Semi-rational engineering of a novel halohydrin dehalogenase from Sneathiella limimaris for the enantioselective synthesis of (S)-5-phenoxymethyl-2-oxazolidinone.

Enantiomerically pure 2-oxazolidinones are widely used as chiral auxiliaries in organic synthesis, but there is an unmet need for more effective methods to access these compounds. Here we report the identification and semi-rational engineering of the halohydrin dehalogenase SlHHDH from Sneathiella limimaris for the highly enantioselective ring-opening of phenyl glycidyl ether (PGE) with cyanate to yield (S)-5-phenoxymethyl-2-oxazolidinone. After single and combinatorial mutagenesis, the best enantioselective triple mutant, F15W/A137T/N179L achieved an enantioselectivity of 97 %, with an E value of 154.

Engineering Injectable and Highly Interconnected Porous Silk Fibroin Microspheres for Tissue Regeneration.

Injectable porous microspheres represent a promising therapeutic platform for cell delivery, drug delivery, and tissue regeneration. Yet, the engineering of silk fibroin microspheres with a highly interconnected porous structure remains an unsolved challenge. In this study, a simple and efficient method is developed that does not require the use of organic solvents to prepare silk fibroin microspheres with a predictable structure.

Vina-GPU 2.1: Towards Further Optimizing Docking Speed and Precision of AutoDock Vina and Its Derivatives.

AutoDock Vina and its derivatives have established themselves as a prevailing pipeline for virtual screening in contemporary drug discovery. Our Vina-GPU method leverages the parallel computing power of GPUs to accelerate AutoDock Vina, and Vina-GPU 2.0 further enhances the speed of AutoDock Vina and its derivatives.

tsRNA modifications: An emerging layer of biological regulation in disease.

Background: Transfer RNA (tRNA)-derived small RNA (tsRNA) represents an important and increasingly valued type of small non-coding RNA (sncRNA). The investigation of tRNA and tsRNA modification crosswalks has not only provided novel insights into the information and functions of tsRNA, but has also expanded the diversity and complexity of the tsRNA biological regulation network.

Aim Of Review: Comparing with other sncRNAs, tsRNA biogenesis show obvious correlation with RNA modifications from mature tRNA and harbor various tRNA modifications.

A Novel tsRNA, mG-3' tiRNA Lys, Promotes Bladder Cancer Malignancy Via Regulating ANXA2 Phosphorylation.

Emerging evidence indicates that transfer RNA (tRNA)-derived small RNAs (tsRNAs), originated from tRNA with high abundance RNA modifications, play an important role in many complex physiological and pathological processes. However, the biological functions and regulatory mechanisms of modified tsRNAs in cancer remain poorly understood. Here, it is screened for and confirmed the presence of a novel mG-modified tsRNA, mG-3'-tiRNA Lys (mtiRL), in a variety of chemical carcinogenesis models by combining small RNA sequencing with an mG small RNA-modified chip.

Circular RNA DLGAP4 Inhibits Ischemic Stroke-Induced Microglia M1 Polarization and Proinflammatory Cytokine Production, Possibly through the NF-κB Pathway.

Circular RNA DLGAP4 (circ_DLGAP4) participates in the progression of ischemic stroke (IS), but whether it could regulate microglia activation to affect IS injury is unclear. This study aimed to explore the effect of circ_DLGAP4 on IS-induced microglia polarization and inflammatory cytokines, and the underlying mechanism. BV-2 cells (microglia) were transfected with circ_DLGAP4 overexpression (oeCirc), short hairpin RNA plasmid (shCirc), or corresponding negative control plasmids (oeNC and shNC).

Enhancing mA modification of lncRNA through METTL3 and RBM15 to promote malignant progression in bladder cancer.

Objective: Bladder cancer is one of the most prominent malignancies affecting the urinary tract, characterized by a poor prognosis. Our previous research has underscored the pivotal role of mA methylation in the progression of bladder cancer. Nevertheless, the precise relationship between N6-methyladenosine (mA) regulation of long non-coding RNA (lncRNA) and bladder cancer remains elusive.

MEAs-Filter: a novel filter framework utilizing evolutionary algorithms for cardiovascular diseases diagnosis.

Cardiovascular disease management often involves adjusting medication dosage based on changes in electrocardiogram (ECG) signals' waveform and rhythm. However, the diagnostic utility of ECG signals is often hindered by various types of noise interference. In this work, we propose a novel filter based on a multi-engine evolution framework named MEAs-Filter to address this issue.

Microstructure and Mechanical Properties of AlTiVCuN Coatings Prepared by Ion Source-Assisted Magnetron Sputtering.

The AlTiVCuN coatings were deposited by magnetron sputtering with anode layer ion source (ALIS) assistance, and the microstructure and mechanical properties were significantly affected by the ion source power. With increasing the ion source power from 0 to 1.0 kW, the deposition rate decreased from 2.

Identifying the pathophysiological traits of obstructive sleep apnea during dexmedetomidine sedation.

Dexmedetomidine (DEX) has been described as a safe sedative in clinical practice, but its effects on the pathophysiological traits of obstructive sleep apnea (OSA) are unclear. We estimated the effects of DEX sedation on the four key pathophysiological traits of OSA (pharyngeal collapsibility, dilator muscle function, arousal threshold, and loop gain) in adult patients with OSA by conducting a secondary analysis of a prospective diagnostic trial. Pathophysiological traits estimated from polysomnography and the respiratory parameters under natural sleep and DEX-induced sleep were compared.

TROP2 translation mediated by dual mA/mG RNA modifications promotes bladder cancer development.

RNA modifications, including adenine methylation (mA) of mRNA and guanine methylation (mG) of tRNA, are crucial for the biological function of RNA. However, the mechanism underlying the translation of specific genes synergistically mediated by dual mA/mG RNA modifications in bladder cancer (BCa) remains unclear. We demonstrated that mA methyltransferase METTL3-mediated programmable mA modification of oncogene trophoblast cell surface protein 2 (TROP2) mRNA promoted its translation during malignant transformation of bladder epithelial cells.

Regulation of ncRNAs involved with ferroptosis in various cancers.

As a special pattern of programmed cell death, ferroptosis is reported to participate in several processes of tumor progression, including regulating proliferation, suppressing apoptotic pathways, increasing metastasis, and acquiring drug resistance. The marked features of ferroptosis are an abnormal intracellular iron metabolism and lipid peroxidation that are pluralistically modulated by ferroptosis-related molecules and signals, such as iron metabolism, lipid peroxidation, system Xc, GPX4, ROS production, and Nrf2 signals. Non-coding RNAs (ncRNAs) are a type of functional RNA molecules that are not translated into a protein.

Targeted mA demethylation of ITGA6 mRNA by a multisite dCasRx-mA editor inhibits bladder cancer development.

Introduction: N6-methyladenosine (mA) modification contributes to the pathogenesis and development of various cancers, including bladder cancer (BCa). In particular, integrin α6 (ITGA6) promotes BCa progression by cooperatively regulating multisite mA modification. However, the therapeutic effect of targeting ITGA6 multisite mA modifications in BCa remains unknown.

Vina-GPU 2.0: Further Accelerating AutoDock Vina and Its Derivatives with Graphics Processing Units.

Modern drug discovery typically faces large virtual screens from huge compound databases where multiple docking tools are involved for meeting various real scenes or improving the precision of virtual screens. Among these tools, AutoDock Vina and its numerous derivatives are the most popular and have become the standard pipeline for molecular docking in modern drug discovery. Our recent Vina-GPU method realized 14-fold acceleration against AutoDock Vina on a piece of NVIDIA RTX 3090 GPU in one virtual screening case.

N-methyladenosine mediates Nrf2 protein expression involved in PM2.5-induced pulmonary fibrosis.

It has been reported that particulate matter with an aerodynamic diameter of <2.5 µm (PM2.5) could induce epithelial-mesenchymal transition (EMT)- and extracellular matrix (ECM)-related pulmonary fibrosis (PF).

Multifaceted Roles of the -Methyladenosine RNA Methyltransferase METTL3 in Cancer and Immune Microenvironment.

As the most abundant internal mRNA modification in eukaryotic cells, -methyladenosine (mA) has emerged as an important regulator of gene expression and has a profound impact on cancer initiation and progression. mRNA mA modification is regulated by mA methyltransferases, demethylases and reader proteins to fine tune gene expression at the post-transcriptional level. The most well-studied mA methyltransferase, METTL3, plays critical roles in regulating gene expression and affecting the outcome of various cancers.

Accelerating AutoDock Vina with GPUs.

AutoDock Vina is one of the most popular molecular docking tools. In the latest benchmark CASF-2016 for comparative assessment of scoring functions, AutoDock Vina won the best docking power among all the docking tools. Modern drug discovery is facing a common scenario of large virtual screening of drug hits from huge compound databases.

Construction of chitosan scaffolds with controllable microchannel for tissue engineering and regenerative medicine.

Microchannels are effective means of enabling the functional performance of tissue engineering scaffolds. Chitosan, a partial deacetylation derivative of chitin, exhibiting excellent biocompatibility, has been widely used in clinical practice. However, development of chitosan scaffolds with controllable microchannels architecture remains an engineering challenge.

Impact of acute kidney injury on in-hospital outcomes in Chinese patients with community acquired pneumonia.

Background: Acute kidney injury (AKI) is a frequent complication of community acquired pneumonia (CAP). However, the impact of AKI on in-hospital outcomes of patients with CAP in the Chinese population remains unclear.

Methods: Patients diagnosed with CAP were evaluated in this retrospective observational study.

Effect of Different Deposition Pressure on Diamond Films Deposited by Hot Filament Chemical Vapor Deposition.

A hot filament chemical vapor deposition (HFCVD) method was adopted to deposit diamond films at deposition pressures ranging from 2-6 kPa. The effects of deposition pressure on the deposition rate, phase structure, and microstructure of diamond films were investigated. The surface morphology, grain size, micro-structure, and growth rate of the diamond films were analyzed using scanning electron microscopy, X-ray diffraction (XRD), and Raman spectrometry.

Biomimetic angle-ply multi-lamellar scaffold for annulus fibrosus tissue engineering.

Constructing a biomimetic scaffold that replicates the complex architecture of intervertebral disc annulus fibrosus (AF) remains a major goal in AF tissue engineering. In this study, a biomimetic angle-ply multi-lamellar polycaprolactone/silk fibroin (PCL/SF) AF scaffold was fabricated. Wet-spinning was used to obtain aligned PCL/SF microfiber sheets, and these were excised into strips with microfibers aligned at +30° or -30° relative to the strip long axis.

[SLFN14 inhibits LINE-1 transposition activity].

Long interspersed nuclear element-1 (LINE-1) is the only active autonomous transposon in the human genome. Its transposition frequently induces host genome instability, leading to a variety of genetic diseases, including cancers. The host factors play important roles in inhibiting LINE-1 retrotransposition.

Correlation between C slope and cervical lordosis in patients after expansive open-door laminoplasty.

To investigate the correlation between C slope and cervical lordosis in patients after expansive open-door laminoplasty (EOLP). We retrospectively analyzed 57 patients who underwent EOLP between June 2013 and January 2017 in the Department of Spinal Surgery of our hospital. The operation time, intraoperative blood loss and follow-up time were recorded.

A Multisensor Data Fusion Method Based on Gaussian Process Model for Precision Measurement of Complex Surfaces.

As multisensor measurement technology is rapidly applied in industrial production, one key issue is the data fusion procedure by combining several datasets from multiple sensors to obtain the overall geometric measurement. In this paper, a multisensor data fusion method based on a Gaussian process model is proposed for complex surface measurements. A robust surface registration method based on the adaptive distance function is firstly used to unify the coordinate systems of different measurement datasets.

Circular RNA DLGAP4 is down-regulated and negatively correlates with severity, inflammatory cytokine expression and pro-inflammatory gene miR-143 expression in acute ischemic stroke patients.

This study aimed to investigate the expression of circular RNA DLGAP4 (circ-DLGAP4) and its correlation with severity, inflammation, inflammatory cytokine levels as well as microRNA-143 (miR-143) expression in acute ischemic stroke (AIS) patients. One hundred and seventy AIS patients and 170 non-AIS controls were enrolled in this study. PBMC and serum from all participants were collected.