Single-cell RNA sequencing reveals a key regulator ZmEREB14 affecting shoot apex development and yield formation in maize.

Shoot apical meristem (SAM) is the origin of aerial structure formation in the plant life cycle. However, the mechanisms underlying the maize SAM development are still obscure. Here, approximately 12 700 cells were captured from the 5-day-old shoot apex of maize using a high-throughput single-cell transcriptome sequencing.

Discovery, Synthesis, and Activity Evaluation of Novel Five-Membered Sulfur-Containing Heterocyclic Nucleosides as Potential Anticancer Agents In Vitro and In Vivo.

A series of novel five-membered sulfur-containing heterocyclic nucleoside derivatives were designed, synthesized, and evaluated for their anticancer activities in vitro and in vivo. The structure-activity relationship studies revealed that some of them showed obvious antitumor activities in several cancer cell lines. Among them, compound exhibited remarkable antiproliferative activity against HeLa cells and was more potent than cisplatin (IC = 2.

Discovery of Novel Diaryl-Substituted Fused Heterocycles Targeting Katanin and Tubulin with Potent Antitumor and Antimultidrug Resistance Efficacy.

Disrupting microtubule dynamics has emerged as a promising strategy for cancer treatment. However, drug resistance remains a challenge hindering the development of microtubule-targeting agents. In this work, a novel class of diaryl substituted fused heterocycles were designed, synthesized, and evaluated, which were demonstrated as effective dual katanin and tubulin regulators with antitumor activity.

Genome-edited rabbits: Unleashing the potential of a promising experimental animal model across diverse diseases.

Animal models are extensively used in all aspects of biomedical research, with substantial contributions to our understanding of diseases, the development of pharmaceuticals, and the exploration of gene functions. The field of genome modification in rabbits has progressed slowly. However, recent advancements, particularly in CRISPR/Cas9-related technologies, have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases, including cardiovascular disorders, immunodeficiencies, aging-related ailments, neurological diseases, and ophthalmic pathologies.

Discovery of chiral 1,4-diarylazetidin-2-one-based hydroxamic acid derivatives as novel tubulin polymerization inhibitors with histone deacetylase inhibitory activity.

Tubulin and histone deacetylase have been clinically proven as promising targets for cancer therapy. Herein, we describe the design and synthesis of chiral 1,4-diarylazetidin-2-one-based hydroxamic acids as novel tubulin/HDAC dual inhibitors. Among them, compound 12a was validated to effectively disrupt tubulin polymerization, and exhibited potent HDAC1/8 inhibitory activities.

Discovery of a 2,6-diarylpyridine-based hydroxamic acid derivative as novel histone deacetylase 8 and tubulin dual inhibitor for the treatment of neuroblastoma.

Herein, two series of HDAC/tubulin dual inhibitors via introducing the key pharmacophore of HDAC inhibitor into the skeletons of 2,6-diarylpyridine and 2'-arylchalcone were synthesized. Among them, 2,6-diarylpyridine-based hydroxamic acid 10a exhibited good inhibitory activity against HDAC8 (IC = 117 nM) with 50-fold and 42-fold high selectivity relative to HDAC1 and HDAC6, respectively. Meanwhile, 10a disrupted tubulin polymerization effectively and exhibited potent antiproliferative activity against BE-(2)-C cell line, with IC value of 17 nM.

Targeting the tumor microenvironment by an enzyme-responsive prodrug of tubulin destabilizer for triple-negative breast cancer therapy with high safety.

In response to the long-term potential toxicity concerns of tubulin destabilizer, an enzyme-responsive prodrug therapy for triple-negative breast cancer was developed based on the different β-glucuronidase levels between tumor and normal tissues in this study. All the prodrugs synthesized herein showed remarkable stability in phosphate buffer and bovine serum solution, among which 17a was found to be more susceptible to enzymatic cleavage. 17a exhibited excellent selectivity between the in vitro antiproliferative activities against β-glucuronidase-pretreated and -untreated cancer cells (IC (+Enz) = 8.

Effect of Physical Properties of a Gas on the Refrigeration Temperature Drop of Vortex Tubes Used in Oil and Gas Fields.

The composition of natural gas can vary considerably across different oil and gas fields. Such compositional variation is primarily reflected in the distinctive physical properties of natural gas. However, during practical application in an oil and gas field, a refrigeration temperature drop in a vortex tube is often observed because vortex tubes generally have low intrinsic refrigeration efficiencies.

Design, synthesis and antitumor evaluation of novel chiral diaryl substituted azetidin-2-one derivatives as tubulin polymerization inhibitors.

A novel class of diaryl substituted azetidin-2-one derivatives were designed, asymmetrically synthesized, and evaluated for antiproliferative activities. The in vitro antitumor assay revealed that among the 4-aryl-substituted 1-(3,4,5-trimethoxyphenyl)azetidin-2-ones (B series), most possessed moderate to strong activities, with compound B7c that bears a 2-naphthyl substituent being the most potent one (IC 0.16-0.

Bifunctional chiral selenium-containing 1,4-diarylazetidin-2-ones with potent antitumor activities by disrupting tubulin polymerization and inducing reactive oxygen species production.

Organoselenium compounds have attracted growing interests as promising antitumor agents over recent years. Herein, four series of novel selenium-containing chiral 1,4-diarylazetidin-2-ones were asymmetrically synthesized and biologically evaluated for antitumor activities. Among them, compound 7 was found to be about 10-fold more potent than its prototype compound 1a, and compound 9a exhibited the most potent cytotoxicity against five human cancer cell lines, including a paclitaxel-resistant human ovarian cancer cell line A2780T, with IC values ranging from 1 to 3 nM.

Novel diaryl-2H-azirines: Antitumor hybrids for dual-targeting tubulin and DNA.

Multiple-target drugs may achieve better therapeutic effect via different pathways than single-target ones, especially for complex diseases. Tubulin and DNA are well-characterized molecular targets for anti-cancer drug development. A novel class of diaryl substituted 2H-azirines were designed based on combination of pharmacophores from Combretastatin A-4 (CA-4) and aziridine-type alkylating agents, which are known tubulin polymerization inhibitor and DNA damaging agents, respectively.

Design, Synthesis, and Activity Evaluation of Novel Acyclic Nucleosides as Potential Anticancer Agents and .

In the present work, 103 novel acyclic nucleosides were designed, synthesized, and evaluated for their anticancer activities and . The structure-activity relationship (SAR) studies revealed that most target compounds inhibited the growth of colon cancer cells , of which 3-(6-chloro-9-purin-9-yl)dodecan-1-ol () exhibited the most potent effect against the HCT-116 and SW480 cells with IC values of 0.89 and 1.

Amentotaxins C-V, Structurally Diverse Diterpenoids from the Leaves and Twigs of the Vulnerable Conifer and Their Cytotoxic Effects.

A phytochemical investigation of the MeOH extract of the leaves and twigs of , a relict vulnerable coniferous species endemic to China, led to the isolation and characterization of 35 diterpenoids/norditerpenoids. Twenty of these are new, including 11 -kaurane-type (amentotaxins C-M, -, respectively), three icetexane-type [= 9(10→20)-abietane-type (amentotaxins N-P, -, respectively)], four -labdane-type (amentotaxins Q-T, -, respectively), and two isopimarane-type [amentotaxins U () and V ()] compounds. Their structures were elucidated on the basis of spectroscopic data, single-crystal X-ray diffraction, the modified Mosher's method, and electronic circular dichroism data analyses.

Discovery of a chiral fluorinated azetidin-2-one as a tubulin polymerisation inhibitor with potent antitumour efficacy.

Inhibition of tubulin polymerisation with small molecules has been clinically validated as a promising therapy for multiple solid tumours. Herein, a series of chiral azetidin-2-ones were asymmetrically synthesised and biologically evaluated for antitumour activities. Among them, a chiral fluorinated azetidin-2-one, 18, was found to exhibit the most potent activities against five cancer cell lines, including a drug-resistant cell line, with IC values ranging from 1.

Discovery of Novel Aryl Carboxamide Derivatives as Hypoxia-Inducible Factor 1α Signaling Inhibitors with Potent Activities of Anticancer Metastasis.

In order to discover novel hypoxia-inducible factor 1 (HIF-1) inhibitors for the cancer metastasis treatment, 68 new aryl carboxamide compounds were synthesized and evaluated for their inhibitory effect by dual luciferase-reporter assay. Based on five rounds of investigation on structure-activity relationships step by step, compound was discovered as the most active inhibitor (IC = 0.32 μM) with no obvious cytotoxicity (CC > 50 μM).

Design, synthesis, antitumor activities and biological studies of novel diaryl substituted fused heterocycles as dual ligands targeting tubulin and katanin.

Microtubule is one of the important targets for cancer treatment. A novel class of diaryl substituted imidazo[4,5-c]pyridin-2-ones and imidazo[4,5-c]pyridines were designed based on combination principles by merging the structures of β-lactams and purine-type compounds known as tubulin polymerization inhibitor and katanin activity up-regulator, respectively. Their antitumor activities were evaluated in vitro and the mechanism was elucidated, leading to the identification of 1,6-diaryl-1H-imidazo[4,5-c]pyridin-2(3H)-one 20b as the first bifunctional agent that can target both tubulin and katanin simultaneously.

Design, synthesis, biological evaluation and cocrystal structures with tubulin of chiral β-lactam bridged combretastatin A-4 analogues as potent antitumor agents.

A diverse of chiral β-lactam bridged analogues of combretastatin A-4 (CA-4), 3-substituted 1,4-diaryl-2-azetidinones, were asymmetrically synthesized and biologically evaluated, leading to identify a number of potent anti-proliferative compounds represented by 14b and 14c with IC values of 0.001-0.021 μM, against four human cancer cell lines (A2780, Hela, SKOV-3 and MDA-MB-231).

Design, synthesis, and biological evaluation of hydantoin bridged analogues of combretastatin A-4 as potential anticancer agents.

A series of novel hydantoin-bridged analogues of combretastatin A-4 (CA-4) were designed, synthesized and evaluated for antiproliferative activities in vitro and in vivo. The most potent compound 8d, showed potent cytotoxicity against four human cancer cell lines with IC values of 0.186-0.

Potent Antitumor Activities and Structure Basis of the Chiral β-Lactam Bridged Analogue of Combretastatin A-4 Binding to Tubulin.

A series of chiral β-lactam bridged analogues (3-substituted 1,4-diaryl-2-azetidinones) of combretastatin A-4 (CA-4) were synthesized asymmetrically, and their antitumor activities were evaluated in vitro and in vivo. The cocrystal structure of tubulin in complex with compound 9 was determined by X-ray crystallography, which showed that 9 binds to the same site as colchicine with similar binding mode, and the absolute configuration of its C-4 was first identified and demonstrated to be critically important for their antiproliferative activities.