A macrocyclic ruthenium(III) complex RuIII(N2O2)Cl2Cl (Ru‐1) is reported as an inhibitor of angiogenesis and an anti‐tumor compound. The complex is relatively non‐cytotoxic towards endothelial and ...cancer cell lines in vitro, but specifically inhibited the processes of angiogenic endothelial cell tube formation and cancer cell invasion. Moreover, compared with known anti‐cancer ruthenium complexes, Ru‐1 is distinct in that it suppressed the expression of vascular endothelial growth factor receptor‐2 (VEGFR2), and the associated downstream signaling that is crucial to tumor angiogenesis. In addition, in vivo studies showed that Ru‐1 inhibited angiogenesis in a zebrafish model and suppressed tumor growth in nude mice bearing cancer xenografts.
Anti‐angiogenic Ru(III): A macrocyclic ruthenium(III) complex is found to inhibit endothelial cell angiogenesis and cancer cell invasiveness, to suppress the protein and mRNA expression of VEGFR2 and the VEGFR downstream signaling pathways and to display in vivo anti‐tumor activities.
A critical step in advancing the practical application of copper‐based organic light‐emitting diodes (OLEDs) is to bridge the large gap between device efficiency and operational stability at ...practical luminance. Described is a panel of air‐ and thermally stable two‐coordinate CuI emitters featuring bulky pyrazine‐ (PzIPr) or pyridine‐fused N‐heterocyclic carbene (PyIPr*) and carbazole (Cz) ligands with enhanced amide‐Cu‐carbene bonding interactions. These CuI emitters display thermally activated delayed fluorescence (TADF) from the 1LL′CT(Cz→PzIPr/PyIPr*) excited states across the blue to red regions with exceptional radiative rate constants of 1.1–2.2×106 s−1. Vapour‐deposited OLEDs based on these CuI emitters showed excellent external quantum efficiencies and luminance up to 23.6 % and 222 200 cd m−2, respectively, alongside record device lifetimes (LT90) up to 1300 h at 1000 cd m−2 under our laboratory conditions, highlighting the practicality of the CuI‐TADF emitters.
Carbene‐copper‐amide thermally activated delayed fluorescence (TADF) emitters featuring π‐annulated N‐heterocyclic carbene ligands show exceptional radiative rate constants of 1.1–2.2×106 s−1 and can deliver stable and high‐performance full‐color CuI‐based organic light‐emitting diodes (OLEDs) with device lifetimes (LT90) up to 1300 hours at 1000 cd m−2 and ultra‐high brightness up to 222 200 cd m−2.
The application of long-read sequencing using the Oxford Nanopore Technologies (ONT) MinION sequencer is getting more diverse in the medical field. Having a high sequencing error of ONT and limited ...throughput from a single MinION flowcell, however, limits its applicability for accurate variant detection. Medical exome sequencing (MES) targets clinically significant exon regions, allowing rapid and comprehensive screening of pathogenic variants. By applying MES with MinION sequencing, the technology can achieve a more uniform capture of the target regions, shorter turnaround time, and lower sequencing cost per sample.
We introduced a cost-effective optimized workflow, ECNano, comprising a wet-lab protocol and bioinformatics analysis, for accurate variant detection at 4800 clinically important genes and regions using a single MinION flowcell. The ECNano wet-lab protocol was optimized to perform long-read target enrichment and ONT library preparation to stably generate high-quality MES data with adequate coverage. The subsequent variant-calling workflow, Clair-ensemble, adopted a fast RNN-based variant caller, Clair, and was optimized for target enrichment data. To evaluate its performance and practicality, ECNano was tested on both reference DNA samples and patient samples.
ECNano achieved deep on-target depth of coverage (DoC) at average > 100× and > 98% uniformity using one MinION flowcell. For accurate ONT variant calling, the generated reads sufficiently covered 98.9% of pathogenic positions listed in ClinVar, with 98.96% having at least 30× DoC. ECNano obtained an average read length of 1000 bp. The long reads of ECNano also covered the adjacent splice sites well, with 98.5% of positions having ≥ 30× DoC. Clair-ensemble achieved > 99% recall and accuracy for SNV calling. The whole workflow from wet-lab protocol to variant detection was completed within three days.
We presented ECNano, an out-of-the-box workflow comprising (1) a wet-lab protocol for ONT target enrichment sequencing and (2) a downstream variant detection workflow, Clair-ensemble. The workflow is cost-effective, with a short turnaround time for high accuracy variant calling in 4800 clinically significant genes and regions using a single MinION flowcell. The long-read exon captured data has potential for further development, promoting the application of long-read sequencing in personalized disease treatment and risk prediction.
To facilitate the identification of candidate molecular biomarkers that are linked to the pathogenesis of hepatocellular carcinoma (HCC), we investigated protein‐expression profiles of 146 tissue ...specimens including 67 pairs of tumors and adjacent non‐tumors resected from HCC patients as well as 12 normal livers by 2‐DE. Among the 1800 spots displayed in the liver proteome, a total of 90 protein species were found to be significantly different between the three groups (P < 0.05). Three of the top candidate markers up‐regulated in HCC, with high receiver operating characteristic (ROC) curves, were identified by MS/MS analysis and belonged to the chaperone members: heat‐shock protein (Hsp)27, Hsp70 and glucose‐regulated protein (GRP)78. Over‐expression of these chaperone proteins in HCC tissues was confirmed by Western blotting and immunohistochemistry. In correlation with clinico‐pathological parameters, expression of Hsp27 was linked to α‐fetoprotein level (P = 0.007) whereas up‐regulation of GRP78 was associated with tumor venous infiltration (P = 0.035). No significant association of Hsp70 with any pathologic features was observed. The present HCC proteome analysis revealed that in response to the stressful cancerous microenvironment, tumor cells strived to increase the expression of chaperone proteins for cyto‐protective function and to enhance tumor growth and metastasis.
According to Karl Popper's critical rationalism, criticism is the only way we have of systematically detecting and learning from our mistakes so as to get nearer to the truth. Meanwhile, it is ...arguable that the emphasis of Confucianism on creating a hierarchical and harmonious society can easily lead to submission rather than opposition, producing a conformist rather than critical mind. A question arises here as to whether Confucianism tends to denigrate criticism and thus run counter to critical rationalism. In this paper, I first argue that Confucianism prizes criticism and critical discussion, for which ample justification can be found in Confucian classics. Then I compare Confucianism with critical rationalism and assess the compatibility between them.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Summary
AC-DIAMOND (v1) is a DNA-protein alignment tool designed to tackle the efficiency challenge of aligning large amount of reads or contigs to protein databases. When compared with the ...previously most efficient method DIAMOND, AC-DIAMOND gains a 6- to 7-fold speed-up, while retaining a similar degree of sensitivity. The improvement is rooted at two aspects: first, using a compressed index of seeds with adaptive-length to speed-up the matching between query and reference sequences; second, adopting a compact form of dynamic programing to fully utilize the parallelism of the SIMD capability.
Availability and implementation
Software source codes and binaries available at https://github.com/Maihj/AC-DIAMOND/
Supplementary information
Supplementary data are available at Bioinformatics online.
Despite recent discoveries of novel animal bocaparvoviruses, current understandings on the diversity and evolution of bocaparvoviruses are still limited. We report the identification and genome ...characterization of a novel bocaparvovirus, rat bocaparvovirus (RBoV), in brown rats (Rattus norvegicus) in China. RBoV was detected in 11.5%, 2.4%, 16.2% and 0.3% of alimentary, respiratory, spleen and kidney samples respectively, of 636 brown rats by PCR, but not in samples of other rodent species, suggesting that brown rats are the primary reservoir of RBoV. Six RBoV genomes sequenced from three brown rats revealed the presence of three ORFs, characteristic of bocaparvoviruses. Phylogenetic analysis showed that RBoV was distantly related to other bocaparvoviruses, forming a distinct cluster within the genus, with ≤55.5% nucleotide identities to the genome of ungulate bocaparvovirus 3, supporting its classification as a novel bocaparvovirus species. RBoV possessed a putative second exon encoding the C-terminal region of NS1 and conserved RNA splicing signals, similar to human bocaparvoviruses and canine bocaparvovirus. In contrast to human, feline and canine bocaparvoviruses which demonstrates inter/intra-host viral diversity, partial VP1/VP2 sequences of 49 RBoV strains demonstrated little inter-host genetic diversity, suggesting a single genetic group. Although the pathogenicity of RBoV remains to be determined, its presence in different host tissues suggests wide tissue tropism. RBoV represents the first bocaparvovirus in rodents with genome sequenced, which extends our knowledge on the host range of bocaparvoviruses. Further studies are required to better understand the epidemiology, genetic diversity and pathogenicity of bocaparvoviruses in different rodent populations.
•A novel rat bocaparvovirus was discovered in brown rats in China.•Sequencing of six rat bocaparvovirus genomes showed a putative second exon and splicing signals.•Wide tissue tropism and limited genetic diversity was observed.
The COVID-19 pandemic, with its need for distancing, has necessitated the use of virtual care in never-before-seen volumes. This review article aims to provide a primer on virtual care for ...cardiovascular professionals in Canada. The technology to facilitate remote patient interactions is already available, but barriers exist. Adequate and effective cardiac virtual care must be further developed given the need for rapid evaluation and close ongoing follow-up of patients, as seen in the areas of management of heart failure, cardiac rehabilitation, electrophysiology, and hypertension. Many Canadian organizations have published resources to assist health care providers and patients navigate the unfamiliar virtual care landscape. Although there are concerns surrounding issues such as patient privacy, access to technology, language discrepancies, and billing, these deficits provide opportunities for growth by health care organizations and technology companies. The integration of virtual care, home-based devices, and disruptive technologies emphasize the trend toward virtualization of health care, with the potential for greater personalization of health care interactions and continuity of care. Funding models were rapidly developed at the beginning of the COVID-19 pandemic, and although some provinces have deemed these changes as permanent, the status from other provinces remains unknown. The foundations to support virtual care as a key modality for health care delivery in Canada have been built, and further developments may strengthen its viability as a long-term option.
Dans le contexte de la pandémie de COVID-19 et de la distanciation sociale qu’elle impose, le recours aux soins de santé virtuels a atteint des sommets historiques. Le présent article de synthèse est une introduction aux soins de santé virtuels destinée aux professionnels de la santé cardiovasculaire du Canada. La technologie permettant de faciliter les interactions à distance avec les patients existe déjà, mais il y a des obstacles à sa mise en œuvre. Des soins de santé virtuels adéquats et efficaces doivent être développés davantage en cardiologie compte tenu de la nécessité d’une évaluation rapide et d’un suivi étroit et continu des patients, notamment quand il est question de prise en charge de l’insuffisance cardiaque, de réadaptation cardiaque, d’électrophysiologie ou d’hypertension. De nombreux organismes canadiens ont publié des ressources pour aider les fournisseurs de soins et les patients à trouver leurs repères dans l’univers peu connu des soins de santé virtuels. Les questions telles que la protection des renseignements personnels des patients, l’accès à la technologie, les différences linguistiques et la facturation soulèvent des préoccupations. Néanmoins, les lacunes constituent des possibilités de croissance pour les organismes de soins de santé et les entreprises technologiques. L’intégration des soins de santé virtuels, des dispositifs à domicile et des technologies perturbatrices met en lumière la tendance à la virtualisation des soins de santé, allant de pair avec la possibilité d’accroître la personnalisation des interactions et la continuité des soins. Des modèles de financement ont été rapidement élaborés au début de la pandémie de COVID-19. Bien que certaines provinces aient reconnu le caractère permanent des changements; la position des autres provinces demeure inconnue. Les conditions de base sont réunies pour que les soins de santé virtuels soient reconnus en tant que modalités clés de la prestation des soins de santé au Canada, et d’autres développements pourraient en renforcer la viabilité en tant qu’option à long terme.
Copper(I) complexes of tris(thioimidazolyl)borates (R′TmR), including Cu(TmPh)(PR″3) (R″ = Ph, Cu1; Cy, Cu2) and Cu(R′TmPh)(PR″3)+ (R′ = N-methylimidazole; R″ = Ph, Cy) were prepared and ...characterized by spectroscopic methods. The X-ray crystal structures of Cu1 and Cu2 feature a tripodal TmPh ligand coordinated in κ3-S,S,S mode. Using Cu2 as a catalyst (loading: 1 mol %), the aziridination of styrenes and sulfimidation of thioanisoles with PhINTs at RT for 3 and 0.5 h, respectively, both resulted in product yields of up to 99%. Cu2 also catalyzed intramolecular amination of the aryl C–H bond of vinyl azides with up to 98% yield. DFT calculations were performed to gain insight into the mechanism of the Cu2-catalyzed aziridination reaction.
PDF
