Effects of Nanocomposite Derivatives of Ni-Fe, Ni-Co, Ni-Co-Fe Prussian Blue Analogues on the Thermal Decomposition Performance of Nitrocellulose.

The incorporation of nanomaterials generated from Prussian blue (PB) derivatives has emerged as a promising strategy to significantly improve the properties of energetic materials. In this study, we comprehensively investigated the influence of nanomaterials derived from PB on the thermal decomposition characteristics of energetic materials. To achieve this goal, we prepared nanomaterials using coprecipitation and heat treatment methods with PB derivatives as catalysts. Advanced techniques such as X-ray diffraction, scanning electron microscopy, transmission electron microscopy, Brunauer-Emmett-Teller (BET) analysis for specific surface area and pore size, and X-ray photoelectron spectroscopy were employed to thoroughly characterize these nanomaterials. Differential scanning calorimetry was used to assess the thermal behavior of nitrocellulose (NC), and the relevant kinetic parameters were determined through thermal decomposition kinetics calculations and analysis. This work revealed the influence of catalysts on the NC decomposition process and provided comprehensive insights into the effect of integrating nanomaterials derived from PB derivatives on the thermal decomposition performance of NC. The results of this work demonstrated the possibility of using nanomaterials generated from PB derivatives as effective catalysts to enhance the thermal decomposition characteristics of NC, offering interesting opportunities for their application in the field of high-energy materials.

Influence of Various Flame Temperatures of the Gun Propellant on the Effectiveness of the Erosion Inhibitor and Relevant Mechanisms.

The development of high energy gun propellants faces significant challenges in terms of erosion, partly due to the inadequate effectiveness of erosion inhibitors. In this paper, the influence of quite different flame temperature of five gun-propellants on erosion-reducing efficiency of four representative inhibitors materials (talc/TiO2/ PDMS/Paraffin) were studied in vented erosion vessel tester. From aspects of morphologies and element compositions of erode steel samples, as well as the pressure and heat generated by propellant burning, the relevant erosion-reducing processes and mechanisms were discussed. The results indicated that erosion inhibitors should be appropriately selected according to the type of gun propellant. The erosion of gun propellants having extremely high flame temperature of 3810 K were hardly reduced using talc, TiO2, and PDMS inhibitors, which can generate numerous solid particles aggravating the melt-wipe process. While paraffin exhibits a uniquely positive erosion-reducing efficiency for the gun propellant having a flame temperature of 3810 K, that was attributed to the mitigated melt-wipe process. The inference was further supported by the high-volume cooling gas, resulting from the higher burning pressure of propellants loading with paraffin and excellent heat absorption capacity of paraffin tested with propellants having higher propellant flame temperature. The obtained results indicated that the factors of flame temperature of gun propellants should be taken into the design and composition optimization of an effective inhibitor. This work could provide potential reference for the development of future novel inhibitors, which serves as high energy gun propellants.

Advanced fabrication approach for innovative triple base propellants with enhanced continuous fracture resistance.

This paper initially contrasts the solvent-based and solventless molding processes, subsequently optimizing a sustainable and efficient solventless molding route for both STP and SLTP. Key physicochemical parameters such as extrusion rate, residual volatile solvents, moisture content, and apparent density of both propellant types are meticulously compared. Furthermore, the orientation of crystal particles and the structure of the matrix-bound interface are analyzed. Comprehensive examination of triaxial progressive failure phenomena-including static thermal mechanical responses, quasi-static structural deformation, and dynamic structural damage-is conducted, leading to the formulation of a damage mechanism and model. Subsequently, a structural mechanics model for nitroguanidine micrometer rod-reinforced triple base propellants is established, quantitatively evaluating the influence of nitroguanidine crystal arrangement angles on the structural strength of both propellant types. This study furnishes a theoretical foundation for specialized internal structural and mechanical behaviors through theoretical computations.

PAICS ubiquitination recruits UBAP2 to trigger phase separation for purinosome assembly.

Purinosomes serve as metabolons to enhance de novo purine synthesis (DNPS) efficiency through compartmentalizing DNPS enzymes during stressed conditions. However, the mechanism underpinning purinosome assembly and its pathophysiological functions remains elusive. Here, we show that K6-polyubiquitination of the DNPS enzyme phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthetase (PAICS) by cullin-5/ankyrin repeat and SOCS box containing 11 (Cul5/ASB11)-based ubiquitin ligase plays a driving role in purinosome assembly. Upon several purinosome-inducing cues, ASB11 is upregulated by relieving the H3K9me3/HP1α-mediated transcriptional silencing, thus stimulating PAICS polyubiquitination. The polyubiquitinated PAICS recruits ubiquitin-associated protein 2 (UBAP2), a ubiquitin-binding protein with multiple stretches of intrinsically disordered regions, thereby inducing phase separation to trigger purinosome assembly for enhancing DNPS pathway flux. In human melanoma, ASB11 is highly expressed to facilitate a constitutive purinosome formation to which melanoma cells are addicted for supporting their proliferation, viability, and tumorigenesis in a xenograft model. Our study identifies a driving mechanism for purinosome assembly in response to cellular stresses and uncovers the impact of purinosome formation on human malignancies.

Effect of bFGF gel nano-sustained-release technology on rehabilitation effect of adult heart valve replacement.

the Due to the rapid improvement of economic level, aging and lifestyle changes, the incidence of valvular heart disease continues to increase, and the bFGF gel nano sustained-release technology plays an important role in the rehabilitation of adult heart valve replacement patients. The purpose of this article is to investigate the effect of bFGF gel nano-slow release technology on the rehabilitation effect of adult heart valve replacement patients. The research object was selected from all cases of valve replacement surgery from January 2019 to January 2020, and 216 patients were divided into experimental group and control group, the experimental group carried out the sustained release of bFGF gel nanospheres. The experimental group was 49.76±8.13 years old, including 94 cases of rheumatic heart disease, 13 cases of degenerative valvular disease, and 3 cases of congenital valvular disease, a total of 110 cases. Heart performance tests were performed respectively. The results showed that the incidence of atrial fibrillation, left ventricular hypertrophy and ST-segment depression of 0.1m V in the experimental group were 32.19%, 34.48%, and 19.84%, while the corresponding data in the control group were 62.78%, 52.07%, and 45.87%. It can be seen that bFGF gel nano sustained-release technology is of great significance for the rehabilitation of adult heart valve replacement patients.

Long noncoding RNA BCRP3 stimulates VPS34 and autophagy activities to promote protein homeostasis and cell survival.

BACKGROUND: Autophagy plays important roles in cell homeostasis and protein quality control. Long non-coding RNAs (lncRNAs) have been revealed as an emerging class of autophagy regulators, but the majority of them function in regulating the expression of autophagy-related genes. LncRNAs that directly act on the core autophagic proteins remain to be explored. METHODS: Immunofluorescence staining and Western blotting were used to evaluate the function of BCRP3 in autophagy and aggrephagy. RNA immunoprecipitation and in vitro RNA-protein binding assay were used to evaluate the interaction of BCRP3 with its target proteins. Phosphatidylinositol 3-phosphate ELISA assay was used to quantify the enzymatic activity of VPS34 complex. qRT-PCR analysis was used to determine BCRP3 expression under stresses, whereas mass spectrometry and Gene Ontology analyses were employed to evaluate the effect of BCRP3 deficiency on proteome changes. RESULTS: We identified lncRNA BCRP3 as a positive regulator of autophagy. BCRP3 was mainly localized in the cytoplasm and bound VPS34 complex to increase its enzymatic activity. In response to proteotoxicity induced by proteasome inhibition or oxidative stress, BCRP3 was upregulated to promote aggrephagy, thereby facilitating the clearance of ubiquitinated protein aggregates. Proteomics analysis revealed that BCRP3 deficiency under proteotoxicity resulted in a preferential accumulation of proteins acting in growth inhibition, cell death, apoptosis, and Smad signaling. Accordingly, BCRP3 deficiency in proteotoxic cells compromised cell proliferation and survival, which was mediated in part through the upregulation of TGF-ß/Smad2 pathway. CONCLUSIONS: Our study identifies BCRP3 as an RNA activator of the VPS34 complex and a key role of BCRP3-mediated aggrephagy in protein quality control and selective degradation of growth and survival inhibitors to maintain cell fitness.

Virtual reality for the measurement of SVV and SVH during static head tilt in healthy adults: a novel vestibular test.

BACKGROUND AND OBJECTIVE: Few previous studies have used virtual-reality (VR) technology to measure subjective visual vertical (SVV) and subjective visual horizontal (SVH) during static head tilt (0°, 30°, 45°, 60° and 90°). We propose a novel vestibular test for measuring the normal range of SVV and SVH during static head tilt in healthy adults. METHODS: Eighty healthy adults were included in the study. SVV and SVH were calculated in nine head positions. RESULTS: With head tilt 90° to the right, SVV skewed to the right, and SVH skewed upward. With head tilt 90° to the left, SVV skewed to the left, and SVH skewed downward. SVV was asymmetrical only at a head tilt of 90°. SVV and SVH were similar at all degrees of head tilt, except for 30° to the right, 45° to the left, and 0°. CONCLUSIONS: VR measurements showed that SVV and SVH differed at various degrees of static head tilt. The standardized protocol proposed here may be used to establish a reference range for utricle function when evaluating acute, unilateral vestibular lesions.

Association Analysis of HIMP and SHIMP Quantitative Parameters in Patients With Vestibular Neuritis and Healthy Participants.

Background: The Head Impulse Paradigm (HIMP) and Suppression Head Impulse Paradigm (SHIMP) are objective, quantitative methods that directly test the vestibulo-ocular reflex (VOR) and are increasingly becoming a standard in evaluating patients with vestibular disorders. Objective: The main objective was to assess the correlations between HIMP and SHIMP parameters in patients with superior vestibular neuritis (VN) and healthy participants. Additionally, the correlations between the parameters of each method were analyzed. Methods: A retrospective cohort, non-randomized study was designed. HIMP and SHIMP were performed on 40 patients with VN and 20 healthy participants (40 ears). HIMP and SHIMP parameters were measured and calculated. Pearson's or Spearson's correlations were used to establish the associations among them. Results: A strong positive correlation was found between HIMP and SHIMP gain (Pearson's r = 0.957, p = 0.000), while strong negative correlations were detected between HIMP and SHIMP saccade amplitudes (r = -0.637, p = 0.000) and percentages of overt saccades (r = -0.631, p = 0.000). In HIMP, strong and moderate positive correlations were identified between gain and saccade amplitude (R 2 = 0.726, p = 0.000) and gain and saccade percentage (R 2 = 0.558, p = 0.000), respectively. By contrast, an extremely weak positive correlation was observed between gain and latency (R 2 = 0.053, p = 0.040). In SHIMP, strong and moderate positive correlations were found between gain and saccade percentage (R 2 = 0.723, p = 0.000) and gain and saccade amplitude (R 2 = 0.525, p = 0.000), respectively, but no correlation was detected between gain and latency (R 2 = 0.006, p = 0.490). Conclusions: HIMP and SHIMP-related parameters were highly correlated (inter-method). Within each method (intra-method), moderate to strong correlations in VOR assessment were observed. These results further contribute to our understanding of the relationship between HIMP and SHIMP as well as to the diagnosis.

Application of Supercritical CO2 Foaming Technology for Waste Double-Base Propellants.

This paper used a supercritical CO2 batch foaming process to treat a waste SP double-base propellant, which is a type of double-base propellants containing 58.6% nitrocellulose, 40.0% nitroglycerin, 0.8% centralite, and 0.5% vaseline, to solve a problem of poor stability of industrial explosives directly prepared by the propellant. Experiments show that this process can produce dense pores inside the SP double-base propellant. With the increase of the pressure of supercritical CO2, the number of pores inside the foamed SP double-base propellant increased, and these pores served as hotspots in the detonation reaction. An increased number of hotspots improved the detonation stability of the perfusion explosive. During the explosion, the energy of the perfusion explosive with the foamed SP double-base propellant was released more completely, so the shock wave energy and bubble energy of the explosive gradually increased with the increase of pressure. Therefore, the supercritical CO2 foaming process can promote the treatment technology of waste double-base propellants and can optimize the detonation performance of perfusion explosives by increasing the pressure of supercritical CO2.

Retro-labyrinthine Lesion Site Detected by Galvanic Vestibular Stimulation Elicited Vestibular-evoked Myogenic Potentials in Patients with Auditory Neuropathy.

OBJECTIVE: Auditory neuropathy (AN) is a unique pattern of hearing loss with preservation of hair cell function. The condition is characterized by the presence of otoacoustic emissions (OAE) or cochlear microphonic (CM) responses with severe abnormalities of the auditory brainstem response (ABR). The vestibular branches of the VIII cranial nerve and the structures innervated by it can also be affected. However, the precise lesion sites in the vestibular system are not well characterized in patients with AN. METHODS: The air-conducted sound (ACS) vestibular-evoked myogenic potentials (VEMPs) and galvanic vestibular stimuli (GVS)-VEMPs were examined in 14 patients with AN. RESULTS: On examination of VEMPs (n=14, 28 ears), the absent rates of ACS-cervical VEMP (cVEMP), ACS-ocular VEMP (oVEMP), GVS-cVEMP, GVS-oVEMP and caloric test were 92.9% (26/28), 85.7% (24/28), 67.9% (19/28), 53.6% (15/28), and 61.5% (8/13), respectively. Impaired functions of the saccule, inferior vestibular nerve, utricle, superior vestibular nerve, and horizontal semicircular canal were found in 25.0% (7/28), 67.9% (19/28), 32.1% (9/28), 53.6% (15/28) and 61.5% (8/13) patients, respectively. On comparing the elicited VEMPs parameters of AN patients with those of normal controls, both ACS-VEMPs and GVS-VEMPs showed abnormal results in AN patients (such as, lower presence rates, elevated thresholds, prolonged latencies, and decreased amplitudes). CONCLUSION: The study suggested that patients with AN often have concomitant vestibular disorders. Retro-labyrinthine lesions were more frequently observed in this study. GVS-VEMPs combined with ACS-VEMPs may help identify the lesion sites and facilitate detection of areas of vestibular dysfunction in these patients.

Case Report: Preservation of Otolithic Function After Triple Semicircular Canal Occlusion in a Patient With Intractable Ménière Disease.

Operative measures are considered when medical treatment fails to control vertigo in patients with intractable Ménière disease. The present report discusses a case in which triple semicircular canal occlusion was performed in a 30-year-old female patient who responded poorly to previously performed endolymphatic sac surgery. Her vestibular and auditory functions were evaluated both before and after surgery. Class A control of vertigo was achieved during the 76-month postoperative follow-up period. Ocular and cervical vestibular evoked myogenic potentials could be elicited before and after surgery. This case suggests that relatively long-term preservation of otolithic function can be achieved following triple semicircular canal occlusion, highlighting its potential as an alternative treatment for patients with Ménière disease.

Long Noncoding RNA SNHG16 Facilitates Abdominal Aortic Aneurysm Progression through the miR-106b-5p/STAT3 Feedback Loop.

AIM: Deepening our understanding of the molecular mechanism of abdominal aortic aneurysm (AAA) progression will help set up novel avenues for therapeutic target identification. Our aim here was to unveil the mechanism function of STAT3 in AAA progression. METHODS: We investigated the functional role of STAT3 in AAA by evaluating vascular smooth muscle cell (VSMC) apoptosis and proliferation via terminal deoxynucleotidyl transferase dUTP nick end labeling, western blotting, 5-ethynyl-2´-deoxyuridine, and Cell Counting Kit-8 assays. The interplay of lncRNA-miRNA-mRNA was verified using the luciferase reporter assay and the RNA pull-down, RNA immunoprecipitation, and chromatin immunoprecipitation assays. Quantitative real-time polymerase chain reaction and western blot were utilized to quantitate the RNA and protein levels of the indicated molecules. RESULTS: Inhibition of STAT3 facilitated VSMC proliferation and repressed VSMC apoptosis. Moreover, It was demonstrated that small nucleolar RNA host gene 16 (SNHG16) sponged miR-106b-5p to release STAT3 from the inhibitory effect of miR-106b-5p. SNHG16 led to the upregulation of STAT3, and STAT3 was an upstream factor in the activation of SNHG16 transcription. Moreover, rescue experiments indicated that SNHG16 depended on STAT3 to regulate VSMC apoptosis and proliferation. In vivo assays showed that SNHG16 knockdown retarded the formation of AAA and upregulated STAT3 in vivo. CONCLUSIONS: We identified that SNHG16/miR-106b-5p/STAT3 formed a complex circuitry for the deterioration of AAA via regulating VSMCs, suggesting a possible target for the pathogenesis of AAA.

[Optimal design of neural modulation strategy of vestibular prosthesis].

Objective:To reveal the response characteristics of semicircular canal neurons（SCN） in the nonlinear perceptual interval, and to establish and screen out the precise SCN information coding model and function expression, which lays a foundation for the optimization and improvement of neuromodulation strategy of multichannel vestibular prosthesis. Method:The perceptual electrophysiological information data of the SCNs during the rotational stimulation was recorded in the nonlinear perceptual interval. The nonlinear least-squares algorithm was used to fit the electrophysiological information data to establish the linear-nonlinear models. The Akaike information criterion was used to calculate the goodness of fit of each model to determine the optimal expression function. Result:In the frequency experiment, the accurate information coding model of more than 85% of SCNs is a quadratic polynomial, and the frequency has no significant effect on the linear-nonlinear selection of the SCNs information coding model（P>0.05）. In the amplitude experiment, the accurate information coding model of more than 83.33% of SCNs is quadratic polynomial when the maximum angular velocity is>80 deg/s, and the amplitude has a significant effect on the linear-nonlinear selection of the SCNs information coding model（P=0.038）. Conclusion:The information coding models of SCN population in the nonlinear perceptual interval have two expressions, linear and nonlinear function, which is closely related to angular velocity. The quadratic polynomial function is more accurate and more advantageous and it can be used to design the precise neuromodulation strategy of multichannel vestibular prosthesis.

Improving the thermostability of a GH97 dextran glucosidase by rational design.

This study was aimed at improving the thermostability of dextran glucosidase PspAG97A, a member of the glycoside hydrolase family 97, from Pseudoalteromonas sp. K8. A total of 9 lysine residues were chosen using the TKSA-MC program based on the optimization of surface charge-charge interactions and were mutated to glutamate for shifting the enzyme's isoelectric point off its optimum pH value. Three mutants K75E, K363E and K420E showed enhanced thermostability. The triple mutant, K75E/K363E/K420E, was found to be the best with a 7.3-fold increase in half-life (t1/2) at 33 °C compared to that of the wild-type (WT). Most importantly, this mutant showed comparable enzymatic activity to that of the WT protein. Structural modelling demonstrated that increased surface charge-charge interactions and optimization of surface hydrophobic and electrostatic contacts contributed to the improved thermostability displayed by K75E/K363E/K420E.

STAT3-induced up-regulation of lncRNA NEAT1 as a ceRNA facilitates abdominal aortic aneurysm formation by elevating TULP3.

Long noncoding RNAs (lncRNAs) were viewed as crucial participants in the pathogenesis of abdominal aortic aneurysm (AAA). LncRNA NEAT1 was recognized as an oncogenic gene in various diseases. However, its function and mechanism in AAA were not precisely documented. Here, we explored the functional role and molecular mechanism of NEAT1 in AAA. Functionally, the effect of NEAT1 on the proliferation was assessed by CCK-8 and EdU assay, while its impact on the apoptosis was evaluated through caspase-3/9 activity and TUNEL assays. As a result, we found that NEAT1 knockdown enhanced the proliferation and impaired the apoptosis of vascular smooth muscle cells (VSMCs). Reversely, overexpressed NEAT1 exerted anti-proliferation and pro-apoptosis effects in VSMCs. Mechanically, we found that STAT3 acted as a transcription factor and contributed to NEAT1 transcription by ChIP and luciferase reporter assays. In addition, NEAT1 was confirmed as a sponge of miR-4688 and thereby increase the expression of TULP3 in VSMCs via RIP assay and RNA pull-down assay. Rescue experiments indicted that TULP3 overexpressing countervailed the impact of NEAT1 depletion on AAA biological processes. Conclusively, lncRNA NEAT1 induced by STAT3 was identified as a ceRNA and facilitated AAA formation by targeting miR-4688/TULP3 axis.

BIK ubiquitination by the E3 ligase Cul5-ASB11 determines cell fate during cellular stress.

The BH3-only pro-apoptotic protein BIK is regulated by the ubiquitin-proteasome system. However, the mechanism of this regulation and its physiological functions remain elusive. Here, we identify Cul5-ASB11 as the E3 ligase targeting BIK for ubiquitination and degradation. ER stress leads to the activation of ASB11 by XBP1s during the adaptive phase of the unfolded protein response, which stimulates BIK ubiquitination, interaction with p97/VCP, and proteolysis. This mechanism of BIK degradation contributes to ER stress adaptation by promoting cell survival. Conversely, genotoxic agents down-regulate this IRE1α-XBP1s-ASB11 axis and stabilize BIK, which contributes in part to the apoptotic response to DNA damage. We show that blockade of this BIK degradation pathway by an IRE1α inhibitor can stabilize a BIK active mutant and increase its anti-tumor activity. Our study reveals that different cellular stresses regulate BIK ubiquitination by ASB11 in opposing directions, which determines whether or not cells survive, and that blocking BIK degradation has the potential to be used as an anti-cancer strategy.

Long non-coding RNA HOXB-AS3 promotes myeloid cell proliferation and its higher expression is an adverse prognostic marker in patients with acute myeloid leukemia and myelodysplastic syndrome.

BACKGROUND: Long non-coding RNAs (lncRNAs) represent the majority of cellular transcripts and play pivotal roles in hematopoiesis. However, their clinical relevance in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains largely unknown. Here, we investigated the functions of HOXB-AS3, a lncRNA located at human HOXB cluster, in the myeloid cells, and analyzed the prognostic significances in patients with AML and MDS. METHODS: shRNAs were used to downregulate HOXB-AS3 in the cell lines and the effect was evaluated by quantitative polymerase chain reaction. The proliferation of the cell lines was illustrated by proliferation and BrdU flow assays. Further, we retrospectively analyzed the HOXB-AS3 expression in 193 patients with AML and 157 with MDS by microarray analysis, and evaluated its clinical importance. RESULTS: Downregulation of HOXB-AS3 suppressed cell proliferation. Mechanistically, HOXB-AS3 potentiated the expressions of several key factors in cell cycle progression and DNA replication without affecting the expressions of HOX genes. In AML, patients with higher HOXB-AS3 expression had shorter survival than those with lower HOXB-AS3 expression (median overall survival (OS), 17.7 months versus not reached, P <  0.0001; median relapse-free survival, 12.9 months versus not reached, P = 0.0070). In MDS, patients with higher HOXB-AS3 expression also had adverse prognosis compared with those with lower HOXB-AS3 expression (median OS, 14.6 months versus 42.4 months, P = 0.0018). The prognostic significance of HOXB-AS3 expression was validated in the TCGA AML cohort and another MDS cohort from our institute. The subgroup analyses in MDS patients showed that higher HOXB-AS3 expressions could predict poor prognosis only in lower-risk (median OS, 29.2 months versus 77.3 months, P = 0.0194), but not higher-risk group. CONCLUSIONS: This study uncovers a promoting role of HOXB-AS3 in myeloid malignancies and identifies the prognostic value of HOXB-AS3 expression in AML and MDS patients, particularly in the lower-risk group.

Activation of aryl hydrocarbon receptor reduces carbendazim-induced cell death.

Carbendazim inhibits microtubule assembly, thus blocking mitosis and inhibiting cancer cell proliferation. Accordingly, carbendazim is being explored as an anticancer drug. Data show that carbendazim increased mRNA and protein expressions and promoter activity of CYP1A1. In addition, carbendazim activated transcriptional activity of the aryl hydrocarbon response element, and induced nuclear translocation of the aryl hydrocarbon receptor (AhR), a sign the AhR is activated. Carbendazim-induced CYP1A1 expression was blocked by AhR antagonists, and was abolished in AhR signal-deficient cells. Results demonstrated that carbendazim activated the AhR, thereby stimulating CYP1A1 expression. In order to understand whether AhR-induced metabolic enzymes turn carbendazim into less-toxic metabolites, Hoechst 33342 staining to reveal carbendazim-induced nuclear changes and flow cytometry to reveal the subG0/G1 population were applied to monitor carbendazim-induced cell apoptosis. Carbendazim induced less apoptosis in Hepa-1c1c7 cells than in AhR signal-deficient Hepa-1c1c7 mutant cells. Pretreatment with ß-NF, an AhR agonist that highly induces CYP1A1 expression, decreased carbendazim-induced cell death. In addition, the lower the level of AhR was, the lower the vitality present in carbendazim-treated cells, including hepatoma cells and their derivatives with AhR RNA interference, also embryonic kidney cells, bladder carcinoma cells, and AhR signal-deficient Hepa-1c1c7 cells. In summary, carbendazim is an AhR agonist. The toxicity of carbendazim was lower in cells with the AhR signal. This report provides clues indicating that carbendazim is more potent at inducing cell death in tissues without than in those with the AhR signal, an important reference for applying carbendazim in cancer chemotherapy.

[Investigation of the reverse phase nystagmus in positioning test for benign paroxysmal positional vertigo].

OBJECTIVE: To investigate the clinical significances and formation mechanism by analyzing the characteristics of the reverse phase nystagmus parameters from benign paroxysmal positional vertigo (BPPV) positioning test. METHODS: There were 183 cases with BPPV, including 108 cases (59.0%) of posterior semicircular canal canalithiasis, 55 cases (30.1%) of horizontal semicircular canal canalithiasis, and 15 cases (8.2%) of horizontal and posterior semicircular canal cupulolithiasis and 5 cases (2.7%) of anterior semicircular canalithiasis . The video-nystagmography was utilized in positioning tests to induce nystagmus. The direction, intensity, time parameters characteristic of vertical nystagmus in Dix-Hallpike test and horizontal nystagmus in roll test were analyzed and compared. RESULTS: There were no reversal phase nystagmus in 15 cases of semicircular canal cupulolithiasis and 5 cases of anterior semicircular canalithiasis. After the disappearance of vertical nystagmus which induced by hanging position (the first phase nystagmus) in 108 cases of posterior semicircular canalithiasis of Dix-Hallpike test, there was 54 cases(50.0%) of posterior semicircular canal canalithiasis displayed downward vertical nystagmus (reverse phase nystagmus) . The latency, duration time and intensity of the first phase nystagmus and reverse phase nystagmus were [(2.00 ± 1.10) s, (3.54 ± 1.42) s], [ (16.27 ± 4.95) s, (61.65 ± 33.69)s] and [ (51.80 ± 25.25) °/s, (10.65 ± 6.29)°/s] respectively; 43 cases(78.2%) of horizontal semicircular canal canalithiasis displayed the opposite to turning head (reverse phase nystagmus) after the horizontal nystagmus, similar with turning head disappeared in Roll test. The latency, duration time and intensity of the first phase of nystagmus and reverse phase nystagmus were [ (1.67 ± 1.07) s, (3.57 ± 1.89)s], [ (25.19 ± 9.74) s, (70.48 ± 40.26)s] and [ (68.47 ± 30.18) °/s, (11.22 ± 8.78)°/s] respectively. Comparing with the latency, duration time, intensity of first phase nystagmus and reverse phase nystagmus of posterior and horizontal semicircular canal canalithiasis, the differences had statistical significances (P < 0.05). Comparing with the first phase nystagmus of reverse phase and no reverse phase nystagmus canalithiasis, the difference of nystagmus intensity had statistical significances (P < 0.05); but the differences of latency and duration of nystagmus had no significant difference (P > 0.05). CONCLUSIONS: It is common in PSC-Can and HSC-Can patients that reverse phase nystagmus is one of the clinical features of canalithiasis. It appears in side head position of Rolling test or the hanging of Dix- Hallpike test. More power of the first phase nystagmus has, reverse phase nystagmus will be induced much easier. In comparison of the reverse phase nystagmus, the first phase nystagmus has the shorter incubation and duration, but it has more power. It is helpful to avoid interruptions of clinical statolith positioning and reset since we recognize the reverse phase nystagmus. The mechanism might be similar to the vestibular mirror image nystagmus. It is another form of the vestibular mirror image nystagmus in BPPV patients.

AKT mediates actinomycin D-induced p53 expression.

At high cytotoxic concentrations, actinomycin D (ActD) blocks transcription, decreasing levels of MDM2 and thus causing p53 stabilization. At low cytostatic concentrations, ActD causes ribosomal stress, which decreases MDM2 activity, resulting in p53 stabilization and activation. ActD can thus be used for p53-based cyclotherapy. We analyzed pathways mediating ActD-induced p53 expression. Inhibitors (LY294002, wortmannin, and deguelin) of phosphatidylinositol 3-kinases (PI3K) and AKT, but not inhibitors of MEK1/2, JNK, and p38-MAPK abolished the ActD-induced p53 expression in diverse cell types. RNA interference further supported these results. When AKT was downregulated by small hairpin RNA-AKTs, ActD-induced p53 expression was significantly decreased. ActD caused AKT phosphorylation at Ser473, indicating full activation of AKT. The potential for cancer therapy is discussed.