A sterol analog inhibits hedgehog pathway by blocking cholesterylation of smoothened.

The hedgehog (Hh) signaling pathway has long been a hotspot for anti-cancer drug development due to its important role in cell proliferation and tumorigenesis. However, most clinically available Hh pathway inhibitors target the seven-transmembrane region (7TM) of smoothened (SMO), and the acquired drug resistance is an urgent problem in SMO inhibitory therapy. Here, we identify a sterol analog Q29 and show that it can inhibit the Hh pathway through binding to the cysteine-rich domain (CRD) of SMO and blocking its cholesterylation. Q29 suppresses Hh signaling-dependent cell proliferation and arrests Hh-dependent medulloblastoma growth. Q29 exhibits an additive inhibitory effect on medulloblastoma with vismodegib, a clinically used SMO-7TM inhibitor for treating basal cell carcinoma (BCC). Importantly, Q29 overcomes resistance caused by SMO mutants against SMO-7TM inhibitors and inhibits the activity of SMO oncogenic variants. Our work demonstrates that the SMO-CRD inhibitor can be a new way to treat Hh pathway-driven cancers.

Biomechanical evaluation of Percutaneous endoscopic posterior lumbar interbody fusion and minimally invasive transforaminal lumbar interbody fusion: a biomechanical analysis.

In order to analyze and evaluate the stability of lumbar spine and the risk of cage subsidence after different minimally invasive fusion operations, two finite element models Percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) and minimally invasive transforaminal lumbar interbody Fusion (MIS-TLIF) were established. The results showed that compared with MIS-TLIF, PE-PLIF had better segmental stability, lower pedicle screw rod system stress, and lower risk of cage subsidence. The results suggest that the cage with appropriate height should be selected to ensure the segmental stability and avoid the risk of the subsidence caused by the cage with large height.

Construction and validation of a predictive model for postoperative urinary retention after lumbar interbody fusion surgery.

BACKGROUND: Postoperative urine retention (POUR) after lumbar interbody fusion surgery may lead to recatheterization and prolonged hospitalization. In this study, a predictive model was constructed and validated. The objective was to provide a nomogram for estimating the risk of POUR and then reducing the incidence. METHODS: A total of 423 cases of lumbar fusion surgery were included; 65 of these cases developed POUR, an incidence of 15.4%. The dataset is divided into a training set and a validation set according to time. 18 candidate variables were selected. The candidate variables were screened through LASSO regression. The stepwise regression and random forest analysis were then conducted to construct the predictive model and draw a nomogram. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and the calibration curve were used to evaluate the predictive effect of the model. RESULTS: The best lambda value in LASSO was 0.025082; according to this, five significant variables were screened, including age, smoking history, surgical method, operative time, and visual analog scale (VAS) score of postoperative low back pain. A predictive model containing four variables was constructed by stepwise regression. The variables included age (ß = 0.047, OR = 1.048), smoking history (ß = 1.950, OR = 7.031), operative time (ß = 0.022, OR = 1.022), and postoperative VAS score of low back pain (ß = 2.554, OR = 12.858). A nomogram was drawn based on the results. The AUC of the ROC curve of the training set was 0.891, the validation set was 0.854 in the stepwise regression model. The calibration curves of the training set and validation set are in good agreement with the actual curves, showing that the stepwise regression model has good prediction ability. The AUC of the training set was 0.996, and that of the verification set was 0.856 in the random forest model. CONCLUSION: This study developed and internally validated a new nomogram and a random forest model for predicting the risk of POUR after lumbar interbody fusion surgery. Both of the nomogram and the random forest model have high accuracy in this study.

Percutaneous Endoscopic Posterior Lumbar Interbody Fusion with Unilateral Laminotomy for Bilateral Decompression Vs. Open Posterior Lumbar Interbody Fusion for the Treatment of Lumbar Spondylolisthesis.

Background: Endoscopic lumbar interbody fusion is a new technology that is mostly used for single-segment and unilateral lumbar spine surgery. The purpose of this study is to introduce percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) with unilateral laminotomy for bilateral decompression (ULBD) for lumbar spondylolisthesis and evaluate the efficacy by comparing it with open posterior lumbar interbody fusion (PLIF). Methods: Twenty-eight patients were enrolled in PE-PLIF with the ULBD group and the open PLIF group. The perioperative data of the two groups were compared to evaluate the safety of PE-PLIF with ULBD. The visual analog scale (VAS) back pain, VAS leg pain, and Oswestry Disability Index (ODI) scores of the two groups preoperatively and postoperatively were compared to evaluate clinical efficacy. Preoperative and postoperative imaging data were collected to evaluate the effectiveness of the operation. Results: No differences in baseline data were found between the two groups (p > 0.05). The operation time in PE-PLIF with the ULBD group (221.2 ± 32.9 min) was significantly longer than that in the PLIF group (138.4 ± 25.7 min) (p < 0.05), and the estimated blood loss and postoperative hospitalization were lower than those of the PLIF group (p < 0.05). The postoperative VAS and ODI scores were significantly improved in both groups (p < 0.05), but the postoperative VAS back pain score in the PE-PLIF group was significantly lower than that in the PLIF group (p < 0.05). The excellent and good rates in both groups were 96.4% according to MacNab's criteria. The disc height and cross-sectional area of the spinal canal were significantly improved in the two groups after surgery (p < 0.05), with no difference between the groups (p > 0.05). The fusion rates in PE-PLIF with the ULBD group and the PLIF group were 89.3% and 92.9% (p > 0.05), respectively, the cage subsidence rates were 14.3% and 17.9% (p > 0.05), respectively, and the lumbar spondylolisthesis reduction rates were 92.72 ± 6.39% and 93.54 ± 5.21%, respectively (p > 0.05). Conclusion: The results from this study indicate that ULBD can be successfully performed during PE-PLIF, and the combined procedure is a safe and reliable treatment method for lumbar spondylolisthesis.

Comparison of percutaneous endoscopic and open posterior lumbar interbody fusion for the treatment of single-segmental lumbar degenerative diseases.

BACKGROUND: Endoscopic lumbar interbody fusion has become an emerging technique. Some researchers have reported the technique of percutaneous endoscopic transforaminal lumbar interbody fusion. We propose percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) as an alternative approach. The purpose of this study was to assess the clinical efficacy of PE-PLIF by comparing percutaneous endoscopic and open posterior lumbar interbody fusion (PLIF). METHODS: Thirty patients were enrolled in each group. Demographic data, perioperative data, and radiological parameters were collected prospectively. The clinical outcomes were evaluated by visual analog scale (VAS) and Oswestry Disability Index (ODI) scores. RESULTS: The background data were comparable between the two groups. The mean operation time was longer in the PE-PLIF group. The PE-PLIF group showed benefits in less blood loss and shorter hospital stay. VAS and ODI scores significantly improved in both groups. However, the VAS score of low-back pain was lower in the PE-PLIF group. The satisfaction rate was 96.7% in both groups. The radiological outcomes were similar in both groups. In the PE-PLIF group, the fusion rate was 93.3%, and the cage subsidence rate was 6.7%; in the open PLIF group, the fusion and cage subsidence rates were 96.7% and 16.7%. There were minor complications in one patient in the PE-PLIF group and two in the open PLIF group. CONCLUSIONS: The current study revealed that PE-PLIF is safe and effective compared with open PLIF. In addition, this minimally invasive technique may enhance postoperative recovery by reducing tissue damage and blood loss.

Aculeaquamide A, cytotoxic paraherquamide from the marine fungus Aspergillus aculeatinus WHUF0198.

A new paraherquamide named aculeaquamide A (1) was isolated from an EtOAc extract of Aspergillus aculeatinus WHF0198 culture media together with five known compounds. The structures of the isolated compounds were elucidated by analysis of NMR and MS data, and the absolute configurations of compound 1 was confirmed by CD spectroscopic methods. All isolated compounds were evaluated for their cytotoxicity against three human cancer cell lines, Bel-7402, A549, and HCT-116. Compounds 1 and 2 showed cytotoxicity against Bel-7402 with IC50 values of 3.3 and 1.9 µM, respectively.

A New Fusicoccane-Type Norditerpene and a New Indone from the Marine-Derived Fungus Aspergillus aculeatinus WHUF0198.

A new norditerpene named aculeaterpene A (1) and a new indone named aculeaindone A (2), along with eight known compounds 3-10 were isolated from the culture extract of Aspergillus aculeatinus WHUF0198. The structural characterization of compounds 1 and 2 were performed by spectroscopic analysis, including 1D and 2D NMR and HR-ESI-MS experiments, whereas the absolute configurations were determined by comparing their experimental or calculated ECD spectra. Compound 1 was the first report of fusicoccane-based norditerpene, in which the C-20 was degraded and tured into a hydroxy group.

Treatment of cervical spine metastasis with minimally invasive cervical spondylectomy: A case report and literature review.

BACKGROUND: Cervical spondylectomy for the treatment of cervical tumors is traumatic, causes bleeding, and is risky. This study reports on the experience with minimally invasive cervical spondylectomy for a cervical metastasis and reviewed the literature on cervical spondylectomy. The purpose was to reduce the risk and trauma of spondylectomy. CASE SUMMARY: A 60-year-old woman presented with cervical pain and radiating pain in the left upper limb for more than 2 mo. Preoperative diagnosis was C4 metastasis of thyroid cancer. Preoperative visual analogue scale score was 5. American Spinal Cord Injury Association (ASIA) grade was E. Tomita classification was 7. Weinstein-Boriani-Biagini (WBB) classification was A-D, 3-9. Tomita score was 5. Modified Tokuhashi score was 9. Spinal instability neoplastic score (SINS) was 13. The patient underwent minimally invasive cervical spondylectomy on September 28, 2017. The operative time was 200 min; the estimated blood loss was 1200 mL. The operation was successful, without complications. The postoperative visual analogue scale score was 0. The patient remained classified as ASIA grade E at the last follow-up. She accepted regular iodine-131 therapy postoperatively. The serum thyroglobulin (Tg) level of this patient was 299.02 ng/mL at 1 mo after the operation and was 13.57 ng/mL at the last follow-up. There was no local recurrence at the 25-mo follow-up, according to images, single-photon emission computed tomography, and serum Tg levels. Obvious ossification and solid fusion of C3-C5 were found at the last follow-up. CONCLUSION: Minimally invasive cervical spondylectomy with tubular retractor could minimize soft tissue trauma, intraoperative traction injury, and paraspinal muscle injury, accelerating postoperative recovery. This technique requires a rich experience in cervical spine surgery with tubular retractors, so that surgeons can visualize the anatomical structure in a small field.

Synthesis of ursodeoxycholic acid from plant-source (20S)-21-hydroxy-20-methylpregn-4-en-3-one.

A novel synthetic route of producing ursodeoxycholic acid (UDCA) was developed through multiple reactions from cheap and commercially available bisnoralcohol (BA). The key reaction conditions, including solvents, bases and reaction temperatures of the route were investigated and optimized. In the straightforward route for preparation of UDCA, most of the reaction steps have high conversions with average yields of 91%, and overall yield up to 59% (6 steps) from the plant-source BA. Especially in the last step of reduction and hydrolysis, there are five functional groups converted with calcd 97% per conversion in one-pot reaction. This promising route offers economical and efficient strategies for potential large-scale production of UDCA.

[C-MYC Gene and Protein Expression in Paraffin Wax of T Lymphoblastic Lymphoma and Leukemia Patients and Its Effect on the Prognosis].

OBJECTIVE: To explore the relevance between the expression of C-MYC gene and protein of patients with T lymphoblastic lymphoma and leukemia(T-LBL/ALL) and its effect on the prognosis. METHODS: Paraffin specimens from 60 cases of T-LBL/ALL with detailed follow-up during May 2005 to May 2016 were selected as study group; at same time 20 cases of reactive hyperplasia (RH) of lymphonuedes were selected as control group. The immunohistochemical EnVision method was used to mark the terminal deoxynucleotidyl transferase (TDT), myeloperoxidase (MPO), Ki-67 and C-MYC immune tissue. RESULTS: C-MYC gene rupture and copy number increase did not occur in 20 cases of RH.The expression of C-MYC protein did not correlate with C-MYC gene copy number increase. The expression rate of C-MYC protein was 66.7% (40/60), and 20 cases of lymph node RH was all negative (0/20), as compared with the positive expression rate of protein C-MYC, the difference was statistically significant (P<0.05). The Ki-67 positive index and mediastinal bloadening had influence on the expression of C-MYC protein (P<0.05), the sex, primary site, symptoms, age, AnnArbor stage and lactate dehydrogenase (LDH) level and bone marrow involvement have no influence on it, there was no statistically significant difference (P>0.05). The 8q24 chromosome breakage occurred in 6 cases (10%), and the number of copies increased in 11 cases (18.3%). C-MYC gene copy number increase and C-MYC gene rupture in a total 20 cases of reactive hyperplasia of lymph nodes did not occur. CONCLUSION: C-MYC gene may play an important role on the development of T-LBL/ALL. It can be an independent prognosis factor.

Tuberculous Spondylitis Following Kyphoplasty: A Case Report and Review of the Literature.

Tuberculous spondylitis of the augmented vertebral column following percutaneous vertebroplasty or kyphoplasty has rarely been described. We report an unusual case of tuberculous spondylitis diagnosed after percutaneous kyphoplasty (PKP). A 61-year-old woman presented to our institution complaining of back pain following a fall 7 days before. Radiologic studies revealed an acute osteoporotic compression L1 fracture. The patient denied history of pulmonary tuberculosis (TB) and there were no signs of infection. The patient was discharged from hospital 4 days after undergoing L1 PKP with a dramatic improvement in her back pain. Two years later, the patient was readmitted with a 1 year history of recurrent back pain. Imaging examinations demonstrated long segmental bony destruction involving L1 vertebra with massive paravertebral abscess formation. The tentative diagnosis of tuberculous spondylitis was made, after a serum T-SPOT. The TB test was found to be positive. Anterior debridement, L1 corpectomy, decompression, and autologous rib graft interposition, and posterior T8-L4 instrumentation were performed. The histologic examination of the resected tissue results confirmed the diagnosis of spinal TB. Anti-TB medications were administered for 12 months and the patient recovered without sequelae. Spinal TB and osteoporotic vertebral compression fractures are similar clinically and radiologically. Spinal surgeons should consider this disease entity to avoid misdiagnosis or complications. Early surgical intervention and anti-TB treatment should be instituted as soon as the diagnosis of spinal TB after vertebral augmentation is made.

Conversion of fibroblasts to neural cells by p53 depletion.

Conversion from fibroblasts to neurons has recently been successfully induced. However, the underlying mechanisms are poorly understood. Here, we find that depletion of p53 alone converts fibroblasts into all three major neural lineages. The induced neuronal cells express multiple neuron-specific proteins and generate action potentials and transmitter-receptor-mediated currents. Surprisingly, depletion does not affect the well-known tumorigenic p53 target, p21. Instead, knockdown of p53 upregulates neurogenic transcription factors, which in turn boosts fibroblast-neuron conversion. p53 binds the promoter of the neurogenic transcription factor Neurod2 and regulates its expression during fibroblast-neuron conversion. Furthermore, our method provides a high efficiency of conversion in late-passage fibroblasts. Genome-wide transcriptional analysis shows that the p53-deficiency-induced neurons exhibit an expression profile different from parental fibroblasts and similar to control-induced neurons. The results may help to understand and improve neural conversion mechanisms to develop robust neuron-replacement therapy strategies.

Metabolic profiles of prokaryotic and eukaryotic communities in deep-sea sponge Neamphius huxleyi [corrected]. indicated by metagenomics.

The whole metabolism of a sponge holobiont and the respective contributions of prokaryotic and eukaryotic symbionts and their associations with the sponge host remain largely unclear. Meanwhile, compared with shallow water sponges, deep-sea sponges are rarely understood. Here we report the metagenomic exploration of deep-sea sponge Neamphius huxleyi [corrected] . at the whole community level. Metagenomic data showed phylogenetically diverse prokaryotes and eukaryotes in Neamphius huxleyi [corrected]. MEGAN and gene enrichment analyses indicated different metabolic potentials of prokaryotic symbionts from eukaryotic symbionts, especially in nitrogen and carbon metabolisms, and their molecular interactions with the sponge host. These results supported the hypothesis that prokaryotic and eukaryotic symbionts have different ecological roles and relationships with sponge host. Moreover, vigorous denitrification, and CO2 fixation by chemoautotrophic prokaryotes were suggested for this deep-sea sponge. The study provided novel insights into the respective potentials of prokaryotic and eukaryotic symbionts and their associations with deep-sea sponge Neamphius huxleyi [corrected].

[Experimental investigation of the chemical effect of direct current arc plasma igniter].

To study the chemical effect of direct current arc plasma igniter, the emission spectrum of plasma jet was measured, and the active particles produced by the interaction of plasma jet with atmospheric air were analyzed. The NO and CO volume fractions were measured quantificationally by smoke analyzer at the 8cm downstream the plasma igniter exit, and the changing law between arc current and NO, CO volume fractions was obtained. The results show that the plasma jet interacting with atmospheric air produced active particles (H, O, N), charged particles (O2 +, N2+), and excited particles (N2 (A3), N2 (B3), N2 (C3), N2 (a1), O2 (a1), O2 (b1)). The NO and CO volume fractions increased with rising of are current and feedstock argon flow rate.

Connection of DFT molecular orbital eigenvalues with the observable oxidation potentials/oxidation energies.

It is demonstrated that the negative highest occupied molecular orbital eigenvalues of a molecule S in the gas phase, -HOMO(S,g), and in solution, -HOMO(S,s), and the negative lowest unoccupied molecular orbital eigenvalue of its cation S(+) in solution, -LUMO(S(+),s), are good approximations to the oxidation energy, the energy for removing an electron out of a molecule in solution. This observation is based on the DFT calculations using the B3LYP exchange-correlation functional with a basis set of 6-311+G(d,p) and the polarizable continuum model (PCM) for computing solvation energies for a set of 22 middle-size molecules/radicals.

[Progress on the research of acupuncture for smoking cessation in foreign and domestic].

Up to December of 2011, the domestic and overseas literatures of acupuncture for smoking cessation are searched and collected through Pubmed, CNKI, Wanfang and Chongqing VIP databases, which are analyzed from treatment method, action mechanism, influencing factors of efficacy and efficacy evaluation research and so on. The result shows that (1) acupuncture has positive effect on smoking cessation, and large clinical trials has been carried out. However, most of them are needling methods and the short-term effect observation, which lack of long-term efficacy research of withdrawal symptoms, especially continuous withdrawal symptoms and index of life quality. (2) Because of unified clinical treatment, manipulation standard and curative effect criteria, it is difficult to make comparison among them. (3) The study of mechanism on acupuncture for smoking cessation is not of in-depth. In future, clinical research project of acupuncture on smoking cessation should be optimized and regulated, including the unified treatment, manipulation standard and curative effect criteria, also long-term researches with large-scale samples should be launched to confirm effect ofacupuncture for smoking cessation to further discuss its action mechanism.

Impact of mixed land-use practices on the microbial water quality in a subtropical coastal watershed.

Surface runoff water is an important non-point source of fecal pollution to downstream water; however, there is a lack of systematic studies on the microbial quality of surface runoff water from watersheds with mixed land uses. In this study water samples from 12 surface runoff holding water bodies (SRW), which collected runoff from various patterns of land use within the St. Lucie watershed along the southeastern coastline of Florida, were collected monthly for 22 months. The concentration of fecal indicator bacteria (FIB) and frequency of detection of Salmonella and host specific markers (HF183, CF128, CF193, and HS-esp) were determined, and their associations with land use, rainfall, and water physico-chemical parameters were investigated. Higher FIB concentrations were observed from urban land and cattle ranch sites. Within the same primary land use pattern, different sub-patterns did not have the same level of FIB: golf communities contributed less to fecal pollution than residential areas, and plant nursery sites contained relative higher FIB concentrations than other agricultural sites. Salmonella, CF128, and CF193 markers were more frequently detected from the cattle ranch sites. In contrast the frequency of detecting human specific markers (HF183 and HS-esp) was much higher in residential sites. Rainfall positively affected the concentration of FIB and occurrence of Salmonella, possibly by providing more inputs or mobilizing the sources from sediments. Water temperature, dissolved organic carbon (DOC), and nutrient levels were positively correlated with FIB concentrations and occurrence in SRW, possibly by promoting their growth and survival. This study indicated the need for site specific mitigation strategies to improve SRW and downstream water quality.

[Experimental investigation on plasma assistant combustion actuator in argon/air].

In order to obtain the characteristics of argon/air plasma assistant combustion actuators, experiments of three different actuators with normal, paratactic and meshy electrode configurations were respectively performed in argon/air mixture firstly, the results showed that the shape of electrode has little influence on the discharge characteristics. Then normal electrode was applied to study spectrum and discharge characteristics under the condition of 100% air and 10% argon/90% air. The comparison showed that, though in mixture the law of discharge characteristic was the same as that of pure air, discharge current and emission spectrum were strengthened, and initial discharge voltage reduced from 27 to 24 kV.

[Study of ignition characteristic of DC voltage plasma ignitor].

The changing law between interelectrode current, discharge characteristic and jet characteristic of plasma ignitor under different inlet Ar pressure and working current was researched by adopting self-made plasma ignitor. Still, four channels CCD spectrometer was adopted to measure the spectrum characteristic at the exit of ignitor and electron temperature of plasma was calculated according to the spectrum characteristic. The results show that the interelectrode current gradually reduced with rising inlet Ar pressure; The jet length of plasma ignitor firstly increased then reduced with rising inlet Ar flowrate, and also increased with rising working current; The working current of plasma ignitor reduced with rising inlet Ar flowrate, and increased with rising source output current; the electron temperature of plasma ignitor jet increased with rising working current and reduced with rising Ar flowrate. The research results are of certain guidance meanings and reference values for the practical application of plasma ignition system in aeroengine.