MicroRNAs（miRNAs） are small,non-coding RNAs that negatively adjust gene expression in multifarious biological processes.However,the regulatory effects of miRNAs on Schwann cells remain poorly ...understood.Previous microarray analysis results have shown that miRNA expression is altered following sciatic nerve transaction,thereby affecting proliferation and migration of Schwann cells.This study investigated whether miR-148b-3p could regulate migration of Schwann cells by directly targeting cullin-associated and neddylation-dissociated 1（Cand1）.Up-regulated expression of miR-148b-3p promoted Schwann cell migration,whereas silencing of miR-148b-3p inhibited Schwann cell migration in vitro.Further experiments confirmed that Candl was a direct target of miR-148b-3p,and Candl knockdown reversed suppression of the miR-148b-3p inhibitor on Schwann cell migration.These results suggested that miR-148b-3p promoted migration of Schwann cells by directly targeting Candl in vitro.
DNA vector-based Stat3-specific RNA interference (si-Stat3) blocks Stat3 signalling and inhibits prostate tumour growth. However, the antitumour activity depends on the efficient delivery of ...si-Stat3. The effects on the growth of mouse prostate cancer cells of si-Stat3 delivered by hydroxyapatite were determined in this study. RM-1 tumour blocks were transplanted into C57BL/6 mice. CaCl₂-modified hydroxyapatite carrying si-Stat3 plasmids were injected into tumours, and tumour growth and histology were determined. The expression levels of Stat3, pTyr-Stat3, Bcl-2, Bax, Caspase3, VEGF and cyclin D1 were measured by western blot analysis. Amounts of apoptosis in cancer cells were analysed with immunohistochemistry and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) assay. The results showed that hydroxyapatite-delivered si-Stat3 significantly suppressed tumour growth up to 74% (P < 0.01). Stat3 expression was dramatically downregulated in the tumours. The immunohistochemistry and TUNEL results showed that si-Stat3-induced apoptosis (up to 42%, P < 0.01). The Stat3 downstream genes Bcl-2, VEGF and cyclin D1 were also strongly downregulated in the tumour tissues that also displayed significant increases in Bax expression and Caspase3 activity. These results suggest that hydroxyapatite can be used for the in vivo delivery of plasmid-based siRNAs into tumours.
This paper investigates the problem of target position estimation with a single-observer passive coherent location（PCL） system. An approach that combines angle with time difference of arrival（ATDOA） ...is used to estimate the location of a target. Compared with the TDOA-only method which needs two steps, the proposed method estimates the target position more directly. The constrained total least squares（CTLS） technique is applied in this approach. It achieves the Cramer–Rao lower bound（CRLB） when the parameter measurements are subject to small Gaussian-distributed errors. Performance analysis and the CRLB of this approach are also studied. Theory verifies that the ATDOA method gets a lower CRLB than the TDOA-only method with the same TDOA measuring error. It can also be seen that the position of the target affects estimating precision.At the same time, the locations of transmitters affect the precision and its gradient direction.Compared with the TDOA, the ATDOA method can obtain more precise target position estimation.Furthermore, the proposed method accomplishes target position estimation with a single transmitter,while the TDOA-only method needs at least four transmitters to get the target position. Furthermore,the transmitters＇ position errors also affect precision of estimation regularly.
Objective To investigate the association between ambient air pollution and hospital emergency admissions in Beijing. Methods In this study, a semi-parametric generalized additive model （GAM） was used ...to evaluate the specific influences of air pollutants （PM10, SO2, and NO2） on hospital emergency admissions with different lag structures from 2009 to 2011, the sex and age specific influences of air pollution and the modifying effect of seasons on air pollution to analyze the possible interaction. Results It was found that a 10μg/m3 increase in concentration of PMlo at lag 03 day, SO2 and NO2 at lag 0 day were associated with an increase of 0.88%, 0.76%, and 1.82% respectively in overall emergency admissions. A 10 lag/m3 increase in concentration of PM10, SO2 and NO2 at lag 5 day were associated with an increase of 1.39%, 1.56%, and 1.18% respectively in cardiovascular disease emergency admissions. For lag 02, a 10 μg/m3 increase in concentration of PM10, SO2 and NO2 were associated with 1.72%, 1.34%, and 2.57% increases respectively in respiratory disease emergency admissions. Conclusion This study further confirmed that short-term exposure to ambient air pollution was associated with increased risk of hospital emergency admissions in Beijing.
Differential expression of mi RNAs occurs in injured proximal nerve stumps and includes mi RNAs that are firstly down-regulated and then gradually up-regulated following nerve injury.These mi RNAs ...might be related to a Schwann cell phenotypic switch.mi R-30 c,as a member of this group,was further investigated in the current study.Sprague-Dawley rats underwent sciatic nerve transection and proximal nerve stumps were collected at 1,4,7,14,21,and 28 days post injury for analysis.Following sciatic nerve injury,mi R-30 c was down-regulated,reaching a minimum on day 4,and was then upregulated to normal levels.Schwann cells were isolated from neonatal rat sciatic nerve stumps,then transfected with mi R-30 c agomir and co-cultured in vitro with dorsal root ganglia.The enhanced expression of mi R-30 c robustly increased the amount of myelin-associated protein in the co-cultured dorsal root ganglia and Schwann cells.We then modeled sciatic nerve crush injury in vivo in Sprague-Dawley rats and tested the effect of perineural injection of mi R-30 c agomir on myelin sheath regeneration.Fourteen days after surgery,sciatic nerve stumps were harvested and subjected to immunohistochemistry,western blot analysis,and transmission electron microscopy.The direct injection of mi R-30 c stimulated the formation of myelin sheath,thus contributing to peripheral nerve regeneration.Overall,our findings indicate that mi R-30 c can promote Schwann cell myelination following peripheral nerve injury.The functional study of mi R-30 c will benefit the discovery of new therapeutic targets and the development of new treatment strategies for peripheral nerve regeneration.
Through analyzing the braking system of mine hoist and the current testing method of braking parameters, this paper proposes a direct test method for braking parameters when the mine hoist runs at ...low speed. The inspection and display of braking torque, idle motion time and braking stroke can be achieved by a two-stage computer system consisted of SCM AT89S52 and PC computer.
Background Sunitinib has been proved an effective new option for treatment of metastatic renal cell carcinoma （mRCC）. Analysis of clinical data of 22 patients, who were exposed to sunitinib for at ...least 1 year, was conducted to evaluate the long-term efficacy and safety of sunitinib for the treatment of mRCC. Methods A total of 54 patients with mRCC were treated with sunitinib malate, 50 mg/d orally, on a 4-weeks-on and 2-weeks-off dosing schedule in Peking University First Hospital. Treatment continued until disease progression, unacceptable adverse events （AEs）, or death. Among them, 22 patients continued treatment for at least I year. The clinical data of these 22 patients were prospectively collected for analysis. AEs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0. Tumor response was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors. Results Median progression-free survival was 19.5 months until last follow-up. The best efficacy results achieved were complete response, partial response, and stable disease for 2, 9, and 11 patients, respectively. Objective response rate was 50%. The most common AEs were hand-foot syndrome （95%） and hypertension （91%）. Other common AEs were thyroid-stimulating hormone elevation （82%）, platelet decrease （77%）, and loss of appetite （77%）. Only one patient withdrew from treatment for cardiac infarction. Another nine patients experienced dose modifications or short-term suspensions. Conclusion Long-term exposure to sunitinib malate showed encouraging efficacy in the treatment of mRCC. At the same time, the tolerability was good.
Arthrogryposis,renal dysfunction and cholestasis(ARC)syndrome(OMIM 208085)is an autosomal recessive disorder that is caused by mutations in 2 interacting genes VPS33B and VIPAS39.Mutations in VPS33B ...gene account for most cases of ARC.As low or normal gamma-glutamyl transpeptidase(GGT)activity has been described in all patients with ARC syndrome identified so far,ARC syndrome is a possible diagnosis for low GGT cholestasis.Here we describe a Chinese patient with neonatal cholestasis and a high GGT level in three consecutive tests.She had other typical manifestations of ARC syndrome,including arthrogryposis multiplex congenita,renal involvement and ichthyosis.Genetic study of the VPS33B gene further confirmed the diagnosis by identification of compound heterozygosity of two known disease-causing mutations,c.403+2T>A and c.1509-1510insG.The mechanism of high GGT in this patient is unclear.Nevertheless,this case indicates that ARC syndrome cannot be excluded from the differential diagnosis of neonatal cholestasis even if high GGT activity is found.
Fractional thermoelastic models have been formulated from classical thermoelasticity or extended thermoelasticity, i.e. Lord-Shulman or Green-Naghdi theory. It seems different authors have different ...physical pictures on such topic, for instance, there exist several approaches from Lord-Shulman model to fractional order ones. This work is aimed to simplify the theoretical frameworks by clarifying connections between existed models. To this end, a new fractional thermoelasticity is established by directly extending classical thermoelasticity with the aids of new forms of fractional derivatives, i.e. Caputo-Fabrizio, Atangana–Baleanu and Tempered-Caputo definitions. All definitions are introduced into Fourier's law by a unified way with relaxation time incorporated. Theoretically, the present model may be simplified into existed fractional theory. Numerically, it has the capability of describing thermoelastic behaviors from fractional Lord-Shulman models. For numerical studies, Laplace transform method is adopted, and a two-layered structure subjected to thermal heating is considered, from which the effects of different fractional derivatives and relaxation time are firstly uncovered. And then, the influences of material constants of two layers, especially with interfacial conditions, are discussed in detail. Finally, some concluding remarks are made.
•A new fractional thermoelasticity is established using CF, AB and TC fractional derivative definitions.•All fractional derivatives are introduced into Fourier's law by a unified way with relaxation time.•The present model has the capability of describing thermoelatic behaviors of fractional LS models.•The effects of different fractional derivatives and material constants on transient responses are discussed.
Sensory neurons are distinguished by distinct signaling networks and receptive characteristics. Thus, sensory neuron types can be defined by linking transcriptome-based neuron typing with the sensory ...phenotypes. Here we classify somatosensory neurons of the mouse dorsal root ganglion （DRG） by high-coverage single-cell RNA-sequencing （10 950 ±1 218 genes per neuron） and neuron size-based hierarchical clustering. Moreover, single DRG neurons responding to cutaneous stimuli are recorded using an in vivo whole-cell patch clamp technique and classified by neuron-type genetic markers. Small diameter DRG neurons are classified into one type of low-threshold mechanoreceptor and five types of mechanoheat nociceptors （MHNs）. Each of the MHN types is further categorized into two subtypes. Large DRG neurons are categorized into four types, including neurexophilin 1-expressing MHNs and mechanical nociceptors （MNs） expressing BAil-associated protein 2-like I （Baiap211）. Mechanoreceptors expressing trafficking protein particle complex 3-like and Baiap211-marked MNs are subdivided into two subtypes each. These results provide a new system for cataloging somatosensory neurons and their transcriptome databases.
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