Utilising an in silico model to predict outcomes in senescence-driven acute liver injury.

Currently liver transplantation is the only treatment option for liver disease, but organ availability cannot meet patient demand. Alternative regenerative therapies, including cell transplantation, aim to modulate the injured microenvironment from inflammation and scarring towards regeneration. The complexity of the liver injury response makes it challenging to identify suitable therapeutic targets when relying on experimental approaches alone.

Harnessing 4f Electron Itinerancy for Integrated Dual-Band Redox Systems Boosts Lithium-Oxygen Batteries Electrocatalysis.

In-depth comprehension and manipulation of band occupation at metal centers are crucial for facilitating effective adsorption and electron transfer in lithium-oxygen battery (LOB) reactions. Rare earth elements play a unique role in band hybridization due to their deep orbitals and strong localization of 4 f electrons. Herein, we anchor single Ce atoms onto CoO, constructing a highly active and stable catalyst with d-f a dual-band redox center.

The Protective Efficacy of a SARS-CoV-2 Vaccine Candidate B.1.351V against Several Variant Challenges in K18-hACE2 Mice.

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.

Combination Targeted Therapy in Relapsed Diffuse Large B-Cell Lymphoma.

Background: The identification of oncogenic mutations in diffuse large B-cell lymphoma (DLBCL) has led to the development of drugs that target essential survival pathways, but whether targeting multiple survival pathways may be curative in DLBCL is unknown.

Methods: We performed a single-center, phase 1b-2 study of a regimen of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR) in relapsed or refractory DLBCL. In phase 1b, which included patients with DLBCL and indolent lymphomas, four dose levels of venetoclax were evaluated to identify the recommended phase 2 dose, with fixed doses of the other four drugs.

Reverse metabolomics for the discovery of chemical structures from humans.

Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for in public metabolomics datasets to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans, including N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids.

A new method for multiancestry polygenic prediction improves performance across diverse populations.

Polygenic risk scores (PRSs) increasingly predict complex traits; however, suboptimal performance in non-European populations raise concerns about clinical applications and health inequities. We developed CT-SLEB, a powerful and scalable method to calculate PRSs, using ancestry-specific genome-wide association study summary statistics from multiancestry training samples, integrating clumping and thresholding, empirical Bayes and superlearning. We evaluated CT-SLEB and nine alternative methods with large-scale simulated genome-wide association studies (~19 million common variants) and datasets from 23andMe, Inc.

Overall Survival with Osimertinib in Resected -Mutated NSCLC.

Background: Among patients with resected, epidermal growth factor receptor ()-mutated, stage IB to IIIA non-small-cell lung cancer (NSCLC), adjuvant osimertinib therapy, with or without previous adjuvant chemotherapy, resulted in significantly longer disease-free survival than placebo in the ADAURA trial. We report the results of the planned final analysis of overall survival.

Methods: In this phase 3, double-blind trial, we randomly assigned eligible patients in a 1:1 ratio to receive osimertinib (80 mg once daily) or placebo until disease recurrence was observed, the trial regimen was completed (3 years), or a discontinuation criterion was met.

Establishment of Dissolution Based on Similarity with Dissolution: A Case Study on Aripiprazole.

dissolution that predicts the performance of solid preparations is extremely important in formulation optimization. Fraction absorbed () has been used to screen dissolution protocols based on the idea of - correlation (IVIVC) but failed to increase the success rate due to the inaccuracy of the . The essence of IVIVC is the correlation between dissolution and dissolution.

Identification and characterization of a MAPT-targeting locked nucleic acid antisense oligonucleotide therapeutic for tauopathies.

Tau is a microtubule-associated protein (, tau) implicated in the pathogenesis of tauopathies, a spectrum of neurodegenerative disorders characterized by accumulation of hyperphosphorylated, aggregated tau. Because tau pathology can be distinct across diseases, a pragmatic therapeutic approach may be to intervene at the level of the tau transcript, as it makes no assumptions to mechanisms of tau toxicity. Here we performed a large library screen of locked-nucleic-acid (LNA)-modified antisense oligonucleotides (ASOs), where careful tiling of the locus resulted in the identification of hot spots for activity in the 3' UTR.

The chromosome-level genome for provides crucial insights into Anacardiaceae evolution and urushiol biosynthesis.

The lacquer tree ( (Stokes) F.A. Barkley) is an important tree with economic, industrial, and medicinal values.

Validation of Artificial Intelligence Cardiac MRI Measurements: Relationship to Heart Catheterization and Mortality Prediction.

Background Cardiac MRI measurements have diagnostic and prognostic value in the evaluation of cardiopulmonary disease. Artificial intelligence approaches to automate cardiac MRI segmentation are emerging but require clinical testing. Purpose To develop and evaluate a deep learning tool for quantitative evaluation of cardiac MRI functional studies and assess its use for prognosis in patients suspected of having pulmonary hypertension.

Sex Differences in Characteristics, Treatments, and Outcomes Among Patients Hospitalized for Non-ST-Segment-Elevation Myocardial Infarction in China: 2006 to 2015.

Background: Sex differences in clinical characteristics and in-hospital outcomes among patients with non-ST-segment-elevation myocardial infarction have been described in Western countries, but whether these differences exist in China is unknown.

Methods: We used a 2-stage random sampling design to create a nationally representative sample of patients admitted to 151 Chinese hospitals for non-ST-segment-elevation myocardial infarction in 2006, 2011, and 2015 and examined sex differences in clinical profiles, treatments, and in-hospital outcomes over this time. Multivariable logistic regression models adjusting for age or other potentially confounding clinical covariates were used to estimate these sex-specific differences.

Accuracy of Reduction Depths of Tooth Preparation for Porcelain Laminate Veneers Assisted by Different Tooth Preparation Guides: An In Vitro Study.

Purpose: To evaluate the accuracy (trueness and precision) of reduction depths of guided veneer preparation assisted by four tooth preparation guides.

Materials And Methods: Fifty resin artificial teeth were randomly divided into five groups (n = 10): a freehand group (F), silicone guide group (S), thermoplastic guide group (T), 3D printed uniform guide group (D), and 3D printed auto-stop guide group (A). A preparation for a window veneer on the maxillary right central incisor was performed by two surgeons who used tooth preparation guides for assistance.

dissolution of poorly water-soluble drugs: Proof of concept based on fluorescence bioimaging.

‒ correlation (IVIVC) of solid dosage forms should be established basically between and dissolution of active pharmaceutical ingredients. Nevertheless, dissolution profiles have never been accurately portrayed. The current practice of IVIVC has to resort to absorption fractions ( ).

Rational design of signal peptides for improved MtC1LPMO production in Bacillus amyloliquefaciens.

A high-throughput screening system was established by employing enhanced green fluorescent protein as a screenable fusion tag to evaluate the expression and secretion of a lytic polysaccharide monooxygenase (MtC1LPMO) using 20 Sec-type signal peptides (SPs) from Bacillus amyloliquefaciens 111018. Among these, 10 SPs were found to be better than the native SP of MtC1LPMO. The protein expression and secretion levels using SP12 (MNITNWAAILQLQSMALQSISNTGTASS) were the highest among all SPs, with 4.

CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells.

A number of clinically validated drugs have been developed by repurposing the CUL4-DDB1-CRBN-RBX1 (CRL4CRBN) E3 ubiquitin ligase complex with molecular glue degraders to eliminate disease-driving proteins. Here, we present the identification of a first-in-class GSPT1-selective cereblon E3 ligase modulator, CC-90009. Biochemical, structural, and molecular characterization demonstrates that CC-90009 coopts the CRL4CRBN to selectively target GSPT1 for ubiquitination and proteasomal degradation.

Osimertinib in Resected -Mutated Non-Small-Cell Lung Cancer.

Background: Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor () mutation-positive advanced non-small-cell lung cancer (NSCLC). The efficacy and safety of osimertinib as adjuvant therapy are unknown.

Methods: In this double-blind, phase 3 trial, we randomly assigned patients with completely resected mutation-positive NSCLC in a 1:1 ratio to receive either osimertinib (80 mg once daily) or placebo for 3 years.

Relationships between Bond Strength and Spectroscopic Quantities in H-Bonds and Related Halogen, Chalcogen, and Pnicogen Bonds.

A large number of systems were studied that contain either a H-bond (HB) or the closely related halogen (X), chalcogen (Y), or pnicogen (Z) bond. Many of the same relationships between the strength of the HB and spectroscopic parameters apply as well to the other noncovalent bonds. There is a very nearly linear relationship between the interaction energy and the red shift that occurs within the stretching frequency of the pertinent F-A covalent bond of the Lewis acid (where A refers to H, X, Y, or Z).