Activating p53 with a Mutant-Specific Small Molecule.

is the most commonly mutated gene in cancer, but it remains recalcitrant to clinically meaningful therapeutic reactivation. We present here the discovery and characterization of a small molecule chemical inducer of proximity that activates mutant p53. We named this compound TRanscriptional Activator of p53 () due to its ability to engage mutant p53 and BRD4 in a ternary complex, which potently activates mutant p53 and triggers robust p53 target gene transcription.

[Values of Serum Ferritin, Folic Acid and Vitamin B in Treatment of Multiple Myeloma with Bortezomib Combined with Chemotherapy].

Objective: To investigate the value of serum ferritin, folic acid and vitamin B in the treatment of multiple myeloma (MM) with bortezomib combined with chemotherapy.

Methods: Clinical data of 40 MM patients admitted to our hospital from January 2020 to August 2022 and 40 hematology outpatients during the same period were reviewed. All MM patients were treated with bortezomib combined with chemotherapy.

Plane-wave medical image reconstruction based on dynamic Criss-Cross attention and multi-scale convolution.

Background: Plane-wave imaging is widely employed in medical imaging due to its ultra-fast imaging speed. However, the image quality is compromised. Existing techniques to enhance image quality tend to sacrifice the imaging frame rate.

Proteomics-Based Discovery of First-in-Class Chemical Probes for Programmed Cell Death Protein 2 (PDCD2).

Chemical probes are essential tools for understanding biological systems and for credentialing potential biomedical targets. Programmed cell death 2 (PDCD2) is a member of the B-cell lymphoma 2 (Bcl-2) family of proteins, which are critical regulators of apoptosis. Here we report the discovery and characterization of 10 e, a first-in-class small molecule degrader of PDCD2.

ARU-GAN: U-shaped GAN based on Attention and Residual connection for super-resolution reconstruction.

Plane-wave ultrasound imaging technology offers high-speed imaging but lacks image quality. To improve the image spatial resolution, beam synthesis methods are used, which often compromise the temporal resolution. Herein, we propose ARU-GAN, a super-resolution reconstruction model based on residual connectivity and attention mechanisms, to address this issue.

Directed S2 Glycosylation Employing an Amide-Functionalized 1-Naphthoate Platform Featuring a Selectivity-Safeguarding Mechanism.

This work implements a catalytic S2 glycosylation by employing an amide-functionalized 1-naphthoate platform as a latent glycosyl leaving group. Upon gold-catalyzed activation, the amide group enables the S2 process by directing the attack of the glycosyl acceptor via H-bonding interaction, which results in stereoinversion at the anomeric center. Unique in this approach is that the amide group also enables a novel safeguarding mechanism by trapping oxocarbenium intermediates and, hence, minimizing stereorandom S1 processes.

Structure-Based Design of Y-Shaped Covalent TEAD Inhibitors.

Transcriptional enhanced associate domain (TEAD) proteins together with their transcriptional coactivator yes-associated protein (YAP) and transcriptional coactivator with the PDZ-binding motif (TAZ) are important transcription factors and cofactors that regulate gene expression in the Hippo pathway. In mammals, the TEAD families have four homologues: TEAD1 (TEF-1), TEAD2 (TEF-4), TEAD3 (TEF-5), and TEAD4 (TEF-3). Aberrant expression and hyperactivation of TEAD/YAP signaling have been implicated in a variety of malignancies.

An S2-Type Strategy toward 1,2--Furanosides.

The stereoselective construction of 1,2- furanosidic linkage is synthetically challenging. A strategy that applies to all furanose types remains elusive. In this work, a solution is developed based on gold catalysis and the deployment of the directing-group-on-leaving-group strategy, where a basic oxazole group in the gold-activated leaving group facilitates the stereoinvertive attack by glycosyl acceptors.

Ultrasound-based radiomics XGBoost model to assess the risk of central cervical lymph node metastasis in patients with papillary thyroid carcinoma: Individual application of SHAP.

Objectives: A radiomics-based explainable eXtreme Gradient Boosting (XGBoost) model was developed to predict central cervical lymph node metastasis (CCLNM) in patients with papillary thyroid carcinoma (PTC), including positive and negative effects.

Methods: A total of 587 PTC patients admitted at Binzhou Medical University Hospital from 2017 to 2021 were analyzed retrospectively. The patients were randomized into the training and test cohorts with an 8:2 ratio.

Positive and Negative Themes Depicted in Television Shows Targeted Toward Adolescents.

The American Academy of Pediatrics has previously expressed concerns about the thematic content of television (TV) and the amount of time children spend viewing TV. The objective of this study was to determine the positive and negative themes depicted in a select number of TV shows targeted toward adolescents. We analyzed the thematic content depicted in the first season of 26 Netflix TV shows.

Generation and Screening of Antigen-Specific Nanobodies from Mammalian Cells Expressing the BCR Repertoire Library Using Droplet-Based Microfluidics.

Nanobodies, also known as VHHs, originate from the serum of Camelidae. Nanobodies have considerable advantages over conventional antibodies, including smaller size, more modifiable, and deeper tissue penetration, making them promising tools for immunotherapy and antibody-drug development. A high-throughput nanobody screening platform is critical to the rapid development of nanobodies.

Dissecting the Landscape of Activated CMV-Stimulated CD4+ T Cells in Humans by Linking Single-Cell RNA-Seq With T-Cell Receptor Sequencing.

CD4+ T cells are crucial in cytomegalovirus (CMV) infection, but their role in infection remains unclear. The heterogeneity and potential functions of CMVpp65-reactivated CD4+ T cell subsets isolated from human peripheral blood, as well as their potential interactions, were analyzed by single-cell RNA-seq and T cell receptor (TCR) sequencing. Tregs comprised the largest population of these reactivated cells, and analysis of Treg gene expression showed transcripts associated with both inflammatory and inhibitory functions.

A "Traceless" Directing Group Enables Catalytic S2 Glycosylation toward 1,2--Glycopyranosides.

Generally applicable and stereoselective formation of 1,2--glycopyranosidic linkage remains a long sought after yet unmet goal in carbohydrate chemistry. This work advances a strategy to this challenge via stereoinversion at the anomeric position of 1,2- glycosyl ester donors. This S2 glycosylation is enabled under gold catalysis by an oxazole-based directing group optimally tethered to a leaving group and achieved under mild catalytic conditions, in mostly excellent yields, and with good to outstanding selectivities.

Obesity and malnutrition in critically ill patients with acute myeloid leukemia: Prevalence and impact on mortality.

Objectives: Obese patients have an increased risk of developing acute myeloid leukemia (AML), which in turn predisposes to malnutrition. Obesity has been associated with improved survival in critically ill patients (obesity paradox), but this effect seems to disappear when adjusting for malnutrition. How obesity and malnutrition interplay to affect mortality in critically ill patients with AML has not been addressed and was the objective of this study.

A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients.

Purpose: Combinations of bortezomib (Velcade), cyclophosphamide and dexamethasone have shown significant efficacy and safety for patients of newly diagnosed multiple myeloma (NDMM). In this study, we compared the efficacy and safety of modified VCD regimens with novel changes in bortezomib dose and schedule for NDMM.

Methods: Eighty-five NDMM patients from multiple centers were randomly assigned to a high-dose (1.

Modulating the function of ATP-binding cassette subfamily G member 2 (ABCG2) with inhibitor cabozantinib.

Cabozantinib (XL184) is a small molecule tyrosine kinase receptor inhibitor, which targets c-Met and VEGFR2. Cabozantinib has been approved by the Food and Drug Administration to treat advanced medullary thyroid cancer and renal cell carcinoma. In the present study, we evaluated the ability of cabozantinib to modulate the function of the ATP-binding cassette subfamily G member 2 (ABCG2) by sensitizing cells that are resistant to ABCG2 substrate antineoplastic drugs.