF reconstruction (32.97 ± 2.65 vs. 26.94 ± 1.52, p = 0.001), and the RC of MRF reconstruction were lower (2.80 ± 0.55 vs. 3.67 ± 0.38, p = 0.001). In addition, MRF reconstruction and No-MRF reconstruction have the similar incidence of postoperative complications (p = 0.156). No hemorrhage or necrosis of the greater omentum flap was observed in any of the patients. Conclusions: Greater omentum flap transplantation can significantly improve the symptoms of LARS at 12 weeks after ileostomy closure and we expect it to become a new surgical procedure for the treatment of low rectal cancer. [ABSTRACT FROM AUTHOR]

Background: KRAS gene is the most common type of mutation reported in colorectal cancer (CRC). KRAS mutation-mediated regulation of immunophenotype and immune pathways in CRC remains to be elucidated.Methods: 535 CRC patients were used to compare the expression of immune-related genes (IRGs) and the abundance of tumor-infiltrating immune cells (TIICs) in the tumor microenvironment between KRAS-mutant and KRAS wild-type CRC patients. An independent dataset included 566 cases of CRC and an in-house RNA sequencing dataset were served as validation sets. An in-house dataset consisting of 335 CRC patients were used to analyze systemic immune and inflammatory state in the presence of KRAS mutation. An immue risk (Imm-R) model consist of IRG and TIICs for prognostic prediction in KRAS-mutant CRC patients was established and validated.Results: NF-κB and T-cell receptor signaling pathways were significantly inhibited in KRAS-mutant CRC patients. Regulatory T cells (Tregs) was increased while macrophage M1 and activated CD4 memory T cell was decreased in KRAS-mutant CRC. Prognosis correlated with enhanced Tregs, macrophage M1 and activated CD4 memory T cell and was validated. Serum levels of hypersensitive C-reactive protein (hs-CRP), CRP, and IgM were significantly decreased in KRAS-mutant compared to KRAS wild-type CRC patients. An immune risk model composed of VGF, RLN3, CT45A1 and TIICs signature classified CRC patients with distinct clinical outcomes.Conclusions: KRAS mutation in CRC was associated with suppressed immune pathways and immune infiltration. The aberrant immune pathways and immune cells help to understand the tumor immune microenvironments in KRAS-mutant CRC patients. [ABSTRACT FROM AUTHOR]

A T4B hepatic flexure of colon cancer that had invaded the liver, gall bladder, and pancreas/duodenum was removed through a D3 expanded right hemicolectomy + pancreaticoduodenectomy +sectional VI and VII hepatic segmentectomy. [ABSTRACT FROM AUTHOR]

Different opinions exist on the relationship between the C-reactive protein-to-albumin ratio (CAR) and the prognosis of colon cancer. This study is aimed at evaluating the relationship between CAR and prognosis of stage II–III colon cancer and establishing a clinical prognosis model. Patients were randomised to a training set (566 cases) and validation set (110 cases). The relationship between CAR and clinicopathological variables was calculated, and the Kaplan-Meier method was used to analyse the overall survival (OS) rate of colon cancer. In the training set, colon cancer independent risk factors were included in the prognosis model and then tested in the validation set. The accuracy and discrimination of the model were assessed using the C-index and calibration curves. Compared with patients with low CAR, patients with high CAR showed significantly poorer survival (P = 0.020). In the multivariate analysis, CAR, carcinoembryonic antigen (CEA), lymph node metastasis, operation mode, and perineural invasion were identified as independent prognostic indicators and adopted to establish the prediction model. The C-index of the nomogram for predicting OS reached 0.751 in the training set and 0.719 in the validation set. The calibration curve exhibited good consistency. In the present study, the CAR may be an independent prognostic factor for stage II–III colon cancer, and the nomogram has a certain predictive value. However, further prospective large-sample research needs to be conducted to validate our findings. [ABSTRACT FROM AUTHOR]

Lung cancer is one of most common malignant cancer worldwide. It is emerging that PCYT1A, a rate-limiting enzyme required for the biosynthesis of phosphatidylcholine, is associated with cancer progression. However, the biological functions and underlying molecular mechanisms of PCYT1A in lung adenocarcinoma is still unknown. Here we found that PCYT1A suppressed lung adenocarcinoma cancer cell proliferation and migration. Mechanically, PCYT1A served as a novel negative regulator of mTORC1 signaling. PCYT1A knockdown enhanced the malignant proliferation and migration of lung adenocarcinoma cells by activating mTORC1. The promoting effects of PCYT1A silencing on cell proliferation and migration could be abolished when mTORC1 signaling was inhibited by rapamycin or RAPTOR depletion. Importantly, PCYT1A high expression predicted longer survival of lung cancer patients. The expression of PCYT1A was also negatively correlated with mTORC1 activation in the clinical lung cancer samples. We therefore reveal that PCYT1A suppresses proliferation and migration by inhibiting the mTORC1 signaling pathway in lung adenocarcinoma. PCYT1A shows as a potential promising biomarker in lung adenocarcinoma. PCYT1A inhibits mTORC1 activation to suppress lung adenocarcinoma cell proliferation and migration. Low expression of PCYT1A by knocking down PCYT1A activates mTORC1 signaling thereby promoting cell proliferation and migration in lung adenocarcinoma cells, which can be reversed by mTORC1 inhibition by Rapamycin or RAPTOR knockdown. mTORC1 activation is negatively correlated with PCYT1A expression in lung adenocarcinoma clinical samples, revealing that PCYT1A/mTORC1 axis may be a potential target for lung cancer treatment. Image 1 • PCYT1A suppresses proliferation and migration in lung adenocarcinoma. • PCYT1A suppresses the malignant biological behavior in a mTORC1 dependent manner in lung adenocarcinoma. • PCYT1A is negatively correlated with mTORC1 activation in lung cancer clinical samples. • PCYT1A/mTORC1 axis may be a potential target for lung cancer treatment. [ABSTRACT FROM AUTHOR]

Purpose: The overall survival (OS) of patients diagnosed with stage II‐III colorectal cancer (CRC) can vary greatly, even between patients with the same tumor stage. We aimed to design a nomogram to predict OS in resected, stage II‐III CRC and stratify patients with CRC into different risk groups. Patients and Methods: Based on data from 873 patients with CRC, we used univariate Cox regression analysis to select the significant prognostic features, which were subjected to the least absolute shrinkage and selection operator (LASSO) regression algorithm for feature selection. Cross‐validation was used to confirm suitable tuning parameters (λ) for LASSO logistic regression. Then, the nomogram was used to estimate 3‐ and 5‐year OS based on the multivariable Cox regression model. The survival curves of the two groups were produced using the Kaplan‐Meier method. Risk group stratification was performed to assess the predictive capacity of the nomogram. Results: Preoperative mean platelet volume, preoperative platelet distribution width, monocytes, and postoperative adjuvant chemotherapy were identified as independent prognostic factors by LASSO regression and integrated for the construction of the nomogram. The nomogram provided good discrimination, with C‐indices of 0.67 and 0.69 for the training and validation sets, respectively. Calibration plots illustrated excellent agreement between the nomogram predictions and actual observations for 3‐ and 5‐year OS. Moreover, a significant difference in OS was shown between patients stratified into different risk groups (P <.001). Conclusion: We constructed and validated an original predictive nomogram for OS in patients with CRC after surgery, facilitating physicians to appraise the individual survival of postoperative patients accurately and identify high‐risk patients who need more aggressive treatment and follow‐up strategies. [ABSTRACT FROM AUTHOR]

Fluoropyrimidine-based chemotherapy is an essential component of systemic chemotherapy for colorectal cancer (CRC). The immune response is implicated in chemotherapy-induced cytotoxicity. Here, we reported an immune risk (Imm-R) model for prognostic prediction in patients receiving fluoropyrimidine-based chemotherapy. Gene expression profiles and corresponding clinical information were collected from four data sets and divided into training set (n = 183) and validation set (validation set1: n = 34; validation set2: n = 99). The composition of 22 tumor-infiltrating immune cells (TIICs) populations was characterized with the CIBERSORT deconvolution algorithm. A prognostic Imm-R model for predicting overall survival was established by performing least absolute shrinkage and selection operator (LASSO) penalized COX regression analysis. T follicular helper cells and M0 macrophages were associated with better survival, while eosinophils were associated with worse survival. TIICs signature was constructed based on the above three immune cell types. Furthermore, a Imm-R model was created by integrating TIICs signature with immune-related genes (IRGs), which effectively in distinguishing CRC patients with poorer prognosis. The Imm-R model was associated with activation of the TGF-beta signaling and suppression of DNA damage. Results of this research provide new insights into the role of immunity for in fluoropyrimidine-based chemotherapy as well as a useful tools to predict the outcome of CRC patients receiving fluoropyrimidine-based chemotherapy. [ABSTRACT FROM AUTHOR]

Vascular invasion (VI) is an important feature for systemic recurrence and an indicator for the application of adjuvant therapy in colorectal cancer (CRC). Preoperative knowledge of VI is important in determining whether adjuvant therapy is necessary, as well as the adequacy of surgical resection. In the present study, a predictive nomogram for VI in patients with CRC was constructed. The prediction model consisted of 664 eligible patients with CRC, who were divided into a training set (n=468) and a validation set (n=196). Data were collected between August 2013 and April 2018. The feature selection model was established using the least absolute shrinkage and selection operator regression model. Multivariable logistic regression analysis was used to construct the predictive nomogram. The performance of the nomogram was evaluated by calibration, discrimination and clinical usefulness. Differentiation, computed tomography (CT)-based on N stage (CT N stage), hemameba and tumor distance from the anus (cm) were integrated into the nomogram. The nomogram exhibited good discrimination, with an area under the curve (AUC) of 0.731 and good calibration. Application of the nomogram in the validation cohort showed acceptable discrimination, with an AUC of 0.710 and good calibration. Decision curve analysis revealed that the nomogram was clinically useful. These findings suggests, to the best of our knowledge, that this may be the first nomogram for individual preoperative prediction of VI in patients with CRC, which may promote preoperative optimization strategies for this selected group of patients. [ABSTRACT FROM AUTHOR]

Background and Aim. Colorectal cancer (CRC) is the third most lethal cancer globally. This study sought to determine the feasibility of using red cell distribution width-to-lymphocyte ratio (RLR) as a tool to facilitate CRC detection. Methods. Seventy-eight healthy controls, 162 patients diagnosed with CRC, and 94 patients with colorectal polyps (CP) from June 2017 to October 2018 were retrospectively reviewed. Clinical data were obtained to analyze preoperative RLR level, and receiver operating characteristic (ROC) curve analysis was performed to estimate the potential role of RLR as a CRC biomarker. Results. RLR was higher in patients with CRC than in healthy participants (P < 0.05). ROC analysis indicated that combined detection of RLR and CEA appears to be a more effective marker to distinguish among controls, CP, and CRC patients, yielding 56% sensitivity and 90% specificity. RLR levels were significantly greater in those who had more advanced TNM stages (P < 0.05) and patients with distant metastasis stages (P < 0.05). Conclusions. RLR might serve as a potential biomarker for CRC diagnosis. [ABSTRACT FROM AUTHOR]

• Two kinds of abnormal biomechanical stimulation models were used both in vivo and in vitro. • Temporomandibular joint osteoarthritis is related to mitochondrial injury. • Mitochondrial injury can be caused by an increase in nitric oxide. • Targeting mitochondrial pathway can be a strategy for the treatment of osteoarthritis. Chondrocyte apoptosis is a pathological manifestation of osteoarthritis. The goal of this report was to explore the role of nitric oxide in chondrocyte apoptosis in osteoarthritic mandibular condylar cartilage. This study used our reported experimental unilateral anterior crossbite in vivo rat model and chondrocyte fluid flow shear stress in vitro model. In the in vivo model, apoptosis in the mandibular condylar cartilage was assessed by detection of the TUNEL-positive cells, the expression levels of inducible nitric oxide synthase (iNOS), caspase-9, and caspase-3. In the in vitro model, mitochondrial injury was evaluated, the nitric oxide and superoxide dismutase (SOD) production levels were measured, and the cytochrome C (Cyt C) expression level was detected. The expression levels of apoptosis-related proteins B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, and poly-ADP-ribose polymerase 1 (PARP1) were analyzed in both in vivo and in vitro models. The effects of iNOS inhibitor on chondrocyte apoptosis were also investigated. The data indicated that the unilateral anterior crossbite induced cartilage degeneration with enhanced cell apoptosis and stimulated the expression of caspase-3/-9 and iNOS. The fluid flow shear stress upregulated the expression of iNOS, SOD, and nitric oxide, reduced mitochondrial membrane potential, and promoted Cyt C to enter the cytoplasm. All of these changes were reversed by iNOS inhibitors. The abnormal occlusion stimulated mitochondrial damage and apoptosis of the chondrocytes in the mandibular condylar cartilage mediated by nitric oxide. Inhibiting nitric oxide production could be a therapeutic strategy. [ABSTRACT FROM AUTHOR]

Microwave attenuation materials with high thermal conductivity are required for developing high power microwave technology. In this paper, boron-doped diamond films with different doping concentrations were prepared by microwave plasma chemical vapor deposition. Complex permittivity of the samples was measured in the K-band by using the transmission/reflection method. It was found that the complex permittivity of the diamond films increased with an increase in the boron doping concentration and the diamond films were transformed from a microwave transparent material into a microwave absorbing material. In addition, although thermal conductivity decreased with increasing boron concentration, it remained at a fairly high level. Therefore, boron-doped diamond films could be developed into a microwave attenuation material with extremely high thermal conductivity. Mechanism analysis revealed that the increase in the real part of permittivity mainly resulted from the hopping polarization of bound charges, while the increase in the imaginary part was due to both hopping polarization and valence band conduction. It was found that with the increase in the boron doping concentration, the proportion of the dielectric loss of the first mechanism increased. [ABSTRACT FROM AUTHOR]

Background: Three-dimensional (3D) laparoscopy has the advantages and characteristics of more radical procedures in the treatment of gastric cancer. The objective of this research was to investigate the short-term efficacy and safety of 3D laparoscopic procedures in the treatment of advanced distal gastric cancer. Methods: We retrospectively analyzed the clinical data of 124 patients treated with 3D and two-dimensional (2D) laparoscopic D2 lymphadenectomy for distal gastric cancer at the China Academy of Medical Sciences Cancer Hospital and the Affiliated Cancer Hospital of Guangxi Medical University from January 2014 to January 2015. The effects on operative time, bleeding, hospitalization time, complications, and the number of lymph nodes removed were analyzed. Results: The difference between the general data of the two groups was not statistically significant (P.0.05). In analysis of the subgroups, the number of lymph nodes removed in the 3D laparoscopic group was significantly higher than in the 2D laparoscopic group ([2.52±1.88] vs [2.22±1.80], P=0.001; [2.22±1.80] vs [1.47±1.99], P=0.019). However, the differences among the total number of lymph nodes removed, operative time, intraoperative blood loss, intraoperative complications, postoperative complications, postoperative recovery time, and postoperative hospital stay were not statistically significant. Conclusion: 3D laparoscopic-assisted radical gastrectomy for distal advanced gastric cancer is safe and feasible. [ABSTRACT FROM AUTHOR]

Ultrasensitive, specific, and early identification of Coronavirus Disease (2019) (COVID-19) infection is critical to control virus spread and remains a global public health problem. Herein, we present a novel solid-state electrochemiluminescence (ECL) platform targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody with rapidity and ultrahigh sensitivity, in which a bipolar silica nanochannel array (bp-SNA) is fabricated on indium tin oxide (ITO) electrode for the first time to stably confine the ECL probe of tris(2,2′-bipyridyl) ruthenium (Ru(bpy) 3 2+) under dual electrostatic force. The bp-SNA consists of tightly packed bilayer silica nanochannel array (SNA) with asymmetric surface charges, namely an inner negatively charged SNA (n-SNA) and an outer positively charged SNA (p-SNA), serving as an "electrostatic lock" to enrich and stabilize the cationic Ru(bpy) 3 2+ probe without leakage from the electrode surface. The detection of SARS-CoV-2 IgG antibody could be realized via immobilization of SARS-CoV-2 spike protein on the utmost of Ru(bpy) 3 2+-confined solid-state ECL platform (Ru@bp-SNA). Upon the capture of target SARS-CoV-2 IgG by immune recognition, the formed immunocomplex will block the nanochannel, leading to the hindered diffusion of the co-reactant (tri-n-propylamine, TPrA) and further producing a decreased ECL signal. The developed solid-stated ECL immunosensor is able to determine SARS-CoV-2 IgG with a wide linear range (5 pg mL−1 to 1 μg mL−1), a low limit-of-detection (2.9 pg mL−1), and a short incubation time (30 min). Furthermore, accurate analysis of SARS-CoV-2 IgG in real serum samples is also obtained by the sensor. [ABSTRACT FROM AUTHOR]

Cubic silicon carbide (β-SiC) thin films were synthesized on cemented carbide (WC–Co) substrates as an interlayer for modifying the adhesion of diamond coatings. The influence of varying the hydrogen (H 2 )/tetramethylsilane (TMS) flow ratios on the microstructure, phase composition and adhesion of the β-SiC films was investigated. It was found that with the increase of the H 2 /TMS flow ratios, the SiC crystallite size increases from 6.5 nm to 22.2 nm. When the flow ratio was 40:5, the film was formed of loose cauliflower-like agglomerates, containing SiC granular particles. With the flow ratio increased from 40:5 to 120:5, the films became more uniform and denser, resulting in adhesion enhancement. However, when the ratio increased from 160:5 to 200:5, clusters composed of faceted particles replaced the agglomerates, and the adhesion reduced. The β-SiC film deposited with a H 2 /TMS flow ratio of 120:5 possessed a more uniform and denser structure, as well as better adhesion than the others. After subsequent diamond deposition, homogeneous nanocrystalline diamond coatings were realized on the β-SiC interlayered substrates. Compared with the results on the well-known two-step chemically etched substrates, the diamond coatings deposited on the substrates with the β-SiC interlayer possess excellent adhesion. It was also validated in this research that the β-SiC interlayer deposited with a H 2 /TMS flow ratio of 120:5 was effective in enhancing the adhesion of diamond coatings prepared on WC–Co substrates. [ABSTRACT FROM AUTHOR]

In this paper, bi-layer (SiC + diamond) coatings were synthesized on 0.8-mm-diameter cemented carbide micro-end mills. The influences of SiC interlayers and diamond coatings on the morphologies, phase composition and fracture strength were investigated. The cutting performance of the bi-layer (SiC + diamond) coated tools was validated by dry cutting of aluminum alloys. The results indicated that the binder Co reacted with SiC to form cobalt silicides (i.e., Co 2 Si and CoSi), suggesting that the SiC interlayer suppressed the deleterious effects of Co, successfully. Neither the presence of the SiC interlayer nor the bi-layer coatings reduced the fracture resistance of the tools. The workpieces had a better surface finish after being cut by the coated tools than those cut by the uncoated tools. This result indicated that the bi-layer (SiC + diamond) coated tools exhibited better cutting performance than the uncoated tools. Thus, SiC interlayers were demonstrated as a suitable option for adherent diamond coatings on the cemented carbide components and cutting tools. [ABSTRACT FROM AUTHOR]

SiC films were synthesized on WC-Co substrate as interlayers for improving the adhesion of diamond coatings. The influence of the substrate temperature on the SiC films was investigated. The results showed that when the temperature was 600 °C, the film was formed of loose agglomerates piled up by SiC nanoparticles. As the temperature increased to 850 °C, shell structure composed of SiC particles and graphite replaced the agglomerates. When the temperature exceeded 950 °C, flower-like SiC clusters and graphite spherical particles coexisted in the surface, and Co 2 Si particles embedded at the SiC/substrate interface. SiC films deposited at 600 °C, 850 °C and 950 °C were typically used as interlayer for diamond deposition. The coatings exhibited the similar nano-diamond structure. However, the diamond coating on the interlayer produced at 850 °C possessed the best adhesion; and the diffusion of Co was effectively inhibited by SiC interlayer which would not interfere with the process of diamond deposition. [ABSTRACT FROM AUTHOR]

The maturity of Industrial 4.0 technologies (smart wearable sensors, Internet of things [IoT], cloud computing, etc.) has facilitated the iteration and digitization of rehabilitation assistive devices (RADs) and the innovative development of intelligent manufacturing systems of RADs, expanding the value-added component of smart healthcare services. The intelligent manufacturing service mode, based on the concept of the product life cycle, completes the multi-source data production process analysis and the optimization of manufacturing, operation, and maintenance through intelligent industrial Internet of things and other means and improves the product life cycle management and operation mechanism. The smart product-service system (PSS) realizes the value-added of products by providing users with personalized products and value-added services, service efficiency, and sustainable development and gradually forms an Internet-product-service ecosystem. However, research on the PSS of RADs for special populations is relatively limited. Thus, this paper provides an overview of an IoT-based production model for RADs and a smart PSS-based development method of multimodal healthcare value-added services for special people. Taking the hand rehabilitation training devices for autistic children as a case, this paper verifies the effectiveness and availability of the proposed method. Compared with the traditional framework, the method used in this paper primarily helps evaluate rehabilitation efficacy, personalizes schemes for patients, provides auxiliary intelligent manufacturing service data and digital rehabilitation data for RAD manufacturers, and optimizes the product iteration development procedures by combining user-centered product interaction, multimodal evaluation, and value-added design. This study incorporates the iterative design of RADs into the process of smart PSS to provide some guidance to the RADs design manufacturers. [ABSTRACT FROM AUTHOR]

Herein we demonstrate a simple and rapid electrochemical method for selectively enhanced determination of catechol (CC) or hydroquinone (HQ) isomers in environmental water samples by tailoring the molecular permeability of vertically-ordered mesoporous silica-nanochannel films on electrochemically reduced graphene oxide (VMSF/ErGO). Such VMSF/ErGO composite film was fabricated on the gold electrode (AuE) surface using electrochemically assisted self-assembly approach. The as-prepared electrodes with surfactant micelles (SM) template inside silica nanochannels, designed as SM/VMSF/ErGO/AuE, possess hydrophobic hydrocarbon cores and show preferential response to CC via hydrophobic effect. After removing SM from silica nanochannels, the obtained VMSF/ErGO/AuE displays more sensitive response to HQ, which is due to the hydrogen bond effect between the silanol groups of silica walls and HQ. Given the potential-resolved and high electrocatalytic ability of ErGO, and molecular permeability and anti-fouling ability of VMSF, these two present sensors could detect CC and HQ in lake water with a low limit of detection (18 nM for CC and 16 nM for HQ), and a high sensitivity (0.33 μA/μM for CC and 0.37 μA/μM for HQ), without complicated sample pretreatment. Moreover, the proposed sensors provide a convenient, rapid and economic way for direct analysis of environmental water samples, exhibiting excellent long-term stability. [Display omitted] • Molecular permeability of VMSF on ErGO was tailored. • Selectively enhanced determination of CC or HQ via hydrophobic preconcentration or hydrogen bond effect. • Simultaneous electroanalysis of CC and HQ was due to the underlying ErGO. • Anti-fouling electroanalysis of CC and HQ in lake water arises from the permselectivity of VMSF. [ABSTRACT FROM AUTHOR]

Dual activation of the glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP-1R) has the potential to lead to an effective therapy for the treatment of diabetes and obesity. Here, we report the discovery of a series of peptides with dual activity on GLP-1R and GCGR that were discovered by rational design. Structural elements of oxyntomodulin (OXM), glucagon or exendin-4 were engineered into the selective GLP-1R agonist Xenopus GLP-1 (xGLP-1) on the basis of sequence analysis, resulting in hybrid peptides with potent dual activity at GLP-1R and GCGR. Further modifications with fatty acid resulted in a novel metabolically stable peptide (xGLP/GCG-15) with enhanced and balanced GLP-1R and GCGR activations. This lead peptide was further explored pharmacologically in both db/db and diet-induced obesity (DIO) rodent models. Chronic administration of xGLP/GCG-15 significantly induced hypoglycemic effects and body weight loss, improved glucose tolerance, and normalized lipid metabolism, adiposity, and liver steatosis in relevant rodent models. These preclinical studies suggest that xGLP/GCG-15 has potential for development as a novel anti-obesity and/or anti-diabetic candidate. Considering the equal effects of xGLP/GCG-15 and the clinical candidate MEDI0382 on reverse hepatic steatosis, it may also be explored as a new therapy for nonalcoholic steatohepatitis (NASH) in the future. Image 1 • Novel GLP-1R/GCGR coagonists derivatized from the peptide backbone of XenGLP-1. • xGLP/GCG-15 exhibited enhanced and balanced GLP-1R and GCGR activation potency. • xGLP/GCG-15 showed prominent hypoglycemic effects in db/db mice. • xGLP/GCG-15 significantly induced body weight loss in DIO mice. [ABSTRACT FROM AUTHOR]

In present work, Al-7Si-4Cu alloys with/without 0.28 wt % Cd addition were fabricated. Both alloys were solution treated at 500 °C for 10 h, followed by quenching and subsequently ageing at 165 °C for different times of 0.5–20 h. Results showed that hardness, strength and ductility at peak-aged state for Cd-doped alloy were simultaneously enhanced by comparing with Cd-free alloy. Quantitative analysis results of microstructure indicated that with Cd addition a finer and denser microstructure of θ′ can be obtained. Based on microstructure characterization as well as thermodynamics and kinetics calculations, the mechanism for obtaining a finer and denser θ′ was discussed, which was considered as a result of the pre-precipitation and heterogeneous nucleation effect of Cd-rich particles. Improved mechanical properties for Cd-doped alloy were discussed to be ascribed to the precipitation of larger number density and less size of θ′. The increase of yield strength with Cd was quantitatively described by the strengthening models. The results indicated that yield strength increment in alloy B was dominated by strengthening contribution of finer and denser θ′ precipitates. Image 1 • Al-Si-Cu-Cd alloy was fabricated with finer and denser θ′ by Cd addition. • Hardness, strength and ductility were enhanced simultaneously in the Cd-doped alloy. • Heterogeneous nucleation effect of Cd-rich particles on refining θ′ was found. • Strengthening and toughening mechanisms in the Cd-doped alloy were discussed. [ABSTRACT FROM AUTHOR]

A series of rasagiline-clorgyline hybrids was designed, synthesized and investigated in vitro for their inhibition of monoamine oxidase and amyloid-β aggregation. Most of compounds were found to be selective and highly potent hMAO-B inhibitors showing IC 50 values in the nanomolar, and exhibited a moderate inhibition of amyloid-β aggregation. 7-((5-(methyl(prop-2-yn-1-yl)amino) pentyl)oxy)chroman-4-one (6j) was the most interesting compound identified in this research, endowed with higher hMAO-B potency (IC 50 = 4 nM) and selectivity (SI > 25000) compared to the reference selective inhibitor rasagiline (IC 50 = 141 nM, SI > 355), and exhibited good inhibitory activity against Aβ 1-42 aggregation (40.78%, 25 μM). Kinetic and molecular modeling studies revealed that 6j was a competitive reversible inhibitor for hMAO-B. Moreover, compound 6j displayed low toxicity and good neuroprotective effects in SH-SY5Y cell assay, and could penetrate the blood-brain barrier according to the parallel artificial membrane permeability assay. Pharmacokinetics assay revealed that compound 6j possessed good pharmacokinetic profiles after intravenous and oral administrations. Overall, these results highlighted that compound 6j was an effective and promising multitarget agent against Alzheimer's disease. Image 1 • Twenty rasagiline-clorgyline hybrids were designed and synthesized. • All compounds were highly selective and potent h MAO-B inhibitors. • 6j exhibited low nanomolar inhibition for MAO-B and good inhibition for Aβ 1-42 aggregation. • 6j showed neuroprotective effects and could penetrate the BBB. • 6j had good pharmacokinetic characteristics after intravenous and oral administrations. [ABSTRACT FROM AUTHOR]

Thermal conductivity is required for developing high-power microwave technology. Diamond has the highest thermal conductivity in nature. In this study, a diamond film was synthesized by microwave plasma chemical deposition, and then long and short conductive graphite fibers were introduced to the diamond films by laser ablation. The permittivity of the samples in the K-band was measured using the transmission/reflection method. The permittivity of diamond films with short graphite fibers increased. The increase in real part of permittivity can be attributed to electron polarization, and the increase in the imaginary part can be ascribed to both polarization and electrical conductivity. The diamond films with long graphite fibers exhibited a highly pronounced anisotropy for microwave. The calculation of microwave absorption shows that reflection loss values exceeding −10 dB can be obtained in the frequency range of 21.3–23.5 GHz when the graphite fiber length is 0.7 mm and the sample thickness is 2.5 mm. Therefore, diamond films can be developed into a microwave attenuation material with extremely high thermal conductivity. [ABSTRACT FROM AUTHOR]

It has been known that boron-doped diamond (BDD) is an ideal electrode material since it has the advantages of wide potential window, low background current, good corrosion resistance and strong electrochemical oxidation capability. In this paper, we will show that by preparing BDD as a composite, a new electrode material may be produced. To preparing such a composite, BDD and titanium (Ti) powders have been selected as the electrochemically active material and the matrix, respectively, and spark plasma sintering has been used as the fabrication procedure. Electrochemical tests proved that after an appropriate passivation, surface of the Ti matrix would acquire an insulating property, and the Ti-BDD composite as a whole would possess characteristics of a BDD material, including wide potential window, high oxygen evolution potential and low background current. Degradation tests conducted with glucose solution showed that the composite possessed also good electrochemical oxidation performance and chemical oxygen demand removal capability. Very importantly, accelerated life test proved that the composite as an anode material may have much longer lifetime than that of a BDD coating electrode produced by conventional chemical vapor deposition processes. All these preliminary experimental results suggested that Ti-BDD composite as a new anode material may have bright prospect in electrochemical applications. Unlabelled Image • Boron-doped diamond composite was prepared as a new anode material. • The composite has the same good electrochemical properties as the boron doped diamond coatings. • The composite may have longer lifetime than that of the boron doped diamond coatings. [ABSTRACT FROM AUTHOR]

• Twenty-eight chromanone-dithiocarbamate hybrids were designed and synthesized. • 6c showed potential inhibition for both AChE and Aβ aggregation. • 6c exhibited no acute toxicity in mice and could penetrate the BBB. • 6c could significantly reverse scopolamine-induced memory deficit in vivo. By connecting chromanone with dithiocarbamate moieties through flexible linkers, a series of hybrids as novel multifunctional AChE inhibitors have been designed and synthesized. Most of these compounds displayed strong and excellently selective inhibition to eeAChE as well as potent inhibition to self- and AChE-induced Aβ aggregation. Among them, compound 6c showed the best activity to inhibit eeAChE (IC 50 = 0.10 μM) and AChE-induced Aβ aggregation (33.02% at 100 μM), and could effectively inhibit self-induced Aβ aggregation (38.25% at 25 μM). Kinetic analysis and docking study indicated that compound 6c could target both the CAS and PAS, suggesting that it was a dual binding site inhibitor for AChE. Besides, it exhibited good ability to penetrate the BBB and low neurotoxicity in SH-SY5Y cells. More importantly, compound 6c was well tolerated in mice (2500 mg/kg, po) and could attenuate the memory impairment in a scopolamine-induced mouse model. Overall, these results highlight 6c as a promising multifunctional agent for treating AD and also demonstrate that the dithiocarbamate is a valid scaffold for design of multifunctional AChE inhibitors. [ABSTRACT FROM AUTHOR]