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Biomedical subjects

Ye Tao

Publications and source records attributed to Ye Tao.

17 recordsLinked to original sources

Fragmentomics of plasma mitochondrial and nuclear DNA inform prognosis in COVID-19 patients with critical symptoms.

BACKGROUND: The mortality rate of COVID-19 patients with critical symptoms is reported to be 40.5%. Early identification of patients with poor progression in the critical cohort is essential to timely clinical intervention and reduction of mortality. Although older age, chronic diseases, have been recognized as risk factors for COVID-19 mortality, we still lack an accurate prediction method for every patient. This study aimed to delve into the cell-free DNA fragmentomics of critically ill patients, and develop new promising biomarkers for identifying the patients with high mortality risk. METHODS: We utilized whole genome sequencing on the plasma cell-free DNA (cfDNA) from 33 COVID-19 patients with critical symptoms, whose outcomes were classified as survival (n = 16) and death (n = 17). Mitochondrial DNA (mtDNA) abundance and fragmentomic properties of cfDNA, including size profiles, ends motif and promoter coverages were interrogated and compared between survival and death groups. RESULTS: Significantly decreased abundance (~ 76% reduction) and dramatically shorter fragment size of cell-free mtDNA were observed in deceased patients. Likewise, the deceased patients exhibited distinct end-motif patterns of cfDNA with an enhanced preference for "CC" started motifs, which are related to the activity of nuclease DNASE1L3. Several dysregulated genes involved in the COVID-19 progression-related pathways were further inferred from promoter coverages. These informative cfDNA features enabled a high PPV of 83.3% in predicting deceased patients in the critical cohort. CONCLUSION: The dysregulated biological processes observed in COVID-19 patients with fatal outcomes may contribute to abnormal release and modifications of plasma cfDNA. Our findings provided the feasibility of plasma cfDNA as a promising biomarker in the prognosis prediction in critically ill COVID-19 patients in clinical practice.

Humans↗

Anticancer benzoxaboroles block pre-mRNA processing by directly inhibiting CPSF3.

A novel class of benzoxaboroles was reported to induce cancer cell death but the mechanism was unknown. Using a forward genetics platform, we discovered mutations in cleavage and polyadenylation specific factor 3 (CPSF3) that reduce benzoxaborole binding and confer resistance. CPSF3 is the endonuclease responsible for pre-mRNA 3'-end processing, which is also important for RNA polymerase II transcription termination. Benzoxaboroles inhibit this endonuclease activity of CPSF3 in vitro and also curb transcriptional termination in cells, which results in the downregulation of numerous constitutively expressed genes. Furthermore, we used X-ray crystallography to demonstrate that benzoxaboroles bind to the active site of CPSF3 in a manner distinct from the other known inhibitors of CPSF3. The benzoxaborole compound impeded the growth of cancer cell lines derived from different lineages. Our results suggest benzoxaboroles may represent a promising lead as CPSF3 inhibitors for clinical development.

Cleavage And Polyadenylation Specificity Factor↗

cTrans: generating polypeptide databases from cDNA sequences.

cTrans is a comprehensive utility used to generate polypeptide databases from cDNA sequences. The goal is achieved through integrating four main functions, including retrieving sequences of species of interest from the downloaded packages from dbEST of GenBank, format conversion, checking and deleting vector and adaptor contamination, and translating the cDNA sequences in all six frames and selecting specific translations for database construction in a user-defined length threshold. In addition, this utility is also applicable to cDNA sequences produced by users themselves.

Base Sequence↗

Heart development in Drosophila.

The Drosophila heart, also called the dorsal vessel, is an organ for hemolymph circulation that resembles the vertebrate heart at its transient linear tube stage. Dorsal vessel morphogenesis shares several similarities with early events of vertebrate heart development and has proven to be an insightful system for the study of cardiogenesis due to its relatively simple structure and the productive use of Drosophila genetic approaches. In this review, we summarize published findings on Drosophila heart development in terms of the regulators and genetic pathways required for cardiac cell specification and differentiation, and organ formation and function. Emerging genome-based strategies should further facilitate the use of Drosophila as an advantageous system in which to identify previously unknown genes and regulatory networks essential for normal cardiac development and function.

Animals↗

Synthesis and light-emitting properties of bipolar oligofluorenes containing triarylamine and 1,2,4-triazole moieties.

A facile approach for synthesis of bipolar oligofluorenes, TAZ-OF(n)-NPh, n = 2 or 3 end-capped with hole-transporting diphenylamino and electron-transporting triazole moieties by Suzuki cross-coupling as the key reaction has been developed. This novel bipolar oligofluorenes exhibited blue-emission, high thermal and morphological stabilities. The single-layer OLED based on TAZ-OF(2)-NPh exhibited superior device performance with a maximum luminance of 1128 cd m(-2) and luminance efficiency of up to 0.83 cd A(-1).

Journal Article↗

Early and frequent histological recurrence of Crohn's disease in small intestinal allografts.

BACKGROUND: Recurrence of Crohn's disease in small intestinal allografts, although rarely described, can cause serious morbidity and jeopardize graft survival among transplant recipients with Crohn's disease. However, systematic studies to determine the frequency, predictors, and clinical implications of recurrent Crohn's disease have not been reported METHODS: We analyzed our transplant program's experience with small intestinal allografts in patients with Crohn's disease based on retrospective review of clinical and pathological records and corresponding pathology slides. RESULTS: Of 67 patients undergoing 70 transplantations between 1998 and 2004, six adults (three males, three females; mean age 48.1 years) had Crohn's disease complicated by short gut syndrome and total parenteral nutrition failure. Four survivors surveyed endoscopically for a mean 29 (range, 20-40) months and underwent a mean 37 endoscopic examinations with biopsies (range, 31-44) while on maintenance immunosuppression. Despite absence of any endoscopic or clinical manifestations of Crohn's disease throughout this period, two patients had granulomatous enteritis characteristic of Crohn's disease in multiple biopsies, one patient in 8/44 examinations (18%) ranging from 34 days to 20 months postoperatively and the other in 6/32 examinations (19%) ranging from 20 days to 22 months postoperatively. No comparable changes occurred in 57 other patients without Crohn's disease followed endoscopically under the same protocol CONCLUSIONS: Histological recurrence of Crohn's disease may occur in small intestinal allografts despite the absence of endoscopic and clinical disease manifestations. Such recurrences are probably not rare, may occur as early as 3 weeks after transplantation, and do not necessarily portend early clinical recurrence or mandate aggressive therapy to prevent allograft loss.

Adult↗

New phosphorescent polynuclear Cu(I) compounds based on linear and star-shaped 2-(2'-pyridyl)benzimidazolyl derivatives: syntheses, structures, luminescence, and electroluminescence.

Four dinuclear and trinuclear Cu(I) complexes that contain 2-(2'-pyridyl)benzimidazolyl derivative ligands including 1,4-bis[2-(2'-pyridyl)benzimidazolyl]benzene (1,4-bmb), 1,3-bis[2-(2'-pyridyl)benzimidazolyl]benzene (1,3-bmb), 1,3,5-tris[2-(2'-pyridyl)benzimidazolyl]benzene (tmb), and 4,4'-bis[2-(2'-pyridyl)benzimidazolyl]biphenyl (bmbp) have been synthesized. The formulas of these complexes are [Cu(2)(1,4-bmb)(PPh(3))(4)][BF(4)](2) (1), [Cu(2)(1,3-bmb)(PPh(3))(4)][BF(4)](2) (2), [Cu(3)(tmb)(PPh(3))(6)][BF(4)](3) (3), and [Cu(2)(bmbp)(PPh(3))(4)][BF(4)](2) (4), respectively. The crystal structures of 2-4 have been determined by single-crystal X-ray diffraction analyses. The Cu(I) ions in the complexes have a distorted tetrahedral geometry. For 3, two structural isomers (syn and anti) resulted from two different orientations of the three 2-(2'-pyridyl)benzimidazolyl chelating units were observed in the crystal lattice. Variable-temperature (1)H NMR experiments established the presence of syn and anti isomers for 1-3 in solution which interconvert at ambient temperature. Complexes 1-4 have a weak MLCT absorption band in the 350-450 nm region and display a yellow-orange emission when irradiated by UV light. One unexpected finding is that the yellow-orange emission of complexes 1-4 has a very long decay lifetime (approximately 200 micros) at 77 K. An electroluminescent (EL) device using 4 as the emitter and PVK as the host was fabricated. However, the long decay lifetime of the copper complexes may limit their applications as phosphorescent emitters in EL devices.

Journal Article↗

Diphenylamino end-capped oligofluorenes with enhanced functional properties for blue light emission: synthesis and structure-property relationships.

A novel series of monodisperse asymmetrically and symmetrically substituted diphenylamino end-capped oligofluorenes, OF(2)-NPhR, R = H or An (An = 9-anthryl) and OF(n)-NPh, n = 2-4, has been synthesized by a convergent approach using palladium-catalyzed Suzuki cross-coupling. End-capping of oligofluorenes with diphenylamino group(s) has been shown to offer advantages in terms of lowering their first ionization potentials, enhancing thermal stability, and inducing good amorphous morphological stability. By tuning the number of diphenylamino end-caps and the chain length, the optimal conjugated length for optical and luminescence properties has been determined. Of all the hitherto reported oligofluorenes capable of serving as non-doped blue emitters, OF(3)-NPh, with an optimal conjugated length, exhibits some of the best hole-transport and blue-emitting properties. A maximum luminance of 7500 cd m(-2) and a luminance efficiency up to 1.8 cd A(-1) have been achieved.

Journal Article↗

Organoboron compounds with an 8-hydroxyquinolato chelate and its derivatives: substituent effects on structures and luminescence.

Four new luminescent organoboron complexes have been synthesized and fully characterized. These compounds are four-coordinate boron chelated by either 8-hydroxyquinolato (q) or functionalized 8-hydroxylquinolato ligands, including BPh2(5-(1-naphthyl)-q) (1), BPh2(5-(2-benzothienyl)-q) (2), B(2-benzothienyl)2q (3), and B(2-benzothienyl)2(2-Me-q) (4). All four compounds have a tetrahedral geometry as established by X-ray diffraction analyses. In solution, compounds 1-4 have an emission maximum at 534, 565, 501, and 496 nm, respectively, at room temperature. They emit similar colors in the solid states without red shifts of the emission band due to the lack of significant intermolecular interactions in the crystal lattices. The substituent group at C5 or C2 position of the 8-hydroxyquinolato ligand has been observed to have a significant impact on the emission energy and the emission quantum efficiency of the boron complexes. Molecular orbital calculations (Gaussian 98) showed that the electronic transition of 1 and 2 is a pi-pi* transition centered on the functionalized 8-hydroxyquinolato group and the electronic transition of 3 and 4 is an interligand charge transfer from the 2-benzothienyl ligand to the hydroxyquinolato ring. A double-layer electroluminescent device using 3 as the emitter has been fabricated, which produced a broad emission band with a significant contribution of exciplex emission.

Journal Article↗

Rational design of a mononuclear metal site into the archaeal Rieske-type protein scaffold.

Proteins containing Rieske-type [2Fe-2S] clusters play essential functions in all three domains of life. We engineered the two histidine ligands to the Rieske-type [2Fe-2S] cluster in the hyperthermophilic archaeal Rieske-type ferredoxin from Sulfolobus solfataricus to modify types and spacing of ligands and successfully converted the metal and cluster type at the redox-active site with a minimal structural change to a native Rieske-type protein scaffold. Spectroscopic analyses unambiguously established a rubredoxin-type mononuclear Fe3+/2+ center at the engineered local metal-binding site (Zn2+ occupies the iron site depending on the expression conditions). These results show the importance of types and spacing of ligands in the in vivo cluster recognition/insertion/assembly in biological metallosulfur protein scaffolds. We suggest that early ligand substitution and displacement events at the local metal-binding site(s) might have primarily allowed the metal and cluster type conversion in ancestral redox protein modules, which greatly enhanced their capabilities of conducting a wide range of unique redox chemistry in biological electron transfer conduits, using a limited number of basic protein scaffolds.

Amino Acid Sequence↗

Expression, regulation, and requirement of the toll transmembrane protein during dorsal vessel formation in Drosophila melanogaster.

Early heart development in Drosophila and vertebrates involves the specification of cardiac precursor cells within paired progenitor fields, followed by their movement into a linear heart tube structure. The latter process requires coordinated cell interactions, migration, and differentiation as the primitive heart develops toward status as a functional organ. In the Drosophila embryo, cardioblasts emerge from bilateral dorsal mesoderm primordia, followed by alignment as rows of cells that meet at the midline and morph into a dorsal vessel. Genes that function in coordinating cardioblast organization, migration, and assembly are integral to heart development, and their encoded proteins need to be understood as to their roles in this vital morphogenetic process. Here we prove the Toll transmembrane protein is expressed in a secondary phase of heart formation, at lateral cardioblast surfaces as they align, migrate to the midline, and form the linear tube. The Toll dorsal vessel enhancer has been characterized, with its activity controlled by Dorsocross and Tinman transcription factors. Consistent with the observed protein expression pattern, phenotype analyses demonstrate Toll function is essential for normal dorsal vessel formation. Such findings implicate Toll as a critical cell adhesion molecule in the alignment and migration of cardioblasts during dorsal vessel morphogenesis.

Animals↗

[VUV spectral properties of (Y, Gd) Al3 (BO3)4: Tb].

(Y, Gd)A13 (BO3)4 doped with Ce and Tb were prepared by solid state reaction. The structure, VUV excitation properties, excitation were studied. (Y,Gd)Al3 (BO3)4 belongs to trigonal crystal system with thespace group of R32, and the crystal structure does not change as Tb3+ and Ce3+ ions are doped to the crystal lattice. The host absorption band of (Y,Gd)Al3 (BO3)4:Tb moves to longer wavelength as Gd3+ mol concentration increases. The energy transfer between Gd3+ and Tb3+ is very effective, and the samples with high Gd3+ mol concentrations have high radiant efficiencies. It was found that the luminescence of Tb3+ is quenched by Ce3+ in (Y,Gd)Al3(BO3)4:Ce, Tb under VUV excitation.

Borates↗

Three-coordinate organoboron compounds BAr2R (Ar = mesityl, R = 7-azaindolyl- or 2,2'-dipyridylamino-functionalized aryl or thienyl) for electroluminescent devices and supramolecular assembly.

Eight novel three-coordinate boron compounds with the general formula BAr(2)L, in which Ar is mesityl and L is a 7-azaindolyl- or a 2,2'-dipyridylamino-functionalized aryl or thienyl ligand, have been synthesized by Suzuki coupling, Ullmann condensation methods, or simple substitution reactions (L = p-(2,2'-dipyridylamino)phenyl, 1; p-(2,2'-dipyridylamino)biphenyl, 2; p-(7-azaindolyl)phenyl, 3; p-(7-azaindolyl)biphenyl, 4; 3,5-bis(2,2'-dipyridylamino)phenyl, 5; 3,5-bis(7-azaindolyl)phenyl, 6; p-[3,5-bis(2,2'-dipyridylamino)phenyl]phenyl, 7; 5-[p-(2,2'-dipyridylamino)phenyl]-2-thienyl, 8). The structures of 1, 3, and 5-7 have been determined by X-ray diffraction analyses. These new boron compounds are bright blue emitters. Electroluminescent devices using compound 2 or 8 as the emitter and the electron-transport layer have been successfully fabricated. Molecular orbital calculations (Gaussian 98) have established that the blue emission of compounds 1-8 originates from charge transfer between the pi orbital of the ligand L and the p(pi) orbital of the boron center. The ability of these boron compounds to bind to metal centers to form supramolecular assemblies was demonstrated by treatment of compound 2 with Zn(O(2)CCF(3))(2), which generated a 1:1 chelate complex [2.Zn(O(2)CCF(3))(2)] (10), and also by treatment of compound 4 with AgNO(3), yielding a 2:1 coordination compound [(4)(2).Ag(NO(3))] (11). In the solid state, compounds 10 and 11 form interesting head-to-head and tail-to-tail extended structures that host solvent molecules such as benzene.

Journal Article↗

Synthesis and functional properties of strongly luminescent diphenylamino end-capped oligophenylenes.

Two novel homologous series of oligophenylenes (OPPs) symmetrically end-capped with diphenylamino groups and asymmetrically end-capped with anthryldiphenylamino groups were successfully synthesized by a convergent approach with use of palladium-catalyzed homo- and cross-coupling of arylboronic acids. The absorption maxima of both diphenylamino end-capped OPP series do not vary with the chain length although the molar absorptivities increase sequentially. On the other hand, the emission maxima slightly shift to longer wavelengths when the phenylene unit increases in the series. All the diphenylamino end-capped oligomers exhibit very large fluorescence quantum yields (81-89%). They also exhibit low first ionization potentials, corresponding to the oxidation of the triarylamino moiety, which are essentially unaffected by the oligomeric length extension. The good thermal stabilities of these oligomers allowed the fabrication of multilayer light-emitting devices and their investigations.

Journal Article↗

Defining normal plasma citrulline in intestinal transplant recipients.

Biopsy is the only means to identify intestinal graft rejection. Plasma citrulline (P-Cit) has been proposed as a marker for rejection after intestinal transplant (IT), but normative data is lacking. We analyzed P-Cit in IT recipients without rejection or other histological abnormalities. In 40 patients, P-Cit was measured with a Beckman amino acid analyzer within 24 h of protocol or clinically indicated endoscopic biopsy procured > 6 and < 360 days post-IT. Measurements included for analysis corresponded to normal (or minimally abnormal) biopsies that remained so for 7 days. These criteria were met by 145 samples from 10 adults and 14 children. Overall mean P-Cit (nmol/mL) was 34.0 +/- 19.9. Mean P-Cit was 22.2 +/- 13.2 between 6 and 30 days post-IT, 34.9 +/- 17.2 (p = 0.001) between 30 and 60 days, 43.6 +/- 15.8 between 60 and 90 days (p = 0.001), then stable until the end of the first year. Plasma citrulline was lower in 13 patients with body surface area (BSA) < or = 1 m2 vs. 11 patients with BSA > or = 1.1 m2 (p = 0.0001). Plasma citrulline increased linearly during the first 120 days in both BSA groups (r = 0.573 and r = 0.512; p = 0.0001). Within 3 months after IT, variations in P-Cit based on body size and postop interval should be considered when evaluating the need for histological confirmation of graft dysfunction.

Biopsy↗

Tuning the valence of the cerium center in (Na)phthalocyaninato and porphyrinato cerium double-deckers by changing the nature of the tetrapyrrole ligands.

A series of 7 cerium double-decker complexes with various tetrapyrrole ligands including porphyrinates, phthalocyaninates, and 2,3-naphthalocyaninates have been prepared by previously described methodologies and characterized with elemental analysis and a range of spectroscopic methods. The molecular structures of two heteroleptic [(na)phthalocyaninato](porphyrinato) complexes have also been determined by X-ray diffraction analysis which exhibit a slightly distorted square antiprismatic geometry with two domed ligands. Having a range of tetrapyrrole ligands with very different electronic properties, these compounds have been systematically investigated for the effects of ligands on the valence of the cerium center. On the basis of the spectroscopic (UV-vis, near-IR, IR, and Raman), electrochemical, and structural data of these compounds and compared with those of the other rare earth(III) counterparts reported earlier, it has been found that the cerium center adopts an intermediate valence in these complexes. It assumes a virtually trivalent state in cerium bis(tetra-tert-butylnaphthalocyaninate) as a result of the two electron rich naphthalocyaninato ligands, which facilitate the delocalization of electron from the ligands to the metal center. For the rest of the cerium double-deckers, the cerium center is predominantly tetravalent. The valences (3.59-3.68) have been quantified according to their L(III)-edge X-ray absorption near-edge structure (XANES) profiles.

Journal Article↗

Syntheses, structures, and electroluminescence of Ln(2)(acac-azain)(4)(mu-acac-azain)(2) [acac-azain = 1-(N-7-azaindolyl)-1,3-butanedionato, Ln = Tb(III) and Y(III)].

Two new luminescent lanthanide complexes Ln(2)(acac-azain)(4)(mu-acac-azain)(2) [acac-azain = 1-(N-7-azaindolyl)-1,3-butanedionato, Ln = Tb(III), 1, Y(III), 2] have been synthesized and structurally characterized. These two dinuclear complexes are isostructural with the two lanthanide ions being bridged by two acac-azain ligands. Each of the two metal ions is further chelated by four oxygen atoms from two acac-azain ligands, resulting in a coordination number eight for each metal ion. 1 displays characteristic Tb(III) emission bands while 2 displays weak blue luminescence attributable to the ligand. Single-layer and double-layer electroluminescent devices for compound 1 were fabricated, where compound 1 doped PVK layer functions as both the emitting layer and the hole transport layer and PBD functions as an electron transport layer (in the double-layer device), demonstrating that compound 1 is a promising green emitter in electroluminescent devices.

Journal Article↗