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p-Phenylenediamine antioxidants (PPDs) are rubber antioxidants that can suppress oxidation, heat, or light radiation to delay the aging of polymer components and extend the service life of rubber products. In recent years, PPDs have been found in the environment, and their ecological risks remain largely unknown, which cause widespread concern. In this work, a method of gas chromatography-tandem mass spectrometry (GC-MS/MS) with ultrasonic extraction was developed for the determination of PPDs in zebrafish embryos. In order to have good performance, extraction solvents and sorbents were optimized. Under optimal conditions, embryonic samples were combined with 5 mL of dichloromethane and ultrasonically extracted for 15 min. The extraction procedure was repeated twice, after that the resulting extracts were purified by 0.1 g primary secondary amine (PSA). Based on internal standard method, the analytes were detected using GC-MS/MS in selective reaction monitoring (SRM) mode with optimal parameters. The results showed that the chromatographic peaks of analyte were completely separated, and the baseline was smooth. The correlation coefficient (R2) of each analyte exceeded 0.99 in the concentration range of 0.1-200 μg/L. Method detection limits (MDLs) and method quantification limits (MQLs) were in the range of 0.38-0.68 ng/g and 1.28-2.28 ng/g, respectively. Except for the average recovery of N,N′-bis(methylphenyl)-1,4-benzenediamine (DTPD), which was higher than 120%, the average recoveries of N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), N-phenyl-N′-cyclohexyl-p-phenylenediamine (CPPD) and N-isopropyl-N′-phenyl-1,4-phenylenediamine (IPPD) were 73.1%-109%, and the intra-day and inter-day relative standard deviations (RSDs) were 2.97%-15.0% and 4.76%-18.8%, respectively. In order to demonstrate the feasibility of this method, it was applied to detect PPDs in zebrafish embryos exposed to PPDs. The results indicated that PPD concentrations were 12.5-16.4 ng/g. After calculation, the measured bioconcentration factors of each analyte within 48 h were 1.70-33.6 L/kg. These values were much lower than the corresponding predicted bioconcentration factors, because PPD concentrations in vivo had not reached equilibrium during the exposure time of 48 h. This method is simple, sensitive, and suitable for the detection of PPDs in zebrafish embryos, which facilitates future bioaccumulation and toxicity mechanism studies for a comprehensive assessment of the ecological risks of PPDs.

Objective: To investigate the biomechanical effect of different intervertebral reconstructive heights on adjacent segments following C5/C6 anterior cervical discectomy and fusion (ACDF) through finite element analysis. Methods: A finite element model of intact C4–C7 segments was developed and validated for the present study. Five additional C4–C7 postoperative models were constructed with 100%, 125%, 150%, 175%, and 200% of the benchmark height of C5/C6 on the basis of the intact model. The changes in intradiscal pressure (IDP) and range of motion (ROM) of adjacent segments before and after reconstruction of C5/C6 were analyzed. Results: For the upper adjacent segment (C4/C5), the IDPs under the different loading conditions all increased after reconstruction. The maximum IDPs were 0.387, 0.489, 0.491, and 0.472 MPa under flexion, extension, axial rotation, and lateral bending, respectively, observed at the reconstructive height of 200%. The minimum IDPs were observed at 150% reconstructive height under all loading conditions except extension, and were 57, 86 and 81% of the maximum IDPs under flexion, axial rotation, and lateral bending, respectively. The minimum IDP under extension occurred when the reconstructive height is 125% of the benchmark height. For the lower adjacent segment (C6/C7), the IDPs of postoperative models under all loading conditions also increased compared to the preoperative model. The maximum IDPs after reconstruction under flexion, extension, axial rotation, and lateral bending were 0.402, 0.411, 0.461, and 0.497 MPa, respectively, when the height of the reconstruction was 200% of the benchmark. The minimum IDPs were observed after a reconstruction at 150% of the benchmark, and were 59%, 85%, 82%, and 81% of the maximum IDPs under flexion, extension, axial rotation, and lateral bending loading conditions. Conclusions: The reconstructive height is an important factor affecting the IDP and the ROM of adjacent segments after ACDF. To delay the adjacent segment disease, an intervertebral reconstructive height of 150% is an appropriate height in C5/C6 ACDF. [ABSTRACT FROM AUTHOR]

Objective: To compare the preventive effects of teriparatide and alendronate on the progression of vertebral body collapse in postmenopausal single‐level Kümmell's disease (KD). Methods: From March 2013 to December 2020, the medical records for 53 postmenopausal single‐level KD patients who received conservative treatment with teriparatide (25 patients, teriparatide group) or alendronate (28 patients, alendronate group) were retrospectively reviewed. Midsagittal computed tomography (CT) images were analyzed by ImageJ to assess the intravertebral bone formation (mineralized bone) by calculating the ratio of area of intravertebral mineralized bone (AIMB) to the area of fractured vertebral body (AFVB). The changes in radiological parameters of the fractured vertebral body including kyphosis angle (KA), anterior and posterior border heights (ABH and PBH) and spinal canal diameter (SCD), bone turnover biomarkers (BTMs), and bone mineral density (BMD) were analyzed to evaluate the therapeutic effect. Results: At month 12, the ratio of AIMB to AFVB was significantly greater in teriparatide group (54.28% ± 15.30%) than in alendronate group (35.57% ± 17.61%) (P < 0.001). Sagittal CT substantiated the formation of bone bridge in 16 patients in teriparatide group. No bone bridge was detected in alendronate group. The KA was significantly smaller and the ABH, PBH, and SCD was greater in teriparatide group than in alendronate group (all P < 0.001). The KA increments were significantly smaller in teriparatide group (3.98° ± 1.30°) than in alendronate group (11.43° ± 3.73°) (P < 0.001). The ABH and PBH decrement were significantly lower in teriparatide group (11.96% ± 1.93% and 2.80% ± 2.52%) than in alendronate group (37.04% ± 8.00% and 19.50% ± 8.22%) (both P < 0.001). The BTMs and BMD were significantly greater in the teriparatide group than in the alendronate group. In teriparatide group, KA increment was negatively correlated with the change in PINP (r = −0.781, P < 0.001) and the ratio of AIMB to AFVB (r = −0.592, P = 0.002) from baseline to month 12. The ABH decrement was negatively correlated with the change in PINP (r = −0.612, P = 0.001) and the ratio of AIMB to AFVB (r = −0.806, P < 0.001) from baseline to month 12. Conclusions: In postmenopausal single‐level KD patients, conservative treatment with teriparatide was better than alendronate at preventing the progressive vertebral collapse. [ABSTRACT FROM AUTHOR]

Some traditional protection schemes cannot detect a faulted Powerformer when a stator single-line-to-ground fault occurs in parallel Powerformers. A new discrimination method based on kernel principal component analysis (KPCA) and Fisher discrimination analysis considering the distribution characteristics of the data is proposed in this paper. First, the algorithms of the KPCA and the Fisher discrimination are introduced. In order to increase the correct rate of the fault recognition, a kernel function for the distribution characteristics of the data is selected according to the error rate under the historical fault data, which is different from the existing application validation methods. Then, the detected data in the system model are processed to detect whether a stator single-line-to-ground fault occurred in the Powerformer using the KPCA and the Fisher discrimination analysis based on an optimal kernel function. Finally, simulation results show that the proposed scheme can exactly detect the fault for a Powerformer in different neutral grounding systems when a stator single-line-to-ground fault occurred. [ABSTRACT FROM AUTHOR]

Background: Recent studies have demonstrated that synthetic dsRNAs may produce therapeutic effects in a target-independent manner through stimulation of the toll-like receptor-3 (TLR3)/interferon pathway; as a result, angiogenesis and proliferation of tumor cells are inhibited. Thus, this pathway may become a potential target of dsRNA in tumor suppression. In this study, we evaluated the role of synthetic dsRNA as a TLR3 synergist and by combining with sorafenib in anti-hepatocellular carcinoma (HCC) in vitro and in vivo.Methods: Four dsRNAs were designed and synthesized. One of them that was capable of activating TLR3 most effectively in human HCC cell line (HepG2.2.15) was selected as a TLR3 synergist (called BM-06). Subsequently, the expression of proteins relating to TLR3 signaling pathway, such as NF-κB, caspase 8 survivin, bcl-2 and PCNA affected by BM-06, sorafenib alone or in combination, was compared. The migration, proliferation and apoptosis of HepG2.2.15 cells were evaluated in presence of BM-06, sorafenib alone or in combination of both. The similar treatments were also applied in an SD rat primary HCC model.Results: qRT-PCR data showed that the expression of TLR3 and NF-κB in HepG2.2.15 cells was enhanced. BM-06 was selected as a TLR3 synergist capable of activating the TLR3/interferon pathway most effective among 4 synthetic dsRNAs. The migration and proliferation were significantly inhibited in treated HepG2.2.15 cells with BM-06 or Sorafenib alone as compared with PBS-sham control (P<0.01). However, the role of combination BM-06 with Sorafenib was the most prominent. Tumor cell apoptotic rate was increased by BM-06 or combination when compared to PBS or poly(I:C) (P<0.05). Similarly, in orthotopic HCC SD rats, the effect of the combination was superior to either agent alone on the inhibition of tumor growth and induction of HCC cell apoptosis (P<0.05).Conclusions: dsRNA alone was capable of inhibiting the proliferation of HepG2.2.15 cells and tumor growth of orthotopic HCC SD rats, but the effect of combination of dsRNA with sorafenib was more prominent. These findings implicate the potential role of combined use of a dsRNA, a TLR3 synergist, and sorafenib in inhibition of HCC. [ABSTRACT FROM AUTHOR]

Two new dammarane triterpene glycosides named notoginsenosides Rw 1 (1) and Rw 2 (2) were isolated from the rhizomes of Panax notoginseng, together with 20 known compounds including protopanaxadiol (3), protopanaxatriol (4), ginsenosides Rb1 (5), Rd (6), Re (7), Rg1 (8), Rg2 (9), 20-(S)-Rg3 (10), 20-(R)-Rg3 (11), Rh1 (12), Rh4 (13), Rf (14), 20-O-glucopyranosyl Rf (15), notoginsenosides R1 (16), R2 (17), T5 (18), S (19), T (20), and Fa (21), and koryoginsenoside R1 (22). Based on FABMS, HRFABMS, IR, 1H, 13C, and 2D-NMR (HSQC, HMBC, and COSY) spectral data, the structures of the new compounds were elucidated as 6-O-β-d-xylopyranosyl-20-O-β-d-xylopyranosyl-(1 → 6)-β-d-glucopyranosyldammar-24-ene-3β,6α,12β,20(S)tetraol (1) and 6-O-β-d-xylopyranosyl-(1 → 2)-β-d-glucopyranosyldammar-22-ene-(trans)-3β,6α,12β,20(S), 25-pentaol (2). Compounds 3, 4, 13, and 22 were isolated from P. notoginseng for the first time. [ABSTRACT FROM AUTHOR]

Background: A role for autophagy, a conserved cellular response to stress, has recently been demonstrated in human cancers. Aberrant expression of Beclin-1, an important autophagic gene, has been reported in various human cancers. In the present study, we investigated the significance and relationship between Beclin-1 expression and cell proliferation, apoptosis, microvessel density (MVD) and clinical pathological changes or prognosis in human hepatocellular carcinoma (HCC).Methods: A total of 103 primary HCC patients were involved in the study. Expression of Beclin-1, PCNA, NET-1, Bcl-2, Bax, Survivin in cancer cells and CD34 in stromal microvessels were evaluated immunohistochemically in tissue microarrays comprising 103 cases of HCC and 57 matched adjacent nontumor liver tissues. Correlations between clinicopathological characteristics and survival of HCC patients were explored.Results: The positive rate of Beclin-1 was significantly lower in HCC tissues than adjacent tissues (72.8 vs. 89.5%, χ2 = 6.085, P = 0.015). In HCC, Beclin-1 expression was negatively correlated with cirrhosis background (r = -0.216, P = 0.029), Edmondson grade (r = -0.249, P = 0.011), vascular invasion (r = -0.246, P = 0.012), PCNA (r = -0.242, P = 0.014), NET-1 (r = -0.245, P = 0.013), anti-apoptosis protein Bcl-2 (r = -0.245, P = 0.013) and MVD (r = -0.292, P = 0.003), and positively correlated with pro-apoptosis protein Bax (r = 0.242, P = 0.014).Significant differences in the 5-year survival rates were seen among patients with Beclin-1 strong positive (++) (59.1%, 13/22), moderate positive (+) (28.3%, 15/53) and weak negative expression (-) (14.6%, 7/28) (P = 0.043). Significant differences were detected between Beclin-1 (++) and either Beclin-1 (+) (P = 0.036) or Beclin-1 (-) groups (P = 0.008), but no significant difference between Beclin-1 (+) and Beclin-1 (-) groups (P = 0.281) was observed.Survival rates were positively related to high Beclin-1 co-expressed with low PCNA, NET-1, or Bcl-2, lower MVD, and high Bax. Univariate and multivariate Cox regression analysis revealed that Beclin-1 expression was an independent indicator for overall survival in HCC patients (P < 0.05).Conclusions: The pathogenesis and progression of HCC are associated with reduced autophagy. The expression of Beclin-1 and Bax in HCC tissues may provide a synergistic effect towards inhibiting HCC proliferation, infiltration, metastasis and angiogenesis. Beclin-1 expression may be a valuable prognostic marker of HCC. [ABSTRACT FROM AUTHOR]

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Background: Primary hypertrophic osteoarthropathy (PHO) is a rare disease related to HPGD and SLCO2A1 gene mutation. Gastrointestinal involvement of PHO is even rarer with unknown pathogenesis. Clinical features of GI complication in PHO mimics other auto-immune based bowel entities, such as inflammatory bowel diseases and cryptogenic multifocal ulcerous stenosing enteritis (CMUSE). We aimed to analyze the clinical, genetic, radiological and pathological features of Chinese patients with PHO and determine the difference between PHO patients presenting with and without GI involvement.Methods: We reported two PHO cases with gastrointestinal involvement and reviewed all the studies of PHO in Chinese population published from January 1, 2000, to April 30, 2018. Clinical and genetic presentations of PHO in Chinese patients were analyzed. We compared the characteristics of those patients with gastrointestinal involvement against those without.Results: The two patients were both males with complete-form PHO for more than 10 years. GI related symptoms included diarrhea, chronic gastrointestinal hemorrhage, incomplete intestinal obstruction, anemia, and edema, which were unresponsive to etoricoxib treatment. Radiological examinations revealed segmental intestinal stenosis and thickened intestinal wall. Endoscopic findings included multiple ulcers and mucosal inflammation. Both patients had mutations of SLCO2A1 according to sequence analysis. The surgical pathology revealed chronic inflammation involving the intestinal mucosa and submucosa, similar to histological changes in CMUSE. According to the systemic review of 158 Chinese patients with PHO, 17.2% had gastrointestinal involvement, including peptic ulcer, gastric polyps, hypertrophic gastritis, and segmental intestinal stenosis. Patients with gastrointestinal involvement were more likely to have anemia (40.0% vs. 4.5%, P < 0.001), hypoalbuminemia (16.7% vs. 0.9%, P = 0.003), and myelofibrosis (19.0% vs. 0.9%, P = 0.002) than those without. Most patients with gastrointestinal complication had SLCO2A1 mutation (86.7%, 13 /15).Conclusions: Digestive tract involvement is uncommon in patients with PHO and often presents with anemia, and hypoalbuminemia resulted from intestinal inflammation. The intestinal pathologic characteristics are distinct from Crohn's disease but similar to CMUSE. Mutations in SLCO2A1 might be the pathogenic cause of GI involvement of PHO. NSAIDs may not be effective for PHO patients with gastrointestinal complications. [ABSTRACT FROM AUTHOR]

Then our multivariate analysis showed that NSAID history (OR 4.83; 95% CI, 2.27-10.27; I P i < 0.001), lack of standardization of EFB number (OR 2.99; 95% CI, 1.91-4.68; I P i < 0.001), >= 1.0 cm maximum diameter of the target adenoma (OR 6.18; 95% CI, 1.32-28.99; I P i = 0.021), lobulated shape (OR 2.68; 95% CI, 1.65-4.36; I P i < 0.001), erythema (OR 2.42; 95% CI, 1.50-3.91; I P i < 0.001), erosion (OR 7.12; 95% CI, 3.91-12.94; I P i < 0.001), surface unevenness (OR 2.31; 95% CI, 1.33-4.01; I P i = 0.003) and distal location of the target adenoma (OR 3.29; 95% CI, 1.68-6.41; I P i < 0.001) were significantly associated with the histologically upgrade discrepancies. Colonoscopists could detect more polyps and adenomas with the aid of the CADe (0.90 vs. 0.82, I P i < 0.001; 0.32 vs. 0.30, I P i <0.05), particularly for polyps <5 mm and for flat polyps (0.65 vs. 0.57, I P i < 0.001; 0.74 vs. 0.67, I P i = 0.001, respectively), but the CADe's efficacy could not be reproduced in patients with inadequate bowel preparation and withdrawal time ( I P i = 0.32; I P i = 0.16, respectively). Twenty-six patients suffered from peri-ampullary perforations, fifteen patients suffered from duodenal wall perforations, one patient suffered from a fundus perforation, one patient suffered from a residual gallbladder duct perforation, one patient suffered from a papillary diverticulum perforation, and one patient suffered from an intrahepatic bile duct perforation. The patients were divided into four groups: 19 patients underwent pharmacologic treatment (drug group); 21 patients were treated with EVL (EVL group); 25 patients were treated with PSE (PSE group); and 22 patients underwent EVL plus PSE (EVL + PSE group). [Extracted from the article]

Inspired by the high transition-metal-ion content in mussel glues, and the cross-linking and mechanical reinforcement effects of some transition-metal ions in mussel threads, high concentrations of nickel(II), cobalt(II), and manganese(II) ions have been purposely introduced into the reaction system for dopamine polymerization. Kinetics studies were conducted for the Ni2+-dopamine system to investigate the polymerization mechanism. The results show that the Ni2+ ions could accelerate the assembly of dopamine oligomers in the polymerization process. Spectroscopic and electron microscopic studies reveal that the Ni2+ ions are chelated with polydopamine (PDA) units, forming homogeneous Ni2+-PDA complexes. This facile one-pot approach is utilized to construct transition-metal-ion-PDA complex thin coatings on graphene oxide, which can be carbonized to produce robust hybrid nanosheets with well-dispersed metallic nickel/metallic cobalt/manganese(II) oxide nanoparticles embedded in PDA-derived thin graphitic carbon layers. The nickel-graphene hybrid prepared by using this approach shows good catalytic properties and recyclability for the reduction of p -nitrophenol. [ABSTRACT FROM AUTHOR]