Identification and characterization of isocitrate dehydrogenase 1 (IDH1) as a functional target of marine natural product grincamycin B.

Grincamycins (GCNs) are a class of angucycline glycosides isolated from actinomycete Streptomyces strains that have potent antitumor activities, but their antitumor mechanisms remain unknown. In this study, we tried to identify the cellular target of grincamycin B (GCN B), one of most dominant and active secondary metabolites, using a combined strategy. We showed that GCN B-selective-induced apoptosis of human acute promyelocytic leukemia (APL) cell line NB4 through increase of ER stress and intracellular reactive oxygen species (ROS) accumulation. Using a strategy of combining phenotype, transcriptomics and protein microarray approaches, we identified that isocitrate dehydrogenase 1(IDH1) was the putative target of GCN B, and confirmed that GCNs were a subset of selective inhibitors targeting both wild-type and mutant IDH1 in vitro. It is well-known that IDH1 converts isocitrate to 2-oxoglutarate (2-OG), maintaining intracellular 2-OG homeostasis. IDH1 and its mutant as the target of GCN B were validated in NB4 cells and zebrafish model. Knockdown of IDH1 in NB4 cells caused the similar phenotype as GCN B treatment, and supplementation of N-acetylcysteine partially rescued the apoptosis caused by IDH1 interference in NB4 cells. In zebrafish model, GCN B effectively restored myeloid abnormality caused by overexpression of mutant IDH1(R132C). Taken together, we demonstrate that IDH1 is one of the antitumor targets of GCNs, suggesting wild-type IDH1 may be a potential target for hematological malignancies intervention in the future.

Pseudospins and topological edge states for fundamental antisymmetric Lamb modes in snowflakelike phononic crystal slabs.

The topological transport of Lamb wave in phononic crystal slabs provides a great potential in reinforcing nondestructive testing, high sensitivity sensing, and information processing. In this paper, the authors investigate the pseudospins edge states of fundamental antisymmetric Lamb waves in a snowflakelike phononic slab. Significantly, the fourfold Dirac degeneracy for antisymmetric Lamb mode is accidentally formed at the Γ point with the critical angle of the snowflakelike holes, which does not require the folding of the lattices. Meanwhile, based on the rotating-scatterer mechanism, the mirror symmetry is broken and the topological multipole phase transitions are well induced during the gradual change of the scattering strength among the scatterers with the rotation angle. The topologically protected edge states and its unidirectional robust propagation are further demonstrated. The proposed topological phononic slabs will be a more hopeful option to apply in engineering practices.

The Effects of Different Surgical Approaches on the Perioperative Level of Circulating Tumor Cells in Patients with Non-Small Cell Lung Cancer.

Background To observe and compare the effects of video-assisted thoracoscopic surgery (VATS) and conventional thoracotomy on the levels of circulating tumor cells (CTCs) in patients with non-small cell lung carcinoma (NSCLC). Methods Seventy-nine patients with a diagnosis of NSCLC were enrolled in the study. Forty-three were treated with VATS and 36 were treated with conventional thoracotomy. Blood samples were collected 3 days prior to surgery (d-3), during surgery (d0), and 3 days after surgery (d3). After epithelial cell adhesion molecule (EpCAM)-labeled immunomagnetic cell enrichment, anti-CK-PE and anti-CD45-FITC fluorescent-labeled monoclonal antibodies were added to sort CTCs. Quantification of CTCs was performed using multiparameter flow cytometry. Results The number of CTCs on d0 was significantly higher than on d-3 (5.730 ± 4.266 vs. 4.142 ± 3.971, p = 0.033) in both groups. There was no significant difference in the change of CTCs from before surgery to during surgery in the VATS and conventional thoracotomy (open) groups (1.363 ± 2.924 vs. 1.500 ± 2.315, p = 0.329). However, the increase in number of CTCs from before surgery to after surgery was significantly lower in the VATS group than in the conventional thoracotomy (open) group (2.181 ± 2.962 vs. 9.666 ± 15.641, p = 0.015). Thirty of the 79 patients tested positive for CTCs before surgery (37.97%). All benign lung disease patients and volunteers tested negative for CTCs. Conclusion A smaller increase in CTCs was seen in patients treated with VATS lobectomy than in patients treated with conventional thoracotomy. This reduction in number of postoperative CTCs may improve long-term survival.

Qubit reset with a shortcut-to-isothermal scheme.

Landauer's principle shows that the minimum energy cost to reset a classical bit in a bath with temperature T is k_{B}Tln2 in the infinite time. However, the task to reset the bit in finite time has posted a new challenge, especially for quantum bit (qubit) where both the operation time and controllability are limited. We design a shortcut-to-isothermal scheme to reset a qubit in finite time τ with limited controllability. The energy cost is minimized with the optimal control scheme with and without bound. This optimal control scheme can provide a reference to realize qubit reset with minimum energy cost for the limited time.

[Relationship between serum substance P levels and excessive daytime sleepiness in patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To investigate the relationship between serum Substance P levels and excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: A total of 120 adult habitual snorers treated by respiratory physicians in First Hospital of Quanzhou Affiliated to Fujian Medical University were selected for this study. The patients were grouped as simple snorers and OSAHS by the results of polysomnography test. Thirty patients were in the simple snorer group, among whom 24 were male and 6 were female. Their average age was (48 ± 15) years and average AHI was (2.8 ± 1.6) events/hour. Ninety patients were in the OSAHS group, among whom 78 were male and 12 were female. Their average age was (49 ± 12) years and average AHI was (37.1 ± 23.7) events/hour. EDS was assessed using the Epworth sleepiness scale (ESS). Substance P levels were analyzed with a radioimmunoassay. RESULTS: There was no significant difference in gender, age, and body mass index between the 2 groups. The ESS score for patients with OSAHS was (13 ± 5), higher than that for patients in the simple snorer group (F = 10.299, P < 0.05). With increasing severity of OSAHS, the score increased. The serum Substance P level for OSAHS group was (132 ± 27) ng/L, which was lower than that in the control (F = 3.048, P = 0.031), and decrease in Substance P level was most significant in patients with severe OSAHS. Pearson correlation analysis showed that Substance P levels in OSAHS patients were negatively correlated with ESS scores (r = -0.238, P < 0.05). CONCLUSIONS: Substance P levels were lower in OSAHS patients with higher degree of daytime sleepiness. Daytime sleepiness and Substance P level were interrelated in patients with OSAHS.

Three bianthraquinone derivatives from the mangrove endophytic fungus Alternaria sp. ZJ9-6B from the South China Sea.

Three new bianthraquinone derivatives, alterporriol K (1), L (2) and M (3), along with six known compounds were obtained from extracts of the endophytic fungus Alternaria sp. ZJ9-6B, isolated from the mangrove Aegiceras corniculatum collected in the South China Sea. Their structures were elucidated by one- and two-dimensional NMR spectroscopy, MS data analysis and circular dichroism measurements. Compounds 1, 2 and 3 were first isolated alterporriols with a C-2-C-2' linkage. The crystallographic data of tetrahydroaltersolanol B (7) was reported for the first time. In the primary bioassays, alterporriol K and L exhibited moderate cytotoxic activity towards MDA-MB-435 and MCF-7 cells with IC50 values ranging from 13.1 to 29.1 µM.

Tensile Strength Prediction of Short Fiber Reinforced Composites.

Essentially, every failure of a short fiber reinforced composite (SFRC) under tension is induced from a matrix failure, the prediction of which is of fundamental importance. This can be achieved only when the homogenized stresses of the matrix are converted into true values in terms of stress concentration factors (SCFs) of the matrix in an SFRC. Such an SCF cannot be determined in the classical way. In this paper, a closed-form formula for the longitudinal tensile SCF in the SFRC is derived from the matrix stresses determined through an elastic approach. The other directional SCFs in an SFRC are the same as those in a continuous fiber composite already available. A bridging model was used to calculate the homogenized stresses explicitly, and a failure prediction of the SFRC with arbitrary fiber aspect ratio and fiber content was made using only the original constituent strength data. Results showed that the volume fraction, the aspect ratio, and the orientation of the fiber all have significant effect on the tensile strength of an SFRC. In a certain range, the tensile strength of an SFRC increases with the increase in fiber aspect ratio and fiber volume content, and the strength of the oriented short fiber is higher than that of the random short fiber arrangement. Good correlations between the predicted and the available measured strengths for a number of SFRCs show the capability of the present method.

Serum neuron-specific enolase: A promising biomarker of silicosis.

BACKGROUND: Silicosis is a type of chronic pulmonary fibrosis caused by long-term inhalation of silica dust particles. There has been no ideal biomarker for the diagnosis and differential diagnosis of silicosis until now. Studies have found that elevated neuron-specific enolase (NSE) concentration in the serum of silicosis patients is helpful for diagnosis and severity assessment of the disease. However, the number of cases in these studies was not enough to arouse attention. AIM: To investigate the clinical significance of serum NSE in the diagnosis and staging of silicosis. METHODS: From January 2017 to June 2019, 326 cases of silicosis confirmed in Quanzhou First Hospital Affiliated to Fujian Medical University were included in the silicosis group. A total of 328 healthy individuals or medical patients without silicosis were included in the control group. Serum NSE concentrations of all subjects were determined by electrochemical luminescence. RESULTS: There were no significant differences in sex, age, smoking index and complications between the silicosis and control groups. The mean serum NSE concentration was 26.57 ± 20.95 ng/mL in the silicosis group and 12.42 ± 2.68 ng/mL in the control group. The difference between the two groups was significant (U = 15187, P = 0.000). Among the 326 patients with silicosis, 103 had stage I silicosis, and the mean serum NSE concentration was 15.55 ± 6.23 ng/mL. The mean serum NSE concentration was 21.85 ± 12.05 ng/mL in 70 patients with stage II silicosis. The mean serum NSE concentration was 36.14 ± 25.72 ng/mL in 153 patients with stage III silicosis. Kruskal-Wallis H test suggested that the difference in serum NSE concentration in silicosis patients in the three groups was significant (H = 130.196, P = 0.000). Receiver operating characteristic curve analysis indicated that the area under the curve was 0.858 (95% confidence interval: 0.828-0.888; P = 0.000). When the NSE concentration was 15.82 ng/mL, the Jorden index was the largest, the sensitivity was 72%, and the specificity was 90%. CONCLUSION: Serum NSE concentration may be a promising biomarker for the diagnosis and assessment of severity of silicosis.

Three dimeric naphtho-γ-pyrones from the mangrove endophytic fungus Aspergillus tubingensis isolated from Pongamia pinnata.

Three new dimeric naphtho-γ-pyrones, named rubasperone A (1), rubasperone B (2), and rubasperone C (3), together with two known compounds, rubrofusarin (4) and rubrofusarin B (5), were isolated from the mangrove endophytic fungus Aspergillus tubingensis (GX1-5E). Their structures were determined by spectroscopic methods, including IR, MS, and 1D and 2D NMR. The structures of 1 and 2 were further confirmed by X-ray crystallography. In the bioactivity assays against tyrosinase and α-glucosidase, rubrofusarin (4) exhibited moderate tyrosinase inhibitory activity, with an IC(50) value of 65.6 µM, and rubasperone C (3) showed mild α-glucosidase inhibitory activity, with an IC(50) value of 97.3 µM.

[Treatment of elbow dysfunction under elbow arthroscopy].

OBJECTIVE: To evaluate early clinical outcome after arthroscopic treatment of elbow dysfunction. METHODS: From September 2007 to December 2009, 21 patients with elbow dysfunction were treated with an arthroscopic procedure. All patients had chronic history of elbow dysfunction. Extension lag was 18.2° (10° - 25°) combined with pain. All patients underwent five-portals arthroscopic release and debridement. Postoperative care including anti-infection, rehabilitation and prophylaxis of myositis ossificans were prescribed. All elbows were assessed for increase in ROM and Mayo assessment before and after surgery. Mayo score assessment: ≥ 90 points, excellent; 75 - 89 points, good; 60 - 74 points, common; < 60, bad. Complications were evaluated. RESULTS: At an average follow-up of 19.7 months (6 - 29 months), all patients had improvement of extension and relief of pain. The average lag of extension was 2.4° (0° - 5°). Pre-operative Mayo assessment: good, 13 patients; common, 5 patients; bad, 3 patients. Post-operation Mayo assessment: excellent, 17 patients; good, 4 patients; common, 0 patients; bad, 0 patient. There was no complication in this case serial. CONCLUSIONS: Arthroscopic surgery can minimize trauma and bleeding, and reduce complications. Combined with reasonable rehabilitation, arthroscopic surgery can improve elbow function and appears to be satisfactory management.

Role of long non-coding RNA MALAT1 in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a pathological inflammatory condition of the lungs that is associated with high rates of mortality. Although long non-coding RNAs (lncRNAs) serve a role in lung diseases, their functions in COPD pathogenesis are relatively unknown. The present study aimed to assess the role of differentially expressed lncRNAs in COPD. Expression profile analysis of six lncRNAs in age-matched COPD and non-COPD tissues were conducted. Among the six tested lncRNAs, metastasis-associated in lung adenocarcinoma transcript 1 (MALAT1) was the most consistently overexpressed in COPD lung tissue specimens. To model COPD in vitro, human lung fibroblasts were treated with transforming growth factor-ß (TGF-ß) and MALAT1 was knocked down by small interfering RNA. This promoted cell viability and concurrently inhibited the expression of mesenchymal proteins, fibronectin and α-smooth muscle actin. In COPD, cell senescence is linked to the activation of mammalian target of rapamycin complex 1 (mTORC1). Upon gene silencing of MALAT1 in non-TGF-ß-treated cells, cells demonstrated constitutive activation of mTORC1, which was assessed by the protein expression levels of mTORC1 substrate S6 kinase (S6K1). By contrast, upon MALAT1 silencing in the TGF-ß-treated cells, mTORC1 activation was not suppressed, despite the mesenchymal cell markers protein expression levels being downregulated. Thus, lncRNA MALAT1 may represent a potent biomarker in COPD patients and may act as a target for both diagnostic and therapeutic purposes.

[Prevalence of obstructive sleep apnea-hypopnea syndrome in adults aged over 20 years in Fuzhou city].

OBJECTIVE: To investigate the prevalence and risk factors of obstructive sleep apnea-hypopnea syndrome (OSAHS) in adults aged over 20 years in Fuzhou city, there fore to provide epidemiological data for prevention and treatment of the disease, and establishing a data base for prospective study. METHODS: A total of 5500 subjects were derived from a random and cluster sampling of the population in 5 districts of Fuzhou city. They were asked to answer the questions from a questionnaire at home. According to the degree of snoring, 315 subjects with a snoring score > or = 3 degree and 100 subjects with a snoring score = 2 degree were selected at random to undergo polysomnography for a whole night. The prevalence of the disease was estimated and the risk factors for OSAHS were analyzed. RESULTS: 4595 subjects (83.55%) responded, and validated questionnaires were obtained from 4286 subjects (effective power 93.28%); of whom 606 (14.14%) subjects had habitual snoring. The estimated prevalence of OSAHS defined by apnea-hypopnea index (AHI) > or = 5 and Epworth sleepiness scale (ESS) > or = 9 was 4.78%. Multivariate analysis revealed that age, smoking, family snoring, neck-circumference, waist circumference, and abnormality of the upper airway were significant risk factors for OSAHS. CONCLUSIONS: The estimated prevalences of snoring and OSAHS in adults aged over 20 years in Fuzhou city was high. Strategies based on the epidemiological data in Fuzhou city are needed to cut down the prevalence and harm of OSAHS by controlling modifiable risk factors.

Thermally tunable topological edge states for in-plane bulk waves in solid phononic crystals.

The remarkable properties of topological insulators have inspired numerous studies on topological transport for bulk waves, but the demonstrations of topological edge states with tunable frequency are few attempts. Here, we report on the active frequency tunability of topologically protected edge states for in-plane bulk waves by applying a thermal field. We find that the center frequency of topological band gap is shifted down and the band width is enlarged as the temperature increases. Meanwhile, the frequency range of topologically protected edge states is also shifted to low frequency region with the higher temperature. Furthermore, the robust propagation of in-plane bulk waves along a desired path is demonstrated within different frequency bands. The tunable frequency for both topological band gaps and topologically protected edge states achieves the active control of the transport for in-plane bulk waves, which may dramatically facilitate practical applications of novel phononic devices.

Topologically protected edge states for out-of-plane and in-plane bulk elastic waves.

Topological phononic insulators (TPnIs) show promise for application in the manipulation of acoustic waves for the design of low-loss transmission and perfectly integrated communication devices. Since solid phononic crystals exist as a transverse polarization mode and a mixed longitudinal-transverse polarization mode, the realization of topological edge states for both out-of-plane and in-plane bulk elastic waves is desirable to enhance the controllability of the edge waves in solid systems. In this paper, a two-dimensional (2D) solid/solid hexagonal-latticed phononic system that simultaneously supports the topologically protected edge states for out-of-plane and in-plane bulk elastic waves is investigated. Firstly, two pairs of two-fold Dirac cones, respectively corresponding to the out-of-plane and in-plane waves, are obtained at the same frequency by tuning the crystal parameters. Then, a strategy of zone folding is invoked to form double Dirac cones. By shrinking and expanding the steel scatterer, the lattice symmetry is broken, and band inversions induced, giving rise to an intriguing topological phase transition. Finally, the topologically protected edge states for both out-of-plane and in-plane bulk elastic waves, which can be simultaneously located at the frequency range from 1.223 to 1.251 MHz, are numerically observed. Robust pseudospin-dependent elastic edge wave propagation along arbitrary paths is further demonstrated. Our results will significantly broaden its practical application in the engineering field.

High-Surface-Area and Porous Co2P Nanosheets as Cost-Effective Cathode Catalysts for Li-O2 Batteries.

To enable lithium-oxygen batteries for practical applications, the design and efficient synthesis of nonprecious metal catalysts with high activity and stable structural properties are demanded. The objective is to accelerate the sluggish kinetics of both oxygen reduction reaction and oxygen evolution reaction by facilitating electronic/ionic transport and improving oxygen diffusion in a porous structure. In this study, high-surface-area and porous cobalt phosphide (Co2P) nanosheets are synthesized via an environmentally safe hydrothermal method, where red phosphorous is used as the phosphorous source. It was found that the as-prepared Co2P/acetylene black (AB) composite delivered enhanced electrochemical performances, such as high capacities of 2551 mA h g-1 (based on the total weight of Co2P and AB) or 5102 mA h g-1 (based on the weight of Co2P or AB) and a good cycle life of more than 1800 h (132 cycles) in lithium-oxygen battery. The rational design of the Co2P/AB porous oxygen electrode structure provides sufficient accessible reaction sites and a short diffusion path for electrolyte penetration and diffusion of O2.

Simultaneous multi-band valley-protected topological edge states of shear vertical wave in two-dimensional phononic crystals with veins.

The introduction of the concept of valley pseudospin to phononic crystals has made a remarkable topologically protected interface transport of sound, which opens a novel research area referred to as valley Hall topological insulators. Here, we demonstrate the simultaneous multi-band edge states of shear vertical waves in two-dimensional phononic crystals with veins. The multi-band edge states are topologically valley-protected and are obtained by simultaneously gapping multiple Dirac points at K (or K') under the inversion symmetry breaking. As the relative radius of the two adjacent steel columns varies, the band diagram undergoes a topological transition which can be characterized by topological charge distributions and opposite valley Chern numbers. Subsequently, the vortex chirality of the bulk valley modes is unveiled. With numerical simulations, simultaneous multi-band valley dependent edge states and the associated valley-protected backscattering suppression around the curved waveguide are further demonstrated. Our work could become a promising platform for applications of multi-functional topological acoustic devices.

[The effect of different intensity exercise on skeletal muscle fiber MHC subtype transformation and CaN/NFATc1 signaling pathways].

OBJECTIVE: To study the effect of different intensity exercise on skeletal muscle fiber myosin heavy chain(MHC) subtype transformation and CaN/NFATc1 signaling pathways. METHODS: Twenty-four Male SD rats (2-month old) were randomly divided into normal control group (NC), moderate intensity exercise group (ME, grade 5°, speed 18 m/min), heavy intensity exercise group (HE, grade 10°, 26.8 m/min). The rats in exercise groups were treated with treadmill training for eight weeks. The type I and type Ⅱ muscle fibers were determined by ATPase staining method. MHC subtype was separated by SDS-PAGE. The activity of CaN was determined by colorimetric method. The content of NFATc1 protein in skeletal muscle was detected by immune imprinting technology. RESULTS: ①Skeletal muscle fiber density changes:the type I and Ⅱ fiber number density of quadriceps in ME group were increased significantly (P<0.05), but in HE group, only the type Ⅱ fiber surface density was increased significantly (P<0.05). The type I fiber number density of soleus in ME and HE group was increased significantly (P<0.05). ②The changes of fibers MHC subtype percentage in skeletal muscle:the percentages of MHC I and type Ⅱa of quadriceps in ME group were increased (P<0.05), while the percentage of MHC Ⅱb was decrease (P<0.05). The percentage of MHC I in soleus was increased, while the percentages of MHCⅡa and Ⅱb were decreased. ③The activity of CaN and the content of NFATc1 protein in ME group were increased significantly (P<0.05). CONCLUSIONS: The heavy and moderate intensity exercise may induce skeletal muscle MHC type transforming from fast to slow. At the same time, the activity of CaN and the expression of NFATc1 protein are increased accompanying the changes of skeletal muscle fibers subtype.

[Intravenous contrast imaging in diagnosis of acute renal allograft rejection: a comparative study with color flow Doppler imaging].

OBJECTIVE: To assess the value of intermittent contrast second harmonic imaging (SHI) incorporating acoustic densitometry in the diagnosis of acute renal allograft rejection in comparison with color Doppler flow imaging (CDFI) for determining the resistance index (RI). METHODS: Eight canine models of acute renal allograft rejection were established, subjected subsequently to examinations with SHI and acoustic densitometry to determine the acoustic density. Color flow Doppler was also performed to determine RI, and serum creatinine (Cr) levels were measured. RESULTS: The time-intensity curve (TIC) showed that the area under the curve, the peak intensity (PI) and RI all had linear correlation with serum Cr levels, with the correlation coefficient gamma of 0.978, 0.972 and 0.708 respectively (by SPSS10.0). CONCLUSION: Intermittent contrast SHI is effective to evaluate the perfusion of renal allograft, and when combined with acoustic densitometry, the resultant TIC parameters are in closer correlation with acute renal allograft rejection than RI.

[Effect of latent asymptomatic toxoplasmosis on glucose metabolism in brain of mice].

OBJECTIVE: To explore the effect of latent asymptomatic Toxoplasma gondii infection on glucose metabolism in brain of mice. METHODS: Twenty mice were randomly divided into two groups: a Toxoplasma infected group and normal control group. The mice in the Toxoplasma infected group were inoculated with 0.3 ml of brain suspension in saline containing ten Toxoplasma gondii tissue cysts, avirulent Toxoplasma gondii Prugniaud (PRU, a Type II strain). The mice in the control group received 0.3 ml of saline orally. Six monthes after the infection, the glucose metabolism changes in the mouse brain were evaluated by MicroPET, then all the mice were sacrificed and the brain tissues were observed histopathologically. RESULTS: Compared with the normal controls, the infected mice demonstrated profound and widespread brain pathology, and MicroPET indicated a significant glucose metabolism reduction in the brain of asymptomatic Toxoplasma gondii infected mice. CONCLUSION: Chronic Toxoplasma gondii infection maybe results in the glucose metabolism reduction in the brain of mice.