A line search filter approach for the system of nonlinear equations

AbstractSome constrained optimization approaches have been recently proposed for the system of nonlinear equations (SNE). Filter approach with line search technique is employed to attack the system of nonlinear equations in this paper. The system of nonlinear equations is transformed into a constrained nonlinear programming problem at each step, which is then solved by line search strategy. Furthermore, at each step, some equations are treated as constraints while the others act as objective functions, and filter strategy is then utilized. In essence, constrained optimization methods combined with filter technique are utilized to cope with the system of nonlinear equations

Profiling and Identification of the Metabolites of Evodiamine in Rats using Ultra–Performance Liquid Chromatography with Linear Ion Trap Orbitrap Mass Spectrometer

Purpose: To develop a highly sensitive and specific ultra-performance liquid chromatography with linear ion trap Orbitrap mass spectrometer (UPLC-LTQ-Orbitrap) method to profile and identify the metabolites of evodiamine in rats.Methods: First, blood samples were collected after oral administration of evodiamine to rats (50 mg/kg). Next, the plasma samples were pretreated using a solid-phase extraction (SPE) method. Finally, all the samples were analyzed by ultra-performance liquid chromatography LTQ-Orbitrap mass spectrometry (UPLC-LTQ- Orbitrap) coupled with electrospray ionization source (ESI) in negative mode.Results: A total of 7 metabolites (2 phase I and 4 phase II metabolites, including 4 new metabolites, viz, 10-hydroxyevodiamine sulfate, 10-hydroxyevodiamine sulfate, 10-hydroxyevodiamine glucuronide and 3-hydroxyevodiamine glucuronide) as well as the parent drug itself , were detected and identified based on accurate mass measurements, fragmentation patterns, and chromatographic retention times. The in vivo metabolic reactions of evodiamine in rats were hydroxylation, hydroxylation + sulfate conjugation, and hydroxylation + glucuronidation.Conclusion: These results provide better understanding of the metabolism of evodiamine as well as strong indications of the effective forms of the drug in vivo.Keywords: Evodiamine, Ultra–performance liquid chromatography with linear ion trap-Orbitrap, Hydroxyevodiamine sulfate, Hydroxyevodiamine glucuronide, Metabolite

Recurrent deletions of ULK4 in schizophrenia : a gene crucial for neuritogenesis and neuronal motility

Peer reviewedPublisher PD

Comparative proteome analysis revealed the differences in response to both Mycobacterium tuberculosis and Mycobacterium bovis infection of bovine alveolar macrophages

Tuberculosis (TB), attributed to the Mycobacterium tuberculosis complex, is one of the most serious zoonotic diseases worldwide. Nevertheless, the host mechanisms preferentially leveraged by Mycobacterium remain unclear. After infection, both Mycobacterium tuberculosis (MTB) and Mycobacterium bovis (MB) bacteria exhibit intimate interactions with host alveolar macrophages; however, the specific mechanisms underlying these macrophage responses remain ambiguous. In our study, we performed a comparative proteomic analysis of bovine alveolar macrophages (BAMs) infected with MTB or MB to elucidate the differential responses of BAMs to each pathogen at the protein level. Our findings revealed heightened TB infection susceptibility of BAMs that had been previously infected with MTB or MB. Moreover, we observed that both types of mycobacteria triggered significant changes in BAM energy metabolism. A variety of proteins and signalling pathways associated with autophagy and inflammation-related progression were highly activated in BAMs following MB infection. Additionally, proteins linked to energy metabolism were highly expressed in BAMs following MTB infection. In summary, we propose that BAMs may resist MTB and MB infections via different mechanisms. Our findings provide critical insights into TB pathogenesis, unveiling potential biomarkers to facilitate more effective TB treatment strategies. Additionally, our data lend support to the hypothesis that MTB may be transmitted via cross-species infection

<i>Bauhinia</i> (Leguminosae) Fossils from the Paleogene of Southwestern China and Its Species Accumulation in Asia

Extant Bauhinia (Leguminosae) is a genus of 300 species of trees, shrubs, and lianas, widely distributed in pantropical areas, but its diversification history in southeastern Asia, one of its centers of highest diversity, remains unclear. We report new fossils of three Bauhinia species with cuticular preservation from the Paleogene of Puyang Basin, southwestern China. Our finding likely extends the emergence of Bauhinia in Asia to the late Eocene. Together with previously reported fossil records, we show that the diversification of Bauhinia in Asia and the phenomenon of a small region harboring multiple Bauhinia species in southwestern China could be traced back to the Paleogene

Electron spin resonance resolves intermediate triplet states in delayed fluorescence.

Molecular organic fluorophores are currently used in organic light-emitting diodes, though non-emissive triplet excitons generated in devices incorporating conventional fluorophores limit the efficiency. This limit can be overcome in materials that have intramolecular charge-transfer excitonic states and associated small singlet-triplet energy separations; triplets can then be converted to emissive singlet excitons resulting in efficient delayed fluorescence. However, the mechanistic details of the spin interconversion have not yet been fully resolved. We report transient electron spin resonance studies that allow direct probing of the spin conversion in a series of delayed fluorescence fluorophores with varying energy gaps between local excitation and charge-transfer triplet states. The observation of distinct triplet signals, unusual in transient electron spin resonance, suggests that multiple triplet states mediate the photophysics for efficient light emission in delayed fluorescence emitters. We reveal that as the energy separation between local excitation and charge-transfer triplet states decreases, spin interconversion changes from a direct, singlet-triplet mechanism to an indirect mechanism involving intermediate states

MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma

<p>Abstract</p> <p>Background</p> <p>MiR-221 and miR-222 (miR-221/222) are frequently up-regulated in various types of human malignancy including glioblastoma. Recent studies have reported that miR-221/222 regulate cell growth and cell cycle progression by targeting p27 and p57. However the underlying mechanism involved in cell survival modulation of miR-221/222 remains elusive.</p> <p>Results</p> <p>Here we showed that miR-221/222 inhibited cell apoptosis by targeting pro-apoptotic gene PUMA in human glioma cells. Enforced expression of miR-22/222 induced cell survival whereas knockdown of miR-221/222 rendered cells to apoptosis. Further, miR-221/222 reduced PUMA protein levels by targeting PUMA-3'UTR. Introducing PUMA cDNA without 3'UTR abrogated miR-221/222-induced cell survival. Notably, knockdown of miR-221/222 induces PUMA expression and cell apoptosis and considerably decreases tumor growth in xenograft model. Finally, there was an inverse relationship between PUMA and miR-221/222 expression in glioma tissues.</p> <p>Conclusion</p> <p>To our knowledge, these data indicate for the first time that miR-221/222 directly regulate apoptosis by targeting PUMA in glioblastoma and that miR-221/222 could be potential therapeutic targets for glioblastoma intervention.</p