Light control and optical path design method for stabilized zoom systems based on deformable mirrors.

We extend the design methodology for stabilized zoom systems by analyzing the stable convergence of singular points in the solution region for image plane shift compensation and continuous zooming. Using lens group magnification as key parameters, we analyze the stability of singular points related to the descending gradient of the zoom equation and the positions of extremum points within the solution region. These singular points and their solution regions are identified and correspond to solutions of specific optical path structures.

Discovery, Characterization, and Structure of a Cell Active PAD2 Inhibitor Acting through a Novel Allosteric Mechanism.

Peptidyl arginine deiminases (PADs) are important enzymes in many diseases, especially those involving inflammation and autoimmunity. Despite many years of effort, developing isoform-specific inhibitors has been a challenge. We describe herein the discovery of a potent, noncovalent PAD2 inhibitor, with selectivity over PAD3 and PAD4, from a DNA-encoded library.

Re-Evaluating PIN1 as a Therapeutic Target in Oncology Using Neutral Inhibitors and PROTACs.

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) has emerged as a promising therapeutic target for cancer treatment. However, the current PIN1 inhibitors have shown limited efficacy in animal models, leaving the question of whether PIN1 is a proper oncologic target still unanswered. By screening a 1 trillion DNA-encoded library (DEL), we identified novel nonacidic compounds.

Gearbox fault diagnosis method based on lightweight channel attention mechanism and transfer learning.

In practical engineering, the working conditions of gearbox are complex and variable. In varying working conditions, the performance of intelligent fault diagnosis model is degraded because of limited valid samples and large data distribution differences of gearbox signals. Based on these issues, this research proposes a gearbox fault diagnosis method integrated with lightweight channel attention mechanism, and further realizes the cross-component transfer learning.

Optimization of PROTAC Ternary Complex Using DNA Encoded Library Approach.

The proteolysis targeting chimera (PROTAC) strategy results in the down-regulation of unwanted protein(s) for disease treatment. In the PROTAC process, a heterobifunctional degrader forms a ternary complex with a target protein of interest (POI) and an E3 ligase, which results in ubiquitination and proteasomal degradation of the POI. While ternary complex formation is a key attribute of PROTAC degraders, modification of the PROTAC molecule to optimize ternary complex formation and protein degradation can be a labor-intensive and tedious process.

Extendible ghost imaging with high reconstruction quality in strong scattering medium.

Ghost imaging (GI) possesses significant application prospects in scattering imaging, which is a classic example of underdetermined conversion problem in optical field. However, even under the framework of single-pixel imaging (SPI), a challenge remains unresolved, i.e.

PAC-FragmentDEL - photoactivated covalent capture of DNA-encoded fragments for hit discovery.

We describe a novel approach for screening fragments against a protein that combines the sensitivity of DNA-encoded library technology with the ability of fragments to explore what will bind. Each of the members of the library consists of a fragment which is linked to a photoactivatable diazirine moiety. Split and pool synthesis combines each fragment with a set of linkers with the version of the library reported here containing some 70k different compounds, each with an individual DNA code.

Expanding the DNA-encoded library toolbox: identifying small molecules targeting RNA.

DNA-encoded library (DEL) technology is a powerful tool for small molecule identification in drug discovery, yet the reported DEL selection strategies were applied primarily on protein targets in either purified form or in cellular context. To expand the application of this technology, we employed DEL selection on an RNA target HIV-1 TAR (trans-acting responsive region), but found that the majority of signals were resulted from false positive DNA-RNA binding. We thus developed an optimized selection strategy utilizing RNA patches and competitive elution to minimize unwanted DNA binding, followed by k-mer analysis and motif search to differentiate false positive signal.

Effect of cattle farm exposure on oropharyngeal and gut microbial communities and antibiotic resistance genes in workers.

Livestock farms are recognized as the main sources of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) with potential implications for human health. In this study, we systematically analyzed microbiome composition, distribution of ARGs and mobile genetic elements (MGEs) in the oropharynx and gut of workers in cattle farms and surrounding villagers, cattle feces and farm air, and the relationship of microbial communities among farm air, cattle feces and farmworkers (oropharynx and gut). Exposure to the farm environment may have remodeled farmworkers' oropharynx and gut microbiota, with reduced microbial diversity (P < 0.

A Novel Scalarized Scaffold Hopping Algorithm with Graph-Based Variational Autoencoder for Discovery of JAK1 Inhibitors.

We have developed a graph-based Variational Autoencoder with Gaussian Mixture hidden space (GraphGMVAE), a deep learning approach for controllable magnitude of scaffold hopping in generative chemistry. It can effectively and accurately generate molecules from a given reference compound, with excellent scaffold novelty against known molecules in the literature or patents (97.9% are novel scaffolds).

Time-course miRNA alterations and SIRT1 inhibition triggered by adolescent lead exposure in mice.

Sirtuin 1 (SIRT1), the NAD-dependent histone deacetylase, has been extensively investigated due to its cognitive protective effect. Studies suggest microRNAs (miRNAs) and histone modifications are key epigenetic regulators of gene expression and play important role in brain development. We previously showed that cognitive impairment by lead (Pb) was associated with downregulation of SIRT1, but the epigenetic role of this is unclear.

Attenuation of Pb-induced Aβ generation and autophagic dysfunction via activation of SIRT1: Neuroprotective properties of resveratrol.

This study examined the neuroprotective properties of resveratrol (Res) and its target sirtuin1 (SIRT1) against lead (Pb)-mediated toxicity and discovered that both resveratrol treatment and SIRT1 overexpression restored blocked autophagic flux as well as reduced β-amyloid (Aβ) contents. Four-week-old male C57BL/6 mice were employed to consumed 0.2% Pb(Ac) solution or deionized water for 3 months followed by 12 months of Res (50 mg/kg BW) or vehicle gavage.

Resveratrol reverses hippocampal synaptic markers injury and SIRT1 inhibition against developmental Pb exposure.

Lead (Pb) exposure damages synaptic structural plasticity that results in cognitive impairment. Resveratrol, a natural polyphenolic compound, is one of the most potent agonists of silencing information regulator 1 (SIRT1) discovered to date. However, the effects of SIRT1 on synaptic functional plasticity in early life Pb exposure are not well studied.

Description method with automatically configurable Gaussian radial basis function for complex freeform surface.

The description of deformable mirror (DM) surface, which is usually a complex freeform surface, affects the measurement speed and accuracy in a real-time interferometric measurement system with a DM as the dynamic compensator. We propose an accurate and fast description method with automatically configurable Gaussian radial basis function. The distribution and shape factors of GRBFs are related to the complexity of the surface with sufficient flexibility to improve the accuracy, and the fitting results are automatically obtained using a traversal optimization algorithm, which can improve the fitting speed by reducing the number of time-consuming calculations.

Resveratrol improved hippocampal neurogenesis following lead exposure in rats through activation of SIRT1 signaling.

Lead (Pb) poses a potential environmental risk factor for cognitive dysfunction during early life and childhood. Resveratrol is considered a promising antioxidant with respect to the prevention of cognitive deficits and act as a potent SIRT1 agonist. Herein, this study aims to investigate the profile of neurogenesis markers following Pb exposure and to determine the regulatory role of resveratrol in this process.

Synthetic system design method for off-axis stabilized zoom systems with a high zoom ratio.

Stabilized zoom systems possess the advantages such as the simplified system layout, improved system stability, enhanced imaging performance, and a high zoom speed. The complex system design to achieve high performances requires calculations or investigations of the initial system for optimization and improvements, and thus, specific design techniques are pursued. In this study, we propose an automatic optical design scheme of synthetic characteristics for the off-axis stabilized zoom systems, which using focal length variable (FLV) opto-electronic elements and with a high zoom ratio.

Fluoride exposure and intelligence in school-age children: evidence from different windows of exposure susceptibility.

Background: The intellectual loss induced by fluoride exposure has been extensively studied, but the association between fluoride exposure in different susceptibility windows and children's intelligence is rarely reported. Hence, we conducted a cross-sectional study to explore the association between fluoride exposure in prenatal and childhood periods and intelligence quotient (IQ).

Methods: We recruited 633 local children aged 7-13 years old randomly from four primary schools in Kaifeng, China in 2017.

Exploring Aldol Reactions on DNA and Applications to Produce Diverse Structures: An Example of Expanding Chemical Space of DNA-Encoded Compounds by Diversity-Oriented Synthesis.

A DNA-encoded chemical library (DECL) is built with combinatorial chemistry, which works by bringing chemical fragments together to generate diverse structures. However, chemical diversity of DNA-encoded chemical libraries is often limited by DNA compatible synthetic reactions. This report shows a conceptual strategy to expand chemical space of DNA-encoded chemical libraries by incorporation of diversity-oriented synthesis in DECL synthesis.

Characterization of Specific -α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library.

Two novel compounds were identified as Naa50 binders/inhibitors using DNA-encoded technology screening. Biophysical and biochemical data as well as cocrystal structures were obtained for both compounds ( and ) to understand their mechanism of action. These data were also used to rationalize the binding affinity differences observed between the two compounds and a MLGP peptide-containing substrate.

Method for Training Convolutional Neural Networks for In Situ Plankton Image Recognition and Classification Based on the Mechanisms of the Human Eye.

In this study, we propose a method for training convolutional neural networks to make them identify and classify images with higher classification accuracy. By combining the Cartesian and polar coordinate systems when describing the images, the method of recognition and classification for plankton images is discussed. The optimized classification and recognition networks are constructed.

Fluoride exposure and CALCA methylation is associated with the bone mineral density of Chinese women.

Excessive exposure to fluoride has been reported to affect bone mineral density (BMD). CALCA expression plays a critical part in bone formation. However, the role of CALCA in the association between fluoride and BMD is not known.