dCasMINI-mediated therapy rescues photoreceptors degeneration in a mouse model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is characterized by degeneration of rod and cone photoreceptors that progresses to irreversible blindness. Now, there are no mutation-agnostic approaches to treat RP. Here, we utilized a single adeno-associated virus (AAV)-based CRISPR activation system to activate phosphodiesterase 6B (Pde6b) to mitigate the severe degeneration in mice.

Decoding AI ethics from Users' lens in education: A systematic review.

In recent years, Artificial Intelligence (AI) has witnessed remarkable expansion, greatly benefiting the education sector. Nonetheless, this advancement brings forth several ethical dilemmas. The existing research on these ethical concerns within the educational framework is notably scarce, particularly when viewed from a user's standpoint.

Development of compact transcriptional effectors using high-throughput measurements in diverse contexts.

Transcriptional effectors are protein domains known to activate or repress gene expression; however, a systematic understanding of which effector domains regulate transcription across genomic, cell type and DNA-binding domain (DBD) contexts is lacking. Here we develop dCas9-mediated high-throughput recruitment (HT-recruit), a pooled screening method for quantifying effector function at endogenous target genes and test effector function for a library containing 5,092 nuclear protein Pfam domains across varied contexts. We also map context dependencies of effectors drawn from unannotated protein regions using a larger library tiling chromatin regulators and transcription factors.

The influence of environmental factors on the job burnout of physical education teachers in tertiary education.

This study takes environmental factors and individual factors as variables to explore the deep internal mechanism of the impact of a comprehensive environment on higher education physical education (PE) teachers' job burnout. Little research has been done on how environmental factors affect the internal mechanism of college and university PE teachers' job burnout through individual factors (e.g.

Understanding learners' perceptions of ChatGPT: A thematic analysis of peer interviews among undergraduates and postgraduates in China.

ChatGPT, an artificial intelligence (AI)-driven language model engineered by OpenAI, has experienced a substantial upsurge in adoption within higher education due to its versatile applications and sophisticated capabilities. Although prevailing research on ChatGPT has predominantly concentrated on its technological aspects and pedagogical ramifications, a comprehensive understanding of students' perceptions and experiences regarding ChatGPT remains elusive. To address this gap, this study employed a peer interview methodology, conducting a thematic analysis of 106 first-year undergraduates and 81 first-year postgraduate students' perceptions from diverse disciplines at a comprehensive university in East China.

Mechanisms of calcium homeostasis orchestrate plant growth and immunity.

Calcium (Ca) is an essential nutrient for plants and a cellular signal, but excessive levels can be toxic and inhibit growth. To thrive in dynamic environments, plants must monitor and maintain cytosolic Ca homeostasis by regulating numerous Ca transporters. Here we report two signalling pathways in Arabidopsis thaliana that converge on the activation of vacuolar Ca/H exchangers (CAXs) to scavenge excess cytosolic Ca in plants.

Applying ChatGPT to tackle the side effects of personal learning environments from learner and learning perspective: An interview of experts in higher education.

This paper investigates the capacity of ChatGPT, an advanced language model created by OpenAI, to mitigate the side effects encountered by learners in Personal Learning Environments (PLEs) within higher education. A series of semi-structured interviews were conducted with six professors and three Information and Communication Technology (ICT) experts. Employing thematic analysis, the interview data were assessed, revealing that the side effects stemming from the learner and learning perspectives could be primarily categorized into cognitive, non-cognitive, and metacognitive challenges.

Effective interactive engagement strategies for MOOC forum discussion: A self-efficacy perspective.

This mixed methods sequential explanatory study identified and explained the features of engagement strategies for MOOC forum discussion that help low-achieving students make significant progress. Triangulated data were collected from MOOC learners' (n = 335) scores in two reading assessments, their posts to the embedded online discussion forum, and their self-reflection learning journals. Based on learning progress between pre- and post-assessment tasks, MOOC learners are divided into three groups: 1) little, 2) moderate, and 3) significant progress.

Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of .

This study was envisaged to identify a strain of bacteria isolated from the gill of mandarin fish. Identification and characterization of the bacterial strain were performed using morphological characteristics, growth temperature, physiological and biochemical tests, antibiotic sensitivity tests, artificial infection tests, and 16S rRNA gene sequencing homology analysis. The results showed that the bacterium was Gram-negative, with flagella at the end and the side.

How education level influences internet security knowledge, behaviour, and attitude: a comparison among undergraduates, postgraduates and working graduates.

During the pandemic, the prevailing online learning has brought tremendous benefits to the education field. However, it has also become a target for cybercriminals. Cybersecurity awareness (CSA) or Internet security awareness in the education sector turns out to be critical to mitigating cybersecurity risks.

Nested epistasis enhancer networks for robust genome regulation.

Mammalian genomes have multiple enhancers spanning an ultralong distance (>megabases) to modulate important genes, but it is unclear how these enhancers coordinate to achieve this task. We combine multiplexed CRISPRi screening with machine learning to define quantitative enhancer-enhancer interactions. We find that the ultralong distance enhancer network has a nested multilayer architecture that confers functional robustness of gene expression.

Development and validation of a PLE scale from academic administrative perspective (PLES-AA) in tertiary education: A pilot study in China.

The study aims to construct and validate a rubric to assess the effectiveness of PLEs from an academic administrative perspective (PLER-AA) in tertiary education in China. A qualitative-quantitative sequential mixed-method design was used for the scale validation. A total of 206 teachers and administrative staff participated in the Confirmative Factor Analysis (CFA), which supported the 4-dimensional scale, with policy (n = 4), program design (n = 4), curriculum/instruction (n = 4), and capacity (n = 4).

The influence of social education level on cybersecurity awareness and behaviour: a comparative study of university students and working graduates.

A multitude of studies have suggested potential factors that influence internet security awareness (ISA). Some, for example, used GDP and nationality to explain different ISA levels in other countries but yielded inconsistent results. This study proposed an extended knowledge-attitude-behaviour (KAB) model, which postulates an influence of the education level of society at large is a moderator to the relationship between and .

Multiplexed genome regulation in vivo with hyper-efficient Cas12a.

Multiplexed modulation of endogenous genes is crucial for sophisticated gene therapy and cell engineering. CRISPR-Cas12a systems enable versatile multiple-genomic-loci targeting by processing numerous CRISPR RNAs (crRNAs) from a single transcript; however, their low efficiency has hindered in vivo applications. Through structure-guided protein engineering, we developed a hyper-efficient Lachnospiraceae bacterium Cas12a variant, termed hyperCas12a, with its catalytically dead version hyperdCas12a showing significantly enhanced efficacy for gene activation, particularly at low concentrations of crRNA.

The influence of picture book design on visual attention of children with autism: a pilot study.

Taking 22 children with mild and moderate autism as subjects and using the TobiiX 120 eye-tracker to record their eye movements in visual search of images in picture books, the characteristics of the process of autistic children viewing picture books were explored. Two measures, fixation counts and gaze duration, were used alongside attention heatmap, to explore the visual patterns among children with autism viewing two types of researcher-made picture books and an ordinary picture book. Using a within-subject design, it was found that children with autism could sustain longer gaze duration and have more fixation points on the effective area of the picture book content when viewing researcher-made picture books than when viewing the ordinary picture book, suggesting better visual attention to single-object and single-pattern picture books.

Engineered miniature CRISPR-Cas system for mammalian genome regulation and editing.

Compact and versatile CRISPR-Cas systems will enable genome engineering applications through high-efficiency delivery in a wide variety of contexts. Here, we create an efficient miniature Cas system (CasMINI) engineered from the type V-F Cas12f (Cas14) system by guide RNA and protein engineering, which is less than half the size of currently used CRISPR systems (Cas9 or Cas12a). We demonstrate that CasMINI can drive high levels of gene activation (up to thousands-fold increases), while the natural Cas12f system fails to function in mammalian cells.

Relationship between duration and extent of oedema and visual acuity outcome with ranibizumab in diabetic macular oedema: A post hoc analysis of Protocol I data.

Background/objectives: This post hoc analysis explores the relationship between residual oedema exposure after ranibizumab treatment initiation and long-term visual acuity outcome in eyes with centre-involved diabetic macular oedema (DMO).

Subjects/methods: Eyes randomised to the ranibizumab + prompt or deferred laser treatment arms in the Protocol I trial and with observed central retinal thickness (CRT) readings at baseline and ≥1 follow-up visits (n = 367) were stratified by 1) oedema duration (number of study visits with CRT ≥ 250 µm during the first 52 weeks of ranibizumab treatment); and 2) oedema extent (amount of excess CRT [≥ 250 µm] at each study visit, averaged over the first 52 weeks). Associations between measures of residual oedema and best-corrected visual acuity (BCVA) were assessed in multiple regression analyses.

Anti-CRISPR-mediated control of gene editing and synthetic circuits in eukaryotic cells.

Repurposed CRISPR-Cas molecules provide a useful tool set for broad applications of genomic editing and regulation of gene expression in prokaryotes and eukaryotes. Recent discovery of phage-derived proteins, anti-CRISPRs, which serve to abrogate natural CRISPR anti-phage activity, potentially expands the ability to build synthetic CRISPR-mediated circuits. Here, we characterize a panel of anti-CRISPR molecules for expanded applications to counteract CRISPR-mediated gene activation and repression of reporter and endogenous genes in various cell types.

CRISPR-Mediated Programmable 3D Genome Positioning and Nuclear Organization.

Programmable control of spatial genome organization is a powerful approach for studying how nuclear structure affects gene regulation and cellular function. Here, we develop a versatile CRISPR-genome organization (CRISPR-GO) system that can efficiently control the spatial positioning of genomic loci relative to specific nuclear compartments, including the nuclear periphery, Cajal bodies, and promyelocytic leukemia (PML) bodies. CRISPR-GO is chemically inducible and reversible, enabling interrogation of real-time dynamics of chromatin interactions with nuclear compartments in living cells.

A CRISPR-dCas Toolbox for Genetic Engineering and Synthetic Biology.

Programmable control of gene expression is essential to understanding gene function, engineering cellular behaviors, and developing therapeutics. Beyond the gene editing applications enabled by the nuclease CRISPR-Cas9 and CRISPR-Cas12a, the invention of the nuclease-dead Cas molecules (dCas9 and dCas12a) offers a platform for the precise control of genome function without gene editing. Diverse dCas tools have been developed, which constitute a comprehensive toolbox that allows for interrogation of gene function and modulation of the cellular behaviors.

ASSOCIATION BETWEEN EARLY ANATOMIC RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY AND LONG-TERM OUTCOME IN DIABETIC MACULAR EDEMA: An Independent Analysis of Protocol i Study Data.

Purpose: This post hoc analysis explores the relationship between early retinal anatomical response and long-term anatomical and visual outcomes with ranibizumab in center-involved diabetic macular edema.

Methods: Eyes randomized to the ranibizumab plus prompt laser and ranibizumab plus deferred laser treatment arms in the Protocol I study were categorized according to their proportional reduction (<20 vs. ≥20%) in central retinal thickness (CRT) after 12 weeks.

Streptomyces virginiae PPDC Is a New Type of Phenylpyruvate Decarboxylase Composed of Two Subunits.

Streptomyces virginiae phenylpyruvate decarboxylase (PPDC) has not been identified before. Two putative branched-chain α-keto acid dehydrogenase subunit genes bkdC and bkdD from S. virginiae are similar to halves of other PPDC coding sequences.

CRISPR-Cpf1 assisted genome editing of Corynebacterium glutamicum.

Corynebacterium glutamicum is an important industrial metabolite producer that is difficult to genetically engineer. Although the Streptococcus pyogenes (Sp) CRISPR-Cas9 system has been adapted for genome editing of multiple bacteria, it cannot be introduced into C. glutamicum.

Mutagenesis of Key Residues in the Binding Center of l-Aspartate-b-Semialdehyde Dehydrogenase from Escherichia coli Enhances Utilization of the Cofactor NAD(H).

L-Aspartate-β-semialdehyde dehydrogenase (ASADH) is a key enzyme in the aspartate pathway. In bacteria, ASADH is highly specific for the cofactor NADP(+) rather than NAD(+). Limited information on cofactor utilization is available, and neither the wild-type protein nor the available mutants could utilize NAD(+) efficiently.

Involvement of ROP6 and clathrin in nodulation factor signaling.

The symbiotic association between the legume Lotus japonicus and the nitrogen-fixing bacterium Mesorhizobium loti results in the formation of root nodules. This process begins with the recognition of the rhizobial nodulation factor (NF) by the NF receptors (NFR) at the cell surface of the host roots. The downstream signaling cascades after NFR recognition have not been fully characterized.