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Background: Shenzao dripping pill (SZDP) is empirically prescribed for treating cardiac diseases. Nevertheless, there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic effects. The objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia (CMI) in a rat model. Methods: In this study, we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of SZDP. The integration of network pharmacology and metabolomics was conducted to investigate the mechanisms. Molecular docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated targets. Results: The results showed that SZDP was able to improve T wave voltage, reverse CMI abnormalities in ejection fraction and fractional shortening, and restore histopathological heart damage. Metabolomics results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration, mainly affecting purine metabolism. 13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for CMI. Integrating network pharmacology and metabolomics, thiopurine S-methyltransferase (TPMT), xanthine dehydrogenase/oxidase (XDH), bifunctional purine biosynthesis protein ATIC (ATIC), and cytochrome p450 1A1 (CYP1A1) were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan, Deoxyribose 1-phosphate and Phosphoribosyl formamidocarboxamide. Conclusion: SZDP has a therapeutic effect on CMI by regulating metabolite levels, acting on the targets of TMPT, XDH, ATIC, and CYP1A1, and reducing cardiomyocyte injury and myocardial fibrosis. [ABSTRACT FROM AUTHOR]

In this paper, we construct a class of non-weight modules over the affine-Virasoro algebra of type A1 by taking the tensor product of irreducible U(h)-free modules of rank 1 with irreducible highest weight modules. The irreducibility and the isomorphism classes of these modules are determined. Moreover, we show that these tensor product modules are different from the known non-weight modules. Finally, we realize some tensor product modules as induced modules from modules over certain subalgebras of the affine-Virasoro algebra of type A1, and give sufficient and necessary conditions for these induced modules to be reducible. [ABSTRACT FROM AUTHOR]

In this article, we exploit the theory of graded module categories with semi-infinite character developed by Soergel (Character formulas for tilting modules over Kac-Moody algebras, Represent. Theor. 2 (1998), 432-448) to study representations of infinite-dimensional Lie algebras of vector fields W(n), S(n) and H(n) (n ≥ 2), and obtain a description of indecomposable tilting modules. The character formulas for those tilting modules are determined. [ABSTRACT FROM AUTHOR]

Hierarchical clustering based on semantic feature thresholds is well applied in data mining. However, this method uses systematic sampling to select the edge points of the region during the region merging phase, resulting in the problems of under-consolidation and computational complexity when region merging based on the Euclidean distance criterion. To solve this problem, an improved hierarchical clustering method is proposed, which adopts the weighted Euclidean distance and optimizes the components of region combination. According to the orientation of the centers of two region clustering and the geometric relation among the edge points, two novel type of edge point selection strategies are established to reduce the number of edge points involved in the operation and ensure that the selected ones possess the minimum Euclidean distance in all edge point combinations. Experimental results show that the main advantages of this research project lie in its high clustering accuracy and less average clustering time. [ABSTRACT FROM AUTHOR]

The type VI secretion system (T6SS) is a class of sophisticated cell contact-dependent apparatus with anti-eukaryotic or anti-bacterial function. Klebsiella pneumoniae is one of the most common bacterial pathogens with resistance to the carbapenem antibiotics. However, little is known about the antibacterial T6SS in K. pneumoniae. Using core-component protein searches, we identified a putative T6SS gene cluster on the chromosome of the carbapenemase-producing K. pneumoniae (CRKP) strain HS11286. Intraspecies and interspecies competition assays revealed an antibacterial function of the HS11286 T6SS. The phospholipase Tle1KP was found to be an effector protein that is transferred by T6SS. The overexpression of this effector gene in the periplasm caused severe growth inhibition of Escherichia coli. A sub-inhibitory concentration of b-lactam antibiotics stimulated the expression and secretion of the HS11286 T6SS and enhanced T6SS-dependent killing. It suggested that the antibiotics might be an impact factor for the T6SS secretion and antibacterial activity. [ABSTRACT FROM AUTHOR]

Background: Keratoconus normally presents as a sporadic disease. Although different studies have found sequence variants of the visual system homeobox 1 (VSX1) gene associated with keratoconus in humans, no research has detected such variants in sporadic keratoconus patients from China. To investigate the possibility of VSX1 being a candidate susceptibility gene for Chinese patients with sporadic keratoconus, we performed sequence screening of this gene in such patients.Methods: Whole DNA was obtained from the leukocytes in the peripheral venous blood of 50 patients with sporadic keratoconus and 50 control subjects without this ocular disorder. Polymerase chain reaction single-strand conformation polymorphism analysis and direct DNA sequencing technology were used to detect sequence variation in the five exons and splicing regions of the introns of the VSX1 gene. The sequencing results were analyzed using DNAstar software.Results: One novel missense heterozygous sequence variant (p.Arg131Pro) was found in the first exon of the VSX1 gene in one keratoconus patient. Another heterozygous sequence variant (p.Gly160Val) in the second exon was found in two keratoconus patients. These variants were not detected in the control subjects. In the third intron of the VSX1 gene, c.8326G > A nucleotide substitution (including heterozygous and homozygous change) was also discovered. The frequency of this variation did not differ significantly between patients and controls, it should belong to single-nucleotide polymorphism of the VSX1 gene. Bioinformatic analysis also predicted that one missense sequence variation (p.Arg131Pro) may not cause a pathogenic change.Conclusions: In this study, we added one novel missense sequence variation (p.Arg131Pro) in the coding region of the VSX1 gene to the range of VSX1 coding region variations observed in patients with sporadic keratoconus from China. Our work suggests that VSX1 sequence variants might be involved in the pathogenesis of sporadic keratoconus, but their precise role in disease causation requires further investigation. [ABSTRACT FROM AUTHOR]

DNA replication initiation is a central event in the cell cycle, and it is strictly controlled by multiple regulatory mechanisms. Our previous work showed that acetylation of residue lysine (K) 178 prevents DnaA from binding to ATP, which leads to the inhibition of DNA replication initiation. Here, we show that another residue, K243, is critical for DnaA full activity in vivo. K243 can be acetylated, and its acetylation level varies with cell growth. A homogeneous, recombinant DnaA that contains N+-acetyllysine at K243 (K243Ac) retained its ATP/ADP binding ability, but showed decreased binding activity to the oriC region. A DNase I footprinting assay showed that DnaA K243Ac failed to recognize DnaA boxes I3, C1, and C3, and, thus, it formed an incomplete initiation complex with oriC. Finally, we found that acetyl phosphate and the deacetylase CobB can regulate the acetylation level of K243 in vivo. These findings suggest that DnaA K243 acetylation disturbs its binding to low-affinity DnaA boxes, and they provide new insights into the regulatory mechanisms of DNA replication initiation. [ABSTRACT FROM AUTHOR]

Extracellular vesicles have emerged as important mediators of intercellular communication and play an active role in cancer, including breast cancer. Despite limited studies, initial observations suggest that these vesicles are important in breast physiology and pathophysiology. We here, in brief, describe their potential use as future biomarkers and therapeutic agents in breast cancer. Extracellular vesicles in blood and breast fluid may have a great potential to detect and predict the presence of breast cancer, and extracellular vesicles modulation may emerge as a therapeutic approach in cancer therapy. [ABSTRACT FROM AUTHOR]

The article discusses the study which identifies the potential proteins in acetyltransferase Pat- or deacetylase CobB-mediated acetylation through screening Salmonella Typhimurium's genome library using the bacterial two-hybrid system.

Background: Reis-Bücklers corneal dystrophy (RBCD) was consistently reported as a corneal dystrophy only affected Bowman's layer and superficial corneal stroma, and superficial keratectomy was a recommendation surgery for treatment in literatures. The study reported new histopathological and ultrastructural findings in RBCD caused by the Arg124Leu mutation of transforming growth factor induced (TGFBI) gene in a four-generation Chinese pedigree.Methods: Subjects including eight patients and seven unaffected family members received slit-lamp biomicroscopy and photography. DNA was obtained from all subjects, and exons 4 and 11 to 14 of TGFBI gene were analyzed by polymerase chain reaction and the products were sequenced. Anterior segment optical coherence tomography (AS OCT) and in vivo confocal microscopy were conducted for ten eyes of five patients. Based on the results of AS OCT and in vivo confocal microscopy, deep anterior lamellar keratoplasty (DLKP) using cryopreserved donor cornea was applied for four eyes of four patients. Four lamellar dystrophic corneal buttons were studied by light and transmission electron microscopy, and TGFBI immunohistochemistry.Results: Eight patients had typical clinical manifestations of RBCD presenting recurrent painful corneal erosion starting in their early first decades, along with age-dependent progressive geographic corneal opacities. TGFBI sequencing revealed a heterozygous mutation, Arg124Leu in all eight patients. Anterior segment optical coherence tomography and in vivo confocal microscopy showed the dystrophic deposits involved not only in subepithelial and superficial stroma, but also in mid- or posterior stroma in four examined advanced eyes. Light microscopy showed Bowman's layer was absent, replaced by abnormal deposits stain bright red with Masson's trichrome. In superficial cornea, the deposits stacked and produced three to five continuous bands parallel to the corneal collagen lamellae. In mid- to posterior stroma, numerous granular or dot- like aggregates were heavily scattered, and most of them presented around the nuclei of stromal keratocytes. Transmission electron microscopy revealed the multiple electron-dense rod-shaped deposits aggregated and formed a characteristic pattern of three to five continuous bands in superficial cornea, which were similar to those seen under light microscopy. In mid- to posterior stroma, clusters of rod-shaped bodies were scattered extracellular or intracellular of the stromal keratocytes between the stromal lamellae suggesting the close relationship between mutated proteins and keratocyte.Conclusions: The study offer evidences indicating DLKP is a viable treatment option for advanced RBCD to avoid recurrence, and the mutated TGFBIp in dystrophic corneas are of keratocytes origin. [ABSTRACT FROM AUTHOR]

Pterygium is a common ophthalmic disease affecting humans only. Extensive epidemiological data have demonstrated a causative effect of chronic ultraviolet (UV) radiation on pterygia. Progress has been made in determining the origin of pterygia, their nasal predilection and wing-shaped appearance, and the roles of UV radiation in the initiation and the development of pterygia. In the present review, the current understanding of the involvement of UV radiation in the pathogenesis of pterygia is summarized. This involvement includes the alteration of limbal stem cells and fibroblasts that contribute to the initiation of pterygia and the induction of various pro-inflammatory cytokines, growth factors and matrix metalloproteinases that promote the progression of pterygia. Further elucidation of the roles of UV radiation in the pathogenesis of pterygia may help to encourage individuals at risk of developing pterygia to take preventive measures and aid researchers in the development of novel targeted therapeutic agents to treat pterygia. [ABSTRACT FROM AUTHOR]

Salmonella causes a range of diseases in different hosts, including enterocolitis and systemic infection. Lysine acetylation regulates many eukaryotic cellular processes, but its function in bacteria is largely unexplored. The acetyltransferase Pat and NAD(+)-dependent deacetylase CobB are involved in the reversible protein acetylation in Salmonella Typhimurium. Here, we used cell and animal models to evaluate the virulence of pat and cobB deletion mutants in S. Typhimurium and found that pat is critical for bacterial intestinal colonization and systemic infection. Next, to understand the underlying mechanism, genome-wide transcriptome was analyzed. RNA sequencing data showed that the expression of Salmonella pathogenicity island 1 (SPI-1) is partially dependent on pat In addition, we found that HilD, a key transcriptional regulator of SPI-1, is a substrate of Pat. The acetylation of HilD by Pat maintained HilD stability and was essential for the transcriptional activation of HilA. Taken together, these results suggest that a protein acetylation system regulates SPI-1 expression by controlling HilD in a posttranslational manner to mediate S. Typhimurium virulence. [ABSTRACT FROM AUTHOR]

Highly Ga-doped ZnO (GZO) films of thicknesses d = 5, 25, 50, and 300 nm, grown on 160-nm ZnO buffer layers by molecular beam epitaxy, had 294-K Hall-effect mobilities μH of 64.1, 43.4, 37.0, and 34.2 cm²/V-s, respectively. This extremely unusual ordering of μH vs d is explained by the existence of a very high-mobility Debye tail in the ZnO, arising from the large Fermi-level mismatch between the GZO and the ZnO. Scattering theory in conjunction with Poisson analysis predicts a Debye-tail mobility of 206 cm²/V-s at the interface (z = d), falling to 58 cm²/V-s at z = d + 2 nm. Excellent fits to μH vs d and sheet concentration ns vs d are obtained with no adjustable parameters. [ABSTRACT FROM AUTHOR]

Lipoprotein NlpI of Escherichia coli is involved in the cell division, virulence, and bacterial interaction with eukaryotic host cells. To elucidate the functional mechanism of NlpI, we examined how NlpI affects cell division and found that induction of NlpI inhibits nucleoid division and halts cell growth. Consistent with these results, the cell division protein FtsZ failed to localize at the septum but diffused in the cytosol. Elevation of NlpI expression enhanced the transcription and the outer membrane localization of the heat shock protein IbpA and IbpB. Deletion of either ibpA or ibpB abolished the effects of NlpI induction, which could be restored by complementation. The C-terminus of NlpI is critical for the enhancement in IbpA and IbpB production, and the N-terminus of NlpI is required for the outer membrane localization of NlpI, IbpA, and IbpB. Furthermore, NlpI physically interacts with IbpB. These results indicate that over-expression of NlpI can interrupt the nucleoids division and the assembly of FtsZ at the septum, mediated by IbpA/IbpB, suggesting a role of the NlpI/IbpA/IbpB complex in the cell division. [ABSTRACT FROM AUTHOR]

Further reduction of the efficiency droop effect and further enhancements of internal quantum efficiency (IQE) and output intensity of a surface plasmon coupled, blue-emitting light-emitting diode (LED) by inserting a dielectric interlayer (DI) of a lower refractive index between p-GaN and surface Ag nanoparticles are demonstrated. The insertion of a DI leads to a blue shift of the localized surface plasmon (LSP) resonance spectrum and increases the LSP coupling strength at the quantum well emitting wavelength in the blue range. With SiO2 as the DI, a thinner DI leads to a stronger LSP coupling effect, when compared with the case of a thicker DI. By using GaZnO, which is a dielectric in the optical range and a good conductor under direct-current operation, as the DI, the LSP coupling results in the highest IQE, highest LED output intensity, and weakest droop effect. [ABSTRACT FROM AUTHOR]

Two sets of light-emitting diodes (LEDs) based on two epitaxial structures of different p-GaN layer thicknesses for demonstrating the effects of localized surface plasmon (LSP) coupling with the quantum wells (QWs) in the LEDs are compared. In the first set based on the epitaxial structure of thick p-GaN, to reduce the distance between the Ag nanoparticles (NPs) and QWs for increasing the LSP coupling strength, Ag NPs are filled into a hole array fabricated on the p-GaN layer. In the second set based on the epitaxial structure of thin p-GaN, Ag NPs are fabricated on the top surface of the p-GaN layer. The LSP-coupled LEDs show the significant enhancements of internal quantum efficiency and LED output intensity even though the coverage of the transparent conductor, GaZnO, red-shifts the LSP resonance peak such that the LSP resonance at the QW emission wavelength becomes weaker. [ABSTRACT FROM PUBLISHER]

The void structures and related optical properties after thermal annealing with ambient oxygen in regularly patterned ZnO nanrorod (NR) arrays grown with the hydrothermal method are studied. In increasing the thermal annealing temperature, void distribution starts from the bottom and extends to the top of an NR in the vertical (c-axis) growth region. When the annealing temperature is higher than 400°C, void distribution spreads into the lateral (m-axis) growth region. Photoluminescence measurement shows that the ZnO band-edge emission, in contrast to defect emission in the yellow-red range, is the strongest under the n-ZnO NR process conditions of 0.003 M in Ga-doping concentration and 300°C in thermal annealing temperature with ambient oxygen. Energy dispersive X-ray spectroscopy data indicate that the concentration of hydroxyl groups in the vertical growth region is significantly higher than that in the lateral growth region. During thermal annealing, hydroxyl groups are desorbed from the NR leaving anion vacancies for reacting with cation vacancies to form voids. [ABSTRACT FROM AUTHOR]

Background: Mycotic keratitis in human cornea has been rarely reported to be associated with a co-infection of filamentous fungi and yeast. This paper aims to report a case of mycotic keratitis concurrently infected by Exserohilum mcginnisii and Candida parapsilosis. Case presentation: A Chinese female presented two superposed corneal infiltrates with different size and texture on her left eye. In vivo confocal microscopy showed hyper-reflective multiple linear with highly branching structures distributing in the anterior corneal stroma. Inoculations of the corneal lesion scrape concurrently grew two similar superposed colonies on Sabouraud dextrose and chocolate agar plate. The larger colony exhibited mould, cottony and floccose at the edge, while the smaller one showed creamy and shiny surface. Modified slide culture for mould revealed hyphae were septate, and conidia were brown, smooth-walled, cylindrical to slight clavate with 6 to 13 pseudosepta. Based on the morphology of microscopic and macroscopic characteristics, the mould was identified as Exserohilum mcginnisii. Smear of the non-mould colony showed ellipse or ovoid budding yeast-like cells with abundant pseudomycelium. Vitek Yeast Biochemical Card test identified the yeast as Candida parapsilosis. With treatment of combined oral itraconazole with topical amphotericin B, a complete resolution of the corneal infiltrate was achieved within 1.5 months. Conclusion: This is the first documented case of human corneal infection by Exserohilum mcginnisii, and also the first report providing evidence of mycotic keratitis in human cornea concurrently infected by filamentous fungi and yeast. [ABSTRACT FROM AUTHOR]

Background. Low expression or absence of dendritic cell (DC) surface B7molecules can induce immune tolerance or hyporesponse. Whether DCs could induce indirect allogeneic-specific cross-tolerance or hyporesponse to recipient T cells remains unclear. Methods. Generated from C3H/He mice bone marrow cells pulsed with donor antigen from C57BL/6 mice, recipient DCs were incubated with B7 antisense peptide (B7AP). Immune regulatory activities were examined in vitro by a series of mixed lymphocyte reactions. Murine allogeneic carotid artery orthotopic transplantation was performed from C57BL/6 to C3H/He. Recipients were given B7AP-treated DCs 7 days before transplantation. Allograft pathological analysis was done 2 months after transplantation. Results. B7AP-pretreated DCs markedly inhibited T-cell proliferation compared with untreated group. Pretreated T cells exhibited markedly reduced response to alloantigen versus third-party antigen. Pathological analysis of arterial allografts demonstrated significant reduction of intimal hyperplasia in B7-AP pretreated group versus control. Conclusion. Blockade of B7 molecules by B7AP could induce indirect allogeneic-specific hyporesponse and inhibit arterial allograft intimal hyperplasia, which may be involved in future strategies for human allograft chronic rejection. [ABSTRACT FROM AUTHOR]

We studied the microbial diversity in the sediment from the Kongsfjorden, Svalbard, Arctic, in the summer of 2005 based on the analysis of 16S rRNA and 18S rRNA gene clone libraries. The sequences of the cloned 16S rRNA and 18S rRNA gene inserts were used to determine the species identity or closest relatives by comparison with sequences of known species. Compared to the other samples acquired in Arctic and Antarctic, which are different from that of ours, the microbial diversity in our sediment is much higher. The bacterial sequences were grouped into 11 major lineages of the domain Bacteria: Proteobacteria (include α-, β-, γ-, δ-, and ε-Proteobacteria); Bacteroidetes; Fusobacteria; Firmicutes; Chloroflexi; Chlamydiae; Acidobacteria; Actinobacteria; Planctomycetes; Verrucomicrobiae and Lentisphaerae. Crenarchaeota were dominant in the archaeal clones containing inserts. In addition, six groups from eukaryotes including Cercozoa, Fungi, Telonema, Stramenopiles, Alveolata, and Metazoa were identified. Remarkably, the novel group Lentisphaerae was reported in Arctic sediment at the first time. Our study suggested that Arctic sediment as a unique habitat may contain substantial microbial diversity and novel species will be discovered. [ABSTRACT FROM AUTHOR]

A CdZnO/n-ZnO multiple-quantum-well (QW) light-emitting diode (LED), with the QWs and n+-ZnO capping layer grown with molecular beam epitaxy on p-GaN, which is grown with metal-organic chemical vapor deposition, is fabricated and characterized. Because of the weak carrier localization mechanism in the ZnO-based LED, its defect emission is quite strong and dominates the LED output when injection current is low. The blue shift of the LED output spectrum in applying a forward-biased voltage and the large blue-shift range in increasing injection current show the different behaviors of such a ZnO-based LED from those of a nitride LED. [ABSTRACT FROM PUBLISHER]

Pre-Descemet's membrane corneal dystrophy is clinically characterized by the presence of numerous tiny pleomorphic opacities located in the deep stroma immediately anterior to Descemet's membrane. A 35-year-old man, clinically diagnosed with pre-Descemet's corneal dystrophy, was examined by in vivo slit scan confocal microscopy. The pleomorphic structures containing dense hyperreflective inclusions in the posterior stroma were revealed in vivo. To the best of the authors' knowledge, it is consistent with the result of the previous histological study, but different from other reports using in vivo confocal microscopy. [ABSTRACT FROM AUTHOR]

The growth of regularly patterned multi-section GaN nanorod (NR) arrays based on a pulsed growth technique with metalorganic chemical vapor deposition is demonstrated. Such an NR with multiple sections of different cross-sectional sizes is formed by tapering a uniform cross section to another through stepwise decreasing of the Ga supply duration to reduce the size of the catalytic Ga droplet. Contrast line structures are observed in either a scanning electron microscopy or transmission electron microscopy image of an NR. Such a contrast line-marker corresponds to a thin Ga-rich layer formed at the beginning of GaN precipitation of a pulsed growth cycle and illustrates the boundary between two successive growth cycles in pulsed growth. By analyzing the geometry variation of the contrast line-markers, the morphology evolution in the growth of a multi-section NR, including a tapering process, can be traced. Such a morphology variation is controlled by the size of the catalytic Ga droplet and its coverage range on the slant facets at the top of an NR. The comparison of emission spectra between single-, two-, and three-section GaN NRs with sidewall InGaN/GaN quantum wells indicates that a multi-section NR can lead to a significantly broader sidewall emission spectrum. [ABSTRACT FROM AUTHOR]

First, the experimental implementations and theoretical/numerical investigations of surface plasmon (SP) coupled InGaN/GaN quantum-well light-emitting diodes (LEDs) are reviewed. If the p-GaN layer in an LED can be thin, surface metal nanoparticle (NP) is an inexpensive structure for inducing effective SP coupling. When the p-GaN layer is thick, a few metal structures, including metal protrusion, buried metal NP, and embedded metal NP, can be used for effective SP coupling. In the numerical study, an algorithm, including the feedback effect of the induced SP resonance on the radiating behavior of the source dipole, has been proposed for studying the SP coupling effects with an embedded metal NP, a surface metal NP, and a metal protrusion. Then, the theoretical formulations and numerical algorithms for evaluating the radiated power enhancement in the coupling process between two radiating dipoles and the localized surface plasmon (LSP) induced on a nearby Ag NP are built. Three mechanisms are considered in the coupling process for radiated power enhancement, including the interference of the two phase-retarded radiation contributions from the two dipoles, the interaction between the two dipoles, and the LSP resonant coupling. [ABSTRACT FROM AUTHOR]