Transforming Thermally Activated Delayed Fluorescence to Room-Temperature Phosphorescence through Modulation of the Donor in Charge-Transfer Cocrystals.

A cocrystallization strategy is used through incorporation of 1,2,4,5-tetracyanobenzene (TCNB) as an acceptor with halogen-substituent thioxanthone (TX) derivatives as donors. The resulting cocrystals TT-R (R = H, F, Cl, Br, or I) transform the thermally activated delayed fluorescence emission in the TT-H, TT-F, and TT-Cl cocrystals to room-temperature phosphorescence in the TT-Br and TT-I cocrystals. Definite crystal packing structures demonstrate a 1:1 alternative donor-acceptor stacking in the TT-H cocrystal, a 2:1 alternative donor-acceptor stacking in the TT-F and TT-Cl cocrystals, and a separate stacking of donor and acceptor in the TT-Br and TT-I cocrystals.

Oviductal Glycoprotein 1 Promotes Hypertension by Inducing Vascular Remodeling Through an Interaction With MYH9.

Background: Hypertension is a common cardiovascular disease that is related to genetic and environmental factors, but its mechanisms remain unclear. DNA methylation, a classic epigenetic modification, not only regulates gene expression but is also susceptible to environmental factors, linking environmental factors to genetic modification. Therefore, globally screening differential genomic DNA methylation in patients with hypertension is important for investigating hypertension mechanisms.

An NHC-Stabilized H GeBH Precursor for the Preparation of Cationic Group 13/14/15 Hydride Chains.

The synthesis, characterization and reactivity studies of the NHC-stabilized complex IDipp ⋅ GeH BH OTf (1) (IDipp=1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene) are reported. Nucleophilic substitution of the triflate (OTf) group in 1 by phosphine or arsine donors provides access to the cationic group 13/14/15 chains [IDipp ⋅ GeH BH ERR R ] (2 E=P; R, R =H; R = Bu; 3 E=P; R=H; R , R =Ph; 4 a E=P; R, R , R =Ph; 4 b E=As; R, R , R =Ph). These novel cationic chains were characterized by X-ray crystallography, NMR spectroscopy and mass spectrometry.

Proteogenomic characterization of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 normal pancreatic ductal tissues. Proteomic, phosphoproteomic, and glycoproteomic analyses were used to characterize proteins and their modifications.

De Novo Germline and Somatic Variants Convergently Promote Endothelial-to-Mesenchymal Transition in Simplex Brain Arteriovenous Malformation.

[Figure: see text].

Validating Methylated HOXA9 in Bronchial Lavage as a Diagnostic Tool in Patients Suspected of Lung Cancer.

Diagnosing lung cancer requires invasive procedures with high risk of complications. Methylated tumor DNA in bronchial lavage has previously shown potential as a diagnostic biomarker. We aimed to develop and validate methylated in bronchial lavage as a diagnostic biomarker of lung cancer.

Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity.

ASH1L histone methyltransferase plays a crucial role in the pathogenesis of different diseases, including acute leukemia. While ASH1L represents an attractive drug target, developing ASH1L inhibitors is challenging, as the catalytic SET domain adapts an inactive conformation with autoinhibitory loop blocking the access to the active site. Here, by applying fragment-based screening followed by medicinal chemistry and a structure-based design, we developed first-in-class small molecule inhibitors of the ASH1L SET domain.

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Design and optimisation of dendrimer-conjugated Bcl-2/x inhibitor, AZD0466, with improved therapeutic index for cancer therapy.

Dual Bcl-2/Bcl-x inhibitors are expected to deliver therapeutic benefit in many haematological and solid malignancies, however, their use is limited by tolerability issues. AZD4320, a potent dual Bcl-2/Bcl-x inhibitor, has shown good efficacy however had dose limiting cardiovascular toxicity in preclinical species, coupled with challenging physicochemical properties, which prevented its clinical development. Here, we describe the design and development of AZD0466, a drug-dendrimer conjugate, where AZD4320 is chemically conjugated to a PEGylated poly-lysine dendrimer.

Scalable neutral HO electrosynthesis by platinum diphosphide nanocrystals by regulating oxygen reduction reaction pathways.

Despite progress in small scale electrocatalytic production of hydrogen peroxide (HO) using a rotating ring-disk electrode, further work is needed to develop a non-toxic, selective, and stable O-to-HO electrocatalyst for realizing continuous on-site production of neutral hydrogen peroxide. We report ultrasmall and monodisperse colloidal PtP nanocrystals that achieve HO production at near zero-overpotential with near unity HO selectivity at 0.27 V vs.

Multi-platform discovery of haplotype-resolved structural variation in human genomes.

The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per genome.

[Protective effects of exogenous HS to the recovery of hypoxia post-conditioning on aged H9C2 cells and the underling mechanisms].

Objective: To investigate the recovery of protective effects of exogenous hydrogen sulfide (HS) on hypoxia post-conditioning in aged H9C2 cells and its mechanism.

Methods: H9C2 cells (cardiomyocytes line) were treated with 30 μmol/L hydrogen peroxide (HO) for 2 hours, then cultured for 3 days in order to induce cellular aging. Aged H9C2 cells were randomly divided into 5 groups (=8):Control group (Control), hypoxia/reoxygenation group (H/R), H/R + NaHS group, hypoxia post-conditioning (PC) group, PC+NaHS group.

Cytokine-Like 1 Is a Novel Proangiogenic Factor Secreted by and Mediating Functions of Endothelial Progenitor Cells.

Rationale: Endothelial colony forming cells (ECFCs) or late blood outgrowth endothelial cells can be isolated from human cord or peripheral blood, display properties of endothelial progenitors, home into ischemic tissues and support neovascularization in ischemic disease models.

Objective: To assess the functions of CYTL1 (cytokine-like 1), a factor we found preferentially produced by ECFCs, in regard of vessel formation.

Methods And Results: We show by transcriptomic analysis that ECFCs are distinguished from endothelial cells of the vessel wall by production of high amounts of CYTL1.

PD-1 inhibition has only limited clinical benefit in patients with recurrent high-grade glioma.

Objective: To investigate the question of whether salvage therapy with the programmed cell death protein 1 (PD-1)-blocking antibodies nivolumab or pembrolizumab with or without bevacizumab offers clinical or survival benefit in patients with recurrent high-grade gliomas (HGGs).

Methods: This was a single-institution retrospective observational study in 31 adult patients who received pembrolizumab (Keytruda) or nivolumab (Opdivo) with or without concurrent bevacizumab for recurrent high-grade glioma.

Results: Median progression-free survival (mPFS) from first anti-PD-1 dose was 3.

Trial designs for chemotherapy-induced peripheral neuropathy prevention: ACTTION recommendations.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially dose-limiting side effect of neurotoxic chemotherapies. No therapies are available to prevent CIPN. The small number of positive randomized clinical trials (RCTs) evaluating preventive therapies for CIPN provide little guidance to inform the design of future trials.

Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval.

Background: Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability.

Widespread asymmetric response of soil heterotrophic respiration to warming and cooling.

Soil is the largest organic carbon (C) pool in terrestrial ecosystems. Periodic changes in environmental temperature occur diurnally and seasonally; yet, the response of soil organic matter (SOM) decomposition to varying temperatures remains unclear. In this study, we conducted a modified incubation experiment using soils from 16 forest ecosystems in China with periodically and continuously varying incubation temperature to investigate how heterotrophic respiration (R) responds to different temperature patterns (both warming and cooling temperature ranging between 5 and 30°C).

Reduced Integrity of Right Lateralized White Matter in Patients with Primary Insomnia: A Diffusion-Tensor Imaging Study.

Purpose To analyze the integrity of white matter (WM) tracts in primary insomnia patients and provide better characterization of abnormal WM integrity and its relationship with disease duration and clinical features of primary insomnia. Materials and Methods This prospective study was approved by the ethics committee of the Guangdong No. 2 Provincial People's Hospital.

Association of FCGR2A-R/H131 polymorphism with susceptibility to systemic lupus erythematosus among Asian population: a meta-analysis of 20 studies.

The results of studies on association between FCGR2A-R/H131 polymorphism and susceptibility to systemic lupus erythematosus (SLE) in the Asian population are controversial. To derive a more precise estimation on the genetic risk of FCGR2A-R/H131 variant for SLE in Asians, a meta-analysis was performed for genotypes R/R + R/H (dominant effect), R/R (recessive effect), and R allele in fixed/random effects models. Twenty studies involving 4,832 SLE patients and 6,190 controls were included.

Wire network behavior in superconducting Nb films with diluted triangular arrays of holes.

We present results of transport measurements on superconducting Nb films with diluted triangular arrays (honeycomb and kagomé) of holes. The patterned films have large disk-shaped interstitial regions even when the edge-to-edge separations between nearest neighboring holes are comparable to the coherence length. Changes in the field interval of two consecutive minima in the field dependent resistance R(H) curves are observed.

Osmabenzenes from the reactions of a dicationic osmabenzyne complex.

Treatment of the osmabenzyne Os([triple bond]CC(SiMe(3))=C(Me)C(SiMe(3))=CH)Cl(2)(PPh(3))(2) (1) with 2,2'-bipyridine (bipy) and thallium triflate (TlOTf) produces the thermally stable dicationic osmabenzyne [Os([triple bond]CC(SiMe(3))=C(Me)C(SiMe(3))=CH)(bipy)(PPh(3))(2)](OTf)(2) (2). The dicationic osmabenzyne 2 reacts with ROH (R = H, Me) to give osmabenzene complexes [Os(=C(OR)CH=C(Me)C(SiMe(3))=CH)(bipy)(PPh(3))(2)]OTf, in which the metallabenzene ring deviates significantly from planarity. In contrast, reaction of the dicationic complex 2 with NaBH(4) produces a cyclopentadienyl complex, presumably through the osmabenzene intermediate [Os(=CHC(SiMe(3))=C(Me)C(SiMe(3))=CH)(bipy)(PPh(3))(2)]OTf.