Identification of a histone acetyltransferase as a novel regulator of Drosophila intestinal stem cells

AbstractOne of the major challenges in stem cell research is to decipher the controlling mechanisms/genes of stem cell homeostasis. Through an RNAi mediated genetic screen of living animals, we identified an evolutionarily conserved histone acetyltransferase Atac2 as a novel regulator of Drosophila intestinal stem cells (ISCs). Expression of Atac2-RNAi or a dominant negative allele of Atac2 generated more ISCs, while excessive Atac2 or a histone deacetylase inhibitor promoted ISC differentiation without affecting ISC survival or lineage specification. These findings extend our knowledge of epigenetic mechanisms in stem cell regulation

Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer

The aberrant activation of STAT3 is associated with the etiology and progression in a variety of malignant epithelial-derived tumors, including head and neck squamous cell carcinoma (HNSCC) and colorectal cancer (CRC). Due to the lack of an enzymatic catalytic site or a ligand-binding pocket, there are no small-molecule inhibitors directly targeting STAT3 that have been approved for clinical translation. Emerging proteolysis targeting chimeric (PROTAC) technology-based approach represents a potential strategy to overcome the limitations of conventional inhibitors and inhibit activation of STAT3 and downstream genes. In this study, the heterobifunctional small-molecule-based PROTACs are successfully prepared from toosendanin (TSN), with 1 portion binding to STAT3 and the other portion binding to an E3 ubiquitin ligase. The optimized lead PROTAC (TSM-1) exhibits superior selectivity, potency, and robust antitumor effects in STAT3-dependent HNSCC and CRC - especially in clinically relevant patient-derived xenografts (PDX) and patient-derived organoids (PDO). The following mechanistic investigation identifies the reduced expression of critical downstream STAT3 effectors, through which TSM-1 promotes cell cycle arrest and apoptosis in tumor cells. These findings provide the first demonstration to our knowledge of a successful PROTAC-targeting strategy in STAT3-dependent epithelial cancer

Facile Preparation of Bimetallic MOF-derived Supported Tungstophosphoric Acid Composites for Biodiesel Production

In this work, the novel TPA@C-NiZr-MOF catalyst is synthesized by the impregnation of tungstophosphoric acid (TPA) on the NiZr-based metal-organic framework (NiZr-MOF) followed by calcination up to 300 °C. The as-prepared catalyst materials were structurally, morphologically, and texturally characterized by XRD, FTIR, temperature programmed desorption of NH3 ( TPD-NH3 ), N2 physisorption, SEM, TEM, and XPS. The prepared catalyst can be used as an efficient heterogeneous catalyst for biodiesel production from oleic acid (OA) with methanol. The results indicated that, in comparison to TPA@NiZr-MOF, the TPA@C-NiZr-MOF catalyst calcined at 300 °C exhibits excellent catalytic performance probably owing to the synergistic effect between TPA and metal oxide skeletons, high acidity, as well as larger surface area and pore size. Additionally, the TPA@C-NiZr-MOF catalyst can be reused in up to six cycles with an acceptable conversion. This study showed that the bimetallic MOF-derived composite materials can be used as an alternative potential heterogeneous catalyst toward biorefinery applications

Adenosine deaminase acting on RNA 1 (ADAR1) as crucial regulators in cardiovascular diseases: structures, pathogenesis, and potential therapeutic approach

Cardiovascular diseases (CVDs) are a group of diseases that have a major impact on global health and are the leading cause of death. A large number of chemical base modifications in ribonucleic acid (RNA) are associated with cardiovascular diseases. A variety of ribonucleic acid modifications exist in cells, among which adenosine deaminase-dependent modification is one of the most common ribonucleic acid modifications. Adenosine deaminase acting on ribonucleic acid 1 (Adenosine deaminase acting on RNA 1) is a widely expressed double-stranded ribonucleic acid adenosine deaminase that forms inosine (A-to-I) by catalyzing the deamination of adenosine at specific sites of the target ribonucleic acid. In this review, we provide a comprehensive overview of the structure of Adenosine deaminase acting on RNA 1 and summarize the regulatory mechanisms of ADAR1-mediated ribonucleic acid editing in cardiovascular diseases, indicating Adenosine deaminase acting on RNA 1 as a promising therapeutic target in cardiovascular diseases

Efficient Er/O‐Doped Silicon Light‐Emitting Diodes at Communication Wavelength by Deep Cooling

A silicon light source at the communication wavelength is the bottleneck for developing monolithically integrated silicon photonics. Doping silicon with erbium and oxygen ions is considered one of the most promising approaches to produce silicon light sources. However, this method suffers from a high concentration of defects in the form of nonradiative recombination centers at the interface between the crystalline silicon and large Er2O3/ErSi1.7 precipitates during the standard rapid thermal treatment. Here, a deep cooling process is applied to suppress the growth of these precipitates by flushing the high‐temperature Er/O‐doped silicon substrates with helium gas cooled in liquid nitrogen. The resultant light‐emitting efficiency at room temperature is enhanced by two orders of magnitude in comparison with that of the sample treated via standard rapid thermal annealing. The deep‐cooling‐processed Si samples are further processed into light‐emitting diodes. Bright electroluminescence with a main spectral peak at 1536 nm is also observed from the silicon‐based diodes with the external quantum efficiency reaching ≈0.8% at room temperature. Based on these results, the development of electrically driven silicon optical amplifiers or even lasers at communication wavelengths is promising for monolithically integrated silicon photonics.A deep cooling technique is developed for silicon light sources by suppressing the growth of Er/O‐related precipitates. The resultant near‐infrared emission shows efficiency enhancement by two orders of magnitude. Bright electroluminescence with a main spectral peak at 1536 nm is also observed. The external quantum efficiency can reach 0.8% at room temperature.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162702/3/adom202000720.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162702/2/adom202000720-sup-0001-SuppMat.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162702/1/adom202000720_am.pd