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The review also highlights the latest artificial intelligence (AI) technologies, such as generative models, Bayesian deep learning, reinforcement learning, and self-driving laboratories, which have been gaining momentum in drug discovery and chemistry and have potential in drug formulation development.Ribonucleic acid interference (RNAi) is an innovative treatment strategy for a myriad of indications. Non-viral synthetic nanoparticles (NPs) have drawn extensive attention as vectors for RNAi due to their potential advantages, including improved safety, high delivery efficiency and economic feasibility. However, the complex natural process of RNAi and the susceptible nature of oligonucleotides render the NPs subject to particular design principles and requirements for practical fabrication. Here, we summarize the requirements and obstacles for fabricating non-viral nano-vectors for efficient RNAi. To address the delivery challenges, we discuss practical guidelines for materials selection and NP synthesis in order to maximize RNA encapsulation efficiency and protection against degradation, and to facilitate the cytosolic release of oligonucleotides. The current status of clinical translation of RNAi-based therapies and further perspectives for reducing the potential side effects are also reviewed.Artificial intelligence (AI) is redefining how we exist in the world. In almost every sector of society, AI is performing tasks with super-human speed and intellect; from the prediction of stock market trends to driverless vehicles, diagnosis of disease, and robotic surgery. Despite this growing success, the pharmaceutical field is yet to truly harness AI. Development and manufacture of medicines remains largely in a 'one size fits all' paradigm, in which mass-produced, identical formulations are expected to meet individual patient needs. Recently, 3D printing (3DP) has illuminated a path for on-demand production of fully customisable medicines. Due to its flexibility, pharmaceutical 3DP presents innumerable options during formulation development that generally require expert navigation. Leveraging AI within pharmaceutical 3DP removes the need for human expertise, as optimal process parameters can be accurately predicted by machine learning. AI can also be incorporated into a pharmaceutical 3DP 'Internet of Things', moving the personalised production of medicines into an intelligent, streamlined, and autonomous pipeline. Supportive infrastructure, such as The Cloud and blockchain, will also play a vital role. Crucially, these technologies will expedite the use of pharmaceutical 3DP in clinical settings and drive the global movement towards personalised medicine and Industry 4.0.

Routine use of face masks for patients and physicians during intravitreal anti-vascular endothelial growth factor (VEGF) injections has increased with the emergence of the coronavirus disease 2019 pandemic. This study evaluates the impact of universal face mask use on rates and outcomes of post-injection endophthalmitis (PIE).

Retrospective, multicenter, comparative cohort study.

Eyes receiving intravitreal anti-VEGF injections from October 1, 2019, to July 31, 2020, at 12 centers.

Cases were divided into a "no face mask" group if no face masks were worn by the physician or patient during intravitreal injections or a "universal face mask" group if face masks were worn by the physician, ancillary staff, and patient during intravitreal injections.

Rate of endophthalmitis, microbial spectrum, and visual acuity (VA).

Of 505 968 intravitreal injections administered in 110 547 eyes, 85 of 294 514 (0.0289%; 1 in 3464 injections) cases of presumed endophthalmitis occurred in the "no face mask" group, and study, physician and patient face mask use during intravitreal anti-VEGF injections did not alter the risk of presumed acute-onset bacterial endophthalmitis, but there was a reduced rate of culture-positive endophthalmitis. Three months after presentation, there was no difference in VA between the groups.

In a large, multicenter, retrospective study, physician and patient face mask use during intravitreal anti-VEGF injections did not alter the risk of presumed acute-onset bacterial endophthalmitis, but there was a reduced rate of culture-positive endophthalmitis. Three months after presentation, there was no difference in VA between the groups.Contemporary computational microRNA(miRNA)-target prediction tools have been playing a vital role in pursuing putative targets for a solitary miRNA or a group of miRNAs. These tools utilise a set of probabilistic algorithms, machine learning techniques and analyse experimentally validated miRNA targets to identify the potential miRNA-target pairs. Unfortunately, current tools generate a huge number of false-positive predictions. A standardized approach with a single tool or a combination of tools is still lacking. Moreover, sensitivity, specificity and overall efficiency of any single tool are yet to be satisfactory. Therefore, a systematic combination of selective online tools combining the factors regarding miRNA-target identification would be valuable as an miRNA-target prediction scheme. The focus of this study was to develop a theoretical framework by combining six available online tools to facilitate the current understanding of miRNA-target identification.Breast cancer (BC) is a critical health care issue that substantially affects women worldwide. Though surgery and chemotherapy can effectively control tumor growth, metastasis remains a primary concern. Metastatic BC cells predominantly colonize in bone, owing to their rigid osseous nutrient-rich nature. There are recently increasing studies investigating the context-dependent roles of non-coding RNAs (ncRNAs) in metastasis regulation. ncRNAs, including microRNAs, long non-coding RNAs, circular RNAs, and small interference RNAs, control the BC metastasis via altered mechanisms. Additionally, these ncRNAs have been reported in regulating a unique class of genes known as Metastatic suppressors. Ponatinib Metastasis suppressors like BRMS1, NM23, LIFR, and KAI1, etc., have been extensively studied for their role in inducing apoptosis, inhibiting metastasis, and maintaining homeostasis. In this review, we have emphasized the direct regulation of ncRNAs for effectively controlling the distant spread of BC. Furthermore, we have highlighted the ncRNA-mediated modulation of the metastatic suppressors, thereby delineating their indirect influence over metastasis.The astrocyte is a central glial cell and plays a critical role in the architecture and activity of neuronal circuits and brain functions through forming a tripartite synapse with neurons. Emerging evidence suggests that dysfunction of tripartite synaptic connections contributes to a variety of psychiatric and neurodevelopmental disorders. Furthermore, recent advancements with transcriptome profiling, cell biological and physiological approaches have provided new insights into the molecular mechanisms into how astrocytes control synaptogenesis in the brain. In addition to these findings, we have recently developed in vivo cell-surface proximity-dependent biotinylation (BioID) approaches, TurboID-surface and Split-TurboID, to comprehensively understand the molecular composition between astrocytes and neuronal synapses. These proteomic approaches have discovered a novel molecular framework for understanding the tripartite synaptic cleft that arbitrates neuronal circuit formation and function. Here, this short review highlights novel in vivo cell-surface BioID approaches and recent advances in this rapidly evolving field, emphasizing how astrocytes regulate excitatory and inhibitory synapse formation in vitro and in vivo.3-deazaneplanocin A (DzNep) and its 3-brominated analogs inhibit replication of several RNA viruses. This antiviral activity is attributed to inhibition of S-adenosyl homocysteine hydrolase (SAHase) and consequently inhibition of viral methyltransferases, impairing translation of viral transcripts. The L-enantiomers of some derivatives retain antiviral activity despite dramatically reduced inhibition of SAHase in vitro. To better understand the mechanisms by which these compounds exert their antiviral effects, we compared DzNep, its 3-bromo-derivative, CL123, and the related enantiomers, CL4033 and CL4053, for their activities towards the model negative-sense RNA virus vesicular stomatitis virus (VSV). In cell culture, DzNep, CL123 and CL4033 each exhibited 50 percent inhibitory concentrations (IC50s) in the nanomolar range whereas the IC50 for the L-form, CL4053, was 34-85 times higher. When a CL123-resistant mutant (VSVR) was selected, it exhibited cross-resistance to each of the neplanocin analogs, but retained sensitivity to the adenosine analog BCX4430, an RNA chain terminator. Sequencing of VSVR identified a mutation in the C-terminal domain (CTD) of the viral large (L) protein, a domain implicated in regulation of L protein methyltransferase activity. CL123 inhibited VSV viral mRNA 5' cap methylation, impaired viral protein synthesis and decreased association of viral mRNAs with polysomes. Modest impacts on viral transcription were also demonstrated. VSVR exhibited partial resistance in each of these assays but its replication was impaired, relative to the parent VSV, in the absence of the inhibitors. These data suggest that DzNep, CL123 and CL4033 inhibit VSV through impairment of viral mRNA cap methylation and that the L-form, CL4053, based on the cross-resistance of VSVR, may act by a similar mechanism.

Chromatin modifier metastasis-associated protein 1 (MTA1), closely associated with tumor angiogenesis in breast cancer, plays an important role in gene expression and cancer cell behavior. Recently, an association between O-GlcNAc transferase (OGT) and MTA1 was identified by mass spectroscopy. However, the potential relationship between MTA1 and O-GlcNAc modification has not yet explored.

In the current study, the role of MTA1 and its O-GlcNAc modification in breast cancer cell genotoxic adaptation was investigated through quantitative proteomics, chromatin immunoprecipitation followed by sequencing (ChIP-seq), transcriptome analysis, and loss- and gain-of-function experiments.

We demonstrate that the O-GlcNAc modification promotes MTA1 to interaction with chromatin and thus changes the expression of target genes, contributing to breast cancer cell genotoxic adaptation. MTA1 is modified with O-GlcNAc residues at serine (S) residues S237/S241/S246 in adriamycin-adaptive breast cancer cells, and this modification improves the genome-wide interactions of MTA1 with gene promotor regions by enhancing its association with nucleosome remodeling and histone deacetylation (NuRD) complex. Further, O-GlcNAc modification modulates MTA1 chromatin binding, influencing the specific transcriptional regulation of genes involved in the adaptation of breast cancer cells to genotoxic stress.

Our findings reveal a previously unrecognized role for O-GlcNAc-modified MTA1 in transcriptional regulation and suggest that the O-GlcNAc modification is a key to the molecular regulation of chemoresistance in breast cancers.

Our findings reveal a previously unrecognized role for O-GlcNAc-modified MTA1 in transcriptional regulation and suggest that the O-GlcNAc modification is a key to the molecular regulation of chemoresistance in breast cancers.