Site-specific N-glycosylation characterization requires intact N-glycopeptide analysis based on suitable tandem mass spectrometry (MS/MS) method. Electron-transfer/higher-energy collisional dissociation (EThcD), stepped collision energy/higher-energy collisional dissociation (sceHCD), higher-energy collisional dissociation-product-dependent electron-transfer dissociation (HCD-pd-ETD), and a hybrid mass spectrometry fragmentation method EThcD-sceHCD have emerged as valuable approaches for glycoprotein analysis. However, each of them incurs some compromise, necessitating the systematic performance comparisons when applied to the analysis of complex clinical samples (e.g., plasma, urine, cells, and tissues). Herein, we compared the performance of EThcD-sceHCD with those previous approaches (EThcD, sceHCD, HCD-pd-ETD, and sceHCD-pd-ETD) in the intact N-glycopeptide analysis, and determined its applicability for clinical N-glycoproteomic study. The intact N-glycopeptides of distinct samples, namely, plasma from prostate cancer (PCa) patients, urine from immunoglobulin A nephropathy (IgAN) patients, human hepatocarcinoma cell line (HepG2), and thyroid tissues from thyroid cancer (TC) patients were analyzed by these methods. We found that EThcD-sceHCD outperformed other methods in the balance of depth and accuracy of intact N-glycopeptide identification, and sceHCD and EThcD-sceHCD have good complementarity. EThcD-sceHCD holds great potential for biomarker discovery from clinical samples.
To investigate the effect that folic acid-modified polyrotaxanes(FPP) transfered siRNA CD47 to inhibit melanoma proliferation, the expression of CD47 in clinical melanoma patients was tested by Western blot and RT-PCR, respectively. Physical performance of FPP(siRNA-CD47: CD47) nanoparticles was tested by Malvern particle size instrument and scanning electron microscope. The clone formation experiment demonstrated that FPP(CD47) nanoparticles inhibited the growth of clones. Invasion assay revealed that FPP(CD47) inhibited migration of B16F10 cells. Tumor bearing mice were used in the experiment to test the efficacy of FPP(CD47) treatment. Compared with the control group, high expression of CD47 was observed in the clinical melanoma patients. FPP(CD47) nanoparticle size at 80 nm exhibited a potential of 10 m V; compared with FPP(Con), fluorescence intensity was significantly reduced to 4.2% and B16F10 cell clone formation was decreased by 91% in the FPP(CD47) treatment. Tumor volume of tumor-burdened mice was decreased by 90% with FPP(CD47) treatment. FPP(CD47) lowered CD47 protein and m RNA expression in the tumor. This study suggests that FPP may transfer siRNA CD47 into the cancer cells to inhibit melanoma growth effectively.
Objective This study was performed to compare the clinical efficacy of three internal fixation methods for distal clavicle fractures (Neer type II): clavicular hook plate (Group A), anatomical plate (Group B), and arthroscopic Endobutton (Group C). Methods From 2001 to 2014, 58 patients with Neer type II distal clavicle fractures were treated at our institution. The clinical results were assessed with the visual analog scale (VAS), Constant score, and Simple Shoulder Test (SST) score. Results All patients had anatomic reduction and bone healing at the final follow-up. Groups B and C had considerably less intraoperative blood loss than Group A. The incision was significantly shorter in Group C than in Groups A and B. The mean VAS score was significantly higher in the affected than unaffected shoulder. The Constant and SST scores were significantly higher in the unaffected than affected shoulder. The VAS, Constant, and SST scores of the affected shoulders were not significantly different among the three groups. Conclusions Arthroscopic Endobutton fixation has long-term clinical results similar to those of other surgical protocols for distal clavicle fractures (Neer type II). We recommend this technique because of less blood loss, shorter incision length, and less shoulder irritation than other methods.
Magnetic fluid containing Fe(3)O(4) as mother nucleus was prepared by chemical coprecipitation and treated with dextran-70 for surface modification. The dextran-70-modified magnetic fluid was reacted with 6-bromohexanoic acid and their chemical stability was studied, with the structure characterized by using laser granulometer, X-ray diffraction, Fourier-transform infrared analysis and transmission electron microscopy. The results showed that the magnetic fluid with surface modification by dextran-70 exhibited high stability in the presence strong alkali or acid. No chemical changes occurred in the magnetic Fe(3)O(4) nucleus surrounded by alkali-treated dextran-70 and the organic chain linked to the surface dextran rendered the reaction to the anti-cancer drug such as mitomycin C possible, suggesting the potential of the preparation as a drug carrier.
The wide geographical distribution of Eurasian wild boar (Sus scrofa) provides a natural model to study the adaptation to cold climate. Here, we conducted whole-genome sequencing and analyses for wild boar populations from cold (northern and northeastern Asia) and relatively warm regions (southeastern Asia and southern China). With genome-wide scans of four methods, we detected candidate genes underlying cold-adaptation with significant enrichment of pathways related to thermogenesis, fat cell development, and adipose tissue regulation. We further found two positively selected variants, rs341219502 in IGF1R (Insulin-Like Growth Factor 1 Receptor) and rs327139795 in BRD4 (Bromodomain Containing 4), which showed the highest cold-warm differentiation among all regulatory and exonic variants, respectively. Allele frequency distribution revealed that they are absent in outgroup species and warm-region wild boar but nearly fixed in cold-region populations, suggesting their de novo origins in cold-region populations. The historical demography during the last 25,000-50,000 years does not support the hypothesis that the sweep signal on the two variants resulted from genetic drift. We also found three genes (SLCO1C1, PDE3A, and TTC28) with selection signals in both wild boar and indigenous human populations from Siberia, which suggests convergent molecular adaptation in mammals. Our study indicates that molecular adaptive evolution is underlying the remarkable environmental flexibility of wild boar.
Abstract Background As one of the most common congenital abnormalities in male births, cryptorchidism has been found to have a polygenic etiology according to previous studies of common variants. However, little is known about genetic predisposition of rare variants for cryptorchidism, since rare variants have larger effective size on diseases than common variants. Methods In this study, a cohort of 115 Chinese probands with cryptorchidism was analyzed using whole-genome sequencing (WGS), alongside 19 parental controls and 2136 unaffected men. Additionally, CRISPR-Cas9 editing of a conserved variant was performed in a mouse model, with MRI screening utilized to observe the phenotype. Results In 30 of 115 patients (26.1%), we identified four novel genes ( ARSH , DMD , MAGEA4 , and SHROOM2 ) affecting at least five unrelated patients and four known genes ( USP9Y , UBA1 , BCORL1 , and KDM6A ) with the candidate rare pathogenic variants affecting at least two cases. Burden tests of rare variants revealed the genome-wide significances for newly identified genes ( p < 2.5×10 -6 ) under the Bonferroni correction. Surprisingly, novel and known genes were mainly from X chromosome (seven on X and one on Y) and all rare X-chromosomal segregating variants exhibited a maternal inheritance rather than de novo origin. CRISPR-Cas9 mouse modeling of a splice donor loss variant in DMD (NC_000023.11:g.32454661C>G), which resides in a conserved site across vertebrates, replicated bilateral cryptorchidism phenotypes, confirmed by Magnetic resonance imaging (MRI) at 4 and 10 weeks. Conclusion Our results revealed the role of the DMD gene mutation in causing cryptorchidism. The results also suggest that maternal-X inheritance of pathogenic defects could have a predominant role in the development of cryptorchidism.
Abstract The wide geographical distribution of Eurasian wild boar ( Sus scrofa ) offers a natural experiment to study the thermoregulation. Here, we conducted whole-genome resequencing and chromatin profiling experiments on the local populations from cold regions (northern and northeastern Asia) and warm regions (southeastern Asia and southern China). Using genome-wide scans of four methods, we detected candidate genes underlying cold-adaptation with significant enrichment of pathways related to thermogenesis, fat cell development, and adipose tissue regulation. We also found two enhancer variants under positive selection, an intronic variant of IGF1R (rs341219502) and an exonic variant of BRD4 (rs327139795), which showed the highest differentiation between cold and warm region populations of wild boar and domestic pigs. Moreover, these rare variants were absent in outgroup species and warm-region wild boar but nearly fixed in cold-region populations, suggesting their de novo origins in cold-region populations. The experiments of CUT&Tag chromatin profiling showed that rs341219502 of IGF1R is associated with the gain of three novel transcription factors involving regulatory changes in enhancer function, while rs327139795 of BRD4 could result in the loss of a phosphorylation site due to amino acid alteration. We also found three genes ( SLCO1C1, PDE3A , and TTC28 ) with selection signals in both wild boar and native human populations from Siberia, which suggests convergent molecular adaptation in mammals. Our study shows the adaptive evolution of genomic molecules underlying the remarkable environmental flexibility of wild boar.
To investigate the biomechanics effect due to unilateral cortical bone defect of different size in long tubular bone.Seventy-six pieces of Sanhuang cock tibial were randomly divided into 7 groups. The unilateral diaphyses cortical were drilled holes of different size, include 1.5, 2.0, 2.5, 3.0, 3.5, and 4.5 mm, performed three-points bend single experiment. The intact bone cortical group was control group.When there were bone structure destructions, the maximum of the bend load between 3 groups which bone defect diameter were 1.5 mm, 2.0 mm, and control was not significant difference (P = 0.824, 0.865), but the maximum of the bend load between 3 groups which bone defect diameter were 2.5, 3.0, and 3.5 mm decreasing about 14 percent of the control group (P = 0.015, 0.010, 0.021). and the maximum of the bend load which bone defect diameter were 4.5 mm decrease about 23 percent of the control group (P = 0.001).If the diameter of bone cortical defect is within 22.63 +/- 1.39 percent of bone cortical outer diameter, there was no reduction of the bend load. If the diameter of bone cortical defect is beyond 29.36 +/- 2.07 percent of bone cortical outer diameter, it decreases the maximum bend load of the long tubular bone, but the reduced range is not complete with direct ratio to the bone defect size.
Layer spacing of vanadium oxide can be effectively expanded by metal ion, however, its conductivity and electrochemical kinetics still require improvement. This work expands the layer spacing using manganese ion and help to improve conductivity and electrochemical kinetics by graphene. The results demonstrate that the layer spacing can be adjusted from 12.1 Å for pristine vanadium oxide (VOH) to 13.6 Å for manganese vanadium oxide (MnVO). Due to graphene introduction, it decreases to 11.6 Å for manganese vanadium oxide/graphene composite (MnVO-0.05–8/GN-15). Notably, the optimized composite delivers higher specific capacity of 507.5 mAh g−1 for MnVO-0.05–8/GN-15 than that of MnVO (410.4 mAh g−1) and VOH (370.1 mAh g−1) at current density of 0.5 A g−1. Furthermore, the MnVO-0.05–8/GN-15 exhibits fast Zn2+ ion diffusion ability, achieving high energy density of 403.51 Wh kg−1 and retaining an excellent cycle stability of 85.7% after 2000 cycles at a current density of 3 A g−1.
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