Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results.

Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual adeno-associated virus (AAV) serotype 1 carrying human OTOF transgene is safe and associated with functional improvements in patients with autosomal recessive deafness 9 (DFNB9). The protocol was subsequently amended and approved to allow bilateral gene therapy administration.

CT perfusion imaging of the liver and the spleen can identify severe portal hypertension.

Purpose: To determine if hepatic and splenic perfusion parameters are useful in identifying severe portal hypertension (SPH).

Methods: The study enrolled 52 patients who underwent perfusion CT scan within one week before the hepatic venous pressure gradient (HVPG) measurement. A commercial software package was used for post-processing to generate hepatic and splenic perfusion parameters.

AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial.

Background: Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9.

An efficient numerical method on modified space-time sparse grid for time-fractional diffusion equation with nonsmooth data.

In this paper, we focus on developing a high efficient algorithm for solving -dimension time-fractional diffusion equation (TFDE). For TFDE, the initial function or source term is usually not smooth, which can lead to the low regularity of exact solution. And such low regularity has a marked impact on the convergence rate of numerical method.

Intermittent versus continuous control of tracheal cuff pressure in patients undergoing mechanical ventilation: A systematic review and meta-analysis.

Aims And Objectives: To evaluate the effects and safety of intermittent versus continuous control of cuff pressure in patients with mechanical ventilation.

Background: Tracheal cuff pressure management is vital to the prognosis of patients with mechanical ventilation.

Design: A meta-analysis.

Re-engineering the adenine deaminase TadA-8e for efficient and specific CRISPR-based cytosine base editing.

Cytosine base editors (CBEs) efficiently generate precise C·G-to-T·A base conversions, but the activation-induced cytidine deaminase/apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (AID/APOBEC) protein family deaminase component induces considerable off-target effects and indels. To explore unnatural cytosine deaminases, we repurpose the adenine deaminase TadA-8e for cytosine conversion. The introduction of an N46L variant in TadA-8e eliminates its adenine deaminase activity and results in a TadA-8e-derived C-to-G base editor (Td-CGBE) capable of highly efficient and precise C·G-to-G·C editing.

Engineering a precise adenine base editor with minimal bystander editing.

Adenine base editors (ABEs) catalyze A-to-G transitions showing broad applications, but their bystander mutations and off-target editing effects raise safety concerns. Through structure-guided engineering, we found ABE8e with an N108Q mutation reduced both adenine and cytosine bystander editing, and introduction of an additional L145T mutation (ABE9), further refined the editing window to 1-2 nucleotides with eliminated cytosine editing. Importantly, ABE9 induced very minimal RNA and undetectable Cas9-independent DNA off-target effects, which mainly installed desired single A-to-G conversion in mouse and rat embryos to efficiently generate disease models.

Research on safety and compliance of imported microbial inoculants using high-throughput sequencing.

Microbial inoculants are widely used in wastewater treatment, soil remediation, and biological control. Safety and compliance for active constituents are considered to be the most important measures of imported microbial inoculants. Microbial inoculants composition was commonly identified by phenotypic culture, which is time-consuming and labor intense with occasionally false negative results provided, and can only be tested for specific species.

Dual base editor catalyzes both cytosine and adenine base conversions in human cells.

Although base editors are useful tools for precise genome editing, current base editors can only convert either adenines or cytosines. We developed a dual adenine and cytosine base editor (A&C-BEmax) by fusing both deaminases with a Cas9 nickase to achieve C-to-T and A-to-G conversions at the same target site. Compared to single base editors, A&C-BEmax's activity on adenines is slightly reduced, whereas activity on cytosines is higher and RNA off-target activity is substantially decreased.

Increasing the efficiency and targeting range of cytidine base editors through fusion of a single-stranded DNA-binding protein domain.

Cytidine base editors are powerful genetic tools that catalyse cytidine to thymidine conversion at specific genomic loci, and further improvement of the editing range and efficiency is critical for their broader applications. Through insertion of a non-sequence-specific single-stranded DNA-binding domain from Rad51 protein between Cas9 nickase and the deaminases, serial hyper cytidine base editors were generated with substantially increased activity and an expanded editing window towards the protospacer adjacent motif in both cell lines and mouse embryos. Additionally, hyeA3A-BE4max selectively catalysed cytidine conversion in TC motifs with a broader editing range and much higher activity (up to 257-fold) compared with eA3A-BE4max.

Correction to: Increasing targeting scope of adenosine base editors in mouse and rat embryos through fusion of TadA deaminase with Cas9 variants.

In the original publication the grant number is incorrectly published. The correct grant number should be read as "17140901600". The corrected contents are provided in this correction article.

Arabidopsis ENOR3 regulates RNAi-mediated antiviral defense.

Viruses can infect host plants to cause severe diseases and substantial agricultural loss, while plants have evolved RNA interference (RNAi) strategy to defend against viral infection. Despite enormous efforts, only a few host proteins in RNAi pathway were shown to mediate antiviral defense, including RNA-dependent RNA polymerase 1 (RDR1), RDR6, DICER-LIKE 2 (DCL2) and DCL4. In this study, we carried out a genetic screen for antiviral factors of RNAi pathway in Arabidopsis rdr6 background via inoculation with a 2b-deficient Cucumber Mosaic Virus (CMV-Δ2b).

and Mediate RNAi-Based Antiviral Immunity.

RNA intereferencing (RNAi) pathway regulates antiviral immunity and mediates plant growth and development. Despite considerable research efforts, a few components in RNAi pathway have been revealed, including ARGONAUTEs (AGOs), DICER-LIKEs (DCLs), RNA-dependent RNA polymerase 1 and 6 (RDR1/6), and ALTERED MERISTEM PROGRAM 1 (AMP1). In this study, we performed a forward genetic screening for enhancers of via inoculation of CMV2aTΔ2b, a 2b-deficient Cucumber Mosaic Virus that is unable to suppress RNAi-mediated antiviral immunity.

QTL mapping of cucumber fruit flesh thickness by SLAF-seq.

Cucumber is an agriculturally and economically important vegetable crop worldwide. Fruit flesh thickness is an important trait for cucumber and also a central determinant of yield, yet little is known about the underlying mechanism of this trait. In this study, bulked segregant analysis (BSA) combined with specific length amplified fragment sequencing (SLAF-seq) was applied to finely map the gene that underlies fruit flesh thickness in cucumber.

A high-density genetic map of cucumber derived from Specific Length Amplified Fragment sequencing (SLAF-seq).

High-density genetic map provides an essential framework for accurate and efficient genome assembly and QTL fine mapping. Construction of high-density genetic maps appears more feasible since the advent of next-generation sequencing (NGS), which eases SNP discovery and high-throughput genotyping of large population. In this research, a high-density genetic map of cucumber (Cucumis sativus L.

The development and evaluation of a computerized diagnosis scheme for pneumoconiosis on digital chest radiographs.

Purpose: To diagnose pneumoconiosis using a computer-aided diagnosis system based on digital chest radiographs.

Methods: Lung fields were first extracted by combining the traditional Otsu-threshold method with a morphological reconstruction on digital radiographs (DRs), and then subdivided into six non-overlapping regions (region (a-f)). Twenty-two wavelet-based energy texture features were calculated exclusively from each region and selected using a decision tree algorithm.

Diagnosis of pancreatic carcinoma based on combined measurement of multiple serum tumor markers using artificial neural network analysis.

Background: Artificial neural network (ANN) has demonstrated the ability to assimilate information from multiple sources to enable the detection of subtle and complex patterns. In this research, we evaluated an ANN model in the diagnosis of pancreatic cancer using multiple serum markers.

Methods: In this retrospective analysis, 913 serum specimens collected at the Department of General Surgery of Beijing Friendship Hospital were analyzed for carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and carcinoembryonic antigen (CEA).

Support vector machine model for diagnosing pneumoconiosis based on wavelet texture features of digital chest radiographs.

This study aims to explore the classification ability of decision trees (DTs) and support vector machines (SVMs) to discriminate between the digital chest radiographs (DRs) of pneumoconiosis patients and control subjects. Twenty-eight wavelet-based energy texture features were calculated at the lung fields on DRs of 85 healthy controls and 40 patients with stage I and stage II pneumoconiosis. DTs with algorithm C5.

The Accumulation of Crocin and Geniposide and Transcripts of Phytoene Synthase during Maturation of Gardenia jasminoides Fruit.

Gardenia fruit (fruit of Gardenia jasminoides Ellis) is used as a natural pigment resource and a Chinese traditional medicine. The white mesocarp turning orange or red that occurs during gardenia fruit maturation arises from the production and accumulation of the apocarotenoids, especially crocin-1, which is derived from carotenoid. Meanwhile, the major medical component geniposide is accumulated in gardenia fruit.