Case Report: Two different acromelic dysplasia phenotypes in a Chinese family caused by a missense mutation in and a literature review.

Background: Acromelic dysplasia caused by mutation includes acromicric dysplasia (AD), geleophysic dysplasia 2 (GD2), and Weill-Marchesani syndrome 2 (WMS2). All three diseases share severe short stature and brachydactyly. Besides phenotypic similarity, there is a molecular genetic overlap among them, as identical gene mutations have been identified in patients with AD, GD2, and WMS2.

Discovery of benzamide-based PI3K/HDAC dual inhibitors with marked pro-apoptosis activity in lymphoma cells.

Inhibition of PI3K and histone deacetylase (HDAC) activity simultaneously using a single molecule appears to be a promising approach for cancer treatment. Current PI3K/HDAC dual inhibitors commonly use hydroxamate moiety as zinc binding group, which lack HDAC isoform selectivity and have potential genotoxicity. In this study, a novel series of benzamide-based PI3K/HDAC dual inhibitors were rationally designed and synthesized.

Image Reconstruction Using Supervised Learning in Wearable Electrical Impedance Tomography of the Thorax.

Electrical impedance tomography (EIT) is a non-invasive technique for visualizing the internal structure of a human body. Capacitively coupled electrical impedance tomography (CCEIT) is a new contactless EIT technique that can potentially be used as a wearable device. Recent studies have shown that a machine learning-based approach is very promising for EIT image reconstruction.

Al-induced CsUGT84J2 enhances flavonol and auxin accumulation to promote root growth in tea plants.

Although Al is not necessary or even toxic to most plants, it is beneficial for the growth of tea plants. However, the mechanism through which Al promotes root growth in tea plants remains unclear. In the present study, we found that flavonol glycoside levels in tea roots increased following Al treatment, and the Al-induced UDP glycosyltransferase CsUGT84J2 was involved in this mechanism.

Synthesis and bioactivity evaluation of ferrocene-based hydroxamic acids as selective histone deacetylase 6 inhibitors.

Histone deacetylase 6 (HDAC6) is involved in multiple regulatory processes and emerges as a promising target for treating cancer and neurodegenerative diseases. Benefited from the unique sandwich conformation of ferrocene, a series of ferrocene-based hydroxamic acids have been developed as novel HDAC6 inhibitors in this paper, especially the two ansa-ferrocenyl complexes with ICs at the nanomolar level. [3]-Ferrocenophane hydroxamic acid analog II-5 displays the most potent inhibitory activity on HDAC6 and establishes remarkable selectivity towards other HDAC isoforms.

First-in-Class Hydrazide-Based HDAC6 Selective Inhibitor with Potent Oral Anti-Inflammatory Activity by Attenuating NLRP3 Inflammasome Activation.

In this study, we report the first highly selective HDAC6 inhibitor with hydrazide as the zinc-binding group (ZBG), which displays superior pharmacokinetic properties to the current hydroxamic acid inhibitors. Structure-activity relationship study reveals that ethyl group substituent hydrazide-based ZBG and cap group with more substantial rigidity and larger volume increase the HDAC6 selectivity of designed compounds. Representative inhibitor exhibits potent HDAC6 inhibitory activity with an IC value of 0.

Grain-boundary-rich layered double hydroxides a boron-assisted strategy for the oxygen evolution reaction.

This study reports a facile boron-assisted strategy to prepare NiFe LDHs with rich grain boundaries. The formation of these grain boundaries originates from the imperfect oriented attachment between primary LDH particles transformed from amorphous borides/borates. The obtained grain-boundary-rich NiFe LDHs exhibit excellent oxygen evolution reaction activity.

Potent Hydrazide-Based HDAC Inhibitors with a Superior Pharmacokinetic Profile for Efficient Treatment of Acute Myeloid Leukemia In Vivo.

As "Michael acceptors" may induce promiscuous responses in mammalian cells by reacting with various proteins, we modified the cinnamamide of our previous hydrazide-based HDAC inhibitors (HDACIs) to deactivate the Michael reaction. Representative compound is 2-5 times more potent than lead compound in both HDAC inhibitory activity (IC = 0.43-3.

Design, synthesis and biological evaluation of hybrid of ubenimex-fluorouracil for hepatocellular carcinoma therapy.

In our previous study, we discovered a ubenimex-fluorouracil (5FU) conjugates BC-02, which displays significant in vivo anti-tumor activity, however, the instability of BC-02 in plasma limits its further development as a drug candidate. Herein, we designed and synthesized four novel ubenimex-5FU conjugates by optimizing the linkers between ubenimex and 5FU based on BC-02. Representative compound 20 is more stable than BC-02 in human plasma and displays about 100 times higher CD13 inhibitory activity than the positive control ubenimex.

A GLUT1 inhibitor-based fluorogenic probe for Warburg effect-targeted drug screening and diagnostic imaging of hyperglycolytic cancers.

Increased expression of glucose transporters, especially GLUT1 has been proven to be involved in the Warburg effect. Therefore, GLUT1-targeted oncological approaches are being successfully employed for clinical tumor diagnostic imaging (e.g.