Multi-helix beams generated with binary helico-conical phase patterns.

In this paper, we generate a type of double helico-conical beam (HCB) by binarizing the modified helico-conical phase (MHCP). The diffraction patterns of the double HCBs were analyzed theoretically and experimentally. The relative position of the double HCBs can be adjusted arbitrarily by introducing a blazed grating only. In addition, the superposition of multiple binary MHCPs can be used to generate multi-helix beams. Accordingly, the diffraction patterns of the multi-helix beams were also analyzed theoretically and experimentally. The results demonstrated that the number and relative position of multi-helix beams can be adjusted by the number of superimposed MHCP profiles and the azimuth factor θ j, respectively. This kind of arrayed HCB will be potentially applied in the fields of optical manipulation and multiplexed holography.

Self-healing properties of symmetrical power-exponent-phase vortices.

The self-healing properties of symmetrical power-exponent-phase vortices (SPEPVs) are analyzed in this paper. By placing an obstacle in the optical path of SPEPVs, we simulated the propagation of the obstructed SPEPVs and verified the self-healing of the beam theoretically. We also explored the influence of external factors (e.g., obstacle size and position) and internal parameters (topological charge l and power exponent n) on the self-healing effect of obstructed SPEPVs. Furthermore, the energy flow density, similarity coefficient, effective self-healing distance, and diffraction efficiency of the obstructed SPEPVs were also discussed. The results demonstrated that the transverse energy flows around the obstructed region of SPEPVs will recover with the propagation distance increased, and the effective self-healing distance gradually increases linearly with the obstacle size r x increased. The self-healing characteristic gives the petal-like SPEPVs the ability to trap microparticles three-dimensionally.

Relationship between circadian rhythm-related genes and extracellular matrix: implications for sleep deprivation.

BACKGROUND: Sleep deprivation (SD) can lead to the development of various pathological disorders. The extracellular matrix (ECM) compositions and circadian rhythm genes are two pivotal variables of SD. However, their relationships remain undefined during SD. METHODS: A mouse SD model was established using a modified multiplatform water environment method. The expression of nerve growth factor (NGF) in mouse hippocampus was detected by an immunofluorescence (IF) method. Protein expression was assessed by western blot, and mRNA analysis was performed by quantitative real-time PCR (qRT-PCR). The differentially expressed genes after SD, the genes associated with stromal score, and gene expression correlation were analyzed by bioinformatic analysis. RESULTS: The mouse model of SD was successfully established, as evidenced by the changed morphology, increased Bax and NGF levels, and downregulated Bcl-2 in mouse hippocampus after SD. The differentially expressed genes after SD were closely associated with the ECM compositions. The ECM composition metalloproteinase 9 (MMP9) was under-expressed in mouse hippocampus after SD. The hippocampal MMP9 expression was correlated with the expression levels of circadian genes PER2, PER3, TIMELESS, FBXL3, and NFIL3. PER2 and TIMELESS were upregulated in mouse hippocampus after SD. CONCLUSION: The current findings suggest a correlation between ECM composition MMP9 and circadian rhythm-related genes PER2 and TIMELESS in mouse hippocampus after SD, providing a novel understanding of the disorders after SD.

Adoptive Transfer of NKG2D CAR mRNA-Engineered Natural Killer Cells in Colorectal Cancer Patients.

By fusing the extracellular domain of the natural killer (NK) cell receptor NKG2D to DAP12, we constructed a chimeric antigen receptor (CAR) to improve NK cell tumor responses. An RNA electroporation approach that provides transient expression of the CAR was adopted as a risk mitigation strategy. Expression of the NKG2D RNA CAR significantly augmented the cytolytic activity of NK cells against several solid tumor cell lines in vitro and provided a clear therapeutic benefit to mice with established solid tumors. Three patients with metastatic colorectal cancer were then treated with local infusion of the CAR-NK cells. Reduction of ascites generation and a marked decrease in number of tumor cells in ascites samples were observed in the first two patients treated with intraperitoneal infusion of low doses of the CAR-NK cells. The third patient with metastatic tumor sites in the liver was treated with ultrasound-guided percutaneous injection, followed by intraperitoneal infusion of the CAR-NK cells. Rapid tumor regression in the liver region was observed with Doppler ultrasound imaging and complete metabolic response in the treated liver lesions was confirmed by positron emission tomography (PET)- computed tomographic (CT) scanning. Our results highlight a promising therapeutic potential of using RNA CAR-modified NK cells to treat metastatic colorectal cancer.

Measurement of Fetal Mesencephalon and Pons Via Ultrasonographic Cross Sectional Imagining.

OBJECTIVES: This study evaluated the feasibility of measuring the fetal mesencephalon and pons by ultrasonographic cross sectional imaging to detect fetal central nervous system developmental abnormalities. MATERIALS AND METHODS: Fetal ultrasonographic measurements included: Fetal mesencephalon anteroposterior diameters (MAD), mesencephalon transverse diameters (MTD), pons anteroposterior diameter (PAD) and proximal transverse diameters (PTD). RESULTS: Nine-hundred ninety fetuses were imaged. Thirty-eight fetuses (observation group) presented central nervous system abnormalities; 952 fetuses without imaged abnormalities were utilized as the reference (control) group. Fetal MAD, MTD, PAD, and PTD in control fetuses showed a linear correlation with gestational age. Thirty-eight fetuses had 40 abnormal measurements (8 MAD, 8 MTD, 14 PAD, and 10 PTD), 16 in mesencephalon, and 24 in pons. All data fell below the 95% confidence intervals' lower limits for the corresponding gestational age. CONCLUSION: Using normative data based on 957 fetuses allows detection of size abnormalities of the pons and midbrain during fetal life.

Pulling force and surface tension drive membrane fusion.

Despite catalyzed by fusion proteins of quite different molecular architectures, intracellular, viral, and cell-to-cell fusions are found to have the essential common features and the nearly same nature of transition states. The similarity inspires us to find a more general catalysis mechanism for membrane fusion that minimally depends on the specific structures of fusion proteins. In this work, we built a minimal model for membrane fusion, and by using dissipative particle dynamics simulations, we propose a mechanism that the pulling force generated by fusion proteins initiates the fusion process and the membrane tension regulates the subsequent fusion stages. The model shows different features compared to previous computer simulation studies: the pulling force catalyzes membrane fusion through lipid head overcrowding in the contacting region, leading to an increase in the head-head repulsion and/or the unfavorable head-tail contacts from opposing membranes, both of which destabilize the contacting leaflets and thus promote membrane fusion or vesicle rupture. Our simulations produce a variety of shapes and intermediates, closely resembling cases seen experimentally. Our work strongly supports the view that the tight pulling mechanism is a conserved feature of fusion protein-mediated fusion and that the membrane tension plays an essential role in fusion.

Exploring the shape deformation of biomembrane tubes with theoretical analysis and computer simulation.

The shape deformation of membrane nanotubes is studied by a combination of theoretical analysis and molecular simulation. First we perform free energy analysis to demonstrate the effects of various factors on two ideal states for the pearling transition, and then we carry out dissipative particle dynamics simulations, through which various types of membrane tube deformation are found, including membrane pearling, buckling, and bulging. Different models for inducing tube deformation, including the osmotic pressure, area difference and spontaneous curvature models, are considered to investigate tubular instabilities. Combined with free energy analysis, our simulations show that the origin of the deformation of membrane tubes in different models can be classified into two categories: effective spontaneous curvature and membrane tension. We further demonstrate that for different models, a positive membrane tension is required for the pearling transition. Finally we show that different models can be coupled to effectively deform the membrane tube.

[Chemical Constituents from Roots of Gentiana straminea of Tibetan Medicine].

Objective: To investigate the chemical constituent from the roots of Gentiana straminea. Methods: The constituents were separated by microporous resin,silica gel,Sephadex LH-20 and preparative column chromatography and their structures were elucidated by NMR and MS spectral methods. Results: Twelve chemical constituents were isolated from the roots of Gentiana straminea and their structures were identified as daucosterol( 1),ß-sitosterol( 2),ursolic acid( 3),sweroside( 4),swertiamarin( 5),gentiopicroside( 6),6'-O-acetyl-gentiopicroside( 7),6'-O-ß-D-glucopyranosyl-sweroside( 8),protocatech uic aldehyde( 9),protocatechuic acid( 10),methyl gallate( 11) and dibutyl phthalate( 12). Conclusion: The compounds 8,9,10,11 and 12 are obtained from this plant for the first time.

[Application of two and three-dimensional ultrasound measurement of fetal thymus in fetal intrauterine growth restriction].

OBJECTIVE: To measure the ultrasonic parameters of transverse diameter, anteroposterior diameter and volume of fetal thymus through two and three-dimensional (2D and 3D) probes, establish normal reference range of fetal thymus development and assess the correlation between fetal intrauterine growth restriction and fetal thymus development. METHODS: A total of 53 patients with suspected fetal intrauterine growth restriction (IUGR) at our hospital from December 2012 to May 2014 were selected into the observation group while another 53 cases as the control group corresponding to the former group's gestational week (GA). The transverse and anteroposterior diameters were measured in the three vessel view by 2D-ultrasound and the volume of fetal thymus was measured through 3D ultrasound. The control parameters were analyzed by linear regression analysis. And two groups of parameters were tested by rank sum test. P < 0.05 was deemed significant. RESULTS: The regression equation of fetal thymus transverse diameter and GA was: Y = 0.14X-1.174, R² = 0.766, P < 0.05; the regression equation of fetal thymus anteroposterior diameter and GA was: Y = 0.49X-0.166, R² = 0.792, P < 0.05; the regression equation of fetal thymus volume and GA was: Y = 0.652X-10.611, R² = 0.791, P < 0.05. Two groups underwent rank sum test of fetal thymus transverse diameter, anteroposterior diameter and volume (P < 0.05). CONCLUSION: Fetal thymus transverse diameter, anteroposterior diameter and volume increase with gestational weeks. In IUGR, fetal thymus transverse diameter, anteroposterior diameter and volume are less than those of the same GA fetal thymus.

Systematic Analysis of the Relationship Between Elevated Zinc and Epilepsy.

Previous studies have indicated a potential relationship between zinc and epilepsy. The aim of this study is to investigate the causal relationship between zinc, zinc-dependent carbonic anhydrase, and gray matter volume in brain regions enriched with zinc and epilepsy, as well as explore the possible mechanisms by which zinc contributes to epilepsy. First, this study assessed the risk causality between zinc, carbonic anhydrase, and gray matter volume alterations in zinc-enriched brain regions and various subtypes of epilepsy based on Two-sample Mendelian randomization analysis. And then, this study conducted GO/KEGG analysis based on colocalization analysis, MAGMA analysis, lasso regression, random forest model, and XGBoost model. The results of Mendelian randomization analyses showed a causal relationship between zinc, carbonic anhydrase-4, and generalized epilepsy (p = 0.044 , p = 0.010). Additionally, carbonic anhydrase-1 and gray matter volume of the caudate nucleus were found to be associated with epilepsy and focal epilepsy (p = 0.014, p = 0.003 and p = 0.022, p = 0.009). A colocalization relationship was found between epilepsy and focal epilepsy (PP.H4.abf = 97.7e - 2). Meanwhile, the MAGMA analysis indicated that SNPs associated with epilepsy and focal epilepsy were functionally localized to zinc-finger-protein-related genes (p < 1.0e - 5). The genes associated with focal epilepsy were found to have a molecular function of zinc ion binding (FDR = 2.3e - 6). After the onset of epilepsy, the function of the gene whose expression changed in the rats with focal epilepsy was enriched in the biological process of vascular response (FDR = 4.0e - 5). These results revealed mechanism of the increased risk of epilepsy caused by elevated zinc may be related to the increase of zinc ion-dependent carbonic anhydrase or the increase of the volume of zinc-rich caudate gray matter.

miR-18b inhibits TGF-ß1-induced differentiation of hair follicle stem cells into smooth muscle cells by targeting SMAD2.

Human hair follicle mesenchymal stem cells (hHF-MSCs) are capable of differentiating into smooth muscle cells (SMCs) in response to transforming growth factor-ß (TGF-ß), and thus can be used for cardiovascular tissue engineering and regenerative medicine. However, the precise molecular mechanisms underlying SMC conversion of hHF-MSCs are still undefined. MicroRNAs (miRNAs) are small noncoding RNAs that modulate gene expression post-transcriptionally by binding to the complementary sequences of targeted mRNAs. Accumulating evidence indicates that miRNAs are associated with SMC differentiation in vitro andin vivo. In this study, we revealed that miR-18b was significantly downregulated during TGF-ß1-induced hHF-MSCs differentiation into SMC using miRNA array profiling and quantitative RT- PCR (qRT-PCR). Over-expression of miR-18b in hHF-MSCs led to remarkable downregulation of SMC-specific markers such as SMA and calponin proteins. On the contrary, inhibition of endogenous miR-18b by its antisense oligonucleotide antagomir-18b reversed the changes of SMA and calponin proteins. We also showed that SMAD2, a key transcription regulator in TGF-ß signaling which was involved in SMC differentiation, is regulated by miR-18b. miR-18b could suppress the expression of SMAD2 protein by targeting the 3'UTR of SMAD2 gene without affecting its mRNA level in hHF-MSCs. Moreover, knockdown of SMAD2 by RNA interference could block the effect of inhibition of miR-18b on SMC differentiation, indicating that SMAD2 contributed to miR-18b mediated regulation of TGF-ß-induced SMC differentiation. In conclusion, this study demonstrated that miR-18b regulated the TGF-ß1-induced differentiation of hHF-MSCs into SMCs by targeting SMAD2 gene, and provided novel insights into the regulatory mechanisms of TGF-ß-induced SMC differentiation.

Interface contact and modulated electronic properties by in-plain strains in a graphene-MoS2 heterostructure.

Designing a specific heterojunction by assembling suitable two-dimensional (2D) semiconductors has shown significant potential in next-generation micro-nano electronic devices. In this paper, we study the structural and electronic properties of graphene-MoS2 (Gr-MoS2) heterostructures with in-plain biaxial strain using density functional theory. It is found that the interaction between graphene and monolayer MoS2 is characterized by a weak van der Waals interlayer coupling with the stable layer spacing of 3.39 Å and binding energy of 0.35 J m-2. In the presence of MoS2, the linear bands on the Dirac cone of graphene are slightly split. A tiny band gap about 1.2 meV opens in the Gr-MoS2 heterojunction due to the breaking of sublattice symmetry, and it could be effectively modulated by strain. Furthermore, an n-type Schottky contact is formed at the Gr-MoS2 interface with a Schottky barrier height of 0.33 eV, which can be effectively modulated by in-plane strain. Especially, an n-type ohmic contact is obtained when 6% tensile strain is imposed. The appearance of the non-zero band gap in graphene has opened up new possibilities for its application and the ohmic contact predicts the Gr-MoS2 van der Waals heterojunction nanocomposite as a competitive candidate in next-generation optoelectronics and Schottky devices.

[Corrigendum] Overexpression of HES6 has prognostic value and promotes metastasis via the Wnt/ß-catenin signaling pathway in colorectal cancer.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that Fig. 2 on p. 1266 and Fig. 5 on p. 1269 contained some apparent errors in terms of the assembly of the various data panels. Specifically, Fig. 2D appeared to contain a pair of overlapping images, and Figs. 5D and 8A also appeared to include overlapping images. However, the authors were able to consult their original data, and assess where the errors had been made during the compilation of these figures. The corrected versions of Figs. 2 (showing the correct data for the '5T' panel in Fig. 2D) and 5 (showing alternative data) are shown on the subsequent pages. The authors regret the errors that were made during the preparation of the published figures, and confirm that these errors did not grossly affect the conclusions reported in the study. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish a Corrigendum, and all the authors agree to this Corrigendum. Furthermore, they apologize to the readership for any inconvenience caused. [the original article was published in Oncology Reports 40: 1261­1274, 2018; DOI: 10.3892/or.2018.6539].

Recovery Infectious Enterovirus 71 by Bac-to-Bac Expression System in vitro and in vivo.

Enterovirus 71 (EV71) is one of the most important etiological agents for hand-foot-mouth disease. Compared with coxsackievirus A16 infection, EV71 infection is often associated with severe central nervous system complications, such as encephalitis, encephalomyelitis, and acute flaccid paralysis in infants and young children. In this study, we constructed a recombinant baculovirus with T7 ribonucleic acid polymerase under the control of a cytomegalovirus promoter and simultaneously engineered the T7 promoter upstream of a full-length EV71 complementary deoxyribonucleic acid. After transduction into mammalian cells, typical cytopathic effects (CPEs) and VP1 signals were detected in cells transfected with recombinant baculovirus. Additionally, viral particles located in the cytoplasm of human rhabdomyosarcoma cells (Rd) and Vero cells were observed by electron microscope, indicating that EV71 was recovered using a Bac-to-Bac expression system in vitro. After four passages, the rescued virus had a growth curve and plaque morphology similar to those of the parental virus. Furthermore, the Vp1 gene and the protein from the mouse brain were detected by reverse transcription polymerase chain reaction and immunohistochemistry after intracerebral injection of purified recombinant baculovirus. Typical CPEs were observed after inoculation of the supernatant from mouse brain to Rd cells, revealing a reconstruction of EV71 in vivo. Thus, we established a new approach to rescue EV71 based on a baculovirus expression system in vitro and in vivo, which may provide a safe and convenient platform for fundamental research and a strategy to rescue viruses that currently lack suitable cell culture and animal models.

[Effect of combination of taxol and celecoxib on reversing multidrug resistance human breast cancer cells (MCF-7/ Taxol) and explore its underlying mechanism].

OBJECTIVE: To investigate the reversal effect of Celecoxib and Taxol on multidrug resistance (MDR) human breast cancer cells (MCF-7/Taxol) and its underlying mechanism. METHODS: After establishing the resistance cell lines of human breast cancer on Taxol (MCF-7/Taxol), the effects of the drugs on the toxicity of MCF-7/Taxol cells and the reversal effect of Celecoxib on MDR were determined by CCK-8 assay. The cells were divided into seven groups (A: MCF-7; B: MCF-7/Taxol; C: MCF-7/Taxol + 0.03 microg/mL Taxol; D: MCF-7/ Taxol + 0 .03 microg/mL Taxol + 3 microg/mL Celecoxib; E: MCF-7/Taxol + 0.03 microg/mL Taxol-6 /g/mL Celecoxib; F: MCF-7/Taxol + 3 microg/mL Celecoxib; G: MCF-7/Taxol + 6 microg/mL Celecoxib). The mRNA levels of MDR1 and BCRP in these treated cells were also determined by reverse transcription-polymerase chain reaction (RT-PCR), the protein levels of P-gp and BCRP in these treated cells were also determined by Western blot method. RESULTS: Compared with the Taxol control, the cytotoxicity effects was obviously increased by combination of Taxol and Celecoxib (P < 0.05). Compared with the vehicle control, Taxol up-regulated mRNA and protein levels of P-gp, whereas Celecoxib down-regulated mRNA and protein levels of P-gp and BCRP (P < 0.05). CONCLUSION: Celecoxib has reversal effect on MDR in MCF-7/Taxol cells, it's possible mechanism might be related to reduce the protein expression of COX-2, the inhibition of P-gp, BCRP mRNA and protein overexpression.

Radial aggregation of proteins prevails over axial aggregation on membrane tubes.

Tubular membrane structures are abundant in living cells and participate in various cell activities with the help of specific proteins. This complicated protein-membrane interaction raises a largely unclear question of how cells create, maintain and eliminate membrane nanotubes with a variety of proteins involved. To simplify the question and to give a common mechanism, we simply model membrane proteins as various solid nanoparticles (NPs) of different shapes, instead of considering the detailed structure of different proteins. With this minimal model of membrane proteins, we use molecular simulations to study the common features for protein self-assembly on membrane tubes. Both molecular simulations and energy analysis reveal that on tubular membrane surfaces, the radial aggregation structure of spherical NPs prevails over axial aggregation. We demonstrate that anisotropic deformation of membrane tubes by NP adhesion leads to a direction-dependent (effective) inter-NP attraction, which controls the direction of NP assembly. Moreover, this radial aggregation morphology seems to be independent of the shape of NPs, except for NPs with a length comparable to the tube diameter. This observation indicates that proteins with strong adhesion to a membrane tube tend to form ring-like aggregates, and this finding offers an insight into how proteins play their roles in generating, maintaining and breaking tubular membrane structures.

The combination of platelet count and lymphocyte to monocyte ratio is a prognostic factor in patients with resected breast cancer.

Many inflammation indicators have been reported to be related with patient outcomes in various cancers. Previous studies have evaluated the combination of platelet (PLT) and lymphocyte to monocyte ratio (COP-LMR) as a systemic inflammatory marker for prognostication in lung cancer, yet its prognostic role among breast cancer patients remains unclear.In the present study, a total of 409 breast cancer patients with surgical resection were retrospectively investigated. The receiver operating characteristic (ROC) curve was used to choose the optimal cut-off value of PLT and lymphocyte to monocyte ratio (LMR). Patients were classified into 3 groups according to the score of COP-LMR, and its relationship with various clinicopathological factors and breast cancer prognosis were further evaluated.The ROC curve analysis showed that COP-LMR had a higher area under the ROC curve for the prediction of 5-year disease-free survival and overall survival than PLT or LMR alone. Multivariable analysis showed that an elevated COP-LMR was an independent predictor of poor disease-free survival (P = .032) and overall survival (P = .005). Subgroup analysis revealed that COP-LMR was still significantly associated with prognosis in both luminal A and luminal B subtypes.Preoperative COP-LMR is a potential prognostic factor in breast cancer patients who underwent surgery.

Controlling Nutritional Status (CONUT) score is a prognostic factor in patients with resected breast cancer.

The present study aimed to determine the correlation between controlling nutritional status (CONUT) and prognosis in resected breast cancer patients. Totally, 861 breast cancer patients with surgical resection in West China Hospital of Sichuan University between 2007 and 2010 were included. The relationship between CONUT and various clinicopathological factors as well as prognosis was evaluated. The results showed that the optimal cutoff value for CONUT to predict the 5-year survival was 3 and CONUT had a higher area under the ROC curve (AUC) for 5-year disease free survival (DFS) and overall survival (OS) prediction compared with the neutrophil lymphocyte ratio (NLR) and prognostic nutritional index (PNI). High CONUT was significantly correlated with older age, lymph node involvement, advanced T-stage, and surgery type. In the multivariate analysis, CONUT-high patients had worse DFS and OS, when compared with CONUT-low patients. In conclusion, preoperative CONUT is a useful marker for predicting long term outcomes in breast cancer patients after curative resection.

Design of Small Nanoparticles Decorated with Amphiphilic Ligands: Self-Preservation Effect and Translocation into a Plasma Membrane.

Design of nanoparticles (NPs) for biomedical applications requires a thorough understanding of cascades of nano-bio interactions at different interfaces. Here, we take into account the cascading effect of NP functionalization on interactions with target cell membranes by determining coatings of biomolecules in biological media. Cell culture experiments show that NPs with more hydrophobic surfaces are heavily ingested by cells in both the A549 and HEK293 cell lines. However, before reaching the target cell, both the identity and amount of recruited biomolecules can be influenced by the pristine NPs' hydrophobicity. Dissipative particle dynamics (DPD) simulations show that hydrophobic NPs acquire coatings of more biomolecules, which may conceal the properties of the as-engineered NPs and impact the targeting specificity. Based on these results, we propose an amphiphilic ligand coating on NPs. DPD simulations reveal the design principle, following which the amphiphilic ligands first curl in solvent to reduce the surface hydrophobicity, thus suppressing the assemblage of biomolecules. Upon attaching to the membrane, the curled ligands extend and rearrange to gain contacts with lipid tails, thus dragging NPs into the membrane for translocation. Three NP-membrane interaction states are identified that are found to depend on the NP size and membrane surface tension. These results can provide useful guidelines to fabricate ligand-coated NPs for practical use in targeted drug delivery, and motivate further studies of nano-bio-interactions with more consideration of cascading effects.