Search

Highlights • The genetic variant rs145204276 is associated with the susceptibility of OS. • Patients with genotype del/del of rs145204276 had significantly higher expression of GAS5 in the OS tissues. • SNP rs145204276 could play a functional role in the development and progression of OS by altering the methylation status of GAS5 promoter., Background Previous studies showed that genetic variant rs145204276 in the promoter region of GAS5 was associated with the development of human cancer including colorectal cancer and hepatocellular cancer. This study aimed to investigate the role of rs145204276 in the development of osteosarcoma (OS). Methods 132 OS patients and 1270 healthy controls were recruited for the genotyping analysis of rs145204276. Promoter methylation level of GAS5 was determined for all patients. The tumor tissues and the adjacent normal tissue were collected from 42 patients during surgery and the relative expression of GAS5 was then quantified by Real-time PCR. The Chi-square test was used to determine the difference of genotype and allele frequency between the patients and the controls. The gene expression and the percentage of methylation alleles were compared among different genotypes of rs145204276 with One-way ANOVA test. Results Compared with the controls, patients were found to have significantly lower rate of genotype del/del (7.6% vs. 8.7%, p = 0.024). The frequency of allele del was significantly lower in the patients than in the controls (23.5% vs. 30.1%, p = 0.021). Compared with than patients with genotype ins/ins, those with genotype del/del had remarkably higher expression of GAS5 (0.0033 ± 0.0019 vs. 0.0018 ± 0.0006, p

Objectives: Previous pharmacogenetics studies showed that genetic variants could be indicative of the response to chemotherapy. We aimed to investigate whether variants of FasL, MSH2, ABCC5, CASP3 and CYP3A4 are associated with the outcome after chemotherapy-based treatment in osteosarcoma. Methods: 132 osteosarcoma patients who had completed the neoadjuvant chemotherapy in our center were included. 5-year progression-free survival (PFS) was assessed from the initial treatment to the earliest sign of disease progression or death from any cause. 5 SNPs were genotyped using TaqMan SNP Genotyping Assay, including rs763110 of FasL, rs4638843 of MSH2, rs939338 of ABCC5, rs2720376 of CASP3 and rs4646437 of CYP3A4. Patients were classified into two groups according to the 5-year PFS (event/no event). The chi-square test was used to analyze difference of genotype frequency. Logistic regression analysis was used to determine the independent predictors of the PFS rate. Results: The overall 5-year PFS was 61.4% (81/132). Genotype TT/CT of rs763110 and genotype GG/AG of rs939338 were significantly associated with the event of 5-year PFS (p = 0.028 for rs763110; p = 0.039 for rs939338). Patients with no risk allele showed a 5-year PFS of 73.7% (42/57), which was significantly higher than a PFS of 54.2% (26/48) for patients with one risk allele and 48.1% (13/27) for patients with two different risk alleles (p = 0.03). Logistic regression analysis showed that allele T of FasL rs763110 and allele G of ABCC5 rs939338 were independent risk factors of the 5-year PFS. The ORs were 2.14 (95%CI = 1.13–3.35, p = 0.01) for rs763110 and 1.73 (95%CI = 1.05–2.52, p = 0.03) for rs939338, respectively. Conclusions: The association of variants of FASL and ABCC5 with survival outcome after chemotherapy was validated in patients with osteosarcoma. Our findings may provide a new insight into a more personalized treatment for patients with osteosarcoma. Keywords: Pharmacogenetics, Osteosarcoma, Variants, FASL, ABCC5

A metal-free hydrogenation of 2-quinolinecarboxylates has been realized by using 5 mol% of B(C6F5)3 as catalyst. A variety of tetrahydroquinolines were obtained in 57–99% yields. An attempt for the asymmetric hydrogenation with chiral boron Lewis acids generated from chiral dienes afforded very low ee’s.

Background To investigate the effectiveness of tibiotalocalcaneal arthrodesis with a retrograde nail and allograft in limb salvage surgery for patients with distal tibia osteosarcoma. Methods 5 patients diagnosed as distal tibia osteosarcoma underwent ankle arthrodesis with a retrograde nail in our hospital. During the follow-up, radiographic views of the ankle joint were taken in two planes to assess bone healing and axis alignment. Other measurements of outcomes included procedure-related complications, local recurrence, and metastasis. Functional outcomes were evaluated with the Musculoskeletal Tumor Society (MSTS) scoring system. Results Postoperative complications occurred in 4 patients, including 4 cases of mild subcutaneous fluid and 1 case of screw breakage. All patients showed stable ankle and could stand or walk with the assistance of crutch before the complete union between allograft and host bone. One patient died due to multiple bone and pulmonary metastasis at 1 year after surgery. As for the other 4 patients, they were followed-up regularly for a mean period of 42 months. No local recurrence or distant metastasis occurred in any of these four patients. All the 4 patients expressed satisfaction with the outcome. According to MSTS scale, the mean postoperative functional score was 74.3%±4.4% (range, 70%–81%). Conclusions Intramedullary retrograde nail for distal tibia osteosarcoma could produce a satisfactory outcome in terms of functional results and complications. Excellent stabilization of the ankle joint can be achieved through this technique, as it allows patients to perform much earlier postoperative weight-bearing exercise.

Aim: Recurrence of giant cell tumor of bone (GCTB) in the soft tissue is rarely seen in the clinical practice. This study aims to determine the prevalence of soft tissue recurrence of GCTB, and to characterize its radiographic features. Methods: A total of 291 patients treated by intralesional curettage for histologically diagnosed GCTB were reviewed. 6 patients were identified to have the recurrence of GCTB in the soft tissue, all of whom had undergone marginal resection of the lesion. Based on the x-ray, CT and MRI imaging, the radiographic features of soft tissue recurrence were classified into 3 types. Type I was defined as soft tissue recurrence with peripheral ossification, type II was defined as soft tissue recurrence with central ossification, and type III was defined as pure soft tissue recurrence without ossification. Demographic data including period of recurrence and follow-up duration after the second surgery were recorded for these 6 patients. Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate functional outcomes. Results: The overall recurrence rate was 2.1% (6/291). The mean interval between initial surgery and recurrence was 11.3 ± 4.1 months (range, 5â17). The recurrence lesions were located in the thigh of 2 patients, in the forearm of 2 patients and in the leg of the other 2 patients. According to the classification system mentioned above, 2 patients were classified with type I, 1 as type II and 3 as type III. After the marginal excision surgery, all patients were consistently followed up for a mean period of 13.4 ± 5.3 months (range, 6â19), with no recurrence observed at the final visit. All the patients were satisfied with the surgical outcome. According to the MSTS scale, the mean postoperative functional score was 28.0 ± 1.2 (range, 26â29). Conclusions: The classification of soft tissue recurrence of GCTB may be helpful for the surgeon to select the appropriate imaging procedure to detect the recurrence. In addition, the marginal resection can produce a favorable outcome for the patients. Keywords: Giant cell tumor of bone, Recurrence, Prevalence, Radiographic features

Photocatalytic degradation based on semiconductor is a potential technology for water pollution treatment by utilizing light irradiation. As a new p-type semiconductor material, CuBi2O4 is favored by researchers due to its excellent photocatalytic properties. Herein, a group of CuBi2O4 nanospheres were synthesized by simple hydrothermal method, in which the formation and transformation process of CuBi2O4 microsphere structure was studied by adjusting the hydrothermal reaction time. On this basis, a series Z-Scheme heterojunctions with different mass ratios of CuBi2O4/CdMoO4 nanocomposites were constructed and the formation mechanism of Z-scheme heterojunction was described detailedly. The results of the study confirmed that CuBi2O4/CdMoO4 (10 %) composites exhibited excellent photocatalytic activity, with a high degradation rate of 95.36 % for MB under visible light irradiation, by comparison with bare CuBi2O4 and CdMoO4. In order to improve the quantum efficiency, doping CdMoO4 onto CuBi2O4 greatly improved the surface charge migration rate of CuBi2O4 and reduced the rate of electron-hole pairs recombination. The degradation rate of CuBi2O4/CdMoO4 (10 %) remained over 85 % after three times cycling experiments, demonstrating that the heterojunction has good repeatability and stability. The free radical trapping experiments demonstrated that the h+ and O2– were the main substances involved in photocatalytic oxidation-reduction, which match the energy band, and was consistent with the mechanism of Z-Scheme heterojunctions. This study stated that establishment of a novel CuBi2O4/CdMoO4 heterojunction composite photocatalyst is a new ideal way to carry out environmental pollution treatment and clean energy.

A novel Ag/ CuBi2O4/ Ag2MoO4 composite was successfully prepared by ion exchange as well as reduction methods. The crystal structure, surface chemical composition and micromorphology characteristics of the samples were determined by a variety of testing methods and the optical properties of all synthesized catalysts were described in detail by PL, UV–Vis DRS and SPS. The ternary Ag/ CuBi2O4/ Ag2MoO4 composites were superior to other samples in visible light catalytic degradation of methylene blue (MB), it was mainly attributed to the interaction between CuBi2O4 and Ag2MoO4 and the SPR effect of Ag nanoparticles, which resulted in a significantly higher separation efficiency of photogenerated electrons and holes. Meanwhile, the degradation efficiency of MB was still maintained above 80% by three recycling experiments. Finally, a possible mechanism for photocatalytic degradation was proposed.

In this paper, we study battery capacity design for battery electric vehicles (BEVs). The core of such design problems is to find a good tradeoff between minimizing the capacity to reduce financial costs of drivers and increasing the capacity to satisfy daily travel demands. The major difficulty of such design problems lies in modeling the diversity of daily travel demands. Based on massive trip records of taxi drivers in Beijing, we find that the daily vehicle miles traveled (DVMT) of a driver (e.g., a taxi driver) may change significantly in different days. This investigation triggers us to propose a mixture distribution model to describe the diversity in DVMT for various driver in different days, rather than the widely employed single distribution model. To demonstrate the merit of this new model, we consider value-at-risk and mean-variance battery capacity design problems for BEV, with respect to conventional single and new mixture distribution models of DVMT. Testing results indicate that the mixture distribution model better leads to better solutions to satisfy various drivers.

The frequent and inappropriate use of antibiotics aggravate the variation and evolution of multidrug-resistant bacteria, posing a serious threat to public health. Nosiheptide (NOS) has excellent lethality against a variety of Gram-positive bacteria, however the physical and chemical drawbacks hamper its routine application in clinical practice. In this study, by using NOS as the starting material, a total of 15 NOS analogues (2a-4e) were semi-synthesized via its dehydroalanine residue reacting with monosubstituted anilines. In vitro antimicrobial susceptibilities of NOS and its analogues against two methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) clinical isolates were determined by broth microdilution assay to determine the minimum inhibitory concentration (MIC). Antimicrobial susceptibility testing data shown that most of the NOS analogues had a better antibacterial effect than the parent compound, with compound 3c exhibiting the highest antibacterial activity against VRE (MIC = 0.0078 mg/L) and MRSA (MIC 0.0039 mg/L). Molecular docking of synthetic compounds was also performed to verify the binding interactions of NOS analogues with the target. Our data indicated that compound 3c possesses stronger and more complex intermolecular force than other analogues, which is consistent with the results of the biological activity evaluation. Overall, this study identified a number of potential antibacterial NOS analogues that could act as potent therapeutic agents for multidrug-resistant bacterial infections.

The microstructural evolution, corrosion resistance and mechanical properties of an as-forged Mg–6.7%Zn–1.3%Y–0.6%Zr alloy before and after solid solution treatment (T4) were investigated. Results revealed that the proposed T4 treatment can improve corrosion resistance of the alloy. Based on the microstructural observations, such improvement in corrosion resistance incurred by the T4 treatment was mainly ascribed to the elimination of the inhomogeneous distribution associated with the MgZn 2 precipitates formed during hot forging process. However, due to the limited precipitation of nano-scale I-Mg 3 Zn 6 Y particles, the strength of the T4 treated specimen was slightly degraded.

Objectives: Previous genome-wide association study showed that GLDC/IL33 loci were associated with overall survival in patients with osteosarcoma (OS). We performed a replication study to explore whether variants of GLDC/IL33 are associated with the survival of OS patients and to further verify their functional role in the gene expression. Methods: A total of 216 patients with OS were enrolled. The overall survival time was calculated from the date of diagnosis till the date of last follow-up or mortality. Two SNPs were genotyped, including rs55933544 and rs74438701. OS specimens were obtained from 72 patients during surgery. The gene expression level of IL33 and GLDC was evaluated by qPCR. Patients were classified into two groups according to the 5-year overall survival (death/survival). The chi-square test was used to analyze difference of genotype frequency. The Student t-test was used to compare the gene expression level between different genotypes. Cumulative survival time was calculated by the Kaplan–Meier method and analyzed by the log-rank test. Results: Genotype TT of rs55933544 was significantly associated with the event of death (0.176 vs. 0.061, p

Thiostrepton, a natural peptide macrocycle, is of great interest due to its structural complexity and numerous biological activities, including anti-bacterial, anti-tumor, and anti-plasmodial activities. The quinaldic acid (QA) moiety-containing side ring (loop 2) was proven to play an important role in carrying out these functions. Previously, we proposed biosynthetic logic for thiostrepton loop 2 and demonstrated the formation mechanism of QA. Herein, we report the discovery and efficient synthesis of a biologically active alkaloid, that is, a key intermediate involved in the thiostrepton biosynthetic pathway. A chemo-enzymatic method was performed to synthesize the molecule, and a series of analogs were prepared for bioassays, which included the examination of anti-bacterial and anti-tumor activities.

Background context As the biomechanical foundation of the spine, the pelvis was found to display rotation in the transverse plane in adolescent idiopathic scoliosis (AIS). However, the possible factors influencing the pelvic axial rotation (PAR) and its mechanism in patients with AIS remain unclear. Purpose To characterize the PAR in AIS patients with right major thoracic (MT) or major left thoracolumbar/lumbar (TL/L) curve and to explore the associated influencing factors and probable mechanism of compensation by analyzing the association between PAR and other spinal radiographic parameters. Study design Retrospective study. Patient sample All patients with the primary diagnosis of AIS from January 2008 to November 2009 were retrieved from our scoliosis database. Outcome measures Age, Cobb angle, and apex rotation of the main curve and the compensatory curve, curve flexibility, and PAR. Methods One-hundred thirty-two patients with right MT (14.7±1.8 years, 48±6.9°) and 83 patients with left major TL/L (14.7±1.5 years, 46±6.6°) were retrospectively reviewed. On standing full-spine posteroanterior radiographs, the PAR was quantified by the left/right hemi-pelvis width ratio (L/R ratio); then the subjects in both MT and major TL/L groups were divided into two subgroups: L/R ratio ≤1 (pelvis rotated to the right, R-PAR group); and L/R ratio >1 (pelvis rotated to the left, L-PAR group). Comparisons of all variables were performed between the L- and R-PAR subgroups; correlation and regression analysis were carried out to identify the influencing factors of PAR. Results The majority of the MT and major TL/L patients (75.8% vs. 60.2%) displayed right pelvic rotation, which was in the same direction as the thoracic curve. The incidence of R-PAR was greater in the MT patients than the major TL/L ones (p=.016). Lumbar flexibility in MT patients with R-PAR was greater than in MT patients with L-PAR (0.96±0.27 vs. 0.81±0.33, p=.038), which was contrary to the findings in the major TL/L patients (L-PAR>R-PAR, 0.79±0.15 vs. 0.70±0.22, p=.024). In the MT patients with R-PAR, the L/R ratio showed significant positive correlations with the lumbar Cobb angle (r=0.424) as well as with the apex rotation (r=0.488), which was further identified as an influencing factor (R=0.418) of the PAR. Significant positive correlations between L/R ratio and thoracic apex rotation (r=0.361) also were detected. Conclusion The majority of AIS patients with right MT or left major TL/L curves were found to have PAR to the right, in the same direction as the thoracic curve. The lumbar flexibility and apex rotation significantly influenced the PAR direction and magnitude. Moreover, the pelvis might be involved in compensation for the MT deformity through its connection with the lumbar spine.

Nosiheptide is an archetypal thiopeptide antibiotic, possessing a characteristic macrocyclic core that contains a 6-membered heterocycle central to multiple azol(in)es and dehydroamino acids. The discovery of the ribosomal origin of thiopeptides revealed a unifying theme, showing that the structural complexity arises from post-translational modifications (PTMs) of precursor peptides. Thiopeptide framework formation proceeds via cyclodehydration/dehydrogenation (for azol(in)es), dehydration (for dehydroamino acids), and cycloaddition (for the central heterocycle domain). This common process has not been reproduced in vitro, partly due to the poorly understood logic of thiopeptide biosynthetic pathways. Utilizing nosiheptide biosynthesis as a model system, we herein consider how nature coordinates a number of highly interwined, common and specific PTMs to accomplish the complexity of ribosomally synthesized and post-translationally modified peptides.

A series of proline-derived C 1 -symmetric chiral tetradentate N ligands and their manganese complexes have been synthesized and characterized. Their applications in enantioselective epoxidations of α,β-enones were explored reaching good yields and up to 71% ee at room temperature.

SummaryThiostrepton (TSR), often referred as to a parent compound in the thiopeptide family, is a bimacrocyclic member that features a quinaldic acid (QA) moiety-containing side ring appended to the characteristic core system. QA biosynthesis requires an unusual ring-expanding conversion, showing a methyl transfer onto and a rearrangement of the indole part of L-tryptophan to give a quinoline ketone. Herein, we report that the process involves the activities of the radical methyltransferase TsrT, aminotransferase TsrA, dehydrogenase TsrE, and cyclase TsrD. TsrU, a stereospecific oxidoreductase, catalyzes the further conversion of the ketone into an enantiomerically pure S-alcohol. Elucidation of this chemistry, which is common in the biosynthesis of a number of thiopeptides sharing a QA side ring system, facilitates analog generation, as shown by the achievement of region-specific fluorination of thiostrepton with the improved antibacterial activity.

A series of Mn-complexes with tetradentate N 4 ligands, introducing aromatic groups into 2-pyridylmethyl positions of N,N′-dimethyl-N,N′-bis(2-pyridylmethyl)ethane-1,2-diamine ( mep ), N,N′-dimethyl-N,N′-bis(2-pyridylmethyl)cyclohexane- trans -diamine ( mcp ), have been synthesized and applied for epoxidation of olefins using H 2 O 2 as the oxidant. The Mn-complexes still possessed an octahedral mononuclear structure in a cis -α topology. These complexes showed good regioselectivity, high yields and turnover frequency (even up to 228,000 h −1 ) with low catalyst loading (0.1–0.01 mol%) for epoxidation of a family of olefins (including internal aromatic olefins, internal and terminal aliphatic olefins and diolefins).

A dimeric salen ligand derived from L-tartaric acid was synthesized through linking two salen units with 1,6-dibromohexane. The corresponding Ti complex was proved to be an efficient catalyst for asymmetric addition of trimethylsilyl cyanide to aldehydes, providing the corresponding optically active trimethylsilyl ether of cyanohydrins with moderate to good enantiomeric excesses and excellent yields under relatively low catalyst loading condition.

Two new tetradentate ligands derived from salen have been prepared and their titanium complexes are used as chiral catalysts in the enantioselective silylcyanation of aldehydes, which give the silyl ethers of cyanohydrins in moderate to good enantiomeric excesses.

A series of chiral salan (salalen) ligands, easily prepared from the aldehyde derived from chiral binaphthol, are effective ligands for the titanium-catalyzed asymmetric epoxidation of olefins with aqueous H2O2 as the oxidant. One of the titanium–salan complexes was determined by X-ray crystallography.

Chiral N -oxide salen ligands and their corresponding Al complexes were synthesized. Notably, the catalytic activity and asymmetric induction ability of the bifunctional N -oxide salen-Al for asymmetric cyanosilylation were compared with that of bi-component catalyst system including chiral pyrrolidine salen–Al complex and Ph 3 PO. Interestingly, introducing N -oxide group in salen unit could enhance the activity and enantioselectivity of bifunctional catalyst without further adding Ph 3 PO as co-catalyst and inverse configurations were generated from the two systems. In addition, excellent yields and high ee values could be obtained under milder conditions in bifunctional catalyst system compared with that of bi-component catalyst system.