Identification of chemical inhibitors targeting long noncoding RNA through gene signature-based high throughput screening.

Scalable methods for functionally high-throughput screening of RNA-targeting small molecules are currently limited. Here, an RNA knockdown gene signature and high-throughput sequencing-based high-throughput screening (HTS) were integrated to identify RNA-targeting compounds. We first generated a gene signature characterizing the knockdown of the long non-coding RNA LINC00973.

Multifaceted roles of cGAS-STING pathway in the lung cancer: from mechanisms to translation.

Lung cancer (LC) remains one of the most prevalent and lethal malignancies globally, with a 5-year survival rate for advanced cases persistently below 10%. Despite the significant advancements in immunotherapy, a substantial proportion of patients with advanced LC fail to respond effectively to these treatments, highlighting an urgent need for novel immunotherapeutic targets. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has gained prominence as a potential target for improving LC immunotherapy due to its pivotal role in enhancing anti-tumor immune responses, augmenting tumor antigen presentation, and promoting T cell infiltration.

Molecular glue triggers degradation of PHGDH by enhancing the interaction between DDB1 and PHGDH.

Cancer stem cells (CSCs) play a pivotal role in tumor initiation, proliferation, metastasis, drug resistance, and recurrence. Consequently, targeting CSCs has emerged as a promising avenue for cancer therapy. Recently, 3-phosphoglycerate dehydrogenase (PHGDH) has been identified as being intricately associated with the regulation of numerous cancer stem cells.

Structural, antioxidant activity, and stability studies of jellyfish collagen peptide-calcium chelates.

The aim of this study was to prepare and characterize jellyfish collagen peptide (JCP)-calcium chelates (JCP-Ca) using peptides with different molecular weights. Further analysis revealed that the low-molecular-weight jellyfish collagen peptide (JCP1) had a higher chelation rate. Structural characterization showed that functional groups such as N-H, C[bond, double bond]O, and -COO were involved in the formation of JCP-Ca, which shifted towards a more ordered and regular structure, and smaller-molecular-weight peptides were more likely to form a denser structure.

Unmasking the silent culprit: recurrent exercise-induced acute kidney injury in a Chinese adolescent with renal hypouricemia.

Primary renal hypouricemia (RHUC) is a rare autosomal recessive disorder with a mean duration of end-stage acute kidney injury (EIAKI) of 14 days. The pathogenesis of EIAKI in patients with RHUC remains unclear. Several hypotheses have been proposed, including those related to the renal vasoconvulsive effect and the elevating effect of xanthine oxidase (XO).

Neratinib impairs function of m6A recognition on AML1-ETO pre-mRNA and induces differentiation of t (8;21) AML cells by targeting HNRNPA3.

Acute myeloid leukemia (AML) is frequently linked to genetic abnormalities, with the t (8; 21) translocation, resulting in the production of a fusion oncoprotein AML1-ETO (AE), being a prevalent occurrence. This protein plays a pivotal role in t (8; 21) AML's onset, advancement, and recurrence, making it a therapeutic target. However, the development of drug molecules targeting AML1-ETO are markedly insufficient, especially used in clinical treatment.

Characterisation and comparison of enzymatically prepared donkey milk whey protein hydrolysates.

This study evaluated the structural characteristics, processing properties, and antioxidant properties of hydrolysates prepared from donkey milk (DM) whey protein using different proteases (Alcalase, Neutrase, papain, and Flavourzyme). The results showed that enzymatic hydrolysis significantly increased hydrolysate solubility and reduced average particle size compared to those of DM whey protein. Neutrase and Flavourzyme hydrolysates exhibited higher degrees of hydrolysis (DH), along with elevated emulsification properties and surface hydrophobicity.

Two-Dimensional Lanthanide Metal-Organic Framework Heterostructures for Noninvasively Photoresponsive High-Security Photonic Barcodes.

Stimuli-responsive micro/nanoscale photonic barcodes show great capacity for encryption and anticounterfeiting technologies due to multiple authentications, yet their application is commonly restricted by invasive stimuli. Herein, we report noninvasive light-stimulated high-security photonic barcodes based on spatially assembled photoresponsive two-dimensional (2D) 1,3,5-benzenetribenzoate (BTB)@Ln-MOF host-guest heterostructures. The photoluminescence (PL) spectra information on BTB@Ln-MOF heterostructures could be precisely controlled by the different wavelengths of ultraviolet (UV) light trigger.

Phosphate-rich cellulose beads for efficient cesium extraction from aqueous solutions: a novel approach for cellulose utilization.

In this work, phosphate-rich cellulose beads (CBPs) were first used for cesium extraction from aqueous solutions. These green, abundant, cheap, and renewable CBPs demonstrated a high adsorption capacity and fast absorption rate. Besides, the CBPs also exhibited excellent stability and recycling performance, as well as good selectivity.

Design, synthesis and evaluation of a pyrazolo[3,4-d]pyrimidine derivative as a novel and potent TGFβ1R1 inhibitor.

The transforming growth factor β1 (TGFβ1)/SMAD signaling pathway regulates many vital physiological processes. The development of potent inhibitors targeting activin receptor-like kinase 5 (ALK5) would provide potential treatment reagents for various diseases. A significant number of ALK5 inhibitors have been discovered, and they are currently undergoing clinical evaluation at various stages.

Discovery of Selective and Potent ATR Degrader for Exploration its Kinase-Independent Functions in Acute Myeloid Leukemia Cells.

ATR has emerged as a promising target for anti-cancer drug development. Several potent ATR inhibitors are currently undergoing various stages of clinical trials, but none have yet received FDA approval due to unclear regulatory mechanisms. In this study, we discovered a potent and selective ATR degrader.

Bioaerosols in the coastal region of Qingdao: Community diversity, impact factors and synergistic effect.

Atmospheric bioaerosols are influenced by multiple factors, including physical, chemical, and biotic interactions, and pose a significant threat to the public health and the environment. The nonnegligible truth however is that the primary driver of the changes in bioaerosol community diversity remains unknown. In this study, putative biological association (PBA) was obtained by constructing an ecological network.

Heterozygosity analysis of spontaneous 2n female gametes and centromere mapping of the diploid Hevea brasiliensis based on full-sib triploid populations.

Unreduced megagametophytes via second-division restitution were confirmed through heterozygosity analysis, and four candidate physical centromeres of rubber were located for the first time. The evaluation of maternal heterozygosity restitution (MHR) is vital in identifying the mechanism of 2n gametogenesis and assessing the utilization value of 2n gametes. In this study, three full-sib triploid populations were employed to evaluate the MHR of 2n female gametes of rubber tree clone GT1 and to confirm their genetic derivation.

Sophoridine derivative 6j inhibits liver cancer cell proliferation via ATF3 mediated ferroptosis.

Liver cancer is one of the most lethal malignancies with an annual death of over 830,000 cases. Although targeted therapeutic drugs have achieved certain clinical efficacy, only sorafenib and lenvatinib are currently marketed as first-line targeted drugs to treat patients with advanced liver cancer. Therefore, developing more drugs are urgently needed.

Design and discovery of new selective and potent VEGF receptor 2 tyrosine kinase inhibitors.

A series of novel substituted 4-anilinoquinazolines and their related compounds were designed and prepared by 3D modeling as potential inhibitors of VEGFR-2. Evaluation of VEGFR inhibitory activities suggested that compound I10 was a more potent (IC = 0.11 nM) VEGFR-2 inhibitor than most of the listed drugs.

Structure optimization and discovery of novel compound for the treatment of insertion mutations within exon 20 of EGFR and HER2.

In previous decades, patients with the most active EGFR mutations in non-small cell lung cancer (NSCLC) have significantly benefited from EGFR tyrosine kinase inhibitors (TKIs). However, a minority with EGFR and HER2 exon 20 mutations are inherently resistant to treatment. Several molecular TKIs (such as TAK788 and Poziotinib) were recently discovered and demonstrated as effective inhibitors against the most prevalent HER2 or EGFR exon 20 mutations.

Oncogenic SIRT7 inhibits GATA4 transcriptional activity and activates the Wnt signaling pathway in ovarian cancer.

Objective: Sirtuin-7 (SIRT7) is a class III histone deacetylase that plays an important role in cancer development and frequently overexpressed in carcinomas. In this study, the tumor-supporting role and underlying mechanisms of SIRT7 were characterized in ovarian cancer (OC) aggressiveness.

Methods: SIRT7 expression was examined in OC tissues and cells.

Discovery of novel and bioavailable histone deacetylases and cyclin-dependent kinases dual inhibitor to impair the stemness of leukemia cells.

Acute myeloid leukemia (AML) has been confirmed as one of the most lethal heterogeneous clonal diseases. In addition to being essential for the development and progression of leukemia, leukemic stem cells (LSCs), a subpopulation of leukemia cells with stem cell characteristics, are also primarily responsible for the development of leukemia relapse and drug resistance. Elimination of stemness and induction of AML cell differentiation would become a promising and effective therapeutic strategy.

Induction, Proliferation, Regeneration and Kinsenoside and Flavonoid Content Analysis of the (Wall.) Lindl Protocorm-like Body.

(Wall.) Lindl has been used in Chinese herbal medicine for treating various ailments. However, its wild resources are endangered, and artificial cultivation of the plant is limited by the low regeneration rate of conventional propagation methods.

Research Advances in Genetic Mechanisms of Major Cucumber Diseases Resistance.

Cucumber ( L.) is an important economic vegetable crop worldwide that is susceptible to various common pathogens, including powdery mildew (PM), downy mildew (DM), and Fusarium wilt (FM). In cucumber breeding programs, identifying disease resistance and related molecular markers is generally a top priority.

A stable and highly luminescent 3D Eu(III)-organic framework for the detection of colchicine in aqueous environment.

The metal-organic framework materials have an important application as sensors. In this work, a microporous three-dimensional (3D) Eu(III)-organic framework (Eu-MOF), [Eu(3,5-bct)(phen)(ox)(HO)]·HO, was constructed from 3,5-bis(3'-carboxyphenyl)-1,2,4-triazole (3,5-Hbct), oxalate (ox) and 1,10-phenanthroline (phen) as a luminescent sensor. The free volume was found to be 15.

MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer.

Background: MicroRNAs (miRNAs) have been reported to play significant roles in non-small-cell lung cancer (NSCLC). However, the roles of microRNA (miR)-1915-3p in NSCLC remain unclear. In this study, we aimed to explore the biological functions of miR-1915-3p in NSCLC.

A Novel Anticancer Stem Cell Compound Derived from Pleuromutilin Induced Necroptosis of Melanoma Cells.

Necroptosis has been recently confirmed as a non-apoptotic form of programmed cell death. Discovery of novel chemical entities, capable of inducing necroptosis of cancer cells, is likely to act as an alternative strategy for dealing with drug resistance clinically. In this study, the identification of a novel Pleuromutilin derivative (compound ) is presented, capable of significantly increasing the cellular level of ROS and inducing melanoma cancer cell death via necroptosis.

Proteolysis-Targeting Chimera (PROTAC) Modification of Dovitinib Enhances the Antiproliferative Effect against FLT3-ITD-Positive Acute Myeloid Leukemia Cells.

Acute myeloid leukemia (AML) refers to one of the most lethal blood malignancies worldwide. FLT3-ITD mutation is recognized as the most common one that predicted a poorer prognosis. There have been many prominent FLT3-ITD inhibitors approved by the FDA for clinical therapies.

Integration of organic and inorganic photothermal probes for enhanced photothermometric sensing of silver ions.

A new signal-amplified photothermometric sensor of Ag was explored based on a simple yet effective integration of inorganic and organic photothermal probes, mainly depending on the successful exploitation of a dual-signal transduction channel originating from the inherent photothermal property and the peroxidase-like activity of Prussian blue nanocubes (PB NCs).