Engineered IscB-ωRNA system with expanded target range for base editing.

As the evolutionary ancestor of Cas9 nuclease, IscB proteins serve as compact RNA-guided DNA endonucleases and nickases, making them strong candidates for base editing. Nevertheless, the narrow targeting scope limits the application of IscB systems; thus, it is necessary to find more IscBs that recognize different target-adjacent motifs (TAMs). Here, we identified 10 of 19 uncharacterized IscB proteins from uncultured microbes with activity in mammalian cells.

CRISPR-CasRx-mediated disruption of Aqp1/Adrb2/Rock1/Rock2 genes reduces intraocular pressure and retinal ganglion cell damage in mice.

Glaucoma affects approximately 80 million individuals worldwide, a condition for which current treatment options are inadequate. The primary risk factor for glaucoma is elevated intraocular pressure. Intraocular pressure is determined by the balance between the secretion and outflow of aqueous humor.

Evaluation of a New All-in-One Optical Biometer and Comparison With a Validated Swept-source OCT Biometer.

Purpose: To assess agreement between a new all-in-one non-contact optical biometer based on optical low coherence reflectometry (SW-9000 µm Plus; Suoer) and a swept-source optical coherence tomography biometer (OA-2000; Tomey).

Methods: Each eye was scanned three times in a row by each device at random. The measured ocular parameters included central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), axial length (AL), flat keratometry (Kf), steep keratometry (Ks), mean keratometry (Km), astigmatism, corneal diameter (CD), and pupil diameter (PD).

Precision (repeatability and reproducibility) of papillary and peripapillary vascular density measurements using optical coherence tomography angiography in children.

Importance: Optical coherence tomography angiography (OCTA) has been widely applied into children, however, few studies have assessed the repeatability and reproducibility of papillary and peripapillary VD in healthy children.

Objective: To assess the precision of papillary and peripapillary vascular density (VD) measurements using optical coherence tomography angiography (OCTA) and analyze the effects of the signal strength index (SSI) and axial length (AL) on precision estimates.

Design Setting And Participants: This was a prospective observational study.

Enhancement and Repair of Degenerative Intervertebral Disc in Rats Using Platelet-Rich Plasma/Ferulic Acid Hydrogel.

Background: Intervertebral degenerative disc (IDD) disease is one of the most common clinical conditions causing low back pain. The main objective of this study was to investigate the repair effect of platelet-rich plasma (PRP) and ferulic acid (FA) hydrogel compound on degenerative discs in rats in combination with bioengineering technology, which may provide a strong theoretical basis for the future treatment of IDD.

Methods: Forty-five male Sprague-Dawley rats were randomly divided into groups A-F; MRI was performed in each group at 0, 4, and 8 weeks after injection; and disc tissues were obtained after executing the animals.

GNE-493 inhibits prostate cancer cell growth via Akt-mTOR-dependent and -independent mechanisms.

GNE-493 is a novel PI3K/mTOR dual inhibitor with improved metabolic stability, oral bioavailability, and excellent pharmacokinetic parameters. Here GNE-493 potently inhibited viability, proliferation, and migration in different primary and established (LNCaP and PC-3 lines) prostate cancer cells, and provoking apoptosis. GNE-493 blocked Akt-mTOR activation in primary human prostate cancer cells.

The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma.

It is urgent to identify and validate biomarkers for early diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC). Recent studies have proposed p38 gamma (p38γ) as a cyclin-dependent kinase (CDK)-like kinase that phosphorylates retinoblastoma (Rb) to promote cyclins expression and tumorigenesis. Here the Gene Expression Profiling Interactive Analysis (GEPIA) database and results from the local NPC tissues demonstrate that p38γ is significantly upregulated in NPC tissues, correlating with poor overall survival.

Poly(N-isopropylacrylamide)-Based Thermoresponsive Composite Hydrogels for Biomedical Applications.

Poly(N-isopropylacrylamide) (PNIPAM)-based thermosensitive hydrogels demonstrate great potential in biomedical applications. However, they have inherent drawbacks such as low mechanical strength, limited drug loading capacity and low biodegradability. Formulating PNIPAM with other functional components to form composited hydrogels is an effective strategy to make up for these deficiencies, which can greatly benefit their practical applications.

Joint Learning of Multiple Latent Domains and Deep Representations for Domain Adaptation.

In domain adaptation, the automatic discovery of multiple latent source domains has succeeded by capturing the intrinsic structure underlying the source data. Different from previous works that mainly rely on shallow models for domain discovery, we propose a novel unified framework based on deep neural networks to jointly address latent domain prediction from source data and deep representation learning from both source and target data. Within this framework, an iterative algorithm is proposed to alternate between 1) utilizing a new probabilistic hierarchical clustering method to separate the source domain into latent clusters and 2) training deep neural networks by using the domain membership as the supervision to learn deep representations.

Crystal structure of EGFR T790M/C797S/V948R in complex with EAI045.

Lung cancer is the leading cause of cancer deaths. Epidermal growth factor receptor (EGFR) kinase domain mutations are a common cause of non-small cell lung cancers (NSCLCs), a major subtype of lung cancers. Patients harboring most of these mutations respond well to the anti-EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib initially, but soon develop resistance to them in about half of the cases due to the emergence of the gatekeeper mutation T790M.

Structural pharmacological studies on EGFR T790M/C797S.

Drug-resistance is a major challenge in targeted therapy of EGFR mutated non-small cell lung cancers (NSCLCs). The third-generation irreversible inhibitors such as AZD9291, CO-1686 and WZ4002 can overcome EGFR T790M drug-resistance mutant through covalent binding through Cys 797, but ultimately lose their efficacy upon emergence of the new mutation C797S. To develop new reversible inhibitors not relying on covalent binding through Cys 797 is therefore urgently demanded.

Effect of volatile-char interaction on the NO emission from coal combustion.

To clarify the effects of volatile-char interaction on the redistribution of fuel-N to N2 during devolatilization and the reduction of NO through gas-solid reactions during combustion, two types of experiments were performed on a novel reactor. The separate combustion of volatile and char and the combustion of entrained pulverized coal, and the formation of NO was examined between 800 and 1100 degrees C by using four typical Chinese coals with different ranks. The effect of volatile-char interaction on fuel-N conversion to NO during combustion was elucidated through comparing the NO emissions from the two types of combustion experiments.